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O Serri

Publications and source records attributed to O Serri.

At least 19 recordsLinked to original sources
PubMed1998

Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-alpha production in NIDDM patients after gliclazide treatment.

OBJECTIVE: To evaluate the effect of gliclazide administration to NIDDM patients on 1) monocyte adhesion to cultured endothelial cells, 2) plasma cytokine and lipid peroxide levels, and 3) monocyte cytokine production. RESEARCH DESIGN AND METHODS: Poorly controlled glyburide-treated diabetic patients (n = 8) and healthy control subjects (n = 8) were recruited. At the beginning of the study, glyburide was replaced by an equivalent hypoglycemic dose of gliclazide. Serum and monocytes were isolated from blood obtained from control and diabetic subjects before and after 3 months of treatment with gliclazide. RESULTS: Plasma lipid peroxide levels and monocyte adhesion to endothelial cells are enhanced in NIDDM patients, and gliclazide administration totally reverses these abnormalities. Before gliclazide treatment, serum levels of cytokines did not differ in the control and the diabetic groups, with the exception of an enhancement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 in NIDDM subjects. Basal and lipopolysaccharide (LPS)-stimulated monocyte production of interleukin-1 beta, IL-6, and IL-8 did not differ between the two groups. Furthermore, basal monocyte production of TNF-alpha was similar in the control and the diabetic groups, whereas a marked increase in the LPS-stimulated monocyte production of TNF-alpha was observed in the NIDDM group. Gliclazide treatment lowered LPS-stimulated TNF-alpha production by diabetic monocytes to levels similar to those observed in control subjects. CONCLUSIONS: Gliclazide administration to NIDDM patients inhibits the increased adhesiveness of diabetic monocytes to endothelial cells and reduces the production of TNF-alpha by these cells. These results suggest that treatment of NIDDM subjects with gliclazide may be beneficial in the prevention of atherosclerosis associated with NIDDM.

Animals↗
PubMed1997

Gliclazide decreases cell-mediated low-density lipoprotein (LDL) oxidation and reduces monocyte adhesion to endothelial cells induced by oxidatively modified LDL.

Low-density lipoprotein (LDL) oxidation has been suggested to play a key role in the pathogenesis of atherosclerosis, a major complication of diabetes mellitus. Gliclazide, a second-generation sulfonylurea, is widely used in the treatment of type II diabetes mellitus. Recently, a free-radical-scavenging activity of gliclazide has been reported. In the present study, we examined the effects of gliclazide on cell-mediated LDL oxidation and monocyte adhesion to endothelial cells induced by oxidatively modified LDL. Incubation of human monocytes and bovine aortic endothelial cells (BAE cells) with increasing concentrations of gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) resulted in a dose-dependent diminution of cell-mediated LDL oxidation as assayed by measurement of thiobarbituric acid (TBA)-reactive substances (TBARS). In addition, exposure of BAE cells to gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) induced a dose-dependent diminution of the oxidized LDL-induced monocyte adhesion to BAE cells as measured by the myeloperoxidase (MPO) assay. The effects of glyburide, another second-generation sulfonylurea, were also tested on cell-mediated oxidation of LDL and LDL-induced monocyte adhesion to the endothelium. No significant effect of this drug was observed on these two processes. These results therefore demonstrate that gliclazide is effective in vitro in reducing both cell-mediated LDL oxidation and monocyte adhesion to the endothelium. These findings suggest a potential beneficial effect of gliclazide in the prevention of atherosclerosis in diabetic patients.

Animals↗
PubMed1997

Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of dexfenfluramine.

OBJECTIVE: Hyperactivity of the HPA axis is a possible mechanism underlying abdominal obesity. We aimed to evaluate in premenopausal women with abdominal obesity, (i) the hypothalamic-pituitary-adrenal (HPA) axis responses to direct pituitary stimulation with corticotrophin releasing hormone (CRH) and to opioid blockade with naloxone, and (ii) the interaction between short-term serotoninergic activation with dexfenfluramine (dF), a serotonin-release agonist, and these responses. DESIGN AND SUBJECTS: Eight obese women (mean BMI, 35 kg/m2) with waist to hip ratio (WHR) > 0.85 were tested with CRH (1 microgram/kg i.v.) and naloxone (125 micrograms/kg i.v.) before and at the end of two treatment periods with dF (15 mg twice daily for 7 days) and placebo (washout 7 days) in a cross-over design. Eight normal weight control women were tested with CRH and naloxone. RESULTS: Prior to treatment, ACTH and cortisol responses to naloxone (areas under the curve) were significantly higher in obese women then in control women (P = 0.027 and P = 0.035 respectively) dF treatment resulted in significant (P < 0.05) reduction of ACTH and cortisol increments. In contrast, ACTH and cortisol responses to CRH were not significantly different in obese and control subjects and were unaffected by dF treatment. CONCLUSION: We conclude that women with abdominal obesity have hyperreactivity of the HPA axis to opiod blockage and that dexfenfluramine treatment reduces this hyperactivity.

