Evaluation of In vitro and In vivo Performance of Granisetron In situ Forming Implants: Effect of Sterilization, Storage Condition and Degradation

Purpose: To investigate the effect of various solvent systems and gamma irradiation on the in vitro and in vivo performance of granisetron HCl injectable phase-sensitive in situ forming implants (ISFIs).Methods: ISFIs were prepared by mixing and sterilized by gamma  irradiation. Effect of solvent system was studied. Injectability, polymer degradation and stability studies (4 and 25 oC for 4 months), viscositymeasurements, as well as in vitro and in vivo (in rabbits) drug release, and also histological examinations for biocompatibility studies (in rabbits and rats) were carried out.Results: ISFIs showed good injectability from 20-gauge needle and their in vitro drug release increased in the following rank order of solvent/solvent combinations: dimethylsulphoxide (DMSO) > DMSO:prophylenecarbonate (PC) > DMSO:triacetin(TA) > DMSO:benzylbenzoate (BB). DMSO:PC incorporating ISFI gave zero order (r2 = 0.9503) drug release for 21 days; application of gamma irradiation accelerated drug release with a difference factor (f1) of 53 but zero order release (r2 = 9690) was maintained. Following test results for DMSO:PC including ISFI as decrease in molecular weight of polymer was descriptive for drug release behavior and  sterilization effect, additionally dynamic viscosities decreased in line with polymer degradation and all forms of this ISFI showed plastic flow(fresh, irradiated, aged at 4 and 25 oC for 4 months). In vivo performance showed steady state plasma drug concentrations between 2 to 21 days with value of 0.55 ± 0.03 ìg/ml and biocompatibility was confirmed by  histological results obtained at specific stages of tissue reactions, and also by lack of fibrous capsule formation.Conclusion: An ISFI for long-term antiemetic therapy achieved in this  preliminary study is promising and, therefore, further investigations are required.Keywords: Implant, Poly(DL-lactide-co-glycolide), Granisetron, Gamma irradiation, Sterilization, Degradation, Viscosity, Stability, Pharmacokinetic, Biocompatibility

Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

Abstract Background To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC). Methods Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs. Results Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs. Conclusion Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses.</p

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

<p>Abstract</p> <p>Background</p> <p>Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity.</p> <p>Aim</p> <p>To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats.</p> <p>Method</p> <p>White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2^ndgroup HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10^thweek (start time for treatments) for 4 weeks.</p> <p>Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed.</p> <p>Results</p> <p>Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.</p> <p>Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR) significantly increased in HFD in comparison with the control group. The treatment with L-carnitine or HMF improved the condition. HFD elevated hepatic MDA and lipid peroxidation associated with reduction in hepatic GSH and catalase activity; whereas administration of L-carnitine or herbal extract significantly ameliorated these hepatic alterations.</p> <p>Conclusion</p> <p>HFD induced obesity associated with a disturbed lipid profile, defective antioxidant stability, and high values of IR parameters; this may have implications for the progress of obesity related problems. Treatment with L-carnitine, or HMF extract improved obesity and its associated metabolic problems in different degrees. Also HMF has antioxidant, hypolipidaemic insulin sensitizing effects. Moreover HMF might be a safe combination on the organs whose functions were examined, as a way to surmount the obesity state; and it has a distinct anti-obesity effect.</p

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Metabarcoding of the kombucha microbial community grown in different microenvironments

Introducing of the DNA metabarcoding analysis of probiotic microbial communities allowed getting insight into their functioning and establishing a better control on safety and efficacy of the probiotic communities. In this work the kombucha poly-microbial probiotic community was analysed to study its flexibility under different growth conditions. Environmental DNA sequencing revealed a complex and flexible composition of the kombucha microbial culture (KMC) constituting more bacterial and fungal organisms in addition to those found by cultural method. The community comprised bacterial and yeast components including cultured and uncultivable microorganisms. Culturing the KMC under different conditions revealed the core part of the community which included acetobacteria of two genera Komagataeibacter (former Gluconacetobacter) and Gluconobacter, and representatives of several yeast genera among which Brettanomyces/Dekkera and Pichia (including former Issatchenkia) were dominant. Herbaspirillum spp. and Halomonas spp., which previously had not been described in KMC, were found to be minor but permanent members of the community. The community composition was dependent on the growth conditions. The bacterial component of KMC was relatively stable, but may include additional member—lactobacilli. The yeast species composition was significantly variable. High-throughput sequencing showed complexity and variability of KMC that may affect the quality of the probiotic drink. It was hypothesized that the kombucha core community might recruit some environmental bacteria, particularly lactobacilli, which potentially may contribute to the fermentative capacity of the probiotic drink. As many KMC-associated microorganisms cannot be cultured out of the community, a robust control for community composition should be provided by using DNA metabarcoding.National Academy of Sciences of Ukraine (N47/2013)http://www.amb-express.comhb201

MEDICAL MYCOLOGY

This study was planned to determine the risk factors of candidemia, and the most common Candida species causing bloodstream infections. A case-control study which included adult patients was conducted over a 1-year period at tertiary-care educational hospitals in Turkey. A total of 83 candidemia episodes were identified during the study period. Candida albicans was the most common species recovered (45.8%) followed by Candida tropicalis (24.1%) Candida parapsilosis (14.5%) and Candida glabrata which was isolated from only four (4.8%) patients. Presence of a urethral catheter (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.09-5.19; P = 0.02), previous use of antibiotics (OR 2.61; 95% CI 1.05-6.46; P = 0.03), RBC transfusions (OR 2.14; 95% CI 1.16-3.94; P = 0.01) and parenteral nutrition (OR 4.44; 95% CI 2.43-8.11; P < 0.01) were found as independent risk factors for candidemia. TPN (Total Parenteral Nutrition) was an independent risk factor for both C. albicans and non-Candida albicans Candida species (P < 0.001). Most of the risk factors were invasive procedures and former medications. We conclude that a great number of candidemia cases are preventable by means of reduction of unnecessary invasive procedures and the use of antimicrobials.</