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Biomedical subjects

V Popović

Publications and source records attributed to V Popović.

At least 19 recordsLinked to original sources
PubMed2003

Growth-hormone response to combined stimulation with GHRH plus GH-releasing peptide-6 in obese patients with polycystic ovary syndrome before and after short-term fasting.

Controversial data were reported on GH response to different provocative stimuli in obese patients with polycystic ovary syndrome (PCOS). The objective of our study was to assess the effect of short-term fasting on GH response to combined stimulus with GHRH+GH-releasing peptide-6 (GHRP-6) in obese patients with PCOS and possible relation with leptin and insulin changes during fasting. Twelve obese PCOS women and nine obese control women participated in 3-day fasting. GH response, IGF-I, insulin and leptin were measured after GHRH+ GHRP-6, before and after short-term fasting. Obese PCOS patients had significantly greater GH peak after GHRH+GHRP-6 before fasting. Enhanced response to GH stimulation was found after fasting without substantial differences between obese PCOS and obese controls. Insulin and leptin significantly decreased, while insulin sensitivity significantly improved in both groups during fasting. In conclusion, obese PCOS patients have peculiar type of GH response to GHRH+GHRP-6 before fasting, possibly due to enhanced sensitivity of somatotrophs. Observed changes in insulin and leptin may participate in modulation of enhanced GH response after short-term fasting to GHRH+GHRP-6 in PCOS and obese controls.

Adult↗
PubMed2000

Serum leptin levels in patients with acromegaly before and after correction of hypersomatotropism by trans-sphenoidal surgery.

It has been shown that GH excess is associated with decreased leptin levels and decreased body fat mass. Reports regarding the effect of GH on serum leptin levels are inconsistent. We studied leptin secretion in 20 acromegalics before and 2 months after trans-sphenoidal surgery and in 20 gender-, age-, and body mass index (BMI)-matched control subjects. The mean 8-h leptin concentration for each subject was measured from a pool formed of samples collected hourly beginning at 2200 h until 0600 h the next morning. In a subgroup of 10 acromegalics, leptin pulsatility was assessed for the same period of time in 10-min sampling intervals. Basal GH, insulin-like growth factor-I (IGF-I), insulin, glucose, and lipids levels were measured. Area under the curve for insulin (AUCins) during oral glucose tolerance test was calculated. Control subjects and acromegalics had similar BMI, but patients with active acromegaly had significantly lower mean leptin level (mean +/- SEM; in men, 2.6+/-0.4 vs. 7.1+/-1.1 microg/L, P = 0.003; in women, 16.0+/-3.4 vs. 23.5+/-3.1 microg/L; P = 0.036). Mean 8-h leptin correlated with BMI (r = 0.57, P = 0.007, in controls; r = 0.70, P = 0.001, in patients). In stepwise regression analysis with mean 8-h leptin as a dependent variable, BMI (P<0.001) and gender (P = 0.01) in acromegalics entered the equation, whereas in control subjects gender, free fatty acids, insulin, and age accounted for 99.3% in leptin variability. After surgery, BMI did not change significantly; and glucose (P = 0.014), GH (P<0.001), and IGF-I (P<0.001) levels together with AUCins (P = 0.002) decreased, whereas mean leptin concentration rose significantly and attained normal levels (4.1+/-0.8 microg/L, P = 0.028) in acromegalic men and (23.6+/-4.7 microg/L, P = 0.003) in acromegalic women. Correlation between leptin level and BMI was preserved after surgery (r = 0.62, P = 0.005). In stepwise regression analysis, free fatty acids (P = 0.04) contributed to 26.8% of the variance in corrected-leptin (for BMI and gender). Leptin concentration peak height and interpeak nadir level rose significantly (P = 0.033 and P = 0.037) after surgery by Cluster analysis, without significant changes in leptin pulse frequency and incremental peak amplitude. Nocturnal rise of leptin (mathematically described by a cubic curve) was characterized by an acrophase just after midnight, before and after surgery. The amplitude and the average leptin concentration of the cubic fit increased significantly after surgery (P = 0.028 and P< 0.001). In conclusion in acromegalic patients: 1) leptin secretion maintains the pulsatility and nocturnal rise; 2) the gender-based leptin differences are preserved; 3) GH-IGF-I normalization leads to a rise in leptin that is not related to changes in BMI; and 4) the possible role of rise in leptin levels when assessing clinical and metabolic outcome of therapy in acromegalic patients deserves additional studies.

