The myogenic response in uremic hypertension

The myogenic response in uremic hypertension.BackgroundThe constriction of resistance arteries in response to an increase in transmural pressure, the myogenic response, is thought to be an important determinant of peripheral vascular resistance and therefore of arterial blood pressure. Since raised peripheral resistance is known to occur in uremic hypertension, abnormal myogenic constriction might be responsible. We sought to assess the myogenic response of resistance arteries from the subtotal nephrectomy rat model of uremic hypertension.MethodsUremic Wistar-Kyoto (WKYU) rats, and sham-operated normotensive (WKYC) and spontaneously hypertensive (SHRC) controls were studied in parallel. Skeletal muscle arteries were mounted on a pressure myograph and allowed to develop myogenic constriction. The active internal diameter was measured at increasing lumen pressures from 20 to 200 mm Hg. Vascular smooth muscle then was relaxed in a calcium free solution containing nitroprusside, and the passive internal diameter measured at the same pressure steps. The ratio of active to passive diameter at any given pressure was used to assess the myogenic response.ResultsMyogenic constriction was not increased in either WKYU or SHRC compared to WKYC at pressures up to 180 mm Hg.ConclusionsIncreased myogenic tone is not the cause of uremic hypertension

Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan

<p>Abstract</p> <p>Background</p> <p>Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia.</p> <p>Methods</p> <p>A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed.</p> <p>Results</p> <p>Twenty-eight (19.6%) vs. 16 (11.2%); <it>P </it>= 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, <it>P </it>= 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; <it>P </it>= 0.04) were significantly associated with pre-eclampsia.</p> <p>Conclusion</p> <p>Placental malaria was associated with pre-eclampsia. Further research is needed.</p

IN SILICO PHARMACOKINETICS AND MOLECULAR DOCKING OF THREE LEADS ISOLATED FROM TARCONANTHUS CAMPHORATUS L.

Objective: To investigate the pharmacokinetic and toxicity profiles and spectrum of biological activities of three phytochemicals isolated from Tarconanthus camphoratus L. Methods: Several integrated web based in silico pharmacokinetic tools were used to estimate the druggability of Hispidulin, Nepetin and Parthenolide. Afterward, the structural based virtual screening for the three compounds' potential targets was performed using PharmMapper online server. The molecular docking was conducted using Auto-Dock 4.0 software to study the binding interactions of these compounds with the targets predicted by PharmMapper server. Results: The permeability properties for all compounds were found within the limit range stated for Lipinski׳s rule of five. Only Parthenolide proved to be able to penetrate through blood brain barrier. Isopentenyl-diphosphate delta-isomerase (IPPI), uridine-cytidine kinase-2 (UCK-2) and the mitogen-activated protein kinase kinase-1 (MEK-1) were proposed as potential targets for Hispidulin, Nepetin and Parthenolide, respectively. Nepetin and Parthenolide were predicted to have anticancer activities. The activity of Nepetin appeared to be mediated through UCK-2 inhibition. On the other hand, inhibition of MEK-1 and enhancement of TP53 expression were predicted as the anticancer mechanisms of Parthenolide. The three compounds showed interesting interactions and satisfactory binding energies when docked into their relevant targets. Conclusion: The ADMET profiles and biological activity spectra of Hispidulin, Nepetin and Parthenolide have been addressed. These compounds are proposed to have activities against a variety of human aliments such as tumors, muscular dystrophy, and diabetic cataracts.Keywords: Tarconanthus camphoratus L., Hispidulin, Nepetin, Parthenolide, In silico pharmacokinetic, Molecular docking, PharmMapper server, and Auto-Dock 4.0 softwareÂ

Impact of JAK2V617F mutational on haematologic features in Sudanese patients with essential thrombocythemia and thrombotic risk assessment

