Lee Silverman Voice Treatment (LSVT) has well-documented treatment efficacy for individuals with hypokinetic dysarthria associated with Parkinson's disease (PD). Positive changes have been noted after treatment not only for vocal loudness but also for many other speech dimensions, including intonation (monotonicity). There have been few studies investigating the effect of LSVT on lexical tone which, like intonation, is controlled by variations in fundamental frequency. This study involved 12 Cantonese speakers with idiopathic PD who were enrolled in a standard LVST treatment protocol. Speech data were collected 3-4 days before treatment and 1 day after treatment. A wide variety of perceptual and acoustic variables were analyzed. The results showed significant improvements in loudness and intonation after treatment, but no significant changes in lexical tone. These results have theoretical implications for the relationship between tone and intonation and for models of the physiological control of fundamental frequency. Lee Silverman Voice Treatment (LSVT), which focuses on increasing vocal loudness, was developed for the treatment of voice and speech impairment in individuals with Parkinson's disease (PD). The treatment protocol involves intensive treatment delivery  and has been fully described elsewhere . LSVT haAn estimated 60–70% of the world's languages are tonal ; that is There have been few studies of hypokinetic dysarthria in speakers of lexical tonal languages. Cantonese speakers with PD have been found to demonstrate similar characteristics, in terms of disrupted dimensions of speech, as English and Japanese speakers with the disease . LexicalThe aim of the current study was to determine whether LSVT, which has well-documented success in improving monotone speech (as well as other disordered speech dimensions) in individuals with PD, would have a similar positive impact on lexical tone errors. The speaker participants were 12 Cantonese speakers with idiopathic PD . All these participants received regular medication for PD that was unchanged throughout the course of the study, except for one participant whose medication was modified during the study. Improvements in speech due to dopamine-type medication are believed to be small and are highly varied across different individuals ; hence, Treatment was provided by 12 qualified native Cantonese speech-language therapists who had recently completed an LSVT certification course. The standard LSVT treatment protocol was followed . All 12  The data reported here were collected three or four days before treatment and one day after treatment. All data were collected by investigators who were not involved in delivering the treatment. Recordings were made in a quiet room with background noise level of less than 43 dB. Speech samples were recorded using an Aardvark Direct Mix USB 3 Soundcard and Audacity 1.2.6. An AKG C 525 S or Shure SM48 low-noise unidirectional microphone was held at a mouth-to-microphone distance of 10 cm. A wide range of speech stimuli was employed; this study focuses only on a 30-second speech sample extracted from a standard reading passage (the Chinese “Barbra Streisand” passage ). All seThe perceptual rating tasks were conducted individually in a sound-attenuated booth using Windows media player running on a Compaq Presario V3000 laptop and Sennheiser HD 212Pro headphones. The order of the rating tasks was randomized across listeners to control for order effects. Monotonicity was rated by the 12 student-listeners using a visual analogue scale (VAS). The left side of a 10 cm line was labeled “normal” and the right side “extremely monotone.” The listeners were asked to mark a cross on the line to represent their judgment of each speaker's monotonicity.  Lexical tone was analyzed using two tasks, tone transcription, and tone error identification. Data from one speaker were excluded due to presence of a dialect that affected tone. The first task used syllables extracted from the reading passage. Three tokens were included for each of the six tones. These single-word tokens were randomized across speakers and time. Each token was transcribed by the listeners by writing down the tone value . The second task involved extracting ten phrases from the reading paragraph, which totalled 65 syllables. Three tokens were included for each of the six tones. This task was conducted subsequent to the main experiment, due to poor intrarater reliability for the tone transcription task. The listeners for this task were three experienced speech-language therapists who were asked to listen to the sentences, follow the written text, and circle any syllable that they perceived to be in error. Standard deviation of fundamental frequency (SDFO) was used as the acoustic correlate for monotonicity. Mean F0 and SDFO values were calculated from the 30-second reading passage sample, using the autocorrelation algorithm in Praat, Version 5.1 . The F0 For lexical tone, fundamental frequency (FO) was measured for each extracted syllable . The voiced segment of each of the eighteen stimuli was identified auditorially, by listening to the signal, and visually, from a wideband spectrogram and an amplitude waveform display. The voiced segment was defined as the third cycle from the start to the third cycle from the end . F0 was r, P  <  0.01); interrater reliability was 0.71 . Intrarater reliability for tone transcription was 0.51  and interrater reliability was 0.91 . Intrarater reliability for the tone error identification task was 0.96  and interrater reliability was 0.70 . Intrarater reliability for monotonicity (based on repeating the stimuli from two speakers) was 0.70  and interrater reliability was 0.95  for both acoustic measures.Inter- and intrarater reliabilities for the acoustic measures were calculated by repeating the analysis for two speakers by the investigator and a second rater. Intrarater reliability was 0.99  was carried out for analysis of the perceptual measures of voice quality, vocal loudness, intonation, and rate, while a two-way, repeated-measures ANOVA was carried out for analysis of lexical tone accuracy (the error identification task). A repeated measure multivariate analysis of variance (MANOVA) was also computed for the four acoustic variables, with a separate three-way ANOVA for lexical tone.F = 19.97,P  <  0.001.The mean perceptual rating for the speech dimension “monotone” on the 10 cm VAS scale, where a higher number indicated more severely monotone speech, was 3.13 (SD  =  1.84) before therapy and 2.34 (SD  =  1.72) after therapy. This decrease in monotonicity was statistically significant, F  =  0.13, P  =  0.724.The mean accuracy of lexical tone, based on transcription, was 54.02 (SD  =  0.16) before therapy and 56.62 (SD  =  0.17) after therapy. Statistical analysis was not conducted for this measure because of the low intrarater reliability of the task. The mean accuracy of lexical tone based on identifying inaccurate tones was 97.72 (SD  =  0.03) before treatment and 97.64 (SD  =  0.03) after treatment. This difference was not statistically significant, F  <  0.001, P  =  0.9. However, examination of individual data revealed an increase in SDST for six of the twelve subjects. Two participants had a noticeable decrease in SDST after treatment (S1 and S11). The results for individual speakers are shown in Mean SDF0, in semitones (STSD), was 3.259 (SD  =  0.83) before treatment and 3.256 (SD  =  0.93) after treatment. There was no significant treatment effect, F  =  7.80, P  <  0.05, tone, F  =  17.95, P  <  0.001 and time point, F  =  23.28, P  <  0.001. The main effect of time indicated that overall mean F0 was higher after treatment than before treatment. A statistically significant difference was also indicated in the interaction of tone and time point, F  =  14.95, P  <  0.001. This confirmed that different tones have different frequencies at different time points and it is not related to any changes in treatment. No significant changes in time-tone, time-time point and time-time point-tone interactions were shown. This indicates that treatment effects were the same across all tones and all time points and implies that the F0 contour pattern of each tone had no significant statistical changes from before to after treatment.A three-way repeated measures ANOVA was used to analyze the lexical tone data with the within-group factors of time (pre and posttreatment), tone , and time points . Significant main effects were observed for time, The F0 patterns for all speakers were examined individually, in order to identify individual changes or patterns. For this analysis, F0 was not converted to semitones. Findings for the speakers with PD were compared with previously reported normative data for nonimpaired Cantonese speakers , 22. AllTwo of the twelve participants demonstrated similar F0 contour patterns before and after treatment to the nonimpaired speakers across all six tones. Although not detailed here, significant group treatment effects were additionally found for the dimensions of excessive soft voice and excessive loud voice  and for sound pressure level and mean fundamental frequency . Thes LSVT has well-established efficacy for the treatment of speech disorders in individuals with hypokinetic dysarthria associated with PD. The results of this study showed that the treatment approach was also successful with this group of Cantonese speakers with PD, based on several traditional outcome measures, as noted above. This was consistent with the results of a previous small-scale study with Cantonese speakers . The mai For the disordered speech dimension of “monotone”, there was a significant improvement for the group, based on listeners' perceptual ratings. That is, the speakers were less monotone after treatment. In contrast with the perceptual findings, statistical analysis of the group results for the acoustic correlate of monotonicity, SDST, showed no significant difference before and after treatment for the group. This was inconsistent with previous reports of LSVT treatment in both English speakers  and CanP  >  0.05). The finding of relatively intact lexical tone in Cantonese speakers with PD, as judged perceptually, was consistent with previous findings [ Tone was analysed perceptually using two different methods. The first employed transcription of isolated syllables extracted from the reading passage. Statistical analysis was not undertaken for this task, due to the low intrarater reliability. However, examination of the results indicated similar findings before and after therapy . Difficulties with transcribing tone from isolated syllables have been previously reported . In viefindings , 10.  Acoustic analysis of tone also revealed no significant differences before and after treatment, for the group. This was consistent with the results our previous small-scale study . However This study confirmed previous reports of relatively intact lexical tone in Cantonese speakers with Parkinson's disease , 10. It


