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[en] Oral iodized oil is used as a therapeutic and prophylactic measure for all forms iodine deficiency in areas of high goitre endemicity where iodized salt distribution was not possible. The effect of oral iodine supplementation on total goitre rate (%TGR) and urinary iodine excretion among school children 4 to 16 years of age was studied. In the first group (n=57) 200mg oral iodized oil reduced % TGR from 31.6% to 17.5% and 33.3% to 24.6% in males and females respectively, while in the second group (n=53), 400mg iodine reduced the % TGR from 34.0% to 20.8% in males and 35.9% to 24.5%) in females after 13 months of intervention. The results suggest that: (i) 200mg is likely equally effective as 400mg for iodine deficiency disorders control and prevention among children and (ii) iodine could be administered annually rather than bi-annually[4 Tables, 13 refs]
[en] In Japan, transarterial infusion chemotherapy using cisplatin (CDDP-TAI) is frequently used for advanced hepatocellular carcinoma (HCC). Moreover, oral chemotherapy with S-1, an oral fluoropyrimidine derivative, has also elicited promising responses in HCC patients. We determined the recommended dosage for CDDP-TAI plus S-1 combination therapy for advanced HCC. Twelve Child–Pugh class A or B patients with advanced HCC who met the eligibility criteria were enrolled in this phase I trial. Patients received CDDP-TAI (infusion, day 1) plus S-1 (oral administration, days 1–21) every 5 weeks until disease progression. Cisplatin (65 mg/m"2) was administered with S-1 at 50 mg · m"-"2 day"-"1 (level 1, 3 patients), 60 mg · m"-"2 day"-"1 (level 2, 3 patients), or 80 mg · m"-"2 day"-"1 (level 3, 6 patients). The total number of treatment courses was 25 (median, 2 courses/patient; range, 1–6 courses). Dose-limiting toxicity was not observed in any patient at any level; therefore, the recommended dosage for cisplatin and S-1 in combination was level 3. Grade 3 adverse events were elevated alanine aminotransferase levels (2 patients), elevated aspartate aminotransferase levels (2 patients), anemia (1 patient), and decreased platelet counts (1 patient). Median progression-free survival and overall survival were 73 days and 328 days, respectively. The disease control rate was 58% (7/12); 17% (2/12) of patients achieved partial response and 42% (5/12) achieved stable disease. CDDP-TAI plus S-1 is safe for the treatment of HCC. The recommended dosage for further evaluation of this combination therapy in phase II studies is 65 mg/m"2 CDDP and 80 mg/m"2 S-1. UMIN; number: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function
[en] Registration of pesticides with the National Pesticide Board must undergo laboratory testing for short-term and long-term health effects. Laboratory animals such as rats are purposely fed with high doses of the pesticide to cause toxic effects. The objectives of this study are to investigate the effect of Bacillus thuringiensis-based Bafog-1 (S) and Ecobac-1 (EC) against Sprague Dawley rats, to assess the toxicity of these Bt products. The acute oral and acute dermal toxicity studies were co ducted according to OECD (Organisation for Economic Co-operation and Development) Guideline for Testing of Chemicals 425 (2001) and 402 (1987), respectively. The oral LD_5_0 of Ecobac-1 (EC) and Bafog-1 (S) on female rats is more than 5000 mg kg"-"1, when administered orally with dose of 175 mg kg"-"1, respectively. Correspondingly, the LD_5_0 for dermal administration of both Bt products is more than 2000 mg kg"-"1 for both male and female rats. There was no toxic symptom observed during the two weeks observation period in male and female rats. Post-mortem of the dermally treated animals at the end of the experiment did not show changes or adverse effect in the rats' internal organs, indicating these two products are non-toxic to rats. Bt as an environmental-friendly microbial insect cide is generally not toxic to human, domestic animals and vertebrates. (author)
[en] Highlights: • Cambinol inhibits spread of AD synaptosome derived tau seeds, from donor to recipient cells. • Cambinol inhibits nSMase2 through targeting the DK-switch in its active site. • Cambinol inhibits EV-mediated tau propagation. • Cambinol has low brain permeability and inhibition of nSMase activity in vivo. Targeting of molecular pathways involved in the cell-to-cell propagation of pathological tau species is a novel approach for development of disease-modifying therapies that could block tau pathology and attenuate cognitive decline in patients with Alzheimer's disease and other tauopathies. We discovered cambinol through a screening effort and show that it is an inhibitor of cell-to-cell tau propagation. Our in vitro data demonstrate that cambinol inhibits neutral sphingomyelinase 2 (nSMase2) enzyme activity in dose response fashion, and suppresses extracellular vesicle (EV) production while reducing tau seed propagation. Our in vivo testing with cambinol shows that it can reduce the nSMase2 activity in the brain after oral administration. Our molecular docking and simulation analysis reveals that cambinol can target the DK-switch in the nSMase2 active site.
[en] Highlights: • Phe-Trp (FW) evoked the strongest enteroendocrine cell response out of 338 dipeptides. • Phe-Trp-Gly-Lys (FWGK) exhibited more potent hypotensive effects than FW in SHRs. • Vasorelaxing and antihypertensive effects of FWGK were associated with the CCK system. We previously reported that an orally administered dipeptide, Arg-Phe (RF), which causes enteroendocrine cell responses, lowered blood pressure in spontaneously hypertensive rats (SHRs). In this study, we found that Phe-Trp (FW), induced the most potent enteroendocrine cell responses out of total 338 dipeptides. An FW analogue, Phe-Trp-Gly-Lys (FWGK), which was effectively produced by tryptic digestion of bovine serum albumin, decreased blood pressure after oral administration. The minimum effective dose of FWGK (50 μg/kg) was 1/300 of that of RF (15 mg/kg). FWGK stimulated cholecystokinin (CCK) secretion in the enteroendocrine cells and exhibited vasorelaxing and antihypertensive effects via the CCK1 system.
[en] Wearing of the oral and labial piercing may cause many local and general complications developing early or late after the piercing insertion. The complications range from simple tooth damage to life-threatening situations. In prevention all piercing wearers have be followed up by a dentist twice a year at least. The teenage population has be informed about the piercing risks, especially on the tongue. (author)
[en] Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)
[en] To compare the efficacy and safety of oral misoprostol with prostaglandin E2 vaginal tablets for ripening of cervix and induction of labour at term. Study Design: A non blinded, randomised, controlled trial. Place and Duration of Study: Department of Obstetrics and Gynaecology, Pakistan Air Force Hospital, Air Headquarters Islamabad from July 2005 to January 2006. Patients and Methods: Hundred pregnant women with a singleton live pregnancy, at term (37-42 weeks) with cephalic presentation were selected for induction of labour for various indications having a Bishop's score of < or =5. These women were randomly allocated to receive either 100 micro gm of misoprostol rally repeated four hourly to a maximum of four doses or a 3mg PGE2 tablet vaginally repeated six hourly to a maximum of two doses. Main outcomes measured: Cervical score before and after oral misoprostol and prostaglandin E2 vaginal tablets, vaginal birth within 24 hours of first prostaglandin dose, no of patients having failed induction, caesarean sections (all), caesarean section for fetal distress and uterine hyperstimulation with associated changes in fetal heart rate. Results: Over the period of one year 100 women were recruited for the study, 50 to the misoprostol group and 50 to the vaginal prostaglandin E2 group. There was no significant differences between the two treatment groups in the primary outcomes: improvement in bishops score in both the groups, no of patients with failed induction in both the groups misoprostol 2/50 (4%) v PGE2 3/50 (6%) , vaginal birth achieved in 24 hours (misoprostol 27/50 (54%) v PGE2 29/50 (58%), caesarean sections 14/50 (28%) v 12/50(24%) caesarean section for fetal distress 4/50((8%) v 5/50(9%); uterine hyperstimulation with fetal heart rate changes 2/50 ((4%) v none in the PGE2 group.). Neonatal outcomes were not significantly different in the two groups. Conclusion: Oral misoprostol in strength of 100 micro gm has similar efficacy to vaginal PGE2 tablets for ripening of cervix and induction of labour, although difference in outcomes between the two routes is not significant but data on optimal dosage regimes and safety are still lacking. (author)
