Study of serum cortisol levels in complicated and uncomplicated Plasmodium vivax malaria patients

Background: Malaria results in pathological changes in various body organs, as the parasite invade and multiply in circulating red blood cells. Despite of advances in diagnostic and treatment modalities, worldwide incidences of malaria are significant. Current study was conducted to investigate serum cortisol level changes as a promising biomarker for risk prediction in malaria and to study adrenal insufficiency in malaria patients.Methods: Current investigation was a prospective observational study, conducted on complicated and uncomplicated Plasmodium vivax malaria patients. Serum cortisol levels in patients were investigated through immunoassay using direct chemiluminescent technology and were statistically correlated with Plasmodium vivax malaria infection.Results: Results of present investigation revealed that on day 1 there was significant difference in mean serum cortisol levels between the Plasmodium vivax malaria patients and control group and cortisol levels were significantly higher in complicated Plasmodium vivax malaria patients compared to uncomplicated cases on day 1 and 7. Cortisol levels were observed to be normal on day 1 and 7 in uncomplicated malaria cases and in patients with bleeding manifestations, renal failure and jaundice. In 10 out of 15 cases of cerebral malaria, significant increase in serum cortisol levels were observed on day 1, while on day 7 levels were normal in all 15 cases.Conclusions: Rise in serum cortisol level had a positive correlation with temperature and thus can be useful to predict the severity of disease in Plasmodium vivax malaria patients. No cortisol insufficiency was observed in during active and convalescent stages of illness

Study of clinical features and laboratory investigations for effective management of hyponatremia

Background: Hyponatremia, a common electrolyte disorder is mostly observed in hospitalized elderly patients. It is a potential cause of morbidity, mortality and has significant economic impact on the patient and health care system. The aim of the present study was to investigate the risk factors, clinical features and management of hyponatremia in hospitalized patients to reduce its incidence and minimize the associated complications.Methods: Current study was conducted in a tertiary care hospital SSMC, Tumkur). Patients were evaluated for the underlying cause of hyponatremia through detailed history and physical examination followed by appropriate laboratory investigations based on urine sodium, serum and urine osmolality. Patients with hyponatremia were classified into categories based on clinical investigations and accordingly treated with suitable therapy.Results: Constitutional symptoms, confusion, fever, vomiting, respiratory symptoms, abdominal pain, loose stools, coma, convulsions and other miscellaneous symptoms were observed in history of hyponatremic patients. Most common etiology was found to be SIADH followed by extrarenal losses, renal failure, cirrhosis, CCF, drug in take and glucocorticoid deficiency. Management of hyponatremia was done using hypertonic saline, administration of diuretics, fluid restriction therapy, administration of vaptans and combination of hypertonic saline and vaptans as  treatment alternatives, no potential complications were observed during treatment of hyponatremia.Conclusions: The possible cause of hyponatremia should always be determined, asoutcomeinsevere hyponatremiais governed by etiology and not merely by serum sodium levels. The correction of hyponatremia helps to improve the prognosis of the underlying disease and to prevent further complications

Field Investigation on the Prevalence of Trypanosomiasis in Camels in Relation to Sex, Age, Breed and Herd Size

Blood samples were collected from 240 camels (183 male and 57 female) of four breeds from six districts of Sindh. An overall infection was determined as 11.25%. Species of Trypanosoma was identified as Trypanosoma evansi. District wise infection was found to be 2.5, 7.5, 12.5, 15.00, 22.5 and 7.5% in Hyderabad, Mirpur Khas, Umerkot, Badin, Thatta and Larkana, respectively. A higher infection was found in females (15.79%) as compared to males (9.84%). Highest (14.96%) infection was noted in age group >7 years, followed by 8.57 and 4.65% in 3 to 7 years and less than to 3 years old camels, respectively. Four breeds of camels were surveyed and the highest infection rate was found in Sakrai breed (21.82%), followed by 16.67, 6.15 and 5.95% in Kharai, Sindhi and Dhati breeds respectively. When herd size was considered, infection rate was 1.67, 6.67, 15.00 and 21.67% in herds possessing 1 to 5, 6 to 10, 11 to 20 and more than 20 animals, respectively

