Optimization of Lovastatin Self-Nanoemulsifying Solid Dosage Form

ACKNOWLEDGEMENTS: I am very thankful to Dr Sanjay S. Patel for his great support for this research work. We are also thankful to Manager of Abitech Corporation, USA, Corel Chemical Ltd., Ahmedabad, and Torrent Pharmaceuticals Ltd., Ahmedabad for providing us necessary ingredients. We are thankful to Shri B. M. Shah College of Pharmaceutical Education and Research, Modasa for providing technical support in form of instruments and guidance.Aim: The aim of present study was to develop and optimized self-nanoemulsifying solid dosage form (SNESDF) of Lovastatin for enhancing its solubility. Lovastatin (whose water solubility is 0.4 x 10-3 mg/mL) is considered to be a reasonable drug because of its high log P value (4.3) and good solubility in oils. Materials and Methods: The formulations were optimized by Box-Behnken statistical design in which the independent variables like Ratio of surfactant: co-surfactant (X1), oil: surfactant co surfactant (X2), and % Aerosil (X3). The formulations were characterized for its dependent variables such as Droplet size (Y1), transmittance (Y3), percentage of drug released within 5 minutes (Y3), and within 15 minutes (Y4). Results and Conclusion: Droplet size and zeta potential of the optimized batch was found to be 21.89 nm and -6.4 mV, respectively. 44.32 % and 90.78 % of the drug was found to be released within 5 min and 15 min, respectively. Hence, by formulating into SNESDF, the solubility of Lovastatin was found to be significantly improved.Objetivo: El objetivo del presente estudio fue desarrollar y optimizar la auto-nanoemulsión forma de dosificación sólida (SNESDF) de la Lovastatina para aumentar su solubilidad. Lovastatina (cuya solubilidad en agua es 0,4 x 10-3 mg / ml) se considera que es un fármaco razonable debido a su alto valor de log P (4,3) y una buena solubilidad en aceites. Materiales y Métodos: Las formulaciones fueron optimizadas por el diseño estadístico Box-Behnken en el cual las variables independientes como relación de tensioactivo: tensioactivo co-(X1), aceite: tensioactivo co tensioactivo (X2), y% Aerosil (X3). Las formulaciones se caracterizan por sus variables dependientes, tales como tamaño de la gota (Y1), la transmitancia (Y3), el porcentaje de fármaco liberado en 5 minutos (Y3), y dentro de 15 minutos (Y4). Resultados y Conclusiones: tamaño de la gota y el potencial zeta del lote optimizado resultó ser 21,89 nm y -6,4 mV, respectivamente. 44,32% y 90,78% del fármaco se encontró que se libera dentro de 5 min y 15 min, respectivamente. Por lo tanto, mediante la formulación en SNESDF de lovastatina , se encontró que la solubilidad mejoraba significativamente

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

Clinical and endoscopic features of pill-induced esophagitis

Background: Medication can cause an injury in the esophagus by local and systemic effect, leading to esophagitis. Many such medications have been identified as a cause of pill-induced esophagitis. This study was performed to evaluate the clinical and endoscopic findings of pill-induced esophagitis.Methods: This was retrospective observational study, conducted among patients diagnosed endoscopically with pill-induced esophagitis at Ansh gastroenterology clinic, Ahmedabad, India, from April 2017 to March 2021. The data of these patients were recorded in pre-designed case record form by evaluating their past medical records.Results: Total 90 patients were diagnosed with pill-induced esophagitis. Retrosternal chest pain (68.9%), odynophagia (41.1%), dysphagia (25.6%), and epigastric pain (14.4%) were common clinical findings. The major culprit medications were antibiotics, and NSAIDs (non-steroidal anti-inflammatory drugs). Common esophageal endoscopic findings were ulcer (84.4%), erosion (17.8%), and active ulcer bleeding (12.2%). Kissing ulcers were observed in the majority (46.7%) of cases. The majority of ulcer and erosion were located in middle third of the esophagus. All the patients were recovered within 6 to 10 days after treatment with PPIs (proton pump inhibitors) and/or antacids, and withdrawal of the causative medication.Conclusions: Pill-induced esophagitis commonly manifests as retrosternal chest pain, odynophagia and dysphagia, and endoscopy reveals kissing ulcer and erosion in the majority of cases. The condition can be treated with PPIs and/or antacids, and withdrawal of the offending medication.

Sadašnjost i budućnost stentova za restenozu koji otpuštaju lijekove

Drug-eluting stents (DESs) prevail in the treatment of carotid artery diseases in the interventional cardiology world owing to their efficacy for significant reduction of restenosis. A current successful DES requires a polymer coating for drug delivery. Clinical trials examining several pharmaceutical agents have demonstrated marked reduction in restenosis following stenting. The development of DES is one of the major revolutions in the field of interventional cardiology. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but, on the other hand, it must also enhance re-endothelialization in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Although DES have significantly reduced the angiographic restenosis rate and have improved clinical outcomes, late thrombosis and restenosis remain an important subject of ongoing research.Stentovi koji otpuštaju lijekove (DESs) koriste se u kardiologiji za terapiju bolesti karotidnih arterija jer značajno smanjuju restenozu. Dobar DES ima polimerni sloj za isporuku lijekova. Klinički pokusi u kojima je ispitivano nekoliko agenasa pokazali su značajno smanjenje restenoze nakon ugradnje stenta. Razvoj DES-a jedno je od revolucionarnih otkrića u području interventne kardiologije. Idealni lijek za prevenciju restenoze mora imati antiproliferativni i antimigracijski učinak na stanice glatkih mišića, a s druge strane mora povećavati endotelizaciju kako bi se spriječila tromboza. Osim toga, treba učinkovito inhibirati protuupalni odgovor nakon ozljede arterije. Iako DES značajno smanjuje restenozu krvnih žila, kasna tromboza i restenoza ostaju i dalje problem i predmet brojnih istraživanja

