Adipose tissue cytokines: relation to glycemic control, insulin resistance and biochemical bone markers in type 2 diabetic Saudi male patients

To assess the plasma levels and relations of adipocytokines and biochemical bone markers in type 2 diabetes mellitus [T2DM] Saudi males with insulin resistance. This case-control study included 80 overweight/obese males with T2DM on oral anti-diabetic medications recruited from the diabetic center and 40 healthy lean males of matched age. Measurements included fasting plasma glucose [FBG], fasting plasma insulin, serum calcium [Ca[2 +]], HbA1c, plasma adiponectin and resistin, serum bone-specific alkaline phosphatase [B-ALP], plasma osteocalcin [OC], and plasma osteoprotegerin [OPG]. Waist and hip circumferences were measured. Body mass index, waist/hip ratio [WHR], and insulin resistance [HOMA-IR] were calculated. Compared to the control group, diabetic patients showed significantly both lower adiponectin [p = 0.000] and Ca[2 +] [p = 0.000] but significantly higher resistin [p = 0.000], OC [p = 0.000], B-ALP level [p = 0.000] and OPG [p = 0.000]. After multivariate adjustment in diabetic patients, resistin predicted OC, [beta = -0.30, p = 0.005], WC and resistin predicted Ca[2+] [beta = -0.34, p = 0.035 and beta = -0.25,p = 0.033], adiponectin and resistin predicted B-ALP, [beta = -0.35, p = 0.010 and beta = 0.35, p = 0.004], and FBG, HOMA-IR and age predicted OPG, [beta = -0.66, p = 0.010, beta = 0.58, p = 0.024 and beta = 0.27, p = 0.031 respectively]. Also, FBG, WHR and HOMA-IR predicted adiponectin [beta = -0.79, p = 0.001, beta = -0.60, p = 0.001 and beta = 0.80, p = 0.001 respectively], while OC and OPG predicted HbA1c [beta = -0.32, p = 0.007 and beta = 0.28, p = 0.016 respectively]. Uncontrolled T2DM Saudi males with insulin resistance have abnormal bone markers with unfavorable levels of adipocytokines. Strong associations between bone markers, adipocytokines, insulin resistance and metabolic control may suggest interaction in multiple direction feedback loops exacerbating hyperglycemia

Comparative study of insulin-like growth factor-I, insulin-like growth factor binding protein-3, and bone markers in pregnant normotensive and pre-eclamptic women

The current study was conducted to evaluate the serum OPG, RANKL and osteocalcin, as markers of bone turnover, in pre-eclamptic women compared to normotensive women, and to find out if there were any relationships between biochemical bone markers and IGF-1 and IGFBP-3. The present study included 30 women with pre-eclampsia as group I, GI. Thirty normotensive pregnant controls were included in the study representing group II, GII. All candidates of the study were subjected to routine laboratory investigations, serum IGF-l and IGFBP-3. Measurement of bone formation markers included serum alkaline phosphatase and serum calcium, and serum osteocalcin. Measurement of bone resorption markers included urinary hydroxyl proline, and newly discovered bone turnover markers which are serum osteoprotegerin [OPG] and serum RANKL. A significant decrease of serum alkaline phosphatase, calcium, OPG and IGF-1 were noted in the pre-eclamptic group when compared to the normotensive group. On the contrary, serum osteocalcin, RANKL, and IGFBP-3 showed a significant increase in the pre-eclamptic group when compared to the normotensive group. Bone formation and bone resorption markers showed a significant difference in pre-eclamptic women when compared to normotensive pregnant women. However, it is difficult to compare biochemical markers of bone turnover in this way because of differences in the specificity of the markers for bone and different metabolism by the liver and kidney in pre-eclamptic women. The high levels of biochemical markers may indicate increased bone turnover in the mother, but there could be some fetal contribution. Further studies are necessary to elucidate the detailed functions of OPG/RANKL on bone metabolism during pregnancy and pre-eclampsia