PHYSICAL AND CHEMICAL QUALITY OF MARKET MILK SOLD AT TANDOJAM, PAKISTAN

The present study was conducted to evaluate the quality of milk sold at Tandojam, Pakistan. A total of 125 milk samples (25 samples from each source) collected from five milk marketing agencies viz direct seller (DS), milk collection center(MCC), milk vendor shop (MVS), hotel (HT) and buffalo dairy farm (DF), which served as control. Acidity of milk obtained from DS, MCC, MVS and HT averaged 0.13, 0.15, 0.12 and 0.13, respectively compared to 0.14 for DF milk. The pH values of milk from MVS (6.54) and HT (6.53) were significantly different (P<0.01) from DS (6.65) and MCC (6.66) and relatively similar (P>0.05) to that of DF milk i.e. 6.65. Viscosity, specific gravity and freezing point of milk procured from DS (1.48, 1.026 and –0.460, respectively), MCC (1.58, 1.026 and –0.470, respectively), MVS (1.34, 1.026 and –0.440, respectively) and HT (1.46, 1.027 and –0.480, respectively) were significantly (P<0.001) lower than DF milk (1.86, 1.031 and -0.551, respectively). Chemical quality of milk procured from DS, MCC, MVS and HT compared to DF milk (control) averaged 13.45, 14.18, 13.19 and 14.06% vs. 16.30% for TS content, 8.25, 8.81, 8.06 and 8.51% vs. 9.79% for SNF content, 5.20, 5.41, 5.13 and 5.54% vs. 6.51% for fat content, 3.85, 3.96, 3.91 and 4.23% vs. 4.35% for protein content, 2.70, 2.77, 2.56 and 3.20% vs. 3.56% for casein content, 3.65, 4.03, 3.34 and 3.52% vs. 4.53% for lactose content and 0.75, 0.78, 0.74 and 0.76% vs. 0.91% for ash content, respectively. All the attributes of chemical quality of milk supplied through four agencies were significantly lower (P<0.05) than DF milk

Poly(β-Amino Ester)-Nanoparticle Mediated Transfection of Retinal Pigment Epithelial Cells In Vitro and In Vivo

A variety of genetic diseases in the retina, including retinitis pigmentosa and leber congenital amaurosis, might be excellent targets for gene delivery as treatment. A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with high efficacy in vitro. We synthesized a combinatorial library of PBAEs and evaluated them for transfection efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify lead polymer structures and transfection formulations. Our optimal polymer (B5-S5-E7 at 60 w/w polymer∶DNA ratio) transfected ARPE-19 cells with 44±5% transfection efficacy, significantly higher than with optimized formulations of leading commercially available reagents Lipofectamine 2000 (26±7%) and X-tremeGENE HP DNA (22±6%); (p<0.001 for both). Ten formulations exceeded 30% transfection efficacy. This high non-viral efficacy was achieved with comparable cytotoxicity (23±6%) to controls; optimized formulations of Lipofectamine 2000 and X-tremeGENE HP DNA showed 15±3% and 32±9% toxicity respectively (p>0.05 for both). Our optimal polymer was also significantly better than a gold standard polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which achieved only 8±1% transfection efficacy with 25±6% cytotoxicity. Subretinal injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1±1×103-fold and 1.5±0.7×103-fold increased GFP expression in the retinal pigment epithelium (RPE)/choroid and neural retina respectively, compared to injection of DNA alone (p = 0.003 for RPE/choroid, p<0.001 for neural retina). The successful transfection of the RPE in vivo suggests that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases

Choriocapillaris and Choroidal Microvasculature Imaging with Ultrahigh Speed OCT Angiography

We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning ~32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and ~6 mm nasal to the fovea at the depths of the choriocapillaris and Sattler's layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging.National Institutes of Health (U.S.) (NIH R01-EY011289-27)National Institutes of Health (U.S.) (NIH R01-EY013178-12)National Institutes of Health (U.S.) (NIH R44-EY022864-01)National Institutes of Health (U.S.) (NIH R01-CA075289-16)United States. Air Force Office of Scientific Research (AFOSR FA9550-10-1-0551)United States. Air Force Office of Scientific Research (AFOSR FA9550-12-1-0499

Determinants of serum levels of vitamin D: a study of life-style, menopausal status, dietary intake, serum calcium, and PTH

Background: Low blood levels of vitamin D (25-hydroxy D3, 25OHD3) in women have been associated with an increased risk of several diseases. A large part of the population may have suboptimal 25OHD3 levels but high-risk groups are not well known. The aim of the present study was to identify determinants for serum levels of 25OHD3 in women, i.e. factors such as lifestyle, menopausal status, diet and selected biochemical variables. Methods: The study was based on women from the Malmo Diet and Cancer Study (MDCS), a prospective, population-based cohort study in Malmo, Sweden. In a previous case-control study on breast cancer, 25OHD3 concentrations had been measured in 727 women. In these, quartiles of serum 25OHD3 were compared with regard to age at baseline, BMI (Body Max Index), menopausal status, use of oral contraceptives or menopausal hormone therapy (MHT), life-style (e. g. smoking and alcohol consumption), socio-demographic factors, season, biochemical variables (i.e. calcium, PTH, albumin, creatinine, and phosphate), and dietary intake of vitamin D and calcium. In order to test differences in mean vitamin D concentrations between different categories of the studied factors, an ANOVA test was used followed by a t-test. The relation between different factors and 25OHD3 was further investigated using multiple linear regression analysis and a logistic regression analysis. Results: We found a positive association between serum levels of 25OHD3 and age, oral contraceptive use, moderate alcohol consumption, blood collection during summer/autumn, creatinine, phosphate, calcium, and a high intake of vitamin D. Low vitamin D levels were associated with obesity, being born outside Sweden and high PTH levels. Conclusions: The present population-based study found a positive association between serum levels of 25OHD3 and to several socio-demographic, life-style and biochemical factors. The study may have implications e. g. for dietary recommendations. However, the analysis is a cross-sectional and it is difficult to suggest Lifestyle changes as cause-effect relationships are difficult to assess

Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration

Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD