Phenytoin as a novel anti-vitiligo weapon

Vitiligo is a psychologically devastating clinical conundrum which affects approximately 1% of the general population. The exact cause of the illness is an enigma, but several hypotheses about its pathogenesis are advanced.The autoimmune hypothesis proposes an autoimmune attack against melanocytes. Although anti-melanocyte autoantibodies have been demonstrated in vitiligo, recent research casts doubt on their pathogenic role and instead supports the involvement of cell-mediated autoimmune response in the pathobiology of this disorder, which is characterized by increase of suppressor T-cells and decrease of the helper/suppressor ratio in association with the presence of type-1 cytokine secreting cytotoxic T cells in the vicinity of disappearing melanocytes.The neural hypothesis proposes that increased release of norepinephrine, a melanocytotoxin, from the autonomic nerve endings in the microenvironment of melanocytes injures these cells. Moreover, norepinephrine induces the catecholamine degrading enzyme monoamine oxidase (MAO), which favors the formation of toxic levels of hydrogen peroxide in the vicinity of melanocytes.Another theory suggests that abnormal permeability of melanosome membrane, which normally prevents the diffusion of toxic melanin precursors into the cytoplasm, may cause melanocyte damage.Phenytoin, the widely-used anticonvulsant, has been employed both topically and systemically in the treatment of some dermatological disorders. The drug has been shown to significantly suppress mitogen-induced activation of lymphocytes and cytotoxic T lymphocyte activity and to polarize the immune response toward the type-2 pathway. It also significantly decreases suppressor T cells and increases the helper/suppressor ratio.At high concentrations, the drug inhibits the release of norepinephrine and the activity of MAO. Moreover, phenytoin is suggested to interact with membrane lipids, which may promote stabilization of the membranes.The hydantoin moiety of phenytoin exerts a direct stimulatory action on melanocytes; facial hyperpigmentation is a recognized side effect of orally administered phenytoin.Altogether, the above evidence suggests that phenytoin could be therapeutically effective against vitiligo. As phenytoin stimulates collagen production and inhibits its breakdown, its concomitant use with topical steroids could prevent steroid-induced skin atrophy while potentiating the anti-vitiligo effect of these agents.     

Fertility of sows mated on different days of the week

The farrowing rates resulting from matings on different days of the week were determined for a 2800-sow intensive piggery in both 1983 and 1984. The results showed that sows mated early in the week achieved a significantly higher farrowing rate than sows mated late in the week (P less than 0.0001). During the seasonal (summer to autumn) infertility period, Wednesday matings resulted in a poor farrowing rate whereas for the rest of the year farrowing rates following Wednesday matings were similar to those for Sunday Monday and Tuesday matings. Consistent results were obtained for data from both years. It is proposed that the stress of regrouping unmated sows on Wednesday to accommodate newly weaned sows is responsible for this decrease in fertility. This study illustrates how detailed analysis of farrowing rates on a day of mating basis can identify a problem which is otherwise masked by weekly data.     

secretion of the major progesterone-induced proteins of the sheep uterus by caruncular and intercaruncular endometrium of the pregnant ewe from days 20–140 of gestation

An experiment was performed to evaluate the types and quantity of proteins secreted by intercaruncular endometrium at days 20, 60, 100 and 140 of gestation and caruncular endometrium from days 100 and 140 of gestation. Tissues were obtained from ewes made unilaterally pregnant. Based on SDS polyacrylamide gel electrophoresis (SDS-PAGE), the major proteins present in uterine fluid at days 60–140 of gestation were the uterine milk proteins (UTM-proteins), a pair of structurally-related, progesterone-induced polypeptides with molecular weights of 55,000 and 57,000. These proteins were also present in uterine fluid at day 20, but the major protein at this time migrated coincident with albumin. Cultured explants of endometrium at all days of pregnancy produced UTM-proteins as their major radiolabelled product for both caruncular and intercaruncular endometrium. The amount of protein secretion in vitro was greater (P<.04) for intercaruncular endometrium than for caruncular endometrium but was not significantly affected by stage of gestation or local presence of the conceptus. Immunohistochemical analysis revealed that UTM-proteins were present in glandular and luminal epithelium of intercaruncular endometrium and in both epithelial and stromal elements of caruncular endometrium. It was concluded that the UTM-proteins are produced earlier than previously described (i.e., day 20). In addition, caruncles contribute to the uterine secretory protein milieu through the secretion of proteins that are similar to that produced by the glandular intercaruncular epithelium.     

Acute nephropathy in young lambs

Acute renal failure was diagnosed by clinical, necropsy and histological criteria in 39 flocks (20 low ground, 13 hill and six marginal upland) in areas served by six veterinary investigation centres. Forty-eight lambs of 12 different breeds or crosses were investigated. The mean age of affected lambs was 38 days (range seven to 84 days); 21 lambs (44 per cent) were aged seven to 28 days, while only eight (17 per cent) were older than two months. Mortality in clinically affected lambs was almost 100 per cent, with no response to various treatments. Histological examination showed that 40 lambs (83 per cent) had nephrosis, while the rest had toxic tubular necrosis, interstitial nephritis or tubular damage associated with oxalate crystal deposits. Only about half of the lambs had any evidence of enteric infections or enteropathy. Acutely ill lambs had azotaemia, haemoconcentration and proteinuria; some lambs had glycosuria or haematuria. Samples of plasma from 22 lambs with nephrosis were compared with similar samples from 82 incontact but asymptomatic lambs. The clinically affected group had significantly elevated plasma urea, creatinine, total protein, globulin, phosphorus and chloride concentrations and significantly reduced plasma calcium concentrations compared with healthy lambs. Affected lambs had a significant reduction also in the calcium:phosphorus ratio. No significant differences between groups was found in plasma concentrations of albumin, glucose, lactate, glycerol, creatine kinase, alkaline phosphatase, sodium, potassium or magnesium.     

Improved feed intake and body weight change in sheep treated with dexamethasone at entry into pens or feedlots

Treatment with the synthetic glucocorticoid dexamethasone sodium phosphate increased the feed intake of sheep within 24 h. A single treatment with the longer-acting compound dexamethasone trimethylacetate had a slower effect, but resulted in improved feed intake and enhanced body weight gain over a period of 7 to 14 days. Treatment was effective in sheep housed individually and in sheep penned in groups. The improvement in body weight gain disappeared 15 to 20 days after a single treatment, but in most studies treated sheep had less variability in weight change than untreated sheep at this time. A statistically significant increase in body weight gain was observed in 8 of 11 trials; in the other 3 trials, it appeared that the feed intake of the untreated sheep was already maximal. Wethers treated with dexamethasone trimethylacetate on arrival at an assembly point for live export arrived in the Middle East 23 days later with a lower mean weight loss, partly because fewer sheep lost a significant amount of weight.     

Use of Lathyrus Sativus L. (var. seminis albi) as a foodstuff for poultry

1. The gross composition of Lathyrus sativus was examined, and its use as a foodstuff for growing chicks over time as well as the influence of supplementation with certain amino acid combinations were studied.

2. Chemical analyses indicated lathyrus to be high in crude protein with adequate concentrations of most inorganic elements and amino acids except methionine and cystine.

3. The performance of growing chicks fed 800 g/kg lathyrus over a four week period was significantly poorer than those given a wheat/ soyabean meal‐based diet (P<0.05), but there appeared to be some adaptation to the antinutritive factors in the lathyrus.

4. Chick performance was markedly improved by dietary methionine supplementation alone (P<0.05); it was slightly better when trypto‐phan was added in combination with methionine but was still inferior to that on a wheat/soyabean meal‐based diet.

5. Supplementation of lathyrus‐based diets with methionine and tryto‐phan may improve chick performance, but it is not sufficient to overcome the effects of antinutritive factors in the legume.