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

Empowering Local Communities through Tourism Entrepreneurship: The Case of Micro Tourism Entrepreneurs in Langkawi Island

The tourism sector has a huge effect in developing countries by providing immense economic opportunities to the local community. Entrepreneurship has been identified as essential actors for creating job opportunities, generating income, increasing standard of living and generally growing the economy. Using the random sampling approach, the questionnaires were distributed to the tourism entrepreneurs in the tourism attraction area in Langkawi Island. During the survey period, only a total of 263 entrepreneurs completed the questionnaires. The objective of this study is to explore the economic empowerment of the tourism entrepreneurship in contributing to income level, creating job opportunities and increasing standard of living. The findings of the study clearly show that the tourism entrepreneur activities contribute positively to income level, jobs, opportunities and standard of living of the local community

Indirect immunofluorescence screening of potential arthritic autoantibodies in systemic lupus erythematosus

Introduction: Joint involvement is common in systemic lupus erythematosus (SLE) patients, however, screening for joint specific autoantibodies in patients is not routinely performed. This may be due to the lack of known antigens and available tissue. The rat musculoskeletal tissue may be a suitable source of antigen to detect arthritic autoantibodies. Method: We tested plasma of SLE patients, with arthritis (N=9) and without arthritis (N=7) as well as plasma from normal individuals (N=7) on fresh sectioned tissue from rat plantar hind paw using indirect immunofluorescence method. Results: Binding of autoantibodies to striation in skeletal muscle cells in the tissue was clearly demonstrable in all samples from SLE with arthritis but not on slides incubated with plasma from normal or SLE without arthritis. Conclusion: Thus, rat plantar tissue may be suitable for detecting autoantibodies from SLE patients that may be involved in the pathogenesis of lupus arthritis

Immediate endoscopic management of complete iatrogenic anterior urethral injuries: A case series with long-term results

BACKGROUND: Urethral injury produces partial or complete disruption of the urethral integrity. Advances in endourology have made endoscopic management of most of these injuries feasible without greatly compromising the final result. We report our institutional experience of immediate endoscopic realignment of complete iatrogenic anterior urethral injury. METHODS: From May 1997 to May 2003, seven patients with complete anterior urethral disruption were managed by immediate endoscopy guided splinting of urethra. Retrograde urethroscopy, combined with fluoroscopic guidance and in some cases antegrade cystoscopy through a suprapubic stab cystostomy was performed. A guide wire was negotiated across the disruption. Later, a 16 F Foley catheter was placed for 1–3 weeks. Patients were followed up at 1, 3, 6 and 12 months and then yearly to assess the long-term outcome of endoscopic management. RESULTS: Immediate endoscopic realignment was achieved in all patients. Three patients developed recurrence at six months; that was treated by optical urethrotomy. Only one patient developed multiple recurrences over an average follow-up of 49.2 months (range 7 to 74 months). He was offered open end-to-end urethroplasty at twenty months after third recurrence. Thus immediate endoscopic realignment avoided any further intervention in four patients (57.14%); while after an additional optical urethrotomy, urethroplasty could be avoided in six patients (87.2%). CONCLUSION: Immediate endoscopic realignment of traumatic urethral disruption is a feasible, safe and effective treatment modality for management of patients with iatrogenic complete anterior urethral injuries

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Current Laser Treatments for Benign Prostatic Hyperplasia

The latest technical improvements in the surgical armamentarium are remarkable. In particular, advancements in the urologic field are so exceptional that we could observe the flare-up of robot-assisted laparoscopic radical prostatectomy for prostate cancer and laser prostatectomy for benign prostatic hyperplasia (BPH). Photoselective vaporization of the prostate (PVP) and holmium laser prostatectomy are the most generalized options for laser surgery of BPH, and both modalities have shown good postoperative results. In comparison to transurethral prostatectomy (TURP), they showed similar efficacy and a much lower complication rate in randomized prospective clinical trials. Even in cases of large prostates, laser prostatectomy showed comparable efficacy and safety profiles compared to open prostatectomy. From a technical point of view, PVP is considered to be an easier technique for the urologist to master. Furthermore, patients can be safely followed up in an outpatient clinic. Holmium laser enucleation of the prostate (HoLEP) mimics open prostatectomy because the adenomatous tissue is peeled off the surgical capsule in both procedures. Therefore, HoLEP shows notable volume reduction of the prostate similar to open prostatectomy with fewer blood transfusions, shorter hospital stay, and cost reduction regardless of prostate size. Outcomes of laser prostatectomy for BPH are encouraging but sometimes are unbalanced because safety and feasibility studies were reported mainly for PVP, whereas long-term data are mostly available for HoLEP. We need longer-term randomized clinical data to identify the reoperation rate of PVP and to determine which procedure is the ideal alternative to TURP and open prostatectomy for each patient

Effects of Health Insurance on Perceived Quality of Care Among Latinos in the United States

There is suggestive evidence that lower rates of health insurance coverage increases the gaps in quality and access to care among Latinos as compared with non-Latino whites. In order to examine these potential disparities, we assessed the effects of insurance coverage and multiple covariates on perceived quality of care. To assess the distribution of perceived quality of care received in a national Latino population sample, and the role of insurance in different patient subgroups. Telephone interviews conducted between 2007 and 2008 using the Pew Hispanic Center/Robert Wood Johnson Foundation Latino Health Surveys (Waves 1 and 2). Randomly selected Latino adults aged ≥18 years living in the United States. Pearson χ2 tests identified associations among various demographic variables by quality of care ratings (poor, fair, good, excellent) for the insured and uninsured (Wave 1: N = 3545). Subgroup analyses were conducted among Wave 2 participants reporting chronic conditions (N = 1067). Bivariate and multivariate analyses were conducted to estimate the effects of insurance, demographic variables and consumer characteristics on quality of care. Insurance availability had an odds ratio of 1.47 (95% CI, 1.22–1.76) net of confounders in predicting perceived quality of care among Latinos. The largest gap in rates of excellent/good ratings occurred among the insured with eight or more doctor visits compared to the uninsured (76.2% vs. 54.6%, P < .05). Future research can gain additional insights by examining the impact of health insurance on processes of care with a refined focus on specific transactions between consumers and providers’ support staff and physicians guided by the principles of patient-centered care

Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications

In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promisePublikacja w ramach programu Royal Society of Chemistry "Gold for Gold" 2014 finansowanego przez Uniwersytet Łódzk

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL