http://hdl.handle.net/123456789/2078 البحث عن قناة بحث http://repository.ksu.edu.sa/jspui/simple-search http://hdl.handle.net/123456789/19379 العنوان: Coagulation Inhibitors In Liver Disease<br/><br/>المؤلفون: Fahad Saja, Maha; A, M.A Gader<br/><br/>ملخص: SummaryBackground: Haemostasis is intimately related to liver function since almost all of thehaemostatic factors are synthesized by the liver. Derangements in the haemostatic systeminvariably occur in liver disease and can be associated with life threatening complications,particularly bleeding. Conventional coagulation tests, in the form of PT and APTT, are partof numerous tests used to assess liver function and eventually to reflect the severity of liverdisease as well as the risk of bleeding. However, these tests are not sensitive since theybecome abnormal late in the course of liver disease. Recent evidence suggests that changes inthe levels of natural anticoagulants, specifically protein S and protein C, are more sensitive tohepatocyte dysfunction than the PT and APTT. Depressed levels of protein S and protein Cwere found even in the mildest forms of liver disease when the other coagulation tests andother routine liver function tests were normal.This drop in the protein C and protein S levels in liver disease is mainly attributed toimpaired synthesis by the diseased liver. Cytokines, especially the proinflammatory cytokinesIL-6 and TNF-á, have been implicated in the pathogenesis of various forms of liver ailments,and were also shown to affect the synthesis of protein S and C4BP by the hepatocytes. Thus,the fluctuations in the levels of protein S and C4BP seen in liver disease may be attributed tochanges in the levels of the proinflammatory cytokines, IL-6 and TNF-á.The liver requires vitamin K for the synthesis of functionally active forms of severalhamostatic factors including: prothrombin, factors VII, IX, and X, protein C and protein S.Vitamin K deficiency occurs frequently in liver disease and is thought to contribute to itsassociated coagulopathy. Vitamin K is currently administered to patients with liver disease inan attempt to improve their defective coagulation system. Careful search in the literaturefailed to uncover detailed studies on the efficacy of vitamin K administration in correcting thecoagulation defects seen in liver disease.Objectives. The objectives of the current research were (i) To document the levels ofcoagulation inhibitors, mainly PS and PC, in various degrees of liver dysfunction (hepatitis Bcarriers, chronic hepatitis, liver cirrhosis, and HCC). (ii) To evaluate the potential use of thesenatural coagulation inhibitors as tests of liver function. (iii) To assess the possible role ofcytokines, particularly IL-6 and TNF-á in the changes seen in coagulation inhibitors inpatients with liver disease. (iv) To see whether the administration of vitamin K to patientswith liver disease would affect the levels of vitamin K-dependent coagulation inhibitors, PSand PC.Materials and methods. Two groups were included in the study (i) the liver diseasegroup (n=89), and (ii) the control group (n=50). The liver disease group included fourcategories of patients with various degrees of hepatocyte dysfunction; HB carriers (n=26),chronic hepatitis (n=23), liver cirrhosis (n=20), and HCC (n=20). The patients were recruitedfrom King Khalid University Hospital and Riyadh Military Hospital, Riyadh.The control group comprised healthy subjects recruited randomly from blood donors,academic staff, and volunteers from the general public.Vitamin K (10mg vitamin K1) was administered subcutaneously as a single dose to allliver disease patients. Blood samples were collected on two occasions from each patient; thefirst before vitamin K administration, and the second on the third day following vitamin Kadministration.The following assays were carried out: (i) The coagulation screening tests: prothrombintime (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), (ii)Coagulation factor assays including: fibrinogen and factor VII, (iii) Coagulation inhibitors(protein C, total and free protein S), (iv) C4b-binding protein, (v) PIVKA-II (des-gammacarboxyprothrombin), (vi) Cytokines: Interleukin-6 (IL-6) and tumor necrosis factor-á(TNF-á).Results. Haemostatic parameters and cytokines before vitamin K administration:coagulation screening tests: the PT was significantly prolonged in liver cirrhosis and HCCgroups, while the APTT was significantly prolonged only in the liver cirrhosis group. On theother hand, TT was significantly prolonged in all liver disease groups. Coagulation factors:there was a significant drop in the fibrinogen level only in the liver cirrhosis group, while astatistically significant reduction in FVII levels was observed in both liver cirrhosis and HCCgroups. Coagulation inhibitors: the level of PC dropped significantly in all liver diseasegroups. The reduction in PC levels was greater with the progression of liver disease. Totaland free protein S showed statistically significant reduction only in liver cirrhosis and HCCgroups. Despite the noticeable reduction in the level of total PS in both HB carriers andchronic hepatitis groups when compared to controls, Duncan's multiple range test failed togive statistical support to this difference. However, when t-test was applied a statisticallysignificant difference in total PS levels was noted for both HB carriers and chronic hepatitiswhen compared to controls. C4BP levels showed a statistically significant reduction in allliver disease groups except HB carriers. Cytokines: No significant difference was noted inthe levels of TNF-á between liver disease groups and controls. On the other hand, asignificant elevation in IL-6 levels was seen in both liver cirrhosis and HCC groups. PIVKAIIlevels showed a highly significant elevation only in the HCC group.Comparison of the measured parameters before and after vitamin K administrationamong the different liver disease groups: No difference was detected in any of the abovemeasured parameters after vitamin K administration when compared to its level beforevitamin K administration.Correlations between the different parameters: (a) Between the measured coagulationinhibitors and C4BP: a significant positive correlation was found between C4BP and bothPC and total and free PS. A significant positive correlation was also seen between PC andtotal and free PS. (b) Between cytokines and coagulation inhibitors: a significant negativecorrelation was detected only between IL-6 and PC. (c) PIVKA-II levels did not correlatewith any of the measured vitamin K-dependent factors (FVII, PC, and PS).Comments and conclusions:It is clear that liver disease is associated with derangements in the haemostatic system.Coagulation inhibitors and TT appear to be more sensitive to hepatocyte dysfunction than thePT and APTT. Impaired synthetic function of the liver, as depicted by the reduction in thelevels of these coagulation inhibitors is a major feature of chronic liver disease. Cytokines,especially IL-6, may contribute to the reduction in the coagulation inhibitors seen in liverdisease, specifically those affecting PC.The administration of vitamin K failed to correct the coagulation abnormalities of chronicliver disease and had no effect on the levels of the measured coagulation factors andinhibitors.In conclusion, the results of the current study further support the use of coagulationinhibitors (PS and PC) as markers for liver function. In addition, these results do not lend anysupport to the haemostatic benefits of vitamin K administration to patients with chronic liverdisease, particularly liver cirrhosis.<br/><br/>وصف: Masters Wed, 14 Jan 2009 00:00:00 GMT http://hdl.handle.net/123456789/19378 العنوان: The Effect of Activation of Peroxisome Proliferator-Activated Receptor On Modulating Renal Alterations in the Early Phase of Experimental Diabetic Nephropathy<br/><br/>المؤلفون: Enazy, Maha F.; El-eter, Eman<br/><br/>ملخص: Nephropathy is one of the major clinical manifestations ofmicrovascular disease in diabetic patients. It has been shown thathyperglycemia plays an essential part in diabetic microangiopathy. Earlychanges in diabetic nephropathy include glomerular hypertrophy,hyperfilteration, development of microalbuminuria, followed bydevelopment of glomerular basement membrane thickening, accumulation ofmesangial matrix, and overt proteinuria which may lead toglomerulosclerosis and end stage renal disease (ESRD). This study exploresnew grounds for therapy of diabetic renal changes by investigating effects ofthe anti diabetic type 2 drug peroxisome proliferator-activated receptor-ã(PPAR ã) agonist Rosiglitazon on type 1 induced diabetic nephropathy.Objectives: To examine Rosiglitazone's role in reducing the progression ofdiabetic nephropathy and angiogenic renal alternations in the early phase ofdiabetic nephropathy induced by STZ in rats. This examination is mediatedby kidney function tests, microscopic and macroscopic evaluations of thekidneys, and also via assessing angiogenic factors: Ang-1, Ang-2, theirreceptor Tie-2, and VEGF-A. In order to do this, the following tests wereused: immunohistochemsitry for Ang-1, Ang-2, and Tie-2, western blot wasused for markers Ang-2 and Tie-2 while ELISA test was done to examinethe level of VEGF.Methods: Experimental Groups: Because different doses of Rosiglitazonewere used, six experimental groups (n=8-14 for each) male wistar ratsweighing average 280-300g were recruited for this purpose. Group I wasnon diabetic rats on buffer vehicle (i.e. control), group II was STZ induceddiabetic rats for 4weeks [50mg/kg via intraperitoneal needle], Group III wasSTZ diabetic rats + Rosiglitazone at the dose of (1mg/kg/daily for 4weeks),and Group IV was STZ diabetic rats + Rosiglitazone at (3mg/kg/ daily for4weeks), group V was STZ diabetic rats + Rosiglitazone at the dose of5mg/kg/ daily for 4weeks while group VI was STZ diabetic rats +Rosiglitazone at the dose of 30mg/kg/ daily for 4weeks. All groups weretaking standard rat chow and were subjected to the same living conditions.Kidney Function Tests: This study measured urine flow, urine as well asserum levels of creatinine and also assessed creatinine clearance (CCr),urinary albumin excretion, and BUN.Assessment of Renal Hypertrophy: Absolute and relative kidney weightswere histologically and microscopically assessed for renal hypertrophy.Kidney tissue samples were embedded in 10% formalin and paraffinsections were studied with H&E to assess glomerular hypertrophy.Immunohistochemistry: The study examined the extent of angiogenesis inparaffin embedded kidney sections. Therefore, immunostaining of kidneysections with the following angiogenic protein antibodies were carried out:angiopioten-1 (ang-1), angiopioten-2 (ang-2), and their receptor Tie-2. Theintensity of the staining was semiquantified and statistically analyzed.Western Blot: Western blot analysis was preformed using tissue sampleextracts in order to measure angiogenic factors: ang-2, and Tie-2.Immunisorbent Assay (ELISA): ELISA was used to determine the level ofthe angiogenic marker: vascular endothelial factor (VEGF) in kidney tissueand plasma.Results: This study found that when RSG was administered in low doses(1mg/kg/daily for 4weeks, and 3mg/kg/ daily for 4weeks), the size of kidneysignificantly increased relative to the normal group (1mg: p=<0.001, 3mg:p=<0.005). Also, with the low doses of RSG, the size of the glomerulusgrew significantly larger relative to the normal (1mg: p=<0.01, 3mg:p=<0.002) and to the diabetic untreated group (3mg: p=<0.01). On theother hand, RSG given in 5mg/kg/daily for 4weeks or the high dose of30mg/kg/daily for 4weeks greatly decreased glomerualr size relative to thediabetic untreated samples (5mg: p=<0.002, 30mg: p=<0.0001) althoughnot to the extent of the normal values. Also, when compared to the diabeticuntreated results, these doses of 5mg and 30mg of RSG/kg/daily for 4weekssignificantly decreased kidney size reaching almost normal levels (5mg:p=<0.002, 30mg: p=<0.01). Moreover, low doses of RSG also dramaticallyincreased protein expression of the angiogenic factors: ang-1, ang-2, and tie-2 more than the levels measured for both normal and the diabetic untreatedsamples. Furthermore, when evaluating the immunohistochemistry (IHC)results, 5mg and the high dose of 30mg RSG/kg/daily for 4weeks seemed tohave greatly decreased angiogenic factors to almost normal. Furthermore,kidney function tests were highly improved when diabetic rats were givenhigh doses of RSG (i.e. 30mg/kg/daily for 4weeks) as it decreased Ccrrelative to the diabetic untreated group (p=<0.02). In addition to this,analysis of immunblots for ang-2 showed a significant increase in thisangiogenic marker with the low doses of 1mg and 3mg given/kg/daily for4weeks. The