Neuroendocrine deficiency-mediated development and persistence of pain in fibromyalgia: a promising paradigm?
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Fibromyalgia↗
Biomedical subjects
B I Joffe
Publications and source records attributed to B I Joffe.
Circulating endothelium-related adhesion molecules in black South African patients with Graves' disease.
Elevated serum concentrations of endothelium-associated adhesion molecules occur in Graves' disease. However, no data exist in African subjects, among whom the incidence is rising. Therefore, 20 black South Africans with Graves' hyperthyroidism were evaluated and 10 healthy controls were also studied. Quantitative determinations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-Selectin (sE-Selectin) were performed in serum samples by an enzyme-linked immunosorbent assay. Mean levels of sVCAM-1 were significantly increased in the thyrotoxic patients compared to controls, but this did not apply to the other adhesion molecules. The presence of ophthalmopathy in 12 patients did not further increase the mean sVCAM-1 concentration, and the administration of antithyroid medication in 5 patients had no measurable effect. In conclusion, sVCAM-1 appears to be a useful marker of active Graves' disease in black South Africans although it does not seem to reflect the occurrence of eye involvement in such patients.
Adolescent↗
Efficacy of vitamin E compared with either simvastatin or atorvastatin in preventing the progression of atherosclerosis in homozygous familial hypercholesterolemia.
Over a 4-year period, antioxidant therapy (vitamin E) was compared with high-dose statin therapy in 15 patients with homozygous familial hypercholesterolemia. Carotid intima-media thickness, used as an in vivo assessment of atherosclerosis, progressed rapidly during the period of vitamin E therapy but regressed on statin therapy.
Adolescent↗
Impact of HIV infection and AIDS on prevalence of type 2 diabetes in South Africa in 2010.
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Acquired Immunodeficiency Syndrome↗
Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia.
This study's aim was to determine whether biochemical risk factors such as lipoprotein(a), fibrinogen, homocysteine, and insulin, as well as low-density lipoprotein (LDL) particle size, were predictive of carotid intimamedia thickness (IMT), an early marker of atherosclerosis, in subjects with familial hypercholesterolemia (FH). We also determined whether plasma 8-isoprostane, as a marker of in vivo lipid oxidation, correlated with carotid IMT. Twenty-two homozygous and 20 heterozygous subjects with FH were compared with 20 normocholesterolemic controls. On univariate analysis, plasma total and LDL cholesterol, the cholesterol-years score (CYS), lipoprotein(a), and fibrinogen, but not homocysteine or insulin, were positively related, and high-density lipoprotein (HDL) cholesterol was negatively related to carotid IMT. However, on multivariate analysis, only LDL cholesterol and the CYS predicted carotid IMT (multiple r = 0.82; r2 = 0.68; p <0.0001). The subjects with FH had large rather than small dense LDL particles, and plasma 8-isoprostane levels were not increased. LDL cholesterol and the CYS, or "cholesterol bulk" are the pivotal determinants of atherosclerosis and are the strongest predictors of carotid IMT in FH.
Adult↗
Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.
Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (P<0.0001 and P<0.0005, respectively). T levels were decreased significantly in premenopausal and insignificantly in postmenopausal patients (P<0.0001 and P=0.06, respectively). The following correlations between neurohormonal levels and FIQ scores were found: DHEAS (after adjustment for age) vs. pain (P<0.001) and T (after adjustment for age) versus physical functioning (P=0.002). None of the other neurohormonal levels correlated significantly with any of the FIQ scores. IGF-1 levels were lower in the obese patients as compared to those who were non-obese (P=0.03). The BMI correlated positively with pain (P<0. 001) and inversely with DHEAS levels (P=0.006). After further adjustment for BMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.
Adolescent↗
Amlodipine and physiological responses to brisk exercise in healthy subjects.
Recent studies have questioned the safety of calcium antagonists in general, and short-acting dihydropyridine derivatives in particular. Reasons include excessive catecholamine stimulation after stress. We therefore wanted to assess whether amlodipine, a second generation dihydropyridine with a prolonged plasma half-life, would show a more favourable haemodynamic and biochemical profile after strenuous exercise. For this purpose, we studied 9 healthy volunteers in a double-blind, randomized, placebo-controlled trial. After 10 days of amlodipine, 5 mg orally daily or placebo therapy, volunteers performed a treadmill effort test; the sequence was repeated after a 2-week washout period. Amlodipine caused a significant increase in mean resting heart rate (HR) (from 65 +/- 3 to 70 +/- 3 beats/min, p < 0.05), without changing systolic or diastolic blood pressure (SBP, DBP). Post-exercise haemodynamic responses were similar while on amlodipine or placebo therapy. Amlodipine did not alter the normal profile of resting or exercise-induced metabolic [plasma glucose, serum K+, serum free fatty acid (FFA)] and hormonal [plasma cortisol, growth hormone, prolactin, insulin, epinephrine (EPI) and norepinephrine (NE)] responses--although plasma EPI concentrations dropped significantly lower (p < 0.05) at 5 min and 15 min post-exercise while on the calcium antagonist. We conclude that amlodipine has a largely neutral effect on the physiological profile after brisk exercise in healthy young subjects and that this may prove to be a useful property for a vasodilator drug.
Adult↗
Free fatty acids and insulin levels--relationship to leptin levels and body composition in various patient groups from South Africa.
OBJECTIVE: To investigate the relationship between leptin concentrations, various metabolic indices and body composition in six different groups. DESIGN AND MEASUREMENTS: Anthropometric measurements, fasting plasma glucose, serum insulin, C-peptide, FFA and leptin levels were performed. In the obese and diabetic subjects, body composition was analysed with bio-impedance equipment and as a 5 level CT scan. SUBJECTS: Five lipoatrophic diabetes mellitus (LDM) patients, five normal subjects (N), nine white and nine black obese women (WW, BW), and nine white and nine black diabetic women (DWW, DBW) were investigated after an overnight fast. RESULTS: In both ethnic groups there was a positive correlation between leptin and BMI (black group: r=0.8; P<0.0001, white group: r=0.7, P<0.002) and leptin and SC fat mass (black group: r=0.6; P<0.005, white group: r=0.6; P<0.004). CONCLUSIONS: Across the groups, there were positive linear correlations between leptin concentrations, BMI, SC fat mass and FFA levels. Leptin and FFA concentrations are higher and insulin levels lower in both groups of black women compared to the two groups of white women, despite a similar BMI and body fat mass. In the DBW the large increase in visceral fat mass may be indicative of a more complex relationship between compensatory insulin resistance, elevated FFA levels and leptin secretion.
Adult↗
Atherosclerosis seems not to be associated with hyperinsulinaemia in patients with familial hypercholesterolaemia.
OBJECTIVE: To study the relationship between hyperinsulinaemia, insulin resistance, leptin and atherosclerosis in subjects with familial hypercholesterolaemia (FH). DESIGN: Case-control cross-sectional study. SETTING: Lipid clinic, Johannesburg Hospital, South Africa. SUBJECTS AND METHODS: Fasting serum lipid, glucose, insulin and leptin levels were measured in 24 homozygous FH subjects; 20 FH heterozygotes without coronary artery disease (CAD); 22 heterozygotes with documented CAD; and 20 healthy normocholesterolaemic subjects. Insulin resistance was calculated using the homeostasis model assessment (HOMA) formula. RESULTS: Mean glucose and insulin levels were similar in all 4 groups. There was no significant difference in calculated insulin resistance between any of the groups. There was also no relationship between the degree of insulin resistance and total or LDL-cholesterol levels. Using Spearman's correlation coefficient (Rs) calculated insulin resistance correlated with triglyceride (Rs = 0.27; P<0.05) and inversely with HDL-cholesterol (Rs = -0.26; P<0.05). Fasting insulin concentrations and calculated insulin resistance were similar in FH subjects with overt CAD compared to those without. Leptin levels were higher in the FH subjects with CAD. However, these subjects were older and had a larger body mass index (BMI), and when adjusted for age and BMI, only BMI correlated with leptin levels (multiple r = 0.65; P<0.001). CONCLUSIONS: In the absence of other causes of insulin resistance, FH subjects have normal fasting insulin levels and, in general, they are not insulin resistant. Insulin resistance appears to play little role in the pathogenesis of accelerated atherosclerosis in FH.
Adolescent↗
Lactate and glycerol release from subcutaneous adipose tissue in black and white lean men.