Circulating biomarkers of oxidative stress and endothelial cell dysfunction in preeclampsia

To investigate the role of E-selectin, xanthine oxidase, the anti-oxidant enzyme catalase, and endothelial nitric oxide synthase [eNOS] activity and gene polymorphism in the pathophysiology of preeclampsia. Design: Case control study. Setting: Department of Obstetrics and Gynaecology and Department of Medical Biochemistry, Faculty of Medicine, Alexandria University. Subjects: Thirty preeclampsia patients [15 mild, and 15 severe] and fifteen normotensive controls. Interventions: Plasma samples were assayed for E-selectin and xanthine oxidase. Erythrocyte catalytic activity and eNOS activity in polymorphonuclear leucocytes were determined followed by screening for the Glu 298 Asp eNOS gene variant. Plasma xanthine oxidase and E-selectin were significantly increased and eNOS activity significantly decreased in the pre eclamptic groups compared to controls. Erythrocyte catalase did not differ significantly between groups. The frequency of Glu 298 Asp gene variant was significantly increased in severe preeclampsia. E-selectin, xanthine oxidase and eNOS may be used as clinically useful biomarkers for preeclampsia. The presence of Glu 298 Asp eNOS gene could be a marker for increased risk of developing severe preeclampsia

role of plasma homocysteine and lipoprotein [a] in coronary artery disease

Objective: to study the possible role of homocysteine and lipoprotein [a] as risk factors for premature coronary artery disease [CAD], and to assess their relationship to conventional risk factors

Subjects and Methods: 45 subjects were divided into 3 groups, 15 premature CAD patients without traditional cardiovascular risk factors, 15 premature CAD patients with one or more traditional cardiovascular risk factors [hypertension, diabetes mellitus, cigarette smoking, or dyslipidemia] and 15 healthy normal subjects matched for age and sex [controls]. All were subjected lo estimation of plasma homocysteine [Hcys], plasminogen activator inhibitor-1 [PAI-1] by ELISA, plasma folic acid by radioimmunoassay, plasma lipoproteine a [Lp[a]] by turbidimetry and plasma lipids by colorimetry

Results : this study showed a significant elevated Hcys and low folate levels in premature CAD patients. Significant correlations found between elevated level of PAI-1 and CAE in the two patient groups. There were significant positive correlations between plasma Hcys and that of PAI-I and LDL-C and significant negative correlations between plasma Hcys and that of folate and HDL-c in the patient groups. Plasma Lp[a] was only significantly elevated in premature CAD patients with traditional risk factors

Conclusion : Hcys, folic acid and PAI-1 might serve as independent risk factors for premature CAD in patients with and without traditional coronary risk factors. However. Lp[a] might confer an additional coronary risk factor only in the presence of traditional risk factors

