The pathogenesis of gonococcal urethritis in men: confocal and immunoelectron microscopic analysis of urethral exudates from men infected with Neisseria gonorrhoeae

Confocal and immunoelectron microscopic analysis of urethral exudates from 12 men with gonococcal urethritis showed that Neisseria gonorrhoeae can invade urethral epithelial cells. Studies with acridine orange stain demonstrated that the majority of organisms within urethral epithelial cells were viable at the time of fixation. Three-dimensional modeling of an infected epithelial cell using image analysis of 21 digitized confocal sections stained with YOYO-1 and DiIC 18(3) revealed that gonococcal invasion of these cells occurred in a polar fashion, most likely at the epithelial luminal surface. Serial immunoelectron micrographs showed evidence of membrane fusion with pedestal formation between the gonococcus and the epithelial cell, gonococci within vacuoles, and occasional gonococci free in the cytoplasm. Immunoelectron microscopy studies showed ruptured vacuoles at the cell surface releasing organisms. These studies demonstrate that urethral epithelial cells are invaded by gonococci during the course of infection in males.     

Microalbuminuria as predictor of atherosclerotic cardiovascular disease in IDDM

The aim of this follow-up study was to assess whether slightly elevated urinary albumin excretion, i.e., microalbuminuria, precedes development of atherosclerotic vascular disease in IDDM. Out of 259 IDDM-patients 30 developed vascular disease during 2,457 person-years. Microalbuminuria was significantly predictive of vascular disease (hazard ratio (95% confidence interval) 1.06 (1.02-1.18) per 5 mg/24 hours increase in urinary albumin excretion; p = 0.002). The predictive effect was independent of age, sex, blood pressure, tobacco smoking, serum concentrations of total-cholesterol, HDL-cholesterol, sialic acid, and von Willebrand factor, and of haemoglobin A1c, insulin dose, diabetes duration, and diabetic nephropathy (hazard ratio (95% confidence interval) 1.04 (1.01-1.08) per 5 mg/24 hours increase in urinary albumin excretion; p = 0.03). It is concluded that slightly elevated urinary albumin excretion is an independent predictor of atherosclerotic vascular disease in insulin-dependent diabetes mellitus.     

Guanylyl cyclase receptors and guanylin-like peptides in reptilian intestine

Receptors for guanylin and uroguanylin were identified on the mucosal surface of enterocytes lining the intestine of the bobtail skink (Tiliqua rugosa), king's skink (Egernia kingii), and knight anole (Anolis equestris) by receptor autoradiography using 125I-ST (Escherichia coli heat-stable enterotoxin) as the radioligand. Specific, high-affinity binding of 125I-ST to receptors was found on the microvillus border of enterocytes and little or no specific binding of 125I-ST was observed in other strata comprising the gut wall. The American alligator (Alligator mississippensis) also exhibited receptor binding, but unlike the other three species had relatively high levels of apparent nonspecific binding. A comparison of intestinal cGMP accumulation responses between the American alligator and the knight anole demonstrated a greater magnitude of cGMP responses to ST and guanylin in vitro in the knight anole relative to the tissue cGMP accumulation responses of alligators. Treatment with ST resulted in markedly greater tissue cGMP accumulation responses in both species compared to treatment with guanylin. To complete a paracrine signaling pathway in reptilian intestine, guanylin-like peptides that stimulated cGMP accumulation in human T84 intestinal cells were isolated from the intestinal mucosa of alligators. We conclude that functional receptor-guanylyl cyclases and one or more endogenous guanylin/uroguanylin-like peptides occur in the intestinal tract of reptiles as well as in the intestines of mammals and birds. Thus, higher vertebrates have a conserved signaling pathway that regulates intestinal function through the first-messenger peptides, guanylin and/or uroguanylin, and the intracellular second messenger, cGMP.     