Adrenocorticotropic Hormone↗
PubMed1996

Transsphenoidal adenomectomy for microprolactinomas: 10 to 20 years of follow-up.

BACKGROUND: Transsphenoidal adenomectomy is an effective treatment fo r microprolactinomas. However, postoperative recurrence of hyperprolactinemia is not rare. This study was designed to evaluate the long-term outcome of women with microprolactinomas operated on by transsphenoidal approach. METHODS: We retrospectively studied 64 women with microprolactinomas who underwent transsphenoidal adenomectomy and were followed for 10 to 20 years. RESULTS: Postoperatively, 58 women (90%) had normal plasma prolactin concentrations (<20 microg/L). After a mean of 3.3 years, during which the women were asymptomatic with normoprolactinemia, 25 (43%) had a relapse of hyperprolactinemia (> or = 20 microg/L). However, their evolution varied. Fifteen women had symptomatic hyperprolactinemia. Computed tomography (CT) scans showed recurrent microadenomas in 2 women. The other 10 women had only hyperprolactinemia. Of these women, 5 had transient hyperprolactinemia (29 +/- 4 microg/L) for 5 years, after which prolactin declined to normal 13 +/- 3 microg/L). The remaining five patients had elevated prolactin (31 +/- 3 microg/L) throughout the follow-up period (10 to 20 years). CT scan did not show recurrent adenomas in these women. Thirty-three women remained normoprolactinemic and asymptomatic for a mean period of 12 years (range, 10 to 20 years). CONCLUSIONS: In conclusion, most of the patients with late relapse of hyperprolactinemia have slight functional hyperprolactinemia and remain asymptomatic with no evidence of tumor recurrence.

Adenoma↗
PubMed1996

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Acromegaly↗
PubMed1996

The diagnosis and management of acromegaly: a Canadian consensus report.

OBJECTIVE: To reach a Canadian consensus on the diagnosis and management of acromegaly. OPTIONS DIAGNOSIS: documenting autonomous growth-hormone hypersecretion and imaging of the pituitary. TREATMENT: surgical resection, adjunctive therapy with bromocriptine or octreotide and radiation therapy. OUTCOMES: Reduction of the morbidity and mortality associated with acromegaly. EVIDENCE: Review of international literature. VALUES: Achievement of consensus among a panel of Canadian endocrinologists. BENEFITS, HARMS AND COSTS: Acromegaly is a chronic debilitating condition that is associated with morbidity and mortality. This consensus statement is designed to improve the diagnosis and management of this rare condition in order to minimize the negative outcomes. Costs were not considered. RECOMMENDATIONS: The diagnosis of acromegaly is established by documenting autonomous growth-hormone hypersecretion and by imaging the pituitary. Surgical resection is the cornerstone of treatment; however, adjunctive therapy is often needed. Although growth-hormone reduction is often associated with alleviation of symptoms, an attempt should also be made to normalize levels of growth hormone and its target growth factor, insulin-like growth factor-I (IGF-I). Persistent secretion of excess growth hormone and IGF-I may pose significant long-term health risks. A suggested therapeutic algorithm is provided. The ease of administration of bromocriptine should prompt a trial of therapy with this agent. The subcutaneous use of octreotide is of particular benefit to those patients with persistently high levels of growth hormone and IGF-I that cannot be suppressed by other means. Because acromegaly is relatively rare and complex, its diagnosis and treatment require the concerted efforts of an endocrinologist, an neurosurgeon and a radiation oncologist.

Acromegaly↗
PubMed1995

Intervention in diabetic vascular disease by modulation of growth factors.

Several growth factors have been implicated in the derangements of cellular metabolism and proliferation that occur in diabetes, eg. kidney mesangial expansion, retinal neovascular formation, and acceleration of atherosclerosis in large vessels. These phenomena contribute to the development and progression of diabetic microvascular and macrovascular disease. Pharmacological interventions aimed at reducing growth factor alterations, among other actions in diabetic vasculopathy, include a multitude of classes of drugs, such as angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, lipid-lowering drugs, and somatostatin analogs. New potential interventions, ie, antisense oligonucleotide local delivery, are being applied in growth factor research and may prove beneficial in diabetic macrovascular disease.

Arteriosclerosis↗
PubMed1994

Prolactinoma.

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Bromocriptine↗
PubMed1993

Effects of dexfenfluramine treatment on body weight and postprandial thermogenesis in obese subjects. A double-blind placebo-controlled study.

The purpose of this study was to determine the effects of dexfenfluramine on body weight and post-prandial thermogenesis in obese subjects. Thirty obese subjects, men and women, with an excess weight between 20 and 80% of the ideal weight and aged from 20 to 60 years, participated in this double-blind, placebo-controlled study. During the treatment period, the subjects were not submitted to caloric restriction. Basal metabolic rate and postprandial thermogenesis (following a 400 kcal test meal) measurements were made by indirect calorimetry. Metabolic parameters such as glucose, insulin, thyroid hormones, free fatty acids, beta-hydroxybutyrate, total cholesterol and triglycerides were also measured before the test meal. These measurements were done at baseline, after one week and after three months of treatment. Following the three month treatment period, the mean weight loss of the dexfenfluramine group was 4.6 +/- 1.6 kg (s.e.) (P < 0.01) whereas the placebo group maintained the initial weight. The mean weight loss in the dexfenfluramine group represented 15% of the initial overweight. There was no significant change in either group in basal metabolic rate and postprandial thermogenesis following one week and three months of treatment (P > 0.05). The caloric intake after the treatment period was significantly reduced in the dexfenfluramine group (from 1631 +/- 103 kcal (s.e.) to 1353 +/- 109 kcal (s.e.); P < 0.05); in the placebo group, the changes were not significant (P > 0.05). The plasma concentrations of tri-iodothyronine, total cholesterol and triglycerides were significantly reduced in the dexfenfluramine group (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action.

Somatostatin and somatostatin analogs are known to interact with the GH-insulin-like growth factor (IGF)-I axis by inhibiting GH secretion and consequently hepatic IGF-I production. Indirect evidence suggests that octreotide, a somatostatin analog, reduces serum IGF-I levels relatively more than expected from GH reduction, implying a GH-independent pathway of action. To study the role of octreotide in the regulation of IGF-I production, independently of endogenous GH, we used the hypophysectomized (hypox) rat to measure hepatic IGF-I expression and also employed cultured rat hepatocytes to examine whether octreotide has any direct effect on the production of IGF-I. Forty male hypox Sprague-Dawley rats were randomized into 4 groups to receive daily injections for 3 days of either saline, human GH (hGH) (100 g), octreotide (100 g twice), or both hGH (100 g) and octreotide (100 g twice). GH stimulated serum IGF-I levels to 104 +/- 10 micrograms/liter as compared to saline (26 +/- 2 micrograms/liter). Octreotide alone had no effect, but combining octreotide and hGH significantly reduced the hGH-induced rise in the IGF-I levels (52 +/- 6 micrograms/liter). The relative expression of hepatic IGF-I in the rats treated with hGH increased by 4-fold compared to that in the saline-treated rats. Octreotide administered simultaneously with hGH potently blocked the hGH-induced IGF-I expression to control levels. In cultured hepatocytes, IGF-I mRNA levels maximally stimulated by combining bGH and glucagon were significantly inhibited in the presence of octreotide at low concentrations (0.3 and 3 ng/ml) by 25% and 45%, respectively. In contrast, high concentrations of octreotide (30 and 300 ng/ml) had no significant effect on IGF-I mRNA abundance. We conclude that: 1) octreotide inhibits IGF-I serum levels and hepatic gene expression in the hypox rat; and 2) octreotide can inhibit partially the direct effects of GH and glucagon on hepatic IGF-I production.

Animals↗
PubMed1991

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas.

From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Adenoma↗
PubMed1991

Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

Adult↗
PubMed1991

Effects of acute and prolonged glucose excess on growth hormone release by cultured rat anterior pituitary cells.

The aim of this study was to verify whether prolonged exposure of cultured rat anterior pituitary cells to high glucose can alter growth hormone (GH) release and responsiveness to secretagogues. Therefore, we cultured anterior pituitary cells obtained from normal male Sprague-Dawley rats in presence of normal (6 mM) or high (22 mM) glucose concentrations. After 3 days, the acute effects of glucose, growth hormone-releasing factor (GRF), dibutyryl cyclic AMP(db-cAMP) and somatostatin were studied during 2-hour incubations. High glucose did not alter basal GH release from cells cultured in 6 mM glucose. However, basal GH release from cells cultured in 22 mM glucose was moderately higher in the 2-hour incubation (by 46%) than in cells cultured in 6 mM glucose. In contrast, GH stimulation by GRF or db-cAMP was significantly reduced in cells cultured in 22 mM as compared to cells cultured in 6 mM glucose. This inhibitory effect of high glucose on GRF-stimulated GH release was completely reversible after 24 h of exposure of the cultured cells to 6 mM glucose and testing on the 4th day of culture. Finally, GH inhibition by somatostatin was also attenuated in cells cultured with high glucose. We conclude that prolonged exposure to high glucose could act directly at the pituitary level to modulate GH release and responsiveness.

Animals↗
PubMed1990

Long term treatment with CV 205-502 in patients with prolactin-secreting pituitary macroadenomas.

CV 205-502, a new long-acting nonergot dopamine agonist, was given to 15 patients (6 women and 9 men) with PRL-secreting pituitary macroadenomas. The compound was administered in a single daily dose for a period of 6-12 months. The treatment resulted in normalization of plasma PRL levels (less than or equal to 20 micrograms/L) in 5 of 6 women at a mean dose of 135 micrograms (range, 75-300 micrograms) and in 6 of 9 men at a mean dose of 192 micrograms (range, 75-300 micrograms). Among patients for whom computed tomographic scans were available before and after at least 6 months of therapy, definite tumor shrinkage occurred in 6 of 7 patients. Libido was improved in 5 of 6 women and in 6 of 8 men, galactorrhea disappeared in all cases (3 women and 1 man) and menses resumed in 3 of 5 women. Plasma testosterone rose to normal levels in 3 of 6 men who were not receiving testosterone injections. The PRL response to TRH was blunted in 4 of 6 patients with normalized basal PRL. Serum total cholesterol was reduced by CV 205-502 treatment in women from 5.35 +/- 0.49 to 4.63 +/- 0.51 mmol/L (P = 0.031) and in men from 5.93 +/- 0.89 to 5.28 +/- 0.82 mmol/L (P = 0.045). Side-effects included mainly headache, nausea, and dizziness. One side-effect or more occurred transiently and with mild intensity in 14 patients. No patient discontinued the therapy because of side-effects. In conclusion, CV 205-502 appears to be a safe and valuable compound in the treatment of patients with PRL-secreting macroadenomas.

Adult↗
PubMed1989

Effect of dietary restriction and repeated growth hormone-releasing factor injections on growth hormone response to growth hormone-releasing factor in obese subjects.

The response of serum growth hormone (GH) to a test bolus of growth hormone-releasing factor (GRF) (1 micrograms/kg, IV) was examined in eight obese subjects (166% +/- 8% ideal body weight [IBW] during a weight-maintaining control period and after 2 weeks of hypocaloric feeding (750 kcal). During the period of hypocaloric feeding subjects received either repetitive GRF 1 micrograms/kg, IV (GRF group, n = 6) at 9 AM, 1 PM, and 5 PM three times a week, or saline injections (placebo group, n = 6) at the same intervals. Four subjects were studied twice, several months apart, each receiving GRF and placebo treatments. Nitrogen balance was determined daily throughout the study. We also examined GH response to the GRF test in seven normal-weight subjects (106% +/- 6% IBW]. During the control period, obese subjects demonstrated a blunted GH response to GRF expressed as peak height or GH area under the curve (0 to 120 minutes) compared with normal subjects (P less than .005). At the end of the hypocaloric feeding, mean GH peak height after the GRF test was unchanged in the placebo group compared with the control period. GH release was significantly increased only during the second hour of testing (P less than .025). However, the GRF group demonstrated an increase in both mean GH peak height (P less than .025) and GH release during the first and second hours of testing (P less than .025) compared with the control period. Weight loss and blood glucose, triglycerides, FFA, amino acids, insulin, and T3 changes were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