Dietary isoflavones, the modulator of breast carcinogenesis: Current landscape and future perspectives

Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, UV radiation, and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in BRCA1 and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender, race, ethnicity, weight, reproductive factors, exo- and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work (circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

Role of dietary phytochemicals in modulation of miRNA expression: Natural swords combating breast cancer

The National Cancer Institute had projected breast cancer (BC) as one of the topmost prevalent malignancies around the globe. In many cases, BC becomes resistant to chemotherapy, radiation and hormonal therapies. Traditional BC therapies are associated with adverse side effects, drug resistance and recurrence. Extensive research work has shown that these dietary phytochemicals (DPs) may exert therapeutic effects by regulating the miRNA expression. A large number of DPs have been researched as miRNA regulatory agents against BC and some other DPs have not yet been tested against BC. We have discussed the effects of curcumin, diallyl disulphide, 3,3′ diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane on regulation of expression of BC miRNAs in a wide range of in vitro and in vivo models. We have also shown some of the possible DPs (Oleanolic acid, capsaicin, benzyl isothiocyanate, epigallocatechin gallate, phenethyl isothiocyanate and ursolic acid) that have shown miRNA regulatory activities and have not yet been tested against BC miRNAs. Finally, current limitations, challenges, future perspectives of DPs and BC research are also critically discussed.

Plant-derived anticancer agents: A green anticancer approach

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

Development of cetyl dimethicone based water-in-oil emulsion containing botanicals: Physical characteristics and stability

The aim of current research was to develop a water-in-oil emulsion containing grape seed extract for application in cosmeceuticals. Finally grinded dried grape seeds powder was extracted with hydro alcoholic mixture. Emulsions consisting of different concentrations of cetyl dimethicone [Abile EM90], the nonionic emulsifier, liquid paraffin as oily phase and water as aqueous phase were developed. Color, odor, pH, viscosity, liquefaction, phase separation, centrifugation and thermal stability of the formulated emulsions were observed at various storage temperatures i.e. 8 +/- 0.5[degree sign] C, 25 +/- 0.5[degree sign] C, 40 +/- 0.5[degree sign] C and 40[degree sign] C +/- 0.5[degree sign] C with 70% RH. The stable formulation consist of 16% mineral oil, 4% of ABIL EM 90[registered sign], 4% grape seeds extract, 1% rose oil and 75% distilled water. All the results derived from this study showed good stability over the three months study period which indicates w/o emulsion can be used as carrier of 4% grape seeds extract to enhance desired effects when applied topically

Pharmacokinetic evaluation of ibuprofen controlled release matrix tablets using hydrophilic Eudragit® polymer and co-excipients

The present study was conducted to formulate controlled release dosage forms containing Ibuprofen with Eudragit® S 100 polymer. The tablets were formulated at three different ratios with the polymer to investigate the effect of different concentrations of polymer on in vitro drug release patterns/kinetics and in vivo absorption/pharmacokinetics. Pre-formulation studies were conducted including bulk density, tapped density, compressibility index, Hausner ratio and angle of repose. In vitro studies were conducted using phosphate buffer [pH 7.4] as dissolution medium. In vivo performance was evaluated using albino rabbits. Physico-chemical characteristics [i.e. dimensional tests, weight variation, hardness, friability and drug content determination] fell in the USP acceptable limits. The compressibility index was found to range between 12.02 +/- 0.01% and 18.66 +/- 0.03%, the Hausner ratio varied between 1.02 +/- 0.01 and 1.19 +/- 0.10 and the angle of repose ranged from 15.19 +/- 0.01 to 24.52 +/- 0.10, all indicating better flow properties than the bulk-reference standard. Both bulk and tapped densities also fell in the USP acceptable range. Ibuprofen market tablets showed T[max] of 2.1 +/- 0.4h, which was significantly [P-value <0.05] lower compared to that of the reference standard [i.e. 4.09 +/- 1.3h]. Ibuprofen test formulation has a half-life [T[1/2]] of 16.9 +/- 2.5h, which was significantly [P-value<0.001] higher compared to that of the reference standard [i.e. 9.23 +/- 2.9h]. Eudragit® S 100 polymers can be used efficiently to develop directly compressed prolonged release tablets

