Effects of CDDO-EA in sepsis-induced acute lung injury: mouse model of endotoxaemia.

OBJECTIVE: Aim: The aim of this research is to clarify the potential effect of CDDO-EA against experimentally sepsis induced lung injury in mice. PATIENTS AND METHODS: Materials and Methods: Mice have divided into four groups: Sham group CLP group, Vehicle-treatment group, CDDO-EA-treated group: mice in this group received CDDO-EA 2mg/kg intraperitoneally, 1hr before CLP, then the animals were sacrificed 24hr after CLP. After exsAngpuinations, tissue samples of lung were collected, followed by markers measurement including, TNF-α, IL-1ß, VEGF, MPO, caspase11, Angp-1and Angp-2 by ELISA, gene expression of TIE2 and VE-cadherin by qRT-PCR, in addition to histopathological study. RESULTS: Results: A significant elevation (p<0.05) in TNF-α, IL-1ß, MPO, ANGP-2, VEGF, CASPASE 11 in CLP and vehicle groups when compared with sham group. CDDO-EA group showed significantly lower levels p<0.05, level of ANGP-1 was significantly lower p<0.05 in the CLP and vehicle groups as compared with the sham group. Quantitative real-time PCR demonstrated a significant decrement in mRNA expression of TIE2&ve-cadherin genes p<0.05 in sepsis & vehicle. CONCLUSION: Conclusions: CDDO-EA has lung protective effects due to its anti-inflammatory and antiAngpiogenic activity, additionally, CDDO-EA showes a lung protective effect as they affect tissue mRNA expression of TIE2 and cadherin gene. Furthermore, CDDO-EA attenuate the histopathological changes that occur during polymicrobial sepsis thereby lung protection effect.

LUNG PROTECTIVE EFFECTS OF CLOPIDOGREL IN POLYMICROBIAL SEPSIS.

OBJECTIVE: Aim: The goal of this experiment was to examine if Clopidogrel might protect the lungs during sepsis by modulating the inflammatory and oxidative stress markers. PATIENTS AND METHODS: Materials and Methods: Twenty-four adult male Swiss-albino mice aged 8-12 weeks, with a weighing of 20-30 g, were randomized into 4 equal groups (n=6): sham (Laparotomy without cecal ligation and puncture [CLP]), CLP (laparotomy plus CLP), vehicle (DMSO 1 hour prior to CLP), Clopidogrel (50 mg/g IP 1 hour before to CLP). ELISA was used to assess Lung tissue levels of pro-inflammatory and oxidative stress markers. RESULTS: Results: F2 isoprostane levels were significantly higher in the sepsis group (p<0.05) in comparison with sham group, while Clopidogrel was considerably lower (p<0.05) in the inflammatory and oxidative stress markers in comparison to sepsis group. Histologically, all mice in the sepsis group had considerable (p=0.05) lung tissue damage, but Clopidogrel considerably decreased lung tissue injury (p=0.05). CONCLUSION: Conclusion: Clopidogrel was found to reduce lung tissue cytokine concentrations (IL-1, TNF a, IL-6, F2 isoprostane, GPR 17, MIF) in male mice during CLP-induced polymicrobial sepsis by modulation of pro-inflammatory and oxidative stress cascade signaling pathways, to the best of our abilities, no study has looked at the effect of Clopidogrel on MIF levels.

RISK FACTORS FOR DIABETIC NEPHROPATHY IN DIABETES MELLITUS TYPE 1.

