Drug Quality Control in Kenya: Observation in Drug Analysis and Research Unit during the Period 1996-2000

The Drug Analysis and Research Unit received and analyzed 261 drug samples over a five-year period, 1996 to 2000. Samples were received from regulatory authorities, local industry, non-governmental organizations, hospitals and private practitioners. The samples analyzed constituted 59.8 % locally manufactured and 40.2 % imported products. The overall rate of failure to comply with quality specifications set out in the respective monographs was 21.1 %. This represents 24.6 % and 16.2 % of the locally manufactured and imported drugs, respectively. Key Words: Quality control, active pharmaceutical ingredient content, dissolution. East and Central African Journal of Pharmaceutical Sciences Vol.5(2) 2002: 28-3

Quality of Antiretroviral Drugs Analyzed in the Drug Analysis and Research Unit During 2000-2003

During the period 2000-2003 the Drug Analysis and Research Unit received and analyzed 33 samples of antiretroviral drugs. Locally manufactured products accounted for 57.6 % of the samples, while the imported drugs constituted 42.4 %. The drugs consisted of single, double and triple component preparations. They were subjected to the identity, assay and dissolution tests. 30 samples (90.9 %) complied with compedial specifications for these tests, while 3 failed. The results obtained show that manufacture of quality generic antiretroviral drugs is achievable. Key Words: Antiretroviral, assay, dissolution, nucleoside reverse-transcriptase inhibitor East & Central African Journal of Pharmaceutical Sciences Vol.6(1) 2003: 20-2

Drug Quality Control in Kenya: Observation in the Drug Analysis and Research Unit During the Period 2001-2005

During the five-year period January 2001 to December 2005, the Drug Analysis and Research Unit received and analyzed 394 drug samples. Samples were received from regulatory authorities, local industry, non-governmental organizations, hospitals and private practitioners. The samples analyzed constituted 37.8 % locally manufactured and 62.2 % imported products. In contrast to previous years when failure rates of over 20 % were recorded, the overall rate of failure to comply with compendial quality specifications was 6.1 %, comprising of 8.7 % locally manufactured and 4.5 % imported drugs

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

Persistent demographic differences in colorectal cancer screening utilization despite Medicare reimbursement

BACKGROUND: Colorectal cancer screening is widely recommended, but often under-utilized. In addition, significant demographic differences in screening utilization exist. Insurance coverage may be one factor influencing utilization of colorectal cancer screening tests. METHODS: We conducted a retrospective analysis of claims for outpatient services for Washington state Medicare beneficiaries in calendar year 2000. We determined the proportion of beneficiaries utilizing screening fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, or double contrast barium enema in the overall population and various demographic subgroups. Multiple logistic regression analysis was used to determine the relative odds of screening in different demographic groups. RESULTS: Approximately 9.2% of beneficiaries had fecal occult blood tests, 7.2% had any colonoscopy, flexible sigmoidoscopy, or barium enema (invasive) colon tests, and 3.5% had invasive tests for screening indications. Colonoscopy accounted for 41% of all invasive tests for screening indications. Women were more likely to receive fecal occult blood test screening (OR 1.18; 95%CI 1.15, 1.21) and less likely to receive invasive tests for screening indications than men (OR 0.80, 95%CI 0.77, 0.83). Whites were more likely than other racial groups to receive any type of screening. Rural residents were more likely than urban residents to have fecal occult blood tests (OR 1.20, 95%CI 1.17, 1.23) but less likely to receive invasive tests for screening indications (OR 0.89; 95%CI 0.85, 0.93). CONCLUSION: Reported use of fecal occult blood testing remains modest. Overall use of the more invasive tests for screening indications remains essentially unchanged, but there has been a shift toward increased use of screening colonoscopy. Significant demographic differences in screening utilization persist despite consistent insurance coverage

Regulation of STIM1 and SOCE by the Ubiquitin-Proteasome System (UPS)

