Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity

Previous studies showed that administration of dehydroepiandrosterone (DHEA) to lean and genetically obese Zucker rats reduced body weight. In the present experiments, the effect of DHEA treatment in rats with diet-induced obesity was evaluated. In experiment 1, male Sprague-Dawley rats (300 g) were fed a nonpurified diet (reference group) or a condensed milk-corn oil nonpurified diet [diet-induced obese (DIO) rats] for 7 wk. Then, 0.6% DHEA was included in the food of one-half of the DIO rats (DIO + DHEA rats). After 6 wk, DIO rats weighed 23% more and had greater fat pad weights, cell size and cell number than reference and DIO + DHEA rats. Brown fat mitochondrial respiration was similar in all groups. DIO rats had higher serum cholesterol and triacylglycerol concentrations than reference and DIO + DHEA rats. DIO + DHEA rats had lower serum insulin levels than DIO and reference rats. In experiment 2, male Sprague-Dawley rats (460 g) were fed either the nonpurified diet or the condensed milk diet for 8 wk. Condensed milk-fed rats were then divided into DIO and diet-resistant groups. One-half of the rats in each group were fed 0.6% DHEA for 2 wk. Body weights and serum glucose, insulin, triacylglycerol and triiodothyronine levels were lowered by DHEA treatment in all groups. Liver mitochondrial state 3 respiration rates per gram and per liver and peroxisomal beta-oxidation were higher in DHEA-treated than in control rats. In DIO rats, DHEA treatment appears to interfere with hyperplastic adipose tissue growth. In this strain of rats, DHEA appears to have hypolipidemic and hypoinsulinemic effects.     

Results of penetrating keratoplasty in vascularized corneas.

A retrospective longitudinal study of 105 penetrating keratoplasties for vascularized corneal opacities was done. The results of cases with an etiology of healed trachoma or healed corneal ulcers were compared. The vascularization was graded from Grade I to V depending on the quadrant and type of vascularization. Graft clarity of 2+ or more in cases of trachomatous opacity was achieved in 93% of cases and that after postinfectious opacity in 71.8%. Prognosis was poor in cases where deep vascularization was present in more than two quadrants or more than 180 degrees.     

Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Mouse chromosome 9 quantitative trait loci for soft tissue regeneration: Congenic analysis and fine mapping

Development of gene therapies for wound healing will depend on the identification of the genes involved in wound healing and tissue regeneration. Previous quantitative trait loci (QTL) studies in mice using the ear punch model have shown that major QTL exist on chromosome (Chr) 9 for soft tissue regeneration. In this study, we have developed a congenic line that contains the Chr 9 QTL chromosomal region from super healer MRL/MpJ in the genomic background of poor-healing SJL/J. The phenotypic effect of this QTL was confirmed in male mice, where the congenic line has shown significant healing improvement over SJL. Fine mapping of the Chr 9 QTL region with 23 markers at an average distance of 4.2 Mb using a total of 1,564 MRL/MpJ x SJL/J F(2) mice revealed the presence of at least three QTL peaks, implying that three separate loci may contribute to the phenotypic effect of this QTL. Based on the 2-LOD intervals, the total QTL region was confined to a combined length of no more than 28.2 Mb. Application of a Bayesian shrinkage estimation indicated that a major locus was located in a region of just 1.3 Mb.     

Corneoscleral ulceration in congenital erythropoietic porphyria (a case report)

A case of congenital erythropoietic porphyria, with corneoscleral ulceration, a rare association in this disorder, was reported. Anterior segment ischemia is believed to play an important role in the etiopathogenesis of corneoscleral ulceration. Remarkable improvement occurred with use of topical heparin drops (500 units/ml).     

Inhibin and age in men

OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.