In Vitro Insulin Release from Thermosensitive Chitosan Hydrogel

Recently, great attention has been paid to in situ gel-forming chitosan/glycerol-phosphate (chitosan/Gp) solution due to their good biodegradability and thermosensitivity. This in situ gel-forming system is injectable fluid that can be introduced into the body in a minimally invasive manner prior to solidifying within the desired tissue. At the present study, insulin release from chitosan/Gp solution has been investigated. Insulin in different concentrations was loaded in two formulations of chitosan/Gp solution and in vitro drug release was studied over a period of 3 weeks. Results indicated that the release of insulin from chitosan/Gp gel decreases by increasing in Gp salt and initial insulin concentration. Stability of released insulin was investigated by 8-anilino-1-naphthalenesulfonate probe. Results proved that insulin have been released in its native form. Because of simple preparation and administration, prolonged release of insulin and stability of released insulin, this in situ gel-forming system could be used as a controlled release delivery system for insulin.KEY WORDS: biodegradable, chitosan, controlled release, in situ forming, insulin     

Systematic Review and Meta-Analysis of Validation Studies on a Diabetes Case Definition from Health Administrative Records

Objectives

Health administrative data are frequently used for diabetes surveillance. We aimed to determine the sensitivity and specificity of a commonly-used diabetes case definition (two physician claims or one hospital discharge abstract record within a two-year period) and their potential effect on prevalence estimation.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched Medline (from 1950) and Embase (from 1980) databases for validation studies through August 2012 (keywords: “diabetes mellitus”; “administrative databases”; “validation studies”). Reviewers abstracted data with standardized forms and assessed quality using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. A generalized linear model approach to random-effects bivariate regression meta-analysis was used to pool sensitivity and specificity estimates. We applied correction factors derived from pooled sensitivity and specificity estimates to prevalence estimates from national surveillance reports and projected prevalence estimates over 10 years (to 2018).

Results

The search strategy identified 1423 abstracts among which 11 studies were deemed relevant and reviewed; 6 of these reported sensitivity and specificity allowing pooling in a meta-analysis. Compared to surveys or medical records, sensitivity was 82.3% (95%CI 75.8, 87.4) and specificity was 97.9% (95%CI 96.5, 98.8). The diabetes case definition underestimated prevalence when it was ≤10.6% and overestimated prevalence otherwise.

Conclusion

The diabetes case definition examined misses up to one fifth of diabetes cases and wrongly identifies diabetes in approximately 2% of the population. This may be sufficiently sensitive and specific for surveillance purposes, in particular monitoring prevalence trends. Applying correction factors to adjust prevalence estimates from this definition may be helpful to increase accuracy of estimates.     

Enhancing antimicrobial properties of dyed and finished cotton fabrics

1,2,3-Benzothiazole-7-thiocarboxylic acid-S-methylester (commercially known as Actigard^® AM-87) was utilized to impart cotton fabric durable antimicrobial properties. Finishing treatment was carried out under a variety of conditions. The latter were included, effect of pH, concentration of antibacterial agents, curing temperature and curing time. The effect of fabric construction, mercerization, and dyeing with different dyestuff were also investigated. The study was also extended to investigate the technical feasibility of combining antimicrobial finishing treatment in question with other finishing treatment generally carried out on cotton fabric, like soft finishing and crease recovery finishing. The treated fabrics were monitored for antimicrobial properties before and after washing. The treated fabrics were also evaluated for the physio-mechanical properties like fabric tensile strength, elongation at break (or bursting strength for knitted fabric), wettability, crease recovery angle, whiteness index and roughness. Results obtained show that, the most appropriate conditions for treatment cotton fabric with Actigard^® are: padding the cotton fabric in aqueous solution containing 6% Actigard^® at pH 5 (adjusted using formic acid) then squeezed to wet pick up of 100%, dried at 80 °C for 5 min then cured at 100 °C for 150 s. The untreated cotton fabric did not show any antimicrobial activity towards Staphylococcus aureus or Escherichia coli. Treatment of cotton fabric with Actigard^® improves its antimicrobial properties towards S. aureus or E. coli. It is also observed that, treatment of cotton fabric with Actigard^® marginally decreases fabric tensile strength, elongation at break, roughness and WI, whereas; both wettability and crease recovery angle remain practically intact. This was observed whether the fabric was pre-mercerized or not.     

Development of Eye Position Dependency of Slow Phase Velocity during Caloric Stimulation

The nystagmus in patients with vestibular disorders often has an eye position dependency, called Alexander’s law, where the slow phase velocity is higher with gaze in the fast phase direction compared with gaze in the slow phase direction. Alexander’s law has been hypothesized to arise either due to adaptive changes in the velocity-to-position neural integrator, or as a consequence of processing of the vestibular-ocular reflex. We tested whether Alexander’s law arises only as a consequence of non-physiologic vestibular stimulation. We measured the time course of the development of Alexander’s law in healthy humans with nystagmus caused by three types of caloric vestibular stimulation: cold (unilateral inhibition), warm (unilateral excitation), and simultaneous bilateral bithermal (one side cold, the other warm) stimulation, mimicking the normal push-pull pattern of vestibular stimulation. Alexander’s law, measured as a negative slope of the velocity versus position curve, was observed in all conditions. A reversed pattern of eye position dependency (positive slope) was found <10% of the time. The slope often changed with nystagmus velocity (cross-correlation of nystagmus speed and slope was significant in 50% of cases), and the average lag of the slope with the speed was not significantly different from zero. Our results do not support the hypothesis that Alexander’s law can only be observed with non-physiologic vestibular stimulation. Further, the rapid development of Alexander’s law, while possible for an adaptive mechanism, is nonetheless quite fast compared to most other ocular motor adaptations. These results suggest that Alexander’s law may not be a consequence of a true adaptive mechanism.     

