Correlation of serum 1,25-dihydroxycholecalciferol with the incidence of primary open-angle glaucoma: A cross-sectional study on patients with chronic illnesses.

PURPOSE: Primary open-angle glaucoma (POAG) is a clinical progressive neuropathy which can lead to irreversible blindness if left untreated. A low level of serum Vitamin D3 is a major risk factor for glaucoma, and hence, represents a second target for glaucoma therapy following intraocular pressure (IOP). However, there is still controversy about whether there is a direct correlation between Vitamin D3 deficiency and the risk of increased IOP. This study aims to investigate the correlation between low serum levels of 1,24-dihydroxycholecalciferol and the development of open-angle glaucoma. METHODS: The study included a total of forty-one patients with POAG. Patients were classified into whether they have chronic illnesses such as type 2 diabetes and hypertension. Matching control subjects of 20 healthy controls were also included in the study. Anthropometric measures and venous blood samples were taken from all participants for serum analysis of various biochemical markers including serum 1,25-dihydroxycholecalciferol (1,25(OH)2D) levels. RESULTS: Overall, serum Vitamin D3 levels were 15% significantly lower in the patient's cohort with open-angle glaucoma as compared to the healthy participants (P < 0.05). Among those, 63% of type 2 diabetic participants had significantly low levels of Vitamin D3 (P < 0.01). There was also a significant 70% reduction in serum Vitamin D3 levels among the hypertensive participants, (P < 0.001). CONCLUSION: We concluded that lower serum 1,25(OH) 2D levels were significantly associated with an increased risk of open-angle glaucoma in patients with chronic illnesses.

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.

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).

Correlation of CYP2D6 allelic polymorphism to outcome of acute coronary syndrome in mid-Euphrates Iraqi patients on metoprolol therapy.

This study aims to investigate the different clinically relevant allele variants (allele frequencies) of CYP2D6 gene and to determine whether a specific genotype of CYP2D6 gene (based on genetic polymorphism "allelic types" and combination) have impact on metoprolol effectiveness (clinical outcome) in patients who have acute coronary syndrome (ACS). The study included 250 patients with ACS who were classified into 2 study groups, 125 patients received metoprolol and served as a study group (Group1) and 125 who received no metoprolol therapy (due to contraindication to the medication) and served as a control group (Group 2). Venous blood samples were taken from all participants for DNA extraction. Urine samples were also collected to assess the metabolic ratio using High-performance liquid chromatography (HPLC) technique. There was significant variation in the distribution of Iraqi patients with respect to CYP2D6 allelic polymorphism as compared to similar patients in other countries. Besides, this significant difference existed in patients' outcome in terms of morbidity and mortality in respect to variable genotypes and phenotypes. We recommend a dose individualization of metoprolol in patients with ACS is essential to improve patients' outcome.

Reno-protective effects of TAK-242 on acute kidney injury in a rat model.

Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels.

Herbal extract targets in Leishmania tropica.

The present study aims to investigate the effect of some herbal extract such as phenolic compounds on the viability of Leishmania tropica promastigotes in vitro. Four tested chemical agents (caffeic acid (CA), ferulic acid (FA), syringic acid (SA) and 4-hydroxybenzoic acid (4-HBA)) were used in this study. The viability of Leishmania tropica promastigotes was investigated under five different concentrations (10, 15, 20, 25 and 30 mg/ml) of each agent after (72 h). CA was the most active agent on the promastigotes viability after 72 h exposure to 30 mg/ml concentration so that the parasiticidal effect reach (53 × 10(4)) promastigote/ml. FA is the second agent in parasiticidal effect that parasiticidal effect reach to (50 × 10(4) promastigote/ml) at a concentration (30 mg/ml), 4-HBA is the third agent in parasiticidal effect that reach to (48 × 10(4) promastigote/ml) at a concentration (30 mg/ml), SA is the weakest agent in parasiticidal activity that reach to (44 × 10(4) promastigote/ml) at a concentration (30 mg/ml). It can be concluded that (CA, FA, SA and 4-HBA) possess acidal effect on the Leishmania tropica promastigotes in vitro.

Role of NF-κß and oxidative pathways in atherosclerosis: cross-talk between dyslipidemia and candesartan.