OBJECTIVE: The aim: To find the risk factors of microalbuminuria and estimated Glomerular Filtration Rate (eGFR) in patients with type 1 diabetes mellitus. PATIENTS AND METHODS: Materials and methods: One hundred ten patients of type 1 diabetes mellitus in this cross-sectional study at diabetic and endocrinology center in Al-Najaf during the period from September 2021 to March 2022. All patients were asked about sociodemographic characteristics (age, gender, smoking, duration of DM type1, family history of DM type1), measured (body mass index BMI, blood pressure) and laboratory investigations done to all patients (G.U.E, s. creatinine, lipid profile, HBA1C, calculated estimated Glomerular Filtration Rate (eGFR) and Spot Urine Albumin-Creatinine Ratio (ACR). RESULTS: Results: Out of 110 patients, 62 male and 48 female, the mean age was (22±12). The patients with microalbuminuria (ACR ≥ 30 mg/g) show statistically significant with increase HBA1C, duration of DM type 1, total cholesterol (T.C), low density lipoprotein (LDL), triglycerides (TG) and family history of DM type 1, while there were not statistically significant with age, gender, smoking, BMI, eGFR, high density lipoprotein (HDL) and hypertension. Patients with eGFR<90mL/min/1.73m2 show statistically significant with increase HBA1C, duration of DM type1, LDL, TG, T.C, while significantly decrease in HDL and there were not statistically significant with age, gender, smoking, family history of DM type 1, BMI and hypertension. CONCLUSION: Conclusions: The degree of glycemic control, duration of type1 (DM) and dyslipidemia were associated with increased microalbuminuria and reduced eGFR (nephropathy). Family history of DM type1 was risk factor for microalbuminuria.

ASSESSMENT OF THE ASSOCIATION OF SEROTONIN TRANSPORTER GENE (5-HTTVNTR & 5-HTTLPR) POLYMORPHISM IN PATIENTS WITH FIBROMYALGIA SYNDROME.

OBJECTIVE: The aim: To study the clinical and the genetic association of 5-HTTVNTR and the 5-HTTLPR polymorphisms in women with FMS. PATIENTS AND METHODS: Materials and methods: 105 FMS patients and 105 controls were enrolled in the study. Polymerase chain method was used to analyse the 5-HTTLPR & 5-HTTVNTR gene polymorphism. The psychopathology status of the 105 FMS patients and 105 healthy controls was assessed using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. RESULTS: Results: In FMS patients and controls, the 10/10, 10/12, and 12/12 genotypes of the 5-HTTVNTR polymorphism were found in 3.8% and 2.9%, 20% and 15.2%, and 76.28% and 81.90%, respectively. Additionally, the L/L, S/L, and S/S genotypes of the 5-HTTLPR polymorphism were found in 4.8% and 2.9%, 36.2% and 40%, 59% and 57.1%, in FMS patients and healthy controls, respectively. There were no significant differences in the frequency of genotypes between FMS patients and controls. There were no significant differences in the BDI and the SCL-90-R scores according to the serotonin transporter genotypes. CONCLUSION: Conclusions: We found no significant difference between 5-HTT gene polymorphism (5-HTTVNTR and 5-HTTLPR) and the psychiatric test results (P>0.05) in FMS patients. Hence, we conclude that serotonin gene polymorphism (5-HTTLPR & 5-HTTVNTR) is not associated with FMS in north Indian women. Our results suggests that the serotonin transporter polymorphism does not seem to be a susceptibility factor for FMS.

NEPHROPROTECTIVE EFFECT OF GAMMA-SECRETASE INHIBITOR ON SEPSIS- INDUCED RENAL INJURY IN MOUSE MODEL OF CLP.