Stress-induced subsensitivity to catecholamines depends on the estrous cycle

In this article we compare how sensitivity to the chronotropic effect of noradrenaline and adrenaline of right atria isolated from female rats is modified after repeated swimming or foot-shock stress, under the influence of the estrous cycle. Right atria from stressed female rats sacrificed at diestrus were subsensitive to both catecholamines, irrespective of the stressor agent. However, although subsensitivity to noradrenaline was of similar intensity, subsensitivity to adrenaline was more pronounced in right atria from foot shock stressed rats as opposed to swimming-stressed rats. Identical stress protocols did not induce any alteration in atrial sensitivity to catecholamines when the stressed female rats were sacrificed at estrus. We conclude that the stress reaction concerning the mediation of cardiac chronotropism by catecholamines is related to the severity of the stressor agent and is strongly influenced by the estrous cycle.     

Effects of prenatal androgenization, melengestrol acetate, and Synovex-H on feedlot performance, carcass, and sensory traits of once-calved heifers

Three studies were designed using a 2 x 2 factorial arrangement of treatments within each experiment to evaluate the effects of various management techniques on growth and carcass traits of once-calved heifers. In Exp. 1, 33 yearling (16 control [C] and 17 prenatally androgenized [PA]) and 39 once-calved (20 C and 19 PA) nonpregnant heifers were used to evaluate the effects of age and PA. Once-calved heifers were approximately 31 kg heavier (P < .03) on-test, initially consumed 11% more (P < .01) DM, and gained 11% faster (P < .08), but had similar (P = .44) gain to feed ratios (.138 vs. .131) as yearlings. Growth performance was not affected by PA. The yearling and once-calved heifers were then slaughtered at approximately 707 and 1,080 d of age, respectively. Despite maturity differences (P < .01), marbling scores (P = .26) and percentage of choice carcasses (P = .27) were similar. However, on the basis of newly accepted grading changes, percentage of once-calved heifer carcasses grading choice decreased from 57.3 to 34.4%. Organoleptic properties did not differ. Experiments 2 and 3 were then conducted to evaluate effects of commercially available products (melengestrol acetate [MGA] and Synovex-H) on feedlot characteristics of heifers following weaning of their first calf. In Exp. 2, 48 once-calved Simmental-based heifers were fed during the summer to a constant compositional fat thickness of .8 cm. Experiment 3 was conducted in the late fall and early winter, during which 52 moderately sized heifers were fed for 116 d postweaning and slaughtered. Performance of heifers in Exp. 2 was not affected by MGA. However, heifers fed MGA in Exp. 3 gained 9% faster (P < .05) than controls. In Exp. 2, Synovex-H tended to improve ADG (P < .09) and feed efficiency (P < .07), but did not affect performance in Exp. 3. Most carcass traits were not affected by either treatment. Nonpregnant, once-calved heifers seem to have a large capacity for efficient weight gain as compared with yearling heifers. However, hormonal compounds, such as testosterone propionate provided pre- or postnatally (Synovex-H), and MGA do not appear to provide the consistent, positive responses often seen with younger, more typical feedlot heifers.     

The study of outcomes for CAPD versus hemodialysis patients

Tacrine [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA), Cognex] is a potent acetylcholinesterase inhibitor recently approved for treatment of mild-to-moderate Alzheimer's disease. The potential for THA and/or a metabolite of THA to accumulate in brain tissue was investigated by autoradiographic and metabolic profiling techniques in rats given single and multiple doses of [14C]THA. In addition, the brain-to-plasma distribution time course of orally administered 1-hydroxy-THA (1-OH-THA, 24 mg/kg), a primary rat metabolite with anticholinesterase activity, was also examined. Results from a 16 mg/kg single-dose study showed THA to cross the blood-brain barrier readily and concentrate in brain tissue, approximately 5-fold compared with plasma. The metabolite 1-OH-THA was found in much lower amounts relative to THA and when given separately at a similar dose the levels in brain tissue were comparable with plasma concentrations. After multiple-dose administration, THA concentrations in brain tissue were approximately 3-fold higher than those achieved after a single oral dose. However, concentration of 1-OH-THA metabolite increased only 50%. These data suggest a marked difference between the ability of THA and 1-OH-THA to accumulate in brain tissue and may reflect differences in lipophilicity as estimated by calculated log p values. The relevance of THA accumulation in brain tissue to delays observed in THA clinical management of Alzheimer's disease remains to be established.