Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Pattern of drug compliance in leprosy patients attending urban centres--a longitudinal study

The pattern of drug compliance in 485 leprosy patients attending urban leprosy centres in Bombay was studied for 2 years. The study subjects included 113 patients with paucibacillary leprosy under dapsone monotherapy, 241 patients with paucibacillary leprosy under multidrug therapy and 131 patients with multibacillary leprosy under multidrug therapy. Their urine samples had been checked at least 6 times during the 2 years by DDS tile test at the time of their clinic attendance. The urine test results were not disclosed to the patients, but patients showing negative results were counselled about the need for regular drug intake. 35% of the patients were "Regular through out", 13% were "Irregular through out" and the other 52% who "Tended to be irregular" in their drug intake became "Regular" after counselling. Regularity in drug compliance was better in patients on multidrug therapy than in those on monotherapy. It is suggested that periodic testing of urine for checking for regularity of drug intake and subsequent counselling of patients should be made a routine practice to maintain drug compliance at a high level.     

Minimally invasive mitral valve surgery

BACKGROUND: To reduce surgical trauma and the drawbacks associated with sternotomy, we performed robotically controlled, video-assisted mitral valve surgery, using either the port-access or the transthoracic clamp technique. METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78 males, 143 females) underwent mitral valve surgery through a small right minithoracotomy using the port-access endovascular cardiopulmonary bypass system. Mitral valve exposure was facilitated with an endoscope attached to a voice-controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated camera positioning. Twenty-six patients underwent mitral valve repair and 195 had valve replacement. In 197 patients, mitral valve surgery was the primary operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/- 1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re-exploration for bleeding. There was no late death or re-operation on mean follow-up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared with those of our previous 220 patients who underwent mitral valve surgery with the median sternotomy approach. CONCLUSIONS: The use of video and robotic assistance in port-access mitral valve surgery not only minimizes the length of the incision, but also gives full visualization of the entire mitral valve apparatus. This approach provides comparable results with the sternotomy approach, as well as marked advantages of reduced intensive care unit stay. ,ower blood transfusion requirement, better cosmesis and earlier hospital discharge.     

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing,docking and molecular dynamics simulation study

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

Inhibitory potential of ilimaquinone (marine sponge metabolite) against nine essential SARS-CoV-2 target proteins, employing a molecular interaction and dynamics simulation approach.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population

Context:

Critically ill patients requiring mechanical ventilation frequently need sedatives and analgesics to facilitate their care. Dexmedetomidine, a short-acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic properties.

Aims:

The objective of this study was to evaluate the efficacy and safety of dexmedetomidine in comparison to propofol in the management of sedation for post-operative intensive care unit (ICU) patients, as a sedative agent.

Settings and Design:

Teaching hospital, A phase III, prospective, open, randomized and comparative.

Materials and Methods:

Thirty patients who were ambulatory and who required the post-operative mechanical ventilation or post-operative sedation were enrolled, in which 15 patients received Dexmedetomidine and remaining 15 patients received propofol. All these patients were treated for the period of 8 to 24 h.

Statistical Analysis Used:

Data were analyzed using Student''s t-test and Chi-square test. The value of P < 0.05 was considered as statistically significant.

Results:

Demographic data were comparable. Pulse rate, respiratory rate and blood pressure were comparable. Depth of sedation and extubation time were similar. To maintain analgesia throughout the study period, patients receiving propofol infusions required significantly more analgesics than patients receiving Dexmedetomidine.

Conclusions:

Dexmedetomidine appears to be a safe and acceptable ICU sedative agent when both the clinician''s and patient''s perspectives are considered.     

Knockdown of leptin A expression dramatically alters zebrafish development

Using morpholino antisense oligonucleotide (MO) technology, we blocked leptin A or leptin receptor expression in embryonic zebrafish, and analyzed consequences of leptin A knock-down on fish development. Embryos injected with leptin A or leptin receptor MOs (leptin A or leptin receptor morphants) had smaller bodies and eyes, undeveloped inner ear, enlarged pericardial cavity, curved body and/or tail and larger yolk compared to control embryos of the same stages. The defects persisted in 6-9days old larvae. We found that blocking leptin A function had little effect on the development of early brain (1day old), but differentiation of both the morphant dorsal brain and retinal cells was severely disrupted in older (2days old) embryos. Despite the enlarged pericardial cavity, differentiation of cardiac cells appeared to be similar to control embryos. Formation of the morphants' inner ear is also severely disrupted, which corroborates existing reports of leptin receptor expression in inner ear of both zebrafish and mammals. Co-injection of leptin A MO and recombinant leptin results in partial rescue of the wild-type phenotype. Our results suggest that leptin A plays distinct roles in zebrafish development.     

Recurrent pelvic organ prolapse: International Urogynecological Association Research and Development Committee opinion

Introduction and hypothesis

This committee opinion paper summarizes available evidence about recurrent pelvic organ prolapse (POP) to provide guidance on management.

Method

A working subcommittee from the International Urogynecological Association (IUGA) Research and Development Committee was formed. The literature regarding recurrent POP was reviewed and summarized by individual members of the subcommittee. Recommendations were graded according to the 2009 Oxford Levels of Evidence. The summary was reviewed by the Committee.

Results

There is no agreed definition for recurrent POP and evidence in relation to its evaluation and management is limited.

Conclusion

The assessment of recurrent POP should entail looking for possible reason(s) for failure, including persistent and/or new risk factors, detection of all pelvic floor defects and checking for complications of previous surgery. The management requires individual evaluation of the risks and benefits of different options and appropriate patient counseling. There is an urgent need for an agreed definition and further research into all aspects of recurrent POP.