A critical evaluation of information in drug promotional brochures for validity as per WHO criteria

Background: Promotion of drugs through publication of promotional literature is a standard practice of pharmaceutical companies. This study is aimed at critically analyzing the drug promotional brochures.Methods: Observational study was conducted in Department of Pharmacology, Government Medical College Amritsar according to WHO guidelines. 100 brochures of different pharmaceutical companies were collected at random from various OPDs of a tertiary care hospital.Results: Only 14 % of total brochures demonstrated overall adherence to WHO guidelines. Safety information was lacking in 88%. Irrelevant pictures were found in 66% brochures while relevant illustrated information was included in only 23 % of brochures. Out of total illustrations found relevant (n=44), 45.5% did not quote any reference, and results didn’t match with original study in 11.4%.Conclusions: Our study points towards big lacuna in drug promotional brochures, an important source of drug information. Low percentage of adherence to the guidelines in the study reflects commercial interest of pharmaceutical companies and lack of will to correctly disseminate the drug related information

Effect of Sucrose and Growth Regulator's Level on Ginger Micropropagation

Ginger is most important cash crop of the hilly region of Nepal. However, availability of disease free planting material (rhizome) is the major problem faced by Nepalese farmers. Tissue culture is the only option to produce disease free rhizome of ginger. Suitable culture media combination is most important for the production of planting material in ginger through tissue culture. Therefore, effect of different level of sucrose and growth regulators on micro-propagation of ginger was studied using local collection ‘Kaski Local'. Early stage bud was used as explant. MS basal media with different level of sucrose and growth regulators was used as tissue culture media. 30 g/L sucrose, 30 g/L sucrose+5mg/L BA, 30 g/L sucrose+5 mg/L BA+0.5 mg/L NAA, 60 g/L sucrose+5mg/L BA, 60 g/L sucrose+5 mg/L BA+0.5mg/L NAA, 90 g/L sucrose+5 mg/L BA was used in this study. The explants were surface sterilized, cultured and incubated at 25±2°C, 90-95% relative humidity and 14:10 hours light:dark photoperiod for 8 weeks. Increased level of the sucrose increased the rhizome weight, however, addition of NAA produced more positive effect for this. MS basal media with 60 g/L sucrose+5 mg/L BA+0.5 mg/L NAA produced higher rhizome weight.Journal of Nepal Agricultural Research Council Vol.3 2017: 45-4

Coffee Production in Kavre and Lalitpur Districts, Nepal

Coffee (Coffea spp) is an important and emerging cash crop having potential to provide farmers employment and income generation opportunities. This crop is well adapted to the climatic conditions of mid-hills of Nepal. Thus, majority of the farmers are attracted towards cultivation of coffee because of demands in national and International market. Coffee is now becoming integral part of farming system in rural areas. However, information on performance of coffee and farmers response has not been well documented. Therefore, we undertook the present work to analyze demography, ethnicity, household occupation, literacy status, average land holding, coffee cultivation area, livelihood and sources of income of coffee growers, production and productivity, pricing, cropping pattern of the coffee and problesm faced by them in mid hill district of Kavrepalanchowk (hereafter ‘Kavre') and Lalitpur Districts. All the samples were taken randomly and selected from coffee producing cooperative of Kavre and Lalitpur. Our analysis showed that the male farmer dominant over female on adopting coffee cultivation in both districts with higher value in Kavre. Brahmin and Chetri ethnic communities were in majority over others in adopting the coffee cultivation. Literate farmers were more dominant over illiterates on adopting the coffee cultivation, The mean land holding was less, ranging from 0.15 to 2.30 ha for coffee cultivation, the history of coffee cultivation in Kavre showed that highest number of farmers were engaged in coffee farming from last 16 years. The mean yield of fresh cherry was 1027.20 kg/ha in Kavre, while it was 1849.36 kg/ha in Lalitpur. The study revealed that majority of the coffee plantations were between 6-10 years old. The major problems facing by coffee farmers were diseases spread, lack of irrigation facility and drying of plants. Despite of that the coffee farming was one of the rapidly emerging occupations among the farmers in both district of Nepal

Generating Demand for Alternative Protein in Low- and Middle- Income Countries: Opportunities and Experiences from Nutritious and Sustainable Market Solutions

Protein consumption and the demand for high-value nutritional products is growing rapidly in emerging markets. The projected growth of the alternative protein industry may position it well to meet this demand while addressing environmental sustainability and ethical standards. However, adoption of alternative protein products over traditional animal-sourced proteins is not always a clear choice, with factors such as consumer preferences and habitual behaviors influencing consumer decisions. Insights and considerations associated with generating demand for alternative protein products in low- and middle-income countries (LMIC) were identified through 3 case studies: the OBAASIMA Project in Ghana, the Egg Initiative in Ethiopia, and the World Food Programme Farming Coalition project in Armenia. Key findings emphasize the importance of local sourcing, positive messaging, and integration within existing diets and behaviors. Therefore, these factors will be essential for the adoption of novel alternative protein products in LMIC

Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis

B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL

Phenotype and Clinical Outcomes of Titin Cardiomyopathy.

BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis

Phenotype and Clinical Outcomes of Titin Cardiomyopathy

BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis

Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles

Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting

Enhancing Chemotherapy Response with Bmi-1 Silencing in Ovarian Cancer

Undoubtedly ovarian cancer is a vexing, incurable disease for patients with recurrent cancer and therapeutic options are limited. Although the polycomb group gene, Bmi-1 that regulates the self-renewal of normal stem and progenitor cells has been implicated in the pathogenesis of many human malignancies, yet a role for Bmi-1 in influencing chemotherapy response has not been addressed before. Here we demonstrate that silencing Bmi-1 reduces intracellular GSH levels and thereby sensitizes chemoresistant ovarian cancer cells to chemotherapeutics such as cisplatin. By exacerbating ROS production in response to cisplatin, Bmi-1 silencing activates the DNA damage response pathway, caspases and cleaves PARP resulting in the induction apoptosis in ovarian cancer cells. In an in vivo orthotopic mouse model of chemoresistant ovarian cancer, knockdown of Bmi-1 by nanoliposomal delivery significantly inhibits tumor growth. While cisplatin monotherapy was inactive, combination of Bmi-1 silencing along with cisplatin almost completely abrogated ovarian tumor growth. Collectively these findings establish Bmi-1 as an important new target for therapy in chemoresistant ovarian cancer