F. compactum (1.4 × 106  propagules ml−1) on broomrape tubercles. F. compactum alone infected all the inoculated tubercles but did not kill any significant number. Infested tomato roots that were inoculated with mycelia plus pectinase (20 U ml−1) had over 50% tubercles dead one week after treatment. Those inoculated with mycelia plus cellulase (20 U ml−1) had above 60% mortality. Mixtures of mycelial plus the two enzymes (10 U ml−1 of each enzyme) showed synergy. The activity catalyzed by an enzyme is a measure of the amount of enzyme present. It was shown that, in a 1 mg (10 U mg−1) cellulase used, 0.055 mg pectinase (1.1 U mg−1) is present. This explains why mycelial plus cellulase mix contends with mycelial plus the two enzymes.The use of enzyme could facilitate pathogen penetration into plant host. Here the combination of cellulase and pectinase was ascertained on the pathogenicity of  Orobanche spp.) are fully parasitic flowering plants that lack chlorophyll; hence they penetrate roots of susceptible hosts, removing water, minerals and sugars. Orobanche aegyptiaca Pers. (Egyptian broomrape) attacks dicotyledonous crops cultivated around the Mediterranean, causing massive yield losses [Orobanche generally maintains a close relationship with the host and so it is unreasonable to attack it using herbicides because the latter may adversely affect the nontarget host. Despite research on Orobanche spp. for over three decades, yield losses still abound because there is no sustainable method for controlling the parasite. Broomrapes (d losses . Broomrad losses . OrobancFusarium compactum (Wollenw.) Gordon, used in this study is a pathogen of broomrape plants. The inundative biocontrol approach, with repeated applications of the biocontrol agent, generates a state of equilibrium with a very low level of weed density as a result of the artificial inoculation of the biocontrol agent but the fungi are not sufficiently virulent for field release, regardless of the amount used. A series of experiments were conducted using F. compactum, a biological control agent that infects Orobanche without affecting the roots of tomato.Acremonium sp, Aspergillus spp and Fusarium sp, [Trichoderma spp. [Zymomonas [Trichoderma viride. A hydrolytic enzyme plays an important role in the pathogenicity of plants by facilitating fungal penetration through the host cell wall [F. compactum on tomato plants infested with broomrape. A semiaxenic polyethylene bag system was used that allowed easy visual observation of the fungal infection of the tubercles. This study reports that the addition of pectinase and cellulase alone or in mixtures enhanced the virulence of F. compactum on broomrape.Some fungi are reported to have pectinolytic and/or cellulolytic enzymes . Pectinsrium sp, , Trichodrma spp. , 7, Zymoymomonas , and mutymomonas . In thisell wall , 11. Expell wall  or celluell wall  indicateF. compactum was cultured on potato glucose agar  in Petri dishes incubated at 25°C. Subcultures were grown in 100 ml potato glucose broth  in 250 ml Erlenmeyer flasks. Chloramphenicol (50 mg l−1) was added to the broth to restrict possible bacterial contamination. The cultures were left on a rotary shaker (Brunswick Scientific) at 150 rpm for 48 h. F. compactum mycelia were harvested on Miracloth , rinsed with distilled water to remove remaining spores and excess medium, and harvested by vacuum filtration. The washed hyphae were chopped at 6,000 rpm for 2 min with a homogenizer (IKA T18 basic Ultra-Turrax USA), resuspended in sterile water, and the propagule concentrations of chopped mycelia were estimated after serial dilution and plating.Broomrape seeds were kindly provided by Dr. J. Hershenhorn of the Newe Yaar Research Center . Surface sterilizing seeds ensure that the fungal infection on the seeds is from deliberate infection. Thus, about 13 mg seeds in small bags formed of Miracloth were wetted and surface sterilized in 80% ethanol for 1 min and in a mixture of 1% sodium hypochlorite in 0.01% aqueous Tween 20 for 10 min. The seeds were rinsed three times in sterile distilled water. Tomato transplant plugs at the two to three leaf stages in Speedling Insert Trays were purchased from Hishtil Inc, Ashkelon, Israel. The seedlings were cultured for later use as host plants in the broomrape studies.F. compactum was tested in the semiaxenic polyethylene bag system; briefly about 13 mg of dry surface-disinfected seeds  were sprinkled on wet Whatman GF/A glass-fiber sheets  in each bag. The broomrape seeds were conditioned for a 7 d period on the wet glass-fiber sheets. A tomato seedling with three or four expanded leaves and washed roots was fixed inside each polyethylene bag containing conditioned broomrape seeds. The plant roots in each bag were moistened by capillary action with forty ml of modified Hoagland's solution in the base of each bag [μE/m2/s  produced by six 40 W cool white fluorescent tubes suspended 35 cm above the benches. Two ml of 5-μg ml−1 GR-24 (synthetic germination stimulant) were added to each bag with a pipette to augment the tomato root exudates. This spreads by capillary action. The broomrape seeds germinated, attached to tomato roots, and formed small tubercles during the following 2 weeks. The pathogenicity of each bag . ModifieOrobanche-infested tomato plants were in such a way that the tubercle numbers and sizes were almost the same. The virulence of the fungus was determined with and without various concentrations of either pectinase  and/or cellulase . The effect of cellulase concentration (10 to 20 U ml−1) on tubercle death was similarly determined at a constant inoculum level. Thereafter, the virulence of the fungus with the two enzymes was determined in combination at varying ratios. Control plants were mock-inoculated with either sterile distilled water containing 0.01% Tween 20 or 4 to 20 U ml−1 of single or combined enzyme preparations but without fungal mycelia. Tubercles on the tomato plants infested with broomrape were counted and the diameters were measured with a ruler, with the assumption that the tubercles are perfectly spherical. The treatments consisted of F. compactum or F. compactum plus cellulase (4 to 20 U ml−1). This work was carried out under containment. Allocation of treatment to −1), freshly made for each experiment as a solution containing 10 U ml−1, and was checked for pectinase activity. Enzyme blank served as the control. Pectinase activity was measured in a reaction mixture consisting of 533 μl of 1% polygalacturonic acid (pectin), 400 μl of 50 mM sodium acetate buffer at pH 5.0 and 67 μl of the cellulase. The mixture was incubated at 37°C for 10 min as outlined by Tonukari et al. [μl aliquot of the reaction mixture was mixed with 1.5 ml of 1% 4-hydroxybenzhydrazide  in 0.5 M NaOH. The mixture was heated at 100°C for 10 min, and cooled on ice water. The experiment was performed three times in six replicate tubes. Each sample was assayed three times. Absorbance was measured at 410 nm against the zero time blank as outlined by Lever [max tunable microplate reader. Pectinase activity of the cellulase was calculated from a standard curve prepared with a D-galacturonic acid (Sigma). One unit of enzyme forms 1 μmol of galacturonic acid from polygalacturonic acid in 1 min under the conditions of the assay.One ml of aqueous fungal cellulase samples , infected (diseased), or dead (black and soft). The experiments were performed twice, with three replications per treatment. Data are presented for the tubercles present at the time of inoculation. Values are means and standard errors of the means obtained using SAS statistical package .F. compactum plus pectinase in both experiments were always better than those achieved by the fungus without pectinase  were investigated in the presence of pectinase. Pectinase alone had no effect on the tubercles. F. compactum alone killed 30% of broomrape tubercles at the suboptimal inoculum levels (F. compactum (3.84 × 105 propagules ml−1) combined with 11 U ml−1 pectinase killed more broomrape tubercles than the F. compactum alone  on broomrape tubercles could be synergistic through the joint action of the enzymes (10 U ml−1 of each enzyme)  (−1)  mix provoked about the same level of infection as mycelia in solution with cellulase and pectinase (10 U ml−1 of each enzyme)  . The bro enzyme) . F. compt number . Infesteber (−1)  had over−1) (−1)  had abovompactum . The res enzyme) .F. compactum will effectively enhance the fungal biocontrol potential: thus, it was tested. At various enzyme compositions, the actions of pectinase and/or cellulase enhanced the virulence of F. compactum on broomrape. The F. compactum treatment (1.05 × 105 propagules ml−1) that caused only a hypersensitive reaction (9% death) on the tubercles caused about 35 to 85% tubercle death when the tubercles were treated with mixtures that contained mycelia, pectinase, and cellulase in various ratios  cellulase preparation, 0.055 mg pectinase (1.1 U mg−1) is present. This means the 10 U cellulase has a 0.06 U of detectable pectinase. This, however, is not statistically significantly different from the blank.The activity catalyzed by an enzyme is a measure of the amount of enzyme present. It was observed that cellulase seems to overshadow pectinase in the spray mix. Thus, it was necessary to ascertain whether the cellulase is pure. Values pooled from three sets of experiment showed that in a 1 mg  at fungal inoculation. Tubercles are usually present at the germination phase and later become parasitic. In this study, the tubercles were mostly at the germination phase. In apparently healthy tubercles, it may be possible to find diseased tubercles  result in a loss of structural integrity in the tubercle and characteristic damage. Symptom development was accelerated by probably tubercle cell expansion by the enzymes. The enzyme substrate range and mechanism of action could partly explain the interaction between F. compactum and the enzymes on broomrape tubercles. The pathogenicity of F. compactum plus the enzyme mix observed could rarely be observed without pectinase and cellulase at the inoculum level used. Besides, neither pectinase nor cellulase was ordinarily able to injure and kill broomrape at the concentration used (max. 20 U ml−1), demonstrating that the broomrape tubercle infection and death observed are due to the addition of a mycoherbicidal organism. The role of pectinase and cellulase in the degradation of cell wall material as observed in this study corresponds with the reports of many authors [As demonstrated in this study, u et al. . F. comp authors , 18, 19. authors . In thissed max.  U ml−1, β-glucosidase in an enzyme preparation may affect the result of cellulase assays, for example, for the estimation of activities of extracellular cellulase enzymes produced by Trichoderma. As pointed out by Kumpoun and Motomura [β-glucosidase or other enzymes, such as cellobiose phosphorylase, which are required for cellobiose metabolism and to enhance cellulose hydrolysis but which are not, strictly speaking, cellulases or rhamnosidase and β-glucosidase activities in pectinase [A 0.6% pectinase activity was detected in the cellulase preparation. It is known that the level of Motomura , the pecectinase  could fuF. compactum infection on broomrape, F. oxysporum pathogenicity on broomrape was not enhanced by pectinase and/or cellulase. Thus, although F. oxysporum and F. compactum belong to the same genus, they may have different mycoherbicidal mechanisms. Mycelia of F. compactum did not penetrate nor show apparent damage to the tomato roots [F. compactum. The latter fact adds to the commercial value of F. compactum as a potential mycoherbicide when sufficiently virulent. Contrary to some of the findings associated with enhanced to roots  as also


Itrifal Saghir  has been widely used in traditional medicine. And brings health benefits such as antioxidant effect and scavenger of hydroxyl radicals and nitric oxide radicals activity and substantiated in traditional medicine a anti-obesity.Herbal combination of n = 31) or placebo (n = 31), 2 times daily for 12 weeks. Measures of body weight, BMI, waist circumference (WC), hip circumference (HC), were assessed at baseline and once every four weeks during the 12 week treatment period. The safety was evaluated by means of measuring the liver and kidney function. Homeostasis model of insulin resistance (HOMA-IR) was calculated as [fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5].In this study we aimed to assess the efficacy of this herbal medicinal on reduction of weight and body mass index (BMI) of simple obese subjects in comparison with placebo. Obese subjects aged between 16 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial using a parallel design. Subjects were randomly assigned to take 5 grams of either the Itrifal Saghir , the mean of decrease in waist circumference was 4.01 cm , and the mean decrease in hip circumference was 3. 21 cm  in treated subjects. No adverse effects or significant changes in liver and kidney function tests were observed in both placebo and treated groups.Itrifal Saghir appears to produce a positive effect on weight loss in obese subjects. Obesity is recognized as an important metabolic disorder and a major public health issue which affects a large number of people around the world. According to the World Health Organization (WHO), obesity is rated among the 10 most preventable disease of clinical and public health -5, hyperor Emblica officinalis Gaertn. (Euphorbiaceae), Terminalia chebula Retz. (Combretaceae), and Terminalia belerica Retz. (Combretaceae) and formulated for the treatment and management of obesity. It is also claimed that Itrifal Saghir produces beneficial effects on heath and helps the digestive tract to work at optimal level , Terminalia bellerica Roxb (Family combretaceae) (PMP-625). (Combretaceae) and Phyllanthus emblica L. (Family euphorbiaceae) (PMP-626), were purchased from local market and authenticated at Botanical of Traditional Medicines School of Tehran University of Medical Sciences. A voucher specimen was preserved in our laboratory for future reference. Seeds from individual fruits were removed and the dried fruit pulp was crushed to powder using a grinder. Itrifal Saghir was prepared from these powders by mixing them in equal proportions 1:1:1) based on Al-Qanun fit-tib Formula  and main:1:1 base2).All the participants underwent physical examination and anthropometric evaluations at the time of recruitment and follow-up visits. By means of a special questionnaire, the demographic information and medical history were collected. At each visit participants were also queried about changes in medications and adverse events. Height was measured with a wall-mounted Stadiometer and weight was measured while wearing light clothes without shoes on a calibrated balance beam scale with error of nearest ± 0.1 kg (Gmbh & co.kg. Germany. Ser. no. 5769/59092207. Model 769/32/994). BMI was calculated according to the formula: BMI = body weight (BW) / squared height . Hip circumference was measured at the maximum circumference over the buttocks; by soft, non-stretchable plastic tape. Blood pressure was measured two times  using a standard calibrated mercury sphygmomanometer on the right hand after the participants had been sitting for at least 15 minutes. The mean of two measurements were recorded as the blood pressure. Heart rate and temperature also were recorded. Diet stability was verified using the 24-hour diet recalls at baseline and end of the study. Blood collections for serological data were conducted only at the first and the last visit (week 12). The peripheral blood samples were obtained following 8 hours overnight fasting. All measurements were performed at the laboratory of endocrine and metabolism research center of Tehran University of Medical Sciences.The serological data included cholesterol, low density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides, fasting insulin and glucose (FBS), glycosylated hemoglobin HbA1c), Prothrombin time (PT), and renal functions tests such as creatinine, and liver functions tests such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) tests and other tests such as uric acid. All the measurements were carried out according to standardized established method  software was used for all statistical analysis . ResultsA total of 62 subjects were randomly assigned into two groups, treated and placebo group (31 patients in each group). Age of the patients ranged from 16 to 60 years. No significant difference in regards to age, gender, level of education, marital status, and waist circumference was observed between two groups  were found after 12 weeks of treatment, while no remarkable changes in these variables were noticed in placebo group as shown in Table The mean of fasting blood sugar increased from 94.72 ± 8.96 to 99.20 ±10.55 in the placebo group and decreased from 96.86 ± 12.16 to 94.20 ± 9.78 in the Itrifal Saghir group after 12 weeks (ρ = 0.006). The mean fasting serum insulin decreased from 18.46 ± 10.91 to14.76 ± 8.00 in the Itrifal Saghir group and increased from 18.24 ± 7.21 to 19.91 ± 8.55 in the placebo group after 12 weeks (ρ = 0.01).The mean value of ALT decreased from 24.10 ± 9.18 to 18.90 ± 8.07 in the Itrifal Saghir group that was statistically significant comparing to placebo group ρ = .003). And the mean of uric acid decreased from 6.09 ± 1.07 to 5.78 ± 1.17 in the Itrifal Saghir group that was statistically significant comparing to placebo group (ρ = .05). Other Serological characteristics are shown in Table . And theThe comparing between start and end of systolic blood pressure level from 119.66 ± 17.80 mmHg and 117.50 ± 18.03 mmHg  at baseline to 120.22 ± 20.08 mmHg and 119.77 ± 18.61 mmHg at 12 week and the mean diastolic blood pressure level from 78.83 ± 10.05 mmHg and 78.83 ± 10.56 mmHg at baseline to 80.00 ± 12.14 mmHg and 79.77 ± 10.74 mmHg at week 12 in intervention group and the mean systolic blood pressure level from 122.00 ± 16.22 mmHg and 121.16 ± 14.66 mmHg  at baseline to 121.15 ± 20.52 mmHg and 122.30 ± 23.05 mmHg at 12 week and the mean diastolic blood pressure level from 81.66 ± 9.31 mmHg and 81.66 ± 9.49 mmHg at baseline to 78.07 ± 10.31 mmHg and 80.38 ± 11.98 mmHg at 12 week in placebo group, independent samples t-test revealed changes were not statistically significant in both groups.There were no significant changes in renal function or in levels of liver-associated enzymes among any of the treatment groups. Itrifal Saghir was generally well tolerated without statistically significant differences in rates of any adverse events.The present study evaluated weight reduction, a combination of three herbal remedies that are traditionally known for their weight reduction effects. In traditional medicine, mild overweight is generally accepted while severe obesity is considered a suitable condition to be treated using specific medicinal plants, body exercises and food consumption control. The Itrifal Saghir combination contained Seedless plants of: Terminalia chebula Retz., Terminalia belerica Roxb., and Emblica officinalis l. in equal parts. These ingredients should be mixed with almond oil and then kneaded with froth less honey and be kept in the vessel for further use . In thisWe need to mention some limitations that we have faced in this study. These limitations are mostly common in studies involving human subjects. First, the traditional medicine have two main variable: one which exist in human including mezaje (temperament) and racial/ethnic, sex, age, territory, season, occupation and second is the herbal drugs which are natural products and their chemical composition, therefore, varies depending on several factors, such as geographical source of the plant material, climate in which it was grown, time of harvest, etc. These variations can result in bioavailability differences in humans. Indeed in this study our subjects were assessed only for 12 weeks, therefore we could not have any conclusion about long term efficacy of this compound. Another, we did not recommend a specific diet in this study.The Itrifal Saghir brought a significantly greater weight loss than placebo during the study period in obese individuals. This was accompanied by a significant improvement in the waist and hip circumference. Itrifal Saghir possesses antioxidant and free radical scavenging and anti hyperlipidemia and lower fasting properties that could have applications in metabolic as well as other physiological complications in which there is an increase in oxidative stress. These new findings warrant further exploration into the active compound of Itrifal Saghir and the potential of its newly discovered weight loss benefits. However further study for evaluation of mechanism involved in this process is highly suggested.BMI: Body mass index; WC: Waist circumference; HC: Hip circumference; LDL: Low density lipoprotein cholesterol; HDL: High-density lipoprotein cholesterol; FBS: Fasting blood glucose; GTT: Glucose tolerance test; HbA1c: Glycosylated hemoglobin; PT: Prothrombin time; AST: Aspartate transaminase; ALT: Alanine transaminase; ALP: Alkaline phosphatase; Homa: Homeostasis model assessment; WBC: White blood cells; RBC: Red blood cells; INR: International Normalized Ratio; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; NS: Not statistically significant.The authors declare that they have no competing interests.SHK participated involved have made substantial contributions to conception and design, in the sequence alignment, acquisition of data, and analysis and interpretation of data, and drafting the manuscript and have given final approval of the version to be publish. KAR participated involved in revising. SHR participated involved in design, interpretation of data, and revising, have given final approval of the version to be publish. MME participated involved in revising. MK participated involved in revising. SAK participated involved have made substantial contributions to conception. OS participated involved have made substantial contributions to conception. All authors read and approved the final manuscript.Appendix 1. Carbomer 934P. Appendix 2. Table of standard laboratory test.Click here for file


Aedes aegypti, molluscicidal activity against Biomphalaria glabrata, and toxicity against Artemia salina. Extracts of Ulva lactuca (Chlorophyta), Padina gymnospora, Sargassum vulgare (Phaeophyta), Hypnea musciformis, and Digenea simplex (Rhodophyta) were prepared using different solvents of increasing polarity, including dichloromethane, methanol, ethanol, and water. Of the extracts screened, the dichloromethane extracts of H. musciformis and P. gymnospora exhibited the highest activities and were subjected to bioassay-guided fractionation in hexane and chloroform. The chloroform fractions of the P. gymnospora and H. musciformis extracts showed molluscicidal activity at values below 40 μg·mL−1 , and the chloroform and hexane fractions of P. gymnospora showed larvicidal activity at values below 40 μg·mL−1 . The crude extracts were not toxic to A. salina, whereas the chloroform and hexane fractions of P. gymnospora (788.277 μg·mL−1 and 706.990 μg·mL−1) showed moderate toxicity, indicating that the toxic compounds present in these algae are nonpolar.This study investigated the biological activities of five benthic marine algae collected from Northeastern Region of Brazil. The tested activities included larvicidal activity against  Marine environments, particularly in the tropics, have greater species richness than tropical forests. These diverse species are capable of producing a wide variety of chemical compounds with unique structures and functions, and many of these compounds can be used for the development of novel drugs , 2. As aThe secondary metabolites of marine algae are analogous to those of terrestrial plants with respect to the production of terpenes, aromatic compounds, acetogenins, amino acid derivatives, and polyphenols . Many ofThe Brazilian Northeast Region is the poorest region of Brazil and has the worst Human Development Indices in the country . Most ofUlva lactuca Linnaeus, Padina gymnospora (Kutzing) Sonder, Sargassum vulgare