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Biomedical subjects

J Alaghband-Zadeh

Publications and source records attributed to J Alaghband-Zadeh.

At least 19 recordsLinked to original sources
PubMed1999

Circulating stress hormone and insulin concentrations in acute coronary syndromes: identification of insulin resistance on admission.

We re-examined, in the context of modern practice, plasma insulin and stress hormone concentrations in patients admitted to hospital with acute coronary syndromes. Venous blood sampling was carried out prior to anti-thrombotic therapy in 148 patients with myocardial infarction (MI); 76 patients with unstable angina (UA) pectoris were also studied, together with 27 patients with non-cardiac chest pain (NCP). There were significant progressive increases in the concentrations of catecholamines, cortisol, glucose and insulin from NCP to UA to MI patients. Hyperglycaemia (glucose >8 mmol/l) was present in over 50% of MI patients. The plasma cortisol and insulin levels were both significantly positively correlated with the glucose concentration on admission. Only the cortisol concentration was correlated with peak cardiac enzyme levels. The glucose and insulin concentrations on admission in 141 MI and UA patients were related to insulin resistance, as judged from subsequent insulin and glucose concentrations measured while fasting and during a glucose tolerance test. The product of admission insulinxglucose (divided by 25; the admission insulin-resistance index, or AIRI) was significantly correlated with indices of insulin resistance, and was significantly higher (approximately double) in the MI group (7. 81+/-0.76) and the UA group (6.88+/-1.19) than in the control NCP group (3.59+/-0.06; Kuskul-Wallis: P=0.0001), implying that the insulin levels in the first two groups were approximately twice as high as is appropriate for the glucose levels. The ethnic origin of 20% of the patients was the Indian subcontinent; admission insulin and glucose levels in this subgroup were higher than in the non-Asians across all the groups with chest pain. Cortisol was the only stress hormone that was raised in proportion to the size of the infarct, and is a likely partial cause of the elevation in blood glucose. The high insulin levels were related to the prevalence of insulin resistance, and this was particularly important in the Asian subgroup presenting with MI and UA. Thus it appears feasible to identify acute coronary syndrome patients who are insulin-resistant at a time (on admission) when alternative early therapeutic strategies can be instituted.

Acute Disease↗
PubMed1999

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone.

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.

Adult↗
PubMed1998

The relationship of fetal serum markers of bone metabolism to gestational age.

The aim of this study is to determine the pattern of fetal bone metabolism by measuring umbilical cord levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP). PICP and ICTP directly monitors the rate of bone formation and resorption, respectively. Samples were obtained at the time of delivery from 20 healthy women with pregnancies at different gestations. There is a significant inverse correlation between fetal levels of PICP and ICTP, and gestation (PICP r=-0.504, p=0.023; ICTP r=-0.713, p < 0.001), and between ICTP and birth weight (r=-0.466, p=0.038), but the birth weight effect is a function of gestational age. Therefore, both bone formation and resorption decrease with gestational age. Although contrary to the suggestion that fetal ossification increases at the end of pregnancy, such changes may be due to the shift from growth to maintenance.

Adult↗
PubMed1998

Maternal and fetal plasma levels of markers of bone metabolism in gestational diabetic pregnancies.

The aim of this study is to determine whether gestational diabetes has any effect on maternal and fetal bone metabolism. We collected maternal and umbilical cord blood samples from 19 women with gestational diabetes and 19 controls at the time of delivery. The plasma levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were used to monitor the rate of bone formation and degradation respectively. There is a significant correlation between the 1 hour postprandial blood glucose and the maternal levels of ICTP (r = 0.560, P = 0.004), but there was no significant difference in maternal or fetal levels of PICP and ICTP between the study and control groups (P = 0.411 maternal PICP, P = 0.241 maternal ICTP, P = 0.365 fetal PICP and P = 0.781 fetal ICTP). In the gestational diabetes group, there was a significant correlation between maternal and fetal ICTP (r = 0.694, P = 0.001), but there was no correlation between maternal and fetal levels of PICP (r = 0.334, P = 0.175). Although the maternal levels of ICTP is related to the 1 hour postprandial blood glucose level, gestational diabetes does not affect the maternal or umbilical cord levels of the serum markers of bone metabolism.

