Screening of blood donors for idiopathic CD4+ T-lymphocytopenia

BACKGROUND: The recent recognition of idiopathic CD4+ T-lymphocytopenia (ICL) had led to concern that an unknown immunodeficiency virus may be transmissible by transfusion. STUDY DESIGN AND METHODS: To evaluate the prevalence and significance of low CD4+ values among blood donors, CD4+ data on 2030 blood donors who were negative for antibody to human immunodeficiency virus type 1 (HIV-1) were compiled. Those with CD4+ values below ICL cutoffs (< 300 CD4+ T cells/microL, or < 20% CD4+ T cells) were recalled for follow-up investigations. Serial CD4+ data on 55 homosexual men who seroconverted during prospective follow-up and data on 139 anti-HIV-1-positive blood donors initially evaluated in 1986 were reviewed as well. RESULTS: Five seronegative donors (0.25%) had absolute CD4+ counts < 300 cells per microL and/or < 20 percent. On follow-up, all five donors had immunologic findings within normal ranges, lacked HIV risk factors, and tested negative for HIV types 1 and 2 and human T-lymphotropic virus type I and II infections by antibody and polymerase chain reaction assays. Four of five donors reported transient illness shortly after their low CD4+ count donations. The median interval from HIV-1 seroconversion to an initial CD4+ value below ICL CD4+ cutoffs was 63 months for infected homosexual men. Of 139 HIV-1-infected blood donors studied 1 to 2 years after seropositive donations, 34 (24%) had CD4+ counts < 300 cells per microL and/or < 20 percent. CONCLUSION: Low CD4+ counts are rare among anti- HIV-1-negative volunteer blood donors and are generally associated with transient illnesses. If any unknown virus progresses similarly to HIV- 1, CD4+ count donor screening would be a poor surrogate for its detection.     

Silymarin prevents the toxicity induced by benzo(a)pyrene in human erythrocytes by preserving its membrane integrity: An in vitro study

Silymarin, the purified extract from milk thistle Silybum marianum (L.) Gaertn, consists mainly of four isomeric flavonolignans: silibinin, isosilibinin, silidianin, and silichristin. The present study was carried out to evaluate the protective potential of silymarin in human erythrocytes against in vitro exposure to the carcinogen benzo(a)pyrene (B(a)P). Erythrocytes isolated from human blood were divided into four groups and treated with Vehicle [Group I], B(a)P (300 μM) [Group II], Silymarin (500 μM) + B(a)P (300 μM) [Group III], and Silymarin alone (500 μM)] [Group IV]. Silymarin treatment maintains the integrity of erythrocytes by preventing hemolysis, protein thiol oxidation and by decreasing the activity of AChE. SEM observations indicate that B(a)P induced significant alteration in the morphology of erythrocytes to echinocytes, which may be due to the interaction of B(a)P with the membrane's outer phopholipid monolayer. The light microscopic and SEM images show that silymarin treatment maintains the normal discocytic morphology of erythrocytes. The protective effect of silymarin might be attributed to its chemical structure and membranotrophic nature. The components silibinin, silydianin, and silychristin have OH in the 3rd, 5th, and 7th carbon atoms that may account for its increased antioxidant activity and removal of ROS formed during B(a)P metabolism. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 165–175, 2014.     

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction

Background: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. Method and results: One hundred thirty‐five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty‐nine patients (66%) had severe AVS (aortic valve area <0.6 cm²/m² BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R²= 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R²= 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R²= 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). Conclusions: In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se. (Echocardiography 2011;28:695‐702)     

Diabetes and driving

More than 69 million Indians are suffering from diabetes, of which a substantial proportion of the population are currently holding or will seek in the future the license to drive. Driving essentially requires multitasking with visuospatial skills at the same time and thus the management of diabetes in individuals which should demonstrate a proper detection and treatment of diabetes-related hypoglycemia will predict the capacity of driving any motor vehicle. Repeated hypoglycemia-related neuroglycopenia causes increased risk of neurocognitive dysfunction leading to visuospatial skills deficiency. Eight percent of dementia may be attributed to diabetes. Potential causes of driving impairment associated with diabetes are acute hypoglycemia, and its unawareness, retinopathy, neuropathy related to foot that affects ability to use pedals, IHD, cerebrovascular disease, somnolence and sleep disorder associated with obesity, use of pain relieving medications and antidepressant, and cognitive dysfunction and thus should be reviewed properly before issuing a driving license. Medical evaluation and documentation of acute and chronic complications of drivers by a registered medical practitioner at pre-determined intervals may be considered as a legal necessity to identify at-risk drivers. Secretagogues have a higher incidence of hypoglycemia compared to someone who is on metformin alone. On the other hand, hypoglycemia is more frequent in an insulin-treated patient of both type 1 and type 2 diabetes. In many countries as well as in European Union (EU), it is necessary to review medical fitness in every 3 years by the authority; a person should not have any severe hypoglycemic event in preceding 12 months and a driver must have awareness of hypoglycemia and its management. According to Canadian diabetes association consensus statement, review should be done every 2 years; a person should not have any severe hypoglycemic event in preceding 6 months, and according to ADA position statement evaluation should be done every 2–5 years. Medical fitness certificate should be reviewed at frequent intervals; the authorities should enforce strict regulation on suspension and revocation of driving license. Information to the authorities should be promptly done by doctors or patients. Decision should be based on medical evaluation, but hypoglycemia that occurs due to medication change and during sleep does not warrant for disqualification as it may be corrected with proper dietary changes and dose adjustments. Any driver with suspended license should be re-assessed in the next 6 months for their medical fitness and hypoglycemic profile and if found suitable, the license can be revoked. Physicians should participate and should assess patient’s physical and mental status, medical condition and treatment, list of medications which may impair driving performance, and any disease-related complication that lead to impaired driving or dangerous driving. Patient education is the most important factor to prevent any motor accident related to their medical condition and should be trained to prevent acute and chronic complications of diabetes.     

Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

Background  

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.