expression of ang-2 with the 5mg/kg/daily for 4weeks dose waslower than that of 1mg and 3mg RSG doses given per kg/daily for 4weeks,but was considerably higher than the normal group protein expression. Onthe other hand, the high dose of 30mg/kg/daily for 4weeks has significantlydecreased the protein expression of ang-2. Tie-2 western blot analysisrevealed that it generally increased with the different RSG doses but thesignificant result here is the noticeable increase of Tie-2 in the normal and30mg RSG groups. Furthermore, VEGF is known to signify angiogenesis;and for that, ELISA of plasma VEGF was done but it didn’t yield productiveresults; and hence, tissue samples were used and the study found that thehigh dose of the drug (30mg/kg/daily for 4weeks) considerably decreasedVEGF level when compared with the diabetic untreated group.Conclusion: The results of this study indicate that when RSG is given inhigh doses (e.g. 30mg/kg/daily for 4weeks), it can ameliorate diabeticnephropathy; precisely, the resulting angiogenesis and glumerularhypertrophy while low doses of RSG (1mg, 3mg both given per kg/daily for4weeks) can worsen the condition.<br/><br/>وصف: Masters Mon, 29 Mar 2010 00:00:00 GMT http://hdl.handle.net/123456789/19377 العنوان: Diaphyseal Nutrient Foramina in human upper and lower limb long bones<br/><br/>المؤلفون: Shaheen, Sameera Yassin; Ibrahim, Dr. Ahmed Fathalla<br/><br/>ملخص: Diaphyseal Nutrient Foramina in Human Upper and Lower LimbLong BonesThe aim of the present study was to study the diaphyseal nutrientforamina in human upper and lower limb long bones. The material ofthe present study consisted of 180 adult human long bones of theupper (30 humeri, 30 radii, 30 ulnae) and lower (30 femora, 30 tibiae,30 fibulae) limbs. For each bone, the number, position, size, directionand obliquity of their nutrient foramina were studied. With theexception of femur, the majority of nutrient foramina in all bonesstudied were single in number and were secondary in size. Most of thenutrient foramina were concentrated in the middle third of the bonewith the exception of tibia in which nutrient foramina werepredominantly observed in its proximal third. Nutrient foramina weremostly located on the anterior surface of the shaft of bones of upperlimb and on the posterior surface of the shaft of bones of lower limb.The direction of nutrient foramina followed the growing end theory,with variations in the direction observed in some fibulae. The resultsof the present study confirmed previous findings regarding the numberand position of nutrient foramina in the long bones of the limbs andprovided clinical information concerning the nutrient foramina whichcould be useful as reference for surgical procedures.<br/><br/>وصف: Masters Sat, 13 Jun 2009 00:00:00 GMT http://hdl.handle.net/123456789/19376 العنوان: study of the variations in the main arterial branching patterns of the human upper limb<br/><br/>المؤلفون: mansour zaher, Walid abbas; M., Mujahid Khan<br/><br/>ملخص: In anatomy, “Normal” means “within the normal range of variation” (Moore and Dalley 2006). This means that normality embraces a range of morphologies and includes those that are commonly found, and others called variations because they are less frequent but not considered abnormal (Sañudo et al. 2003). Each human body possesses a unique configuration and has its complement of variations (Willan and Humpherson 1999). Littleis known about such variability of human anatomy. A recent compendium of anatomical variation (Bergman et al. 2003) testified to the heterogeneity of our knowledge in this regard.A basic law of vascular anatomy is that the only thing which remains constant is its variabi 1993). The variation in the vascular pattern is more frequently observed in the living than in among people of different races (Uzun and Seelig 2000). Some arteries have more variation al. 1953; Keen 1961; Tountas and Bergman 1993), the most frequent are those involving a s continues into the forearm and have therefore attracted more attention than variations affect (Rodríguez-Niedenführ et al. 2003). Variations in the origin and course of principal arteries practical importance for the surgeons, radiologists and anatomists<br/><br/>وصف: Masters Mon, 15 Jun 2009 00:00:00 GMT