Wellens Syndrome: prevalence, risk factors and coronary angiographic variation. A cross-sectional study.

BACKGROUND: Wellens syndrome complicates acute coronary syndrome and, if unmanaged, can lead to immanent myocardial infarction. This study aimed towards determining the prevalence of Wellens syndrome among acute coronary syndrome patients while focusing on both types and identifying the associated risk factors, then exploring the variation in affected coronary arteries within patients fulfilling Wellens syndrome criteria. METHODS: Implementing a descriptive cross sectional hospital based observational study design, at Ahmed Gasim Teaching Hospital for Cardiac Surgery and Renal Transplantation in Khartoum North, Sudan, the study was conducted following using a non probability convenience sampling of patients fitting the inclusion criteria. Data was collected using closed ended structured questionnaires. Ethical clearance was obtained from relevant authorities. Statistical analysis was done using descriptive and comparative data analysis with the aid of the SPSS software, and STROBE guidelines were followed. RESULTS: A total of 120 patients were included, 70 males and 50 females, majority in their fifth decade. 14 patients had no documented risk factors. 42.5% had STEMI, 34.2% had NSTEMI and 23.3% had unstable angina. Patients fulfilling Wellens syndrome criteria were 18 (15%), 55.6% of them were type A and 44.4% were type B. Most frequently encountered risk factor among Wellens syndrome patients was Diabetes (50%). Out of 16 Wellens syndrome patients who underwent coronary angiography, 50% had mid LAD involvement, most were type A; 25% had proximal LAD involvement and 25% had normal coronary angiography. There was some association between Wellens syndrome and NSTEMI, but no significant association with any specific risk factor. CONCLUSION: Wellens syndrome complicates 15% of acute coronary syndrome patients with a 55.6% possibility of becoming type A, it can present even without a specific predisposing risk factor and coronary angiographic variation other than the proximal part of the LAD artery may occur, including multiple vessels involvement. This is a descriptive cross sectional study conducted at Ahmed Gasim Teaching Hospital in Sudan, to determine the prevalence and risk factors of Wellens syndrome. Data was collected using questionnaires and analyzed with the SPSS software. Out of 120 patients, 14 patients had no documented risk factors. 34.2% had NSTEMI and 23.3% had unstable angina. Patients fulfilling Wellens syndrome criteria were 18 (15%). The commonest risk factor among Wellens syndrome patients was Diabetes (50%). 50% of Wellens syndrome patients had mid LAD involvement. The study concluded that Wellens syndrome is not rare, it can present without specific risk factor and coronary angiographic variation other than the proximal LAD artery can occur.

Matrix metalloproteinase 3 and 9 as genetic biomarkers for the occurrence of cardiovascular complications in coronary artery disease: a prospective cohort study.

BACKGROUND: Matrix metalloproteinases (MMPs) are widely expressed in atherosclerosis lesions. The disequilibrium of MMPs driving to an overexpression or a lack of its level can be influenced by genetic variations. MMP-3 and MMP-9 may be affected by specific polymorphisms like - 1612 5 A/6A and the - 1562 C/T respectively. We aim in the present study to investigate prospectively the association between the - 1612 5 A/6A MMP-3 and - 1562 C/T MMP-9 polymorphisms and clinical outcomes in patients with coronary artery disease (CAD). This study is elaborated to reveal whether one of these polymorphisms is a probable predictor of cardiovascular complications in this CAD cohort. METHODS AND RESULTS: A total of 168 patients with CAD were prospectively followed up over a period of 5 years. Genotypes for the MMP-3 (-1612 5 A/6A) and MMP-9 (-1562 C/T) polymorphisms were performed using PCR-RFLP. Their levels were measured by ELISA in Sandwich test during the follow-up period, 39 cardiovascular outcomes occurred with 21 repeat targets for revascularization, 3 patients with Myocardial infarction, 8 for heart failure, 5 for Stroke and 2 for cardiovascular mortality. The MMP-3 5 A/6A polymorphism was related to the disease on the contrary of the MMP-9 -1562 C/T. Patients carrying the 5 A allele had a higher level of MMP-3 level and those who carried the 6 A allele had lower level (p = 0.04). After applied multivariable Cox-hazard models we revealed that the 6 A allele is independently associated to the disease complication. Kaplan-Meier survival test revealed that individuals having the 6 A allele had a lower survival rate than those with the 5 A allele (p = 0.04). CONCLUSION: Our study suggests the disruption of the MMP-3 level may be due to the existence of the polymorphism - 1612 residing in its promoter region. MMP-3 can be considered as a marker of diagnosis and prediction in cardiovascular events.

