Erectile Dysfunction Is Not Independently Associated with Cardiovascular Death: Data from the Vitamins and Lifestyle (VITAL) Study

IntroductionErectile dysfunction (ED) is a significant problem among aging men. ED is independently associated with cardiovascular (CV) events (angina, myocardial infarction, and stroke).AimWe sought to determine if ED was associated with CV death.Main Outcome MeasuresRisk of CV death in men with ED.MethodsExactly 31,296 men in Washington aged 50–76 completed a questionnaire in 2000–2002 on supplements, diet, exercise, personal health, and ED. ED was determined by one question: “Have you experienced impotence in the last year?” We excluded patients with a history of coronary artery disease or stroke. Participants linked yearly through 2008 to the Washington State Death Certificate System. CV death was defined by death certificates listing CV‐related deaths (International Classification of Diseases 10th Revision [ICD‐10] codes: I00‐I15, I20‐I52, and I60‐I99). We performed multivariate Cox proportional hazard regression adjusting for age, marital status, race, education, self‐rating of health, body mass index (BMI), antihypertensive/lipid‐lowering drug use, diabetes, family history of CV disease, smoking, and exercise.ResultsAbout 7,762 men had ED and there were 486 CV deaths over 7.8‐year average follow‐up. The typical man who suffered CV death was older, single, reporting poor health, taking antihypertensives, higher BMI, a smoker, a diabetic, and had a family history of CV disease. When adjusting for age, marital status, and education only, men with ED had a 23% increased risk of CV death (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.01, 1.49). With further adjustment for known risk factors for CV disease (diabetes, treatment for hypertension or hyperlipidemia, family history of myocardial infarction/stroke, BMI, and exercise), ED no longer predicted CV death (HR 0.93, 95% CI 0.76, 1.15).ConclusionsIn this community‐based cohort, ED was not independently associated with an elevated risk of CV death. These data do not contradict prior data associating ED and CV events but rather suggest that ED may be a manifestation of other known risk factors for CV disease. Hotaling JM, Walsh TJ, Macleod LC, Heckbert S, Pocobelli G, Wessells H, and White E. Erectile dysfunction is not independently associated with cardiovascular death: Data from the Vitamins and Lifestyle (VITAL) study. J Sex Med 2012;9:2104–2110.     

Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenic Escherichia coli as a prophylactic against diarrhea

ABSTRACT

Background

. Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A.     

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.     

Developing ultra deformable vesicular transportation of a bioactive alkaloid in pursuit of vitiligo therapy

ObjectiveTo develop transfersomal formulation integrated with piperine intended for vitiligo.MethodsFilm hydration technique was employed in the preparation of transfersomes. Modified diffusion cell, consistency tester were fabricated for ex vivo diffusion studies and spreadability studies respectively while tape stripping method was integrated with tissue extraction in the determination of tissue drug concentration.ResultsWhen film hydration technique was used for, ultradeformable vesicles (transfersomes) of piperine in soabean phosphatidylcholine was formed with (67.11±0.22) to (70.55±3.62) and (60.12±1.04) to (80.43±0.14) mean size (μ) and entrapment efficiency (%) respectively. Transfersomes are capable of crossing the pores in permeability barriers extremely efficient even if the transfersome radius (t_r) is much greater than the pore size (r_pore) ie., tr/r_pore? 0.25 the driven flux rate depends on the transdermal osmotic gradient. The vesicles describes elasto-mechanical character of vesicles while penetrating through the pores. The proviso is that the vesicular membrane elasticity is dynamically to the local stress by the external. Diffusion and Spreadability studies showed maximum diffusion when the lipid was kept minimum. Tape stripping and tissue extraction method for the tissue drug retention showed that (75.25±1.72)% drug was retained in the dermis.ConclusionSpan 80 was preferred over tween 80 in terms of dermal retention. Size and encapsulation was slightly altered by phosphatidylcholine concentration. The kinetics, efficiency and the transfersome mediated transport can be tailored for trans-epidermal, deep tissues and systemic depending on the vesicular composition, dose and form. Thus we have offered a successful drug delivery of piperine targeting the deep epidermis.     

In ova angiogenesis analgesic and anti inflammatory potency of Aerva Monsoniae (Amaranthaceae)

ObjectiveTo evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae) by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound.MethodsThe whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 μ g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed.ResultsThe phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 100 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses.ConclusionsThe parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.     

Leukemia inhibitory factor upregulates cytokine expression by a murine stromal cell line enabling the maintenance of highly enriched competitive repopulating stem cells

Attempts to maintain or expand primitive hematopoietic stem cells in vitro without the concomitant loss of their differentiative and proliferative potential in vivo have largely been unsuccessful. To investigate this problem, we compared the ability of three cloned bone marrow (BM) stromal cell lines to support the growth of primitive Thy- 1lo Sca-1+H-2Khi cells isolated by fluorescence-activated cell sorting from the BM of Ly-5.2 mice treated 1 day previously with 5-fluo- rouracil. Sorted cells were highly enriched in cobblestone area-forming cells (CAFC), but their frequency was dependent on the stromal cell lines used in this assay (1 per 45 cells on SyS-1; 1 per 97 cells on PA6). In the presence of recombinant leukemia inhibitory factor (LIF), CAFC cloning efficiency was increased to 1 per 8 cells on SyS-1 and 1 per 11 cells on PA6, thus showing the high clonogenicity of this primitive stem cell population. More primitive stem cells with competitive repopulating potential were measured by injecting the sorted cells into lethally irradiated Ly-5.1 mice together with 10(5) radioprotective Ly-5.1 BM cells whose long-term repopulating ability has been "compromised" by two previous cycles of marrow transplantation and regeneration. Donor-derived lymphocytes and granulocytes were detected in 66% of animals injected with 50 sorted cells. To quantitate the maintenance of competitive repopulating units (CRU) by stromal cells, sorted cells were transplanted at limiting dilution before and after being cultured for 2 weeks on adherent layers of SyS-1, PA6, or S17 cells. CRU represented 1 per 55 freshly sorted cells. CRU could be recovered from cocultures supported by all three stromal cell lines, but their numbers were approximately-sevenfold less than on day 0. In contrast, the addition of LIF to stromal cultures improved CRU survival by 2.5-fold on S17 and PA6 cells (approximately two-fold to threefold decline), and enabled their maintenance on SyS-1. LIF appeared to act indirectly, because alone it did not support the proliferation of Thy- 1lo Sca-1+H-2Khi cells in stroma-free cultures. Polymerase chain reaction (RT-PCR) analysis revealed that Interleukin-1beta (IL-1 beta) IL-2, IL-6, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, transforming growth factors, LIF, and Steel Factor (SLF) mRNAs were upregulated in SyS-1 within 1 to 6 hours of LIF-stimulation. To determine if increased expression of SLF by LIF-stimulated SyS-1 cells could account for their capacity to support stem cells, sorted calls were cocultured on simian CV-E cells that were transfected with an expression vector encoding membrane-bound SLF, or supplemented with soluble SLF. In both cases, SLF synergized with IL-6 produced endogenously by CV-E cells enabling CAFC growth equivalent to that on LIF-stimulated SyS-1. CAFC development on LIF- stimulated SyS-1 could also be completely abrogated by an anti-SLF antibody. These data provide evidence for a role of LIF in the support of long-term repopulating stem cells by indirectly promoting cytokine expression by BM stroma. Furthermore, we have used quantitative assays to show a maintenance of CRU numbers, with retention of in vivo function following ex vivo culture.