OBJECTIVE: The aim: This study was set out to assess the potential protective impact of MK0752 (a gamma secretase inhibitor) on sepsis-induced renal injury through modulation of inflammatory and oxidative stress pathways. PATIENTS AND METHODS: Materials and methods: Twenty-four Swiss-albino mice aged between eight and twelve week and weighted twenty to thirty-seven grams were randomly allocated into four groups (n=6 in each group). Sham group (laparotomy without cecal ligation and puncture (CLP), sepsis group (laparotomy with CLP), vehicle-treated group (equivalent volume of DMSO before the CLP), MK0752 treated group (5 mg/kg) single daily dose for three days before the CLP. Blood samples were used to assess the serum levels of urea and creatinine. The kidneys were used to assess tissue levels of the TNF-α, IL-10, IL-6, TNFR1, VEGF, notch1, jagged1 and tissue damage by histopathological analysis. RESULTS: Results: The current study shows that pretreatment with MK0752 ameliorates the renal damage by significantly reducing the proinflammatory cytokines and notch1 signaling. CONCLUSION: Conclusions: Taken together, these results suggest that MK0752 could be protective against the renal injury induced by sepsis through its ameliorative impact on renal architecture and modulating cytokines and Notch1 singling pathway. Further studies regarding the role of Notch signaling pathways would be worthwhile.

ROLE OF PRE-CESAREAN SECTION CEFOTAXIME IN AMELIORATED POST-CESAREAN COMPLICATION.

OBJECTIVE: The aim: The purpose of this study was to examine the efficacy of cefotaxime before and after skin incision in avoiding post-operative infection complications in caesarean section women, also evaluation the efficacy of cefotaxime in reducing post-caesarean section complications. PATIENTS AND METHODS: Materials and methods: We conducted 150 women who undergoing caesarean section in the Obstetrics & Gynecological Department, Babylon government from January, 2021 to March, 2021. The caesarean operations were done by using standard protocols. Each patient was examined daily and post-operative infectious. Women were randomly divided into three groups; each group contains 50 women; Group 1: (control) given normal saline 12 hr. before and after skin incision. Group 2 (pre-operation antibiotic): given single dose of cefotaxime 1 g intravenously 12 hr. before skin incision, and Group 3 (post-operation antibiotic): given single dose of cefotaxime 1 g intravenously 12 hr after operation. RESULTS: Results: The outcome measures were post-operative febrile morbidity, healing period and urinary tract infections, in addition to socioeconomic state of each woman. CONCLUSION: Conclusions: cefotaxime pre-cesarean section could ameliorate post-operative problems such as infection of surgical wound, febrile, and urinary tract infections.

UNRAVELING THE CLINICO-GENETIC ASSOCIATION OF CATECHOL-O-METHYLTRANSFERASE-RS4680 G>A GENE POLYMORPHISM IN WOMEN WITH FIBROMYALGIA SYNDROME.

OBJECTIVE: The aim: To determine the clinical and the genetic association of the COMT rs4680 SNP in women with FMS. PATIENTS AND METHODS: Materials and methods: Extracted DNA from peripheral blood samples were utilized as template for the PCR and RFLP analysis. RESULTS: Results: A significant difference was found in the distribution of the COMT genotype between FMS patients and controls (P<0.05). The frequency of GG, AG, AA genotypes were 12%, 72%, 21% in FMS patients and 32%, 62%, 11% in controls. The clinical features of FMS reveal that FIQR and the severity of pain measured by VAS were significantly associated with the COMT rs4680 SNP (P=0.042; P=0.016). The co-dominant model for GG verse v. AG genotype (P=0.004) and AG v. AA genotype (P=0.002) has shown to be high risk for FMS. An increased risk of FMS in the dominant model for (AG+AA) v. GG genotype (P=0.001) and no significant difference was found between (GG+AG) v. AA genotype (P=0.08) in the recessive model. The result indicated that A allele considerably increase the risk of FMS (P=0.004) in comparison to the G allele. CONCLUSION: Conclusions: AA genotype and A allele of the COMT rs4680 SNP were significantly associated with severity in FMS patients and also plays a significant role in the clinical manifestation of this disease.

EVALUATION OF THE EFFECT OF TOPICALLY APPLIED METHYLSULFONYLMETHANE AND THEIR COMBINATION WITH MINOXIDIL SOLUTION FOR IMPROVEMENT OF HAIR GROWTH IN MALE MICE.