Efficacy of intraoperative cine-portogram for complicated portal vein reconstruction in pediatric living donor liver transplantation.

Sufficient PV flow is necessary to achieve successful PV reconstruction in pediatric LDLT. IOCP can be used to assess the severity of PV stenosis and to identify potential portosystemic collateral pathways. The present study reviewed the utility of IOCP and the outcomes of patients who underwent assessment with an IOCP. Consecutive primary LDLTs were performed in 488 pediatric recipients between November 2005 and October 2019. IOCP was used in patients who were unable to achieve sufficient PV flow after the ligation of collaterals. In total, 11 patients underwent IOCP to assess potential portosystemic collateral pathways. The median age and body weight was 8 months (IQR, 6-11 months) and 6.6 kg (IQR, 5.7-8.9 kg), respectively. The reasons for using the IOCP were recurrent PV thrombus in seven patients and insufficient PV flow in four patients. IOCP revealed remaining collaterals in six patients and residual hypoplastic PV in eight patients. Two patients required additional interruption of the potential collaterals under IOCP, which were unable to be recognized as a dominant portosystemic collateral pathway on preoperative imaging. All eight patients with residual hypoplastic PV required vein graft interposition for the complete removal of the hypoplastic PV. All the patients are currently doing well with a median follow-up period of 4.9 years (IQR, 2.2-5.6 years). IOCP can be an effective tool for precisely detecting occult portosystemic collateral pathways and for assessing the patency of the PV anastomosis in pediatric LDLT.

Late T cell-mediated rejection may contribute to poor outcomes in adolescents and young adults with liver transplantation.

Although poor long-term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L-TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L-TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10-24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L-TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow-up period of 6.7 years. A total of 304 patients in C group had a mean follow-up period of 6.3 years (P = .28). The incidence of L-TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L-TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non-adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L-TCMR was significantly higher in the AYA group (P = .04). A high incidence of L-TCMR was observed in AYA group irrespective of non-adherence. AYA patients with L-TCMR should be followed carefully due to the poor results of post-treatment biopsy and the need for intensive immunosuppressive therapy.

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population.

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome. Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1 C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians. Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1 C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p = 0.012 and p < 0.001, respectively). Conclusions: Our work showed a significant association between the -1 C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.

Matrix metalloproteinase-3 predicts clinical cardiovascular outcomes in patients with coronary artery disease: a 5 years cohort study.

Matrix metalloproteinases (MMPs) are implicated in atherosclerosis evolution into a coronary artery disease (CAD). They could be used as biomarkers for a predictive approach when they are studied simultaneously. We aim in our study to demonstrate prospectively in patients with history of CAD that MMPs level is linked to clinical cardiovascular outcomes. Two hundred and eighteen patients diagnosed with CAD were followed prospectively for 5 years in the Cardiology Department of la Rabta Hospital University. Clinical cardiovascular outcomes during the period of the cohort were recorded. Measures were performed for biological and matrix markers at baseline. MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2 were measured by ELISA in Sandwich assay. Fifty-nine cardiovascular outcomes occurred during the cohort period. By multivariate analysis, only MMP-3 persisted as a predictor for cardiovascular events even after adjustment. This metalloproteinase have been shown to be an independent predictor for cardiovascular outcomes (HR = 3.01; CI (1.3-6.95). The found cut-off value by receiver operating curve (ROC) was used for Kaplan-Meier analysis and revealed that patients with MMP-3 level higher than 9.3 ng/mL had a lower survival rate (p = 0.03). MMP-3 baseline level in patients with history of CAD is a potential predictor for cardiovascular outcomes.

Association of matrix metalloproteinase 3 and endogenous inhibitors with inflammatory markers in mitral valve disease and calcification.

Calcific mitral valve stenosis (MVS) is a common disease characterized by extensive remodeling of the extracellular matrix via matrix metalloproteinases (MMPs). The mechanism of calcification due to extensive matrix remodeling remains unclear. In this study, we investigated the relationship between MMP-3, tissue inhibitors of metalloproteinases (TIMPs) as well as pro-inflammatory cytokines and the phenomenon of calcification in MVS. 212 patients having rheumatic mitral stenosis (RMS) and 155 healthy control subjects were recruited in the Cardiology Department of La Rabta Hospital University. Levels of MMP-3, TIMPs, IL-6 and TNF-α were measured by ELISA sandwich assay, hs-CRP was measured by immunoturbidimetry. Plasma levels of MMP-3, TIMP-1 and MMP-3/TIMP-2 ratio were lower only in RMS women in comparison to the control group. Calcification degree correlated positively with MMP-3 in women and men. In addition, calcification was correlated positively with MMP-3/TIMPs ratio in women patients. The inflammatory parameters were positively associated with extracellular matrix turnover biomarkers in men patients. In patients, the level of MMP-3 was increased in men and women with a calcification score ≥ 5. In addition, MMP-3 level predicted the occurrence of calcification. At ROC curves analysis, the cut-off MMP-3 level was in women was 9.21 ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was 12.84 ng/ml (sensitivity 78.6%, specificity 77.8%). The high levels of MMP-3 and the biomarkers of inflammation contribute to valvular remodeling and calcification of the mitral valve.

Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.

Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-cholesterol and high blood pressure). Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice. We questioned the potential capacity of curcumin, contained in Curcuma longa extract (Biocurcuma™), to attenuate the risperidone-induced metabolic dysfunction. Two groups of mice were treated once a week, for 22 weeks, with intraperitoneal injection of risperidone (Risperdal) at a dose 12.5 mpk. Two other groups received intraperitoneal injection of the vehicle of Risperdal following the same schedule. Mice of one risperidone-treated groups and of one of vehicle-treated groups were fed a diet with 0.05% Biocurcuma™ (curcumin), while mice of the two other groups received the standard diet. Curcumin limited the capacity of risperidone to reduce spontaneous motricity, but failed to impede risperidone-induced increase in food intake. Curcumin did not reduce the capacity of risperidone to induce weight gain, but decreased visceral adiposity and decreased the risperidone-induced hepatomegaly, but not steatosis. Furthermore, curcumin repressed the capacity of risperidone to induce the hepatic over expression of enzymes involved in lipid metabolism (LXRα, FAS, ACC1, LPL, PPARγ, ACO, SREBP2) and decreased risperidone-induced glucose intolerance and hypertriglyceridemia. Curcumin decreased risperidone-induced increases in serum markers of hepatotoxicity (ALAT, ASAT), as well as of one major hepatic pro-inflammatory transcription factor (NFκB: p105 mRNA and p65 protein). These findings support that nutritional doses of curcumin contained in Curcuma longa extract are able to partially counteract the risperidone-induced metabolic dysfunction in mice, suggesting that curcumin ought to be tested to reduce the capacity of risperidone to induce the metabolic syndrome in human.

Cardiomyopathy induced by incessant ventricular tachycardia originating in the vicinity of the His bundle.

A 04-year-old boy was referred to our institution with severe, progressive heart failure of 4-months duration associated with a persistent wide QRS tachycardia with left bundle branch block and severe left ventricular dysfunction. Because of incessant wide QRS tachycardia refractory to antiarrhythmic drugs, he was referred for electrophysiological study. The ECG was suggestive of VT arising from the right ventricle near the His area. Electrophysiological study revealed that origin of tachycardia was septum of the right ventricle, near His bundle, however the procedure was not successful and an inadvertent complete atrioventricular conduction block occurred. The same ventricular tachycardia recurred. A second procedure was performed with a retrograd aortic approach to map the left side of the interventricular septum. The earliest endocardial site for ablation was localized in the anterobasal region of left ventricle near His bundle. In this location, one radiofrequency pulse interrupted VT and rendered it not inducible. The echocardiographic evaluation showed partial reversal of left ventricular function in the first 3 months. The diagnosis was idiopathic parahisian left ventricular tachycardia leading to a tachycardia mediated cardiomyopathy, an extremely rare clinical picture in children.

Atrial flutter ablation by femoral approach in a woman with azygos continuation of an interrupted inferior vena cava and dual chamber pacemaker.