Hippophae rhamnoides oil-in-water [O/W] emulsion improves barrier function in healthy human subjects

This study aimed to investigate the changes in skin barrier function in human subjects, following long-term topical application of Hippophae rhamnoides oil-in-water [O/W] emulsion whereas effects were measred using non-invasive probes like tewameter and corneometer. For this purpose, two stable oil-in-water [O/W] emulsions were formulated one with 5% Hippophae rhamnoides extract and other without extracts. Thirteen healthy, male subjects with a mean age 27 +/- 4.8 years were enrolled after their informed consents. The subjects were instructed to apply either the active formulation or the base formulation over 84 days while they were not known with the contents of either formulation. Biometrological measurements of skin hydration and transepidermal water loss [TEWL] were performed on both sides of the face in each volunteer at baseline and on day 07, 14, 21, 28, 42, 56, 70 and 84. The statistical analysis revealed formulation with 5% plant extract was superior compared to placebo [base formulation] as formulation with extract have shown extremely significant improvements in skin hydration [p=0.0003] and TEWL [p=0.0087] throughout treatment course. Moreover, a significant [p

Fabrication, physicochemical characterization and preliminary efficacy evaluation of a W/O/W multiple emulsion loaded with 5% green tea extract

Complex multiple emulsions have an excellent ability to fill large volumes of functional cosmetic agents. This study was aimed to encapsulate large volume of green tea in classical multiple emulsion and to compare its stability with a multiple emulsion without green tea extract. Multiple emulsions were developed using Cetyl dimethicone copolyol as lipophilic emulsifier and classic polysorbate-80 as hydrophilic emulsifier. Multiple emulsions were evaluated for various physicochemical aspects like conductivity, pH, microscopic analysis, rheology and these characteristics were followed for a period of 30 days in different storage conditions. In vitro and in vivo skin protection tests were also performed for both kinds of multiple emulsions i.e. with active (MeA) and without active (MeB). Both formulations showed comparable characteristics regarding various physicochemical characteristics in different storage conditions. Rheological analysis showed that formulations showed pseudo plastic behavior upon continuous shear stress. Results of in vitro and in vivo skin protection data have revealed that the active formulation has comparable skin protection effects to that of control formulation. It was presumed that stable multiple emulsions could be a promising choice for topical application of green tea but multiple emulsions presented in this study need improvement in the formula, concluded on the basis of pH, conductivity and apparent viscosity data.

Emulsões múltiplas complexas possuem excelente habilidade de agregar grandes quantidades de agentes cosméticos funcionais. Este estudo teve por objetivo encapsular grandes volumes de chá verde em uma emulsão múltipla clássica e comparar sua estabilidade com a emulsão múltipla sem o extrato do chá verde. Emulsões múltiplas são desenvolvidas usando cetil dimeticona copoliol como emulsificante lipofílico e o clássico polissorbato-80 como emulsificante hidrofílico. As emulsões múltiplas foram avaliadas por meio de vários aspectos fisico-químicos como condutividade, pH, análise microscópica e reologia. Estas características foram observadas por um período de 30 dias sob diferentes condições de armazenamento. Testes de proteção da pele in vivo e in vitro foram realizados para ambos os tipos de emulsões testadas, i.e. com o ativo em estudo (MeA) e sem ativo (MeB). Ambas as formulações apresentaram características comparáveis no que diz respeito aos diferentes fatores físico-químicos avaliados sob diferentes condições de armazenamento. A análise reológica mostrou que as formulações apresentaram comportamento pseudo-plástico sob contínuo estresse de cisalhamento. Os resultados dos testes in vivo e in vitro sobre a proteção da pele revelaram que a formulação ativa promoveu efeitos comparáveis à formulação controle. Nossos dados mostraram que emulsões múltiplas estáveis poderiam ser escolhas promissoras para a aplicação tópica do chá verde. Entretanto, a fórmula das emulsões múltiplas apresentadas neste estudo precisam ser melhoradas no que diz respeito ao pH, condutividade e viscosidade aparente.

