Ethanol Induces Microglial Cell Death via the NOX/ROS/PARP/TRPM2 Signalling Pathway

Microglial cells are the primary immune cell resident in the brain. Growing evidence indicates that microglial cells play a prominent role in alcohol-induced brain pathologies. However, alcohol-induced effects on microglial cells and the underlying mechanisms are not fully understood, and evidence exists to support generation of oxidative stress due to NADPH oxidases (NOX_-mediated production of reactive oxygen species (ROS). Here, we investigated the role of the oxidative stress-sensitive Ca2+-permeable transient receptor potential melastatin-related 2 (TRPM2) channel in ethanol (EtOH)-induced microglial cell death using BV2 microglial cells. Like H2O2, exposure to EtOH induced concentration-dependent cell death, assessed using a propidium iodide assay. H2O2/EtOH-induced cell death was inhibited by treatment with TRPM2 channel inhibitors and also treatment with poly(ADP-ribose) polymerase (PARP) inhibitors, demonstrating the critical role of PARP and the TRPM2 channel in EtOH-induced cell death. Exposure to EtOH, as expected, led to an increase in ROS production, shown using imaging of 2’,7’-dichlorofluorescein fluorescence. Consistently, EtOH-induced microglial cell death was suppressed by inhibition of NADPH oxidase (NOX) as well as inhibition of protein kinase C. Taken together, our results suggest that exposure to high doses of ethanol can induce microglial cell death via the NOX/ROS/PARP/TRPM2 signaling pathway, providing novel and potentially important insights into alcohol-induced brain pathologies

Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK)

<p>Abstract</p> <p>Background</p> <p>Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK) that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region.</p> <p>Study design</p> <p>A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR) was calculated.</p> <p>Results</p> <p>Out of total 174 patients, 130 (74.71%) showed ETR and 44 (25.28%) did not show ETR. In district Bunir, out of 52 patients, 36 (69.23%) showed ETR and 16 (30.79%) did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18%) were negative for HCV RNA and 8 (10.81%) were resistant to therapy. In Peshawar, out of 22, 16 (60%) were negative and 6 (40%) were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA), out of 18 only 10 (55.5%) were negative and 8 (44.45%) were positive for active HCV infection.</p> <p>Conclusion</p> <p>It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3) in KPK.</p

Multi–drug resistance and &#946;–lactamase production among clinical isolates of staphylococci

Thirty–eight isolates of staphylococci isolated from diseased eyes of human were distinguished as methicillin resistant S. aureus (MRSA) 11, methicillin sensitive S. aureus (MSSA) 19, and coagulase negative staphylococci (CNS) 8 isolates. Antibiotic resistance against &#946;–lactam antibiotics was exhibited by 81.81–100% of the isolates belonging to MRSA, followed by MSSA (0–89.47%) and CNS (25–87.50%). Similarly, resistance to other antibiotics like streptomycin, tetracycline, doxycycline and nalidixic acid was also higher among MRSA isolates than MSSA and/or CNS isolates. Overall resistance was higher to penicillin–G (78.95%) followed by ampicillin (73.68%), cefixime and nalidixic acid (68.42% each), cloxacillin (60.52%), streptomycin (57.89%), methicillin (39.40%) and least to tetracycline and doxycycline (21.05% each). Resistance to &#946;–lactam drugs was common and cross–resistance was observed in several strains. Multiple antibiotic resistance in staphylococci was exhibited by 73.68% of the isolates. All the MRSA strains showed resistance to multiple antibiotics. Minimum inhibitory concentrations (MIC) of &#946;–lactam antibiotics ranged from 6.25&#956;g/ml to 2000&#956;g/ml. High level of MIC value (&#8805;800&#956;g/ml) was detected against penicillin, ampicillin and cloxacillin in the 15, 7 and 21 isolates respectively. The &#946;–lactamases of few isolates showed substrate specificity, hydrolyzing one or more &#946;–lactam antibiotics. No significant difference was noticed in the production of &#946;–lactamase among the three groups of staphylococci (MRSA, MSSA and CNS). No co–relation was established between the resistance level against antibiotics and &#946;– lactamases production in the staphylococci isolates from diseased eyes. Staphylococci associated with the human eye infection showed resistance to &#946;–lactams and other antibiotics and &#946;–lactamase production is a common traits. Keywords: MRSA, &#946;–lactamase, antibiotics, antibiotic resistance, &#946;–lactamase, coagulase negative staphylococci Journal of Tropical Microbiology and Biotechnology Vol. 2(1) 2006: 18-2

