Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Respiratory and other health risks among poultry-farm workers and evaluation of management practices in poultry farms

The current study was conducted on eight poultry farms in Lahore and Sheikhupura to monitor environmental conditions, determine workers’ health status and assess the implementation of standard management practices. Environmental monitoring, a health questionnaire survey and a respiratory function test were carried out. Seventy-one respondents were selected for the health assessment survey and lung function test. The results showed that the evaluated air-quality parameters, except for temperature and humidity, were well below the permissible occupational limits. Maximum temperature recorded was 32.75 ºC, while the highest humidity level was 85.5%. Farms were shown to be compliant with standard guidelines and management practices. The workers’ health survey indicated lower prevalence of work-related symptoms as compared to previous studies. However, most workers were not subjected to overall physical hazards, 21.1% of workers suffered from heat-induced dermatosis, and 38% suffered from heat exhaustion. Eye problems (watery, redness and itchiness) were experienced by 16.9% to 31%. Reported respiratory symptoms included wheezing during colds (18.3%), wheezing other than during colds (1.4%), chest tightness (16.9%), shortness of breath along with chest tightness (9.9%), regular breathing difficulties (14.1%), and coughing (15.5%). Observed lung function pattern, as measured by FEV1/FVC ratio, was 87 ± 17.7, with 65% workers having ‘restrictive’ disorder and 21% normal lung function pattern, while 21% presented ‘obstructive’ lung function. The study concludes an overall better health and safety management in the selected poultry farms.

Respiratory and other health risks among poultry-farm workers and evaluation of management practices in poultry farms

The current study was conducted on eight poultry farms in Lahore and Sheikhupura to monitor environmental conditions, determine workers health status and assess the implementation of standard management practices. Environmental monitoring, a health questionnaire survey and a respiratory function test were carried out. Seventy-one respondents were selected for the health assessment survey and lung function test. The results showed that the evaluated air-quality parameters, except for temperature and humidity, were well below the permissible occupational limits. Maximum temperature recorded was 32.75 ºC, while the highest humidity level was 85.5%. Farms were shown to be compliant with standard guidelines and management practices. The workers health survey indicated lower prevalence of work-related symptoms as compared to previous studies. However, most workers were not subjected to overall physical hazards, 21.1% of workers suffered from heat-induced dermatosis, and 38% suffered from heat exhaustion. Eye problems (watery, redness and itchiness) were experienced by 16.9% to 31%. Reported respiratory symptoms included wheezing during colds (18.3%), wheezing other than during colds (1.4%), chest tightness (16.9%), shortness of breath along with chest tightness (9.9%), regular breathing difficulties (14.1%), and coughing (15.5%). Observed lung function pattern, as measured by FEV1/FVC ratio, was 87 ± 17.7, with 65% workers having ‘restrictive disorder and 21% normal lung function pattern, while 21% presented ‘obstructive lung function. The study concludes an overall better health and safety management in the selected poultry farms.(AU)

An assessment of Pakistani pharmacy and medical students’ knowledge of black box warnings / Una evaluación del conocimiento de estudiantes de medicina y de farmacia en Pakistán sobre alertas de medicamentos / Uma avaliação sobre o acesso de estudantes paquistaneses de medicina e farmácia ao conhecimento das advertências das caixas de tarja preta

Food and Drug Administration delivers the black box warnings (BBW) which should appear on the leaflets of medicines for patient awareness and the prescription of drugs indicating its highly fatal adverse effects to human body. The aim of this study was to assess the knowledge of Pakistani pharmacy and medical students about BBW. A questionnaire containing contents about BBW was given to the 1st, 2nd and 3rd professional year pharmacy and medical students from different pharmacy and medical institutes. A 76 percent survey response rate was observed. It was observed that student’s knowledge about BBW improves in association with the promotion in professional years of pharmacy and medical education. The results indicate that student’s knowledge about black box increases with the study level. Training in black box warnings should be implemented in pharmacy and medical institutions influencing the meaningful ways to educate and train pharmacy and medical students, and help these students to get recent knowledge about black box warnings so that, in future, they may perform an ethical practice in their respective fields.