OBJECTIVE: The aim: The purpose of this research was to find out the effect of Methylsulfonylmethane in minimizing hair loss. PATIENTS AND METHODS: Materials and methods: Twenty adult Wister Albino mice weighing 25-35g and aged 6-7 weeks were employed. Male mice's coat hairs on the dorsal skin were carefully clipped and then colored. Mice were randomly assigned into four groups, each with five animals: (1) Control group: Treated with D.W. (2), Minoxidil (5%) treated group (3), Methylsulfonylmethane (10%) treated group (4), Methylsulfonylmethane plus Minoxidil treated group. RESULTS: Results: We found that the tissue level of 8-isoprastanein the groups receiving medication are considerably lower than in the control (D.W.). We also discovered that the serum tissue vascular endothelial growth factor levels in the groups receiving medication are considerably greater than those in the control (D.W.) groups. On the other hand, we discovered that hair growth, hair follicle expansion and hair follicle number are much higher in the groups receiving medication than in the control groups. CONCLUSION: Conclusions: We concluded that MSM, through its antioxidant and anti-inflammatory properties, dramatically reduces hair loss in male mice.

THE NEUROPROTECTIVE EFFECT OF TOCILIZUMAB IN BRAIN ISCHEMIA REPERFUSION INJURY.

OBJECTIVE: The aim: This research was conducted to assess the possible neuroprotective effect of Tocilizumab in brain ischemic reperfusion injury in rats. PATIENTS AND METHODS: Materials and methods: 24 adult Sprague-Dawley rats were divided into four groups randomly. The sham group was given anesthesia at the same time as the other groups and was in the same condition as the other groups. Control group: 1 h of ischemia followed by 4 h of reperfusion. The vehicle group was the same as the control, but they were given the vehicle intraperitoneally (1 ml/kg of 0.9 % NaCl) for 7 days before the ischemia. The treatment group as the control group, but they were given tocilizumab (8 mg/ kg) intraperitoneally for 7 days before ischemia. RESULTS: Results: control group, inducing ischemia/reperfusion increased infarction size considerably (p<0.001), when comparison to the control and vehicle groups, tocilizumab at dose (8 mg/kg) showed a significantly (p<0.001) smaller infraction area. CONCLUSION: Conclusions: In a cerebral ischemia/reperfusion, a reduction in infarction area in injected with Tocilizumab medication was considered neuroprotective for cerebral ischemia/reperfusion.

THE RISK OF ACUTE KIDNEY INJURY AFTER ELECTIVE VERSUS EMERGENCY CORONARY INTERVENTION.

OBJECTIVE: The aim: A serious and common complication after percutaneous coronary intervention is acute kidney injury, which is associated with an increased risk of renal, cardiovascular and even mortality; therefore, early prognosis and identification of patients at higher risk are essential for early initiation of preventive measures. The aim of this study is to predict and compare the risk for the development of CI-AKI in patient with ACS who undergo emergency PCI or elective (i.e. after medical stabilization) PCI by utilizing the sensitivity of serum NGAL as an early and reliable predictor for CI-AK. PATIENTS AND METHODS: Materials and methods: The study include 37 patients with acute coronary syndrome, baseline serum creatinine, complete blood count and pre and two hours post operative serum neutrophil gelatinase-associated lipocalin were measured and all patients underwent percutaneous coronary intervention according to the standard protocol used in Al Najaf Cardiac Center. RESULTS: Results: This is a Two-Arm study that included a total of 37 patients with acute coronary syndrome aged 38-83 years. Eighteen of them had emergency percutaneous coronary intervention while the remaining 19 had elective percutaneous coronary intervention (after medical stabilization). Elevation of serum neutrophil gelatinase-associated lipocalin level two hours after percutaneous coronary intervention was found to be significantly higher among emergency percutaneous coronary intervention group compared to elective group. CONCLUSION: Conclusions: Acute coronary syndrome patients are undergoing emergency percutaneous coronary intervention are at an increasing risk for the development of contrast induced acute kidney injury than those undergoing elective percutaneous coronary intervention.

EVALUATION OF COVID-19 VACCINES EFFICACY IN IRAQI PEOPLES.

OBJECTIVE: The aim: The present study was carried out on patients recovered from COVID-19, including those patients who have taken vaccine and those who have not. PATIENTS AND METHODS: Materials and methods: The patients were recruited via an online panel and surveyed at different regions of Iraq from June 1, 2021, to August 30, 2021. RESULTS: Results: Our results demonstrated that the highest percentage of people recommended Pfizer vaccine followed by Sinopharm, while AstraZeneca vaccine was least recommended. CONCLUSION: Conclusions: The efficacy of different vaccines differed significantly; the highest effectiveness was observed with Pfizer vaccine followed by AstraZeneca and Sinopharm with effectiveness ranging from 94%, 89%, and 74%, respectively. Further, the highest percentage of re-infected patients was observed with Sinopharm vaccine followed by Astra Zeneca and Pfizer vaccine, respectively. Also, the highest percent of re-infection with masking used was seen in the case of Sinopharm vaccine followed by AstraZeneca and Pfizer vaccine. Although, we observed that post-vaccination symptoms were lowest than pre-vaccination symptoms, the percent of asymptomatic cases post-vaccination was highest than pre-vaccination cases for all vaccines.

NEPHROPROTECTIVE EFFECT OF OLMESARTAN ON RENAL ISCHEMIA REPERFUSION INJURY IN MALE RATS: THE ROLE OF NRF2/HO-1 SIGNALING PATHWAY.

OBJECTIVE: The aim: To investigate the Nephroprotective potential of Olmesartan in RIRI via modulation of the Nrf2/OH-1 signaling pathway. PATIENTS AND METHODS: Materials and methods: Thirty male rats were equally divided into four groups. The sham group was exposed to surgical conditions without induction of RIRI. The control group was exposed to ischemia by clamping the renal pedicles for 30 min, followed by 2h of blood restoration. The vehicle-treated group was received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 min before clamping. RESULTS: Results: Olmesartan-treated group was pretreated with Olmesartan a dose of 10 mg/kg IP; 30 min prior to induction of ischemia. Following 30 min of ischemia, the clamps were released and allowed to the reperfusion for 2 h. Blood samples were collected to examine the levels of serum urea and creatinine. Kidney tissue was used to measure the levels of cytokines (TNFα, IL6, MCP, BAX, BCL2 and isoprostane F2. Immunohistochemistry was used to assess the levels of Nrf2 and HO-1. Histological analyses were used to detect the tubular damage in the kidney. CONCLUSION: Conclusions: The results showed that Olmesartan alleviates renal tissue damage through activating the antioxidant effect mediated by Nrf2 signaling.

LUNG PROTECTIVE POTENTIAL EFFECT OF ZILEUTON DURING ENDOTOXAEMIA MODEL IN MALE MICE.

OBJECTIVE: The aim: This study was undertaken to investigatethe possible lung protective potential effect of zileuton during polymicrobial sepsis, through modulation of inflammatory and oxidative stress pathway. PATIENTS AND METHODS: Materials and methods: 24 adult male Swiss-albino mice aged 8-12 weeks, with a weight of 25-35g, were randomized into 4 equal groups n=6, sham (laparotomy without CLP), CLP (laparotomy with CLP), vehicle (equivalent volume of DMSO 1 hour prior to CLP), and Zileuton (5 mg/kg 1 hour prior to CLP) group. After 24 hrs. of sepsis, the lung tissue harvested and used to assess IL-6, IL-1B, IL-17, LTB-4,12(S) HETE and F2-isoprostane as well as histological examination. RESULTS: Results: Lung tissue inflammatory mediators IL-6, IL-1B, IL-17, LTB, 12 (S) HETE) and oxidative stress were carried out via ELISA. Lung tissue levels of IL-6, IL-1B, IL-17, LTB4, 12(S) HETE and oxidative stress (F2 isoprostan)level were significantly higher in sepsis group (p<0.05) as compared with sham group, while zileuton combination showed significant (p<0.05) lower level in these inflammatory mediators and oxidative stress as comparedto sepsis group. Histologically, All mice in sepsis group showed a significant (p<0.05) lung tissue injury, while in zileuton pretreated group showed significantly (p<0.05) reduced lung tissue injury. CONCLUSION: Conclusions: The results of the present study revealed that zileuton has the ability to attenuate lung dysfunction during CLP induced polymicrobial sepsis in male mice through their modulating effects on LTB4,12(S) HETE and oxidative stress downstream signaling pathways and subsequently decreased lungtissue levelsof proinflammatory cytokines (IL-1ß, and IL-6,IL-17).

