FORMULATION AND EVALUATION OF A CHITOSAN-PVA-GELLAN INSULIN IMPLANT

Objective: The purpose of this study was to ascertain the applicability of degradable materials for fabrication of an insulin release system.Methods: Insulin implants were prepared by using poly (vinyl alcohol) (PVA), gellan and chitosan by solution casting method. The prepared implants were evaluated for swellability, content uniformity, potency and purity of insulin in implants, scanning electron microscopy studies, in vitro release studies, in vitro degradation studies using lysozyme, stability studies and circular dichroism spectroscopy.Results: The swelling degree of the implants was found to be in the range of 1.07-1.56. The diffusion coefficient of water through the implant was found to depend on the calcium chloride (CaCl2) concentration. The diffusion coefficient of insulin through the chitosan-PVA-gellan in the early stages was found to be in the range of 1.99´10-5 cm2/sec to 5.24´10-5 cm2/sec and at later stages in the range of 6.9´10-6 cm2/sec to 1.10´10-5 cm2/sec. The weight of the implants was 48±0.58 mg. The insulin content in the implants was 9.86±0.10 mg. The potency of insulin extracted from the implants was 27.11±0.75 U/mg or 95.12±2.61 % of the control insulin. The in vitro release studies showed that insulin was released completely in a period of 13-19 d depending on the composition of the implant. The increase in CaCl2 retarded the rate of insulin release whereas the increase in PVA content leads to the rapid release of insulin. The device was found to undergo significant weight loss due to enzyme mediated degradation.Conclusion: These studies provide validity for the potential utility of chitosan-PVA-gellan implant systems for the delivery of insulin. The studies also demonstrate that insulin maintained its integrity within the implant system. Implants showed the complete release of insulin in 19 d and the release of insulin from the implants depended on the amount of CaCl2

Evaluation of Mechanical and Metallurgical Properties of Dissimilar Materials by Friction Welding

AbstractFriction welding has been widely used to metals with dissimilar materials due to solid state joining process and shows good mechanical properties. In this study, the effect of mechanical and metallurgical properties of austenitic stainless steel (304L) and copper were experimentally investigated by tensile and hardness test while the metallurgical properties of optical, scanning electron microscopy and atomic force microscopy was used to analyze the microstructure of the welded joint. The joints were also examined with EDX line in order to understand the phases formed during welding. The material is evaluated by tensile test and their strength is determined and the hardness test measurements are examined in base metal and heat affected zone. The bonded materials of austenitic stainless steel and copper joint were produced by varying the friction pressure, upset pressure and rotational speed through Taguchi's orthogonal array. The highest tensile strength obtained in friction welded joint was 2.52% higher than parent material of copper. The effects of metallurgical characterization are discussed based on the microstructural studies

Optimizing the utility of anorectal manometry for diagnosis and therapy: A roundtable review and recommendations

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders

Solvent-induced β-hairpin to helix conformational transition in a designed peptide

An octapeptide containing a central Aib-Gly- segment capable of adopting β-turn conformations compatible with both hairpin (βII' or βI′) and helical (βI) structures has been designed. The effect of solvent on the conformation of the peptide Boc-Leu-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VIII; Boc: t-butyloxycarbonyl; OMe: methyl ester) has been investigated by NMR and CD spectroscopy. Peptide VIII adopts a well-defined β-hairpin conformation in solvents capable of hydrogen bonding like (CD3)2SO and CD3OH. In solvents that have a lower tendency to interact with backbone peptide groups, like CDCl3 and CD3CN, helical conformations predominate. Nuclear Overhauser effects between the backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding, backbone chemical shifts, and vicinal coupling constants provide further support for the conformational assignments in different solvents. Truncated peptides Boc-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VII), Boc-Val-Val-Aib-Gly-Leu-Val-OMe (VI), and Boc-Val-Aib-Gly-Leu-OMe (IV) were studied in CDCl3 and (CD3)2SO by 500 MHz 1H-NMR spectroscopy. Peptides IV and VI show no evidence for hairpin conformation in both the solvents. The three truncated peptides show a well-defined helical conformation in CDCl3. In (CD3)2SO, peptide VII adopts a β-hairpin conformation. The results establish that peptides may be designed, which are poised to undergo a dramatic conformational transition

Surgical Interventions and the Use of Device-Aided Therapy for the Treatment of Fecal Incontinence and Defecatory Disorders

The purpose of this clinical practice update expert review is to describe the key principles in the use of surgical interventions and device-aided therapy for managing fecal incontinence (FI) and defecatory disorders. The best practices outlined in this review are based on relevant publications, including systematic reviews and expert opinion (when applicable). Best Practice Advice 1: A stepwise approach should be followed for management of FI. Conservative therapies (diet, fluids, techniques to improve evacuation, a bowel training program, management of diarrhea and constipation with diet and medications if necessary) will benefit approximately 25% of patients and should be tried first. Best Practice Advice 2: Pelvic floor retraining with biofeedback therapy is recommended for patients with FI who do not respond to the conservative measures indicated above. Best Practice Advice 3: Perianal bulking agents such as intra-anal injection of dextranomer may be considered when conservative measures and biofeedback therapy fail. Best Practice Advice 4: Sacral nerve stimulation should be considered for patients with moderate or severe FI in whom symptoms have not responded after a 3-month or longer trial of conservative measures and biofeedback therapy and who do not have contraindications to these procedures. Best Practice Advice 5: Until further evidence is available, percutaneous tibial nerve stimulation should not be used for managing FI in clinical practice. Best Practice Advice 6: Barrier devices should be offered to patients who have failed conservative or surgical therapy, or in those who have failed conservative therapy who do not want or are not eligible for more invasive interventions. Best Practice Advice 7: Anal sphincter repair (sphincteroplasty) should be considered in postpartum women with FI and in patients with recent sphincter injuries. In patients who present later with symptoms of FI unresponsive to conservative and biofeedback therapy and evidence of sphincter damage, sphincteroplasty may be considered when perianal bulking injection and sacral nerve stimulation are not available or have proven unsuccessful. Best Practice Advice 8: The artificial anal sphincter, dynamic graciloplasty, may be considered for patients with medically refractory severe FI who have failed treatment or are not candidates for barrier devices, sacral nerve stimulation, perianal bulking injection, sphincteroplasty and a colostomy. Best Practice Advice 9: Major anatomic defects (eg, rectovaginal fistula, full-thickness rectal prolapse, fistula in ano, or cloaca-like deformity) should be rectified with surgery. Best Practice Advice 10: A colostomy should be considered in patients with severe FI who have failed conservative treatment and have failed or are not candidates for barrier devices, minimally invasive surgical interventions, and sphincteroplasty. Best Practice Advice 11: A magnetic anal sphincter device may be considered for patients with medically refractory severe FI who have failed or are not candidates for barrier devices, perianal bulking injection, sacral nerve stimulation, sphincteroplasty, or a colostomy. Data regarding efficacy are limited and 40% of patients had moderate or severe complications. Best Practice Advice 12: For defecatory disorders, biofeedback therapy is the treatment of choice. Best Practice Advice 13: Based on limited evidence, sacral nerve stimulation should not be used for managing defecatory disorders in clinical practice. Best Practice Advice 14: Anterograde colonic enemas are not effective in the long term for management of defecatory disorders. Best Practice Advice 15: The stapled transanal rectal resection and related procedures should not be routinely performed for correction of structural abnormalities in patients with defecatory disorders

Improving aneurysm-related outcomes: Nationwide benefits of endovascular repair

ObjectivesEndovascular aneurysm repair (EVAR) has changed the practice of abdominal aortic aneurysm (AAA) surgery. We examined a national Medicare database to establish the effect of EVAR introduction into the United States.MethodsA 5% random sample of inpatient Medicare claims from 2000 to 2003 was queried using International Classification of Diseases, 9th Revision (ICD-9) diagnosis and procedure codes. An EVAR procedure code was available after October 2000. Occurrences were multiplied by 20 to estimate yearly national volumes and then divided into the yearly Centers for Medicare and Medicaid Services (CMS) population of elderly Medicare recipients for rates per capita, reported as cases per 100,000 elderly Medicare recipients. Statistical analysis was performed by using χ2, Student’s t test, nonparametric tests, and multiple regression analysis, with significance defined as P ≤ .05.ResultsElective AAA repairs averaged 87.7 per 100,000 Medicare patients between 2000 and 2003, with EVAR has steadily increasing to 41% of elective repairs in 2003. From 2000 to 2003, overall elective AAA mortality declined from 5.0% to 3.7% (P < .001), while open repair mortality remained unchanged. EVAR patients are significantly older than patients treated with open repair. From 2000 to 2003 patients >84 years receiving EVAR increased to 62.7% (P < .001). Overall hospital length of stay (LOS) decreased from 8.6 days in 2000 to 7.3 days in 2003, P < .001, but increased for open AAA patients. EVAR patients were more likely to be discharged home rather than to skilled facilities. Average elective repair hospital charges were not different between groups, but Medicare reimbursement was lower for EVAR, with a higher proportion cases classified as DRG 111 (major cardiovascular procedure without complications). EVAR was used in 10.6% of ruptured AAA repairs in 2003, with a significant reduction in mortality compared with open repairs for rupture (31.8% vs 50.8%; P < .001).ConclusionsEVAR is replacing open surgery without an increase in overall case volume. EVAR is responsible for overall decrease in operative mortality even in ruptured aneurysms while decreasing utilization variables. Reimbursement to hospitals is shrinking, however

FORMULATION AND EVALUATION OF SIMVASTATIN GASTRORETENTIVE DRUG DELIVERY SYSTEM

Objective: The aim of this study was to formulate and evaluate gastro retentive drug delivery system (GRRDS) using an effervescent approach for simvastatin.Methods: Floating tablets were prepared using directly compressible polymers hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and carboxymethylcellulose sodium (NaCMC). The prepared tablets were subjected to pre-formulation studies like Compressibility index, Hausner ratio and post compression parameters like buoyancy/floating test and In vitro dissolution study.Results: Drug-excipient compatibility studies performed with the help of FTIR instrument indicated that there were no interactions. The DSC thermogram of the formulations revealed that crystalline form of simvastatin existed in the formulation which was confirmed by X-ray powder diffraction. Dissolution studies indicated that there was a decrease in the drug release with an increase in the polymer viscosity. The tablets prepared with low-viscosity grade HPMC K4M exhibited short Buoyancy Lag Time and floated for a longer duration as compared with formulations containing high viscosity grade HPMC K100M. The ‘n' value for dissolution studies for all the formulations was found to be in the range of 0.647 to 0.975 indicating non-Fickian or anomalous drug transport. Conclusion: The drug release rate and floating duration of tablets depended on the nature of the polymer and other added excipients. The release rate of the drug can be optimized by using different ratios of polymers and other excipients. The formulation F8 achieved the optimized batch and complied with all the properties of the tablets

Effect of V-shaped Ribs on Internal Cooling of Gas Turbine Blades

Thermal efficiency and power output of gas turbines increase with increasing turbine rotor inlet temperature. The rotor inlet temperatures in most gas turbines are far higher than the melting point of the blade material. Hence the turbine blades need to be cooled. In this work, simulations were carried out with the leading edge of gas turbine blade being internally cooled by coolant passages with V-shaped ribs at angles of 30°, 45° or 60° and at three aspect ratios (1:1, 1:2 and 2:3). The trailing edge of the blade was cooled by cylindrical and triangular pin-fin perforations in staggered and inline arrangements. Numerical analyses were carried out for each configuration of the cooling passages. The best cooling passages for leading edge and trailing edge were deduced by comparing the results of these analyses. It was found that using V-shaped ribs and fins induces a swirling flow, which in turn increases the velocity gradient and hence produces an improvement in heat transfer. The results show that under real time flow conditions, the application of V-shaped ribs and pin-fin perforations is a very promising technique for improving blade life

An Evaluation of the sliding Wear Behaviour of SiC Particles Reinforced Copper Alloy Composite Materials

The present paper aims at evaluation of the sliding wear behaviour of SiC particles reinforced copper (phosphor-bronze) alloy composite materials studied as a function of sliding speed and applied loads under unlubricated conditions. The content of SiC particles in the composites was varied from 1-5% in steps of 2% by weight. A pin-on-disc wear testing machine was used to evaluate the wear rate, in which EN24 steel disc was used as the counterface. Loads of 20-160 N in steps of 20 N and speeds of 1.25, 1.56, 1.87 m/s were employed. The results indicated that the wear rate of both the composites and the matrix alloy increased with increase in load and sliding speed. However, the composites exhibited lower wear rate than the alloys.It was found that above a critical applied load, there exists a transition from mild to severe wear both in the unreinforced alloy and in the composites. But the transition loads for the composites were much higher than that of the unreinforced alloy. The transition loads increase with the increase in weight % of SiC particles, but decrease with the increase in sliding speeds. SEM analysis of the wear surfaces as well as the sub-surfaces are used to explain the observations made

M.leprae binds to a 28-30 kDa phosphorylated glycoprotein of rat peripheral nerve

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