Ethnomedical Knowledge of Plants used by the Tribal people of Purandhar in Maharashtra, India

This study presents the results of a field survey of the plants used medically by the tribal people of Purandhar in Maharashtra, India. Tribes like Dhangars and Gowlis inhabit the dry deciduous forests of the region. This is an effort to record the valuable ethnomedical knowledge of these Purandhar tribes. A total of 77 species belonging to 30 families and 56 genera were included. These plants are used to treat various aliments, discomforts and diseases like whooping cough, asthma, diabetes, diphtheria, conjunctivitis, snake bite, scorpion bite, etc

A study of effect of Nigella sativa oil in paracetamol induced hepatotoxicity in albino rats

Background: Acetaminophen (paracetamol) toxicity is a common cause of drug‑induced hepatotoxicity in children and adults. Specific treatment of paracetamol induced hepatitis is available in the form of N‑acetylcysteine only. Nigella sativa (NS) is used for the treatment of various ailments. Many studies have shown that NS plant has hepatoprotective potential. Hence, this study study was carried out to explore the prophylactic and therapeutic effect of NSoil against hepatotoxicity induced by paracetamol.Methods: Hepatotoxicity was induced in rats by paracetamol and it was assessed using biochemical parameters such as serum (Sr.) alanine aminotransferase (ALT), Sr. aspartate aminotransferase (AST), Sr. bilurubin, Sr. alkaline phosphatase, and Sr. total protein. In addition, histopathological score was also assessed. The therapeutic and prophylactic effect of NSoil administration on paracetamol induced hepatotoxicity was investigated by using above mentioned biochemical and histopathological parameters.Results: Paracetamol administration leads to rise in serum liver enzymes ad fall in Sr. total protein levels. NS oil has heptoprotective effect. NS oil significantly reversed changes in serum levels of AST, ALT, alkaline phophatase, bilurubin, and total protein produced by paracetamol. Furthermore, histopathological changes produced by paracetamol were reversed.Conclusion: This study demonstrated that NS oil has hepatoprotective effect.NS oiladministration can prevent or reverse the hepatotoxicity induced by paracetamol

A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma

OBJECTIVES: Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity. MATERIAL AND METHODS: Primary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities. RESULTS: Eighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3-4 toxicities. CONCLUSION: On-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short

Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice

© 2015 Abdelraouf et al.Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC. Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently. Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features. Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

© 2015 Pender et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogenedriven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCRddPCRMutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma

Dizajniranje, sinteza, kinetika hidrolize i farmakodinamski profili konjugata aceklofenaka s histidinom i alaninom

The gastrointestinal toxicity associated with aceclofenac can be reduced by condensing its carboxylic acid group with methyl esters of amino acids like histidine and alanine to give amide linkage by the Schotten-Baumann method. Physicochemical characterization of the conjugates was carried out by various analytical and spectral methods. The synthesized conjugates were also subjected to in vitro hydrolysis in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF + 80 % human plasma at pH 7.4. The release of free aceclofenac from histidine and alanine conjugated aceclofenac showed negligible hydrolysis in SGF compared to SIF. This indicated that the conjugates do not break in stomach, but release aceclofenac in SIF. Both synthesized conjugates showed excellent pharmacological response and encouraging hydrolysis rate in SIF and SIF + 80 % human plasma. Marked reduction of the ulcer index and comparable increase in analgesic and anti-inflammatory activities were obtained in both cases compared to aceclofenac alone. These findings suggest that the conjugates are better in action compared to the parent drug and have fewer gastrointestinal side-effects.Gastrointestinalna toksičnost aceklofenaka može se umanjiti kondenzacijom karboksilne skupine aceklofenaka s metilnim esterima aminokiselina poput histidina i alanina, pri čemu se stvaraju nove amidne veze po Schotten-Baumannovoj metodi. Fizikokemijska karakterizacija konjugata provedena je različitim analitičkim i spektralnim metodama. Nadalje, praćena je hidroliza sintetiziranih konjugata in vitro u simuliranoj gastričnoj tekućini (SGF) pri pH 1,2, simuliranoj intestinalnoj tekućini (SIF) pri pH 7,4 i simuliranoj intestinalnoj tekućini s 80 % humane plazme pri pH 7,4. Oslobađanje aceklofenaka iz konjugata s histidinom, odnosno alaninom, bilo je zanemarivo u SGF-u, u odnosu na oslobađanje u SIF-u. To ukazuje da su konjugati stabilni u želucu, dok se u SIF-u iz njih oslobađa aceklofenak. Oba konjugata daju izvrstan farmakološki odgovor i zadovoljavajući stupanj hidrolize u SIF-u i smjesi SIF-a i humane plazme. Oba konjugata pokazala su značajno smanjenu ulcerogenost i pojačano analgetsko i protuupalno djelovanje u odnosu na aceklofenak. Rezultati ukazuju na prednost konjugata u odnosu na samu ljekovitu tvar