Development, characterization and antioxidant activity of polysorbate based O/W emulsion containing polyphenols derived from Hippophae rhamnoides and Cassia fistula

The objective of this study was to develop a pharmaceutical O/W emulsion containing plant-derived polyphenol extracts and evaluate its stability and antioxidant activity. O/W emulsions were prepared using ionic surfactant polysorbate 80 (Tween 80®). The odorwas adjusted with few drops of blue sea fragrance. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was used to evaluate the antioxidant activity of the plant extracts alone and emulsions containing these extracts. Physical stability was assessed by submitting the emulsions to storage at 8 ºC, 25 ºC, 40 ºC and 40 ºC + 70% RH (relative humidity) for two months. Various physical characteristics of emulsions monitored, include color, creaming, liquefaction, centrifugation and pH. Brookfield rotational rheometer was used to determined viscosities and rheological behavior of emulsions. Different types of emulsion were determined microscopically, while pH values of emulsions were measured by a pH meter. Electrical conductivity data confirmed that the outer phase was water. Samples presented an acceptable pH value for an external topical use. Shear thinning behaviour was observed for all emulsions. The polyphenol-rich-plant-derived extracts alone and the extract containing emulsions showed good antioxidant activities. This research confirmed that the method used was suitable for preparing emulsions with Hippophae rhamnoids and Cassia fistula extracts, suggesting that those emulsions are suitable for topical use.

O presente estudo objetivou o desenvolvimento de uma emulsão farmacêutica óleo-água contendo extratos de plantas ricos em polifenóis, a comparação à sua formulação-controle e a avaliação de sua estabilidade, assim como de sua capacidade antioxidante. Extrato concentrado de Hippophae rhamnoids e Cassia fistula foi encapsulado no interior da fase oleosa da emulsão O/W. As emulsões foram preparadas usando o tensoativo iônico monooleato sorbital de polioxietileno (Tween 80®). O odor foi ajustado pela adição de algumas gotas de fragrância azul do mar. O ensaio do DPPH (1,1-difenil-2-picrilidrazil) foi utilizado para avaliar a atividade antioxidante dos extratos de plantas sozinhos e nas emulsões contendo os extratos. A estabilidade física foi avaliada submetendo os cremes a diferentes temperaturas de estocagem, como a 8 ºC, 25 ºC e 40 ºC e a 40% + 70% de umidade relativa por um período de 2 meses. As características físicas das emulsões foram monitoradas por 2 meses incluindo cor, cremosidade, liquefação, centrifugação e pH. O reômetro rotacional de Brookfield foi utilizado para determinar a viscosidade e o comportamento reológico das emulsões. O programa Rheocalc Brookfield foi utilizado para análise dos dados. As características organolépticas também foram avaliadas. O tipo de emulsão foi determinado microscopicamente, enquanto o pH das emulsões foi avaliado por meio de um pHmetro. A estabilidade farmacêutica esperada das emulsões foi alcançada dentro dos dois meses de estudo. Os resultados da condutividade elétrica confirmaram que a fase externa da emulsão era composta de água. O pH das amostras estava dentro da normalidade para uso tópico. A emulsão apresentou boa fragrância e pode ser retirada da pele com água após a aplicação, características desejáveis em emulsões O/W. Os extratos vegetais ricos em polifenóis isolados ou nas emulsões apresentaram boa atividade antioxidante. Nossos estudos confirmaram que o método utilizado foi adequado para preparar a emulsão semi-sólida contendo extratos de Hippophae rhamnoids e Cassia fistula. Nossos achados sugerem que emulsões contendo extratos de Hippophae rhamnoids e Cassia fistula são adequados para o uso tópico.

Knowledge, attitude and practices of barbers about hepatitis B and C and its transmission in Larkana city, Pakistan

