Single‑walled and multi‑walled carbon nanotubes based drug delivery system: Cancer therapy: A review.

Carbon nanotubes (CNTs) are advanced nano‑carrier for delivery of drugs especially anti‑cancer drugs. In the field of CNT‑based drug delivery system, both single‑walled carbon nanotubes (SWCNTs) and multi‑walled nanotubes (MWCNTs) can be used for targeting anticancer drugs in tissues and organs, where the high therapeutic effect is necessary. Benefits of the carbon nanotubes (CNTs) in drug delivery systems are; avoiding solvent usage and reducing the side effects. Therefore, the present review article described about achievement of SWCNTs and MWCNTs to deliver the anticancer drugs with different cancerous cell lines.

Clinicopathologic features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor mutational status.

INTRODUCTION: We performed retrospective analysis of 106 patients with lung cancer for which formalin‑fixed paraffin‑embedded tissues was available. Their epidermal growth factor receptor (EGFR) mutation status and treatment outcomes are described. MATERIALS AND METHODS: All patients with confirmed non–small cell lung cancer (NSCLC) during Jan 2008 to Dec 2010 were included. EGFR sequencing was performed with ABI PRISM 310 genetic analyzer. RESULTS: Forty‑two (39.6%) patients had mutation in one of the four exons characterized. Patients whose EGFR mutational status was not available at presentation before the start of treatment were started on chemotherapy, n = 46 (43.39%). If EGFR mutational analysis was available and mutations were present, the patients were started on either upfront tyrosine kinase inhibitor (TKI), n = 15 (14.15%) or if on chemotherapy arm were allowed to finish six cycles and then start with maintenance TKIs, n = 26 (24.52%). The median progression free survival for patients with and without mutations was 11 months (95% CI,7-14) and 9 months (95% CI,7-10) respectively. A median PFS of 14 months (95%CI, 12-16) was seen in the mutation‑positive group that received both chemotherapy followed by switch maintenance with TKIs versus 8 months (95%CI, 7-8 months) in the group that received only TKI. CONCLUSION: The prevalence of EGFR mutations in this population of NSCLC patients was 39.6% with exon 19 mutation being the most common. The observed benefit of addition of chemotherapy over TKI in EGFR mutation‑positive group raises the question, can we offer the therapy of chemotherapy–TKI combination to EGFR mutation‑positive lung cancer patients as shown in the present study.

An Unusual Presentation of Churg-Strauss Disease (Allergic Angiitis and Granulomatosis).

We present a case of a 45-year-old female with history of four days of fever and rash with swelling over both limbs diagnosed on postmortem autopsy as Churg-Strauss disease and further give a brief overview of the disease.

The foliar trichomes of Hypoestes aristata (Vahl) Sol. ex Roem. & Schult var aristata (Acanthaceae) a widespread medicinal plant species in tropical sub-Saharan Africa: with comments on its possible phylogenetic significance

The micromorphology of foliar trichomes of Hypoestes aristata var. aristata was studied using stereo, light and scanning microscopy (SEM). This genus belongs to the advanced angiosperm family Acanthaceae, for which few micromorphological leaf studies exist. Results revealed both glandular and non-glandular trichomes, the latter being more abundant on leaf veins, particularly on the abaxial surface of very young leaves. With leaf maturity, the density of non-glandular trichomes decreased. Glandular trichomes were rare and of two types: long-stalked capitate and globose-like peltate trichomes. Capitate trichomes were observed only on the abaxial leaf surface, while peltate trichomes were distributed on both adaxial and abaxial leaf surfaces.

