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.     

Post-transplant infections: single center experience from the developing world.

OBJECTIVE: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. METHODS: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. RESULTS: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). CONCLUSIONS: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.     

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.