Novel Amiloride Derivatives That Inhibit Bacterial Motility across Multiple Strains and Stator Types.

The bacterial flagellar motor (BFM) is a protein complex that confers motility to cells and contributes to survival and virulence. The BFM consists of stators that are ion-selective membrane protein complexes and a rotor that directly connects to a large filament, acting as a propeller. The stator complexes couple ion transit across the membrane to torque that drives rotation of the motor. The most common ion gradients that drive BFM rotation are protons (H+) and sodium ions (Na+). The sodium-powered stators, like those in the PomA/PomB stator complex of Vibrio spp., can be inhibited by sodium channel inhibitors, in particular, by phenamil, a potent and widely used inhibitor. However, relatively few new sodium motility inhibitors have been described since the discovery of phenamil. In this study, we characterized two possible motility inhibitors, HM2-16F and BB2-50F, from a small library of previously reported amiloride derivatives. We used three approaches: effect on rotation of tethered cells, effect on free-swimming bacteria, and effect on rotation of marker beads. We showed that both HM2-16F and BB2-50F stopped rotation of tethered cells driven by Na+ motors comparable to phenamil at matching concentrations and could also stop rotation of tethered cells driven by H+ motors. Bead measurements in the presence and absence of stators confirmed that the compounds did not inhibit rotation via direct association with the stator, in contrast to the established mode of action of phenamil. Overall, HM2-16F and BB2-50F stopped swimming in both Na+ and H+ stator types and in pathogenic and nonpathogenic strains. IMPORTANCE Here, we characterized two novel amiloride derivatives in the search for antimicrobial compounds that target bacterial motility. These compounds were shown to inhibit flagellar motility at 10 µM across multiple strains: from nonpathogenic Escherichia coli with flagellar rotation driven by proton or chimeric sodium-powered stators, to proton-powered pathogenic E. coli (enterohemorrhagic E. coli or uropathogenic E. coli [EHEC or UPEC, respectively]), and finally, sodium-powered Vibrio alginolyticus. Broad antimotility compounds such as these are important tools in our efforts to control virulence of pathogens in health and agricultural settings.

Vitamin D Profile in Juvenile Idiopathic Arthritis Patients in a Tertiary Care Hospital in Bangladesh.

There are multi-factorial causes of decrease in bone mass in Juvenile Idiopathic Arthritis (JIA) patients who correlate with the duration of active disease. By measuring the vitamin D level we can assess the deficiency or insufficiency earlier and can predict the risk of osteoporotic bone fracture & can give appropriate supplementation of vitamin D & calcium. This study was done to determine the status of serum 25(OH)D in patients with JIA and to see the relationship among various subtypes and disease duration. In this cross sectional study 30 (Thirty) newly diagnosed cases of JIA attending the pediatric rheumatology clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2014 to December 2015 were included. Thirty age and sex matched control were selected and serum 25(OH)D was measured in cases and controls. Among JIA patients, 60% and among controls 33% had hypo-vitaminosis D. In JIA group the mean level of serum 25(OH)D was lower than control group and the result is statistically significant in cases of poly-articular JIA and systemic JIA (SJIA). There is significant difference of the mean values of vitamin D levels in JIA and control groups for the cases of hypo-vitaminosis D. Level of serum 25(OH)D significantly decreased as disease duration continue increased. More than half of JIA patients had hypo-vitaminosis D. It is more significant in cases of poly-articular JIA and systemic JIA (SJIA). There was negative relationship between serum 25(OH)D level and disease duration.

Effect of Intravenous Paracetamol with Bupivacaine Scalp Nerve Block on Haemodynamics Response as Well as Anaesthetic Requirements during Supratentorial Craniotomies.

Noxious stimuli during craniotomy may encourage hypertension and tachycardia, which may rise to morbidity in patients with intracranial hypertension. After craniotomy a moderate level of postoperative pain observed. The objective of this study was to observe the effect of intravenous paracetamol with bupivacaine scalp nerve block (SNB) on haemodynamics response as well as anaesthetic & analgesic requirements during supratentorial craniotomies. This is a single-blind, placebo-controlled, randomized clinical trial carried out in the Neurosurgery operation theatre from August 2015 to July 2017 under supervision of Department of Anaesthesia, Analgesia and Intensive Care Medicine of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. A total of 40 patients aged 18-60 years with supratentorial space occupying lesion undergoing craniotomy under general anaesthesia who were attended in the department of Neurosurgery, BSMMU were enrolled in this study and they were divided randomly into two groups, 20 patients in each. The Group A received 100ml normal saline infusion and 0.25% bupivacaine (20ml) in scalp block, while the Group B received intravenous injection paracetamol (1gm) and 0.25% bupivacaine (total 20ml) in scalp block. Statistical analyses were obtained Statistical Packages for Social Sciences (SPSS-22). The mean systolic blood pressure varied within the normal range in both groups. The mean DBP of Group B remained significantly lower than that of Group A in different follow up except at 30 minutes and 60 minutes after dura incision. However, mean MAP of Group B remained significantly lower than that of Group A in different time interval. The mean heart rate of Group B remained significantly lower than that of Group A. The mean intraoperative propofol as well as fentanyl requirements were significantly decreased in Group B in comparison to Group A. The combination of intravenous paracetamol with bupivacaine scalp nerve block provides better intra-operative haemodynamic stability and neurosurgical compliances for the patients undergoing supratentorial craniotomies under general anaesthesia.