Effects of abiotic stress on biomass and anthocyanin production in cell cultures of Melastoma malabathricum

Plant cell cultures could be used as an important tool for biochemical production, ranging from natural coloring (pigments) to pharmaceutical products. Anthocyanins are becoming a very important alternative to synthetic dyes because of increased public concern over the safety of artificial food coloring agents. Several factors are responsible for the production of anthocynin in cell cultures. In the present study, we investigate the effects of different environmental factors, such as light intensity, irradiance (continuous irradiance or continuous darkness), temperature and medium pH on cell biomass yield and anthocyanin production in cultures of Melastoma malabathricum. Moderate light intensity (301 - 600 lux) induced higher accumulation of anthocyanins in the cells. The cultures exposed to 10-d continuous darkness showed the lowest pigment content, while the cultures exposed to 10-d continuous irradiance showed the highest pigment content. The cell cultures incubated at a lower temperature range (20 ± 2 ºC) grew better and had higher pigment content than those grown at 26 ± 2ºC and 29 ± 2ºC. Different medium pH did not affect the yield of cell biomass but anthocyanin accumulation was highest at pH 5.25 - 6.25.

Targeting protein acetylation for improving cancer therapy.

Acetylation is one of the most important post-translational modification of proteins determining the structure, function and intracellular localization that plays an important role in the signal transduction pathways related to diverse cell functions, both during unstimulated and stress conditions. Protein acetylation in cells is regulated by a co-ordinated action of histone acetyl transferases (HAT) and histone deacetylases(HDAC) that ensures the maintenance of homeostasis and execution of activities related to damage response viz. DNA repair, cell cycle delay, apoptosis and senescence. Since inhibition of histone deacetylation, stalls the progress of many nuclear events including proliferation and damage response events on the one hand and the levels of deacetylases are elevated in many tumours on the other. Histone deacetylase has been among the targets for the development of anticancer drugs and adjuvant. The recent observation showing acetylation of proteins by calreticulin (an endoplasmic reticulum resident protein) with a high efficiency when polyphenolic acetates are the acetyl group donating molecules and acetyl CoA as weak substrate extends the realm of protein acetylation beyond HAT/HDAC combination. Elucidation of the relative roles of HAT/HDAC mediated acetylation viz. a calreticulin mediated acetylation in cell function under a variety of stress conditions would hold key to the design of drugs targeting protein acetylation system.

Abnormal Doppler flow velocimetry in the growth restricted foetus as a predictor for necrotising enterocolitis.

BACKGROUND: Obstetric decision- making for the growth restricted foetus has to take into consideration the benefits and risks of waiting for pulmonary maturity and continued exposure to hostile intra-uterine environment. Necrotising Enterocolitis (NEC) results from continued exposure to hostile environment and is an important cause of poor neonatal outcome. AIMS: To evaluate the predictive value of abnormal Doppler flow velocimetry of the foetal umbilical artery for NEC and neonatal mortality. SETTINGS AND DESIGN: A retrospective study carried out at a tertiary care centre for obstetric and neonatal care. MATERIALS AND METHOD: Seventy-seven neonates with birth weight less than 2000 gm, born over a period of 18 months were studied. These pregnancies were identified as having growth abnormalities of the foetus. Besides other tests of foetal well-being, they were also subjected to Doppler flow velocimetry of the foeto-placental vasculature. Obstetric outcome was evaluated with reference to period of gestation and route of delivery. The neonatal outcome was reviewed with reference to birth weight, Apgar scores and evidence of NEC. STATISTICAL ANALYSIS USED: Chi square test. RESULTS: In the group of patients with Absent or Reverse End Diastolic Frequencies (A/R EDF) in the umbilical arteries, positive predictive value for NEC was 52.6%, (RR 30.2; OR 264). The mortality from NEC was 50%. When umbilical artery velocimetry did not show A/REDF, there were no cases of NEC or mortality. Abnormal umbilical or uterine artery flow increased the rate of caesarean section to 62.5% as compared to 17.6% in cases where umbilical artery flow was normal. CONCLUSION: In antenatally identified pregnancies at risk for foetal growth restriction, abnormal Doppler velocimetry in the form of A/REDF in the umbilical arteries is a useful guide to predict NEC and mortality in the early neonatal period.

Clinical research on ayurvedic therapeutics: myths, realities and challenges.