Acromegaly↗
PubMed1999

Growth hormone (GH) response to GH-releasing peptide-6 and GH-releasing hormone in normal-weight and overweight patients with non-insulin-dependent diabetes mellitus.

The growth hormone (GH) response to GH-releasing hormone (GHRH) in patients with non-insulin-dependent diabetes mellitus (NIDDM) was found to be either decreased or normal. The recent introduction of a new and potent GH stimulus, GH-releasing peptide-6 (GHRP-6), allowed further investigation of the functional properties of somatotropes in a variety of metabolic diseases. The aim of the present study was to investigate the response of GH to GHRP-6, GHRH, and GHRP-6 + GHRH in NIDDM patients. Twenty-one patients with NIDDM were divided into two groups: group A, normal weight (body mass index [BMI], 23.31+/-0.62 kg/m2); and group B, overweight (BMI, 27.62+/-0.72 kg/m2). Eight normal-weight control subjects (group C) were studied. Each subject received GHRP-6 (90 microg intravenously [i.v.]), GHRH (100 microg i.v.), and GHRP-6 + GHRH on three separate occasions. There was no difference between the GH response after GHRP-6 in groups A, B, and C in terms of the GH peak (50.95+/-11.55, 51.96+/-7.71, and 70.07+/-15.59 mU/L, P>.05) and the area under the curve (AUC) for GH (2,340.06+/-617.36, 2,684.54+/-560.57, 3,462.78+/-1,223.53 mU/L/120 min, P>.05). A decreased GH response to GHRH was found in group B in comparison to group A (B v A: peak GH response, 8.25+/-1.90 v 22.19+/-8.81, P<.05; AUC GH, 479.62+/-84.0 v 1,443.21+/-743.76, P<.05). There was no difference in the GH response between group A and group C (peak GH response, 22.19+/-8.81 v 26.42+/-6.71, P>.05; AUC, 1,443.21+/-743.76 v 1,476.51+/-386.56, P>.05). There was a significant difference between the same parameters in group B versus group C (8.25+/-1.90 v 26.42+/-6.71, P<.05; AUC, 479.62+/-84.0 v 1,476.51+/-386.56, P<.05). The combined administration of GHRP-6 + GHRH elicited a synergistic GH response in NIDDM patients and controls. There was a significant difference between groups A and B for the GH peak (96.49+/-9.80 v 68.38+/-8.25, P<.05), whereas there was no difference for the AUC (5,111.13+/-703.77 v 3,425.95+/-459.67, P>.05). There was no difference in the peak GH after the combined test between group A and group C (96.49+/-9.80 v 139.82+/-24.16, P>.05), whereas the peak GH in the same test was significantly decreased in group B in comparison to group C (68.38+/-8.25 v 139.82+/-24.16, P<.05). The AUC for GH after combined GHRP-6 + GHRH in group A versus group C was not significantly different (5,111.13+/-703.77 v 9,274.71+/-1,541.46, P>.05), whereas there was a significant difference for the same test between group B and group C (3,425.95+/-459.67 v 9,274.71+/-1,541.46, P<.05). Our results demonstrate that normal-weight NIDDM patients have a preserved GH response to GHRP-6, GHRH, and GHRP-6 + GHRH, and overweight NIDDM patients have a blunted response to GHRH and GHRP-6 + GHRH. The preserved GH response to GHRP-6 in both diabetic groups suggests that the secretory potential of somatotropes is preserved in NIDDM patients. The impairment of the GH response to GHRH in overweight NIDDM patients could be a functional defect due to the obesity, since it could be overridden by administration of GHRP-6.

Area Under Curve↗
PubMed1997

Leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome.

The study was conducted to assess leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome (PCOS). Twenty-two women with PCOS and 19 control healthy women were included in the study, divided into obese and non-obese groups. Leptin was determined using Linco Research radio-immunoassay while insulin sensitivity was calculated from intravenous glucose tolerance tests with frequent blood sampling using MINMOD analysis. Significantly higher basal leptin levels were found in obese compared to non-obese PCOS (31.76 +/- 3.06 vs. 10.42 +/- 2.31 ng/ml; p < 0.05) as well as in obese in comparison to non-obese controls (29.16 +/- 5.06 vs 8.51 +/- 0.88 ng/ml; p < 0.05). A negative correlation was found between insulin sensitivity and leptin levels in both obese (r = -0.2480; p > 0.05) and non-obese PCOS groups (r = -0.4620; p > 0.05). In conclusion, high serum leptin, insulin and testosterone levels together with reduced insulin sensitivity were found in obese PCOS women, suggesting that high leptin levels could be a characteristic of the obese PCOS phenotype.

Adult↗
PubMed1996

Growth hormone response to GHRH, GHRP-6 and GHRH + GHRP-6 in patients with polycystic ovary syndrome.

OBJECTIVE: Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non-classic GH secretagogues and, in particular, to the series of hexapeptides of which GH-releasing peptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, known as GHRP-6) is the most representative. GHRP-6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH + GHRP-6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP-6 and the administration of GHRP + GHRP-6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups. DESIGN: All subjects were studied three times on different days with GHRH (100 micrograms i.v.), GHRP-6 (90 micrograms i.v.) and GHRH + GHRP-6 (100 micrograms + 90 micrograms). PATIENTS: Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m2); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m2); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m2) and Group D (obese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg/m2). MEASUREMENTS: Serum GH was measured using a time-resolved fluoroimmunoassay (Delphia, Pharmacia). RESULTS: After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4 +/- 16.4 vs 20 +/- 4.9 mU/l, P < 0.05) and in AUC for GH between Groups A and B (4667 +/- 1061 vs 947 +/- 236, P < 0.05) while there were no differences between the same groups in GH peak or AUC after GHRP-6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH + GHRP-6 between Groups A and B (211 +/- 26.4 vs 108 +/- 17.6, P < 0.05) as well as between GH AUC in Groups A and B (12068 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in GH peaks or AUC for GH after GHRH + GHRP-6 administration between Groups A and C or Groups B and D. CONCLUSIONS: The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 administration.

Adult↗
PubMed1993

Immunological resistance to human biosynthetic insulin--effects of immunosuppression and plasmapheresis.

A 55-year-old gentleman, after being treated for a short time with a diet and with Chlorpropamide, was switched to purified porcine insulin due to ketonuria and ketoacidosis. After a year the patient developed immunological insulin resistance (mean daily insulin dose: 3.72 U/kg body weight; anti-insulin antibodies 78%). In order to lower anti-insulin antibodies human recombinant DNA insulin was introduced into further therapy. Contrary to expectations, the patient did not reduce whatsoever his anti-insulin antibodies and his daily insulin dose increased up to 5.63 U/kg body weight. Introduction of combined immunosuppressive therapy (prednisone plus azathioprine) together with plasmapheresis resulted in rapid lowering of daily insulin requirement and reduction in anti-insulin antibodies. Immunosuppressive therapy was continued with 10 mg of prednisone and a year later the patients insulin daily requirement was 0.66 U/kg BW while his antibodies were 18%. The possible causes of insulin resistance to human recombinant DNA insulin are discussed as well as the advantage of combined immunosuppressive therapy together with plasmapheresis that was used for rapid lowering of insulin daily requirement and anti-insulin antibodies titer.

Azathioprine↗
PubMed1992

Androgen-producing bilateral large cortical adrenal adenomas associated with polycystic ovaries in a young female.

An association of bilateral large adrenocortical androgen-producing adenomas with polycystic ovaries in a young female is presented. She developed mild hirsutism and secondary amenorrhoea at the age of 17, and was treated for 3 years with an anti-androgen (cyproterone acetate) and ethinyloestradiol. Routine follow-up at the age of 21 showed bilateral large adrenal tumours and polycystic ovaries, together with high serum testosterone and dehydroepiandrosterone sulphate values. Bilateral adrenalectomy was performed, which resulted in lowering of the elevated androgens, and large bilateral adrenocortical adenomas were confirmed histologically. Contrary to expectations, the polycystic appearance of the ovaries persisted after adrenalectomy. This case supports the possible role of adrenal androgens in the pathogenesis of polycystic ovaries as well as the possibility of the persistence of polycystic ovaries without adrenal androgens once they have developed.

Adenoma↗
PubMed1992

[The effect of occupational noxae in the tobacco industry on pulmonary function in exposed workers].

A study was carried out to determine respiratory hazards to workers in tobacco manufacture. The investigations at the workplace included analysis of the work technology and measurements of chemical pollutants and dust concentrations in the work rooms. Ventilatory lung function tests were performed in 95 workers exposed to tobacco dust and in 129 control workers. Results of workplace analysis showed the presence of tobacco dust levels exceeding the maximum permissible concentrations. The values of some lung function tests for exposed workers non-smokers were significantly lower than for control workers non-smokers. They could be attributed to the effect of occupational noxae on the respiratory system.

