Serum levels of soluble receptor activator of nuclear factors-KB ligand [sRANKL], osteoprotegerin [OPG] and bone mineral density in Egyptian osteoporotic elderly women

The aim of this study was to determnine the state of the OPG/RANKL system and its possible role in osteoporotic elderly women. The present study included 40 apparently healthy old osteoporotic women aged 64.5 +/- 4.5 years as group I,[GI] and 30 healthy women of matched age as group II [GII]. The two groups were subjected to complete history taking, thorough clinical examination, routine laboratory investigations, measurement of bone formation markers as serum alkaline phosphatase, serum calcium and serum osteocalcin and measurement of bone resorptiomz markers including: hydroxyproline in urine, serum OPG and serum RANKL CT Bone Density was done as well. In the current study, non significant differences were noted between the 2 studied groups as regard fasting blood glucose, renal amid hepatic function tests. A significant increase in serum alkaline phosphatase and urinary hydroxyproline and a significant decrease in serum calcium and serum osteocalcin was noted in group I compared to group Ii. Serum levels of RANKL were significantly elevated while serum OPG levels were significantly decreased in osteoporotic women compared to healthy controls. Changes in circulating OPG-RANKL correlates with serum osteocalcin and BMD changes. RANKL is an essential cytokine for the formation and activation of osteoclasts and promotes bone resorption, while OPG antagonizes these effects. Estrogen deficiency tilts the RANKL/OPG balance to favor osteoclastic activation and bone loss. RANKL blockade may emerge as a novel therapeutic option for human bone diseases. Further studies are necessary to elucidate the causes of osteoporosis and low bone mass in old women

Levels of circulating soluble cell adhesion molecules in diabetics and in impaired glucose tolerance patients: correlation to stiffness index beta of the common carotid and femoral arteries

The current work was conducted to study the possible relationship between endothelial activation as assessed by the level of circulating soluble VCAM-1, ICAM-1, and E-selectin concentrations and atherosclerotic disease as assessed by the stiffness index 13 of the common carotid and femoral arteries in type 2 diabetic patients and patients with impaired glucose tolerance and the correlation of stiffness index beta of the common carotid artery and femoral artery with the degree of insulin resistance. Subjects and This study entailed 20 patients with type 2 diabetes meilitus, representing group I [GI], and 20 patients with impaired glucose tolerance, representing group II [GII] and 20 healthy subjects of matched age and sex as a control group, III [GIII]. All subjects were subjected to complete history taking and thorough clinical examination including body mass index [BMI]. Routine Laboratory investigations included oral glucose tolerance test [OGTT], glycosylated hemoglobin [HbA[1c]], serum uric acid, serum triglycerides, total serum cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], as well as liver and renal function tests were carried out by using standard commercial methods. The level of urinary microalbumin in GI, and insulin sensitivity assessment through OGTT, in all groups were carried out. Serum levels of the circulating adhesion molecules ICAM-1, VCAM-1 and E-selectin were measured in GI, II, and III by an enzyme-linked immunosorbent assay. All subjects were subjected also to radiological measurement of stiffness indexes beta of the common carotid and femoral arteries by high-resolution ultrasonography. sVCAM was found to be 681.2 +/- 81.8, 551.7 +/- 33.5, 453.4 +/- 28.4 ng/ml in GI, GII, and GIII, respectively. sICAM was found to be 339.4 +/- 18.8, 301 +/- 19.3, 197.8 +/- 9.2 ng/ml in GI, GII, and GIII, respectively. E-selectin was found to be 90.4 +/- 5.7, 69.8 +/- 6.8, 51.1 +/- 6.6 ng/ml in GI, GII, and GIII, respectively. Using LSD, sVCAM, sICAM, and E-selectin were found to be significantly increased in GI when compared to GII and GIII and to be significantly increased in GII when compared to Gill. Concerning stiffness index of carotid artery, it was found to be 28.7 +/- 8.3, 14.7 +/- 1.4, 12.1 +/- 1.6 in GI, GII, and GIII respectively. Using LSD, stiffness index of carotid artery was found to be significantly increased in GI when compared to GII and controls. With reference to stiffness index of femoral artery, it was found to be 30.3 +/- 7.1, 15.4 +/- 1.4, 12.7 +/- 2.4 in GI, GII, and GIII, respectively. Using LSD, stiffness index of the femoral artery, it was found to be significantly increased in GI when compared to GII and controls. It could be concluded that cAMs can be used as a marker of the stiffness index beta of both common carotid and femoral arteries due to the noted significant positive association. Stiffness index beta of both common carotid and femorai arteries are exacerbated in type 2 diabetic patients than in patients with impaired glucose tolerance and controls. The stiffness index beta of both common carotid and femorai arteries are associated with insulin resistance in type 2 diabetes meilitus. Further prospective studies should be carried to ascertain whether insulin resistance may induce the early changes of atherosclerosis in diabetes