La Agencia Reguladora de Alimentos y Medicamentos comunica alertas sobre medicamentos (AM), que debieran aparecer en los prospectos de medicinas, para el conocimiento de los pacientes y la prescripción de medicamentos, indicando sus efectos adversos fatales para el cuerpo humano. El objetivo de este estudio es averiguar el conocimiento de estudiantes de medicina y de farmacia sobre AM. Se entregó un cuestionario con contenidos sobre AM a estudiantes de farmacia y de medicina de primero a tercer año de diferentes institutos médicos y farmacéuticos. Se obtuvo un 76 por ciento de respuesta. Se observó que el conocimiento de los estudiantes sobre AM mejora asociado a la promoción en años profesionales de medicina y farmacia. Los resultados indican que el conocimiento de los estudiantes sobre alerta de medicamentos aumenta con el nivel de estudio. Debería implementarse la formación sobre alerta de medicamentos en farmacia y medicina y ayudar a los estudiantes a tener conocimiento actual sobre alerta de medicamentos de forma que, en el futuro, puedan realizar prácticas éticas en sus campos respectivos.

A Food and Drug Administration disponibiliza as advertências das caixas de tarja preta (BBW) que devem aparecer em bulas de medicamentos para conscientização de pacientes e a prescrição de drogas, indicando seus efeitos adversos altamente fatais para o corpo humano. O propósito deste estudo foi o de de inteirar a cerca do conhecimento de estudantes de medicina e farmácia sobre BBW. Um questionário com conteúdos sobre BBW foi dado a estudantes de farmácia e medicina, do 1º, 2º e 3º ano de diferentes instituições de ensino em farmácia e medicina. Foi observada uma taxa de 76 por cento de resposta dos pesquisados. Observou-se que o conhecimento de estudantes sobre BBW melhora quando se associa à promoção para anos seguintes da educação nas faculdades de farmácia e medicina. Os resultados indicam que o conhecimento dos estudantes sobre as caixas de tarja preta aumenta com o nível de estudo. Treinamento com caixas de tarja preta pode ser implementado em instituições de ensino de farmácia e medicina, influenciando de modo significativo as formas de educação e treinamento de estudantes de farmácia e medicina, e,assim, ajudar estes estudantes a obter conhecimentos recentes sobre medicamentos de tarja preta de modo que, no futuro, elas possam exercer uma prática ética em seus respectivos campos de atuação profissional.

Release of prednisolone and inulin from a new calcium-alginate chitosan-coated matrix system for colonic delivery.

Putative colonic release formulations of calcium (Ca)-alginate coated with chitosan containing two different actives, prednisolone and inulin, were prepared in three different sizes, beads (D50 = 2104 µm) and microparticles (D50 = 354 and 136 µm). The formulations were tested in standard phosphate buffer and biorelevant Krebs bicarbonate buffer at pH 7.4, and were further evaluated in the presence of the bacterium E. coli. Product yield and encapsulation were higher with prednisolone than with inulin. In Krebs bicarbonate buffer, a clear relationship between particle size and prednisolone release was observed. In contrast, release of inulin was independent of the particle size. In phosphate buffer, the particles eroded quickly, whereas in Krebs buffer, the particles swelled slowly. The difference in behavior can be attributed to the formation of calcium phosphate in the phosphate buffer medium, which in turn weakens the Ca-alginate matrix core. In the presence of E. coli, the formulations were fermented and the release of prednisolone was accelerated. In conclusion, the buffer media affects formulation behavior and drug release, with the bicarbonate media providing a better simulation of in vivo behavior. Moreover, the susceptibility of the formulations to bacterial action indicates their suitability as carriers for colonic drug delivery.

First report of a small supernumerary der(8;14) marker chromosome.

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.

Genetic polymorphism of the glutathione-S-transferase P1 gene (GSTP1) and susceptibility to prostate cancer in the Kashmiri population.

Glutathione-S-transferase P1 (GSTP1) is a critical enzyme of the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. To investigate the GSTP1 Ile105Val genotype frequency in prostate cancer cases in the Kashmiri population, we designed a case-control study, in which 50 prostate cancer cases and 45 benign prostate hyperplasia cases were studied for GSTP1 Ile105Val polymorphism, compared to 80 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of GSTP1 Ile105Val in our ethnic Kashmir population, i.e., Ile/Ile, Ile/Val and Val/Val, to be 52.4, 33.3 and 14.3% among prostate cancer cases, 48.5, 37.5 and 14% among benign prostate hyperplasia cases and 73.8, 21.3 and 5% in the control population, respectively. There was a significant association between the GSTP1 Ile/Val genotype and the advanced age group among the cases. We conclude that GSTP1 Ile/Val polymorphism is involved in the risk of prostate cancer development in our population.

Genetic differences between strains of Biomphalaria glabrata (Planorbidae) that are susceptible and unsusceptible to schistosomiasis.

Despite the implementation control programs, schistosomiasis continues to spread throughout the world. Among modern control strategies, vector control is currently being emphasized. Within this context, analysis of the genetic variability of intermediate host snails (Biomphalaria spp) is important because it allows identification of specific sequences of the genome of this mollusk related to susceptibility/resistance to Schistosoma mansoni infection. We investigated Brazilian albino (non-pigmented) and pigmented (wild type) strains of Biomphalaria glabrata; these strains differ in their susceptibility to S. mansoni infection. Genetic variability was studied by RAPD-PCR using different random primers. The electrophoretic patterns resulting from amplification showed specific polymorphic markers for the albino and pigmented strains of B. glabrata. This information will help in the identification and isolation of genes specifically related to susceptibility, demonstrating that RAPD-PCR is an appropriate and efficient methodological approach for analysis of the genetic variability of schistosomiasis vectors.

Schistosome/mollusk: genetic compatibility.

Schistosomiasis remains one of the most prevalent parasitic infections and has significant economic and public health consequences in many developing countries. Economic development and improvement in standard of living in these countries are dependent on the elimination of this odious disease. For the control of Schistosomiasis, understanding the host/parasite association is important, since the host parasite relationship is often complex and since questions remain concerning the susceptibility of snails to infection by respective trematodes and their specificity and suitability as hosts for continued parasite development. Thus, the long term aim of this research is to learn more about the genetic basis of the snail/parasite relationship with the hope of finding novel ways to disrupt the transmission of this disease. In the current research, genetic variability among susceptible and resistant strains within and between Biomphalaria glabrata and B. tenagophila was investigated using RAPD-PCR. The results indicate great genetic variations within the two snail species using three different primers (intrapopulational variations), while specimens from the same snail species showed few individual differences between the susceptible and resistant strains (interpopulational variation).

Schistosome/mollusk: genetic compatibility

Schistosomiasis remains one of the most prevalent parasitic infections and has significant economic and public health consequences in many developing countries. Economic development and improvement in standard of living in these countries are dependent on the elimination of this odious disease. For the control of Schistosomiasis, understanding the host/parasite association is important, since the host parasite relationship is often complex and since questions remain concerning the susceptibility of snails to infection by respective trematodes and their specificity and suitability as hosts for continued parasite development. Thus, the long term aim of this research is to learn more about the genetic basis of the snail/parasite relationship with the hope of finding novel ways to disrupt the transmission of this disease. In the current research, genetic variability among susceptible and resistant strains within and between Biomphalaria glabrata and B. tenagophila was investigated using RAPD-PCR. The results indicate great genetic variations within the two snail species using three different primers (intrapopulational variations), while specimens from the same snail species showed few individual differences between the susceptible and resistant strains (interpopulational variation).

Metformin plus low-dose glimeperide significantly improves Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)) without hyperinsulinemia in patients with type 2 diabetes mellitus.