Biomarkers↗
PubMed1998

Antenatal corticosteroid therapy and risk of osteoporosis.

OBJECTIVE: To assess the risk of maternal osteoporosis associated with antenatal corticosteroid administration for neonatal respiratory distress syndrome prophylaxis. DESIGN: Prospective longitudinal study. SETTING: Maternity unit of Chelsea and Westminster Hospital, London. POPULATION: Fourteen pregnant women who received dexamethasone therapy for fetal lung maturation in anticipation of delivery before 34 completed weeks of gestation. METHODS: Blood samples were collected before dexamethasone administration, 24 hours and 48 hours after the course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the rate of bone formation, and serum levels of cross-linked carboxy terminal telopeptide (ICTP) were measured as a marker of bone resorption. MAIN OUTCOME MEASURES: Changes in the markers of bone turnover following dexamethasone administration. RESULTS: Serum PICP levels dropped 24 hours after dexamethasone therapy (P = 0.001), but partially recovered by 48 hours (P = 0.014) to reach higher than pre-therapy levels at delivery (P = 0.044). Although there were no corresponding changes in the serum levels of ICTP after 24 and 48 hours of therapy, levels increased from pretherapy to delivery (P = 0.006). CONCLUSION: Antenatal corticosteroid therapy leads to a transient suppression of, followed by an increase in, bone formation without any significant alteration in the pattern of bone resorption expected during pregnancy.

Biomarkers↗
PubMed1997

Hypothalamic hypertensive factor: an inhibitor of nitric oxide synthase activity.

Human and rat plasma and rat hypothalamus contain a cytochemically detectable substance, the concentration of which rises with an increase in salt intake. The plasma concentration of this material is also raised in essential hypertension and in the spontaneously hypertensive rat (SHR), the Milan hypertensive rat, and the reduced renal mass (RRM) hypertensive rat. In the normal rat, the greatest concentration is found in the hypothalamus of the SHR and the RRM hypertensive rat. The physicochemical characteristics of this cytochemically detectable hypothalamic hypertensive factor (HHF), including chromatographic behavior and molecular weight range, suggest that it may share features common to a substituted guanidine that is present in established nitric oxide synthase (NOS) inhibitors. It was therefore decided to determine the effect on NOS activity of the HHF obtained from mature SHR. The ability of HHF to inhibit NOS activity was studied on (1) NOS extracted from bovine aorta, rat brain, and human platelets by measuring the conversion of radiolabeled L-arginine to L-citrulline and (2) rat liver NOS measured indirectly with a cytochemical technique based on the stimulation of soluble guanylate cyclase activity in hepatocytes by NO. HHF showed a biphasic inhibitory action on platelet NOS activity that was greater with HHF obtained from SHR than from Wistar-Kyoto rats. HHF also had a biphasic inhibitory effect on hepatocyte NOS activity that was more potent when obtained from SHR. It is proposed that the increase in HHF, a novel form of NOS inhibitor that is elevated in SHR, may be involved in the rise in arterial pressure.

Animals↗
PubMed1996

Hypothalamic and plasma total nitrate/nitrite concentrations in spontaneously hypertensive rats.

Stable end-products of nitric oxide (NO) metabolism, nitrates and nitrites, were measured in hypothalamic extracts and plasma samples of Okamoto spontaneously hypertensive (SH) rats. The mean total nitrate/nitrite concentration was significantly lower in the hypothalami of SH rats compared with the normotensive Wistar Kyoto (WKY) control animals (P < 0.01). In contrast, their plasma concentrations were significantly higher (P < 0.05). These results indicate that the hypertensive state in SH rats is associated with a diminished production of hypothalamic NO, while the raised plasma nitrate/nitrite levels could reflect an increased compensatory endothelial NO synthase activity in these animals compared with the WKY controls.

Animals↗
PubMed1995

Raised serum 11-deoxycortisol in men with persistent acne vulgaris.