Adult↗
PubMed1991

Follicle stimulating hormone-secreting pituitary adenoma: inappropriate secretion and effect of pulsatile luteinizing hormone releasing hormone analogue (buserelin) administration.

A patient with an FSH secreting pituitary adenoma is reported. Elevated FSH and serum free alpha-subunit (SU) with low levels of LH and testosterone (T) were found. Immunostaining showed the presence of alpha-SU, FSH-beta and LH-beta subunits. LHRH analogue (buserelin) was administered in a pulsatile manner, by portable computerized infusion pump sc for ten days. During the first 24 h of treatment FSH, LH (p less than 0.001) and T (p less than 0.01) rose significantly. Ten days later, the expected desensitization phenomenon did not occur, but further increases of T (8.4 +/- 2.6, mean +/- SD, vs 17.4 +/- 4.1 nmol/l, p less than 0.001) and FSH (58.9 +/- 9.6 vs 70.7 +/- 3.8 mlU/ml, p less than 0.001) were registered. LH decreased (12.5 +/- 2.4 vs 7.1 +/- 0.6 mlU/ml, p less than 0.001) at day 10, but remained higher than basal level (5.0 +/- 0.6, p less than 0.001). Free alpha-SU also rose (2.8 +/- 0.4 vs 4.4 +/- 1.7 mlU/ml, p less than 0.001) after ten days of treatment. The chronic stimulatory effect of analogue on LH with a lack of desensitization suggests tumorous secretion despite a partially preserved negative feedback of testosterone. Low basal LH levels, in some patients with FSH secreting tumors may not be due to tumor mass effect, but rather may be the consequence of altered LH production and/or secretion by the tumor. Although buserelin may not have a therapeutic effect, it is of use in differential diagnosis of hypergonadotropinemia.

Adenoma, Chromophobe↗
PubMed1990

How reliable is the euglycaemic hyperinsulinemic clamp test for the confirmation of autonomous endogenous hyperinsulinemia?

Inhibition of C-Peptide secretion by exogenous insulin was studied during euglycemic clamp in 13 patients with histologically verified causes of organic hyperinsulinaemia (10 with beta cell adenoma; 2 with beta cell carcinoma and 1 with beta cell hyperplasia) and in 10 healthy controls. Euglycemic clamps were performed using artificial endocrine pancreas (Clamp Mode 9:1) while insulin infusion (Humulin Normal-Lilly) rate was 0.1 U/kg BW/h. Blood samples for serum insulin (RIA INEP) and C-Peptide (RIA-Biodata) were taken at 0; 30; 60; 90 and 120 min. Statistical analysis was done using SPSS on IBM-PC with Wilcoxon sum rank test and one way ANOVA. All the patients were studied before the operation and in four of them clamp studies were repeated after the operation. Statistically significant suppression of C-Peptide values in 120 min was established in the control group (p less than 0.05) while there was no significant suppression in insulinoma group (p greater than 0.05), except in one patient with beta cell hyperplasia. Various types of responses (suppression, no change, paradoxical increase) were observed after the operation in the insulinoma group. Possible mechanisms and the meanings of the absence of insulin induced C-Peptide suppression in insulinoma group are discussed. It is concluded that euglycemic hyperinsulinemic clamp study could be useful and a complementary test to other established tests for the confirmation of the diagnosis of insulinoma. Further work on beta cell response after the operation in patients with insulinoma is necessary.

Adenoma↗
PubMed1990

A comparison among the effectiveness of growth hormone suppression in active acromegaly of bromocriptine and long acting somatostatin analogue (SMS 201-995).

The aim of our study was to compare the effectiveness of bromocriptine vs. long acting somatostatin analogue (SMS 201-995) on growth hormone suppression in active acromegaly. A twenty year old female, student of law, was previously treated with Parlodel LA 50 mg i.m. injection and then with bromocriptine 30 mg orally for 2.5 years because of active acromegaly and very large intrasellar and suprasellar pituitary adenoma. She was partial bromocriptine responder with mean growth hormone levels prior the treatment 30 mU/L and after bromocriptine 13.7 mU/L and with gross tumor shrinkage. Since she failed to restore menstrual cycles, had clinical signs of the disease, she was taken off bromocriptine and treated with somatostatin analogue (SMS 201-995) 300 mcg s.c. daily and 400 mcg s.c. daily with mean growth hormone levels 10 mU/L. She was also treated with combined treatment (400 mcg s.c. SMS 201-995 plus 30 mg bromocriptine orally) and mean growth hormone levels were 11 mU/L. SMS 201-995 had a long lasting inhibitory effect on growth hormone secretion in acromegaly (p less than 0.01) but in comparison to daily growth hormone levels during bromocriptine treatment no difference was found (p greater than 0.01). Combined treatment with SMS 201-995 and bromocriptine did not achieve greater suppression of daily growth hormone levels than those achieved with SMS 201-995 alone (p greater than 0.1) or with bromocriptine alone (p greater than 0.05). No significant tumor shrinkage during chronic SMS treatment was seen. Severe clinical and biochemical signs of hypoglycaemia were registered on one occasion only during the first month of treatment with SMS 201-995.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1990