Respiratory chain activity in myopathies

Aim: The present study was conducted to find out whether disturbances of respiratory chain enzymes were involved in the pathogenesis of three types of myopathy: Duchenne muscle dystrophy [DMD], limb girdle muscular dystrophy, and steroid-induced myopathies; to assess the extent and nature of these deficits among the three myopathic groups, and to investigate the relation between the severity of muscular disorders- assessed by creatine phosphokinase [CPK] level- and the extent of respiratory chain impairment. Subjects and Fourty myopathic patients as group I [GI]; 10 DMD [GIA], 16 limb girdle dystrophy [GIB], and 14 steroid-induced myopathy [GIC]; and 20 healthy controls as group II [GII] that matches the general features of GI. Cases and controls were subjected to history taking as well as physical examination. Diagnosis of myopathy was established using routine motor and sensory conduction study and concentric needle EMG. Cases and controls were subjected to estimation of respiratory chain complexes; RCI, RCII, RCIII, and RCIV, in neutrophil mitochondria. Results were analysed using t-test between GI and II and F test in between GIA, GIB and GIC. The results revealed a significant decrease of all respiratory chain complexes; RCI, RCII, RCIII, and RCIV; in GI as compared to controls [2878.04 +/- 1085.96 versus 5867.93 +/- 1000.03 micro mol/min/mg protein for RCII, 549.7 +/- 21574 versus 80382+/=119.41 micro mol/min/mg of protein for RCIV, 60654 +/- 162.35 versus 95949 +/- 136.14 micro mol/min/mg of protein for RCIII, and 58.73 +/- 18.08 versus 97.88 +/- 19.06 micro mol/min/mg protein for RCIV. On comparing the 3 subgroups; IA, IB, and IC; the following was found [1] A significant decrease of GIC when compared to GIA and when compared to GIB and when compared to GIB as regards RCI [3234.526 +/- 716.363, 3385.13 +/- 218.603, and 2043.894 +/- 631.967 micro mol/min/mg protein for GIA. GIB, and GIC, respectively, F - 4.331, and P = 0.03]; [2] A significant decrease of GIA when compared to GIB and when compared to GIC as regards RCIV [42.584 +/- 22,9177, 66.947 +/- 10.861, and 60.88 +/- 1532 micro mol/min/mg protein for GIA, GIB, and GIC, respectively, F = 3.67 and P = 0.47]. [3] Nonsignificant difference between GIA, GIB and GIC as regards RCII, and RCIII. Using multiple linear regression analysis between respiratory chain enzymes and CPK, only RCIV showed a statistically significant correlation with CPK. Conclusions: Myopathy could be associated with alterations in respiratory chain enzyme complexes that result in effort intolerance. Such an alteration could be detected in neutrophil mitochondria by an easier noninvasive technique. RCIV could be used as a predictive marker for the occurrence of muscle damage in myopathy

Oxidative stress and neonatal jaundice: an etiological study

This study aimed at investigating the role of oxidative stress in the development of neonatal jaundice. The enzyme activities of erythrocyte glucose-6-phosphate dehydrogenase [G6PD], plasma glutathione peroxidase [GSHPx] and glutathione-S-transferase [GST] were measured by quantitative determination of enzyme activity in 40 jaundiced full term newborns with different peak bilirubin levels [12.5 - 20 mg/dl] [not attributable to any known etiology] and 20 control newborns. The level of plasma advanced oxidation protein products [AOPP], an index of oxidative stress was also measured in these newborns. None of the jaundiced newborns needed phototherapy or exchange blood transfusion before the study. Plasma GSHPx activity was significantly lower in infants with hyperbilirubinaemia compared to control group. However, the enzyme activities of both plasma GST and erythrocyte G6PD as well as plasma AOPP concentrations were significantly higher in jaundiced newborn infants than in the control group. Plasma GSHPx activity demonstrated a significant negative correlation with GST activity, bilirubin concentration and AOPP levels. A significant positive correlation was also evident between serum bilirubin and plasma AOPP concentrations. The results of this study suggest that low GSHPx activity in jaundiced newborn infants might predispose these infants to oxidative stress. This may result in the development of mild oxidative hemolysis and jaundice

Steriod microdose therapy in rheumatoid arthritis patients: impact on bone metabolism

The anti-inflammatory and immuno-suppressive properties of GCs have prompted their extensive use in the management of various diseases including RA. However, the benefits derived from the use of GCs may be offset by the occurrence of GCs related side effects. One of the most important side effects of long-term use of GCs is osteoporosis. Steroid microdose therapy [simply called Microdose Therapy], a university-spin-off technology, is a physician-supervised, 3-step, education program for teaching patient control of GCs for controlling chronic inflammation in arthritic patients. This Microdose Therapy uses very low dose of prednisone [

