Tobacco Imagery in Movies and Web Series Streaming in India and Their Compliance With the Recent Anti-tobacco Rules for Over-the-Top (OTT) Platforms.

INTRODUCTION: Internet access, smartphones, and televisions have significantly boosted over-the-top (OTT) movies and web series viewing in India, especially among youths. Despite restrictions, OTT platforms continue to promote tobacco products. India has recently enforced the revised OTT Rules 2023 effective September 1, 2023, to counter tobacco promotion in OTT shows. This study explores compliance with the OTT Rules 2023 in popular movies and web series on select OTT platforms in India. METHODS: About 29 movies and 31 web series from seven popular OTT platforms as of September 26, 2023, were analyzed in this study. The incidence of tobacco imagery and compliance with the OTT Rules 2023 were assessed using a standardized format with the help of seven trained coders. Descriptive statistics were used to describe instances of tobacco imagery and violations of the provisions of Indian law. RESULTS: The average incidence of tobacco imagery per included show was 3.95. None of the movies and web series fully complied with the provisions of health spots and audio-visual warnings. Only 35.7% of the shows (movies: 57.1%, web series: 14.3%) fully complied with the anti-tobacco static message provisions. The foreign-origin movies had zero compliance with static messages, though they had fewer tobacco images. Half of the shows for children up to 12 years old had tobacco imagery but fully complied with the static warning message provisions. CONCLUSION: The portrayal of tobacco imagery in OTT shows is prevalent, and their poor compliance with the OTT Rules 2023 is a concern. Therefore, monitoring and stricter enforcement of the OTT Rules should be given priority to protect viewers from tobacco promotion in OTT shows.

A Vehicle-to-Grid System for Controlling Parameters of Microgrid System.

The power system for large-scale adoption of hybrid electric vehicles can benefit from a distributed reserve provided by the vehicle-to-grid (V2G) concept. This study suggests a V2G technology that can effectively control frequency on a microgrid throughout a 24-h cycle. When usage is at its lowest in the spring or fall, a microgrid is intended to be large enough to simulate a community of 2000 households. A 1:5 ratio of cars to households is realized by modelling 400 electric vehicles (EVs) as a basic model, indicating a typical case in the future. An in-depth analysis of the voltage, current, reactive, and active power is carried out for a microgrid. By coordinating control of diesel generation, renewable energy source (RES) generation, power exchange, and EV generation, the system frequency of a microgrid can be managed by regulating load demand with V2G devices. The proposed microgrid with V2G effectively manages energy and reduces the uncertain and variable nature of RES power generation with enhanced performance. System parameter variations have been investigated for various operating scenarios, and it has been discovered that error is confined to less than 5%.

Appropriate Method of TIBC Estimation in Reference to Serum Transferrin Levels.

Background The currently available various methods of estimation of total iron binding capacity (TIBC) show marked variation in reference range. Although serum transferrin (TF) level is a sensitive indicator of iron status, its measurement requires immunoassay equipment which may not be available in many routine biochemistry laboratories. So, this study was planned to find the most appropriate method to estimate TIBC. Objectives This study aimed to compare different methods of TIBC estimation and to corelate the TIBC values obtained by different methods with serum TF concentration. Material and Methods This analytical cross-sectional study was performed in the clinical chemistry laboratory of the Biochemistry Department of Medical College Baroda & SSG Hospital, Vadodara, Gujarat, on 250 leftover serum samples destined to be discarded. In all these samples, serum TIBC was estimated by direct method, indirect method, as well as calculated method (iron + unsaturated iron binding capacity [UIBC]) along with the measurement of serum TF level. Statistical Analysis Among the different methods, repeated analysis of variance (ANOVA) analysis and Bland-Altman plot were used to find out significance of difference. Correlation coefficients were found between different methods of TIBC estimation and serum TF levels. Results The means of TIBC by calculated, indirect, and direct methods were 344.51, 342.23, and 378.24 µg/dL, respectively. The mean of serum TF was 295.3 mg/dL. There was statistically significant difference between TIBC by direct and indirect methods and between direct and calculated methods. There was a strong positive correlation between TIBC by direct method and serum TF ( r = 0.888, p < 0.0001), but there was moderate correlation between TIBC by indirect method and serum TF ( r = 0.748, p < 0.04), and between TIBC by calculated method and serum TF ( r = 0.725, p < 0.05). Conclusion Among different methods of estimation of TIBC, direct method is more reliable in reference to serum TF levels.

