In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line.

Objective: To evaluate for direct toxic effects of high glucose concentrations on cellular physiology in GnRH secreting immortalized GT1-1 neurons.

Design: Prospective experimental design.

Setting: In vitro experimental model using a cell culture system.

The effect of diabetes and centrally administered insulin on anterior hypothalamic estrogen receptor alpha immunoreactivity.

Diabetic rats have characteristic reproductive deficits. Peripheral and central (intra-cerebro-ventricular [ICV]) insulin restores the reproductive phenotype to control levels. In this experiment, we evaluated a possible defect in steroid feedback by evaluating hypothalamic estrogen receptor (ER) alpha availability using ERalpha immunocytochemistry.

Intracerebroventricular leptin regulates hepatic cholesterol metabolism.

To elucidate the control of hepatic cholesterol metabolism by leptin, rats were administered IV (intravenous) leptin, ICV (intracerebroventricular) leptin or saline. A single low dose of ICV leptin was as effective as a continuous IV infusion of high-dose leptin at decreasing the activities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase. These results indicate that the hepatic response to leptin is transduced via the central nervous system.

Central insulin administration maintains reproductive behavior in diabetic female rats.

Diabetic female rats have decreased ovulation, reproductive behavior and luteinizing hormone surges. Peripheral insulin treatment restores the phenotype to normal and also corrects many of the metabolic changes. To further evaluate the role of insulin in the specific maintenance of reproductive behavior, rather than administering it peripherally, we gave insulin intracerebroventricularly (ICV) at doses that did not correct the peripheral metabolic changes associated with diabetes such as hyperglycemia.

Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms.

Leptin has been shown to decrease glucose-stimulated insulin secretion in both in vivo and in vitro studies. As some of the effects of leptin have been elicited through both peripheral and central mechanisms, we assessed whether leptin modulates insulin secretion also through the central nervous system. We infused leptin or saline through implanted intracerebro-ventricular (ICV) catheters to chronically catheterized, conscious rats (n=15), 2 h after initiation of hyperglycemic (approximately 11 mM) clamp.

Effect of centrally administered insulin on gonadotropin-releasing hormone neuron activity and luteinizing hormone surge in the diabetic female rat.

Diabetic female rats have decreased ovulation, sexual behavior, and luteinizing hormone (LH) surges. Peripheral insulin treatment restores the phenotype to normal. We administered central insulin and analyzed serum LH during the time of the LH surge in diabetic and non-diabetic animals to determine if central insulin was sufficient to normalize the phenotype.

Hypothalamic insulin signaling is required for inhibition of glucose production.

Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional changes in hypothalamic insulin signaling affect glucose production. The infusion of either insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose production independent of circulating levels of insulin and of other glucoregulatory hormones.

Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats.

We investigated the role of hypothalamic insulin signaling in the regulation of energy balance and insulin action in rats through selective decreases in insulin receptor expression in discrete hypothalamic nuclei. We generated an antisense oligodeoxynucleotide directed against the insulin receptor precursor protein and administered this directly into the third cerebral ventricle. Immunostaining of rat brains after 7-day administration of the oligodeoxynucleotide showed a selective decrease of insulin receptor protein within cells in the medial portion of the arcuate nucleus (decreased by approximately 80% as compared to rats treated with a control oligodeoxynucleotide).

Central administration of oleic acid inhibits glucose production and food intake.

The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was independent of leptin and was accompanied by a decrease in the hypothalamic expression of neuropeptide Y.

Central melanocortin receptors regulate insulin action.

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity.

The effect of diabetes on alpha2-adrenergic receptor activity in the reproductive centers of the female rat brain.

Objective: We hypothesized that known diabetes-induced deficits in female rat reproduction may result in part from decreased central alpha(2)-noradrenergic receptor density or affinity.

Study Design: Female rats were oophorectomized and divided into 2 groups; one group received streptozocin during the operation to induce diabetes, and the other served as a nondiabetic control group. Random blood glucose levels were measured.

Hormonal integration of neurochemical and sensory signals governing female reproductive behavior.

This review focuses on findings from our laboratory regarding mechanisms by which the ovarian steroid hormones, estradiol (E2) and progesterone (P), act in the hypothalamus (HYP) to regulate the expression of lordosis, an important component of female reproductive behavior in rats and many other species. The first section summarizes recent work suggesting that cGMP, perhaps via P-receptor activation, may be an intracellular mediator of the facilitatory actions of a variety of hormones and neurotransmitters on lordosis behavior in E2-primed rats. In the second section, we focus on E2 and P regulation of norepinephrine (NE) neurotransmission in the HYP.

Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes.

Acute intravenous infusions of leptin markedly alter hepatic glucose fluxes (Rossetti, L., Massillon, D., Barzilai, N.

Effects of diabetes and estradiol on norepinephrine release in female rat hypothalamus, preoptic area and cortex.

These studies determined whether diabetes and estradiol treatment altered norepinephrine (NE) release from hypothalamus, preoptic area (POA), and cortical slices from ovariectomized (OVX) female rats. Animals were sacrificed 12 days after the onset of streptozotocin-induced diabetes and 48 h following vehicle or estradiol injection. Brain slices were preloaded with 3H-NE, and release was evoked twice (S and S2) by electrical stimulation.