OBJECTIVE: Acne vulgaris is androgen dependent but the hormonal mechanisms are unclear. Although there have been many studies of serum hormones in women with acne there are few studies in men and the results are conflicting. We have therefore carried out a further study in men. DESIGN AND PATIENTS: Fifty men with acne vulgaris were age-matched against 50 normal men. MEASUREMENTS: Serum levels of dehydroepiandrosterone sulphate (DHEAS), 17 alpha-hydroxyprogesterone, 11-deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay and LH, FSH and oestradiol by automated ELISA. RESULTS: The acne patients had higher levels of androstenedione, median 7.35 nmol/l, (interquartile range 2-7) vs 6.05 (2.3), P = 0.004; testosterone, 21.7 nmol/l (7.5) vs 17.55 (7.7), P = 0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P = 0.007, but also had higher levels of 11-deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P = 0.022. The LH, FSH, 17 alpha-hydroxyprogesterone, DHEAS, oestradiol and SHBG levels were not significantly different. Examination of the Spearman rank correlation coefficient matrices for the serum levels of 17 alpha-hydroxyprogesterone, androstenedione and 11-deoxycortisol showed that the strongest correlation was between androstenedione and 11-deoxycortisol. CONCLUSION: Although there was overlap between the results of the acne patients and controls the acne patients tended to have higher levels of androstenedione, testosterone, free androgen index and 11-deoxycortisol. The higher levels of 11-deoxycortisol are suggestive of 11 beta-hydroyxlase dysfunction which could be due to a primary adrenal defect or a consequence of raised androgens. Also, a pathway between androstenedione and 11-deoxycortisol has been described in sheep and, although unsubstantiated in man, requires consideration.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Measurement of nitric oxide synthase activity in sections of rat liver.

In the previous communication we described a histochemical method for measuring soluble guanylate cyclase (sGC) activity in sections of rat liver. In theory, this method could be used to assess nitric oxide synthase (NOS) activity by the increased sGC activity induced by the additional presence of the substrates for NOS activity. We found that this was correct provided that the concentration of the colloid stabilizer in the reaction medium was decreased to just below the concentration required to fully stabilize the guanylate cyclase activity in the sections. This was related to the fact that the site of NOS activity was different from that of the sGC activity in the hepatocytes, so that the NO generated had to diffuse from the Kupffer cells to the hepatocytes as could occur only in partially unstabilized sections. Optimal concentrations of arginine and of NADPH have been determined for demonstrating NOS activity; the increased reaction was shown to be largely inhibited by methyl-arginine.

Animals↗
PubMed1995

Histochemistry of guanylate cyclase activity.

Guanylate cyclase liberates pyrophosphate from guanosine triphosphate (GTP). In studies published previously, this phosphate is trapped by lead ions even though it is known that free lead ions inactivate a considerable proportion of this enzymatic activity. To overcome the damaging effects of fixation, this study used fresh cryostat sections stabilized with a sufficient concentration of a collagen-derived polypeptide to ensure no measurable loss of guanylate cyclase activity. To avoid the damaging influence of free lead ions, we used a hidden metal capture reagent, i.e., a complex of lead ammonium citrate/acetate that does not react with GTP but which rapidly forms a precipitate with the pyrophosphate liberated by the enzyme. The lead precipitate is then converted into the colored sulfide which is measured in individual cells by microdensitometry. This system was used to measure guanylate cyclase activity in individual cells in unfixed sections of rat liver.

Animals↗
PubMed1995

Raised serum androgens and increased responsiveness to luteinizing hormone in men with acne vulgaris.

We have investigated the hormone profiles and the relationship between serum testosterone and luteinizing hormone in men with long-standing acne vulgaris. In the controls, age correlated with the free androgen index and with serum dehydroepiandrosterone-sulphate, so for the purposes of comparison 33 men with acne vulgaris were age-matched against 33 controls. Compared with controls, the acne patients had higher medians of serum androstenedione, testosterone and free androgen index. In both groups there was a significant correlation between testosterone and luteinizing hormone levels. For a given level of luteinizing hormone the patients with acne tended to have higher levels of serum testosterone than normal controls. These results indicate that in this group of men with long-standing acne there was either increased responsiveness of the target organ to luteinizing hormone or there was an increased amount of androgen-secreting tissue.

Acne Vulgaris↗
PubMed1994

Comparison of paired short Synacthen and insulin tolerance tests soon after pituitary surgery.