Cutting Edge: Bispecific γδ T Cell Engager Containing Heterodimeric BTN2A1 and BTN3A1 Promotes Targeted Activation of Vγ9Vδ2+ T Cells in the Presence of Costimulation by CD28 or NKG2D.

Vγ9Vδ2+ T cell-targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential against a variety of cancers. Recent studies have identified heterodimeric butyrophilin (BTN) 2A1 and BTN3A1 as the molecular entity providing "signal 1" to the Vγ9Vδ2 TCR, but "signal 2" costimulatory requirements remain unclear. Using a tumor cell-free assay, we demonstrated that a BTN2A1/3A1 heterodimeric fusion protein activated human Vγ9Vδ2+ T cells, but only in the presence of costimulatory signal via CD28 or NK group 2 member D. Nonetheless, addition of a bispecific γδ T cell engager BTN2A1/3A1-Fc-CD19scFv alone enhanced granzyme B-mediated killing of human CD19+ lymphoma cells when cocultured with Vγ9Vδ2+ T cells, suggesting expression of costimulatory ligand(s) on tumor cells is sufficient to satisfy the "signal 2" requirement. These results highlight the parallels of signal 1 and signal 2 requirements in αß and γδ T cell activation and demonstrate the utility of heterodimeric BTNs to promote targeted activation of γδ T cells.

Inter-Institutional Collaboration Between Quaternary and Tertiary Hospitals: Cardiac Surgery Impact.

BACKGROUND: An inter-institutional collaboration between a quaternary hospital (QH) with a high volume of cardiac surgery and a community-based, tertiary hospital (TH) with a newly established cardiac surgery program was established. METHODS: We retrospectively reviewed data of patients admitted to the TH between September 2015 and June 2017 for cardiac surgery. The decision to transfer a patient to the QH was based on a Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score of ≥ 3%, the potential need for hemodialysis, and other risk factors. The same team of surgeons performed operations at both hospitals. We analyzed the perioperative outcomes of the patients and the referral pattern. RESULTS: A total of 116 patients met eligibility criteria; 105 underwent surgery at the TH, while 11 were transferred to the QH. Among the 11 patients transferred to the QH, eight had a score of  3% (median = 8.2 [IQR 5.7-25.0]). The patients transferred to the QH prior to surgery had a significantly higher STS-PROM score (P = ≤ .001). Overall, the mortality of patients who underwent surgery at the TH was 0.9% (1/105); while surgeries at the QH had a mortality rate of 0% (0/11). CONCLUSION: The collaborative effort between high-volume cardiac surgery programs and emerging community-based hospitals showed acceptable outcomes in perioperative cardiac surgical mortality. Elevated STS-PROM scores (>3%), previous sternotomy and anticipation of coagulopathy, and low left ventricular ejection fraction or dilated ventricles are factors that influenced the need to transfer from a TH to QH.

LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade.

Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non-small cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibition-resistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1low or checkpoint inhibition-resistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTßR (lymphotoxin ß receptor), without the requirement for a competent Fc domain to engage Fcγ receptors. LIGHT costimulated CD8+ T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.

Application of a Scorecard Tool for Assessing and Engaging Media on Responsible Reporting of Suicide-Related News in India.

BACKGROUND: Each year there are more than 800,000 deaths by suicide across the world, while India alone accounts for one third of female suicides and one fourth of male suicides worldwide. Responsible media reporting of suicide is an important suicide prevention intervention at the population level. There is sufficient evidence to show that the way suicide is reported and portrayed in the media can have a significant impact on individuals experiencing suicidal thoughts and behaviors. Recognizing the important role of the media in suicide prevention, the World Health Organization (WHO) issued guidelines for responsible reporting of suicides by the media. The Press Council of India, in 2019 endorsed WHO's guidelines for media reporting of suicides, however there is no evidence that the Indian media is complying with these guidelines. METHODS: To encourage responsible media reporting, we developed a scorecard to assess and rate media reports on suicide. We reviewed several resource documents that contained guidelines on responsible reporting of suicide. After consulting with a team of experts, we arrived at a scorecard that consisted of 10 positive and 10 negative parameters. RESULTS: We applied the scorecard to 1318 reports on suicide from 9 English language newspapers, with the highest readership in India between the dates of 1 April to 30 June 2020. For the articles analyzed, the average positive score across all newspapers was 1.32 and the average negative score was 3.31. DISCUSSION: The scorecard can be a useful tool to assess media reports on suicide and provide metrics for the same. It can facilitate improved monitoring and engagement with media organizations, who can quickly check their own reporting compliance to the WHO guidelines and compare how well they are performing compared to their peers over time.

Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting.

OBJECTIVES: This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting. METHODS: Liposomes were formulated by dehydration-rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading. KEY FINDINGS: Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression. CONCLUSIONS: Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.

A Successful Case for Deselection of Albino Embryo and Live Birth of Albinism-Free Healthy Baby Followed by PGT-M.

In recent years, Preimplantation genetic testing for monogenic disorders (PGT-M) has gained a lot of focus in the field of assisted reproduction technology, various studies have been published in support of it and many are opposing its role. It has been criticized due to many ethical as well as scientific reasons, but there is no doubt that PGT-M has been one of the most important breakthroughs in in vitro fertilization. A critical aspect of this technology is the possibility that the biopsy itself can adversely affect the quality of embryo and compulsion of embryo freezing. Oculocutaneous albinism (OCA) is a condition which is related to skin, hair, eye color (pigments), where affected individuals typically have very fair skin and white- or light-colored hair. These patients are prone to skin cancers on prolonged sun exposure. It also reduces the pigmentation of the colored part of the eyes (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have problem in vision such as reduced sharpness, involuntary eye movements, and photophobia. Here, we report the successful use of PGT-M and a novel protocol for the preimplantation genetic diagnosis of OCA following trophectoderm cell biopsy from blastocysts and the birth of a healthy infant to a couple having previously affected child.

Vasopressin for Septic Shock in a Medical-Surgical Intensive Care Unit.

BACKGROUND: Critically ill patients often need vasopressors to treat hypotension related to septic shock and to maintain adequate systemic perfusion. Although the 2017 guidelines of the Surviving Sepsis Campaign recommend norepinephrine as first-line therapy, they also state that vasopressin may be considered as an adjunctive agent for patients with refractory shock. Limited evidence is available for directing optimal administration of vasopressin. As such, prescribing practices are not standardized and may vary according to the particular clinician, the clinical scenario, and various patient-specific factors. OBJECTIVES: To review the current practice of administering concomitant norepinephrine and vasopressin therapy to patients with septic shock, to describe variability in vasopressin administration, and to evaluate effects on patient safety in a medical-surgical intensive care unit (ICU). METHODS: This single-centre retrospective chart review involved 100 adult patients admitted to the ICU who received vasopressin and norepinephrine for septic shock between April and December 2017. The data were analyzed with descriptive statistics. RESULTS: The mean time to initiation of vasopressin was 12.0 (standard deviation [SD] 21.6) h after initiation of norepinephrine. The mean dose of norepinephrine at the time of vasopressin initiation was 29.5 (SD 19.7) µg/min. The mean vasopressin dose prescribed was 0.04 (SD 0.03) units/min, with a range of tapering and discontinuation regimens. The mean duration of vasopressin therapy was 49.1 (SD 65.2) h, and vasopressin was discontinued before norepinephrine in 49 of the patients. A total of 60 hypotensive events occurred after vasopressor discontinuation and were more common when vasopressin was discontinued before norepinephrine. CONCLUSIONS: Vasopressin dosing was comparable to that reported elsewhere; however, discontinuation practices were inconsistent. These results show that variability in the literature supporting vasopressin use has led to variability in vasopressin administration and discontinuation practices; however, correlation with improvement in clinical outcomes, such as mortality or ICU length of stay, is unclear, and further research is required to determine the ideal approach to vasopressin use.

CONTEXTE: Les patients gravement malades nécessitent souvent un vasopresseur pour traiter l'hypotension liée au choc septique et pour préserver une perfusion systémique adéquate. Bien que les directives de 2017 de la campagne Surviving Sepsis recommandent la norépinephrine en guise de thérapie de première ligne, elles précisent également que la vasopressine pourrait être envisagée comme agent d'appoint pour les patients présentant des chocs réfractaires. Seules des données probantes limitées soutiennent l'administration optimale de la vasopressine. Les pratiques de prescription proprement dites ne sont pas standardisées et peuvent varier selon le clinicien, le scénario clinique et les divers facteurs particuliers au patient. OBJECTIFS: Examiner la pratique actuelle d'administration de la norépinephrine concomitante à la thérapie de vasopressine aux patients ayant subi un choc septique, décrire la variabilité d'administration de la vasopressine et évaluer les effets sur la sécurité du patient dans une unité de soins intensifs (USI) médicale-chirurgicale. MÉTHODES: Cet examen rétrospectif unicentrique des dossiers portait sur 100 patients adultes admis dans une USI, ayant reçu de la vasopressine et de la norépinephrine en réponse à des chocs septiques entre avril et décembre 2017. Les données ont été analysées à l'aide de statistiques descriptives. RÉSULTATS: Le temps moyen du début de l'administration de la vasopressine était de 12 h (écart type [É.T.] 21,6) après le début de l'administration de la norépinephrine. La dose moyenne de norépinephrine au moment du début de l'administration de la vasopressine était de 29,5 (É.T. 19,7) µg/min. La dose moyenne de vasopressine prescrite était de 0,04 (É.T. 0,03) unités/min, avec une gamme de posologies dégressives et d'abandons. La durée moyenne de la thérapie à la vasopressine était de 49,1 h (É.T. 65,2), et 49 patients ont abandonné la vasopressine avant l'abandon de la norépinephrine. Un total de 60 événements hypotenseurs se sont produits après l'abandon du vasopresseur et ils étaient plus fréquents lors de l'abandon de la vasopressine précédant celui de la norépinephrine. CONCLUSIONS: Le dosage de vasopressine était comparable à celui indiqué dans d'autres études; cependant, les pratiques d'abandon étaient incohérentes. Ces résultats démontrent que l'indétermination de l'information publiée dans la littérature soutenant l'utilisation de la vasopressine a entraîné une fluctuation dans l'administration de la vasopressine et des pratiques d'abandon; cependant, la corrélation entre l'usage de la vasopressine et l'amélioration des résultats cliniques, comme la mortalité ou la durée du séjour en USI, n'est pas claire, et davantage de recherches sont nécessaires pour déterminer l'approche idéale à adopter à l'égard de l'utilisation de la vasopressine.

Formulation and evaluation of liquisolid compacts of itraconazole to enhance its oral bioavailability.

Aim: Formulate and evaluate liquisolid compacts of Itraconazole, a biopharmaceutical classification system class II drug, which has poor bioavailability. Materials & methods: PEG 600 was used as a nonvolatile solvent, Alfacel PH 200 as a carrier and Aerosil 200 as a coating material. The Itraconazole solution upon mixing with a carrier and coating material resulted in a dry powder, which was compressed into tablets. Results & conclusion: The optimized formulation exhibited a significantly higher drug dissolution (90.73% in 90 min) compared with conventional tablets and marketed capsules. The antifungal activity was retained in the formulation. Higher values of Cmax and AUC0-24 of the formulation compared with the plain drug indicated enhancement in oral bioavailability. The formulation was stable at room temperature as well as in accelerated conditions.

CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity.

Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) of targeted antibodies. Preclinically, CD47/SIRPα blockade induces antitumor activity by increasing the phagocytosis of tumor cells by macrophages and enhancing the cross-presentation of tumor antigens to CD8+ T cells by dendritic cells; both of these processes are potentiated by CD40 signaling. Here we generated a novel, two-sided fusion protein incorporating the extracellular domains of SIRPα and CD40L, adjoined by a central Fc domain, termed SIRPα-Fc-CD40L. SIRPα-Fc-CD40L bound CD47 and CD40 with high affinity and activated CD40 signaling in the absence of Fc receptor cross-linking. No evidence of hemolysis, hemagglutination, or thrombocytopenia was observed in vitro or in cynomolgus macaques. Murine SIRPα-Fc-CD40L outperformed CD47 blocking and CD40 agonist antibodies in murine CT26 tumor models and synergized with immune checkpoint blockade of PD-1 and CTLA4. SIRPα-Fc-CD40L activated a type I interferon response in macrophages and potentiated the activity of ADCP-competent targeted antibodies both in vitro and in vivo These data illustrated that whereas CD47/SIRPα inhibition could potentiate tumor cell phagocytosis, CD40-mediated activation of a type I interferon response provided a bridge between macrophage- and T-cell-mediated immunity that significantly enhanced durable tumor control and rejection.

Agonist redirected checkpoint, PD1-Fc-OX40L, for cancer immunotherapy.