CORRELATION BETWEEN RS6265 SNP IN BDNF AND THE CONTEXT OF DIABETES TYPE II INVOLVEMENT IN IRAQI PATIENTS.

OBJECTIVE: The aim: In this study, we looked into the possible link between the G196A polymorphism in the BDNF gene and DM in Iraqi patients. PATIENTS AND METHODS: Materials and methods: By using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, 100 subjects were genotyped for the G196A SNP of the BDNF gene, 50 as DM and 50 as controls, age-sex and ethnically matched healthy controls. Analysis of covariance (ANCOVA) was used to assess the association of this polymorphism, and genotype frequencies were compared between patients and healthy controls. RESULTS: Results: Our result show that patient with the AG (Val-Met) genotype had a 40%of total DM patients than those and GG (Val-Val) genotypes. Therefore, we concluded that as a future aspect of the report the work can be further extended on proteomic level wherein the corresponding change occurred due to the mutation in the protein can be further detected at structural and functional level. CONCLUSION: Conclusions: conclusion of our result was any patient with covid-19 must need to follow up for at least 1 month after recovery to notified of the post-Covid symptoms especially the male gender.

Genetic polymorphism of angiotensin converting enzyme and angiotensin II type 1 receptors and their impact on the outcome of acute coronary syndrome.

This study aims to investigate the impact of ACE (rs4343) and AT1R (rs 5182) genetic polymorphisms on the outcome of acute coronary syndrome (ACS) in patients on captopril. Two hundred and fifty participants with ACS were included in this study (Group 1 (120) participants on captopril 25 mg twice daily and Group 2 (130) participants received no captopril (control study)). Participants were genotyped for ACE (rs4343) and AT1R (rs5182) polymorphisms and the phenotype was determined. ACE polymorphism (rs 4343) GG and GA genotypes are more related to STEMI (OR = 1.7, 1.5 respectively) and NSTEMI (OR = 3, 3.8 respectively), and they were more prone to have Percutaneous Coronary Intervention after ACS attack (OR = 11.6, 14.1 respectively). AT1R (rs 5182) CT genotype is mildly associated with STEMI (OR = 1.1), but also prone to have PCI after ACS attack (OR = 1.6) while TT genotype has a risk to get less improvement (OR = 1.8).

Anti-Atherosclerotic and Anti-Inflammatory Effects of Curcumin on Hypercholesterolemic Male Rabbits.