[en] The finished product I-131 solution, administered orally, must comply with certain microbiological limits established in provision 7352/99 of the National Administration of Drugs, Food and Medical Technology. Within the framework of compliance with this regulatory requirement, a deferred microbiological control was carried out on the Iodo-131 product, after 30 days of decay, to avoid contamination of the area and the dosimetric risk for the analyst. 89 batches corresponding to the productions of the years 2012/2013/2014 were analyzed, in all cases no microbial development was detected. The implementation of this technique generated an accumulation of counter samples in the installation and generation of waste. To evaluate the need or not to continue with hygienic controls in this type of radioactive products, where in addition to the aseptic conditions of the product it is important to control both the operator's exposure and the generation of waste; We proceeded to investigate the behavior of a strain of known concentration, E. coli in this case, located in a closed bottle inside the Iodo-131 product fractionation cell. Evaluating different parameters such as distance, concentration, exposure time and activity. With the above done to obtain conclusions for the subsequent performance of the hygienic control in future batches. (author)
[es]El producto terminado I-131 solución, de administración vía oral debe cumplir con ciertos límites microbiológicos establecidos en la disposición 7352/99 de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica. En el marco del cumplimiento de esta exigencia regulatoria se procedió a realizar el control microbiológico en el producto Iodo-131 en forma diferida, luego de 30 días de decaimiento, para evitar la contaminación del área y el riesgo dosimétrico para el analista. Se analizaron 89 lotes correspondientes a las producciones de los años 2012/2013/2014, en todos los casos no se detectó desarrollo microbiano. La implementación de esta técnica generó acumulación de contramuestras en la instalación y generación de residuos. Para evaluar la necesidad o no de continuar con los controles higiénicos en este tipo de productos radiactivos, donde además de las condiciones asépticas del producto es importante controlar tanto la exposición del operador como la generación de residuos; se procedió a investigar el comportamiento de una cepa de concentración conocida, E. coli en este caso, ubicada en un frasco cerrado dentro de la celda de fraccionamiento del producto Iodo-131. Evaluando distintos parámetros como distancia, concentración, tiempo de exposición y actividad. Con lo anterior hecho obtener conclusiones para la posterior realización del control higiénico en futuros lotes. (author)
[en] Highlights: • Tfh cell fate-mapping mouse was developed. • Tfh cells could be tracked from the effector phase to the memory phase. • Tfh-derived memory cells were localized in the T-B border area and T cell zone. The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato is inducibly expressed in CXCR5+ cells by tamoxifen administration. After the oral administration of tamoxifen, most Tfh cells in Peyer's patches (PP) from Cxcr5CreERT2R26Tomato mice were tdTomato+. To track antigen-specific Tfh cells in vivo, OVA-specific OT-II T cells derived from Cxcr5CreERT2R26Tomato mice were transferred to wild-type mice, and the recipient mice were immunized with OVA followed by tamoxifen administration. CXCR5+ T cells became tdTomato+ and were mainly located in B cell follicles and GC areas 8 days after immunization. Four weeks after immunization, tdTomato+ OT-II T cells migrated from B cell follicles to the T-B border area and T cell zone after CXCR5 downregulation and CCR7 upregulation. These results indicate that Cxcr5CreERT2R26Tomato mice are a useful tool for studying the cell fate of differentiated Tfh cells in vivo and therefore have implications for the development of therapeutic strategies for infectious and autoimmune diseases.