Simultaneous blockade of immune checkpoint molecules and co-stimulation of the TNF receptor superfamily (TNFRSF) is predicted to improve overall survival in human cancer. TNFRSF co-stimulation depends upon coordinated antigen recognition through the T cell receptor followed by homotrimerization of the TNFRSF, and is most effective when these functions occur simultaneously. To address this mechanism, we developed a two-sided human fusion protein incorporating the extracellular domains (ECD) of PD-1 and OX40L, adjoined by a central Fc domain, termed PD1-Fc-OX40L. The PD-1 end of the fusion protein binds PD-L1 and PD-L2 with affinities of 2.08 and 1.76 nM, respectively, and the OX40L end binds OX40 with an affinity of 246 pM. High binding affinity on both sides of the construct translated to potent stimulation of OX40 signaling and PD1:PD-L1/L2 blockade, in multiple in vitro assays, including improved potency as compared to pembrolizumab, nivolumab, tavolixizumab and combinations of those antibodies. Furthermore, when activated human T cells were co-cultured with PD-L1 positive human tumor cells, PD1-Fc-OX40L was observed to concentrate to the immune synapse, which enhanced proliferation of T cells and production of IL-2, IFNγ and TNFα, and led to efficient killing of tumor cells. The therapeutic activity of PD1-Fc-OX40L in established murine tumors was significantly superior to either PD1 blocking, OX40 agonist, or combination antibody therapy; and required CD4+ T cells for maximum response. Importantly, all agonist functions of PD1-Fc-OX40L are independent of Fc receptor cross-linking. Collectively, these data demonstrate a highly potent fusion protein that is part of a platform, capable of providing checkpoint blockade and TNFRSF costimulation in a single molecule, which uniquely localizes TNFRSF costimulation to checkpoint ligand positive tumor cells.

Formulation of 99mTechnetium-labeled leuprolide loaded liposomes and its biodistribution study in New Zealand white female rabbits for assessment of its uterine targeting efficiency.

Leuprolide acetate (LPA), a GnRH analogue, is drug of choice for treatment of uterine fibroids and endometriosis. The current marketed formulations of LPA show severe systemic side effects. This project aims to formulate LPA loaded liposomes to be administered by vaginal route for uterine targeting. Liposomes were prepared by thin film hydration method using 1:1 M ratio of DSPC: Cholesterol and characterized for vesicle size, zeta potential, entrapment efficiency, and loading. Radiolabeling of LPA was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc-labeled complexes was assessed by diethylenetriaminepentaacetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation via vaginal route. Spherical and discrete vesicles of size 189 nm were seen in TEM results with entrapment efficiency and loading of 74.36% and 9.29%w/w, respectively. Liposomes were able to sustain the drug release for 5 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes concentrated and were retained within the uterus for a longer period of time. Uterine targeting of liposomal LPA indicates its potential to overcome the limitations of presently available formulations. Hence, this seems to be a promising approach for targeting the drugs, whose site of action is uterus.

Effect of Simplified One-Step Drilling Protocol on Osseointegration.

This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries. Histomorphometric parameters, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) were analyzed, and no statistical difference between drilling groups and/or implant geometry was found. Time was the only variable that affected BIC and BAFO, suggesting that the two protocols are equally biocompatible and osseoconductive.

A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits.

CONTEXT: Raloxifene hydrochloride (RLH), a selective estrogen receptor modulator, shows antiproliferative and apoptotic effects on Leiomyoma. Its extensive first pass metabolism leads to oral bioavailability of 2%. OBJECTIVE: The aim of this investigation was to formulate RLH-loaded liposomes and study its uterine-targeting efficiency after intravaginal administration. MATERIALS AND METHODS: Liposomes were prepared by thin film hydration method using 1:1 molar ratio of DSPC:Cholesterol and characterized for vesicle size, zeta potential, %entrapment efficiency, loading, drug release and transmission electron microscopy. Radiolabeling of RLH was performed with reduced technetium-99m (99mTc). Binding affinity of 99mTc-labeled complexes was assessed by diethylene triamine penta acetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation intravaginally. RESULTS AND DISCUSSION: Spherical and discrete liposomes of size 119 nm were seen in TEM results. Liposomes had high entrapment efficiency of 90.96% with drug loading of 27.25%w/w. Liposomes were able to sustain the drug release for 6 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes were concentrated and retained within the uterus for a longer period of time. CONCLUSION: Uterine targeting of RLH-loaded liposomes indicates its potential to overcome the limitations of marketed formulation. Drug targeting to site of action anticipates dose reduction needed to elicit the therapeutic effect.

Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

Prevalence of insomnia symptoms in sleep laboratory patients with and without sleep apnea.

We used the Insomnia Severity Index (ISI) to evaluate the prevalence and distribution of insomnia symptoms in 100 adult patients referred for laboratory evaluation of obstructive sleep apnea (OSA). Sixty-one percent met ISI criteria for a moderate to severe degree of insomnia symptoms. The distribution of insomnia symptoms did not differ by OSA severity.