The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats

Peer reviewedPublisher PD

Development and evaluation of ofloxacin orally disintegrating tablets

Bitter taste of ofloxacin, a broad spectrum bactericidal agent, is masked and orally disintegrating tablets were formulated. The bitter taste is masked by forming complex between drug and weak cation exchange resins, Tulsion 335 and Indion 204. Effect of pH and drug:resin ratio on the drug loading was studied. Maximum drug loading was observed at pH 6. Ratio of 1:2 of drug:resin masked almost complete bitterness of ofloxacin. Formation of complexes was confirmed by IR spectroscopy. Physical characterization of taste masked complexes was carried out. Present work envisages the taste masking of ofloxacin and development of orally disintegrating tablets. The effect of pH and resin quantities on drug loading were studied to find the optimum conditions of drug loading for complete taste masking. Effect of superdisintegrants like sodium starch glycolate, croscarmellose sodium and polyplasdone XL at varying level on physical parameters of compressed tablets was also assessed. The formulations containing 5 % w/w polyplasdone XL showed about 90 % of drug release within 5 minutes. No significant differences were observed in the physical parameters of resinates as well as tablets prepared from Tulsion 335 and Indion 204.O gosto amargo de ofloxacina, agente bactericida de largo espectro, é mascarado e formularam-se comprimidos dispersíveis. O sabor amargo é mascarado pela formação de complexo entre o fármaco e resinas de troca catiônica fraca, Tulsion 335 e Indion 204. Efeito do pH e da proporção fármaco: resina sobre a carga de fármaco foi estudada. Carga de fármaco máxima foi observada em pH 6. Proporção 1:2 do fármaco: resina mascarou quase completamente o gosto amargo de ofloxacina. A formação de complexos foi confirmada por espectroscopia no IV. Caracterização física dos complexos de sabor mascarado foi realizada. O presente trabalho preconiza o mascaramento do gosto de ofloxacina e desenvolvimento decomprimidos por via oral, se desintegrando. O efeito do pH e da resina quantidades de carga de fármaco foram estudadas paraencontrar as condições óptimas de carga de fármaco para dissimulação do saborcompleto. Efeito da superdisintegrants como amido glicolato de sódio, croscarmelose sódica e Polyplasdone XL em diferentes níveis de parâmetros físicos de comprimidos também avaliados foi avaliada. As formulações contendo 5 %w/w Polyplasdone XL mostraram cerca de 90% de libertação do fármaco no prazo de 5 minutos. Não foram observadas diferenças significativas nos parâmetros físicos de resinatosbem como comprimidos preparados a partir de Tulsion 335 e Indion 204

Trust and contextual engagement with the PEPPER system: The qualitative findings of a clinical feasibility study

Background and aims. PEPPER (Patient Empowerment through Predictive PERsonalised decision support) is an EU-funded research project which aims to improve self-management of type 1 diabetes (T1D). The system comprises an AI insulin bolus recommender, coupled with a safety system. The aim of the qualitative arm of this clinical feasibility study was to examine the context of participants’ interaction with the PEPPER system and identify incidents where bolus recommendations were trusted and accepted. Methods. This was a multicentre (UK and Spain) non-randomised open-labelled 6-week pilot study. Thirteen adults with T1D participated in weekly telephone interviews to explore the context of their interactions and responses to PEPPER. Data was thematically analysed through conceptual frameworks for engagement with healthcare digital behaviour change interventions. Results. Participants reported their key interactions as responding to PEPPER bolus recommendations, inputting carbohydrate values, interpreting continuous glucose monitoring (CGM) values through visualization of personal data and dealing with safety alarms. Two themes were associated with trust and engagement with the system; ‘feeling monitored’ and ‘feeling in control’. The incidents where participants trusted PEPPER also enhanced personal expertise of T1D through insights provided by the safety system such as low glucose basal insulin for pump users. Benefits were balanced against technical challenges of the system, which were used to improve the PEPPER application and enhance user experience. Conclusion. Some participants suggested that even access to PEPPER for a temporary period could positively influence self-management strategies. Contextual interviewing is a valuable tool in mobile application development for diabetes decision support systems

