Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Combination of pancreas volume and HbA1c level predicts islet yield in patients undergoing total pancreatectomy and islet autotransplantation

Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r² = .657 and r² = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.     

The hypothalamic–pituitary–gonadal axis and prostate cancer: implications for androgen deprivation therapy

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.     

Hypertension and erectile dysfunction: The role of endovascular therapy in Asia

The prevalence of erectile dysfunction (ED) is above 40% in both Asian and non‐Asian male populations after the age of 40 years. The prevalence of ED among hypertensive patients is approximately double than that in normotensive population. Pelvic arterial insufficiency is the predominant cause of ED in men aged over 50 years. Stenosis in any segment of the iliac–pudendal–penile arterial system, which is considered an erectile‐related arterial axis, could lead to ED. Pharmacotherapy with lifestyle modification is effective in alleviating sexual dysfunction, yet a substantial number of patients still develop ED. Given the established applicability of angioplasty for the entire iliac–pudendal–penile arterial system, penile duplex ultrasound, and pelvic computed tomography angiography could be considered as the routine screening tools in ED patients with poor response to phosphodiesterase‐5 inhibitors. Endovascular therapy for pelvic arterial insufficiency‐related ED has been shown to be a safe and effective treatment option in patients who have anatomically suitable vessels and functionally significant stenoses. Clinical improvement was achieved in over 60% of patients at one year following pelvic angioplasty in the PERFECT registry from Taiwan. A 30%‐40% restenosis rate in distal internal pudendal and penile arteries remains a hurdle. Angioplasty for pelvic arterial occlusive disease could be considered as a viable approach to arteriogenic ED.     

Experience of 100 solid organ transplants over a five‐yr period from the first successful pediatric multi‐organ transplant program in India

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow‐up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow‐up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post‐operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.     

Mixed-Micellar Proliposomal Systems for Enhanced Oral Delivery of Progesterone

The objective of our study was to develop a mixed-micellar proliposomal formulation of poorly water-soluble drug progesterone and evaluate the dissolution profile and membrane transport. Several formulations of proliposomes were prepared by mixing different concentrations of lipid, progesterone, polysorbate 80, and microcrystalline cellulose. The mixed-micellar formulation of drug:dimyristoyl-phosphatidycholine:polysorbate 80 (1:20:3.3) exhibited the maximum dissolution (75.27%), while pure progesterone resulted in low dissolution. The above formulation showed a 4-fold increase in transport in Caco-2 cells and a 6-fold increase in transport across the everted rat intestinal sac experiments compared with control. Proliposomal formulations enhance the extent of dissolution and membrane transport of progesterone and serve as ideal carriers for oral delivery of drugs with low water solubility.     

Hypertension and stroke in Asia: A comprehensive review from HOPE Asia

Stroke is the primary cause of disability and vascular death worldwide, including Asia. Asian characteristics that differ from the West lead to higher stroke incidence. Stroke epidemiology studies in Asia have shown varying levels of mortality, incidence, prevalence, and burden of disease. Hypertension is the most prevalent risk factor found in Asia. Besides ethnicity that is associated with stroke incidence, both systolic blood pressure, diastolic blood pressure, and blood pressure variability are positively correlated with stroke incidence. Post‐stroke cognitive impairment is one of the sequelae that affect one‐third of stroke survivors and has become a significant public health concern that is often neglected despite its increasing prevalence. Therefore, it is very important to prevent recurrence by treating stroke optimally and effectively. Increasing awareness and treatment adherence to hypertension, the leading risk factor for stroke, became the main goal in several countries in Asia.