Discordance between growth hormone responses after growth hormone-releasing hormone (GHRH) and insulin hypoglycemia in ectopic GHRH syndrome.

Dynamic studies of growth hormone (GH) secretion were performed in two patients with ectopic GHRH syndrome. Patient 1 (female, 33 years old) had a growth hormone releasing hormone (GHRH) producing carcinoid of the lung with clinical features of acromegaly while patient 2 (50 years old male) had small cell carcinoma of the lung without acromegaly. Insulin hypoglycemia stimulated GH secretion in both patients (i.e. from a basal level of 10 mU/l to 48 mU/l in patient 1, while the respective values in patient 2 were 5 mU/l and 61 mU/l), TRH acutely stimulated GH in both patients. Synthetic GHRH 1-29 (KABI) i.v. bolus 100 micrograms did not stimulate GH release in either patient (i.e. basal GH 14 mU/l and peak 18 mU/l (patient 1); basal GH 4.6 mU/l and peak 8.8 mU/l (patient 2). It is concluded that: 1. prolonged pituitary exposure to GHRH is associated with chronic GH hypersecretion with or without clinical acromegaly; 2. GH response to TRH may be mediated at the pituitary level and results from prolonged exposure to GHRH; 3. the discordant response of GH after GHRH and insulin induced hypoglycemia might suggest the involvement (at least partially) of somatostatin in the mechanism of GH release after hypoglycemia and after GHRH.

Adult↗
PubMed1990

Naloxone interaction with pituitary response to TRH and LHRH test in patients with polycystic ovary syndrome.

The response of TSH, PRL, LH and FSH to combined test with LHRH (Relefact LH-RH, HOECHST; 0.1 mg) and TRH (Relefact TRH, HOECHST; 0.2 mg) was examined before (day I) and after naloxone (Narcanti, DUPONT) bolus of 0.8 mg (day III) in 8 patients with polycystic ovary syndrome (POC) diagnosed by established criteria (hirsutism, oligoamenorrhoea, ultrasound appearance of polycystic ovary and serum LH/FSH greater than 2.0). TSH (RIA-INEP), PRL (MAIA-SERONO), LH (MAIA-SERONO) and FSH (MAIA-SERONO) were determined at -15, 0, 10, 20, 30, 45, 60, 90 and 120 min. The hormone responses were calculated as the areas under hormone curves and tested with Wilcoxon sum rank test. No significant difference was found in the hormone responses before and after naloxone injection. In terms of absolute values lower TSH level was found at 30 min after naloxone administration (14.7 +/- 12.0 vs. 9.73 +/- 7.61; P less than 0.05). In conclusion, our data based on short term naloxone application argue against the significant alteration of the opioid activity in patients with POC.

Adult↗
PubMed1990

[Characteristics of the ventilatory status of the lungs in workers in the electronics industry].

To establish the effects of occupational respiratory noxae on the state of the bronchopulmonary system a study of the working environment and examinations of workers from the electronics industry whose workplaces were near tin baths and in conductor soldering shops were carried out. The following chemical noxae were found to be present in the working environment: lead, tin, calophonium and ethyl alcohol, all in permitted concentrations. Comparison of the state of lung ventilation in workers from the electronics industry (n = 120) and control workers (n = 129) pointed to a major increase in total air flow resistance during calm breathing in the exposed workers. The obstructive changes were mainly localized in the small airways.

Adult↗
PubMed1989

The development of dependence to an octapeptide somatostatin analog: contribution to the study of somatostatin analgesia.

This paper reports the phenomenon of dependence to a somatostatin octapeptide analog used for the treatment of acromegaly and severe headache. The mechanism of this dependence is still unknown, but could be based on the interaction of the somatostatin analog with opioid receptors. Analgesia may be at least partially supported by the opioid modulation of pain transmission, but also by general "appetitive" behavioral activation due to the effect of somatostatin on its receptors.

Acromegaly↗
PubMed1988

Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

Adolescent↗