The ubiquitin proteasome system (UPS) mediates the majority of protein degradation in eukaryotic cells. The UPS has recently emerged as a key degradation pathway involved in synapse development and function. In order to better understand the function of the UPS at synapses we utilized a genetic and proteomic approach to isolate and identify novel candidate UPS substrates from biochemically purified synaptic membrane preparations. Using these methods, we have identified Stromal interacting molecule 1 (STIM1). STIM1 is as an endoplasmic reticulum (ER) calcium sensor that has been shown to regulate store-operated Ca2+ entry (SOCE). We have characterized STIM1 in neurons, finding STIM1 is expressed throughout development with stable, high expression in mature neurons. As in non-excitable cells, STIM1 is distributed in a membranous and punctate fashion in hippocampal neurons. In addition, a population of STIM1 was found to exist at synapses. Furthermore, using surface biotinylation and live-cell labeling methods, we detect a subpopulation of STIM1 on the surface of hippocampal neurons. The role of STIM1 as a regulator of SOCE has typically been examined in non-excitable cell types. Therefore, we examined the role of the UPS in STIM1 and SOCE function in HEK293 cells. While we find that STIM1 is ubiquitinated, its stability is not altered by proteasome inhibitors in cells under basal conditions or conditions that activate SOCE. However, we find that surface STIM1 levels and thapsigargin (TG)-induced SOCE are significantly increased in cells treated with proteasome inhibitors. Additionally, we find that the overexpression of POSH (Plenty of SH3′s), an E3 ubiquitin ligase recently shown to be involved in the regulation of Ca2+ homeostasis, leads to decreased STIM1 surface levels. Together, these results provide evidence for previously undescribed roles of the UPS in the regulation of STIM1 and SOCE function

Structural insights into the production of 3-hydroxypropionic acid by aldehyde dehydrogenase from Azospirillum brasilense

3-Hydroxypropionic acid (3-HP) is an important platform chemical to be converted to acrylic acid and acrylamide. Aldehyde dehydrogenase (ALDH), an enzyme that catalyzes the reaction of 3-hydroxypropionaldehyde (3-HPA) to 3-HP, determines 3-HP production rate during the conversion of glycerol to 3-HP. To elucidate molecular mechanism of 3-HP production, we determined the first crystal structure of a 3-HP producing ALDH, alpha-ketoglutarate-semialdehyde dehydrogenase from Azospirillum basilensis (AbKGSADH), in its apo-form and in complex with NAD(+). Although showing an overall structure similar to other ALDHs, the AbKGSADH enzyme had an optimal substrate binding site for accepting 3-HPA as a substrate. Molecular docking simulation of 3-HPA into the AbKGSADH structure revealed that the residues Asn159, Gln160 and Arg163 stabilize the aldehyde-and the hydroxyl-groups of 3-HPA through hydrogen bonds, and several hydrophobic residues, such as Phe156, Val286, Ile288, and Phe450, provide the optimal size and shape for 3-HPA binding. We also compared AbKGSADH with other reported 3-HP producing ALDHs for the crucial amino acid residues for enzyme catalysis and substrate binding, which provides structural implications on how these enzymes utilize 3-HPA as a substrate

Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with metabolic risk factors. Body mass index (BMI), waist circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) are used to predict the risk of obesity related diseases. However, it has not been examined whether these four indicators can detect the clustering of metabolic risk factors in Chinese subjects.</p> <p>Methods</p> <p>There are 772 Chinese subjects in the present study. Metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were identified according to the criteria from WHO. All statistical analyses were performed separately according to sex by using the SPSS 12.0.</p> <p>Results</p> <p>BMI, waist circumference and WHtR values were all significantly associated with blood pressure, glucose, triglyceride and also with the number of metabolic risk factors in both male and female subjects (all of P < 0.05). According to receiver operating characteristic (ROC) analysis, the area under curve values of BMI, waist circumference and WHtR did not differ in male (0.682 vs. 0.661 vs. 0.651) and female (0.702 vs. 0.671 vs. 0.674) subjects, indicating that the three values could be useful in detecting the occurrence of multiple metabolic risk factors. The appropriate cut-off values of BMI, waist circumference and WHtR to predict the presence of multiple metabolic risk factors were 22.85 and 23.30 kg/m2 in males and females, respectively. Those of waist circumference and WHtR were 91.3cm and 87.1cm, 0.51 and 0.53 in males and females, respectively.</p> <p>Conclusion</p> <p>The BMI, waist circumference and WHtR values can similarly predict the presence of multiple metabolic risk factors in Chinese subjects.</p