role of Thrombomodulin, IL-12, transforming growth factor-beta2 in early onset preeclamsia: a potential biomarker for disease severity

Early onset Preeclampsia is a pregnancy specific heterogeneous syndrome with genetic predisposition ranging from hypertension, proteinuria and edema to severe preeclampsia with complications. A defective implantation and placentation, circulating factors including proinflammatory molecules, cytokines and adhesion molecules have been implicated in the pathogenesis of preeclampsia. Was to assess the clinical value of assaying maternal serum concentration of thrombomodulin [TM] interleukin-12 [IL-12] and transforming growth factor beta-2 [TGF-beta 2], in normotensive, mild and severe preeclamptic pregnant women, and to evaluate the correlation between these factors and the blood pressure, uric acid and creatinine. The second objective was to look for differences between mild and severe early onset preeclampsia, compared with a healthy pregnant and non pregnant cross sectional investigated groups. Serum TM, IL-12 and TGF-beta 2 were measured using enzyme linked immunoassay [ELISA] and enzyme immunoassay respectively in 45 women with preeclampsia divided into 24 mild and 21 severe preeclamptic patients and compared with 21 pregnant normotensive and 20 non pregnant controls. Serum uric acid and creatinine were measured as well. Severe preeclamptic women had significantly increased levels of TM [p<0.01], IL-12 [p<0.01] and TGF-beta 2 p<0.01] compared with women with normal pregnancy and non pregnant women. Serum creatinine and uric acid co1Icentrations were significantly higher in severe preeclamptic patients [1.35 +/- 0.17mg/dL, 7.43 +/- 0.74mg/dL, respectively, mean +/- SD] and did not change significantly in mild preeclamptic women compared with those of healthy normotensive pregnant women. Significant positive correlations existed between serum TGF-beta 2 concentrations and mean arterial blood pressure, TM. serum creatinine and uric acid concentrations in severe pre peclamptic patients. Conclusion: Increase concentration of thrombomodulin, II-12 and TGF-beta 2, in severe preeclamptic patient might explain the shallow placentation, endothelial cell dysfunction and renal involvement described in severe preeclampsia. Measurement of maternal plasma of TM, IL-l2, TGF-beta 2 levels in preeclampsia can be useful biomarker for the assessment of the severity of the disease

Altered bone metabolic markers in type 2 diabetes mellitus: impact of glycemic control

To study the influence of glycemic control on bone minerals and biochemical markers of bone metabolism in patients with type 2 diabetes mellitus. A Case-control study was conducted at Uhod Hospital, KSA from October 2003 to August 2004 to study 60 premenopausal, multipareous female patients with type 2 diabetes mellitus for >5 years, under oral anti-diabetics, with no diabetic complications. They were divided according to their glycemic control into: controlled group [n=22] and poorly controlled group [n=38] and were compared to 30 age matched healthy women. Osteocalcin [OC], urinary deoxypyridinoline [Dpd], Parathyroid hormone [PTH] were measured by chemiluminescent enzyme immunometric assay and 25 hydroxy vitamin D [25 OH-D] was measured by high performance liquid chromatography. In both diabetic groups, there were higher ALP [177 +/- 39.88 and 287 +/- 41.4 mg/dl] and PTH [49 +/- 9.87 and 56.25 +/- 12.3 Pg/ml] than in controls [144 +/- 22.54 mg/dl, 26.9 +/- 5.60 Pg/ml respectively], but lower serum calcium [8.87 +/- 0.3 and 8.79 +/- 0.7 mg/dl], and 25 OH-D [50.9 +/- 12.6, 45.4 +/- 18.9 micro g/l] and osteocalcin [4.09 +/- 1.48 and 1.89 +/- 0.24 ng/ml] than controls [9.96 +/- 1.9l, 57.9 +/- 13.6 micro g/l, 6.5 +/- 1.5 ng/ml respectively], Urinary calcium and urinary Dpd were higher [270.66 +/- 41.7 and 300.56 +/- 55.67 mg/d and 10.8 +/- 4.6, 12.06 +/- 5.12 nM/mM creatinine] than in controls [244.23 +/- 51.5 mg/d, 6.2 +/- 0.8 nM/mM creatinine]. Glycemic indices [FBG, HbA1C] showed significant positive correlation with ALP [r=0.290 and 0.294], urinary calcium [r=0.340 and 0.260] and Dpd [r=0.468 and 0.228]. Our data give evidence of altered bone metabolic markers in both controlled and uncontrolled female patients with type 2 diabetes mellitus with more significant alterations in the uncontrolled group. This could reflect the strong impact of glycemic control on diabetic bone turnover

