Formulation and Evaluation of Tramadol HCl Matrix Tablets Using Carbopol 974P and 934 as Rate-Controlling Agents

Purpose: To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents.Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulosewere also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release modelsResults: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion.Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.Keywords: Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled releas

Posterior Microphthalmos Pigmentary Retinopathy Syndrome

Purpose: To report a case of a rare disease entity Posterior Microphthalmos Pigmentary Retinopathy Syndrome (PMPRS) in a 47-year-old female with a brief review of literature. Case Report: A 47-year-old woman presented with a history of defective vision with an associated difficulty in night vision. Clinical workup was done, which included a thorough ocular examination showing diffuse pigmentary mottling of fundus, ocular biometry showing short axial length with normal anterior segment dimensions, electroretinography showing extinguished response, optical coherence tomography showing foveoschisis, and ultrasonography showing thickened sclera–choroidal complex. Findings were consistent with those reported by other authors with PMPRS. Conclusion: Posterior microphthalmia with or without other ocular and systemic associations should be suspected in cases with high hyperopia. It is mandatory to carefully examine the patient at presentation and close follow-ups are needed to maintain visual function

Green finance, renewable energy investment, and environmental protection: empirical evidence from B.R.I.C.S. countries

Environmental degradation has become a severe concern for the globe; therefore, policymakers in emerging economies are trying to meet the environmental standards. Nowadays, economies have shifted their energy pattern from non-renewable to renewable energy (R.E.U.), but its cost is too high. Undoubtedly, the financial sector also performs well in facilitating such green activities. Therefore, the current study investigates the role of R.E.U. and green finance in environmental quality and collects the data for B.R.I.C.S. economies from 2000 to 2018. The study uses quantile regressions and other advanced techniques to deal with the problems of cross-sectional dependence (C.S.D.) and heterogeneity. The estimated outcomes show that green finance, R.E.U. consumption, and technical innovations perform well in securing the environment by reducing carbon emissions. Likewise, the environmental quality in selected economies is deteriorating due to the rise in non-R.E.U. consumption, economic progress, F.D.I., and trade openness. Therefore, it is time to reshape the local, national and regional growth policies concerning a green investment that can secure our environment. Also, this study proposes future pathways for green finance and other factors relevant to a sustainable environment

Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya

Background: The relationship between glucose-6-phosphate dehydrogenase (G6PD) deficiency and clinical phenomena such as primaquine-sensitivity and protection from severe malaria remains poorly defined, with past association studies yielding inconsistent and conflicting results. One possibility is that examination of a single genetic variant might underestimate the presence of true effects in the presence of unrecognized functional allelic diversity. Methods: We systematically examined this possibility in Kenya, conducting a fine-mapping association study of erythrocyte G6PD activity in 1828 Kenyan children across 30 polymorphisms at or around the G6PD locus. Results: We demonstrate a strong functional role for c.202G>A (rs1050828), which accounts for the majority of variance in enzyme activity observed (P=1.5 × 10-200, additive model). Additionally, we identify other common variants that exert smaller, intercorrelated effects independent of c.202G>A, and haplotype analyses suggest that each variant tags one of two haplotype motifs that are opposite in sequence identity and effect direction. We posit that these effects are of biological and possible clinical significance, specifically noting that c.376A>G (rs1050829) augments 202AG heterozygote risk for deficiency trait by two-fold (OR = 2.11 [1.12 - 3.84], P=0.014). Conclusions: Our results suggest that c.202G>A is responsible for the majority of the observed prevalence of G6PD deficiency trait in Kenya, but also identify a novel role for c.376A>G as a genetic modifier which marks a common haplotype that augments the risk conferred to 202AG heterozygotes, suggesting that variation at both loci merits consideration in genetic association studies probing G6PD deficiency-associated clinical phenotypes. </p

MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC) specifically, the standard isoform (CD44s) has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway.</p> <p>Methods</p> <p>In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested.</p> <p>Results</p> <p>MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA.</p> <p>Conclusion</p> <p>The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing.</p

Percutaneous injuries among dental professionals in Washington State

BACKGROUND: Percutaneous exposure incidents facilitate transmission of bloodborne pathogens such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV). This study was conducted to identify the circumstances and equipment related to percutaneous injuries among dental professionals. METHODS: We used workers' compensation claims submitted to the Department of Labor and Industries State Fund during a 7-year period (1995 through 2001) in Washington State for this study. We used the statement submitted by the injured worker on the workers' compensation claim form to determine the circumstances surrounding the injury including the type of activity and device involved. RESULTS: Of a total of 4,695 accepted State Fund percutaneous injury claims by health care workers (HCWs), 924 (20%) were submitted by dental professionals. Out of 924 percutaneous injuries reported by dental professionals 894 (97%) were among dental health care workers in non-hospital settings, including dentists (66, 7%), dental hygienists (61, 18%) and dental assistants (667, 75%). The majority of those reporting were females (638, 71%). Most (781, 87%) of the injuries involved syringes, dental instruments (77, 9%), and suture needles (23%). A large proportion (90%) of injuries occurred in offices and clinics of dentists, while remainder occurred in offices of clinics and of doctors of medicine (9%), and a few in specialty outpatient facilities (1%). Of the 894 dental health care workers with percutaneous injuries, there was evidence of HBV in 6 persons, HCV in 30 persons, HIV in 3 persons and both HBV and HVC (n = 2) exposure. CONCLUSION: Out of hospital percutaneous injuries are a substantial risk to dental health professionals in Washington State. Improved work practices and safer devices are needed to address this risk

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Excitation of unidirectional exchange spin waves by a nanoscale magnetic grating

Magnon spintronics is a prosperous field that promises beyond-CMOS technology based on elementary excitations of the magnetic order that act as information carriers for future computational architectures. Unidirectional propagation of spin waves is key to the realization of magnonic logic devices. However, previous efforts to enhance the Damon-Eshbach-type nonreciprocity did not realize (let alone control) purely unidirectional propagation. Here we experimentally demonstrate excitations of unidirectional exchange spin waves by a nanoscale magnetic grating consisting of Co nanowires fabricated on an ultrathin yttrium iron garnet film. We explain and model the nearly perfect unidirectional excitation by the chirality of the magneto-dipolar interactions between the Kittel mode of the nanowires and the exchange spin waves of the film. Reversal of the magnetic configurations of film and nanowire array from parallel to antiparallel changes the direction of the excited spin waves. Our results raise the prospect of a chiral magnonic logic without the need for fragile surface states

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance