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Background and objectives The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined. Methods This prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration ( C max ) and trough concentration ( C min ), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding affinity of UB to albumin ( K af ), using R statistical software version 3.5.3. Results Thirty-eight patients took a daily dose of 750 mg terizidone, while one took 500 mg. The amount of cycloserine [median (range)] that emanated from terizidone metabolism was 51.6 (0.64–374) mg. C max ( R 2  = 22%, p  = 0.003) and C min ( R 2  = 10.6%, p  = 0.044) were significantly associated with increased CB concentration. C max was significantly associated with increased K af ( R 2  = 10.1%, p  = 0.048), while high CLm/F was significantly associated with decreased AST/ALT ( R 2  = 21%, p  = 0.003). Conclusions Cycloserine is not interchangeable with terizidone, as amounts are lower than expected. Cycloserine may be a predisposing factor to the development of hyperbilirubinaemia, as CLm/F is affected by hepatic function.

Background The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients. Objective The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen. Methods This was a randomised double-blind study of preterm neonates admitted to neonatal intensive care units. They all received vancomycin 15 mg/kg every 12 h. Blood was sampled just before administration of the third, sixth and ninth vancomycin dose. Pharmacokinetic parameters were estimated using a Bayesian approach implemented in Monolix 2018R2 software. Covariates assessed included postmenstrual age, current weight, creatinine clearance, albumin, gestational age, body surface area and current age. We used Monte Carlo simulations for dose regimen optimisation targeting area under the concentration–time curve up to 24 h (AUC 0–24h ) of ≥ 400 mg × h/L. Results In total, 19 preterm neonates were enrolled in the study with a median age of 14 (3–58) days. A one-compartment model with linear elimination best described the pharmacokinetics of vancomycin. Volume of distribution and clearance was 0.88 L and 0.1 L/h, respectively, for a typical neonate weighing 1.48 kg. Simulation of the current dose regimen showed that 27.5% of the neonates would achieve the target AUC 0–24h of ≥ 400 mg × h/L, and 70.7% of the neonates would achieve it with 12 mg/kg every 8 h. Conclusion The majority of the neonates were under dosed. Vancomycin 12 mg/kg should be administered every 8 h over 1 h infusion to improve the likelihood of achieving the AUC 0–24h target of ≥ 400 mg × h/L. This target is considered optimal for MRSA infections, where the vancomycin minimum inhibitory concentration is ≤ 1 µg/mL.

Arbuscular Mycorrhizal Fungi (AMF) and Rhizobium (RHZ) are key bio-inoculants in sustainable agriculture, known for their symbiotic relationships with plants. However, their effects on soil functions under different proportions of inorganic fertilizers are not well understood. This study, conducted during the Rabi seasons from 2019 to 2021 in alluvial soils of Punjab, India, investigates the impact of AMF and RHZ inoculation on root morphology and rhizospheric soil chemical properties in field pea (Pisum sativum L.). The findings indicate that dual inoculation with AMF and RHZ (RHZ + AMF + N50%+P50%+K100%) significantly enhances root growth and improves soil chemical properties. Despite an initial increase in pH that negatively affected micronutrient availability at 60 days after sowing (DAS), a stabilizing trend at 90 DAS was observed, leading to better availability of Fe, Cu, Mn, and Zn, along with higher Cation Exchange Capacity and macronutrient availability. This dual inoculation strategy is found to maximize profitability in terms of root morphology and soil chemical properties. Notably, lower root Cation Exchange Capacity compared to soil Cation Exchange Capacity may be due to factors like soil structure and root interactions. Principal Component Analysis (PCA) of soil parameters effectively distinguishes between treatments, showing that RHZ and AMF respond differently to various NPK proportions. For instance, treatments T3 (RHZ + N50% + P100% + K100%), T4 (RHZ + N75% + P100% + K100%), and T6 (AMF + N100% + P75% + K100%) are grouped together, while treatments T5 (AMF + N100% + P50% + K100%) and T7 (RHZ + AMF + N50% + P50% + K100%) cluster separately. This suggests that dual inoculation, especially as seen in Treatment T7, is recommended for sustained soil health and enhanced productivity.

The legalisation of cannabis for medicinal use is a contentious space both politically and in the medical community. In 2014, the Medical Innovation Bill introduced by Mario Oriani-Ambrosini MP, aimed to shift the political and legal positions of cannabis as an illegal substance to one available for research and medical use. To date, progress on this has been slow. Cannabis and cannabinoid products are currently available for medicinal use in several countries, including the Netherlands and 29 states in the United States. Locally, anecdotal reports suggest that many of our patients with chronic medical conditions are using cannabis and cannabis-derived or cannabinoid products for symptom alleviation.