OBJECTIVE: Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic beta-cells, which have been studied by using euglycemic/hyperinsulinemic clamps. However, it is difficult to study insulin resistance and beta-cell failure by these techniques in humans. Therefore, the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and beta-cell activity by using a mathematical model, Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)). RESEARCH DESIGN AND METHODS: Seventy type 2 diabetic patients were randomly assigned to one of three therapeutic regimens: (A) metformin + American Diabetic Association (ADA)-recommended diet + physical activity; (B) metformin + low-dose glimepiride + ADA diet + physical activity; or (C) ADA diet + physical activity (no drugs). Blood samples were obtained before and after the treatment to determine serum levels of fasting and post-prandial blood glucose, fasting insulin, and glycosylated hemoglobin (HbA1c), and HOMA(IR) and HOMA(beta-cell) were calculated. RESULTS: Fasting and post-prandial levels of glucose, HbA1c, and fasting insulin and calculated HOMA(IR) and HOMA(beta-cell) values before treatment were significantly higher than the respective values after treatment for all groups of patients (P < 0.01). Significant differences were also found when comparing the treatment-induced reduction in fasting blood glucose (51.8%; P < 0.01), post-prandial blood glucose (55.0%; P < 0.05), and HOMA(IR) (65.3%; P < 0.01) in patients of Group B with that in patients receiving other therapeutic options (Groups A and C). CONCLUSIONS: Metformin plus low-dose glimepiride (plus ADA diet and physical activity) is a more effective treatment for type 2 diabetes than either metformin plus ADA diet and physical activity or ADA diet and physical activity alone. Determination of HOMA(IR) and HOMA(beta-cell) values is an inexpensive, reliable, less invasive, and less labor-intensive method than other tests to estimate insulin resistance and beta-cell function in patients with type 2 diabetes mellitus.

Genetic markers between Biomphalaria glabrata snails susceptible and resistant to Schistosoma mansoni infection.

The analysis of the genetic variability related to susceptibility to Schistosoma mansoni infection in the vector of the genus Biomphalaria is important in terms of a better understanding of the epidemiology of schistosomiasis itself, the possible pathological implications of this interaction in vertebrate hosts, and the formulation of new strategies and approaches for disease control. In the present study, the genetic variability of B. glabrata strains found to be resistant or susceptible to S. mansoni infection was investigated using DNA amplification by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The amplification products were analyzed on 8% polyacrylamide gel and stained with silver. We selected 10 primers, since they have previously been useful to detect polymorphism among B. glabrata and/or B. tenagophila. The results showed polymorphisms with 5 primers. Polymorphic bands observed only in the susceptible strain. The RAPD-PCR methodology represents an adequate approach for the analysis of genetic polymorphisms. The understanding of the genetic polymorphisms associated to resistance may contribute to the future identification of genomic sequences related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni and to the development of new strategies for the control of schistosomiasis.

Genetic markers between Biomphalaria glabrata snails susceptible and resistant to Schistosoma mansoni infection

The analysis of the genetic variability related to susceptibility to Schistosoma mansoni infection in the vector of the genus Biomphalaria is important in terms of a better understanding of the epidemiology of schistosomiasis itself, the possible pathological implications of this interaction in vertebrate hosts, and the formulation of new strategies and approaches for disease control. In the present study, the genetic variability of B. glabrata strains found to be resistant or susceptible to S. mansoni infection was investigated using DNA amplification by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The amplification products were analyzed on 8 percent polyacrylamide gel and stained with silver. We selected 10 primers, since they have previously been useful to detect polymorphism among B. glabrata and/or B. tenagophila. The results showed polymorphisms with 5 primers. Polymorphic bands observed only in the susceptible strain. The RAPD-PCR methodology represents an adequate approach for the analysis of genetic polymorphisms. The understanding of the genetic polymorphisms associated to resistance may contribute to the future identification of genomic sequences related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni and to the development of new strategies for the control of schistosomiasis

Genetic variation between susceptible and non-susceptible snails to Schistosoma infection using random amplified polymorphic DNA analysis (RAPDs).

