Enhanced brain delivery with lower hepatic exposure of lazaroid loaded nanostructured lipid carriers developed using a design of experiment approach.

The current study was designed to develop and optimize lazaroid loaded nano-structured lipid carriers (LAZ-NLCs) using design of experiment approach for enhancing lazaroid brain exposure. Response surface plots were used to determine the effects of independent variables (amount of PEGylating agent and liquid lipid) on dependent variables (particle size, zeta potential and encapsulation efficiency), while numerical optimization was used for optimizing LAZ-NLCs composition. The optimal LAZ-NLCs were spherical in shape with measured size of 172.3 ±â€¯3.54 nm, surface charge of -4.54 ±â€¯0.87 mV and encapsulation efficiency of 85.01 ±â€¯2.60%. The optimal LAZ-NLCs were also evaluated for hemolytic potential, storage stability and solid-state properties. The plasma pharmacokinetics along with brain and hepatic distributions of control lazaroid citrate solution and optimal LAZ-NLCs formulation were evaluated in Sprague-Dawley rats after the single bolus intravenous administration. The optimized LAZ-NLCs and the control lazaroid citrate solution had similar plasma pharmacokinetic profiles; however, differential organ bio-distributions were observed. The lazaroid exposure in brain was enhanced by two times with a decreased liver exposure by half for the NLCs group compared to the solution group.

UPLC-MS/MS assay of 21-aminosteroid (lazaroid U74389G) for application in pharmacokinetic study.

Lazaroids are potent inhibitors of lipid peroxidation, both in vitro and in vivo. Additionally, a member of the lazaroid family, U-74389G (LAZ) has been shown to have specific radio-protective and anti-proliferative effects. However, there is no quantitative analytical method developed for measuring the therapeutic levels of LAZ for the aforementioned effects. This article highlights the development and validation of a sensitive UPLC-MS/MS method for the quantification of LAZ, and its subsequent application in pharmacokinetic studies in rats with the lower limit of quantification (LLOQ) of 1.95 ng/mL. LAZ and internal standard diadzein (IS) were separated using ACQUITY UPLC(®) BEH C18 column. Gradient elution was used at a flow rate of 0.45 mL/min with mobile phases consisting of 0.1% formic acid in water and 0.1% formic in acetonitrile. LAZ (m/z 612→260) and IS (m/z 255→199) were detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in a positive mode on QTRAP(®) 5500 System. The UPLC-MS/MS method was validated as per the US FDA Guidelines for Bio-analytical Validation. LAZ was extracted from rat plasma (100 µL) using protein precipitation by acetonitrile with mean recovery and matrix factor in range of 47.7-56.1%, and 85.6-89.4%, respectively. The calibration curve for LAZ was linear in the range of 1.95-250 ng/mL. The inter-day and intra-day accuracy and precision values for LLOQ, low, medium, high and very high concentration QC samples were within ±15%. LAZ was tested under different storage conditions, for short-term bench-top stability (1h and 3h at 25°C), long-term stability (1 month at -80°C), freeze-thaw cycle stability (1 cycle and 3 cycles) and stability of processed samples in auto-sampler (24h at 10°C) with stability values within ±15% range of nominal concentrations. The validated UPLC-MS/MS method was further applied to a pharmacokinetic study in rats after a single intravenous dose of LAZ at 5 mg/kg.

Effect of marinades on the formation of heterocyclic amines in grilled beef steaks.

Heterocyclic amines (HCAs) are suspected human carcinogens formed in muscle foods during high temperature grilling or cooking. Inhibition of HCAs by commercial marinades rich in polyphenolic antioxidant containing spices was evaluated with beef round steaks cooked at 204 degrees C (400 degrees F). Treatment effects on the levels of 4 HCAs were investigated: 2-amino-3,8-dimethylimidazo[4,5-flquinoxaline (MeIQx), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), 1-methyl-9H-pyrido[4,3-b]indol (harman), and 9H-pyrido[4,3-blindol (norharman). The marinades were formulated according to the package label instruction in an oil, water, and vinegar mixture, and the steaks were treated for 1 h prior to grilling. All 3 marinades, Caribbean, Southwest, and herb, significantly decreased the imidazo-azaarene HCAs (MeIQx, PhIP) as contrasted to controls and liquid blanks. The Caribbean mixture showed the highest decrease in the total HCA content (88%), followed by the herb (72%) and Southwest (57%). With a few exceptions there were significant decreases in HCAs for treatments with only the marinade bases (ingredients without any spices/herbs). As measured by high-performance liquid chromatography (HPLC), the marinades contained considerable amounts of the polyphenolic antioxidants carnosic acid, carnosol, and rosmarinic acid with Caribbean being the highest. Commonly available spice-containing marinades can be effective inhibitors of HCA formation and provide reduced exposure to some of the carcinogens formed during grilling.

Seroepidemiology of hepatitis A in voluntary blood donors from Pune, western India (2002 and 2004-2005).

Recently, a changing pattern of hepatitis A epidemiology has been reported in the Indian population indicating a rise in the rate of hepatitis A infection among adults. The study's objective was to assess anti-HAV prevalence in voluntary blood donors from middle and high socioeconomic strata. Serum samples collected from voluntary blood donors from Pune city and its suburbs in the years 2002 and 2004-2005 were tested for anti-HAV IgG antibodies. Serum samples collected during 2004-2005 were examined for anti-HAV IgM antibodies. Positive samples were tested for HAV-RNA. Agewise anti-HAV positivity was significantly low in adults aged 18-25 years (90.4%) compared to those aged >25 years (97.4%) (P<0.01). A decline in anti-HAV prevalence was significant in 2004-2005 compared to that in 2002 (96.5% vs. 92.1%) (P<0.01). Overall, in both adult age groups, the proportion of anti-HAV positivity was remarkably low in the high socioeconomic group (HSG) (88.96%) compared to that of the middle socioeconomic group (MSG) (95.86%) (P<0.01). Anti-HAV IgM positivity was not significant (~1%), however, presence of HAV-RNA in one of the samples indicated the possibility of horizontal transmission of HAV. Increase in seronegativity to HAV in HSG implicates a rise in the susceptible pool and indicates the need for vaccination against hepatitis A.

Effects of total iron, myoglobin, hemoglobin, and lipid oxidation of uncooked muscles on livery flavor development and volatiles of cooked beef steaks.

Infraspinatus (IN), gluteus medius (GM), and psoas major (PM) steaks were obtained from A- and B-maturity carcasses with either high (⩾6.0) or normal (⩽5.7) pH, and either Slight or Small marbling. Steaks were vacuum aged either 7, 14, 21, or 35d postmortem, and were broiled and served to a highly trained, flavor-profile sensory panel. Steaks with livery flavor were analyzed by gas chromatography/mass spectrometry for flavor compounds. Steaks aged 7 or 35d postmortem were analyzed for myoglobin (Mb) and hemoglobin (Hb) concentrations and for total iron (Fe) (35 d steaks only). The IN had greater Fe (P<0.05) than did the GM or PM. Livery flavor increased (P<0.05) and beef flavor identification decreased (P<0.05) in the GM as Fe increased. The PM had the lowest (P<0.05) Mb/Fe ratios and highest (P<0.05) Hb/Fe ratios. Several statistically significant, but relatively low correlations between 16-, 17-, and 18-carbon chain fatty acids and livery flavor resulted. Thirteen volatile compounds had higher concentrations in steaks with livery flavor than in those without livery flavor. Livery flavor development is a complex trait that can be affected by concentrations of total Fe, Mb, and fatty acids, but the relationships are relatively low.

Early diagnosis of neonatal septicemia by sepsis screen.

A study of 100 neonates with clinical suspicion of septicemia, admitted in neonatal intensive care unit of SCSM General Hospital, Solapur was carried out to assess the utility of various indices of sepsis screen. Bacterial and hematological profile of these neonataes was studied. Parameters of sepsis screen such as leukocyte count, band form to neutrophil ratio, neutrophils with toxic granulations, micro ESR and test for C-reactive protein were analysed to know their sensitivity and specificity.

Histopathological study of endometrium in infertility.

A study of 200 cases of primary and secondary infertility was carried out in the department of pathology, Dr. V.M. Medical College, Solapur. Endometrial specimens were evaluated in the light of menstrual history to find out the incidence of various endometrial changes in cases of infertility. All cases underwent endometrial biopsy premenstrually. Haematoxylin and eosin staining was done for dating of endometrium and diagnosis of corpus luteal defect and anovalutory cycles. PAS stain was done in 50 cases of infertility with control of 25 cases to detect the amount of glycogen. Menstrual problems were seen in 38.2% of patients. Anovulatory infertility was present in 28.2% cases. Luteal phase defect was seen in 20% cases. Cystoglandular hyperplasia was seen in 1.7% cases & tuberculous endometritis was present in 2.6% cases. Glycogen deficiency was seen in 30% cases of luteal phase defect.