Estradiol reduction of alpha 2-adrenoceptor binding in female rat cortex is correlated with decreases in alpha 2A/D-adrenoceptor messenger RNA.

We developed a quantitative RNAse protection assay for alpha 2A/D-adrenoceptor messenger RNA in rats to test the hypothesis that decreases in cortical alpha 2-adrenoceptor binding observed following estrogen treatment of ovariectomized rats correlate with reduced levels of messenger RNA encoding the predominant alpha 2-adrenoceptor subtype expressed in cortex. Estradiol treatment for 48 h reduced cortical alpha 2A/D-adrenoceptor messenger RNA by approximately 50% when compared to ovariectomized, oil-treated control animals. Estradiol down-regulation of alpha 2A/D-adrenoceptor messenger RNA was accompanied by a significant decrease in cortical alpha 2-adrenoceptor density, as measured by 3H-RX821002 binding.

Deficits in reproductive behavior in diabetic female rats are due to hypoinsulinemia rather than hyperglycemia.

These studies determined whether deficits in reproductive behavior observed in streptozotocin (STZ)-induced diabetic female rats are caused by hyperglycemia or loss of insulin. Female Sprague-Dawley rats were ovariectomized and made diabetic by a single ip injection of STZ (75 mg/kg). Reproductive behavior was measured 12 days after the onset of hyperglycemia following the injection of estrogen and progesterone in doses known to restore reproductive behavior in nondiabetic rats.

Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area.

Estradiol treatment for 48 h increases the density of alpha 1B-adrenoceptors in the hypothalamus-preoptic area of ovariectomized female rats by five- to six-fold. Present studies tested the hypothesis that estradiol elevation of hypothalamus-preoptic area alpha 1B-adrenoceptor density is correlated with increased levels of mRNA for this receptor. We developed a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) protocol for measuring brain alpha 1b-adrenoceptor mRNA.

Kinking and coiling of internal carotid artery with and without associated stenosis. Surgical considerations and long-term follow-up.

Although incidence of coiling and kinking of internal carotid artery has been estimated to be from 10% to 16% in general population, respective clinical significance still remains the ground of controversy. Cerebrovascular hemodynamic changes mainly from kinking and in a lesser degree from coiling, have been documented with oculoplethysmographic and angiographic differences, accompanying positional changes of the head. The opposite view however, that similar variations represent a benign and incidental finding, has been also expressed.

Hemoperitoneum secondary to exogastric leiomyosarcoma: a case report.

We present the case of a 50-year-old man with hemoperitoneum secondary to a bleeding exogastric leiomyosarcoma. The patient underwent emergency laparotomy and resection of the mass en block with a segment of the lesser curvature was successfully performed.

Lipomatosis of the ileocecal valve leading to episodes of partial small bowel obstruction.

The cases of two female patients with lipomatosis of the ileocecal valve inducing episodes of intestinal obstruction are presented. A barium enema with air contrast was performed in patient 1; patient 2 was operated on to treat ileus. Resection of the fatty tissue from the ileocecal valve was performed at operation, after histologic diagnosis on frozen section.

Progesterone attenuation of alpha 1-adrenergic receptor stimulation of phosphoinositol hydrolysis in hypothalamus of estrogen-primed female rats.

These experiments examined whether the previously observed abolition by progesterone (P) of alpha 1-adrenergic potentiation of adenylyl cyclase activity in brain slices of estrogen-primed female rats is attributable to a reduced capacity of alpha 1-adrenoceptors to stimulate phosphoinositol hydrolysis. In preoptic area and hypothalamic slices from ovariectomized (OVX) female rats, both norepinephrine (NE) and the alpha 1-adrenergic agonist phenylephrine (PHE) were robust stimulators of inositol phosphate (IP) formation. The NE response was completely blocked by the alpha 1-adrenergic antagonist prazosin.

A thermodynamic analysis of estrogen regulation of alpha 2-adrenoceptor binding.

We previously demonstrated that in vivo estradiol treatment markedly attenuates alpha 2-adrenoceptor function and coupling to G-proteins in the hypothalamus of female rats. Ligand binding studies indicated that 48 h exposure to estradiol decreases the number of alpha 2-adrenergic receptors in the agonist high affinity state. In the present studies, when [3H]RX821002 was used to label brain alpha 2-adrenoceptors, the density of binding sites significantly increased in the hypothalamus and preoptic area 48 h after estrogen treatment.

Postoperative alkaline reflux gastritis following vagotomy.

This study was undertaken to evaluate the incidence and severity of postoperative alkaline reflux gastritis in 798 symptomatic duodenal ulcer patients who had undergone vagotomy. The condition was identified on the basis of the unique endoscopic and histological findings in 116 (14.5%) of them.

Carotid artery surgery and the principle of prophylaxis: recurrence in operated and nonoperated patients.

A total of 700 carotid endarterectomies have been performed over a 24-year period at the authors' institute; of these patients 632 (90.3%) had unilateral and 68 (9.7%) had bilateral disease.

Abdominal aneurysmectomy and determinants of improved results and late survival. Surgical considerations in 672 operations and 1-15 year follow-up.

The present communication is concerned with 672 abdominal aneurysmectomies performed over a period of 24 years. All aneurysms with diameter 4 cm and above, were considered for surgery. Emphasis is given on factors determining post operative results and late survival.