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Nicholas V Emanuele

Publications and source records attributed to Nicholas V Emanuele.

7 recordsLinked to original sources
PubMed2005

The impact of burn injury and ethanol on the cytokine network of the mouse hypothalamus: reproductive implications.

Nearly 50% of the patients admitted to hospitals for burn injuries have detectable levels of alcohol (EtOH) in their circulation. In fact, EtOH is often a causal factor in their injury. It is well known that EtOH as well as burn injury disrupt function of the hypothalamic-pituitary-gonadal (HPG) axis. The cellular mechanisms by which EtOH and/or burn impacts on the HPG are not entirely understood. In the studies reported here, we tested the hypothesis that these injuries mediated their effects by local hypothalamic inflammation. Young adult male mice were subjected to either a 15% total body surface area, full thickness scald, to EtOH, or to both and compared to appropriate controls. They were sacrificed 48 h later. EtOH and burn, as well as the combined injury, consistently and impressively reduced serum testosterone, while increasing hypothalamic concentrations of all three of the pro-inflammatory cytokines, TNFalpha, IL-1beta, and IL-6. In general, the increases induced by burn were greater than those caused by EtOH and the effect of the combined insult was not additive. Hypothalamic concentrations of LHRH were also increased. The data are consistent with the idea that EtOH and/or burn, as models of critical illness, medicate their hypothalamic suppressive effects via increase in pro-inflammatory cytokines.

Animals↗
PubMed2005

Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction.

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague-Dawley rats 35 days old were pair-fed a Lieber-DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.

Animals↗
PubMed2005

Exposure to ethanol induces oxidative damage in the pituitary gland.

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone and decreased or inappropriately normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect in the pituitary. The molecular mechanisms behind this disorder are undefined. A role for ethanol-induced oxidative damage in the pathophysiology is supported by studies in liver, muscle, and heart of experimental animals, but there is limited evidence in the pituitary. We examined markers of oxidative damage to lipids and proteins in pituitaries from rats consuming ethanol for 5, 10, 20, 30, and 60 days in addition to markers of damage to nucleic acids in pituitaries after 60 days of ethanol exposure. There were increases in 8-oxo-deoxyguanosine immunoreactivity, a marker of oxidative damage to nucleic acids, and an overall increase in malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation. Protein carbonylation and protein nitrotyrosination, markers of protein oxidation, were significantly increased after 30 days and 60 days of ethanol consumption, respectively. After 60 days of ethanol exposure, TUNEL assay revealed that cell death in the ethanol-treated pituitaries was not significantly different from that in the pair-fed controls at the time of examination. We also measured serum testosterone, FSH, and LH after ethanol consumption for 5, 10, 20, 30, and 60 days. Through 5 to 60 days of ethanol exposure, testosterone levels were consistently lower whereas LH and FSH were inappropriately unchanged, suggesting pituitary malfunction. These results provide evidence for ethanol-induced oxidative damage at the pituitary level, which may contribute to pituitary dysfunction.

Aldehydes↗
PubMed2004

Calponin is expressed by Sertoli cells within rat testes and is associated with actin-enriched cytoskeleton.

Within seminiferous tubules, Sertoli cells form three types of actin-filament-containing cell junctions, viz., tight junctions, ectoplasmic specializations, and tubulobulbar complexes. These Sertoli cell junctions are involved in the formation of the blood-testis barrier, germ cell translocation, and the release of spermatozoa. Actin and actin-binding proteins are important for these functions. In the present study, a monoclonal antibody against human smooth-muscle-cell calponin detected a 38-kDa protein in a total protein extract of rat testis. The protein has a molecular weight identical to that of aorta calponin and binds calmodulin. Calponin mRNA was detected in the testis and cultured rat Sertoli cells by the reverse transcription/polymerase chain reaction method. Thus, the 38-kDa protein present in the testes is a basic isoform of calponin. In adult rats (70 days of age or older), calponin was detected within seminiferous tubules at sites of Sertoli cell junctions. Cultured Sertoli cells express calponin, whereas cultured spermatogonia do not. When rat testicular tissue was fractionated into cytosol, membrane, and cytoskeleton fractions, calponin was detected in all three fractions. Calcium, potassium, and okadaic acid reduced the amount of calponin associated with the cytoskeleton. These data suggest that Sertoli cells express calponin. The function of calponin within the testis is as yet unknown.

Actins↗
PubMed2002

Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes.

Major clinical trials have shown that excellent glycemic control, sustained over time, can prevent or delay the microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy. No prospective trial has clearly shown that glycemic intervention can prevent the macrovascular complications of diabetes, such as myocardial infarction, cerebrovascular accident, and amputation. However, a number of landmark clinical trials have shown the efficacy of control of blood pressure and lipids and use of antiplatelet agents (mainly aspirin) in protecting the macrovasculature of individuals with diabetes. In this article, glycemic, blood pressure, lipid, and antiplatelet trials relevant to the treatment of people with type 2 diabetes are reviewed.

Clinical Trials as Topic↗
PubMed2002

Alcohol's effects on female reproductive function.

Mild-to-moderate alcohol use has numerous negative consequences for female reproductive function. Animal studies have shown that alcohol consumption disrupts female puberty, and drinking during this period also may affect growth and bone health. Beyond puberty, alcohol has been found to disrupt normal menstrual cycling in female humans and animals and to affect hormonal levels in postmenopausal women. Research has explored the mechanisms of these effects and the implications of these effects for bone health.

Adolescent↗