Globally there is an increasing interest in alternative routes to health such as ayurveda. There is a need to conduct globally acceptable clinical research in ayurvedic therapeutics (AT). Some of the issues in investigating AT in randomised clinical trials (CT) are: selection of appropriate AT, non-drug and/or drug AT, identification of objective outcomes, devising adequate placebo/positive controls, difficulties of blinding, guarding against bias, duration of trials, number of patients, dose optimisation, etc. There is also a need to establish reasonable safety of this therapy in CT. If AT has to complete with new chemical entities and biotechnology products, clinical research and development of AT should be focussed on unmet medical needs utilising principles and practices of modern CT approaches.

Comparative bioavailability study of clonazepam after oral administration of two tablet formulations.

OBJECTIVE: To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. METHODS: A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. RESULTS: The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. CONCLUSION: Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand.

Stevens-Johnson syndrome and toxic epidermal necrolysis-challenges of recognition and management.

Skin adverse drug reactions (ADRs) generally present as transient erythematous macular/papular rashes. However these can many a times be the initial presentation of serious muco-cutaneous ADRs such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). The incidence of SJS varies from 1.2 to 6 per million patient-years and that of TEN to be 0.4 to 1.2 per million patient-years. The pathophysiological mechanism of SJS and TEN have not been fully elucidated. The aetiological factors of SJS and TEN are diverse; drugs being the cause in more than 80% cases of TEN and about 40-50% cases of SJS. Mucous membranes are affected in nearly all cases. The extent of epidermal sloughing may vary and forms a basis for the classification of an individual case as SJS or TEN. Prognosis of SJS is better than that of TEN; mortality rates being about 5% and 30%-40% respectively. Specific therapy for these conditions is yet not available. The use of systemic corticosteroids has been controversial. Early diagnoses can prevent/reduce the morbidity of such serious ADRs. This article provides a brief review of the clinical presentation and management of SJS and TEN.

Comparative bioavailability study of a conventional and two controlled release oral formulations of Tegretol (carbamazepine)--200 mg.

OBJECTIVES: To assess the bioquivalence of carbamazepine (CBZ) controlled release formulation A (Tegretol CR, local) vs formulation B (Tegretol CR, Basel) and confirm their controlled release characteristics by comparing with conventional formulation (Tegretol). METHODS: A three-way randomized cross-over bioavailability study was carried out using CBZ 200 mg tablets of conventional and two controlled release formulations in twelve healthy volunteers. Coded plasma samples were analysed for levels of CBZ by HPLC method. RESULTS: The mean Cmax, Tmax, t1/2 and AUC for formulation A were: 1.67 +/- 0.26 mcg/mL, 24 +/- 0 hr, 47.8 +/- 9.7 hr and 136.7 +/- 25.4 mcg/ml. h; for formulation B were 1.41 +/- 0.31 mcg/mL, 25 +/- 8 hr, 46.9 +/- 7.9 and 119 +/- 32.3 mcg/ml.h and for conventional formulation were 2.43 +/- 3.6 mcg/mL, 9.5 +/- 7.4 hr, 44.6 +/- 9.8 hr and 178.8 +/- 41.9 mcg/ml.h respectively. The fluctuation in plasma concentration within 24 h (peak:trough) were 11.7 +/- 8.14% with conventional formulation as compared to 0% and 1.2 +/- 3.98% with formulation A and B respectively. The mean Tmax for both the controlled release formulations was not statistically significant. On the basis of 90% confidence interval, mean AUC and Cmax values obtained after controlled release formulation A, though statistically significant (P < 0.05) lie well within the prescribed limits of 80-120% as compared to formulation B. Thus both the controlled release formulations were bioequivalent. In comparison to conventional formulation, both controlled release formulations gave lower Cmax, lower AUCs, higher Tmax values, less fluctuation in CBZ plasma concentrations, reduction in ratio of Cmax/AUC values, thus demonstrating controlled release characteristics of the formulation. CONCLUSIONS: Based on the above mentioned parameters both controlled release formulations are bioequivalent and demonstrate controlled release characteristics.

Drug-related problems and adverse drug events: negligence, litigation and prevention.