To measure interstitial glycerol and lactate production from the sc adipose tissue of two regions in nine black and nine white lean men, sc microdialysis was performed in combination with adipose tissue blood flow rates measured with 133Xe clearance. In the postabsorptive state, the plasma glucose and insulin levels of the black men and white men were similar. The black men had higher plasma free fatty acids (825+/-97 vs. 439+/-58 micromol/L; P < 0.005), glycerol (99.5+/-5.1 vs. 54.1+/-3.3 micromol/L; P < 0.0001), and lactate (1056+/-95 vs. 729+/-45 micromol/L; P < 0.01). Interstitial glycerol concentrations in the black and white men were 227 vs. 163 micromol/L (P < 0.01) and 230 vs. 162 micromol/L (P < 0.05) in the abdominal and femoral regions. The adipose tissue blood flow rate was higher in the black men in the abdominal (7.9+/-0.9 vs. 3.1+/-0.5 mL/100 g x min; P < 0.01) and femoral area (5.2+/-0.6 vs. 2.8+/-0.3; P < 0.01). Interstitial lactate concentrations in black and white men were 1976 vs. 1364 micromol/L (P < 0.004) and 1953 vs. 1321 micromol/L (P < 0.004) in the abdominal and femoral regions, respectively. Glycerol release was higher in black men vs. white men for abdominal (0.21+/-0.02 vs. 0.14+/-0.02 micromol/100 g x min; P < 0.02) and femoral (0.22+/-0.02 vs. 0.15+/-0.01; P < 0.05) areas. Postprandially, black men had higher plasma glucose levels [1 h, 9.6+/-0.4 vs. 8.2+/-0.5 mmol/L (P < 0.05); 2 h, 8.9+/-0.4 vs. 7.2+/-0.4 mmol/L (P < 0.01)], but lower plasma insulin levels [1 h, 173+/-13 vs. 264+/-48 pmol/L (P < 0.05); 2 h, 136+/-20 vs. 209+/-34 pmol/L (P < 0.05)]. Plasma free fatty acid, lactate, and glycerol levels remained higher in the black men. After 1 h, lactate release was higher in the black men vs. that in the white men for abdominal (20.5+/-1.6 vs. 14.7+/-2.5 micromol/100 g x min;P < 0.05) and femoral (15.6+/-1.1 vs. 12.1+/-1.8; P < 0.03) areas. We conclude that the black men, who are relatively insulinopenic postprandially, have a brisker lipolysis and also release more lactate from sc fat tissue than white men. These differences in adipose tissue metabolism may be related to differences in the lipid profiles and glucose metabolism previously documented in these ethnic groups.
Adipose Tissue↗
Thyrotropin receptor antibodies in black South African patients with Graves' disease and their response to medical therapy.
Graves' disease is increasing in incidence amongst urban black South Africans. The pathogenic role of thyrotropin receptor antibodies (TRAb), crucial in other populations, has not been formally evaluated in African communities. We therefore prospectively investigated the prevalence of TRAb in 30 consecutive urban black South African patients with classical Graves' disease at the onset of their illness. This was compared with the frequency of thyroid microsomal and thyroglobulin antibodies in the same patients. Ten patients with euthyroid goitres unrelated to Graves' disease and 10 healthy controls were also studied. Twenty of the hyperthyroid patients were retested 4-6 months after starting carbimazole therapy and ten of them again after 1 year. Initially 83% of patients were positive for TRAb as against 54% for thyroid microsomal and 1 7% for thyroglobulin antibodies. After 4-6 months of treatment, 65% of patients still had elevated (>15% inhibition of binding) TRAb titres, while at 1 year this had dropped to 40% (4 out of 10 patients). All positive patients had relapsed biochemically, while TRAb negative patients were all in remission. We conclude that TRAb are a sensitive and specific marker of Graves' disease in black South Africans and closely parallels the response to medical therapy at 1 year. However, their predictive value for delayed relapse requires the study of a larger cohort of patients over a longer time-frame.
Adult↗
Ordered arrangement and rearrangement of chromosomes during spermatogenesis in two species of planarians (Plathelminthes).