Swertiamarin, a natural steroid, prevent bone erosion by modulating RANKL/RANK/OPG signaling.

Bone erosion is a central feature of rheumatoid arthritis (RA) that is characterized by the infiltration of the synovial lining by osteoclasts and lymphocytes. In the present study, swertiamarin a major secoiridoid glycoside was evaluated for anti-osteoclastogenic property to prevent bone erosion in Freund's complete adjuvant (FCA) induced in-vivo model, in-vitro osteoblast and osteoclasts as well as in co-culture system and in-silico molecular docking analysis. The swertiamarin treatment decreased the expression of TRAP, RANKL, and RANK levels and increased the levels of OPG levels significantly in both in vitro and in vivo models. In in vitro, the compound treatment significantly increased the cell proliferation and ALP levels in osteoblast cells; the high proliferation (153.8600±5.23%) and ALP release (165.6033±4.13%) were observed at 50µg/ml concentration of swertiamarin treatment. At the same time the treatment decreased the TRAP positive cells in osteoclast cells; the high reductions of TRAP positive cells (39.32±3.19%) were observed at 50µg/ml of swertiamarin treatment. The treatment modulated the levels of pro-inflammatory cytokines, MMPs and NF-κB levels in osteoblast and osteoclast co-culture system. In in silico analysis swertiamarin had affinity towards the proteins RANK, RANKL and OPG residues with low binding energy -4.5, -3.92 and -5.77kcal/mol respectively. Thus, the results of this study revealed the anti-osteoclastogenic activity of swertiamarin on the prevention of bone destruction.

Macrophage Activation Syndrome in Paediatric Rheumatic Diseases.

Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic disorders, which commonly occurs in systemic juvenile idiopathic arthritis (sJIA).This study was carried out with the aims of describing the clinical features, laboratory findings and outcomes of MAS associated with paediatric rheumatic diseases in the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) and compare these results with previous studies on MAS. This retrospective study was conducted in the paediatric rheumatology wing of the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Clinical and laboratory profile of all the diagnosed cases of MAS were analyzed from the medical records from January 2010 to July 2015. Among 10 MAS patients, 6 were female and 4 were male. Seven patients of systemic JIA, two patients of SLE and one patient with Kawasaki Disease developed MAS in their course of primary disease. Mean duration of primary disease prior to development of MAS was 2.9 years and mean age of onset was 9.1 years. High continued fever and new onset hepatosplenomegaly were the hallmark of the clinical presentation. White blood cell count and platelet count came down from the mean of 16.2 to 10.2×109/L and 254 to 90×109/L. Mean erythrocyte sedimentation rate was dropped from 56 to 29 mm/hr. Six patients had abnormal liver enzyme level (ALT) and 5 had evidence of coagulopathy (prolonged prothrombin time and APTT) at the onset of disease. Hyperferritinnemia were found in all the patients. Bone marrow study was done in 5 patients but features of hamophagocytosis were found only in 2 patients. All patients received intravenous steroid and 3 patients who did not respond to steroid received additional cyclosporine. Mortality rate was 30% in this series. Macrophage activation syndrome is a fatal complication of paediatric rheumatic diseases among which s-JIA was predominant. Early diagnosis and aggressive therapy is essential to reduce the morbidity and mortality of this illness.

Poncet's disease (tubercular rheumatism) - a case report.

Poncet's disease is a rare condition in childhood. It occurs due to immunological reaction to tubercular protein resulting in reactive arthritis and manifest with polyarthritis associated with features of active tuberculosis. We are reporting a case of Poncet's disease that was initially treated as a case of Juvenile Idiopathic Arthritis (JIA) without any improvement. The diagnosis was made clinically from history and physical findings with supportive radiological findings and confirmed by granulomatous changes on FNAC. Our patient improved dramatically after treatment with anti-tubercular drugs. Though very rare, Poncet's disease should be strongly considered in the differential diagnosis of fever and polyarthritis of obscure cause, especially in tubercular endemic countries like ours.

Moebius syndrome with Taussig-Bing anomaly.

We report a 6 years old male child, presented with difficulty in swallowing, crying and smiling from early infancy and recurrent episodes of cyanosis on exertion for about 2 years. He had facial dysmorphism, clubbing and polydactyly and right sided lower motor neuron type of facial nerve palsy. On examination and relevant investigations findings were consistent with Moebius syndrome and Taussig-Bing anomaly. Moebius syndrome comprises of congenital facial nerve palsy with or without palsy of the other cranial nerves and the associated organ system malformations. Taussig-Bing anomaly is a rare congenital heart malformation consisting of a transposed aorta, a large pulmonary artery which arises primarily from the right ventricle and ventricular septal defect. Simultaneous occurrence of Moebius syndrome and Taussig-Bing anomaly has not yet been reported in the past.