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

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

Can sPLA2-IIA, sICAM be a predictor of atherogenic susceptibility in Egyptian rheumatoid arthritis patients: correlative study to other atherogenic parameters

Aim: The aim of the present study was to investigate the state of sPLA2-IIA and sICAM-1 in the plasma of RA patients and their possible role as risk factors for atherogenic susceptibility in those patients. Subjects and Twenty rheumatoid arthritis patients [group I] and 20 healthy controls of matched age and sex [group II] were subjected to estimation of ESR, CRP, plasma total cholesterol, triglycerides, HDL-C, LDL-C, secretory phospholipase A2 group II A [sPLA2-IIA] by ELISA method and soluble intra-cellular adhesion molecule-1 [sICAM-1] by ELISA method and plasma Lp[a] by turbidimetry method. The results revealed a significant increase of all of the bllowing in RA patients as compared to controls: 1] sPLA2-IIA [112.05 +/- 13.22 versus 14.06 +/- 2.04, P=0.000], 2] sICAM [332.05 +/- 13.64 versus 266.25 +/- 9.24, P=0.000], 3] Lp[a] [18.36 +/- 2.1 versus 11.46 +/- 0.8, P=0.0001]. A significant decrease of HDL in patients as compared to controls [47.3 +/- 4.6 versus 66.45 +/- 8.16, P=0.000] while no significant differences were found in total cholesterol, triglycerides, and LDL-C in patients when compared to controls. A correlation was found between CRP, as an inflammatory marker, and sPLA2-IIA, sICAM, Lp[a] and LDL-C in RA patients and a correlation was also found between LDL, as an atherogenic marker, and sPLA2-IIA, sICAM, and Lp[a]. Conclusions: sPLA2-IIA and sICAM may contribute to atherogenesis in RA patients. Further studies are needed in the future to settle whether they are early markers of atherogenesis or not. Further studies are also needed to detect the benefit of using anti-ICAM as a preventive measure against coronary atherosclerosis in RA patients

Study of the relation of interleukin-6, essential fatty acids, and estrogen in bone metabolism in elderly women

The aim of this study was to evaluate and assess the relation of interleukin-6, essential fatty acids, and estrogen to the development of osteoporosis in women of different age groups. This study was carried on 40 women divided in two groups: the first group [GI] included 20 apparently healthy women above 65 years and the second group [GII] included 20 healthy women between 20-30 years of age. Serum osteocalcin, estrogen, interleukin-6 by ELISA, Urinary hydroxyproline by ELISA, essential fatty acid in the blood by Gas Liquid Chromatography, serum calcium, and phosphorus were estimated as well as bone density. The current study revealed a significant decrease of serum estrogen in GI when compared to GII [p<0.05], a significant increase of serum interleukin-6, osteocalcin, urinary hydroxyproline in GI when compared to GII [p<0.05], a significant decrease of bone density in GI when compared to GII [p<0.05]. A significant strong positive correlation between interleukin-6 and bone density in both groups were found. From this study, it is concluded that low estrogen level and high interleukin-6 could be used as a predictor for the occurrence of low bone density and the production of osteoporosis with the subsequent occurrence of fractures in post menopausal women

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