Lefamulin: novel pleuromutilin drug for community acquired bacterial pneumonia

The advent and spread of antimicrobial resistance has led to a global public health emergency necessitating development of new antimicrobial drugs. Community acquired bacterial pneumonia (CABP) contributes a major portion of societal burden with increasing morbidity due to evolution of drug resistant strains. Lefamulin is a novel pleuromutilin antibiotic with unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50s bacterial ribosome. The drug displays activity against Gram positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumonia, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded Gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains). Lefamulin is available in both intravenous (IV) and per oral (PO) formulation, exhibits high nonlinear plasma protein binding with low unbound concentrations, higher concentrations in lung epithelial lining fluid (ELF) than in plasma, and a half-life of approximately 10 hour. The recommended IV dose is 150 mg twice daily over 1 hour or a PO dose of 600 mg twice daily. Most common adverse drug reactions injection site reactions, hepatic enzyme elevation, nausea, diarrhoea, hypokalemia, insomnia, and headache. Clinical trials for lefamulin have been positive and Phase 3 data suggest similar efficacy when compared to moxifloxacin with or without linezolid in CABP. Also, the documented resistance and cross-resistance with other Gram-positive antibacterials remains low. With Nabrivia Pharmaceuticals having already received US FDA approval in August 2019, lefamulin may soon be a new addition to the mounting armoury of drugs against CABP.

Amisulpride: tackling postoperative nausea and vomiting not a nightmare any more

Vomiting and nausea remains concern in postoperative patients for anaesthesiologists and surgeons. Patients remain at risk for adverse medical consequences as wound dehiscence, dehydration, electrolyte derangement’s and gastric aspiration. This entity delays discharge and is one of the causes of unanticipated admission after ambulatory surgery. Presently dopamine (D2), serotonin (5-HT3), and histamine (H1) antagonists are widely used prophylactic agents, as is the corticosteroid dexamethasone, but the incidence of postoperative nausea and vomiting (PONV) is still appreciable. Safety concerns as QT interval prolongation has led to nearly phasing out of use of D2-antagonist Droperidol, a potent and most favoured formulation. With minimal studies and randomized studies to back up the efficacy of existing modalities viz 5HT-antagonist, promethazine, metoclopramide and dimenhydrinate for management of postoperative nausea and vomiting, need for evaluation, study and incorporation into formulary for management was always persisting. Amisulpride is an anti-psychotic agent, used routinely in >50 countries worldwide is a potent but atypical D2-antagonist with minimal adverse profile mainly QT interval prolongation, extrapyramidal signs and symptoms, which had plagued out other members of same class. In addition to D2 antagonism this drug exhibits potent antagonist action against D3 receptors, implicated in the emetic response. In pre clinical studies and multiple randomized controlled multicenter studies the effectiveness and safety of low dose intra venous Amisulpride was established and approved as Barhemsys @Acacia Pharma by US Food and drug administration in February 2020. This drug will soon add to protocol-based management of PONV

Prospective randomised study of cases of pelvic fracture urethral distraction defects managed by early alignment versus initial suprapubic urinary diversion with delayed urethroplasty

Background: In complex pelvic fracture urethral distraction defects (PFUDD), early management prevents incidence of devastating complications such as urinary incontinence, restenosis and urethra cutaneous fistula. The aim of the present study was to study the outcome of patients with PFUDD undergoing early alignment (either by rail roading or endoscopic) compared with initial suprapubic urinary diversion with delayed urethroplasty.Methods: This was a prospective randomized study done at KGMU, Lucknow; having PFUDD during the period from June 2014 to July 2017. Patients with PFUDD were randomized in to two groups. Group A included 22 patients and managed by supra pubic cystostomy followed by delayed urethroplasty. Group B included 23 patients and managed by primary alignment by rail-roading and early endoscopic alignment. Patients were followed up after 6 weeks, 3 months and 6 months for measuring the primary and secondary outcomes during follow up.Results: The most common age group that sustained pelvic fracture urethral distraction defects injury are male of 21-40 years. In group A, stricture was present in all patients at 6 weeks post-surgery. Open urethroplasty was done at 3 months in 60% and 10% patients at 6 months.  In group B, stricture was present in 80% at 6 weeks, 40% at 3 months and 10% at 6 months. The incidence of ED in group A at 6 weeks, 3 months, was 25% patient which reduced to 20% at 6 months. In group B, ED was present in 30% patients 6 weeks, 3 months and which reduced to 25% at 6 months. No incontinence was observed in both groups.Conclusions: Primary realignment has significant benefits compared to SPC as realignment approach is associated with a 50%-55% decrease in stricture formation

Antinociceptive activity of the leaf essential oil of Coleus aromaticus Benth

The present study was undertaken to evaluate the possible antinociceptive effect of Coleus aromaticus Benth oil. The pain sensitivity was assessed by the acetic acid induced writhing and hotplate models in mice. The essential oil exhibited a significant reduction in acetic acid induced writhing response, a dose dependent increase in reaction time against thermal pain and a moderate motor impairment at analgesic doses and significant reduction in endurance time at higher dose on rotarod apparatus. These experimental results suggest that essential oil (250 and 500 mg/kg) produced analgesic effect in mice and may be a candidate for the development of pharmacological agents used in the pain management.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Spontaneous Rectal Perforation with Transanal Evisceration of the Small Bowel: A Rare Case Report

Transanal evisceration of the small bowel is a rare surgical emergency. Rectal perforation in such cases is usually due to an underlying rectal prolapse. We report a case of a middle aged (45 years) male with spontaneous rectal perforation and transanal evisceration of the small bowel. Approximately 150 cm of small bowel had eviscerated transanally and the patient required emergent abdominal exploration, reposition of the small bowel, and repair of the rectal perforation. Small bowel evisceration through the anal verge is an emergent condition and the aim was to prevent life threatening complications related to sepsis

Phospholipase C: underrated players in microbial infections

During bacterial infections, one or more virulence factors are required to support the survival, growth, and colonization of the pathogen within the host, leading to the symptomatic characteristic of the disease. The outcome of bacterial infections is determined by several factors from both host as well as pathogen origin. Proteins and enzymes involved in cellular signaling are important players in determining the outcome of host–pathogen interactions. phospholipase C (PLCs) participate in cellular signaling and regulation by virtue of their ability to hydrolyze membrane phospholipids into di-acyl-glycerol (DAG) and inositol triphosphate (IP3), which further causes the activation of other signaling pathways involved in various processes, including immune response. A total of 13 PLC isoforms are known so far, differing in their structure, regulation, and tissue-specific distribution. Different PLC isoforms have been implicated in various diseases, including cancer and infectious diseases; however, their roles in infectious diseases are not clearly understood. Many studies have suggested the prominent roles of both host and pathogen-derived PLCs during infections. PLCs have also been shown to contribute towards disease pathogenesis and the onset of disease symptoms. In this review, we have discussed the contribution of PLCs as a determinant of the outcome of host-pathogen interaction and pathogenesis during bacterial infections of human importance

Selaginella bryopteris

The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs