Clinical impact of plasma concentrations of first-line antituberculosis drugs.

BACKGROUND: The clinical significance of low antituberculosis (anti-TB) drug concentrations has not been fully elucidated. OBJECTIVES: To investigate the clinical consequences of first-line drug concentrations in adult patients with drug-susceptible pulmonary TBin South Africa (SA). METHOD: We conducted a pharmacokinetic study nested within the control arm of the Improving Treatment Success (IMPRESS) trial(NCT02114684) in Durban, SA. During the first 2 months of treatment, participants received weight-based dosing of first-line anti-TBdrugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drugadministration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes wereassessed using World Health Organization criteria. RESULTS: We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below thetherapeutic range in 39/43 (90.7%) for rifampicin, 32/43 (74.4%) for isoniazid, 27/42 (64.3%) for pyrazinamide and 5/41 (12.2%) forethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did notfind a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the endof treatment, and there were no relapses during the 12-month follow-up period. CONCLUSION: Treatment outcomes were favourable despite low drug concentrations as defined by current reference thresholds.

Erratum: One welfare: Linking poverty, equid ownership and equid welfare in the brick kilns of India - ERRATUM.

[This corrects the article DOI: 10.1017/S0962728600032504.].

Antivirals for the treatment of mild and moderate COVID-19 in South Africa.

While the majority of COVID-19 cases in South Africa (SA) are mild, patients with severe COVID-19 requiring hospitalisation present with significant morbidity and mortality and place a substantial burden on healthcare services. Given the low vaccine uptake in SA and other low- and middle-income countries in sub-Saharan Africa, the high prevalence of comorbidities and limited healthcare system capacity, evidence-based interventions that reduce the risk of severe disease and death should be considered for implementation. Several antiviral classes have been newly developed or repurposed to treat COVID-19 early after infection to retard progression to severe disease and reduce the risk of death, particularly in the elderly and/or in patients with comorbidities. COVID-19 antivirals such as remdesivir, nirmatrelvir/ ritonavir and molnupiravir are safe and cost-effective and have received either full approval or emergency use authorisation from regulators. Using a proposed test-and-treat strategy, judicious use of antivirals could be impactful.

Altered drug exposures of first-line TB drugs in a moxifloxacin-containing treatment regimen.

BACKGROUND: Pharmacokinetic variability arising from drug-drug interactions and pharmacogenetics may influence the effectiveness of treatment regimens for TB. The Improving Treatment Success Trial compared the WHO-recommended standard treatment in TB patients with an experimental regimen substituting ethambutol with moxifloxacin (MFX) in Durban, South Africa.METHODS: Non-linear mixed-effects modelling was used to investigate the population pharmacokinetics of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA). A total of 25 single-nucleotide polymorphisms, including pregnane-X-receptor, were selected for analysis.RESULTS: TB drug concentrations were available in a subset of 101 patients: 58 in the MFX arm and 43 in the control arm. Baseline characteristics were well-balanced between study arms: median age and weight were respectively 36 years and 57.7 kg; 75.2% of the patients were living with HIV. Although weight-based drug dosing was the same in the two arms, we found that RIF exposure was increased by 19.3%, INH decreased by 19% and PZA decreased by 19.2% when administered as part of the MFX-containing regimen. Genetic variation in pregnane-X-receptor (rs2472677) was associated with a 25.3% reduction in RIF exposure.CONCLUSION: Optimised weight-based TB treatment dosing is essential when RIF, INH and PZA are co-administered with fluoroquinolones. The reduction in RIF exposure associated with pharmacogenetic variation is worrying.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Idiopathic fibrosing mediastinitis.

Fibrosing mediastinitis is rare in settings where histoplasmosis is not endemic. An idiopathic form of the disease may present with indistinguishable features and requires methodical exclusion of competing differential diagnoses. We report the case of a 30-year old female patient who presented with intermittent haemoptysis for the past 2 years with no constitutional symptoms. Computed tomography of the chest revealed a prominent right bronchial arterial circulation with a mass-like lesion, which encased and attenuated the right pulmonary trunk and adjacent structures. Endobronchial ultrasonography with transbronchial fine-needle aspiration showed a paucicellular aspirate with no evidence of malignancy or granulomas. Fungal infection, tuberculosis, sarcoidosis, IgG4-disease, and connective tissue disease were ruled out by appropriate serological, molecular, and microbiological tests. A diagnosis of idiopathic fibrosing mediastinitis was therefore made by exclusion and the patient was successfully treated with oral corticosteroids.

KN95 filtering facepiece respirators distributed in South Africa fail safety testing protocols.

BACKGROUND: Given the global shortage of N95 filtering facepiece respirators (FFP2 in Europe) during the COVID-19 pandemic, KN95 masks (Chinese equivalent of the N95 and FFP2) were imported and distributed in South Africa (SA). However, there are hardly any published independent safety data on KN95 masks. OBJECTIVES: To evaluate the seal, fit and filtration efficiency of several brands of KN95 masks marketed for widespread use in SA healthcare facilities, using standardised testing protocols. METHODS: The verifiability of manufacturer and technical details was first ascertained, followed by evaluation of the number of layers comprising the mask material. The testing protocol involved a directly observed positive and negative pressure user seal check, which if passed was followed by qualitative fit testing (sodium saccharin) in healthy laboratory or healthcare workers. Quantitative fit testing (3M) was used to validate the qualitative fit testing method. The filtration efficacy and integrity of the mask filter material were evaluated using a particle counter-based testing rig utilising aerosolised saline (expressed as filtration efficacy of 0.3 µm particles). Halyard FLUIDSHIELD 3 N95 and 3M 1860 N95 masks were used as controls. RESULTS: Twelve KN95 mask brands (total of 36 masks) were evaluated in 7 participants. The mask type and manufacturing details were printed on only 2/12 brands (17%) as per National Institute of Occupational Safety and Health and European Union regulatory requirements. There was considerable variability in the number of KN95 mask layers (between 3 and 6 layers in the 12 brands evaluated). The seal check pass rate was significantly lower in KN95 compared with N95 masks (1/36 (3%) v. 12/12 (100%); p<0.0001). Modification of the KN95 ear-loop tension using head straps or staples, or improving the facial seal using Micropore 3M tape, enhanced seal test performance in 15/36 KN95 masks evaluated (42%). However, none of these 15 passed downstream qualitative fit testing compared with the control N95 masks (0/15 v. 12/12; p<0.0001). Only 4/8 (50%) of the KN95 brands tested passed the minimum filtration requirements for an N95 mask (suboptimal KN95 filtration efficacy varied from 12% to 78%, compared with 56% for a surgical mask and >99% for the N95 masks at the 0.3 µm particle size). CONCLUSIONS: The KN95 masks tested failed the stipulated safety thresholds associated with protection of healthcare workers against airborne pathogens such as SARS-CoV-2. These preliminary data have implications for the regulation of masks and their distribution to healthcare workers and facilities in SA.

The parental effects of body size on developmental phenotype in Harmonia axyridis.

Body size is a trait with many potential impacts on fitness. Adult body size can affect the strength of condition-dependent parental effects that determine offspring phenotypes, with potentially important transgenerational consequences. In a preliminary experiment, larval food deprivation (30 min daily access) created Harmonia axyridis Pallas (Coleoptera: Coccinellidae) females that weighed <50% of controls reared on ad libitum food (eggs of Ephestia kuehniella Zeller). Although only 1/3 of larvae survived to adulthood in the 30 min treatment, adult pairs produced eggs that were not significantly different in size from those of pairs fed ad libitum as larvae. Less extreme larval food deprivation (4 h daily access) was used to create a cohort of H. axyridis that weighed <60% of controls reared on ad libitum food. Small couples had lower 20-day fecundities and reduced egg fertility relative to large couples. Both egg and pupal periods were shortest when both parents were small, and longest when both parents were large, with reciprocal crosses intermediate. There were no consistent effects of parental body size on larval development time, but the progeny of small females mated to large males pupated later than other treatments. Progeny of large pairs had the heaviest adult weights at emergence, and progeny of small pairs, the lightest, with the progeny of reciprocal crosses intermediate. Small females produced the lightest female offspring, whereas small males sired the lightest male offspring, suggesting stronger responses to epigenetic signals from parents of the same sex. These results indicate that H. axyridis cohorts maturing with abundant food will produce progeny with larger potential body size and fitness, whereas those experiencing food limitation will confer size and fitness limitations to the subsequent generation, with potentially important implications for short-term population dynamics.

A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.

Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, n = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, n = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, n = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, n = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.

Quantifying pearl millet response to high temperature stress: thresholds, sensitive stages, genetic variability and relative sensitivity of pollen and pistil.

The objectives were to (1) quantify high temperature (HT) stress impacts at different growth stages (season long, booting to seed-set and booting to maturity) on various yield components; (2) identify the most sensitive stage(s) to short episodes of HT stress during reproductive development; (3) understand the genetic variations for HT stress tolerance based on cardinal temperatures for pollen germination; and (4) determine relative sensitivity of pollen and pistil to HT stress and associated tolerance or susceptible mechanisms in pearl millet. High temperature stress (≥36/26°C) imposed at different stages and durations caused decrease in number of seeds, individual seed weight and seed yield. Two periods (10-12 days and 2-0 days before anthesis) were identified as most sensitive to short episodes of stress, causing maximum decreases in pollen germination percentage and seeds numbers. HT stresses of ≥36/26°C results in floret sterility. Pistils were relatively more sensitive than pollen grains, causing decreased number of seeds and seed yield. HT stress increased the reactive oxygen species contents and decreased the activity of the antioxidant enzymes in both pollen and pistils. Under HT stress, pistils had relatively higher reactive oxygen species and lower antioxidant enzymes activity compared with pollen grains, which explains greater susceptibility of pistils.

Do specialist pulmonologists appropriately utilise thoracic surgery for drug-resistant pulmonary tuberculosis? A survey.

BACKGROUND: Adjuvant lung resection in patients with drug-resistant tuberculosis (DR-TB) not only is cheaper than a 2-month course of drug therapy for multidrug-resistant tuberculosis (MDR-TB) but also, more importantly, has a higher cure rate than medical therapy alone. The cure rate for some MDR-TB patients treated with adjuvant lung resection is about 90%. With the more severe forms of DR-TB, surgical cure rates in selected patients remain high, whereas cure rates decrease when only medical therapy is used. In addition, adjuvant lung resection for DR-TB in selected patients with HIV co-infection does not appear to have a higher complication rate. OBJECTIVES: To determine whether specialist pulmonologists in South Africa utilise thoracic surgical intervention for DR-TB appropriately. METHODS: A cross-sectional survey was conducted among pulmonologists of the South African Thoracic Society. The study tool was a predesigned, anonymous questionnaire that included 17 closed-ended questions about the role of cardiothoracic surgery in the management of DR-TB. RESULTS: A 50% response rate was achieved. The majority of respondents did not know the indications for adjuvant lung surgery in the setting of DR-TB, but would have altered their referral behaviour had they been aware of these indications. CONCLUSION: Participating pulmonologists' uncertainty regarding optimal use of adjuvant lung resection for DR-TB suggests the need for local guidelines and education initiatives relevant to the management of these patients. These strategies should include the participation of both the pulmonologist and the cardiothoracic surgeon.

The evaluation and surgical management of post-intubation tracheal strictures at a thoracic surgery referral centre in South Africa.

BACKGROUND: The surgical treatment of tracheal stenosis following endotracheal intubation or tracheostomy is well described in the developed world. OBJECTIVES: To describe our surgical experience with this pathology, and highlight the nuances of its diagnosis and management in South Africa. METHODS: We reviewed the clinical records and archived imaging of all patients who underwent tracheal resection and reconstruction for post-intubation tracheal stenosis between 1 July 2003 and 31 July 2014 in the Department of Cardiothoracic Surgery at Inkosi Albert Luthuli Central Hospital, Durban, South Africa. RESULTS: During the study period, 42 patients underwent tracheal resection. We evaluated the preoperative bronchoscopic characteristics of the tracheal stricture in all patients, and computed tomography (CT) was used as an adjunct in 28 (66%) patients. The stricture lengths determined by CT and intraoperative measurement were strongly correlated (r (27)=0.506, p=0.006), and the stricture lengths determined by bronchoscopy and intraoperative measurement were weakly correlated (r (41)=0.201, p=0.209). A total of 36 patients (85.7%) underwent surgery via a cervical approach and 6 (14.3%) via a right thoracotomy approach. There was no early mortality, and surgery was complicated by vocal cord palsy in 4 cases, restenosis in 2 cases, infection in 1 case and paraparesis in 1 case. CONCLUSION: Tracheal resection for the treatment of post-intubation tracheal stenosis can be undertaken safely with minimal complications in the developing world, with the vast majority of lesions approached via a cervical approach. A preoperative evaluation of the stricture using CT is an accurate technique for planning tracheal resection and reconstruction.

Sensitivity of sorghum pollen and pistil to high-temperature stress.

High temperature (HT) decreases seed set percentage in sorghum (Sorghum bicolor [L.] Moench). The relative sensitivity of pollen and particularly pistil and the mechanistic response that induces tolerance or susceptibility to HT are not well known and hence are the major objectives of this research. The male sterile (ATx399) and fertile (RTx430) lines were exposed to 30/20 °C (optimum temperature), 36/26 °C (HT1 ), and 39/29 °C (HT2 ) from the start of booting to seed set in a controlled environment. Similarly, in the field, HT stress was imposed using heat tents. HT stress decreased pollen germination. Relatively high levels of reactive oxygen species and decreased antioxidant enzyme activity and phospholipid unsaturation were observed in pollen compared to pistil under HT. The severe cell organelle damage was observed in pollen and pistil at 36/26 and 39/29 °C, respectively. The seed set percentage was higher in HT-stressed pistil pollinated with optimum-temperature pollen. Direct and reciprocal crosses indicate that pollen was more sensitive with larger decreases in seed set percentage than pistil under HT stress. The negative impact was greater in pollen than pistil at lower temperatures. Overall, pollen was more sensitive than pistil to HT stress because it is more susceptible to oxidative damage than pistil.

Hidden leprosy cases in tribal population groups and how to reach them through a collaborative effort.

BACKGROUND: Tribal populations are an underserved population group and access to health services is a major challenge for them. Since leprosy treatment is integrated with the general health services, identifying leprosy cases is not be easy in these settings and they remain as endemic reservoirs, unless greater efforts are made to reach them. METHODOLOGY: An active search operation was conducted in the tribal colonies in four pre-identified Health & Nutrition Clusters, Nellore district, Andhra Pradesh, India, in 2013. After a brief training, village health nurses and selected volunteers covered all the households, showing flash cards with photos of leprosy cases and enquiring if there was any resident with a similar condition. Suspects were listed and examined by the district leprosy supervisor and field coordinators from Damien Foundation. Follow up interviews were done after one year to assess the treatment completion rate. RESULTS: Village health workers covered 47,574 people living in the tribal colonies and identified 325 leprosy suspects. Among them, 70 were confirmed as new leprosy cases. The prevalence of previously undetected leprosy cases was found to be 14.7/10,000. Out of 70 cases, 19 (27%) were children, 35 (50%) were female, 32 (45.7%) were classified as MB leprosy, 6 (8.6%) had a leprosy reaction and 11 (15.7%) persons had Grade 2 disability at the time of diagnosis. The treatment completion rate was found to be 74% at the end of one year. CONCLUSION: The study reveals a very high burden of leprosy among the tribal population and demonstrates how resources can be mobilized from government, NGO and local community sources to promote early case detection among underserved population groups.

Relationship between stimulation train characteristics and dynamic human skeletal muscle performance.

AIM: The purpose of the present study was to investigate the effect of activation frequency on dynamic human muscle performance for a range of train durations and number of pulses during free limb movement. METHODS: The quadriceps femoris muscles of 10 subjects were activated with stimulation trains with different activation frequency, train durations and number of pulses. The peak excursion produced in response to each train was the dependent measure of muscle performance. RESULTS: The excursion-frequency (for a 300-ms train duration) and excursion-train duration (for trains with frequencies of 10, 30 or 59 Hz) relationships could each be fit with a two-parameter exponential equation (R(2) values > 0.97). Because the number of pulses in a stimulation train is a function of both train duration and frequency, the excursion produced as a function of the number of pulses was characterized by a three-parameter exponential equation that represented this combined relationship. The relationship between the measured and predicted excursions in response to a wide range of stimulation trains had a R(2) = 0.96. In addition, one-way repeated measures analyses of variance (anovas) showed that the frequency at which the maximum excursion was produced increased with an increase in the number of pulses in the trains tested. CONCLUSION: These results show the importance of train duration and the number of pulses contained within a train on the relationship between activation frequency and human skeletal muscle performance.

Potential antidepressants: pharmacology of 2-(4-methyl piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile in rodent behavioural models.

Serotonin type 3 (5-HT3) antagonists, which find an unflinching place in the management of nausea and emesis are presently screened for their neuro-pharmacological potential in various animal models. In the present study, 2-(4-methyl piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile (NA-2) with an optimal log P and pA2 value comparable to that of ondansetron was screened in rodent models of depression. The acute and chronic (14 days) treatment of the synthetic compound exhibited antidepressant-like effects at the lower dose levels in mice forced swim test (FST). A typical and similar dose-immobility profile was observed in both mice FST and tail suspension test (TST). Interaction studies in FST revealed the reversal of mCPP induced immobility, attenuation of antidepressant effects of fluoxetine and desipramine. Chronic NA-2 treatment restored the behavioural deficits in olfactory bulbectomized (OBX) rats as indicated by reduction in hyperactivity in novel open field test. This preliminary study points to a serotonergic mechanism behind the antidepressant-like effects of NA-2 and invigorates further investigation of analogous compounds in various other models of depression.

Microwave-assisted solvent-free synthesis of 3-[(4-substituted piperazin-1-yl)alkyl] imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones as serotonin3 (5-HT3) receptor antagonists.

A series of novel 3-[(4-substituted piperazin-1-yl)alkyl]imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones were prepared by microwave irradiation using alumina as solid support and also by a conventional method. The compounds were characterized by spectral data and the purity was ascertained by microanalysis. The synthesized compounds were evaluated for 5-hydroxytryptamine3 antagonisms in a longitudinal muscle-myenteric plexus preparation from guinea pig ileum against the 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine. Among the test compounds, 3-[2-(4-methylpiperazin-1-yl)ethyl]imidazo[2,1-b][1,3]benzothiazol-2(3H)-one (3b) showed most favorable 5-hydroxytryptamine3 antagonism (pA2 6.7) in the isolated guinea pig ileum.

Cancer chemotherapy-induced nausea and vomiting: role of mediators, development of drugs and treatment methods.

The development of serotonin 5-HT3 receptor antagonists dramatically improved the treatment of chemotherapy-induced nausea and vomiting. Ondansetron, a serotonin 5-HT3 receptor antagonist in combination with dexamethasone is widely used to treat chemotherapy-induced nausea and vomiting. This treatment regimen is effective against acute nausea and vomiting, but fails to control delayed nausea and vomiting. Metoclopramide along with other antiemetics are used to treat delayed nausea and vomiting. The high doses of metoclopramide needed may produce extra pyramidal side effects. The recent developments of 5-HT3 and dopamine D2 dual receptor antagonists have been found to exhibit a broad spectrum of activity against peripherally and centrally acting stimuli, but are not much effective against delayed emesis associated with chemotherapy. In various animal models, neurokinin NK1 receptor antagonists showed promising results against acute and delayed emesis, but the clinical trials revealed that triple therapy (NK1 receptor antagonist, 5-HT3 receptor antagonist and dexamethasone) is superior than standard therapy (5-HT3 receptor antagonist & dexamethasone) or NK1 receptor antagonist alone, in controlling acute as well as delayed nausea and vomiting. Ginger, which is used traditionally for controlling emesis induced by various stimuli, also showed good activity against chemotherapy-induced nausea and vomiting in animal models. Non-pharmacological methods such as acupressure and acustimulation are good adjunct methods in treating nausea and vomiting. Since many mediators are involved in emesis induced by chemotherapy, cocktail treatment is proven to be more efficacious than a single drug, but increases treatment costs. So there is a need of further research in this field to get economically useful methods for the treatment of acute and delayed chemotherapy-induced nausea and vomiting.

Pregnenolone metabolism in testicular homogenates of macaques (Macaca fascicularis): some effects of relaxin and freezing.

The metabolism of varying quantities of pregnenolone has been studied in nuclei-free homogenates from Macaca fascicularis testes by using capillary gas chromatography, after derivatization of metabolites as O-methyl oximes/trimethylsilyl ethers. Evidence was obtained indicating that both pathways for testosterone biosynthesis were operating. 5-Androstene-3 beta, 17 beta-diol was formed in especially high quantities. Two 16-androstenes, namely 5,16-androstadien-3 beta-ol and 5 alpha-androst-16-en-3 beta-ol, were also quantitatively important as metabolites. Co-incubation of stored homogenates with relaxin resulted in 80-100% reduction of the formation of all metabolites quantified except for 5 alpha-androst-16-en-3-one, which was stimulated. Freezing the homogenates at -10 degrees C for 3 weeks resulted in marked 4- to 6-fold reduction in the yields of testosterone and of the 5-ene and 4-ene metabolites from pregnenolone.