Proizvodne varijable koje utječu na svojstva peleta u peletiranju taljenjem sa smjesom voskova u sferonizatoru za laboratorijsku proizvodnju

The purpose of the study was to evaluate the suitability of laboratory scale spheronizer for the production of spherical pellets loaded with diltiazem hydrochloride by wax combination. The 1:1 combination of cetyl alcohol and hydrogenated castor oil, as low and high melting point waxes, were used. The various production variables affecting the different characteristics of pellets and the process efficiency were evaluated. Drug loaded pellets were evaluated for drug release in distilled water. Bowl temperature primarily affects the sphericity and adhesion of pellets to the bowl. Mass temperature has a pronounced effect on size, size distribution and sphericity of pellets. Wax concentration affects all characteristics of pellets but adhesion was least affected. The effect of these three variables can be compensated by optimizing the friction plate speed. It has been found that the highest yield of pellets (8501400 m) with maximum sphericity can be produced by using 45 C bowl temperature, 52 C mass temperature and 1400 rpm friction plate speed.Cilj rada bio je pripraviti sferične pelete u laboratorijskom sferonizatoru koristeći smjesu voskova. Cetilni alkohol kao vosak niskog tališta i hidrogenirano ricinusovo ulje kao vosak visokog tališta, upotrebljeni su u omjeru 1:1. Proučavan je utjecaj proizvodnih varijabli na svojstva peleta i efikasnost proizvodnje te brzinu oslobađanja ljekovite tvari iz peleta u destiliranoj vodi. Na sferičnost i adhezivnost peleta najviše utječe temperatura peletiranja. Temperatura mase ima i značajan utjecaj na veličinu, raspodjelu veličine peleta i sferičnost. Koncentracija voska utječe na sva svojstva peleta, ali najmanje na adhezivnost. Učinak tih triju varijabli može se kompenzirati optimiziranjem brzine ploče za trenje. Pronađeno je da najveće iskorištenje peleta (8501400 microm) s najboljom sferičnošću ako je temperatura peletiranja 45 oC, temperatura mase 52 oC, a brzina ploče za trenje 1400 rpm

Eptifibatide is associated with significant cost savings and similar clinical outcomes to abciximab when used during primary percutaneous coronary intervention for ST-elevation myocardial infarction: An observational cohort study of 3863 patients.

INTRODUCTION: Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. METHODS: This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. RESULTS: In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73-1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71-1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). CONCLUSION: This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

IV sotalol use in pediatric and congenital heart patients: A multicenter registry study

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to \u3e465 milliseconds after the infusion, with 3 (4%) to \u3e500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications

Quantification of Morphological Modulation, F-Actin Remodeling, and PECAM-1 (CD-31) Redistribution in Endothelial Cells in Response to Fluid-Induced Shear Stress Under Various Flow Conditions

Cardiovascular diseases (CVDs) are the number one cause of death globally. Arterial endothelial cell (EC) dysfunction plays a key role in many of these CVDs, such as atherosclerosis. Blood flow-induced wall shear stress (WSS), among many other pathophysiological factors, is known to significantly contribute to EC dysfunction. The present study reports an in vitro investigation of the effect of quantified WSS on ECs, analyzing the EC morphometric parameters and cytoskeletal remodeling. The effects of four different flow cases (low steady laminar (LSL), medium steady laminar (MSL), nonzero-mean sinusoidal laminar (NZMSL), and laminar carotid (LCRD) waveforms) on the EC area, perimeter, shape index (SI), angle of orientation, F-actin bundle remodeling, and platelet endothelial cell adhesion molecule-1 (PECAM-1) localization were studied. For the first time, a flow facility was fully quantified for the uniformity of flow over ECs and for WSS determination (as opposed to relying on analytical equations). The SI and angle of orientation were found to be the most flow-sensitive morphometric parameters. A two-dimensional fast Fourier transform (2D FFT) based image processing technique was applied to analyze the F-actin directionality, and an alignment index (AI) was defined accordingly. Also, a significant peripheral loss of PECAM-1 in ECs subjected to atheroprone cases (LSL and NZMSL) with a high cell surface/cytoplasm stain of this protein is reported, which may shed light on of the mechanosensory role of PECAM-1 in mechanotransduction