Quality Performance of Drugs Analyzed in the Drug Analysis and Research Unit (DARU) during the Period 2006-2010

During the period 2006-2010, the Drug Analysis and Research Unit analyzed 583 samples. The samples comprised 50.6% local and 49.4% imported products. Samples were subjected to compendial or in-house specifications. The failure rate was 12.2% for local products and 14.2% for imports.  Antibacterial products recorded the highest failure rate (21.6%) while  anticancers and drugs acting on the gastrointestinal, respiratory and  reproductive systems all passed in the tests performed. The failure rate for antiprotozoals, antimalarials, antifungals, anthelminthics and analgesics was 14.3%, 12.5%, 11.8%, 8.9% and 11.5%, respectively.Key words: DARU, drug product, assay, dissolution, antimicrobial, antimalaria

Water Solubilization Using Nonionic Surfactants from Renewable Sources in Microemulsion Systems

In this study the effect of temperature, NaCl and oils (hydrocarbons: C8–C16) on the formation and solubilization capacity of the systems of oil/monoacylglycerols (MAG):ethoxylated fatty alcohols (CEO20)/propylene glycol (PG)/water was investigated. The effects of the surfactant mixture on the phase behavior and the concentration of water or oil in the systems were studied at three temperatures (50, 55, 60 °C) and with varied NaCl solutions (0.5; 2; 11%). Electrical conductivity measurement, FTIR spectroscopy and the DSC method were applied to determine the structure and type of the microemulsions formed. The dimension of the microemulsion droplets was characterized by dynamic light scattering. It has been stated that the concentration of CEO20 has a strong influence on the shape and extent of the microemulsion areas. Addition of a nonionic surfactant to the mixture with MAG promotes an increase in the area of microemulsion formation in the phase diagrams, and these areas of isotropic region did not change considerably depending on the temperature, NaCl solution and oil type. It was found that, depending on the concentration of the surfactant mixture, it was possible to obtain U-type microemulsions with dispersed particles size distribution ranging from 25 to 50 nm and consisting of about 30–32% of the water phase in the systems. The conditions under which the microemulsion region was found (electrolyte and temperature—insensitive, comparatively low oil and surfactant concentration) could be highly useful in detergency

Protective Role for the Disulfide Isomerase PDIA3 in Methamphetamine Neurotoxicity

Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Methamphetamine treatment of mice also increased striatal PDIA3 expression. Treatment of primary striatal neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations

Toxicity, Tunneling and Feeding Behavior of the Termite, Coptotermes vastator, in Sand Treated with Oil of the Physic Nut, Jatropha curcas

Oil of the physic nut, Jatropha curcas L. (Malpighiales: Euphorbiaceae), was evaluated in the laboratory for its barrier and repellent activity against the Philippine milk termite Coptotermes vastator Light (Isoptera: Rhinotermitidae). The study showed that J. curcas oil had anti-feeding effect, induced reduction in tunneling activity and increased mortality in C. vastator. Behavior of termites exposed to sand treated with J. curcas oil indicated that it is toxic or repellent to C. vastator. Toxicity and repellent thresholds, were higher than those reported for other naturally occurring compounds tested against the Formosan subterranean termite

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma

BACKGROUND: Angiogenesis is one of the mechanisms most critical to the postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus, finding the molecular markers associated with angiogenesis may help identify patients at increased risk for recurrence and metastasis of HCC. This study was designed to investigate whether CD105 or CD34 could serve as a valid prognostic marker in patients with HCC by determining if there is a correlation between CD105 or CD34 expression and postoperative recurrence or metastasis. METHODS: Immunohistochemical staining for the CD105, CD34 and vascular endothelial growth factor (VEGF) antibodies was performed in 113 HCC tissue specimens containing paracarcinomatous tissue and in 14 normal liver tissue specimens. The quantitation of microvessels identified by anti-CD105 and anti-CD34 monoclonal antibodies and the semiquantitation of VEGF expression identified by anti-VEGF monoclonal antibody were analyzed in conjunction with the clinicopathological characteristics of the HCC and any available follow-up information about the patients from whom the specimens were obtained. RESULTS: CD105 was not expressed in the vascular endothelial cells of any normal liver tissue or paracarcinomatous liver tissue but was expressed in the vascular endothelial cells of all HCC tissue. In contrast, CD34 was expressed in the vascular endothelial cells of normal liver tissue, paracarcinomatous tissue, and HCC tissue in the following proportions of specimens: 86.7%, 93.8%, and 100%, respectively. The microvascular densities (MVDs) of HCC determined by using an anti-CD105 mAb (CD105-MVD) and an anti-CD34 mAb (CD34-MVD), were 71.7 ± 8.3 (SD) and 106.3 ± 10.4 (SD), respectively. There was a significant correlation between CD105-MVD and CD34-MVD (r = 0.248, P = 0.021). Although CD34-MVD was significantly correlated with VEGF expression (r = 0.243, P = 0.024), CD105-MVD was more closely correlated (r = 0.300, P= 0.005). The correlation between microscopic venous invasion and CD105-MVD, but not CD34-MVD, was also statistically significant (r = 0.254, P = 0.018). Univariate analysis showed that CD105-MVD was significantly correlated with the 2-year overall survival rate (P = 0.014); CD34-MVD was not (P = 0.601). Multivariate analysis confirmed that CD105-MVD was an independent prognostic factor and that CD34-MVD was not. CONCLUSION: The anti-CD105 mAb is an ideal instrument to quantify new microvessels in HCC as compared with anti-CD34 mAb. CD105-MVD as compared with CD34-MVD is relevant a significant and independent prognostic indicator for recurrence and metastasis in HCC patients

How many people have had a myocardial infarction? Prevalence estimated using historical hospital data

<p>Abstract</p> <p>Background</p> <p>Health administrative data are increasingly used to examine disease occurrence. However, health administrative data are typically available for a limited number of years – posing challenges for estimating disease prevalence and incidence. The objective of this study is to estimate the prevalence of people previously hospitalized with an acute myocardial infarction (AMI) using 17 years of hospital data and to create a registry of people with myocardial infarction.</p> <p>Methods</p> <p>Myocardial infarction prevalence in Ontario 2004 was estimated using four methods: 1) observed hospital admissions from 1988 to 2004; 2) observed (1988 to 2004) and extrapolated unobserved events (prior to 1988) using a "back tracing" method using Poisson models; 3) DisMod incidence-prevalence-mortality model; 4) self-reported heart disease from the population-based Canadian Community Health Survey (CCHS) in 2000/2001. Individual respondents of the CCHS were individually linked to hospital discharge records to examine the agreement between self-report and hospital AMI admission.</p> <p>Results</p> <p>170,061 Ontario residents who were alive on March 31, 2004, and over age 20 years survived an AMI hospital admission between 1988 to 2004 (cumulative incidence 1.8%). This estimate increased to 2.03% (95% CI 2.01 to 2.05) after adding extrapolated cases that likely occurred before 1988. The estimated prevalence appeared stable with 5 to 10 years of historic hospital data. All 17 years of data were needed to create a reasonably complete registry (90% of estimated prevalent cases). The estimated prevalence using both DisMod and self-reported "heart attack" was higher (2.5% and 2.7% respectively). There was poor agreement between self-reported "heart attack" and the likelihood of having an observed AMI admission (sensitivity = 63.5%, positive predictive value = 54.3%).</p> <p>Conclusion</p> <p>Estimating myocardial infarction prevalence using a limited number of years of hospital data is feasible, and validity increases when unobserved events are added to observed events. The "back tracing" method is simple, reliable, and produces a myocardial infarction registry with high estimated "completeness" for jurisdictions with linked hospital data.</p

Murine GRPR and Stathmin Control in Opposite Directions both Cued Fear Extinction and Neural Activities of the Amygdala and Prefrontal Cortex

Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD). Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR). Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction) than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction) and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction