Treatment of Hepatitis C Virus Infection in Children Less than 12 Years of Age in Developing Countries

The treatment of hepatitis c virus (HCV) infection in children is difficult as few options are available. The standard therapy is combination pegylated interferon (PEG–IFN) α-2a or 2b and ribavirin, and the duration of therapy depends on HCV genotype. New oral drug therapies available for adults have still not been approved for treatment in children. Here, we review the causes of HCV infection in children, the therapeutic options for children, and the side effects of these treatments. The problems faced by physicians managing HCV infection in children less than 12 years of age in a developing country are also discussed.     

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.     

DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention

Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.     

Home diagnostic tests in the state of Qatar: a snapshot of public views, level of awareness and use

Background In Qatar, home diagnostic tests are available over the counter in community pharmacies. While possibly beneficial, these tests have the potential for harm if they are used in the absence of pharmacist counseling. Objectives To determine the public views, level of awareness and use of home diagnostic tests and to evaluate the extent of community pharmacists?? involvement in educating the public about these tests in Qatar. Setting Qatar??s Supreme Council of Health lists 245 community pharmacies in Qatar. Ten community pharmacies were randomly selected from the list as study sites. Method The investigators visited selected pharmacies on different weekdays and at different times of the day. Members of the public who appeared to be over 16?years of age and able to communicate in English or Arabic were randomly approached, provided with the study objectives, and requested to participate. Those who offered oral consent were anonymously interviewed using a multipart survey. Main outcome measures Measures include the public awareness and use of home diagnostic tests and the extent of community pharmacist involvement in educating the public about these tests. Results During the 5-month study period, 297 patients answered the survey (60?% response rate). Most respondents were aware of at least one home diagnostic test (98?%). The top four home diagnostic tests that the respondents had ever heard of included: thermometers (91?%), blood pressure monitors (91?%), blood sugar tests (86?%) and regular pregnancy tests (72?%). Seventy-one percent of respondents had performed at least one home diagnostic test. When asked about the factors that influenced their choice of the home diagnostic tests, the pharmacist was only cited by 7?% of respondents. The majority of respondents (>80?%) agreed that using a home diagnostic test is convenient, comfortable and helps them in early diagnosis and treatment of healthcare conditions. Only 31?% agreed that the pharmacist offered sufficient information on what to do in case the test result turns to be positive. The study results suggest that generally, the public has good attitudes and awareness of home diagnostic tests. However, the results indicate that Qatar community pharmacists are not sufficiently involved in public education about home diagnostic tests. Pharmacists should take a more active role in counseling the public on the proper use of these tests.     

Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis

Vascular endothelial growth factor (VEGF) is a potent angiogenesis mediator. Scant reports are available defining the role of VEGF in active and inactive tubercular meningitis (TBM) with no studies on brain tuberculoma. We quantified VEGF levels by enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) and serum in 20 cases each with active and inactive TBM as well as 22 cases of intraparenchymal tuberculoma. VEGF expression and microvessel angiogenesis quantification was done in 7 cases where tuberculomas were excised. Significantly increased VEGF levels in CSF were found in active TBM cases (106.0+/-50.0 pg/ml) compared to inactive TBM cases (14.7+/-10.0 pg/ml) (p<0.001). Mean serum VEGF levels in active TBM, inactive TBM and tuberculoma were 694.93+/-820.66 pg/ml, 499.61+/-238.33 pg/ml and 541.0+/-389.0 pg/ml, respectively. Immunohistochemical staining of excised tuberculoma demonstrated high expression of VEGF in granulomatous areas with intense positivity in inflammatory mononuclear cells, Langhan's giant cells as well as reactive astrocytes and fibrocytes. A strong positive correlation was observed between microvessel density and VEGF expression. Serial decrease in serum VEGF levels was observed with increasing duration of therapy in tuberculoma. We conclude that increased CSF and serum VEGF levels are a measure of activity of the disease in neurotuberculosis and its gradual decrease over a period of time is probably an indicator of therapeutic response.