Bioequivalence study of two brands of phenytoin sodium 100mg formulations in healthy adult male rabbits

The objective of the study was to compare the bioavailability of a single oral 100 mg dose of two brands of phenytoin sodium formulations available in the Nepalese market. Formulation B was taken as test drug and compared with the innovator brand which was taken as reference standard. A randomized, two-way crossover study was done in six healthy adult male rabbits. All six rabbits received a single oral 100 mg dose of both the formulations with a two-week washout period between the formulations. Blood samples for plasma phenytoin levels were collected at 0.25, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours. The pharmacokinetic parameters of the two brands of phenytoin sodium calculated were area under the concentration versus time curve from time zero to 24 hours (AUC 0-24), Area under the Curve from time zero to infinity (AUC(0-infinity)), peak plasma concentration (C-max) and time of peak concentration (t(max)). Formulation B failed to comply in terms of Area under the Curve (AUC), an important pharmacokinetic parameter to test bioequivalency, which was tested at significance level 0.05. This showed that the test formulation is not bioequivalent with the innovator. Taken together, our preliminary findings suggest that further studies in a large population is needed before switching phenytoin brands once a patient is carefully titrated to a given phenytoin brand

TNFα-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury

TNFα-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated macrophages, modulates inflammation; however, its mechanism of action and role in the activation of macrophages are not fully understood. Here we observed markedly augmented LPS-induced inflammatory lung injury and mortality in TSG6−/− mice compared with WT (TSG6+/+) mice. Treatment of mice with intratracheal instillation of TSG6 prevented LPS-induced lung injury and neutrophil sequestration, and increased survival in mice. We found that TSG6 inhibited the association of TLR4withMyD88, thereby suppressing NF-κB activation. TSG6 also prevented the expression of proinflammatory proteins (iNOS, IL-6, TNFα, IL-1β, and CXCL1) while increasing the expression of antiinflammatory proteins (CD206, Chi3l3, IL-4, and IL-10) in macrophages. This shift was associated with suppressed activation of proinflammatory transcription factors STAT1 and STAT3. In addition, we observed that LPS itself up-regulated the expression of TSG6 in TSG6+/+ mice, suggesting an autocrine role for TSG6 in transitioning macrophages. Thus, TSG6 functions by converting macrophages from a proinflammatory to an anti-inflammatory phenotype secondary to suppression of TLR4/NF-κB signaling and STAT1 and STAT3 activation

Co-existence of gastric adenocarcinoma and neuroendocrine carcinoma: a rare entity

A mixed adenoneuroendocrine carcinoma is a tumor composed of both adenocarcinoma and neuroendocrine carcinoma components, with each comprising  at least one-third of the lesion, as defined by the World Health Organization classification of neuroendocrine neoplasms in 2010.. A 67-years-old male was admitted to the hospital with symptoms suggesting gastric cancer. Histopathology examination from endoscopic biopsy revealed adenocarcinoma. Later partial gastrectomy specimen examination the lesion show presence of well differentiated adenocarcinoma along with neuro endocrine carcinoma.</p

Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/1/pros23533_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/2/pros23533.pd

Relativity in cosmologically preferred frame and the UHECR paradox

The Greisen-Zatsepin-Kuzmin (GZK) cutoff (5 × 1019eV) of special relativity in the observed ultra high energy cosmic rays (UHECR) spectrum is one of the most puzzling paradoxes in physics. Experimentally a number of cosmic ray events have been detected above this GZK limit which is known as UHECR paradox. We propose a resolution of this paradox through a modification of the relativistic kinematics keeping in mind that it should not lead to predictions different from those of special relativity in the well tested domains. It is shown that theoretical limit in UHECR spectrum can be explained in the framework of Lorentz invariance violation (LIV) theories which assume the existence of a preferred frame. The present paper proposes that the velocity of the solar system with respect to the rest frame of the universe plays a role in explaining the paradox. DOI: http://dx.doi.org/10.3126/bibechana.v11i0.10375   BIBECHANA 11(1) (2014) 17-2

Knowledge and attitude on mental disorder among adults in Putalibazar Municipality of Syangja district of Nepal

Purpose: To assess knowledge and attitude on mental disorder among adults in Putalibazar Municipality of Syangja district. Materials and methods: A descriptive cross-sectional study was conducted among adults of the aged group (18-64 years) in Putalibazar Municipality of Syangja district of Nepal. A semi-structured questionnaire was prepared for data collection. Similarly, the Likert scale was used to assess respondent’s attitude levels. SPSS 20 version and MS-Excel were used to analyze the data. The questionnaire was translated into the Nepali language during data collection. Results: The majority (57.3%) respondents responded mental disorder is a health condition involving changes in feeling and emotions. More than half (54.7%) respondents were having poor knowledge and the rest (45.3%) respondents were having a good level of knowledge on mental disorders. Respondents involved in a private job, government job and NGO/INGO have the highest, and housewives have the lowest level of knowledge regarding the mental disorder. Three-fifth respondents (59.7%) were having a negative attitude and the rest two-fifth respondents (40.3%) were having a positive attitude towards mental disorders. Also, the level of knowledge was having a statistically significant relationship with the education (p=0.02) and occupation (p=<0.001) of the respondents. The level of attitude was having a statistically significant relationship with the level of knowledge of the respondents (p=0.004). Conclusions: Good level of knowledge regarding mental disorders was lagging among respondents and a negative attitude seems high. There is an urgent need for public awareness among the adults living in this location. Mass media and anti-stigma campaigns can equally play a vital role to bring change in the attitude level of the respondents