Proyeksi Penerapan Kebijakan Pengenaan Cukai Pada Tas Plastik Di Indonesia

Penggunaan tas plastik pada saat melakukan pembelian barang sudah menjadi suatu fenomena umum di masyarakat. Tas plastik yang saat ini beredar umumnya terbuat dari polychlorinated biphenyl (PCB) yang membutuhkan waktu antara 100 sampai 500 tahun untuk mengurainya. Lamanya proses pengurain ini mengakibatkan jumlah sampah tas plastik memiliki dampak buruk bagi lingkungan. Beberapa negara di dunia sudah mencoba berbagai cara untuk mengurangi jumlah konsumsi tas plastik. Salah satunya dengan menerapkan kebijakan cukai pada tas plastik. Irlandia dan Denmark merupakan dua negara yang sukses dengan kebijakan cukai plastik. Indonesia sebagai negara yang juga memiliki masalah dengan sampah tas plastik diharapkan dapat menerapkan kebijakan serupa agar dapat mengurangi konsumsi tas plastik dan menjaga lingkungan agar tidak tercemar oleh sampah tas plastik. Jenis penelitian yang digunakan adalah kajian literatur. Penelitian ini dilakukan dengan cara melakukan telaah pustaka terhadap dokumen, jurnal, maupun artikel yang terkait dengan topik penelitian. Penelitian ini dianalisis menggunakan Metode Analisis Miles dan Hubberman. Tujuan dari kajian ini adalah untuk memperoleh informasi mengenai efektifitas, faktor penyebab keberhasilan dan faktor penyebab kegagalan kebijakan cukai tas plastik di Irlandia, China, Denmark, Botswana dan Afrika Selatan serta barang pengganti tas plastik dan potensi penerimaan negara apabila Indonesia menerapkan kebijakan ini. Hasil dari analisis ini adalah faktor keberhasilan dan faktor kegagalan dari 5 negara tersebut terfokus pada strategi penerapan tarif, peran pemerintah dan edukasi masyarakat serta produk substitusi tas plastik sehingga dapat digunakan sebagai pertimbangan. Proyeksi penerimaan negara dengan data yang sudah diolah menggambarkan jumlah penerimaan negara apabila kebijakan cukai tas plastik diterapkan di Indonesia

Analisis Layanan Drive Thru Di KPP Pratama Kebayoran Baru Dua Jakarta Selatan.

Penelitian ini berfokus pada keunggulan dan kelemahan layanan drive thru di KPP Pratama Kebayoran Baru Dua Jakarta Selatan. Tujuan dari penelitian ini adalah untuk mengetahui keunggulan dan kelemahan dari layanan Drive Thru. Jenis penelitian ini menggunakan pendekatan kualitatif deskriptif. Teknik pengumpulan data berasal dari wawancara dan dokumentasi. Metode analisis yang digunakan adalah metode analisis data model Miles dan Huberman. Hasil penelitian ini menunjukan bahwa analisis layanan drive thru di KPP Pratama Kebayoran Baru Dua Jakarta Selatan berdasarkan keunggulan yaitu sudah tepat terhadap teori karena memiliki SDM yang unggul dan baik. Pada kelemehan juga sudah tepat terhadap teori karena kurangnya lahan, sosialisasi dan jangka waktu pengadaan layanan drive thru tersebut

Factors Influencing Taxpayers Willingness to Participate in the Voluntary Disclosure Program

Penelitian ini bertujuan untuk menguji pengaruh pengetahuan tentang program pengungkapan sukarela, sanksi perpajakan, dan norma subjektif terhadap kemauan wajib pajak untuk berpartisipasi dalam program pengungkapan sukarela. Responden dalam penelitian ini berjumlah 100 Wajib Pajak Orang Pribadi yang terdaftar di KPP Pratama Banyuwangi dan dikumpulkan menggunakan metode survey dengan instrumen kuesioner dan penentuan sampel menggunakan metode purposive sampling. Metode analisis yang digunakan adalah analisis regresi linear berganda untuk menguji pengaruh dengan menggunakan uji t melalui aplikasi SPSS. Hasil penelitian ini menunjukkan bahwa variabel pengetahuan tentang program pengungkapan sukarela, sanksi perpajakan, dan norma subjektif berpengaruh positif terhadap kemauan wajib pajak untuk berpartisipasi dalam program pengungkapan sukarela

Burial and exhumation history of a Lesser Himalayan schist: Recording the formation of an inverted metamorphic sequence in NW India

Coupled analysis of the pressure–temperature (PT) evolution and accessory phase geochronology of a single sample reveals the burial-uplift history of part of the Lesser Himalaya during the Middle Miocene. Phase-equilibria calculations indicate that a peak temperature of 600–640 °C followed burial to approximately 25 km depth. Laser-ablation monazite geochronology yields a weighted mean 206Pb/238U age of 11.1 ± 2.0 Ma and a Tera-Wasserburg Concordia intercept age of 10.6 ± 0.9 Ma, with no distinguishable age difference between matrix and inclusion grains. Considerations of the likelihood of excess 206Pb further suggest that the crystallization age lies in the range 9–10 Ma. Textural analysis suggests that monazite grew during prograde metamorphism. Peak metamorphic conditions were followed by exhumation and cooling, forming a distinctively tight PT path closure. Both the shape of this path and its relatively young prograde phase distinguish Lesser Himalayan evolution from that typically inferred for the High Himalaya, and allow exploration of the thermal mechanisms that operated in the western Himalaya during the interval ca. 23–6 Ma. The PTt history is characteristic of footwall heating due to rapid overthrusting of hot rock (the Higher Himalaya), followed by incorporation into a thrust sheet that exhumed the sequence rapidly enough to preserve an inverted metamorphic gradient