Measurement Invariance of the Perceived Invalidation of Emotion Scale: An Examination Across Race/Ethnicity, Gender, Sexual Orientation, and Intersection of Identities.

The Perceived Invalidation of Emotions Scale (PIES), developed to measure emotional invalidation, could aid research efforts on various internalizing disorders and minority mental health. A prerequisite for its use includes its psychometric evaluation in diverse samples; thus, the current study aimed to evaluate the psychometric properties of the PIES in a combined sample of minoritized adults (N = 876). Results supported a unidimensional structure of the PIES that was invariant across the two minoritized samples, race/ethnicity, gender, sexual orientation, and intersections of race/ethnicity and sexual orientation. A reduced 7- and 4-item PIES with improved unidimensionality and consequentially more interpretable total scores were generated using item response theory analyses. Significant correlations observed between theoretically relevant constructs of adverse mental health outcomes and the PIES above and beyond identity-based discrimination supported the construct validity of the PIES. Implications include the disproportionate amount of emotional invalidation experienced by individuals with minoritized sexual orientation, which may reflect the recent increases in discrimination faced by these individuals.

Size controlled synthesis of biocompatible gold nanoparticles and their activity in the oxidation of NADH.

Size and shape controlled synthesis remains a major bottleneck in the research on nanoparticles even after the development of different methods for their preparation. By tuning the size and shape of a nanoparticle, the intrinsic properties of the nanoparticle can be controlled leading tremendous potential applications in different fields of science and technology. We describe a facile route for the one pot synthesis of gold nanoparticles in water using monosodium glutamate as the reducing and stabilizing agent in the absence of seed particles. The particle diameter can be easily controlled by varying the pH of the reaction medium. Nanoparticles were characterized using scanning electron microscopy, UV-vis absorption spectroscopy, cyclic voltammetry, and dynamic light scattering. Zeta potential measurements were made to compare the stability of the different nanoparticles. The results suggest that lower pH favours a nucleation rate giving rise to smaller particles and higher pH favours a growth rate leading to the formation of larger particles. The synthesized nanoparticles are found to be stable and biocompatible. The nanoparticles synthesized at high pH exhibited a good electrocatalytic activity towards oxidation of nicotinamide adenine dinucleotide (NADH).

Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: in vitro and in vivo evaluation.

The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 µm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R (2)) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC(0-∞), Kel and t(1/2)) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.

Pre-clinical evidence of enhanced oral bioavailability of the P-glycoprotein substrate talinolol in combination with morin.

Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In order to evaluate the effect of one of such prominent flavonoids, morin, on P-glycoprotein related efflux carriers, measurements of transport characteristics through Ussing chambers, in situ perfusion and in vivo drug absorption studies were performed with the transported, yet not metabolized model compound talinolol.This study investigated the effects of orally administered morin (1.0, 2.5 and 5.0 mg kg(-1)), on the pharmacokinetics of orally (10 mg kg(-1)) and intravenously (1.0 mg kg(-1)) administered talinolol in rats. In the presence of morin, the pharmacokinetic parameters of talinolol were significantly altered in the oral group but not in the intravenous group. The presence of 2.5 and 5.0 mg kg(-1) of morin significantly increased (1.8-2.0 fold, p<0.01) the area under the plasma concentration-time curve and the peak plasma concentration (2.3-3.0 fold, p<0.01) of orally administered talinolol. The absolute bioavailability (F %) of talinolol in the rats pretreated with morin was significantly higher (89.09-98.29%, p<0.01) than the control (52.14%). Talinolol demonstrated asymmetric transport across rat ileum with significantly greater basolateral-to-apical (B-A) permeability than that in the apical-to-basolateral (A-B) direction. The addition of morin resulted in a concentration dependent effect, especially on the secretory transport of talinolol.The present study demonstrates that morin bears the ability to interfere with secretory intestinal transport processes. This might be due to an interaction with P-glycoprotein.

Effect of Lecithin and silymarin on D-galactosamine induced toxicity in isolated hepatocytes and rats.

To investigate Lecithin for its hepatoprotective activity against D-galactosamine (D-GalN) induced toxicity in freshly isolated rat hepatocytes and animal models. Freshly isolated rat hepatocytes were exposed to Dgalactosamine (30 mM) along with/without lecithin (100 µg/ml) and the levels of selected liver enzymes were measured. Thirty six Wistar strain albino rats were used for the in vivo investigations. Lecithin 50 and 100 mg/kg.b.wt were administered for one week by oral route. Liver damage was induced by intra peritoneal administration of 400 mg/kg b.wt D-galactosamine. The antihepatotoxic effect of lecithin was observed in freshly isolated rat hepatocytes at concentration 100 µg/ml and was found to be similar to that of the standard silymarin used. Its in vivo hepatoprotective effect at 100 mg/kg b.wt was comparable with that of the standard silymarin at 100 mg/kg body weight. Lecithin was able to normalise the biochemical levels which were altered due to D-galactosamine intoxication in freshly isolated rat hepatocytes and also in animal models.

Solid dispersions: a review.

Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of a range of hydrophobic drugs. This article reviews the various preparation techniques for solid dispersion and compiles some of the recent technology transfers. The different types of solid dispersions based on the molecular arrangement have been highlighted. Some of the practical aspects to be considered for the preparation of solid dispersions, such as selection of carrier and methods of physicochemical characterization, along with an insight into the molecular arrangement of drugs in solid dispersions are also discussed. Finally, an in-depth rationale for limited commercialization of solid dispersions and recent revival has been considered.

Assessment of cost of illness for diabetic patients in South Indian tertiary care hospital.

BACKGROUND: The impact of diabetes on health-care expenditures has been increasingly recognized. To formulate an effective health planning and resource allocation, it is important to determine economic burden. OBJECTIVE: The objective of this study is to assess the cost of illness (COI) for diabetic inpatients with or without complications. METHODOLOGY: The study was conducted in the medicine wards of tertiary care hospital after ethical approval by the Institutional Ethical Committee. A total of 116 each diabetic with or without complications were selected and relevant data were collected using COI questionnaire and data were analyzed using SPSS version 20. Mann-Whitney U test is used to assess the statistical significant difference in the cost of treatment of diabetes alone and with complications'. P ≤ 0.05 was considered statistically significant. RESULTS: Total COI includes the cost of treatment, investigation, consultation fee, intervention cost, transportation, days lost due to work, and hospitalization. The median of total COI for diabetic care without any complication was Rs. 22,456.97/- per patient per annum and with complication was Rs. 30,634.45/-. Patients on dialysis had to spend 7.3 times higher, and patients with cardiac intervention had to spend 7.4 times higher than diabetic patients without any complication. CONCLUSION: Treatment costs were many times higher in patients with complications and with cardiac and renal interventions. Complications in diabetic patients will increase the economic burden to family and also to the society.

Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation.

Lercanidipine is a vasoselective dihydropyridine calcium antagonist, mainly used for the treatment of hypertension and angina pectoris. However, it suffers from food dependent absorption, poor solubility, low permeability and considerable first pass metabolism, resulting in highly variable and low bioavailability of 10%. Nanoparticles of lercanidipine were incorporated in fast dissolving oral films (FDO) via preparation of nanosuspension by evaporative antisolvent precipitation method. Prepared nanosuspensions were incorporated in FDO without lyophilizing or spray drying. Two nanosuspensions containing PEG 400 and TPGS 1000 as stabilizers, were selected further for incorporation in FDO. Physicochemical and mechanical properties of the optimized films were observed to be within acceptance criteria. SEM images as well as FTIR chemical images of oral films show uniform distribution of nanoparticles in polymeric matrix. The DSC and XRD results proved the poorly crystalline nature of lercanidipine. However thermal processing of film induces crystallinity in hypromellose which results in embedding of amorphous drug nanoparticles in semicrystalline polymeric matrix. Superior dissolution and permeability properties of nanoparticles were confirmed by in vitro dissolution studies and about 4.5-folds higher ex vivo drug permeation was observed from formulation through porcine buccal mucosa. This may give the clue for enhancement of bioavailability in vivo via improving orotransmucosal absorption.

Smart Polymers in Nasal Drug Delivery.

Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones.

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

Temperature sensitive liposomes of plumbagin: characterization and in vivo evaluation in mice bearing melanoma B16F1.

The effectiveness of the combination of thermosensitive liposomes of plumbagin and hyperthermia is described. Small-sized, thermosensitive liposomes were prepared by thin film hydration and subsequent sonication. The liposomes were characterized for size, phase transition temperature, in vitro drug release and stability. The results of particle size analysis indicated that almost 90% of the vesicles were below 0.19 microm size. The phase transition temperature of the liposomes as determined by differential scanning calorimetry was found to be 41.32 degrees C. The results of in vitro release studies in phosphate buffered saline + mouse plasma indicated that maximum drug release (51.25%) occurred at 42 degrees C compared to the less than 9% release at 37 degrees C. Better stability profile was observed when the plumbagin liposomes were stored at 4 degrees C. When combined with localised hyperthermia (43 degrees C, 30 min or 1 h), liposomal plumbagin administered intravenously to C57BL/6J mice bearing melanoma exhibited better anticancer activity as compared to animals treated with an equivalent dose of free plumbagin with or without hyperthermia, which was evident by enhanced volume doubling time and growth delay.

Niosome encapsulated of vincristine sulfate: improved anticancer activity with reduced toxicity in mice.

Nonionic surfactant vesicles (niosomes) are promising drug carriers for anticancer drugs. Niosome encapsulated vincristine sulfate prepared by transmembrane pH gradient drug uptake process (remote loading method) was evaluated for toxicity and antitumour activity after administration to tumour bearing mice. The toxicity of vincristine sulfate was reduced after niosome encapsulation and anticancer activity improved, which may be due to better delivery of vincristine at the tumour site.

Effect of macrophage activation on plasma disposition of niosomal 3H-methotrexate in sarcoma-180 bearing mice.

Methotrexate niosomes were formed by reverse phase evaporation technique using sorbitan monostearate (Span 60) surfactant. The pharmacokinetic parameters of methotrexate (MTX) after macrophage activation via muramyl dipeptide gelatin conjugate were studied and the results compared with those obtained after free MTX and MTX niosomes without macrophage activation. In mice MTX concentrations and tumour regression were higher after macrophage activation.

Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations.

In the present study, matrix type transdermal patches containing glibenclamide were prepared using different ratios of ethyl cellulose (EC)/polyvinylpyrrolidone (PVP) and Eudragit RL-100 (ERL)/Eudragit RS-100 (ERS) by solvent evaporation technique. The possible drug and polymer interaction was studied by infrared spectroscopy, differential scanning calorimetry, and HPTLC analysis. All the prepared formulations were subjected to physicochemical studies (thickness, weight variation, drug content, moisture content and uptake, and flatness), in vitro release and in vitro permeation studies through mouse skin. The results suggested that there was no interaction between drug and polymers. Variations in drug release/permeation profiles among the formulations studied were observed. The microphotographs obtained by scanning electron microscopy showed the formation of pores on the surface of the patches after in vitro skin permeation studies. Based on physicochemical and in vitro skin permeation studies, the formulations with EC:PVP (3:2) and ERL:ERS (4:1) were selected for in vivo experiments. The hypoglycemic activity of the patches in comparison with oral glibenclamide administration was studied for acute (24 h) and long-term (6 weeks) effect in both normal and streptozotocin-induced diabetic mice. Various biochemical parameters (serum levels of high-density lipoprotein-cholesterol, triglycerides, total cholesterol, alanine transaminase, aspertate transaminase, urea, and creatinine and liver protein and glycogen content) and histopathological (liver, pancreas and stomach) studies were carried out in diabetic mice after treating for 6 weeks. The patches were subjected to skin irritation test (by both visual observation and histopathological evaluation), oral glucose tolerance test and pharmacokinetic evaluation in mice. The results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours, which is the major side effect associated with oral route. The patches maintained similar effect during long-term treatment also. The transdermal systems produced better improvement with all the tested biochemical parameters compared to oral administration. They produced improved repair of the tissues after diabetes induced tissue injury and exhibited negligible skin irritation. The pharmacokinetic evaluation showed that the patches could maintain almost steady-state concentration of drug within the pharmacologically effective range for prolonged period of time. The better in vivo performance of the transdermal patches of glibenclamide in comparison with oral administration could be due to day-to-day glycemic control on long-term application.