C. Agardh, Hypnea musciformis (Wulfen in Jacque) J.V. Lamouroux, and Digenea simplex (Wulfen) C. Agardh—all collected from the coast of Alagoas State. The activities tested included larvicidal activity against Aedes aegypti, molluscicidal activity against Biomphalaria glabrata, and toxicity against Artemia salina. This is the first report on the biological activity of marine algae collected from the coast of Alagoas.The present study investigates the biological activities of five marine algae: Ulva lactuca Linnaeus, MAC51238; Phaeophyta—Padina gymnospora (Kutzing) Sonder, MAC51235, and Sargassum vulgare C. Agardh, MAC51236; and Rhodophyta—Hypnea musciformis (Wulfen in Jacque) J.V. Lamouroux, MAC51234, and Digenea simplex (Wulfen) C. Agardh, MAC51231. A voucher specimen of each algae species was deposited in the MAC Herbarium at the Environmental Institute of the city of Maceió, Alagoas (Br), as a reference material.Algae were manually collected from the Riacho Doce beach (9°34′0′′S and 35°39′0′′W) during low tides between October 2007 and July 2009. The collected samples were immediately transported to the Phycology Laboratory of the Biological Sciences Institute (ICBS), Universidade Federal de Alagoas (UFAL). Five species of algae from three divisions were used for this study: Chlorophyta—H. musciformis and P. gymnospora were selected for fractionation because they gave the best yields: 11.86 g (2.58%) and 13.96 g (3.04%), respectively. The yields of the other extracts were less than 0.5 g (0.1%) and were therefore not sufficiently large for fractionation.Algae were washed with distilled water, dried in air-circulating ovens  at 45°C for three hours, and crushed using a MetVisa industrial blender (model type TA-2). The dried and crushed material from each collection and each alga was mixed in equal quantities. To obtain crude extracts, 500 g of dried algae was suspended in 1000 mL of dichloromethane, methanol, ethanol, or water and macerated for 72 hours; this process was repeated three times. The organic extracts were filtered and rotoevaporated  at 25°C–40°C, and the aqueous extract was lyophilized (Edwards Freeze dryer Mod E2 MB of Brazil). Extracts of the respective algal species were stored at 4°C. The dichloromethane extracts of H. musciformis (2.73 g) and P. gymnospora (1.90 g) were suspended in methanol : water (3 : 1) and extracted with hexane and chloroform to yield chloroform and hexane fractions. All solvents were purchased from VERTEC Fine Chemicals of Brazil.For fractionation by liquid-liquid partitioning, the crude extracts of A. aegypti larvae at the Chemistry and Biotechnology Institute of Federal University from Alagoas IQB/UFAL laboratory using the WHO protocol [μg·mL−1. Extracts that led to ≤50% mortality were subjected to more precise tests. In these tests, four replicates were run using 25 larvae in each replicate. The concentrations used were defined based on the preliminary results.Bioassays were run with protocol . The bioμg·mL−1. The activity level of extracts tested was calculated based on the average percent mortality of larvae at 48 hours .Larvae were considered dead when they failed to reach the surface of the solution after the liquid was stirred. Dead larvae counts were performed at 24 hours and 48 hours after the start of the experiment, and the samples were run in quadruplicate. In parallel, control tests were performed with 1% aqueous dimethyl sulfoxide (DMSO) solution and the synthetic larvicide Temephos at 3 A. aegypti larvae, treatments that result in at least 50% mortality within 48 h were selected for subsequent bioassays using different concentrations to determine the concentrations required to kill 10% (LC10), 50% (LC50), and 90% (LC90) of the larvae. Analysis was performed according to the probit method [For t method .Artemia salina toxicity  is largely accepted [Artemia salina Leach nauplii were carried out according to the method described by Bastos and colleagues [Artemia cysts (approximately 1 g·L−1) were added to filtered seawater and maintained at 27–30°C with aeration and under continuous light. Samples that showed ≥30% mortality at 1000 mg·mL−1 in preliminary tests were subjected to quantitative assays. After 24 hours, the nauplii hatched, were collected with a micropipette, and were concentrated in a Petri dish with seawater maintained at the same temperature and luminosity for more than 24 hours. Fifteen grams of each crude extract  was diluted in 5 mL of distilled water. The control solution was prepared with seawater and 0.1% dimethyl sulfoxide (DMSO).accepted  as a parlleagues , with soArtemia nauplii and 50 μL algae extract were placed in each well. Four different concentrations of each extract were tested in six replicates. A control solution was also tested in six replicates. After 24 hours, the number of dead larvae was determined with the aid of a Zoom stereomicroscope. The dead larvae counts also included larvae that remained immobile after stimulation for at least 10 seconds.Ten 50 ≥ 1000 μg·mL−1 to be nontoxic, an LC50 between 500 and 1000 μg·mL−1 to be weakly toxic, and LC50 < 500 μg·mL−1 to be highly toxic. The LC50 values  and their confidence intervals (90% IC and 95% IC) were calculated using probit analysis [The degree of toxicity of each plant extract fraction was determined as recommended by Déciga-Campos et al. . These aanalysis .Biomphalaria glabrata (Say 1818) that were propagated in the laboratory and were descendants of specimens not infected by trematodes.Molluscicidal activity was tested in B. glabrata in an aqueous solution mixed with 0.1% dimethyl sulfoxide (DMSO) containing the extract under investigation at different concentrations (0.10 to 100 μg·mL−1) [Snails were kept in glass tanks at room temperature in a dechlorinated water system for 8 hours with a mixture of soil, sand, and calcium carbonate. During the assay period, they were fed fresh lettuce and fish food. Molluscicidal activity was evaluated by immersing μg·mL−1 for the preliminary tests with the snails. In the preliminary stage, five adult snails were used per concentration. Two sets of controls were used to verify that the snails had normal susceptibility to toxins. The positive control used was niclosamide at 3 μg·mL−1 and the negative control was dechlorinated water. The organisms were exposed to the extracts for 24 hours and observed for 72 hours, with readings and water exchanges every 24 hours. Dead specimens were removed at the time of the readings. The death of the snails was indicated by discoloration, the absence of muscle contractions, bleeding, and the deterioration of body tissues. The algal extract promoted approximately 30% mortality at 100 μg·mL−1. In parallel, control tests were performed with aqueous DMSO solution (0.1%) and the molluscicide niclosamide at 3 μg·mL−1. Probit version 1.5 [90, LC50, and LC10). The World Health Organization (WHO) suggests that crude extracts of plants with LC50 values <40 μg·mL−1  have some potential as molluscicidal or larvicidal compounds [The test solution for each algal extract was prepared at 100 sion 1.5  was usedn = 3). These results were submitted to ANOVA, followed by the Tukey test (P ≤ 0.05). All tests were performed using the Microcal Origin, version 8.0, and Graph Pad Prism, version 5.0.The results shown for the molluscicidal tests represent the average ± standard deviation of three replicates (Ulva lactuca (Chlorophyta), Padina gymnospora, Sargassum vulgare (Phaeophyta), Hypnea musciformis, and Digenea simplex (Rhodophyta)) and the chloroform and hexane fractions of extracts from H. musciformis and P. gymnospora were screened for biological activity. Different concentrations of extracts were tested according to organism susceptibility. The initial concentrations used were 1000 μg·mL−1 for the Artemia salina toxicity test, 500 μg·mL−1 for the Aedes aegypti larvicidal test, and 100 μg·mL−1 for the Biomphalaria glabrata molluscicidal test.The crude dichloromethane, methanol, ethanol, and water extracts from different algal species . Although the mosquito species used in our study was not the same as that used by those authors, both Culex sp. and A. aegypti are vectors of viral diseases, and extracts from H. musciformis showed no lethality against A. aegypti. An analysis of the larvicidal activities of methanol extracts of 20 species of seaweed collected off the coast of India against the second instar larvae of A. aegypti [Lobophora variegata (Phaeophyta-Dictyotaceae) had a relatively high LC50 (70.38 μg·mL−1). In our work, only the hexane and chloroform fractions of P. gymnospora (Phaeophyta) had higher larvicidal potentials .Selvin and Lipton  evaluateH. musciformis and P. gymnospora showed molluscicidal activity against B. glabrata, and their LC50 values were determined to be 11.1460 and 25.8689 μg·mL−1, respectively. The hexane fractions of these two algal species did not show molluscicidal activity sufficient to calculate a lethal concentration  (The LCtoxicity . The resxicities . The chlμg·mL-1) . For theA. salina and found that five brown algae showed values below 1000 μg·mL−1 , Stoechospermum marginatum (612 μg·mL−1), Sargassum swartzii (928 μg·mL−1), and S. binderi (735 μg·mL−1)), whereas only one green alga Caulerpa racemosa (929 μg·mL−1) was toxic. In the same study, these authors found that the hexane fractions of S. marginatum (349 μg·mL−1) and S. swartzii (61 μg·mL−1) were also toxic. In our study, the chloroform and hexane fractions of P. gymnospora  showed low activity, indicating the polar nature of the toxic compounds of this alga.Ara et al.  investigA. salina larvae; the samples included ethanol extracts from red (Rhodophyta), brown (Phaeophyta), and green (Chlorophyta) algae. These authors found that 25 species had significant toxicity, especially Acanthophora spicifera, Galaxaura marginata, Gracilaria dominguensis, Pterocladia capillacea, Padina gymnospora, Ectocarpus breviarticulatus, Chaetomorpha antennina, and Codium decorticatum (50 μg·mL−1). In the present study, the ethanol extract of H. musciformis was not sufficiently lethal to allow the calculation of the LC50, and P. gymnospora was not lethal. Guedes et al. [H. musciformis and P. gymnospora have a selective cytotoxic activity against cancerous cells.Lhuillier et al.  screeneds et al.  found thA. salina, as reported by these authors, is consistent with the findings of this study. These results indicate that these extracts have some potential for the development of products to control vectors of neglected diseases without any important impacts on nontarget organisms, that is, organisms that could be inadvertently affected by toxic substances as a result of sharing an environment or resources with the target species.The generally low toxicity of algal extracts against  Aedes aegypti (based on Aedes aegypti larvae in the fourth instar) and molluscicidal activity against Biomphalaria glabrata (based on the snail). The chloroform fractions of H. musciformis and P. gymnospora might be promising sources of new compounds with molluscicidal activity, and the hexane and chloroform fractions of P. gymnospora could be sources of novel larvicides.The biological activity of two marine algae collected from the coast of Alagoas State showed larvicidal activity againstArtemia nauplii.The primary advantage of using these extracts would be their low cost of production, as the algae from which they were obtained are an abundant resource on the Brazilian coast. These algae are easy to cultivate, and their crude extracts have low off-target toxicity, as demonstrated in the Therefore, we suggest the extension of studies to establish the potential of these extracts for use in natural environments, considering the potential low impact on nontarget organisms.


Introduction. It is a consensus that the postoperative cognitive function is impaired in elderly patients after general anaesthesia, and such category patient takes more time to recover. Xenon is a noble gas with anesthetic properties mediated by antagonism of N-methyl-D-aspartate receptors. With a minimum alveolar concentration of 0.63, xenon is intended for maintaining hypnosis with 30% oxygen. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario. Case Presentation. We report the case of 99-year-old woman who underwent sigmoid colon carcinoma resection with colorectal anastomosis. We carried out the induction phase by propofol, oxygen, fentanil, and rocuronium bromide, and then we proceeded to a rapid sequence endotracheal intubation consequently. The patient was monitored by IBP, NIBP, ECG, cardiac frequency, respiratory rate, capnometry, TOF Guard, blood gas analysis, and BIS. For maintenance we administrated oxygen, remifentanil, rocuronium bromide, and xenon gas 60–65%. Shortly after the end of surgery the patients started an autonomous respiratory activity, and a high BIS level was also recorded. Decision was made by our team to proceed into the emergence phase. The residual neuromuscular block was antagonized by sugammadex, modified Aldrete score was implicated, and we got our patient fully awake without any cognitive dysfunction or delirium. Conclusion. The rapid emergence to full orientation in very elderly patient who had been anesthetized by xenon shows concordance to the high BIS values and the clinical signs of the depth of anesthesia. Aging is an irreversible and progressive physiological phenomena characterized by degenerative changes in the structure and functional reserve of organs and tissues . AdvanceElderly patients (arbitrarily defined as being over 65 years of age) are vulnerable to the adverse effects of anesthesia because of their reduced margin of safety. Morbidity and mortality increase with advancing age, with a steep increase after the age of 75 years . The freElderly patients often take more time to recover completely from the central nervous system effects of general anesthesia, particularly if they were confused or disoriented preoperatively.Over the last decade there has been renewed interest in the use of xenon as an anaesthetic, and xenon has been licensed as an anesthetic in Europe since 2005. Xenon potently inhibits N-methyl-D-aspartate (NMDA) noncompetitively, with little effect on GABAA receptors or non-NMDA glutamatergic receptors.The main beneficial features of xenon anesthesia are fast induction and emergence because of low solubility in blood and tissues, along with remarkably stable hemodynamics even in patients with impaired cardiac function.Xenon has proven to be a safe and well-tolerated anesthetic in clinical trials , 5.In comparison with nitrous oxide, Goto and colleagues found that emergence from xenon anesthesia is 2 or 3 times faster than that from comparable MACs of nitrous oxide/isoflurane and nitrous oxide/sevoflurane anesthesia. Furthermore, xenon compares favorably with other anesthetic agents .A 99-year-old female  was admitted to our hospital and underwent major abdominal surgery  under general anesthesia, and the surgery duration was about 220 minutes. Her medical history revealed mild degree heart failure, chronic normocytic anemia, gastritis, and allergy for NSAIDs and penicillin antibiotics.−1, hematocrit 30.9%, leukocytes 11,500 mm−3 without deviation, platelets 453,000 mm−3, sodium 131 mg·dL−1, potassium 4 mg·dL−1, magnesium 0.58 mg·dL−1, creatinine 0.5 mg·dL−1, and total calcium 8.24 mg·dL−1.Her preoperative laboratory tests: hemoglobin 8.8 mg·dLIn the preoperative room we prepared our patient by antibiotics prophylaxis: ciprofloxacin 2 gm; metronidazole 500 mg and an antiemetic agent; ondansetron 4 mg.Our patient was monitored by pulse oximetry, expiratory capnography, invasive and noninvasive blood pressure, electrocardiogram, bispectral index (BIS), neuromuscular transmission (TOF Guard), and diuresis.A peripheral venous access (20 G) was established in upper right limb, and also a central venous access was done immediately after the induction phase as it was needed for postoperative chemotherapy afterwards.We induced our anesthesia by oxygen, propofol 50 mg, fentanil 100 mcg, and rocuronium bromide 30 mg, and then we proceeded to a rapid sequence endotracheal intubation (tube diameter was 6.5 mm),2 35–40%, the fluid replacement was calculated depending on her diuresis, plasma fluid, intraoperative blood loss, and anemia, and she was refunded by ringer lactate 1500 mL, Nacl 0.9% 1000 mL, fresh plasma fluids 1000 mL, and packed red cells 500 mL.The maintenance of the anesthesia was achieved by continuous infusion of remifentanil in a dose of 0.2 mcg/kg/min, rocuronium bromide 10 mg, xenon 60–65%, and O2O, respiratory frequency 12 incursions per minute, PEEP 5 cm H2O, FiO2 35–40%, and inspiratory/expiratory time ratio 1 : 2, and the exhaled tidal volume was around 380 mL.”A closed-circuit anesthesia machine  was used for xenon gas delivery. The ventilation parameters were the following: “pressure-cycled mechanical ventilation with inhalation pressure indexes of 19 cm HBlood gas analysis was performed twice: 30 minutes after the start and 30 minutes before the end of surgery.++ gluconate in dose of 1 g·10 m−1 , and she was transferred to ICU for close monitoring. In our case we got surprised for the rapid emergence of our patient; this corresponds with the low blood gas partition coefficient of xenon 0.115). We also concluded that the BIS values show sufficient concordance with clinical signs of anesthetic depth and the emergence to full orientation in very elderly patient who had been anesthetized by xenon, and consequently we encourage more studies concerning the use of xenon in general surgery with such category of patients –11. 5. We als


Application of assisted reproductive technologies in buffaloes is limited to some extent by farmers’ inability to detect oestrus because of its poor expression. The present study aimed at investigating reliability of a milk progesterone enzyme-linked immunosorbent assay (ELISA) to assess the ovarian cyclicity during post partum, oestrus and post-breeding periods in water buffaloes.Progesterone concentrations were measured by an ELISA in milk of 23 postpartum buffaloes in relation to oestrus, pregnancy, body condition score (BCS) and milk production. Two milk samples were taken at 10 days intervals, every month starting from day 30 and continued to day 150 post partum. BCS and milk production were recorded during sample collection. Milk samples from bred buffaloes were collected at Day 0 (day of breeding), Days 10–12 and Days 22–24. Defatted milk was preserved at −80°C until analysis. Pregnancy was confirmed by palpation per rectum on Days 70–90.P < 0.05). Buffaloes with a superior BCS had a shorter calving to oestrus interval and produced more milk (P < 0.05).Seventeen buffaloes had 47 ovulatory cycles, one to four in each, 13 were detected in oestrus once (28 % oestrus detection rate). Progesterone concentration ≥1 ng/ml in one of the two 10-day-interval milk samples reflected ovulation and corpus luteum formation. The intervals between calving to first luteal activity and to first detected oestrus varied from 41 to 123 days (n = 17) and 83 to 135 (n = 13) days, respectively. Eight buffaloes were bred in the course of the study and seven were found pregnant. These buffaloes had a progesterone profile of low (<1 ng/ml), high (≥ 1 ng/ml) and high (≥ 1 ng/ml) on Day 0, Days 10–12 and Days 22–24, respectively. Buffaloes cycling later in the postpartum period had fewer missed oestruses (Milk progesterone ELISA is a reliable tool for monitoring ovarian cyclicity and good BCS may be an indicator of resuming cyclicity in water buffalo. Shah et al. reportedet al.[Milk progesterone concentration is a good predictor to determine the functional status of the corpus luteum and ovarian activity in domesticated ruminants . Presiccet al. used plaet al.. Milk iset al.,6. Rectaet al.; findinget al.. UltrasoBCS is a useful indicator of nutritional status and good BCS reflecting positive energy balance leads to earlier resumption of postpartum ovarian cyclicity in cows ,10. TherThe present study aimed at investigating the ovarian cyclicity using milk progesterone ELISA in water buffaloes during the postpartum, oestrus and post mating periods and to relate progesterone levels with BCS, milk production and pregnancy diagnosis by palpation per rectum.Twenty three buffaloes from 23 farms located in six villages of the Mymensingh District, Bangladesh were selected. The study was conducted during the period from June 2006 to March 2007. Each family owned 1 or 2 buffalo cows of the indigenous river type. The age ranged from 4 to 15 years and parity ranged between 0 and 7. The buffaloes were fed on rice straw, cut-and-carry grasses and 0.5 to 1.5 kg milling by-product as concentrate (rice polish and/or mustered oil cake) with limited grazing on roadside and community land. Buffaloes were selected on the basis of similar feeding and management pattern. The animals were monitored regularly to ensure that they were not stressed thus limiting variation of circulating hormone levels .Buffaloes were registered two months before parturition and age, breed, parity, and feeding management information was recorded. Body condition of the buffaloes was scored by using a 1–5 scale (1 = thin and 5 = obese) ,13. Photviz. restlessness, bellowing, vulval swelling, mucous discharge, frequent voiding of small quantities of urine. At every farm visit for milk sampling, the milk production and signs of previous oestrus, i.e. dry or fresh vaginal discharge adhered to the perineum or tail, were recorded. Once detected in heat, the animals were bred by natural mating. Thereafter three additional milk samples were collected. The first one was on Day 0 (day of breeding) while the second and third samples were collected on Days 10–12 and Days 22–24, respectively. Whole milk samples were stored at 4°C for up to two days. The samples were defatted by centrifugation at 1500 g for 30 min at 4°C, the fat-free milk portions were collected and preserved at −80°C until analysed by ELISA.Milk samples were collected directly from the teats of individual buffaloes at the middle of morning milking into a screw-capped plastic tube containing 2-bromo-2-nitro-1, 3-propanediol . Milk sampling was started 30 days post partum and two samples at 10 days interval were collected per month up to 150 days post partum if oestrus was not detected. Farmers were asked, if they saw any signs of oestrus Two-litre fresh milk from a buffalo cow in oestrus was collected and defatted. Activated charcoal  was added (0.25 % w/v) and the milk was stirred one hour at room temperature (around 22°C) and then preserved overnight at 4°C. The charcoal-added milk was centrifuged for 15 min at 1500 g at 4°C, the supernatant was collected and the residual charcoal was filtered by filter paper. Repeated centrifugation and filtration were performed to remove charcoal completely. Then Bronopol was added as a preservative (8 mg/40 ml of milk). Standard solutions of defatted milk containing 100, 10, 5, 2.5, 1.25, 0.63, 0.31 and 0.16 ng/ml progesterone were prepared by using commercially available progesterone . This procedure was done immediately before adding samples and standards in the microtitre plate.et al.[Milk progesterone concentration was determined through a competitive ELISA following the protocol proposed by Rasmussen et al. with minet al.. The intThe genital organs of buffaloes were examined per rectum for pregnancy diagnosis between Day 70 and Day 90 after natural mating.The data on milk progesterone concentration, milk production and BCS against months and days of sampling were presented graphically by using Microsoft Excel. Graphs were prepared with data on milk progesterone concentration, milk production and BCS against months and days of sampling. A progesterone concentration of ≥1.0 ng/ml of skim milk was referred to as a progesterone rise, due to a functional corpus luteum ,16-19. WIntervals between calving and first detected oestrus, calving and first detected progesterone peak (an indicator of earlier ovulation) and calving and conception were calculated. Percentages of buffaloes not detected in oestrus and non-cyclic buffaloes during the study period were calculated. Regression analysis was performed to determine the relationship of BCS at calving and oestrus with the calving to first oestrus interval and with milk production .P < 0.001) linear relationship existed between the post partum BCS and milk yield  and 83 to 135 (n = 13) days, respectively.P < 0.05) higher than those of Day 71–90 (1.33) and Day 91–130 (0.65) postpartum buffaloes. When farmers missed more oestrous cycles, the length of post partum period  increased  was significantly (P < 0.05). However, the BCS scored during the gestation period and at calving did not show any significant effect on the intervals between calving to first rise of milk progesterone and between calving and first detected oestrus.Buffaloes with higher BCS at the time of oestrus detection had shorter interval between calving and first detected oestrus than those with lower BCS  higher than that at Days 10-12 ( 2.0 ± 0.4 ng/ml).Only 8 buffaloes were bred during the study period. Seven buffaloes had a progesterone profile being low (<1 ng/ml), high (≥1 ng/ml) and high (≥1 ng/ml) on Day 0, Days 10–12 and Days 22–24, respectively. These buffaloes were found pregnant on rectal palpation of the genital tract between Day 70 and Day 90. The buffalo with progesterone profiles being low, high and low on Day 0, Days 10–12 and Days 22-24, respectively, returned to oestrus. In pregnant buffaloes, the milk progesterone concentrations (mean ± SEM ) at Days 22–24 (4.8 ± 0.4 ng/ml) were significantly  of buffaloes that had resumed their ovarian cyclicity by Day 150 post partum but the farmers’ oestrus detection rate was low under the assumption that the observed progesterone rise in milk followed an ovulation and a normal cycle. In accordance with these findings, Barkawi et al. showed tet al.-26. Howel.[et al. found thl.[et al..et al.[A poor BCS may have a negative impact on ovarian activity in buffaloes as anoestral buffaloes have lower BCS than buffaloes having oestral cycles . Our stuet al. reportedet al.,33.vs. >1 ng/ml). Similarly, in a study of 17 complete post partum periods in Murrah buffaloes in Sri Lanka, plasma progesterone concentrations remained low (<0.25 ng/ml) for a period ranging from 92 to 210 days [et al.[Anoestral buffaloes had a milk progesterone concentration consistently lower than cyclic buffaloes  helped us making a clear distinction between pregnant and non-pregnant buffaloes and identification of ovarian cyclicity. One non-pregnant buffalo had a progesterone profile of low, high and low on Day 0, Day 12 and Day 22, respectively. Uçar et al. reportedl.[et al. showing l.[et al. who detel.[et al.. In factl.[et al.. In our l.[et al.,17. Thesl.[et al.,39.ELISA was a reliable tool to determine progesterone concentration in milk when investigating post partum ovarian cyclicity in water buffaloes. Oestrus detection needs significant improvement by training farmers to recognise secondary oestus signs and by measuring the progesterone concentration in two samples at 10 days interval if the buffalo cow is not in oestrus at 60 days post partum. This might help the farmers to bred buffaloes in the early post partum period. The nutritional condition throughout the post partum period was important for earlier onset of post partum oestrus in buffaloes.BCS, Body condition score; EDR, Oestrus detection rate; ELISA, Enzyme linked immunosorbent assay; HRP, Horseradish peroxidase; OD, Optical density; SEM, Standard error mean.We have no competing interests to declare in relation to this manuscript.TAB, MS and JB participated in the study design and coordination. TAB, MS, JB and MFI assisted with sample collection and analysis, completed the statistical analysis and drafted the manuscript. SIK participated in ELISA design and analysis. JUA participated in manuscript preparation and revision. All authors read and approved the final manuscript


Pteleopsis hylodendron (Combretaceae) is used in Cameroon and West Africa folk medicine for the treatment of various microbial infections . The antibacterial properties of the methanolic extract and fractions from stem bark of Pteleopsis hylodendron were tested against three Gram-positive bacteria and eight Gram-negative bacteria using Agar-well diffusion and Broth microdilution methods. Antioxidant activities of the crude extract and fractions were investigated by DPPH radical scavenging activity and β-carotene-linoleic acid assays. The methanolic extract and some fractions exhibited antibacterial activities that varied between the bacterial species . The activity of the crude extract is, however, very weak compared to the reference antibiotics (MIC = 0.125–128 μg/mL). Two fractions (FE and FF) showed significant activity (MIC = 0.97 μg/mL) while S. aureus ATCC 25922 was almost resistant to all the tested fractions. In addition, the crude extract and some fractions showed good antioxidant potential with inhibition values ranging from 17.53 to 98.79%. These results provide promising baseline information for the potential use of this plant as well as some of the fractions in the treatment of infectious diseases and oxidative stress. Since the successive introduction of various antibiotics into therapeutics, the sensitivity of pathogenic microorganisms changed a lot so that the proportion of antibiotically resistant strains is currently important , what inPteleopsis hylodendron Mildbr. belongs to the family Combretaceae commonly found in the forest regions of West and Central Africa. The genus Pteleopsis is represented in Africa by ten species but only P. hylodendron is found in Cameroon [P. hylodendron is used to treat measles, chickenpox, sexually transmitted diseases, GE, female sterility, liver and kidney disorders, as well as dropsy [Pteleopsis hylodendron and report here the antibacterial activity on pathogenic bacteria of the gastro-intestinal tract and antioxidant activity of the crude extract and fractions.Cameroon . The aqus dropsy . Phytochs dropsy , 10. In P. hylodendron was collected in February 2009 at Mbeyengue I, Centre region of Cameroon. Identification was done at the National Herbarium in Yaoundé, Cameroon, where a voucher specimen (No 1309/SFRK) has been deposited.The stem bark of + bacteria  and eight Gram− bacteria . The bacterial isolates were obtained from Centre Pasteur of Yaoundé, Cameroon, while the reference strains were obtained from American Type Culture Collection (ATCC). The bacterial strains and isolates were grown at 35°C and maintained on nutrient agar. The bacterial cell suspension was prepared at 1.5 × 108 colony forming units per mL (CFU/mL) following the McFarland 0.5 turbidity standard.Five bacterial strains and six isolates known to be pathogenic of the gastro-intestinal tract were used in this work. These included three GramPteleopsis hylodendron (2.5 kg) was extracted with MeOH  at room temperature to obtain a crude extract (590 g) after evaporation under vacuum. A portion of this extract (100 g) was subjected to silica gel column chromatography (Ø8 cm × L30 cm) eluted successively with pure hexane, hexane-EtOAc (90 : 10–30 : 70), pure EtOAc, EtOAc-MeOH (95 : 5–80 : 20) and pure MeOH. Forty-six fractions of 500 mL each were collected and combined based on their TLC profile into ten major fractions A–J .The air-dried and powdered stem bark of μL) was homogeneously seeded onto Petri dishes containing sterile molten MHA (20 mL). The sterile 6 mm diameter wells were impregnated (50 μL) with different concentrations of plant extract . The dishes were kept for 1 h at room temperature for the diffusion of the extract. Subsequently, dishes were incubated at 35°C for 24 h. Antibiotics  were used as positive control (10 μg–200 μg/mL) and 10% aqueous DMSO was used as negative control. Results were evaluated by measuring the inhibition zones around each well. The assay was done in triplicate and the mean diameters recorded as inhibition zones. We considered that an extract is active when ID was up to 20 mm, and then the strain is known as sensitive; moderately active when ID was between 10 and 20 mm, and then the strain is known as moderate; little or not active when ID was between 0 and 10 mm, and then the strain is known as little sensitive or resistant [Diameters of inhibition zones (ID) were determined using Mueller Hinton Agar (MHA) by the well diffusion method . The bacesistant , 13.μg/mL and 500–0.242 μg/mL). A negative control  and positive control  were included. Each well of 96-well sterile microtitre plate received 100 μL of MHB, 100 μL of test substances and 100 μL of the bacterial inoculum (1.5 × 108 CFU/mL). The plates were covered and incubated at 35°C for 24 h. As an indicator of bacterial growth, 50 μL p-iodonitrotetrazolium violet (INT) dissolved in water was added to the wells and incubated at 35°C for 30 min. MIC values are recorded as the lowest concentration of the substance that completely inhibited bacterial growth that is, the solution in the well remained clear after incubation with INT. Minimum bactericidal concentrations (MBCs) were determined by plating 10 μL from each negative well and from the positive growth control on Mueller Hinton Agar. MBCs were defined as the lowest concentration yielding negative subcultures. The experiments were performed in triplicate. Amoxicillin, ciprofloxacin and gentamicin at the concentration ranging between 128 and 0.062 μg/mL served as positive control.Minimum inhibitory concentrations (MICs) were determined using Mueller Hinton Broth (MHB) by microdilution method . A two-fμg/mL) was mixed with a 0.3 mM DPPH methanol solution and kept for 30 min at room temperature. The decrease in the solution absorbance, due to proton donating of substances was measured at 517 nm. L-Ascorbic acid was used as positive control. The percentage of DPPH radical scavenging activity was calculated using the following formula: The free radical scavenging activity of the extract and fractions on the stable radical DPPH were estimated by the method of Mensor et al. . 1.5 mL β-carotene-linoleic acid mixture was prepared as follows: 1.5 mg β-carotene was dissolved in 3 mL of chloroform, and 75 μL linoleic acid and 600 mg tween 40 were added. Chloroform was completely evaporated using a vacuum evaporator. Then 150 mL distilled water saturated with oxygen was added with a vigorous shaking. 