The pattern of distribution of telomeric DNA (TTAGGG), 28S rDNA, and 5S rDNA has been studied using fluorescence in situ hybridization (FISH) and primed in situ labelling during spermatogenesis and sperm formation in the filiform spermatozoa of two species of planarians, Dendrocoelum lacteum and Polycelis tenuis (Turbellaria, Plathelminthes). In both species, the positions of FISH signals found with each probe sequence are constant from cell to cell in the nuclei of mature sperm. Chromosome regions containing 5S and 28S rDNA genes are gathered in distinct bundles of spiral form. In early spermatids with roundish nuclei, the sites of a given sequence on different chromosomes remain separate. Centromeres (marked by 5S rDNA) gather into a single cluster in the central region of the slightly elongated sperm nucleus. During spermatid maturation, this cluster migrates to the distal pole of the nucleus. In Polycelis, telomeric sites gather into three distinct clusters at both ends and in the middle of the moderately elongated nucleus. These clusters retain their relative positions as the spermatid matures. All the chromosome ends bearing 28S rDNA gather only into the proximal cluster. Our data suggest that structures in the nucleus selectively recognise chromosome regions containing specific DNA sequences, which helps these regions to find their regular places in the mature sperm nucleus and causes clustering of the sites of these sequences located on different chromosomes. This hypothesis is supported by observations on elongated sperm of other animals in which a correlation exists between ordered arrangement of chromosomes in the mature sperm nucleus and clustering of sites of the same sequence from different chromosomes during spermiogenesis.
Animals↗
Unordered arrangement of chromosomes in the nuclei of chicken spermatozoa.
The arrangement of chromosomes in the elongated sperm nuclei of chicken was studied using fluorescence in situ hybridization with probes specific for telomeres of all chromosomes, a microchromosome, the long arm of chromosome 6, the large heterochromatic block on the Z-chromosome, and the same heterochromatic block plus subtelomeric sites on macrochromosomes 1-4. The positions of all probes vary from one sperm to another. No order in chromosome arrangement is apparent. It is suggested that large chromosome size and small chromosome number correlate with constant positions of chromosomes and vice versa. Based on the known quantity of repetitive units of the repeat on the Z-chromosome, the degree of compaction of chromatin in the chicken sperm nucleus is estimated as ca 0.7 Mb/ microm. As judged from the length of the heterochromatic region of the Z-chromosome at the lampbrush stage, the total length of the Z-chromosome in mature sperm is 2.5-4 times that of the sperm nucleus.
Animals↗
Lactate and glycerol release from the subcutaneous adipose tissue of obese urban women from South Africa; important metabolic implications.
Interstitial glycerol and lactate production was measured in the s.c. adipose tissue of two anatomical regions in 10 obese urban black women (BW) and 10 obese urban white women (WW) matched for age, body mass index, waist-hip ratio, diet, and physical activity. This was done with the s.c. microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from 133Xe clearance. Biochemical measurements were done in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used for analyses of body composition. BW responded with lower plasma insulin levels, but higher glucose levels, during the oral glucose tolerance test. BW have higher lactate release from the s.c. adipose tissue, compared with WW, in the postabsorptive state (abdominal: 7.8 +/- 0.9 vs. 2.4 +/- 0.3 micromol/kg x min, P < 0.0001; femoral: 9.1 +/- 0.9 vs. 2.1 +/- 0.3 micromol/kg x min, P < 0.0001) and during the postprandial period (at 1 h, abdominal = 7.3 +/- 0.8 vs. 3.0 +/- 0.4 micromol/kg x min, P < 0.0001, femoral area = 8.1 +/- 1.0 vs. 2.7 +/- 0.4 micromol/kg x min, P < 0.0001; at 2 h, abdominal = 5.7 +/- 0.4 vs. 3.1 +/- 0.3 micromol/kg x min, P < 0.001). The BW also released more glycerol from the sc adipose tissue in the postabsorptive state (abdominal = 1.15 +/- 0.17 vs. 0.65 +/- 0.03 micromol/ kg x min, P < 0.009; femoral = 1.55 +/- 0.19 vs. 0.72 +/- 0.05 micromol/kg x min, P < 0.001) and during the postprandial period (at 1 h, abdominal = 1.05 +/- 0.15 vs. 0.11 +/- 0.02 micromol/kg x min, P < 0.001, femoral = 1.05 +/- 0.12 vs. 0.21 +/- 0.03 micromol/kg x min, P < 0.001; at 2 h, abdominal = 0.31 +/- 0.06 vs. 0.04 +/- 0.01 micromol/kg x min, P < 0.001, femoral = 0.28 +/- 0.07 vs. 0.05 +/- 0.01 micromol/kg x min, P < 0.003). Postprandially, the BW had higher ATBF rates in the abdominal and femoral areas. WW have more visceral fat (150 +/- 2.0 vs. 110 +/- 5.0 cm2, P < 0.05). In conclusion, the insulinopenic BW have a brisker lipolysis and ATBF and release more glycerol and lactate from their sc adipose tissue, both in the postabsorptive state and after an oral glucose tolerance test. These variations in adipose tissue metabolism may contribute to differences observed in the disease profiles of these two groups of women.