This report describes a case of isthmus-dependent atrial flutter ablation by the femoral approach in a 54-year-old woman with a previously unknown absence of the inferior vena cava (IVC) and dual chamber pacemaker. Despite looping of the catheters, ablation and termination of atrial flutter were performed successfully without function alteration of the pacemaker leads.  This is the first report of an inferior-to-superior approach for ablation of atrial flutter in the absence of the perihepatic IVC with the presence of chronic indwelling leads in the area targeted for radiofrequency.

Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian Population.

The prothrombin is the precursor of the serine protease thrombin, a key enzyme in homeostasis. Prothrombin G20210A polymorphism (rs1799963) was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant, and fibrinolytic system. 20210A carriers have an increased risk of thrombosis. In this study, we proposed to determine the prevalence of 20210A prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction. This study included 1290 unrelated Tunisians (1007 male and 283 female) divided in two groups: Four hundred and eighty-seven MI patients (mean age: 52.64 ± 8.98 years) and 803 apparently healthy controls (mean age: 51 ± 8.99). The prothrombin G20210A polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. The distribution of genotypes was in accordance with Hardy-Weinberg equilibrium (p > 0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Male patients with MI had a frequency of 97 % for GG genotype and 3 % for GA+AA genotypes. The control group had a frequency of 99 % for the GG genotype and 1 % for the GA+AA genotypes which is significantly lower than the frequency found in patients (p = 0.01). The same genotype frequencies were found in women (p = 0.032). The MI patient group showed a significantly higher frequency of 20210A allele compared to controls 0.02 versus 0.01 [OR = 3.60 (95 % CI = 1.29-10.53), p = 0.005] in men and 0.015 versus 0.068 [OR = 4.68 (95 % CI = 1.60-14.26), p = 0.001] in women. Our work showed a significant but not independent association between the G20210A polymorphism of the prothrombin gene and MI in the Tunisian population.

Screening strategy to generate cell specific recombination: a case report with the RIP-Cre mice.

Conditional gene knockout technology is a powerful tool to study the function of a gene in a specific tissue, organ or cell lineage. The most commonly used procedure applies the Cre-LoxP strategy, where the choice of the Cre driver promoter is critical to determine the efficiency and specificity of the system. However, a considered choice of an appropriate promoter does not always protect against the risk of unwanted recombination and the consequent deletion of the gene in other tissues than the desired one(s), due to phenomena of non-specific activation of the Cre transgene. Furthermore, the causes of these phenomena are not completely understood and this can potentially affect every strain of Cre-mice. In our study on the deletion of a same gene in two different tissues, we show that the incidence rate of non-specific recombination in unwanted tissues depends on the Cre driver strain, ranging from 100%, rendering it useless (aP2-Cre strain), to ~5%, which is still compatible with their use (RIP-Cre strain). The use of a simple PCR strategy conceived to detect this occurrence is indispensable when producing a tissue-specific knockout mouse. Therefore, when choosing the Cre-driver promoter, researchers not only have to be careful about its tissue-specificity and timing of activation, but should also include a systematical screening in order to exclude mice in which atypical recombination has occurred and to limit the unnecessary use of laboratory animals in uninterpretable experiments.

Metabolic Syndrome, Independent Predictor for Coronary Artery Disease.

BACKGROUND: Metabolic syndrome (MS) was reported to be associated with coronary artery disease (CAD). The aim of the present study was to assess the association between MS and CAD angiographic severity and to search the predictive value of MS and its individual components for CAD. METHODS: 428 patients who underwent elective coronary angiography at the Cardiology Department were included in the study. MS was defined according to National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria. CAD severity was determined by Gensini scors. RESULTS: The proportion of CAD (+) who had MS was significantly higher compared to CAD (-) (63.6% vs. 48.6%, p = 0.020). Gensini score and number of MS components were positively correlated (r = 0.144, p = 0.019). The adjusted predictive abilities for angiographic CAD of MS and its individual components showed that high FBG and high TG are predictive factors for CAD in binary logistic regression analysis (OR = 2.238, 95% CI 1.111 - 4.508, p = 0.024 vs. OR = 2.200, 95% CI 1.078 - 4.492, p = 0.030). The OR for CAD risk of different phenotypes in high FBG and/or HTG shows that this combination increased the OR significantly to 2.307. Among the quartets, the cluster with high BP and low HDL-C was the highest risk (OR = 4.879). However, the combination including all components of MS was a significant contributor to CAD risk. CONCLUSIONS: The MS score correlates with the angiographic severity of CAD. The predictive ability for CAD was stronger with high FBG and high TG and associated low HDL-C and high BP, which seem to act synergistically as risk factors for CAD. Therefore, to prevent or decrease this risk of CAD, clinicians should screen for individual abnormalities of MS, mainly elevated blood glucose level and TG.