1340 μL of this reaction mixture was dispersed to test tubes and 160 μL extract (20 mg/mL) were added, and emulsion system was incubated at 55°C for 105 min. Same procedure was repeated with L-Ascorbic acid used as a standard control and a blank. After this incubation period absorbance of the mixtures were measured at 492 nm. Antioxidative capacity of the extract was compared with those of ascorbic acid and blank.In this assay antioxidant capacity is determined by measuring the inhibition of the volatile organic compounds and the conjugated diene hydroperoxides arising from linoleic acid oxidation . A stockChemical tests were carried out on the methanolic extract and fractions using standard procedures to identify the constituents  as described by Brunetton .P < .05.Data were expressed as mean ± standard deviation. Statistical analysis was carried out using the Waller-Duncan's test. The 12.0 SPSS Windows software was used for this analysis. Differences were considered significant at P. hylodendron was 15.96%. FI (43.08%) and FJ (24.54%) were the most abundant.The % yield of methanolic extract of A, all other substances contained at least one chemical group. Alkaloids, anthocyanins, anthraquinones, flavonoids, glycosides, phenols, polyphenols, saponins, and tannins were present in crude extract while coumarins, sterols, and triterpenes were absent. FB, FC, and FD had a similar chemical composition . It is the same for FG and FH ; FI and FJ .Phytochemical screening revealed the presence of medicinally active constituents. The differences in the composition between crude extract and fractions and between fractions were noted. Except F−, and 10.87–25.00 mm for the Gram+. S. aureus was the most sensitive (ID = 20.00–25.00 mm) while S. aureus ATCC 25922 and E. coli ATCC 11775 were the least sensitive (ID = 11.00–15.00 mm and 10.00–14.75 mm resp.). No activity was recorded at 2.5 mg against P. aeruginosa ATCC 27853. However these values are weak compared with those of the reference antibiotics (ID = 12–40 mm).The results of the antibacterial activity by the Agar-well diffusion method are presented in In view of the results obtained by diffusion method, MIC and MBC values of the crude extract and fractions were established and the results are shown in Tables μg/mL for all the bacteria, isolates, and Gram−; 781–3125 μg/mL for the strains and Gram+. S. paratyphi A was the least sensitive (MIC = 12500 μg/mL). P. aeruginosa ATCC 27853, P. mirabilis and S. aureus were the most sensitive (MIC = 781 μg/mL). The important activity on S. aureus confirms the best activity obtained in solid medium; which revealed this germ as one of the most susceptible. Antibiotics exerted a higher inhibitory effect on bacterial (MIC = 0.125–128 μg/mL) than the methanolic extract.All the bacteria tested were inhibited by the methanolic extract  with MICA, FB, FC and FD on all the bacteria tested , MIC was 0.97 μg/mL, making the substances more active than reference antibiotics. FG had a fairly good activity (MIC = 0.24 μg/mL) on some bacteria  whereas FH, FI and FJ were slightly active (MIC = 125–1000 μg/mL). S. aureus ATCC 25922 was almost resistant to all the fractions (MIC > 1000 μg/mL). The MBC/MIC ratio activity for all the bacteria tested varied between one (1) and eight (8) for the crude extract and between one (1) and twenty (20) for the fractions. According to Marmonier [P. hylodendron were bactericidal on at least 63% and 27% of the bacteria respectively.The fractionation of the methanolic extract showed an inactivity of Fa tested . On the armonier , plant eβ-carotene-linoleic acid assays. The results are presented in Tables μg/mL the methanolic extract, FE, FF, FG, FH, FI and FJ showed a similar activity to that one of L-ascorbic acid. FH  was the most antioxidant fraction (94.05–98.79%) while FA  was the least antioxidant (1.86–21.26%).The antioxidant activity of the methanolic extract and fractions was assessed by the DPPH and P. hylodendron revealed the presence alkaloids, anthocyanins, anthraquinones, flavonoids, glycosides, phenols, polyphenols, saponins and tannins. Other investigators [P. hylodendron collected from East region of Cameroon revealed the presence of triterpenes which were absent in our sample. This difference can be attributed to the difference in the geographical region, soil composition, and age of the plant [Phytochemical screening of the methanolic extract and fractions of tigators , 20 havetigators  and Attatigators  working he plant .Pteleopsis species were reported [P. hylodendron showed variable antibacterial activities dose-dependant on the eleven bacterial strains and isolates tested. These broad spectra of action could be related to their chemical components [S. aureus is the most sensitive. It was reported [S. aureus is one of the most susceptible bacteria to the plant extracts. These values also showed that the Gram− and Gram+ bacteria had a comparable susceptibility. This may suggest that the mode of action of the extract was not related to the cell wall composition.  S. aureus ATCC 25922 which was inhibited completely by the methanolic extract at 3125 μg/mL, was almost resistant to all the fractions. This may suggest that this microbe required high concentrations of the substance tested and synergic effect of chemical compounds as extract. FA, FB, FC, and FD containing only alkaloids did not show any inhibitory effect on the bacteria tested. This may suggest these compounds which also present in the methanolic extract do not have a detectable antibacterial activity. However, alkaloids were reported to possess antibacterial activities [E and FF, most active had a comparable chemical composition that FG. Differences in activity between these fractions could be related to the absence of anthocyanins in FF and anthraquinones in FE. Generally, it is difficult at the sight of results of the phytochemical screening to attribute the activities recorded to a chemical compounds group. The antimicrobial activities of reported , 23. Genmponents . Among tmponents . Due to mponents . Howevermponents . Moreovemponents . MIC valreported  that S. tivities . FE and As L-ascorbic acid, the methanolic extract and some fractions showed great antioxidant potentials. This particularly high activity could be attributed to the presence of phenolic compounds . The antE and FF by their high antibacterial activity could be the base of development of new antibacterial agents with broad spectra. Their purification and pharmacological and toxicity studies are essential.These results provide promising baseline information for the potential use of this plant as well as some of the fractions in the treatment of GE and oxidative stress. F


Rationale: In clinical trials, homogeneous emphysema patients have responded well to upper lobe volume reduction but not lower lobe volume reduction. Materials/Methods: To understand the physiological basis for this observation, a computer model was developed to simulate the effects of upper and lower lobe lung volume reduction on RV/TLC and lung recoil in homogeneous emphysema. Results: Patients with homogeneous emphysema received either upper or lower lobe volume reduction therapy based on findings of radionucleotide scintigraphy scanning. CT analysis of lobar volumes showed that patients undergoing upper  and lower lobe treatment  experienced similar reductions in lung volume. However, only upper lobe treatment (ULT) improved FEV1 (+11.1 ± 14.7 versus −4.4 ± 15.8%) and RV/TLC (−5.4 ± 8.1 versus −2.4 ± 8.6%). Model simulations provided an unexpected explanation for this response. Increases in transpulmonary pressure subsequent to volume reduction increased RV/TLC in upper lobe alveoli, while caudal shifts in airway closure decreased RV/TLC in lower lobe alveoli. ULT, which eliminates apical alveoli with high RV/TLC values, lowers the average RV/TLC of the lung. Conversely, LLT, which eliminates caudal alveoli with low RV/TLC values, has less effect. Conclusion: LLT in homogeneous emphysema is uniformly less effective than ULT. Three month follow-up data, including physiology and CT imaging, is available for 29 patients, 18 in the ULT group and 11 in the LLT group.Ten patients with advanced homogeneous emphysema were included in study NCT011811466, which was initiated following completion and analysis of data from study NCT01051258. All patients in this second study received ULT at four subsegments, two in each upper lobe. Three month follow-up data including physiology and CT imaging is available for nine patients.Screening evaluations in both studies included pulmonary function tests , functional and quality of life assessments, chest CT scan performed at full inspiration, and quantitative scintigraphy perfusion scanning.CT images were generated using a standardized acquisition/reconstruction algorithm . Computer analysis of baseline and post treatment images was performed using commercially available software  to confirm homogeneous emphysema among study patients, and to measure lobar volume reduction in response to ELS treatment at 3 month follow-up. Disease heterogeneity was evaluated quantitatively, and expressed as a Heterogeneity Index (HI), defined as the ratio of % of voxels with a density <−910 HU in the upper lobes (right upper + left upper) to that in the lower lobes (right lower + left lower). Patients were designated as having homogeneous disease if their HI was between 0.85 and 1.15. ELS treatment sites were chosen based upon quantitative scintigraphy perfusion scanning, targeting regions with low perfusion.Baseline and 3 month follow-up physiology and radiology results were used to assess disease distribution, lobar volume reduction, and corresponding physiological responses to treatment.A computer model was developed to simulate the effects of targeted volume reduction on gas trapping. The model can be used to examine physiological response patterns in either heterogeneous or homogeneous disease but was used solely for simulating homogeneous physiology in this analysis.n) and size were independent simulation parameters. Each alveolus was modeled as having a constitutive pressure-volume relationship of the form V = Vmax−−kPtp(z)Ae, where V equals alveolar volume, Ptp(z) transpulmonary pressure as a function of cranio-caudal location (z), A = Vmax−Vmin, Vmax equals alveolar volume at “infinite” inflation pressure, Vmin alveolar volume at 0 inflation pressure, and k the “shape factor” that determines the curvature of the exponential relationship between pressure and volume  from the lung apex, and is equal to Ptp(0)−ρlung(z) × g, where Ptp(0) equals Ptp at the apex, lung tissue density (ρlung) is set equal to 25% of water density, and g is gravitational acceleration. Calculations were performed in Microsoft Excel® to predict: (1) alveolar volumes at full inflation  and full deflation  as a function of cranio-caudal position within the lung; (2) regional alveolar RV/TLC ratios; and (3) overall RV, TLC, and RV/TLC values for the entire lung by integrating results across all alveoli.The lung was modeled as a collection of discrete alveoli arranged in layers from diaphragm to apex. The healthy lung was considered to have 300 million alveoli. Alveolar number (n), increasing the size of alveoli , increasing alveolar gas trapping , increasing k (to simulate iso-volume loss of recoil), and increasing Ptm′ (to simulate premature airway closure and gas trapping due to loss of airway tethering). For the current simulations of homogeneous emphysema, Ptm′ was considered invariant as a function of distance from the lung apex , while Pz)tp at which airway closure occurs. For alveoli located above