Lack of reproducibility of linkage results in serially measured blood pressure data

BACKGROUND: Using the longitudinal Framingham Heart Study data on blood pressure, we analyzed the reproducibility of linkage measures from serial cross-sectional surveys of a defined population by performing genome-wide model-free linkage analyses to systolic blood pressure (SBP) and history of hypertension (HTN) measured at five separate time points. RESULTS: The heritability of SBP was relatively stable over time, ranging from 11.6 to 23.5% (coefficient of variation = 25.7%). However, the variability in linkage results was much greater. The average correlation in LOD scores at any pair of time points was 0.46 for HTN (NPL All LOD) and 0.17 for SBP (Variance Components LOD). No evidence of reproducible linkage results was found, with a mean κ of 0.02 for linkage to HTN and -0.03 for SBP linkage. At loci with potential evidence for linkage (LOD > 1.0 at one or more time points), the correlation was even lower. The coefficient of variation at loci with potential evidence of linkage was 126% for HTN and 135% for SBP. None of 15 chromosomal regions for HTN and only one of 28 regions for SBP with potential evidence for linkage had a LOD > 1.0 at more than two of the five time points. CONCLUSION: These data suggest that, although heritability estimates at different time points are relatively robust, the reproducibility of linkage results in serial cross-sectional samples of a geographically defined population at successive time points is poor. This may explain in part the difficulty encountered in replicating linkage studies of complex phenotypes

Split hand/split-foot malformations: a report of four cases in a family with variable presentations

Split hand/split-foot malformation is a congenital anomaly with failure of development of the central digital rays of hand or foot to a variable extent. It is characterized by hypoplasia/aplasia of the phalanges, toes, metacarpals and metatarsals. The presentation may be an isolated anomaly or may be associated with syndrome and thus have variable pattern of inheritance. We report a family of 10 members; four of which are affected with autosomal recessive pattern of inheritance. We discuss here the clinical presentation, genetic inheritance, prenatal diagnosis and treatment for the malformation

Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.

ObjectiveWe examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.Research design and methodsBetween 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.ResultsObserved apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.ConclusionsEasily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults

Suppression of Optical Feedback in Laser Diodes Using Multilayered Broad-band Ultra-low Reflective Facets-coating

The multilayered anti-reflection coating (ARC) has been designed and implemented on the facets of edge-emitting laser diode in order to achieve ultra-low reflectivity over a broad wavelength range for suppression of optical feedback in the laser cavity. The design of the multilayer ARC has been obtained by a self-developed program based on genetic algorithm (GA) to achieve low-reflectivity of the order of 0.1 % over a spectral width of 50 nm around the central lasing wavelength of 818 nm and successfully implemented on the laser-diode facets. The effects of facets coating on the optical power emission and the spectral response of the lasers have been investigated. It is demonstrated that the simple design of multilayered ARC obtained using a self-developed GA can successfully reduce the optical feedback from the cavity and prevent the lasing action from the structure, which can be very useful for the fabrication of superluminescent Light Emitting Diodes (SLEDs)

Determination of Thickness and Optical Parameters of Thin Films from Reflectivity Spectra Using Teaching-Learning Based Optimization Algorithm

In this paper, we report a simple method to extract thickness and refractive index of thin-film from experimentally measured reflectivity spectra using teaching-learning based optimization (TLBO) algorithm. The algorithm finds thickness and refractive index by fitting an experimentally measured reflectivity spectra with theoretically ones generated by transfer matrix approach. The value of refractive index as a function of wavelength is determined by considering sellmeier dispersion relation. The algorithm is implemented by means of an interactive numerical simulation using LabVIEW as a programming tool. To check the effectiveness of the self-developed program, it is tested on different thin-film samples prepared from some commonly used optical materials such as MgF2, Al2O3 and SiO2 using electron beam evaporation technique. The values of thicknesses and refractive index spectra for different thin-film samples obtained by TLBO algorithm are verified using standard spectroscopic ellipsometry measurements. It is found that there is an excellent agreement between the results obtained by the TLBO algorithm and those by ellipsometry. It is also demonstrated that a simple reflectivity measurements give the valuable information about the thickness and dispersive refractive index over a range of wavelengths, which are obtained by our self-developed simulation program based on TLBO algorithm

Genome-wide linkage analysis of longitudinal phenotypes using σ(2)(A )random effects (SSARs) fitted by Gibbs sampling

The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (σ(2)(A.time)) were estimated to account for ~9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (σ(2)(A)) were estimated to account for ~43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data