study into the expression of the tumor suppressor gene p53 and the oncogene bcl-2 in human breast cancer

In this study, the protein expression of the mutant tumor suppressor gene p53, and oncogene bcl-2 was evaluated in 50 female breast cancer patients using two different techniques, ELISA and western blotting, the relation between these two techniques in relation to protein expression was detected, and the correlations between the expression of these two proteins and the different prognostic parameters of cancer breast were studied. The mean value of bcl-2 in breast cancer patients was statistically significantly higher than those of normal healthy controls using both ELISA and western blotting techniques. A significant positive correlation was found between bcl-2 and both the tumor size and the stage of the tumor which signifies its important role as a prognostic factor in breast cancer. Also over-expression of mutant p53 was detected using both ELISA and western blotting techniques when compared to the normal healthy controls. The only statistically significant correlation between mutant p53 expression and the different prognostic parameters of breast cancer was found to be between p53 the stage of the tumor. When taking predictive cut off levels of bcl-2 at 75U/ml, and mutant p53 at 2.16U/ml, bcl-2 showed the highest sensitivity, specificity anti diagnostic accuracy of [88%, 90%, and 90%] respectively, while mutant P53 showed its highest sensitivity, specificity and diagnostic accuracy [80%, 100%, and 85.7%] at the chosen cut offs. When done in either abnormal and both abnormal double combinations with the same cut offs, the sensitivity, specificity and diagnostic accuracy in the either abnormal combination have improved than either parameter singly, [92%, 100% and 94.29%] respectively, while in both abnormal combination the sensitivity, specificity, and diagnostic accuracy are [64%, 90% and 71.43] respectively. When studying the correlation between the 2 techniques [ELISA and western blotting] used in determination of bcl-2 and P53 expression in breast cancer patients all samples which showed over-expression for mutant P53 and bcl-2 using ELISA technique, also demonstrated over-expression using western blotting technique. The percent of positive expression the mutant P53 and the bcl-2 proteins were higher [76%] and [88%] respectively using western blotting technique when compared to ELISA technique [70%] and [80%] respectively. The results of both techniques were statistically significantly correlated for both P53 and bcl-2. Although western blotting technique has a higher sensitivity compared to ELISA, it has many disadvantages as cost, reproducibility, time consumption and the requirement for high skills

Detection of genetic variabiltiy in non - human isolates of fasciola hepatica and Fasciola gigantica by the RAPD - PCR Technique

The present study showed the molecular characterization of Fasciola gigantica and F. hepatica isolates collected from cows and sheep, using the random amplified polymorphic DNA fragments-polymerase chain reaction [RAPDs-PCR] technique. Optimal standardization of amplification conditions and thermocyclation were made, using genetic markers. The methodology used compared the genetic patterns of the two species [interspecies] and inside each species [intra-species] between cow and sheep and the amplification fragments were between 135 and 741 base pairs of marker. The results showed genetic variations [polymorphisms] of Fasciola gigantica and F. hepatica with amplification fragment based on a 500-400 base pair [bp]. Inside each species, there were genetic variations in bovine and ovine and the amplification fragments were between 600 and 400 base pairs [bp]

Serum vitamin B12 in neural tube defects: a factor behind folate deficiency

Neural tube defects [NTDs] are the most common congenital anomalies of the central nervous system, resulting from failure of the neural tube to close between 3rd - 4th week of gestation. NTDs result from multiple intrinsic and extrinsic factors including maternal folate deficiency. Although clear evidence exists on preventability of a large proportion of neural tube defects by periconceptional folk acid intake, however the exact cause of this deficiency is not established. Hence, the purpose of this study was to determine possible risk factors for the occurrence of NTDs. The relation between maternal serum folate and vitamin B[12] and their infant's levels. Patients and methods: Clinical history and examination, and serum folic acid and vitamin B[12] concentrations [by Radioimmunoassay] were assessed for 20 neonates with neural tube defect [36-39 week of gestation, 11 females and 9 males] and their mothers. They were compared to 20 healthy neonates and their mother as a control group. Infants with NTDs have significantly lower serum levels of folic acid and vitamin B12, compared to healthy infants [p = 0.02 and p = 0.001] respectively. Serum level of vit B12 was significantly lower in mothers of infants with NTDs than mothers of healthy infants [p = 0.01], but there was no significant difference between serum level of folic acid in mothers of infants with NTDs and mothers of healthy infants. There was no significant difference between males and females as regards serum levels of both folic acid and vit B12. Positive correlation was found between gestational age and serum level of folic acid [p = 0.01]. Also, statistically significant positive correlation was found between serum level of vitamin B12 of infants With NTDs and their momers. [p =0.031]. There was significant correlation between serum level of folic acid and serum level of vitamin B12 in mothers of healthy infants [p<0.05]. The study demonstrated that not only folate is deficient in infants with neural tube defects, but vitamin B12 is also deficent in them and their respective mothers. This finding focuses light on the pivotal role vit.B12 deficiency as a corner stone of folate deficiency So deficiency of vitamin B12 rather than folic acid during pregnancy might play a role in the genesis of neural tube defects

effect of calcium modifying agents on mitochondrial oxidative phosphorylation

In this study, preparation of heart mitochondria was isolated from the heart of adult female Wistar rats. The integrity of mitochondrial preparation was assessed by application of the following tests: Respiratory activity, respiratory control index [RCI], ADP: O ratio [relationship between phosphorylation and respiration] and inhibition of oxidative phosphorylation. The determination of mitochondrial protein concentration and measurement of mitochondrial oxidative phosphorylation using Clark-type oxygen electrode were assessed for isolated mitochondria. Verapamil [100-200mu M], bepridil [50-200muM] and palmitoyl DL-carnitine [50-200 muM] produced a significant inhibition of rat heart mitochondrial oxidative phosphorylation. The results demonstrated the ability of calcium antagonists to modify mitochondrial integrity and function under physiological conditions and provided a further evidence of potential ability of these compounds to be effective in the prophylactic treatment of ischemia in vivo condition

Histophysiologial changes in renal functions of hypercholesterolaemic ovariectomized adult rat

The current study was designed to elucidate the histophysiological changes in renal functions as well as the structural and ultrastructural changes in renal functions as well as the structural and ultrastructural changes of kidneys in hypercholesterolaemic intract and ovariectomized rats. Sixty female albino rats were used, half of them were fed on high cholesterol diet for four months, while the other half were fed on ordinary diet. Compared to control intact rats either fed on ordinary diet or high cholesterol diet, ovariectomy produced a significant decrease in serum levels of high density lipoprotein cholesterol [HDL], while serum levels of total cholesterol showed marked elevations. Serum albumin level decreased in both groups after ovariectomy, while albuminurea was present in intact hypercholesterolaemic group and ovariectomized hypercholesterolaemic group. Ovariectomy induced elevation of serum levels of creatinine, urea, uric acid and calcium levels in both groups. Body weight and blood pressure significantly increased after ovariectomy in both groups. Also, ovariectomy induced marked elevation in serum levels of luteinising hormone [LH] and follicle stimulating hormone [FSH] in rats fed on ordinary diet and high cholesterol diet. The histological results showed that, in ovariectomized rats fed ordinary diet, many glomeruli remained intact, moderate glomerular mononuclear cell infiltration and minimal tubular dilatation was observed. In hypercholesterolaemic ovaraiectomized group. Glomerular focal atrophy or necrosis with mononuclear cell infiltration was observed. Collagen laydown in the intersitium with atrophic dilated tubules containing the protein casts. We conclude that sex-related factors regulated by the ovaries may play an inhibitory role in the development of glomerulosclerosis