Since the inclusion of medical profession under Consumer Protection Act, Indian doctors are facing malpractice suits. The incidence of adverse events (AEs) is 3.4-3.7, of adverse drug events (ADEs) is 2.4-6.5 and of adverse drug reactions (ADRs) is 6.7 per 100 hospital admissions. The complications of drug-related problems (DRPs) include therapeutic failure (TF) in 23% and new medical problems (NMPs) in 10% and could lead to serious permanent disability and death in majority (42%). The incidence of negligence in serious ADEs and death is 34% and 51%, respectively. Proportion of preventable ADEs is 28-50%. Errors occur most often in prescribing (39-56%) and result in malpractice claims in 13-25% of cases. Rational prescribing, improved therapeutic knowledge through re-training and effective use of computers in prescribing could prevent errors and reduce economic consequences for patients, doctors and hospitals.

Comparison of absorption rate and bioavailability of two brands of carbamazepine.

OBJECTIVE: To assess the bioavailability of carbamazepine from two brands of carbamazepine--Tegretol 200 and Zen-200. METHODS: A two-way randomised cross-over bioavailability of carbamazepine was carried out in twelve healthy male volunteers. Coded plasma samples were analysed for levels of carbamazepine by high performance liquid chromatography (HPLC) method. Tegretol 200 and Zen-200 were tested for in-vitro dissolution profiles. RESULTS: The mean Cmax, Tmax and t1/2a for Tegretol 200 were: 2.17 +/- 0.42 mcg/mL, 11.67 +/- 6.37 h and 2.72 +/- 1.87 h; for Zen-200 were 3.10 +/- 0.05 mcg/mL, 3.50 +/- 2.11 h and 0.76 +/- 0.76 h respectively. These values were statistically significant. However AUC (0-96 h) value of 150.16 +/- 27.13 mcg/ml.h after Zen-200 was not statistically significant as compared to 128.68 +/- 20.22 mcg/ml.h after Tegretol 200. The in-vitro dissolution profiles of the two formulations were dissimilar. The fluctuations in CBZ levels after Tegretol 200 was significantly less as compared to Zen-200. The absorption profile as judged by parameter 'A' was 50.44 +/- 10.95 for Tegretol 200 and 42.49 +/- 18.89 for Zen-200. CONCLUSION: Based on parameter 'A' and other pharmacokinetic parameters, the marketed generic carbamazepine product, Zen-200 is not bioequivalent to Tegretol 200.

Familial gliomas : a case report.

Two non-twin brothers were found to have intracranial malignant neoplasms. The age of presentation was third and fourth decade but the onset was simultaneous, at the same time. Diagnosis in each of them was made by computed tomography and confirmed by histopathology. Elder among them had cellular ependymoma and the younger had oligodendroglioma. Both the brothers received radiotherapy post operatively and were surviving asymptomatically without any neurological deficit, leading active life as police constable, 12 months after surgical treatment.

Clinical relevance of reduced bioavailability of rifampicin.

Bioavailability (BA) of rifampicin (RMP) is a critical factor in successful treatment of tuberculosis. The BA of RMP can be reduced by pharmaceutical factors, patient factors and drug interactions. Failure of treatment and development of drug resistance are potential consequences of reduction in BA and it is necessary to understand and control the factors influencing BA of RMP.

An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate hypertension.

Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.

Endothelins and anti-endothelins.

Endothelins, endothelin-1 (ET1), endothelin-2 (ET2) and endothelin-3 (ET3), are the most potent vasoconstrictor peptides released by endothelial cells. ET production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products and cytokines, whereas nitric oxide and prostacyclin reduce ET production. ET bind to ETA and ETB receptors and produce marked and sustained rise in blood pressure, intense vasoconstriction of coronary arteries and have positive inotropic and chronotropic effects on myocardium. Besides, they influence neuroendocrine, renal and smooth muscle functions. ET appears to function mostly as a paracrine or an autocrine hormone. ET may have a role in hypertension, atherosclerosis, heart failure, coronary artery disease, renal insufficiency, vascular hypertrophy, respiratory and cerebrovascular conditions. Several antagonists of ET acting at receptor level or influencing endothelin converting enzyme (ECE) are under investigation and have great potential as agents for use in the treatment of wide spectrum of disease entities and as biologic probes for understanding the actions of ET in human beings.