Metformin: Diverse molecular mechanisms, gastrointestinal effects and overcoming intolerance in type 2 Diabetes Mellitus: A review.

Metformin, the first line treatment for patients with type 2 diabetes mellitus, has alternative novel roles, including cancer and diabetes prevention. This narrative review aims to explore its diverse mechanisms, effects and intolerance, using sources obtained by searching Scopus, PubMed and Web of Science databases, and following Scale for the Assessment of Narrative Review Articles reporting guidelines. Metformin exerts it actions through duration influenced, and organ specific, diverse mechanisms. Its use is associated with inhibition of hepatic gluconeogenesis targeted by mitochondria and lysosomes, reduction of cholesterol levels involving brown adipose tissue, weight reduction influenced by growth differentiation factor 15 and novel commensal bacteria, in addition to counteraction of meta-inflammation alongside immuno-modulation. Interactions with the gastrointestinal tract include alteration of gut microbiota, enhancement of glucose uptake and glucagon like peptide 1 and reduction of bile acid absorption. Though beneficial, they may be linked to intolerance. Metformin related gastrointestinal adverse effects are associated with dose escalation, immediate release formulations, gut microbiota alteration, epigenetic predisposition, inhibition of organic cation transporters in addition to interactions with serotonin, histamine and the enterohepatic circulation. Potentially effective measures to overcome intolerance encompasses carefully objective targeted dose escalation, prescription of fixed dose combination, microbiome modulators and prebiotics, in addition to use of extended release formulations.

National Tunisian Study of Cardiac Implantable Electronic Devices: Design and Protocol for a Nationwide Multicenter Prospective Observational Study.

BACKGROUND: In Tunisia, the number of cardiac implantable electronic devices (CIEDs) is increasing, owing to the increase in patient life expectancy and expanding indications. Despite their life-saving potential and a significant reduction in population morbidity and mortality, their increased numbers have been associated with the development of multiple early and late complications related to vascular access, pockets, leads, or patient characteristics. OBJECTIVE: The study aims to identify the rate, type, and predictors of complications occurring within the first year after CIED implantation. It also aims to describe the demographic and epidemiological characteristics of a nationwide sample of patients with CIED in Tunisia. Additionally, the study will evaluate the extent to which Tunisian electrophysiologists follow international guidelines for cardiac pacing and sudden cardiac death prevention. METHODS: The Tunisian National Study of Cardiac Implantable Electronic Devices (NATURE-CIED) is a national, multicenter, prospectively monitored study that includes consecutive patients who underwent primary CIED implantation, generator replacement, and upgrade procedure. Patients were enrolled between January 18, 2021, and February 18, 2022, at all Tunisian public and private CIED implantation centers that agreed to participate in the study. All enrolled patients entered a 1-year follow-up period, with 4 consecutive visits at 1, 3, 6, and 12 months after CIED implantation. The collected data are recorded electronically on the clinical suite platform (DACIMA Clinical Suite). RESULTS: The study started on January 18, 2021, and concluded on February 18, 2023. In total, 27 cardiologists actively participated in data collection. Over this period, 1500 patients were enrolled in the study consecutively. The mean age of the patients was 70.1 (SD 15.2) years, with a sex ratio of 1:15. Nine hundred (60%) patients were from the public sector, while 600 (40%) patients were from the private sector. A total of 1298 (86.3%) patients received a conventional pacemaker and 75 (5%) patients received a biventricular pacemaker (CRT-P). Implantable cardioverter defibrillators were implanted in 127 (8.5%) patients. Of these patients, 45 (3%) underwent CRT-D implantation. CONCLUSIONS: This study will establish the most extensive contemporary longitudinal cohort of patients undergoing CIED implantation in Tunisia, presenting a significant opportunity for real-world clinical epidemiology. It will address a crucial gap in the management of patients during the perioperative phase and follow-up, enabling the identification of individuals at particularly high risk of complications for optimal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05361759; https://classic.clinicaltrials.gov/ct2/show/NCT05361759. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/47525.

Intense exercise training is not effective to restore the endothelial NO-dependent relaxation in STZ-diabetic rat aorta.

BACKGROUND: The aim of this study was to examine the effects of intense physical training on vascular function in streptozotocin-diabetic rats. We focused on the endothelium-dependent relaxation (EDR) induced by acetylcholine (ACh) and stable ADP adenosine-5'- O - (2-thiodiphosphate) (ADPßS). METHODS: Control or diabetic male Wistar rats (n=44) were randomly assigned to sedentary or trained groups. The training program consisted in a regular period of running on a treadmill during 8 weeks (10° incline and up to 25 m/min, 60 min/day). The reactivity of isolated thoracic aorta rings of healthy, diabetic and/or trained has been tested. RESULTS: ACh and ADPßS-induced EDR were observed in phenylephrine (PE) pre-contracted vessels. As compared to sedentary control group, diabetic rats showed an increase in PE-induced contraction and a decrease in ACh and ADPßS-induced EDR (p<0.05). Moreover, there were no increase in ACh and ADPßS-induced EDR in diabetic rats. N-Nitro-L-Arginine Methyl Ester inhibited the nitric oxide synthase in diabetic and control rats, thereby resulting in a strong inhibition of the EDR induced by ACh and ADPßS (10-6 M). CONCLUSION: Diabetes induced an endothelium dysfunction. Nevertheless, our intense physical training was not effective to restore the aorta endothelial function.

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Unlocking geothermal energy for sustainable greenhouse farming in arid regions: a remote-sensed assessment in Egypt's New Delta.

This study introduces a novel approach for assessing geothermal potential in arid regions, specifically Egypt's New Delta Agriculture Mega Project area. The challenge of limited sub-soil temperature profile data was addressed by integrating Global Land Data Assimilation System (GLDAS) weather data. Using the Earth-to-Air Heat Exchanger (EAHE) model, the extracted air and sub-soil temperature profiles the potential for geothermal energy production was estimated. We modeled the annual sinusoidal soil surface periodic heating pattern by utilizing GLDAS ambient air temperature (AAT) and land surface temperature (LST). Using either AAT or LST yielded a Root-Mean-Square Error (RSME) of 0.2°C. The generated sub-soil profiles for the New Delta region showed a temperature variation of no more than 1.5°C at a 4-m depth, making it an optimal depth for EAHE installation. One-pipe EAHE demonstrated a cooling/heating capacity ranging from 400 W (cooling) to -300 W (heating). The study highlights the New Delta region's strong geothermal potential for greenhouse cooling and heating, underlining its suitability as a sustainable energy source in arid areas. It also offers a practical guide for the EAHE application and it emphasizes the global potential for geothermal energy exploration, using innovative GLDAS data to expand sub-soil temperature profile accessibility.

Computational identification of new TKI as potential noncovalent reversible EGFRL858R/T790M inhibitors: VHTS, molecular docking, DFT study and molecular dynamic simulation.

The mutations concerned with non-small cell lung cancer involving epidermal growth factor receptor of tyrosine kinase family have primarily targeted. In this study, we employed a scalable high-throughput virtual screening (HTVS) framework and a targeted compound library of over 50.000 Erlotinib-derived compounds as noncovalent reversible EGFRL858R/T790M inhibitors. Our HTVS work flow leverages include HTVS, SP (Standard Precision) and XP (Extra Precision) docking protocol along with its relative binding free energy calculation, cluster analysis study and ADMET properties. Then we used multiple ns-time scale molecular dynamics (MD) simulations and density functional theory (DFT) precise calculation techniques to elucidate how the bound ligand interact with the complexes conformational states involving motions both proximal and distal to the binding site. Based on glide score and protein-ligand interactions, the highest scoring molecule was selected for molecular dynamic simulation providing a complete insight into the conformational stability. A hyperfine analysis of DFT based refinement strategy highly supported their stability by strong intermolecular interactions. Together, our results demonstrate that the virtually screened top retained molecules present the best moieties introduced to Erlotinib. They exhibit interesting pharmacokinetic properties that can act as potent antitumor drug candidates than the lead compound drug and in some extent tackling the drug resistance problem which offer a springboard for further therapeutic experiments and applications.Communicated by Ramaswamy H. Sarma.