Studies on CGMS Based Short Duration Hybrids of Pigeonpea [Cajanus cajan (L.) Millsp.] in Terms of Combining Ability

To estimate combining ability, twenty seven hybrids were made from 12 parents in a line × tester mating design during Kharif 2015-16 and tested in a Randomized block design with three replications during Kharif 2016-17. Among these parents ICPL 161 and ICPL 149 had desirable GCA effect for grain yield per plant and its contributing characters. Ten crosses exhibited significant positive SCA effect for grain yield. Out of them most promising crosses in terms of grain yield were ICPA 2039 × ICPL 161, ICPA 2156 × ICPL 86022 and ICPA 2039 × ICPL 90048. On the basis of per se performance and combining ability, the parents ICPA 2039, ICPL 88039, ICPL 161 and ICPL 149 can be used for future hybridization programmes

Study of CGMS based Short Duration Hybrids of Pigeonpea [Cajanus cajan (L.) Millsp.] In Terms of Heterosis

Twenty seven pigeonpea [Cajanus cajan (L.) Millsp.] hybrids were developed by hand pollination using three CMS lines (A lines) and nine testers (R lines). These hybrids along with their parents and two standard checks (VL Arhar1 and ICPL 161) were evaluated in a randomized block design with three replications during kharif 2016-17 for the heterosis studies. Results indicated that the crosses ICPA 2039 x ICPL161 and ICPA 2039 x ICPL 90048 had manifested significant heterobeltiosis and standard heterosis over two checks viz., VL Arhar1 and ICPL 161 for grain yield per plant and yield contributing characters. The stability of these promising crosses can be studied across the different environments and feasibility for their commercial utilisation could be tested in further generations

Performance of Parents and Hybrids of Pigeonpea (Cajanus cajan (L.) Millsp.) in terms of Yield and Yield Contributing Characters

Twelve parents were used in the crossing programme to produce 27 hybrids in L×T fashion during kharif 2015-16. In the field conditions, parents and hybrids were planted in Randomized Block Design of three replications and evaluated for the performance in terms of yield and yield contributing characters during kharif 2016-17. Observations were recorded on ten characters viz., plant height, days to 50% flowering, days to maturity, number of primary branches per plant, number of secondary branches per plant, number of pods per plant, number of seeds per pod, 100 seed weight, grain yield per plant and harvest index. It was observed that increase in number of pods per plant directly contributed to increased yield. Among the twenty seven hybrids, ICPA 2039 × ICPL 161, ICPA 2039 × ICPL 90048 and ICPA 2039 × ICPL149 had high grain yield

Phase I clinical trials in patients with advanced non-small cell lung cancer treated within a Drug Development Unit: What have we learnt?

Objectives Despite advances in novel drug development for patients with advanced non-small cell lung cancer (NSCLC), there are still only a limited number of approved treatments. We therefore evaluated the clinical outcomes of patients with advanced NSCLC referred to a dedicated phase I clinical trials unit assessed baseline clinical factors associated with successful enrollment onto phase I trials.Material and methods We conducted a retrospective study involving patients with advanced NSCLC referred to the Drug Development Unit at the RMH between January 2005 and December 2013.Results 257 patients with advanced NSCLC were referred for consideration of phase I trials, of which only 89 (35%) patients successfully commenced phase I trials. The commonest reasons for not entering study included poor ECOG performance status and rapid disease progression. A multivariate analysis identified that ECOG performance status (0-1) and RMH prognostic score (0-1) were associated with successful enrollment onto phase I trials (p<0.001). Single agent therapies included novel agents against the phosphatidylinositol-3 kinase pathway, insulin growth factor-1 receptor and pan-HER family tyrosine kinases. These trial therapies were well tolerated and mainly associated with grade 1-2 adverse events, with a minority experiencing grade 3 toxicities. Nine (10%) patients, 4 with known EGFR or KRAS mutations, achieved RECIST partial responses. Median time to progression was 2.6 months and median overall survival was 8.1 months for patients enrolled.Conclusions Phase I trial therapies were generally well tolerated with potential antitumor benefit for patients with advanced NSCLC. Early referral to drug development units at time of disease progression should be considered to enhance the odds of patient participation in these studies