Impact of the Error Structure on the Design and Analysis of Enzyme Kinetic Models

The statistical analysis of enzyme kinetic reactions usually involves models of the response functions which are well defined on the basis of Michaelis–Menten type equations. The error structure, however, is often without good reason assumed as additive Gaussian noise. This simple assumption may lead to undesired properties of the analysis, particularly when simulations are involved and consequently negative simulated reaction rates may occur. In this study, we investigate the effect of assuming multiplicative log normal errors instead. While there is typically little impact on the estimates, the experimental designs and their efficiencies are decisively affected, particularly when it comes to model discrimination problems.

     

A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease)

Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme (GAA; EC.3.2.1.3) leading to intracellular aggregations of glycogenin muscles. The infantile-onset type is the most life-threatening form of this disease, in which most of patients suffer from cardiomyopathy and hypotonia in early infancy. In this study, a typical case of Pompe disease was reported in an Iranian patient using molecular analysis of the GAA gene. Our results revealed a new c.1824_1828dupATACG mutation in exon 13 of the GAA gene. In conclusion, with the finding of this novel mutation, the genotypic spectrum of Iranian patients with Pompe disease has been extended, facilitating the definition of disease-related mutations.     

Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect

Background

Clinical trials have shown the benefits of statins after acute myocardial infarction (AMI). However, it is unclear whether different statins exert a similar effect in reducing the incidence of recurrent AMI and death when used in clinical practice.

Methods

We conducted a retrospective cohort study (1997–2002) to compare 5 statins using data from medical administrative databases in 3 provinces (Quebec, Ontario and British Columbia). We included patients aged 65 years and over who were discharged alive after their first AMI-related hospital stay and who began statin treatment within 90 days after discharge. The primary end point was the combined outcome of recurrent AMI or death from any cause. The secondary end point was death from any cause. Adjusted hazard ratios (HRs) for each statin compared with atorvastatin as the reference drug were estimated using Cox proportional hazards regression analysis.

Results

A total of 18 637 patients were prescribed atorvastatin (n = 6420), pravastatin (n = 4480), simvastatin (n = 5518), lovastatin (n = 1736) or fluvastatin (n = 483). Users of different statins showed similar baseline characteristics and patterns of statin use. The adjusted HRs (and 95% confidence intervals) for the combined outcome of AMI or death showed that each statin had similar effects when compared with atorvastatin: pravastatin 1.00 (0.90–1.11), simvastatin 1.01 (0.91– 1.12), lovastatin 1.09 (0.95–1.24) and fluvastatin 1.01 (0.80– 1.27). The results did not change when death alone was the end point, nor did they change after adjustment for initial daily dose or after censoring of patients who switched or stopped the initial statin treatment.

Interpretation

Our results suggest that, under current usage, statins are equally effective for secocondary prevention in elderly patients after AMI.Randomized controlled trials (RCTs) have shown that the use of statins after acute myocardial infarction (AMI) are effective in reducing the incidence of both fatal and nonfatal cardiovascular events.^{1,2,3,4,5,6,7,8} Although these trials have significantly influenced post-AMI treatment,^9,10,11,12 it remains unclear whether all statins are equally effective in preventing recurrent AMI and death. Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (class effect).^13,14,15 However, in the absence of comparative data, this assumption requires evaluation. Statins differ in multiple characteristics, including liver and renal metabolism, half-life, effect on other serum lipid components, bioavailability and potency.^16,17,18,19 These differences could potentially influence the extent to which the drugs are beneficial. Despite limited evidence in support of a differential benefit of statins for secondary prevention, preferential prescribing already occurs in practice and cannot be fully explained by the existing evidence or guidelines.²⁰ Comparative data of statins are thus required to inform health care decision-making.A number of RCTs have directly compared statins using surrogate end points, such as lipid reduction,^21,22,23 markers of hemostasis and inflammation^24,25,26 or reduction in number of atherotic plaques.²⁷ However, the extent to which these results can be extrapolated to clinically relevant outcomes remains to be established. The newly released PROVE IT– TIMI 22 trial²⁸ was the first trial to compare 2 statins for cardiovascular prevention. The study showed that atorvastatin used at a maximal dose of 80 mg (intensive therapy) was better than pravastatin at a dose of 40 mg (standard therapy) in decreasing the incidence of cardiovascular events and procedures. The study was, however, conducted to show the benefit associated with increased treatment intensity. It did not compare the drugs by milligram-equivalent doses or by cholesterol-lowering equivalent doses. Moreover, no difference was detected when death alone or the combined outcome of death or AMI was evaluated. Other than the PROVE IT–TIMI 22 trial, few data are currently available from RCTs that compare statins for cardiovascular prevention.²⁹We conducted a population-based study to examine the relative effectiveness of different statins for long-term secondary prevention after AMI. We used retrospective cohorts of elderly patients prescribed statins after AMI in 3 provinces. Five statins were studied: atorvastatin, pravastatin, simvastatin, lovastatin and fluvastatin. The newest statin, rosuvastatin, was not available during the study period and was not considered in this study.     

Influence of Polymer Aggregation and Liquid Immiscibility on Morphology Tuning by Varying Composition in PffBT4T‐2DT/Nonfullerene Organic Solar Cells

The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.