this point, volume is determined by the equation, V = Vmax−−kPtp(z)Ae, and those alveoli nearer the lung apex are more inflated than alveoli nearer the diaphragm. Below the point at which Ptp = Ptm′, alveolar volumes are considered invariant with position (z), and are set equal to the amount of trapped gas at airway closure.Emphysema was modeled by reducing the total number of alveoli  increasing transpulmonary pressure [Ptp(z)] in proportion to the extent of volume reduction. Regional and global RV, TLC, and RV/TLC predicted by the model were then reassessed without changing model parameters of unaffected alveoli.The effects of ELS volume reduction therapy were simulated by: (1) reducing the number of alveoli at specific target sites  to reflect elimination of alveolar units; (2) decreasing t test. Comparisons across 3 or more subgroups were performed by one way analysis of variance. Assessment of statistical differences in categorical outcome measures between groups was assessed by Chi squared testing or Fisher’s exact test. Correlations were performed using the method of Pearson. Statistical significance was based on P values subject to correction for multiple comparisons using the method of Bonferroni.Spirometry and lung volume measurements of participants in studies NCT01051258, and NCT01181466 at baseline and following treatment are presented as mean ± standard deviation. The effect of ELS treatment is summarized as absolute and percentage change from baseline. Statistical significance of changes from baseline for continuous measures was assessed by paired n = 30) and NCT01181466 (n = 10). Complete follow-up results are available for 38. Baseline characteristics, including demographics, smoking history, body mass index (BMI), GOLD classification, and medication use are summarized in Table A total of 40 patients with homogeneous emphysema were enrolled in studies NCT01051258  and anticholinergic agent therapy , 29 were using inhaled corticosteroids, 9 theophylline preparations, 5 oral corticosteroids, and 7 mucolytic agents. Seventeen patients were receiving domiciliary oxygen therapy.n = 38), and for each subgroup is summarized in Table Baseline pulmonary function for the entire group (p = 0.445).CT analysis confirmed the presence of homogeneous emphysema among study patients. The HI for the 38 patients in this analysis was . HI values for ULT patients in study NCT01051258 , LLT patients in study NCT01051258 , and patients in study NCT01181466  were not significantly different .Quantitative CT analysis showed that LLT was associated with a −217 ± 125 mL/treatment lobar volume reduction, and a corresponding 35 ± 32 mL/treatment increase in upper lobe volume. The net volume reduction following LLT measured by CT analysis was −182 ± 121 mL/treatment. ULT was associated with a −265 ± 164 mL/treatment lobar volume reduction, and corresponding 65 ± 17 mL/treatment increase in lower lobe volume. The net volume reduction following ULT measured by CT analysis was −201 ± 166 mL/treatment , FVC , and RV/TLC ratio . Patients who underwent ULT  experienced significant improvements compared to baseline, while patients who underwent LLT did not, despite equivalent lobar volume reduction. Reductions in overall gas trapping, measured physiologically as change from baseline in RV/TLC, were greater for ULT (ΔRV/TLC = −5.4 ± 8.1%) than LLT (ΔRV/TLC = −2.4 ± 8.6%) patients. Fourteen of 18 (78%) patients receiving ULT experienced reductions in RV/TLC while only 4 of 11 (36%) LLT patients experienced reductions .The effects of ELS treatment on pulmonary function in patients with advanced homogeneous emphysema are summarized in Table r = 0.54; p = 0.02), but not in LLT patients , indicating that ULT volume reduction was effective in reducing gas trapping, while LLT volume reduction was not.Change from baseline in RV/TLC at 3 month follow-up correlated significantly with the magnitude of lobar volume reduction assessed by CT imaging in ULT patients  received ULT. Results from this second study confirm the effectiveness of upper lobe ELS treatment in homogeneous emphysema. Bilateral 4-site therapy at 3 month follow-up was associated with improvements in spirometry and overall gas trapping , Vmax , Vmin , k (0.2), and Ptm′ (0 cm H2O), model simulations to predict RV/TLC values for alveoli as a function of vertical distance from the lung apex were performed. Values were consistent with data reported by Milic–Emili in healthy young males . The remaining model parameters  were also varied to simulate the effect of worsening emphysema. Moderate to severe tissue destruction was represented by an increase in Vmin/Vmax from 0.25 to 0.50. Loss in tissue elasticity was represented by an increase in k from 0.2 to 0.3. An increase in airway closing pressure due to loss of airway tethering was represented by an increase in Ptm′ from 0 to 1 cm H2O. Assuming a normal active chest wall compliance curve (red dashed line), the model predicts that these changes would cause marked hyperinflation, gas trapping, and a decrease in lung elastic recoil pressure as shown in Figure Simulations depicting advanced homogeneous emphysema are shown in Figures 2O, a shift in Ptm′ from 1.0 to 0.5 cm H2O, and a decrease in cranio-caudal distance from apex to diaphragmatic dome from 35 to 33 cm while keeping k constant at 0.3 is predicted to have the following physiological impact:Using this model simulation of advanced homogeneous emphysema as a starting point, additional simulations were then performed to evaluate the physiological impact of upper lobe volume reduction and lower lobe volume reduction Figure . The comPtp from 12.5 to 14 cm H2O (labeled “A”);increase RV/TLC for all alveoli remaining in the upper lung fields due to the distending effects of increasing Ptm′ to a lower value (labeled “B”);decreasing RV/TLC values of alveoli in the lower lung fields due to the combined effects of gravity and a shift in causing a caudal shift in the location at which airway closure occurs (labeled “C”).Ptm′ in the gravitation field resulting from volume reduction are predicted to affect gas tapping  of any single alveolus as a function of its anatomic location. It does not, however, reflect how treatment would affect overall gas trapping (RV/TLC) or lung recoil, or how ULT versus LLT would differentially affect lung function. This requires combining the impact of changes in transpulmonary pressure and Ptm′ with the effect of changing alveolar numbers regionally as a result of volume reduction. The effect of volume reduction treatment, in which either 25% of upper lobe alveoli or the equivalent number (20%) of lower lobe alveoli are removed, is shown in Figure The solid red line in Figure Conceptually, lung volume reduction therapy (LVRT) is a straightforward procedure that involves reducing the quantity of hyperinflated lung by eliminating damaged tissue. A simple but elegant physiological model to explain the effects of LVRT on airflow limitation in advanced emphysema was proposed over a decade ago by Fessler and Permutt . This moThe present study presents a novel perspective about the relative effects of upper versus lower lobe lung volume reduction on gas trapping in emphysema. While consistent with the Fessler–Permutt model, this analysis shows that gravitational effects can significantly affect physiological responses to volume reduction by attenuating the impact of LLT. Empirical observations from clinical trial NCT01051258 involving endoscopic ELS treatment in patients with homogeneous emphysema show that only patients treated in the upper lobes consistently experienced physiological benefit. This observation was then prospectively validated in a second study (NCT01181466) in which all patients received ULT. Although the number of patients in both studies was small, the results were highly consistent.1 measured by spirometry, was substantially different following ULT and LLT, however. Computer modeling indicates this is due to two factors not previously recognized as important when considering volume reduction therapy in this population: (1) lung volume reduction, independent of where it is performed, increases the RV/TLC ratio of alveoli in the upper lobes, but decreases RV/TLC ratio of alveoli in the lower lobes as shown in Figure Differences in physiology between ULT and LLT patients following ELS were not due to treatment failure in the LLT cohort. Lobar volume reduction assessed by quantitative CT analysis was similar in the two groups. The impact of ELS on gas trapping assessed as change in RV/TLC measured by plethysmography, and as change in FEVPtm′ and Ptp. Modeling indicates, however, that ULT will always be more effective than LLT in reducing RV/TLC in patients with homogenous emphysema. Figure The differential effect of ULT versus LLT will vary depending upon the baseline severity of gas trapping, the extent of the volume reduction, and the effects of treatment on While these same physiological principles apply when considering LLT in patients with heterogeneous emphysema, the effects of treatment can be quite different (McKenna et al., Ptp and Ptm′ resulting from volume reduction therapy increase RV/TLC of upper lobe alveoli, while lowering RV/TLC of lower lobe alveoli. Removal of upper lobe alveoli reduces the mean RV/TLC of the alveoli remaining in the lung following therapy, while removal of lower lobe alveoli has the opposite effect. As a consequence, the beneficial effects of tissue resection following LLT are offset by an increase in gas trapped within the alveoli that remain. These findings suggest that LVRT for homogeneous emphysema should be limited to patients with upper lobe target sites.In summary, results from two small clinical trials show that lower lobe volume reduction using ELS is less effective than upper lobe volume reduction in patients with advanced homogeneous emphysema. Physiological modeling indicates that this is due primarily to differential effects of the procedure on upper versus lower lobe alveoli. Shifts in Concept/study design – Arschang Valipour, Edward P. Ingenito, Mordechai R. Kramer; Clinical contributions – Arschang Valipour, Mordechai R. Kramer, Franz Stanzel, Axel Kempa, Sherwin Asadi, Oren Fructer, Ralf Eberhardt, Felix J. Herth; Manuscript preparation – Arschang Valipour, Edward P. Ingenito; Manuscript review – Arschang Valipour, Mordechai R. Kramer, Felix J. Herth, Ralf Eberhardt.Dr. Arschang Valipour – No conflicts of interest related to the data in this manuscript. Prof. Mordechai R. Kramer – No conflicts of interest related to the data in this manuscript. Dr. Franz Stanzel – No conflicts of interest related to the data in this manuscript. Dr. Axel Kempa – No conflicts of interest related to the data in this manuscript. Dr. Sherwin Asadi – No conflicts of interest related to the data in this manuscript. Dr. Oren Fruchter – No conflicts of interest related to the data in this manuscript. Dr. Ralf Eberhardt – No conflicts of interest related to the data in this manuscript. Prof. Felix J. Herth – No conflicts of interest related to the data in this manuscript. Dr. Edward Ingenito – A perceived conflict of interest exists for Dr. Ingenito with respect to the data in this manuscript. Dr. Ingenito is a senior medical advisor for Aeris Therapeutics, the company that funded the clinical trials that generated the data included in this study. Dr. Ingenito receives salary support from Aeris Therapeutics and owns stock in the company.