Curcumin has a potent antioxidant and anti-inflammatory properties that may suppress inflammatory component of atherosclerosis. It has been demonstrated that curcumin derivatives can reduce the formation of arterial fatty streaks in cholesterol-fed rabbits. Therefore in this study we evaluated the protective effects of Curcumin on the progression of atherosclerosis. 20 mature rabbits were included for this study; they were randomly divided into four groups each of 5. Group 1: (normal control) were fed corn pellets diet and tab water, group 2: (high cholesterol diet control) were kept on cholesterol rich diet (2% cholesterol) and tab water. Group 3: (cholesterol and rosuvastatin treated group) were kept on cholesterol rich diet (2% cholesterol) and 2.5 mg/kg/day Rosuvastatin dispersed in DW and given orally, group 4: (cholesterol and curcumin treated group) were kept on cholesterol rich diet (2% cholesterol) and 0.2% curcumin added with corn pellets. The study continued for 12 weeks then assessment of serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and PCSK9 was carried out at the end of the study. Total antioxidant activity of curcumin was also determined. Histopathological examination of aortic tissues for atherosclerotic changes was also carried out. Atherogenic (cholesterol rich diet) induced an increment in serum level of TC, LDL, VLDL and TG with concomitant decrement in serum level of HDL and increased atherogenic index. Treatment with curcumin produced substantial reduction in serum TC, LDL, TG with no effect on HDL level thus decreased atherogenic index. Rabbits treated with curcumin showed a significant reduction in the serum level of high sensitive C-reactive protein, ICAM1, VCAM, PCSK9 serum expression and aortic total antioxidant capacity. Curcumin has a potent anti-inflammatory and anti- oxidant effects against atherosclerosis so exerts a protective role by decreasing lipid oxidation and inflammatory markers.

Genetic Polymorphism of Angiotensin II Type 1 Receptors and Their Effect on the Clinical Outcome of Captopril Treatment in Arab Iraqi Patients with Acute Coronary Syndrome (Mid Euphrates).

Genetic variation in the angiotensin II type 1 receptor (AT1R) has an important effect on the outcome of acute coronary syndrome (ACS) initiated treatment with captopril. This study aims to investigate the impact of genetic polymorphism of AT1R (rs5186 and rs275651) on the ACS outcome in Iraqi patients treated with captopril. A total of 250 Iraqi individuals with ACS were included in this case-control study and they were divided into two study groups; Study group 1 included 125 participants who were prescribed captopril, 25 mg twice daily and study group 2 included 125 participants who received no captopril as part of their ACS treatment (control study). The AT1R gene (rs5186) CC genotype was found to be associated with ST-elevation myocardial infarction (STEMI) (Odd's ratio (O.R) = 1.2, P = 0.7), while AC was associated with Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) (O.R = 1.2, P = 0.8). AC genotype is more prone to have Percutaneous coronary intervention (PCI) after ACS attack (O.R = 1.2, P = 0.6). CC genotype had a risk to get less improvement (O.R = 1.6, P = 0.5), so might require higher doses of captopril during acute coronary insult. The AT1R gene (rs275651) AA genotype was associated with UA (O.R = 1.3, P = 0.9). AA and AT genotypes were more prone to have PCI after ACS attack (O.R = 3.9 P = 0.2, O.R = 3.5, P = 0.3 respectively) and thus requiring higher doses of captopril. We conclude that the AT1R rs5186, rs275651 genetic polymorphisms might partially affect the clinical outcome of ACS patients treated with captopril and might have captopril resistance which requires higher doses.

POTENTIAL ROLE OF VITAMIN D3 IN AMELIORATING DOXORUBICIN INDUCED CARDIOTOXICITY IN MALE RATS.

OBJECTIVE: The aim: The goal of this study was to asses if vitamin D3 protect rats against doxorubicin-induced cardiotoxicity. PATIENTS AND METHODS: Materials and methods: Overall twenty-one male rats were divided randomly into three groups (7 rats in each group). Control group in which rats received 0.9% normal saline for two weeks. Doxorubicin group (induced group): rats received 2.5mg/kg three times a week for two weeks and Vitamin D3 group (treated group): vitamin D3 was given in a dose 60000 IU/kg IP as single dose on the first day of the procedure. RESULTS: Results: Doxorubicin caused cardiotoxicity as indicated by a significant elevation (P < 0.01) in TNF-α, IL-6, MDA, cTnI and caspase-3 level, while TAC and Bcl-2 levels significantly (P < 0.01) reduced in cardiac tissues of rats in the doxorubicin group as compared with control group, also doxorubicin caused histological lesions. Vitamin D3 administration show cardioprotective effect reported by significant decrease (P >0.01) incTnI, Bcl2 and TAO as compared with DOX group, also show significant improvement (P >0.01) in cardiomyopathy histological lesions score. CONCLUSION: Conclusions: At their applied doses in the present study, vitamin D3 exerted a significant heart protective effect against cardiotoxicity induced by doxorubicin in rats probably by intrusive with Oxidative-stress, inflammatory response in addition to apoptotic pathway.

THE EFFECT OF SPIRONOLACTONE ON SERUM ELECTROLYTES AND RENAL FUNCTION TESTS IN PATIENTS WITH SEVERE CHRONIC HEART FAILURE.

OBJECTIVE: The aim: To evaluate the effect of single daily 25 mg of spironolactone on serum electrolytes and kidney function tests in patients with severe chronic left sided heart failure. PATIENTS AND METHODS: Materials and methods: 60 patients with severe chronic left sided heart failure were enrolled in this study and they were divided in to 2 equal groups' one group with standard therapy of HF and the other with spironolactone in a dose of 25 mg / day, as an additive therapy to the standard one. Serum electrolytes and kidney function tests were assessed at the beginning of the study and after 3 months. RESULTS: Results: A significant increment in serum potassium (p<0.05) was observed in the spironolactone group after 3 months treatment, while no significant reduction in serum sodium (p>0.05) and no significant increase in serum creatinine and blood urea (p>0.05) was noticed in the same group, control group showed no significant changes (p>0.05), in both serum electrolytes (S.K and S.Na) and renal function tests (S.C and B.U). CONCLUSION: Conclusions: Spironolactone caused a significant elevation of serum potassium level but this elevation is still with the clinically accepted ranges when low dose of spironolactone is used and with intact renal function. Serum creatinine level was not significantly increased with 25 mgl day of spironolactone. We conclude that Renal function tests namely blood urea and serum Creatinine, and serum potassium should be closely monitored in patients on spironolactone therapy especially those patients who use ACEI and ARBs in addition.

NEPHROPROTECTIVE EFFECTS OF CURCUMIN AGAINST CYCLOSPORINE A-INDUCED NEPHROTOXICITY IN RAT MODEL.

OBJECTIVE: The aim: The current study was designed to examine the possible Nephroprotective effects of CMN in preventing nephrotoxicity and oxidative stress caused by chronic administration of CsA in rats. PATIENTS AND METHODS: Materials and methods: This study consisted of four groups and each group was made up of 8 rats. The first group was considered as a control group (received vehicle (0.9%N/S orally, and olive oil S.C), and the rest included the following: CMN group (received CMN in a dose of 30mg/kg/day orally), CsA group (received CsA in a dose of 20mg/kg/day S.C), and CMN plus CsA combination group (received CMN (30mg/kg/day, orally) plus CsA (20mg/kg/day, S.C) for 21days). For each group, the following variables wereassessed: Serum urea concentration, Serum creatinine concentration, initial body weight, final body weight, Tissue MDA level, Tissue GpX1 level, Tissue CAT level, Tissue SOD level, and tissue IL-2 level, and histopathological examination. RESULTS: Results: Mean levels of serum urea and creatinine, tissue MDA, tissue IL-2, and histopathological scores are significantly (P<0.05) increased in the CsA group compared with the control, and CMN groups (normal renal tissue). Tissue SOD, CAT, and GpX1 activities are significantly (P<0.05) decreased in the CsA group compared with the control, and CMN group. Concomitant administration of CMN with CsA resulted in significantly (P<0.05) lower elevated levels of MDA, serum urea, and creatinine, significantly higher levels of antioxidant enzymes, and normalization of the altered renal morphology compared with CsA treated rats. CONCLUSION: Conclusions: CMN has antioxidant and anti-inflammatory properties that protect the kidney from CsA's toxicity.