Objective: We correlated selected haematological parameters in Sudanese essential thrombocythemia (ET) patients based on their homozygous/heterozygous JAK2V617F genotype, as well as the application of thrombotic risk assessment using different thrombotic risk scoring models. Methods: In this single-center study, we evaluated 60 patients with ET at the time of the diagnosis without any prior treatment. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used to determine JAK2V617F mutation status. Complete blood count was evaluated using the Sysmex analyzer. Furthermore, the thrombotic risk assessment of ET patients using different thrombotic risk scoring models was applied. Results: The JAK2V617F mutation was detected in 29/60 patients (48.3%), of whom 23 (38.3% of total) were heterozygous and 6 (10.0%) were homozygous. Compeered to JAK2 wild-type or JAK2 heterozygous patients, JAK2 homozygous patients for JAK2V617F mutation were associated with older age(p < 0.05), significantly higher mean leukocytes count (P =0.001), significantly lower Hb concentration (p < 0.05), and splenomegaly (p < 0.05), while the mean of the platelet counts was slightly higher, although not reached a significant level. We also found two patients who developed thrombotic events throughout follow-up and were initially classified as a low-risk category in the traditional classification. One of them with age < 60 years, hypertension, and JAK2 homozygosity but without thrombosis history, was allocated in a high-risk category by IPSET-t and r- IPSET-t scores. The second patient was stratified in a low-risk category by all scoring models with age < 60 years, hypertension, leukocytosis, unmutated JAK2, and without a history of thrombosis. Conclusions: The JAK2 V617F homozygosity correlated with older age, higher leukocyte count, lower Hb concentration, and a higher risk of thrombosis in Sudanese ET patients. Evaluation of hypertension and identification of JAK2 V617F homozygosity at diagnosis of ET might give the clinician more meaningful prognostic information and so improve the therapeutic management

Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

<p>Abstract</p> <p>Background</p> <p>Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water.</p> <p>Methods</p> <p>HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies.</p> <p>Results</p> <p>39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.</p> <p>No patients had unexplained EPO resistance or biochemical evidence of adynamic bone.</p> <p>Conclusions</p> <p>Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R²= 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.</p

ABO blood group system and placental malaria in an area of unstable malaria transmission in eastern Sudan

<p>Abstract</p> <p>Background</p> <p>Understanding the pathogenesis of malaria in pregnancy and its consequences for both the mother and the baby is fundamental for improving malaria control in pregnant women.</p> <p>Aim</p> <p>The study aimed to investigate the role of ABO blood groups on pregnancy outcomes in an area of unstable malaria transmission in eastern Sudan.</p> <p>Methods</p> <p>A total of 293 women delivering in New Half teaching hospital, eastern Sudan during the period October 2006–March 2007 have been analyzed. ABO blood groups were determined and placental histopathology examinations for malaria were performed. Birth and placental weight were recorded and maternal haemoglobin was measured.</p> <p>Results</p> <p>114 (39.7%), 61 (22.1%) and 118 (38.2%) women were primiparae, secundiparae and multiparae, respectively. The ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128 (O). Placental histopathology showed acute placental malaria infections in 6 (2%), chronic infections in 6 (2%), 82 (28.0%) of the placentae showed past infection and 199 (68.0%) showed no infection. There was no association between the age (OR = 1.02, 95% CI = 0.45–2.2; <it>P </it>= 0.9), parity (OR = 0.6, 95% CI = 0.3–1.2; <it>P </it>= 0.1) and placental malaria infections. In all parity blood group O was associated with a higher risk of past (OR = 1.9, 95% CI = 1.1–3.2; <it>P </it>= 0.01) placental malaria infection. This was also true when primiparae were considered separately (OR = 2.6, 95% CI = 1.05–6.5, <it>P </it>= 0.03).</p> <p>Among women with all placental infections/past placental infection, the mean haemoglobin was higher in women with the blood group O, but the mean birth weight, foeto-placental weight ratio was not different between these groups and the non-O group.</p> <p>Conclusion</p> <p>These results indicate that women of eastern Sudan are at risk for placental malaria infection irrespective to their age or parity. Those women with blood group O were at higher risk of past placental malaria infection.</p

Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study

Background Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTERCHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed