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Objective: To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses., Study Design: In a longitudinal cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy., Results: Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses., Conclusions: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiovascular mortality is the primary cause of death in patients with type 2 diabetes mellitus (T2DM). Recently, clinical trials of the sodium-glucose transport protein 2 (SGLT-2) inhibitors empagliflozin and canagliflozin and of the glucagon-like peptide-1 (GLP-1) agonists liraglutide and semaglutide demonstrated that the agents reduced cardiovascular events. Furthermore, empagliflozin and liraglutide reduced cardiovascular mortality. However, despite the proven cardiac benefits, many but not all provincial formularies have restrictive rules for payment and access for SGLT-2 inhibitors and GLP-1 agonists. These restrictions impede a practitioner's ability to provide optimal care for patients with T2DM and cardiovascular disease. The 2018 Diabetes Canada Guidelines recommend the use of a glucose-lowering agent with proven cardiovascular benefit (ie, empagliflozin, canagliflozin, liraglutide, or semaglutide) as second-line therapy after metformin, for patients with T2DM and cardiovascular disease who fail to achieve the glycemic target of A1C <7% with metformin. We recognize that provinces must allot resources especially when health care budgets are limited and not able to provide all available treatments. However, today we have glucose-lowering agents that reduce mortality in patients at very high cardiovascular risk. Furthermore, for empagliflozin, the cost effectiveness is highly favourable. Consequently, we urge provincial formularies to re-examine the access requirements for SGLT-2 inhibitors and to consider adding GLP-1 agonists use to reflect current evidence and clinical guideline recommendations., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Neem oil, an oil extracted from the seeds of Azadirachta indica has been found to act as a good spermicidal agent. Pre and post coital application of the oil intravaginally prevented pregnancy in rhesus monkey.

NIM-76, the odorous and volatile fraction of neem oil, was investigated for its antifertility activity in vivo in rats, rabbits and rhesus monkeys. The drug is effective when applied before coitus but not so when applied during post-coital stages. It, therefore, appears to act mainly by its spermicidal effect. No alteration in the estradiol (E2) and progesterone (P) values was observed after the application of the drug in monkeys.

Depot-medroxy progesterone acetate (DMPA) was jet deposited into the uterus/cervix of rats, rabbits and rhesus monkeys with the help of a modified jet injection apparatus. Since the drug was delivered under pressure, it was distributed deep into the muscular layers around the place of deposition. After one deposition the drug acted as an effective contraceptive for a period of three months. The merits of this delivery technique are discussed.

The volatile, odorous fraction of neem oil coded as NIM-76 obtained by steam distillation was investigated for in vitro spermicidal activity. The data showed that the minimum concentration which inhibited spermatozoal motility was 0.25 mg/ml for rat and 25 mg/ml for human spermatozoa. The effect of the drug on spermatozoal motility was found to be dose-dependent. The activity of this drug was not altered in the presence of vaginal or cervical mucus. Intra-vaginal application of NIM-76 in rabbits showed no irritation to the vaginal mucosa.

Copper was deposited by iontophoresis into vasa deferentia of animals, using 1 m. amp. current for 30-90 sec. in rat and 3 m. amp. current for 60 sec. in rabbits. The method was effective for a period of 9 months as a contraceptive. The effect of the metal was localised at the site of deposition and there was no effect on other reproductive organs. The mating behaviour and testosterone levels did not change. The utility of the technique in male contraception is discussed.

The effects of castration and testosterone replacement therapy on the histology and biochemical composition (RNA, DNA, total protein, alkaline phosphatase, acid phosphatase, hyaluronidase, sialic acid, glycogen, phospholipids, and glycerylphosphorylcholine [GPC]) of the epididymis of the rabbit and rhesus monkey were investigated. Castration produced marked ponderal, histologic, and biochemical changes in the epididymis. In the androgen-deficient state the tubular diameter and epithelial cell height were reduced and there was an increase in interbular stroma. The levels of RNA, DNA, phospholipids, and GPC were also reduced in castrated animals. Testosterone treatment restored the histologic features and the levels of various biochemical constituents to a great extent but not to the intact control level. The importance of endocrine and exocrine factors of the testis in relation to epididymal function is discussed.

Altitude induced alterations in circulatory levels of PRL, LH, FSH and testosterone were studied in seven eugonadal men at sea level (SL), during their stay at high altitude (HA, 3500 m) and a week after return to SL. The mean plasma PRL level at SL was 5.83 +/- 1.7 SE ng/ml. On day one and seven of arrival at HA, the PRL values of 7.81 +/- 1.81 and 9.21 +/- 1.64 ng/ml respectively were not significantly different (p greater than 0.05) than the initial SL values. However, on day 18 of stay at HA, PRL levels were significantly increased (p less than 0.01) to 17.68 +/- 1.82 ng/ml and returned to initial SL values within seven days of return to SL. A significant decrease (p less than 0.01) in LH and testosterone was observed on seventh day of stay at HA and the decreased levels were maintained till day 18 of observations. Plasma testosterone returned to the initial SL values within a week of return to SL, whereas LH levels remained significantly lower (p less than 0.01). The FSH levels did not show any significant change during their stay at HA or after return to SL. These observations suggest that exposure to altitude is associated with hyperprolactenemia and an impaired pituitary gonadal function. The decreased levels of LH and testosterone at HA could either be due to hypoxic stress per se or secondary to altitude induced hyperprolactenemia.

The changes in the weight, histology and biochemical composition of the epididymis (caput, corpus and cauda segments) in prepuberal rabbit and rhesus monkey in response to testosterone treatment were investigated. The increase in the weight of the organ was accompanied by increased levels of RNA and DNA. Androgen therapy caused an increase in the concentration of sialic acid, phospholipids and glycerylphosphorylcholine and activities of alkaline phosphatase, acid phosphatase and hyaluronidase. The cauda region of the epididymis exhibited relatively higher levels of sialic acid and glycerylphosphorylcholine. These findings are discussed in relation to the functional maturation of the organ and the role of androgen in this process.

Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.