The cortisol responses to hypoglycaemia (insulin tolerance test, ITT) and tetracosactrin (short Synacthen test, SST) were compared after hypophysectomy to evaluate the SST for the assessment of hypothalamo-pituitary-adrenocortical (HPA) axis function in the immediate post-operative period. In 12 patients who were tested a mean of 21 months postoperatively (range 1-96) peak plasma cortisol in the SST correlated with that in the ITT (r = 0.90). Correlation was also seen in 12 patients tested a mean of 9 days (range 4-18) after hypophysectomy (r = 0.73). Basal-peak cortisol increments did not correlate. The peak plasma cortisol response in each test was classified by comparison with a reference value of 550 nmol/L. On this basis there was a notable discrepancy between the ITT and SST results in only one patient who was tested 4 days after hypophysectomy. The close correlation between ITT and SST responses after pituitary surgery extends into the immediate post operative period and indicates that the latter test can be used to screen HPA axis function at this time.

Adolescent↗
PubMed1993

A possible connection between an increased concentration of a cytochemically detectable substance in the hypothalamus of the spontaneously hypertensive rat and certain cerebral cholinergic disturbances.

The hypothalamus of the spontaneously hypertensive rat (SHR) contains an increased concentration of a cytochemically detectable choline-like substance, the physicochemical properties of which are similar to the choline analogue dimethyl methylene immonium. In the hypothalamus of the adult SHR there is an increased turnover of acetylcholine in the cholinergic pressor posterior hypothalamic nucleus and the neurons of the dorsomedial cholinergic depressor nucleus are atrophic, possibly due to diminished cholinergic activity. Both of these changes are pressor. It is suggested that an increased hypothalamic content of a choline-like analogue might either be responsible for, or an indicator of, these abnormalities.

Acetylcholine↗
PubMed1993

Relationship between follicular fluid levels of insulin-like growth factor binding protein-1 and sex steroids from normal human ovarian follicles.

The aim of this study was to examine the possible correlations between follicular fluid insulin-like growth factor binding protein 1 (IGFBP-1) and follicular fluid and serum parameters of granulosa cell function. Twenty-six subjects undergoing diagnostic laparoscopy for infertility had follicular fluid samples collected. Subjects were aged 20-42 years, were having regular ovulatory cycles and either had tubal disease or a partner with male factor infertility. Sex steroids, insulin-like growth factor 1 (IGF-1) and IGFBP-1 were measured by radioimmunoassay. Follicular fluid levels of IGFBP-1 were significantly correlated with levels of estradiol, progesterone in follicular fluid and with serum IGFBP-1 levels, and negatively correlated with follicular fluid androstenedione levels. These results suggests that IGFBP-1 may have a role in the regulation of human ovarian follicles.

Adult↗
PubMed1991

Cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating/Na-K-ATPase-inhibiting activity of plasma and hypothalamus in reduced renal mass hypertension.

Plasma from normal humans and rats on a high sodium intake, and from patients and rats suffering from hereditary hypertension has an increased cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating/Na-K-ATPase inhibiting activity. The hypothalamic content of this activity is also increased by a high sodium intake and in the spontaneously hypertensive rat (SHR). Using cytochemical techniques, the ability of plasma and the hypothalamus of reduced renal mass hypertensive rats to stimulate G6PD activity and to inhibit Na-K-ATPase was measured. The mean G6PD-stimulating capacity of the plasma from the hypertensive and normotensive groups of rats was 351 +/- 67 and 11.42 +/- 1.98 G6PD-stimulating units/mL respectively (P less than .001). The time courses of the ability of plasma from a hypertensive and a normotensive rat to inhibit fresh tissue Na-K-ATPase after 2, 4, 6, and 8 min of exposure demonstrated that the hypertensive rat plasma had a greater capacity to inhibit Na-K-ATPase. The mean G6PD-stimulating capacity of the hypothalamus from the hypertensive and normotensive groups of rats was 252,263 +/- 147,958 X 10(3) and 6.38 +/- 2.35 X 10(3) G6PD-stimulating units per hypothalamus, respectively (P less than .01). It is proposed that the raised concentration of cytochemically detectable G6PD-stimulating/Na-K-ATPase-inhibiting substance in both genetic and nongenetic forms of hypertension may be a manifestation of a communal hypertensinogenic mechanism. Thus, the raised plasma concentration would have a direct peripheral vascular constricting effect and the high hypothalamic concentration would be responsible for a central nervous hypertensinogenic effect.

Animals↗