Adipose Tissue↗
Plasma fatty acid levels in South African interethnic male high school pupils at different ultimate risks of coronary heart disease.
While coronary heart disease (CHD) is responsible for about a quarter of deaths in South African white, coloured and Indian populations, the rate is very low in the black population. Dietary risk factors for CHD include high intakes of saturated fatty acids and cholesterol, with low intakes of mono and polyunsaturated fatty acids. In a characterization study, plasma fatty acid profiles have been determined in seven groups of high school pupils aged 16-18 years, namely, white, rural black, urban black and middle-class and lower socio-economic class coloureds and Indians. Plasma fatty acids were measured by gas liquid chromatography in 20 subjects from each group. Contrary to expectation, urban and rural black pupils had the highest mean molar composition of saturated fatty acids, largely myristic (14:0) and palmitic (16:0) acids. Rural blacks and middle-class coloureds had the highest molar percentage composition of monounsaturated fatty acids, primarily oleic acid (18:1). Again unexpectedly, white, coloured and Indian groups had the highest level of polyunsaturated fatty acids, due entirely to linoleic acid (18:2). As the findings are unrelated to proneness to CHD mortality in the particular communities studied, plasma fatty acid levels are not predictive of the disease. Epidemiologically, there are many examples of lack of correlation in serum lipid levels and proneness to CHD.
Adolescent↗
Clinical characteristics and outcome of hyperglycaemic emergencies in Johannesburg Africans.
In this prospective analysis we investigated the clinical characteristics of black South African diabetic patients admitted to hospital with hyperglycaemic emergencies. The study cases were selected from the medical admissions to an urbanized, Johannesburg academic hospital over a period of 12 months. Only patients with severe diabetic ketoacidosis (DKA) or hyperosmolar non-ketotic hyperglycaemia (HNKH) as defined in the text were included. Over the study period, we identified 58 patients with severe DKA (M: 32, F: 26) and 24 with HNKH (M: 14, F:10). Thirty-two of the patients with DKA (55.2%) were classified as having non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Compared to the 26 subjects with insulin-dependent (Type 1) diabetes mellitus (IDDM), the NIDDM patients were older (51.7 vs 27.7 years) and had a significantly higher body mass index (BMI) (29.4 vs 23.5 kg m(-2), p = 0.002), and glucose levels 47.5 vs 34 mmol l(-1) p = 0.004). Mortality from DKA was 6.8 % and from HNKH 16.6%. Infection was the leading precipitating factor for both DKA and HNKH, followed by first presentation and noncompliance. We conclude that the majority of urban African patients admitted to hospital with DKA have NIDDM. Mortality from DKA among the black Africans in Johannesburg is low and comparable to the mortality in western Europe.
Adult↗
Insulin receptor substrate-1 gene variants in lipoatrophic diabetes mellitus and non-insulin-dependent diabetes mellitus: a study of South African black and white subjects.
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Adolescent↗
Improved glucose tolerance after effective lipid-lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle's cycle in its pathogenesis?
This report describes a patient with lipoatrophic diabetes mellitus (LDM), which is a rare clinical syndrome characterized by lipoatrophy and severe insulin resistance. Although a genetic abnormality is suspected in the development of LDM, no functional mutations in key domains of the insulin receptor gene were detected. Therapy was directed primarily at decreasing the availability of non-esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle's cycle), by the administration of a lipid-lowering drug, bezafibrate. Serial changes in fasting levels of the hormones of glucose homeostasis and lipids were measured, as well as glucose and insulin responses to a 75-g oral glucose challenge at onset and following 3 and 6 months of fibrate therapy. Progressive reductions in the patient's levels of triglycerides and NEFA were paralleled by an improvement in beta-cell function, a decrease in insulin resistance, and the attainment of normal glucose homeostasis. We conclude that the pathogenesis of LDM may be related primarily to abnormal regulation of lipid, rather than glucose, metabolism.
Adolescent↗