Glutathione peroxidase activity in endometrium: effects of sex hormones and cancer

In the present study, we investigated the mechanism of phenylephrine (alpha-1-adrenergic receptor agonist)-induced arachidonic acid release in Japanese white rabbit aortic smooth muscle cells (SMC). When introduced into permeabilized smooth muscle cells, guanosine S-[gamma-thio] triphosphate (GTPgamma S), which activates GTP-binding proteins (G proteins), stimulated arachidonic acid (AA) release. Neomycin, an inhibitor of phosphoinositide (PI) turnover, was almost without effect on GTP[gamma S] stimulated AA release. In addition, pertussis toxin (PT) partially inhibited phenylephrine-stimulated AA release, suggesting that IAP (Islet activating protein)-sensitive G proteins mediate this process. Phenylephrine-stimulated AA release was also inhibited by decreased extracellular calcium and aristolochic acid, suggesting a role for a phospholipase A2 (PLA2). Next PLA2 is reported to be a substrate for mitogen-activated protein (MAP) kinase. We examined the effect of phenylephrine on MAP kinase and c-jun N-terminal kinase (JNK) phosphorylation. Phenylephrine didn't induce phosphorylation of MAP kinase, but did induce phosphorylation of JNK. In addition, cells which were pretreated with PT inhibited the phosphorylation of JNK. These results suggest that IAP-sensitive G protein is involved in the coupling between alpha1-adrenergic receptor (AR) and PLA2 in cultured rabbit aortic SMCs, and that the alpha1-AR-induced AA release is mediated by JNK.     

Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 +/- 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 +/- 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 +/- 0.09 and 0.15 +/- 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 +/- 0.24 and 0.97 +/- 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urothelial changes of the renal papillae in Sprague-Dawley rats induced by long term feeding of phenacetin

Thirty female Sprague-Dawley rats were fed 0.535 per cent phenacetin in the diet for up to 110 weeks. Twenty-six of these rats developed urothelial hyperplasia, partly papillary, of the renal papillae. Twenty-eight rats showed dilatation of the vasa recta frequently associated with thrombus formation and calcification. One phenacetin fed rat had epithelial hyperplasia associated with chronic pyelitis. In 2 of the 30 control rats urothelial hyperplasia was found to be associated with chronic pyelitis. The hyperplastic urothelial changes and vascular changes were often, but not always, present simultaneously. One control rat developed a mammary carcinoma, as compared with 5 rats in the phenacetin group. Four phenacetin fed rats developed carcinoma of the ear duct. The results of the present investigation provide evidence that phenacetin can induce proliferative lesions of the urothelium of the rat renal pelvis with weak carcinogenic activity in the ear duct and mammary glands.     

Urothelial hyperplasia of the renal papillae in female Sprague-Dawley rats induced by long term feeding of phenacetin

Twenty-one of 40 rats fed phenacetin in the diet for up to 86 weeks developed urothelial hyperplasia of the renal papillae. Two of 30 rats in the control group had similar changes associated with chronic pyelitis. The difference is statistically significant (p less than 0.01).     

Changes in plasma glucose, insulin, glucagon, catecholamine, and glycogen contents in tissues during development of alloxan diabetes mellitus in rats

Leishmanial antigens (LAg) were used as a vaccine against Leishmania donovani, the causative agent of visceral leishmaniasis. BALB/c mice, immunized intraperitoneally with 20 micrograms of the antigen in phosphate-buffered saline (PBS) or entrapped in liposomes, were infected intravenously with 2 x 10(7) L. donovani promastigotes. Mice immunized with PBS and empty liposomes showed similar levels of parasite burdens in the liver and spleen. Injection of the antigen alone or entrapped in liposomes, followed with infection, induced significant levels of protection against the disease. After 2 and 4 mo of infection, mice immunized with free antigen induced 7.4% and 50.7% reduction in the liver parasite burden, respectively, compared to control (PBS) mice. With antigen encapsulated in liposome, the liver parasite burden was further reduced by 30.4% and 73% at 2 and 4 mo by infection, respectively. Splenic parasite burden was very low at 2 mo of infection. At 4 mo, the parasite level was reduced by 54.2% with free antigen and 69.3% with antigen entrapped in liposomes. Whereas the protection induced by the free antigen is mainly cell mediated, stimulation of an antibody response together with a strong delayed-type hypersensitivity may be responsible for the better protection with liposomal antigen.     

Changes in the fractional collagen composition of the kidneys in rats under immobilization stress and alloxan diabetes

There were examined 106 patients with purulent-necrotic complications (PNC) of erysipelas and 102 patients without PNC. Significant disorders of the immune status were revealed: the reduction of T-lymphocytes quantity, their subpopulational content dysbalance, the rise of level of a middle- and small-molecular immune complexes. In patients with PNC the immunocorrection conduction is expedient.     

Oxygen consumption and ATPase activity in the corneal epithelium of rabbits with alloxan induced hyperglycemia

PURPOSE: To more fully investigate the effect of hyperglycemia on the aerobic metabolism of the corneal epithelium. METHODS: Corneal epithelial oxygen uptake rates and adenosine triphosphatase (ATPase) activities were measured in alloxan-induced diabetic and control rabbits over a 10 week period. RESULTS: A transient reduction in epithelial oxygen uptake rate was seen at week 1. A chronic 14% reduction in oxygen consumption occurred after 6 weeks of hyperglycemia. Epithelial ouabain-sensitive ATPase activity was unaffected by 10 weeks of hyperglycemia. Epithelial ouabain-insensitive ATPase activity decreased 14% after 10 weeks of hyperglycemia. CONCLUSIONS: Ten weeks of hyperglycemia in the alloxan induced diabetic rabbit was associated with a 14% decrease in corneal oxygen uptake, a 14% decrease in corneal epithelial ouabain-insensitive ATPase activity and no change in corneal epithelial ouabain-sensitive ATPase activity. The Crabtree effect may help explain some of the clinical signs seen in the diabetic cornea as well as explaining why diabetic patients can wear contact lenses with minimal clinical problems.     

Activity of the enzymes participating in purine metabolism of cancerous and noncancerous human kidney tissues

CONTEXT: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. OBJECTIVE: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. DESIGN: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). INTERVENTION: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. MAIN OUTCOME MEASURES: Fatal and nonfatal heart failure. RESULTS: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. CONCLUSION: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.     

Vitamin D3 transport across the intestines and its metabolism in the liver of rats with alloxan diabetes

Vitamin D3 intestinal transport and liver metabolism were studied in rats with alloxan-induced diabetes. The condition was induced by i.v. alloxan injection in a dose of 40 mg/kg b.m. Diabetes development was monitored by blood serum glucose measurements, carried out for 30 days. [3H]-cholecalciferol absorption in the rat intestine was found inhibited in the diabetic animals as against the reference animals, which fact results in disordered entry of vitamin D3 to the body. [3H]-cholecalciferol absorption by the liver is reduced in the examined condition, and the time of its metabolism is increased more than threefold as against the reference animals. The share of vitamin D3 hydroxylation by the liver of diabetic rats is also significantly reduced. The described disorders are responsible, among other things, for the reduction of the levels of vitamin D3 active metabolites in the blood serum of rats with experimental diabetes.     

Activity of lysosomal and nonlysosomal proteases and contents of protein and its degradation products in the blood serum of rats with fibrosarcoma induced by methylcholanthrene

Activity of lysosomal and nonlysosomal proteases and contents of protein and its degradation products in the blood serum of rats with methylcholantrene fibrosarcoma were evaluated. Activity of lysosomal proteases and prolidase and prolinase as well in the blood serum of rats with methylcholanthrene tumour did not differ from the activity of these enzymes in the blood serum of control rats. Only the activity of elastase and collagenase in the blood serum of rats with methylcholanthrene tumour especially with tumour of intermediate and big mass was increased. Content of total protein was decreased in the blood serum of rats with tumour of intermediate and big mass and contents of glycoproteins and alfa-amin nitrogen were increased in comparison to the blood serum of control rats.     

Pilonidal sinus: long term results of excision and closure technic. Review of the literature

The Authors report their experience in the surgical management of pilonidal sinus with modified Leichtling technique. Long term results of various treatments proposed in the past are analyzed: it is not possible to identify a satisfactory procedure for the treatment of pilonidal sinus. Ideal treatment should avoid hospital admission and general anaesthesia, assure a short time of healing, a reduced number of complications, a low risk of recurrence and a minimal time off from work. Authors' variations to the original technique show good results for non recurrent pilonidal sinus and a lower number of failed primary healing. Recurrences are probably related to the patient anatomical status which may be modified only by flattening natal cleft or surgically changing follicles orientation of presacral skin, together with a meticulous hygiene and shaving of the presacral healing area as well as a dietary regimen for obese patients.     

Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the initial events in the pathogenesis of insulin-dependent diabetes mellitus?

When aiming at preventing IDDM in man, knowledge of the molecular mechanisms leading to beta cell destruction may facilitate identification of new possible intervention modalities. A model of IDDM pathogenesis in man suggests that cytokines, and IL-1 in particular, are of major importance in the initial events (Nerup et al 1994) (Fig. 1). In vitro rat experiments demonstrated that rhIL-1 beta inhibits beta cell function and induces beta cell death both in isolated islets of Langerhans and in the isolated perfused pancreatic gland. With the long term goal of identifying new modalities capable of preventing IDDM in man, the aim af this review was to investigate the effects of rhIL-1 beta on beta-cell function and viability in normal rats. This review discussed 1) the pharmacokinetics of IL-1 beta in rats as the basis for choice of route of administration and dose of rhIL-1 beta, 2) the effects and molecular mechanisms of IL-1 beta on temperature and food intake used as control parameters for successful injection of rhIL-1 beta in rats, 3) the effects of one or more injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms leading to IL-1 beta induced beta cell inhibition in vivo, and some possible intervention modalities based on the molecular mechanisms, 5) the effects of IL-1 beta on spontaneous diabetes mellitus in DP BB rats, and 6) the effects and molecular mechanisms of IL-1 beta induced inhibition of thyroid epithelial cell function and aggravated thyroiditis in DP BB rats, compared to the effects of IL-1 beta on rat beta cell function. Finally, this review discussed the effects of IL-1 beta on human beta cells in vitro, and the clinical relevance of these experiments, with special reference to a clinical trial with the aim of preventing IDDM in man. The pharmacokinetic studies suggested that IL-1 beta is distributed according to a two-compartment model with a first-order elimination. Interleukin-1 beta reached all the investigated organs in the rats, was accumulated in kidneys and was excreted in the urine. The data suggested that IL-1 beta also accumulated in the islets of Langerhans. After injection of 4.0 micrograms/kg pathophysiologically relevant concentrations of rhIL-1 beta were reached and intact rhIL-1 beta persisted for up to 5 hrs in plasma. Peripheral injections of IL-1 beta dose-dependently induced fever and anorexia in rats, probably via induction of PGE2 in the brain or in peripheral tissues thereafter passing the blood-brain barrier. Nitric oxide produced by cNOS seems to be a molecular mediator of IL-1 beta induced fever but not of anorexia. Fever and anorexia are well described effects of IL-1 beta in rats, and are as such usefull control parameters of the absorption and biological activity of IL-1 beta after peripheral injection. Injections of rhIL-1 beta to normal, non-diabetes prone rats induced initial beta cell stimulation followed by inhibition, in accordance with in vitro data. Furthermore, induction of peripheral insulin resistance coincided with beta cell inhibition after one daily injection for 5 days, leading to a transient diabetes mellitus-like state, characterized by hyperglycemia and hypoinsulinemia. At this time point, electron-microscopy did not demonstrate beta cell destruction. However, IL-1 beta induced intercellularly edema and microvillous processes on the beta cells, which might be early evidence of apoptosis. The diabetes mellitus-like state was not aggravated if the daily injections were continued beyond 5 days. Daily injections of rhIL-1 beta for 2 to 4 weeks induced formation of blocking IL-1 beta-antibodies in normal rats. Hence, injections exceeding 2 weeks should only be performed using species homologous IL-1 beta. The molecular mechanism of IL-1 beta induced beta cell inhibition in rats in vivo as in vitro, are likely to involve binding of IL-1 beta to the IL-1RtI, since the IL-1RtII is considered to be a decoy receptor. (ABSTRACT TRUNCATED)     

Neurochemical correlates of alloxan diabetes: protein and ribonucleic acid levels in the different regions of the rat brain

The levels of protein and ribonucleic acid in the cerebrum, cerebellum, optic lobes and medulla oblongata of normal and alloxan-diabetic rats were measured. In general, the protein content and levels of ribonucleic acid in the broad compartments of the brain of rat decreased during diabetes.     

Olfactory regulation of maternal behavior in rats: II. Effects of peripherally induced anosmia and lesions of the lateral olfactory tract in pup-induced virgins.

Carried out 3 experiments with virgin female Sprague-Dawley rats to isolate the effects of anosmia on maternal behavior from nonsensory effects of bulbectomy. Anosmia was produced peripherally by nasal infusion of zinc sulfate or centrally by lesioning the lateral olfactory tracts bilaterally. Discrimination tests verified anosmia produced by zinc sulfate. In nearly all cases anosmic Ss exhibited short latency maternal behavior when exposed to young pups. Odors from pups are viewed as delaying the onset of maternal behavior in virgins; females prevented from reacting to these odors are therefore able to receive and to respond more rapidly to those stimuli which elicit maternal behavior. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenergic blockade in diabetic and uninephrectomized rats: effects on renal size and on renal and urinary contents of epidermal growth factor

The glutamatergic transmission system plays a key role in afferent and efferent pathways involved in micturition. By in situ hybridization combined with retrograde Fast Blue labeling, expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor (GluR-A to -D) and N-methyl-D-aspartate (NMDA) receptor (NR1 and NR2A-D) subunit mRNAs were examined in visceromotor and somatomotor neurons of the rat lumbosacral spinal cord. Parasympathetic preganglionic neurons (PGNs) in the intermediolateral nucleus highly expressed GluR-A and GluR-B subunit mRNAs, with very low levels for GluR-C and GluR-D subunits. As for the NMDA receptor, PGNs were associated with abundant signals for NR1 subunit mRNA, but without any NR2 subunit mRNAs. On the other hand, somatomotor neurons in the ventral horn (dorsolateral nucleus) express all four AMPA receptor subunit mRNAs, showing relatively abundant expressions of GluR-C and GluR-D subunit mRNA compared with PGNs. In addition to high levels of NR1 subunit mRNA, dorsolateral nucleus neurons moderately expressed NR2A and NR2B subunit mRNAs. These results suggest that molecular organization of both AMPA and NMDA receptor channels are distinct between PGNs and dorsolateral nucleus neurons. Considering that native NMDA receptors are heteromeric channels composed of NR1 and NR2 subunits, it seems likely that dorsolateral nucleus neurons, not PGNs, are provided with functional NMDA receptors, which could induce activity-dependent changes in synaptic transmission in the efferent pathway for the lower urinary tract.