Relationship of obesity to insulin resistance in Egyptian women: role of leptin

The aim of the present work was to study insulin resistance [IR] in obesity and to detect any possible role of leptin in the mediation of such resistance, as well as its consequences. Subjects and The present study was conducted on twenty obese otherwise healthy women [mean body mass index [BMI], 32.58 +/- 2.09kg/m2] and twenty nonobese healthy control women [mean BMI, 23.13 +/- 1.62kg/m2] of matched age and menopausal status. All subjects were subjected to the following measures: 1] anthropometric measurements including BMI, waist circumference and waist/hip ratio [WHR] [The first parameter was used as a surrogate for overall obesity, while the latter 2 parameters were used as surrogates for abdominal obesity], 2] systolic and diastolic blood pressure [SBP and DBP, respectively] measurements, 3] fasting and 2-hour postoral glucose tolerance test, 4] fasting plasma insulin and fasting plasma glucose/insulin ratio [both are surrogates for IR], 5] fasting serum lipid profile including total cholesterol [TC], high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], triglycerides [TG], free fatty acids [FFAs], and atherogenicity ratio [TC/HDL-C], and 6] plasma leptin. Compared to the nonobese healthy controls, obese women demonstrated statistically significant increase in the measures of abdominal obesity [waist circumference and WHR], both SBP and DBP, glycemic control measures [fasting and 2 hour postoral glucose tolerance test], fasting plasma insulin and leptin levels. Obese women also demonstrated statistically significant decrease in fasting plasma glucose/insulin ratio. They also showed statistically significant dyslipidemia [hyper-cholesterolemia, low HDL-C, high LDL-C, hypertriglyceridemia, and high FFAs] and high atherogenicity ratio. Conclusions: Obesity is frequently accompanied by both insulin resistance ana by leptin resistance that are parallel to each other. Obese subjects have a tendency for increased high blood pressure, increased blood glucose levels and atherosclerosis. They are also dyslipidemic. Hyperleptinemia of obesity may mediate such cardiovascular and metabolic abnormalities. The strong correlation of plasma leptin to the measures of abdominal [visceral] obesity [especially the waist circumference] and the measures of IR [e.g. fasting plasma insulin and fasting plasma glucose/insulin ratio] supports the possibility of the role of leptin in the link between abdominal visceral obesity and IR

Beta2 Microgolbulin amyloidsis in uremic patients

Aim: The aim of this work was designed to study some parameters of uremic- oxidant stress and their impact on the pathogenesis of dialysis- related amyloidosis. Subjects and This study was carried on 40 uremic patients and 10 normal subjects as control group [group l]. Patients were divided into 4 groups according to the duration of hemodialysis. Group II: 10 uremic patients on conservative treatment. Group III: 10 patients on hemodialysis for 1-5 years. Group IV: 10 patients on hemodialysis for 5-10 years. Group V: 10 patients on hemodialysis for more than 10 years. AII patients were subjected to thorough history taking, clinical examination, routine and specific laboratory investigations [plasma and tissue malonyldialdhyde, plasma advanced oxidation protein products, vitamin C and E and beta2 microglobulin concentration]. Histopathological study was done by light and electron microscope and histochemical assay for beta2 microglobulin in the affected tissue. plasma and tissue concentration of MDA were significantly higher among uremic non-dialysed and HD patients than in controls. Plasma AOPP were significantly higher in uremic non-dialysed and HD patients as compared to the control group. Plasma vitamin C was significantly lower in patients than in controls, while its oxidized product [dehydroascorbate] was significantly higher among the same groups as compared to the control group. Plasnma vitamin E was normal among all groups. It was significanthy inversely correlated with plasma MDA. PIasma beta2 M was significantly higher in uremic non-dialysed and HD patient as compared to the control group. Light and electrcon microscopical studies showed no amyloid deposits in group I and II, but in groups III, IV and V the incidence amyloid deposits were 10%, 40% and 70°, respectively. The prevalence of beta2 M amyloid in H patients was positively and significantly correlated to the duration of HD. Immunohistochemical study showed beta2 M deposition in all tissue specimens but the intensity of deposition was higher in uremic patients as compared i the control group. Conclusions: Oxidant-stress is well documented and clearly expressed both at the plasma and tissue levels in uremic and HD patients. It may have an important role in the pathogenesis of DRA through creating a state of carbonyl stress that modifies beta2M increasing its amyloidogenic tendency