Blood borne diseases impose heavy burdens on national economies and individual families due to costs arising from acute and chronic morbidity and mortality. Globally, 2 billion people are infected with hepatitis B virus [HBV]. An estimated 170 million persons are chronically infected with hepatitis C virus [HCV] and 3-4 million persons are newly infected each year. Transmission of hepatitis B and C through infected needles, blades, etc. is well known. Barbers are the important parts of community, as almost every man needs at least monthly visit to barber for hair dressing or shaving. In Pakistan the prevalence of shaving by barbers is reported to be as high as 34%-49% of the male population and it is important to know how barbers perceive the risks in relation to prevention of transmission of hepatitis B and C. To assess the knowledge and attitude of barbers regarding HBV and HCV and find out practices among barbers which may be responsible for transmission of HBV and HCV. Cross-Sectional Study. This study was carried out in the Larkana city during the months of March 2010 to April 2012. A list of the barbers was obtained from the union of barbers and sample was drawn from that sampling frame. There were 422 barbers shops in the city. For sampling purpose Larkana city was arbitrarily divided into five zones [East, West, Central, South and North] and then 10 shops randomly selected from each zone. There were 156 barbers available and eligible for interview. After informed verbal consent, 132 barbers agreed to participate in the study. Data was entered, analyzed by Statistical Program for Social Sciences [SPSS] version 13. A total 132 barbers were interviewed. The mean age of respondents was 28 +/- 10 years, mean years of experience in barbering was 12.7 +/- 10. More than half [63.6%] respondents were married. Majority of the respondents [84.8%] were resident of urban areas. 64% barbers have had knowledge that hepatitis B and C can be transmitted through blood transfusion and sexual contact. Only 6.1% had been vaccinated against the hepatitis B. 70% of the barbers disposed of used blades in regular garbage. 82% washed hands before and after shaving each client, 92.4% cleaned their instruments with disinfectant after shaving the, 99.2% barbers change the blade for each client. The knowledge of barbers regarding the transmission of hepatitis B and C was fairly good but majority of the barbers were not vaccinated against Hepatitis B though they were knew that vaccine is available against the hepatitis B

Retrospective analysis of 68 cases of dengue fever

Dengue is a mosquito-borne febrile disease caused by any of the four serotypes of the dengue virus transmitted by the Aedes aegypti mosquito. To study the clinical manifestations and treatment practices of Dengue cases in Pakistan. Retrospective record based analysis of dengue cases was performed in 3 general hospitals of Punjab during the 2010 outbreak. Only confirmed dengue IgM [ELISA] cases were further analyzed. WHO guidelines were used to evaluate the method of diagnosis and treatment. A total of 125 suspected dengue cases were admitted in these hospitals out of which dengue IgM was positive in 68 cases. Out of 68 cases, 60[88.2%] were of dengue fever and 8[11.8%] were dengue hemorrhage fever. Tourniquet test was not performed in any case. Sixty [88.8%] cases were males. The ages of the patients ranged from 4-60 years. Sixty five patients [96%] had fever followed by myalgia in 48[70%], headache in 33[48.8%], vomiting in 30[44.8%], weakness in 48[38.4%] and abdominal pain in 25[20%] cases. Thrombocytopenia was present in 60 cases [88.8%]. In 54[43.2%] cases platelet count was below 50,000. Leucopenia was present in 45 cases [66.4%]. Analgesics were prescribed in 52 cases. Fluid replacement therapy was used in 59[87.2%] which consisted of either dextrose water or ringer's lactate or normal saline. Antibiotics were prescribed in 47 cases. WHO guidelines were not followed in the diagnosis and management of these cases. WHO guidelines for the diagnosis and management of dengue fever were not followed thus leading to unnecessary treatment and waste of resources

investigation of mechanism of vasodilator activity of 17 beta-estradiol as being geriomic or non-genomic

To determine the vasodilator activity of 17 beta-estradiol as being genomic or non-genomic. The experimental protocol was divided into three groups, In group I aorta of rat was subjected to serial dilutions of norepinephrine and a standard concentration was selected, which produced optimal vasoconstriction. In group II, tissue was challenged with serial dilutions of 17 beta-estradiol in the presence of vascconstriction induced by the standard concentration of norepinephrine. Meanwhile in group III tissue was challenged with serial dilutions of 17 beta-estradiol in presence of standard concentration of norepinephrine after pretreatment with dactinomycin, which was used to inhibit protein synthesis so that genomic mode of action could be blocked. In our study 17 beta-estradiol, after pretreatment with dactinomycin, produced vasodilator activity in the same pattern as obtained without administration of protein synthesis inhibitor in the tissue preconstricted with norepinephrine [P<0.001]. The observations demonstrate the vasodilator activity of the 17 beta-stradiol to be its non-genomic action