PURPOSE: The objective of this study is to assess the effect of the candesartan on the progression of atherosclerosis through the downregulation of NF-κß and interference with oxidative pathway. METHODS: Twenty-four rabbits were assigned to three groups: control group fed normal diet; induced untreated group fed 1% cholesterol diet; and treated candesartan group also fed 1% cholesterol diet. Plasma lipid profiles were measured, and ELISA for plasma cytokines and chemokine was performed. Analyses of NF-κß and VCAM-1 were performed using Western blotting with RT-PCR for NF-κB activity at mRNA. Doppler ultrasound was used to evaluate aortic intima-media thickness, and atheroma was detected by H&E staining. Immunofluorescent staining was performed to confirm accumulation of monocytes and PMNs. RESULTS: Candesartan markedly reduced the levels of the plasma lipid profile including total cholesterol [TC], triglycerides [TG], and LDL-C, while significantly elevating levels in the plasma HDL-C, in addition to reducing cytokine (TNF-α, IL-6, IL-1ß) and chemokine levels (MCP-1). Also, it decreased the aortic malondialdehyde (MDA) concentration and elevated the aortic glutathione (GSH) level compared with untreated animals (P < 0.05). The triplex Doppler ultrasound study confirmed that the candesartan attenuated intima-media thickness at 6 months of study. All candesartan-treated rabbits showed significantly attenuated atherosclerosis lesions with reduced accumulation of monocytes and had significantly reduced VCAM-1 expression and NF-κß activity. CONCLUSION: Candesartan retards the progression of atherosclerosis via interference with NF-κß and oxidative pathways.

Antiatherosclerotic potential of clopidogrel: antioxidant and anti-inflammatory approaches.

BACKGROUND: Atherosclerosis is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the walls of large and medium size arteries. OBJECTIVE: To evaluate the effect of clopidogrel on atherosclerosis progression. MATERIALS AND METHODS: A total of 28 local domestic rabbits were assigned to four groups: normal control, atherogenic control, vehicle control, and clopidogrel treated. Serum triglycerides, total cholesterol, HDL-C, plasma high sensitive C-reactive protein (hsCRP), plasma malondialdehyde (MDA), and plasma reduced glutathione (GSH) were measured at the end of the experiment. Immunohistochemical of aortic atherosclerotic changes were also performed. RESULTS: There was no statistically significant difference between atherogenic control group and vehicle group. Levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH levels were decreased in animals on atherogenic diet. Immunohistochemical analysis showed that aortic expressions of VCAM-1, MCP-1, TNF- α , and IL-17A were significantly increased in atherogenic control group. Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion. Compared to atherogenic control group clopidogrel do not have significant effect on lipid profile. Clopidogrel significantly reduces hsCRP and MDA levels and increases GSH level. Furthermore, clopidogrel treatment significantly reduced aortic expressions parameters and the histopathologic examination of the aortic arch showed a significant reduction of atherosclerotic lesion. CONCLUSIONS: This study outlines how clopidogrel reduces lipid peroxidation, systemic inflammation, and aortic expression of inflammatory markers and hence reduces the progression of atherosclerosis.

Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response.

BACKGROUND: The importance of doxorubicin (Dox), as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in acute doxorubicin-induced toxicity. The aim of this study was to determine the protective effect of vitamin E and telmisartan in acute doxorubicin induced cardiotoxicity. METHODS: Thirty two male Sprague - Dawley rats were involved in this study and were randomly separated into 4 groups, eight rats in each group, one group received normal saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the other two groups also received doxorubicin 20 mg/kg I.P as single dose after seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting assay for ICAM-1, while left ventricular function was analyzed by microcatheter, also estimated the level of oxidative stress parameters (MDA and Catalase) and cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and after treatment period by 48 hours. RESULTS: The immunofluorescent staining showed that administration of vitamin E and telmisartan are attenuated of mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there is marked reduction of myocardial troponin-I levels with improved LV function in vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA, LDH, CK-MB levels significantly (P < 0.01), and were counteracted by administration of vitamin E and telmisartan, but did not significantly affect serum catalase activity. CONCLUSIONS: Antioxidant effect (vitamin E and telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.