Serum matrix metalloproteinases-2 and -9 and tissue inhibitor of matrix metalloproteinase-1 in non-small cell lung cancer patients: a potential role in tumour growth, invasion, and metastasis

The aim of this study was to measure senun levels of matrix metalloproteinases-2and -9 [MMP-2 and -9] and tissue inhibitor of matrix metalloproteinase-1 [TIMP-1] in non-small cell lung cancer [NSCLC] patients and to detect any potential role of these parameters in tumour growth, invasion and metastasis. The present study entailed 49 patients with primary NSCLC and 10 healthy non-smoker volunteers as a control group. All lung cancer patients were subjected to CT imaging and fiberoptic bronchoscopy with biopsy taking for histological diagnosis. Transthoracic fine needle aspiration lung biopsy or open lung biopsy was performed in patients with negative fiberoptic bronchoscopic results. Serum levels of MMP-2, MMP-9, and TIMP-1 were measured in both NSCLC patients and the controls by one-step sandwich enzyme immunoassay specific for each parameter. The current study revealed significant increase in the mean serum levels of MMP-2, MMP-9, and TIMP-1 in NSCLC patients than in the control group [P<0.0001]. It also revealed that 61.22%, 48.99%, and 53.06% of NSCLC patients had respectively serum MMP-2, MMP-9, and TIMP-1 levels higher than the corresponding cutoff values of the mean +2SD in the healthy controls. The study also showed significant positive association between the serum levels of these parameters and the TNM stage of the disease [P = 0.01, 0.03, and 0.01 for MMP-2, MMP-9, and TIMP-1 respectively]. The study also revealed significant differences in serum levels of such parameters in adenocarcinoma [AdC] versus squamous cell carcinoma [SqCC] [P = 0.03 for both MMP-2 and TIMP-1 and 0.02 for MMP-9]. Serum levels of MMP-2, MMP-9, and TIMP-1 are elevated in NSCLC patients and are associated with the TNM stage of the disease suggesting important roles of such parameters in growth, invasion, and metastasis of NSCLC. The elevated levels of such parameters in AdC than in SqCC may relate to the greater tendency of the former for systemic metastasis. This study suggests that serum MMP-2, MMP-9, and TIMP-1 may be used as useful markers of NSCLC invasion and metastasis

Effect of some drugs with immunosuppressive properties on IgE mediated mast cell degranulation and delayed type hypersensitivity

This study was carried out on 60 adult albino rats and 30 mice of cyclosporin A [CsA], methotrexate [MTX], ribavirin and dexamethasone [Dxt] on peritoneal mast cell [PMC] histamine release, passive cutaneous anaphylaxis [PCA] reactions in rats and DTH in mice. The studied animals were divided into three groups: The first was to study the effect of previous drugs on PMC histamine release in actively sensitized rats, the second was to study the effect of previous drugs on PCA in passively sensitized rats and the third was to study the effect of previous drugs on the induction of DTH in mice in vivo. Each group was divided into five subgroups and were pretreated with saline [control] or one of the previously mentioned drugs

Non-pedunculated leiomyoma of the scrotum

Leiomyomas arising from the tunica dartos scroti are rare tumours. We present a case of non-pedunculated leiomyoma of the scrotum, probably the first reported in Kuwait

Steroid micro dose therapy in rheumatoid arthritis patients: clinical and biochemical study

The anti-inflammatory and immunosuppressive properties of GCs have prompted their extensive use in the management of various diseases including RA[1]. However, the benefits derived from the use of GCs may be offset by the occurrence of GCs related side effects. One of the most important side effects of long-term use of GCs is osteoporosis. Steroid Microdose therapy [simply called Microdose Therapy], a university-spin-off technology, is a physician-supervised, 3-step, education program for teaching patient control of GCs for controlling chronic inflammation in arthritic patients. This Microdose therapy uses very low dose of prednisone [