In a significant number of patients presenting with stroke or peripheral embolization, no cause is found despite extensive diagnostic evaluation. We present a case of multiple bilateral renal infarctions and emphasize the possible diagnostic yield of TEE in such cases. A 52 year old female with history of arterial hypertension, reflux esophagitis and smoking presented to the emergencies complaining of acute abdominal and flank pain, radiating from both lumbar areas to the right and left iliac fossa. Other complaints were nausea as well as rectal and vesical tenesmus. Palpation revealed deep tenderness of the right iliac fossa as well as local guarding and rebound tenderness. Costovertebral angle tenderness was present on the right. The patient was afebrile. Urinalysis and abdominal ultrasound were normal. Contrast enhanced abdominal CT scan revealed bilateral multifocal renal infarctions. Laboratory testing was remarkable for leukocytosis, increased CRP, increased LDH and reduced kidney function. As part of the diagnostic workup, the patient underwent 24-h holter monitoring, coagulation screening, transthoracic echocardiography and eventually transesophageal echocardiography. On the latter, free-floating endo-luminal thrombus material arising from a thick, calcified, ruptured atherosclerotic plaque was seen in the descending thoracic aortic artery and was considered the embolic focus. The patients was initiated on long term low dose aspirine and potent lipid lowering therapy. Low molecular weight heparine was administered for one month, until follow up TEE showed the disappearance of intraluminal thrombus material. She was also urged to quit smoking and take up physical exercise and dietary measures in the light of secondary cardiac prevention. Kidney infarction is rare and probably underdiagnosed, and the exact cause remains unknown in a substantial number of cases. Atrial fibrillation is by far the most common cause and needs to be sought after. With our case, we want to stress the possible diagnostic yield of transesophageal echocardiography in patients with peripheral embolus when a previous extensive diagnostic workup (contrast enhanced CT of the abdomen, 24-h holter monitoring, coagulation screening, doppler ultrasound of the renal arteries and transthoracic echocardiography) was unable to identify an underlying cause. Determination of the exact cause is important for a correct treatment (i.e. antiplatelet therapy and lipid lowering therapy, but no long term anticoagulation in this case).

Doc number: 283 Abstract Background: Asystasia gangentica (A. gangetica ) belongs to the family Acanthaceae. It is used to treat hypertension, rheumatism, asthma, diabetes mellitus, and as an anthelmintic in South Africa, India, Cameroun, Nigeria, and Kenya respectively. It has also been reported to inhibit the angiotensin I converting enzyme (ACE) in-vitro . Therefore, the aim of this study is to investigate the in-vivo effect of aqueous leaf extract (ALE) of A. gangetica on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats (SHR); and to elucidate possible mechanism(s) by which it acts. Methods: The ALE of A. gangetica (10-400 mg/kg), angiotensin I human acetate salt hydrate (ANG I, 3.1-100 μg/kg) and angiotensin II human (ANG II, 3.1-50 μg/kg) were administered intravenously. The BP and HR were measured via a pressure transducer connecting the femoral artery to a Powerlab and a computer for recording. Results: A. gangetica significantly (p<0.05), and dose-dependently reduced the systolic, diastolic, and mean arterial BP. The significant (p<0.05) reductions in HR were not dose-dependent. Both ANG I and ANG II increased the BP dose-dependently. Co-infusion of A. gangetica (200 mg/kg) with either ANG I or ANG II significantly (p<0.05) suppressed the hypertensive effect of both ANG I and ANG II respectively, and was associated with reductions in HR. Conclusions: A. gangetica ALE reduced BP and HR in the SHR. The reduction in BP may be a result of actions of the ALE on the ACE, the ANG II receptors and the heart rate.

Doc number: 13 Abstract Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30-120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea ; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violacea -treated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea .

Background: Sexually transmitted infections (STIs) are known risk factors for HIV infection. Goal: The goal of this study was to assess the current and potential future role that community pharmacists in Western Cape, South Africa play in the treatment of STIs. Study Design: A cross-sectional survey of community pharmacists in the Western Cape region of South Africa. A face-to-face interview that ascertained experience with requests from patients for STI treatment, current STI treatment practices, and willingness to provide syndromic STI treatment was administered to head pharmacists. Results: Ninety pharmacies were selected and 85 (94%) of the head pharmacists participated; 55 from an urban area and 30 from a rural area. Pharmacists reported a median of 40 urban clients and 25 rural clients who sought STI treatment from community pharmacists. When provided with a hypothetical clinical situation, 13% of urban and 17% of rural pharmacists identified the correct medication for male urethral discharge, 8% of urban pharmacists and none of the rural pharmacists identified correct treatment for genital ulcers, and none of the pharmacists identified the correct medication for vaginal discharge. Fifty-three percent of pharmacists in urban regions and 47% of pharmacists in rural regions expressed willingness to provide syndromic STI treatment. Independent predictors of willingness to provide syndromic treatment were knowledge of the link between HIV transmission and STIs (adjusted odds ratio [OR]: 13.78; 95% CI: 2.69, 70.66), past experience prescribing syndromic STI treatment (OR: 11.1; 95% CI: 1.14, 108.6), and male gender (OR: 4.38; 95% CI: 1.15, 16.7). Conclusions: Pharmacists are frequently called upon to provide STI treatment but have limited knowledge of correct treatment recommendations. Training pharmacists to provide syndromic STI treatment may be one strategy to reduce STI morbidity and HIV transmission.