Susceptibility of snails to infection by certain trematodes and their suitability as hosts for continued development has been a bewildering problem in host-parasite relationships. The present work emphasizes our interest in snail genetics to determine what genes or gene products are specifically responsible for susceptibility of snails to infection. High molecular weight DNA was extracted from both susceptible and non-susceptible snails within the same species Biomphalaria tenagophila. RAPD was undertaken to distinguish between the two types of snails. Random primers (10 mers) were used to amplify the extracted DNA by the polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis (PAGE) and silver staining. The results suggest that RAPD represents an efficient means of genome comparison, since many molecular markers were detected as genetic variations between susceptible and non-susceptible snails.

The heroin epidemic in New York City: current status and prognoses.

Since 1989, heroin production worldwide has risen; in New York City, as its purity rose and prices fell, street-level markets were restructured and offered heroin in addition to cocaine and crack (which had been popular during the 1980s). While officials estimate that there are between 500,000 and one million hard-core, chronic heroin users nationwide, evidence of supplemental users heralding another heroin era includes: more overdoses and overdose deaths, greater demand for treatment, larger seizures of heroin at all levels of distribution and related arrests, and broader media coverage. In this article, the authors describe the characteristics of populations in which there may have been a percentage increase of new users, such as young middle- or upper-class European-Americans, young Puerto Ricans and recent Haitian and Russian immigrants. The abstinence of young African-Americans is also noted. The article ends with a preliminary needs assessment of the new users in the areas of health (including AIDS), housing, employment, treatment, arrest and imprisonment.

Crack: new directions in drug research. Part 1. Differences between the marijuana economy and the cocaine/crack economy.

Crack use and trafficking in low-income, minority communities in New York City have pushed into prominence many aspects of drug use/misuse and distribution which had formerly received inadequate attention. For example, the generation and reinvestment of drug incomes are important determinants of how various drugs are experienced. While in retrospect marijuana trafficking appears to have been an almost benign affair, crack trafficking is fast-paced, ruthless, steeped in violence, and impoverishes everyone who becomes engaged in it. In this part the differences between rates, volumes, and methods of income generation related to the use and distribution of marijuana and cocaine are elaborated. The contrast raises a question: Do economies like drug distribution follow a particular rhythmic pattern (capital accumulation during the benign marijuana passage followed by capital depletion in the overheated crack era), and how is it related to the changing demands of the regional economy? Viewed from this perspective, drug distributors and users appear not so much as "deviant" or "alienated" or as a "reserve pool of labor," but rather as a type of labor force which does indispensable work for the whole society.

From Ganja to crack: Caribbean participation in the underground economy in Brooklyn, 1976-1986. Part 2. Establishment of the cocaine (and crack) economy.

Shortages in the supply of marijuana, which became acute around 1981, caused Rastafari marijuana distributors very reluctantly to disregard religious injunctions against the use of any psychoactive substance except marijuana, and to experiment with the use and distribution of cocaine hydrochloride powder for intranasal administration and, later, for smoking (freebase and crack). This experimentation proved ruinous, and many were retired ignominiously from drug distribution. In the crack era they have been succeeded by completely new social, cultural, and economic arrangements.

From Ganja to crack: Caribbean participation in the underground economy in Brooklyn, 1976-1986. Part 1. Establishment of the marijuana economy.

The involvement of Caribbean youth in drug distribution (marijuana from the mid-1960s to 1981; cocaine hydrochloride powder and crack from 1981 to 1987, the time of writing) throughout the Circum-Caribbean area and in North America is described. Social, economic, and cultural outcomes of these engagements are highlighted, and the relationship between the underground economy of drugs and the corporate, capitalist economy is explored. Responding to high rates of unemployment and to other problems of migrant adaptation, young Caribbean African males established a multimillion dollar marijuana (ganja) trading network which linked cultivators on the islands with exporters/importers and street-level distributors in North American cities. By 1976, its participants had become Rastafarians, or followers of an ideology of self-reliance and indigenous development. Following its precepts, they reinvested marijuana revenues to revive cottage industry and agriculture. In Caribbean or minority neighborhoods, therefore, marijuana was a "positive vibration" and its distributors were lionized.