PcrG protects the two long helical oligomerization domains of PcrV, by an interaction mediated by the intramolecular coiled-coil region of PcrG

PcrV is a hydrophilic translocator of type three secretion system (TTSS) and a structural component of the functional translocon. C-terminal helix of PcrV is essential for its oligomerization at the needle tip. Conformational changes within PcrV regulate the effector translocation. PcrG is a cytoplasmic regulator of TTSS and forms a high affinity complex with PcrV. C-terminal residues of PcrG control the effector secretion

Polyphosphate kinase is involved in stress-induced mprAB-sigE-rel signalling in Mycobacteria

Polyphosphate kinase 1 (PPK1) helps bacteria to survive under stress. The ppk1 gene of Mycobacterium tuberculosis was overexpressed in Escherichia coli and characterized. Residues R230 and F176, predicted to be present in the head domain of PPK1, were identified as residues critical for polyphosphate (polyP)-synthesizing ability and dimerization of PPK1. A ppk1 knockout mutant of Mycobacterium smegmatis was compromised in its ability to survive under long-term hypoxia. The transcription of the rel gene and the synthesis of the stringent response regulator ppGpp were impaired in the mutant and restored after complementation with ppk1 of M. tuberculosis, providing evidence that PPK1 is required for the stringent response. We present evidence that PPK1 is likely required for mprAB-sigE-rel signalling. σE regulates the transcription of rel, and we hypothesize that under conditions of stress polyP acts as a preferred donor for MprB-mediated phosphorylation of MprA facilitating transcription of the sigE gene thereby leading finally to the enhancement of the transcription of rel in M. smegmatis and M. tuberculosis. Downregulation of ppk1 led to impaired survival of M. tuberculosis in macrophages. PolyP plays a central role in the stress response of mycobacteria

Rare association of central pontine myelinolysis with infantile tremor syndrome

Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating diseases, pontine neoplasm and different metabolic diseases. We report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS). ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes of hair and skin and anemia in malnourished children. Though first reported in Indian subcontinent many identical cases were reported from around the world. Our case is a 15 month old child with generalized tremor, mild hepatosplenomegaly with features of grade II malnutrition including skin and hair changes. All the signs and symtoms of tremor improved after treatment with the World Health Organization (WHO) protocol for protein energy malnutrition (PEM) and administration of propranolol without any side effects

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting in a tertiary care teaching hospital of Sikkim

Aim: Spontaneous voluntary adverse drug reaction (ADR) reporting is paramount to the success of the Pharmacovigilance Programme of India. There has however been minimal and sporadic voluntary reporting of ADR's at the ADR Monitoring Centre (AMC) Gangtok, Sikkim. Knowledge, perception, attitude, and awareness of health professionals are determinants of reporting practices. This questionnaire study aims at evaluating these indicators in the teaching hospital attached to the Medical Institute and find out methods to improve existing reporting practices. Materials and Methods: This is a cross-sectional questionnaire-based observational study carried out in the Medical, Surgical and Pathology Departments of the Teaching Hospital, Gangtok, Sikkim over a period of 2 months. The questionnaires were filled by the respondents and returned back to us within the next 24 h. Data obtained from filled questionnaires were thereby analyzed. Results: The overall correct response rate to the knowledge-based questions was 56.3%. While 97% of respondents were of the view that ADR reporting was necessary, 35% of the respondents felt that the difficulty in deciding the causality of an ADR discouraged them from reporting. 79% of the respondents were not aware of the presence of an AMC affiliated to the hospital, and 87% of the respondents admitted that they were not sending filled ADR forms to the AMC. Conclusions: The study indicates that the respondents have an average knowledge and positive attitude toward ADR reporting and pharmacovigilance. There is however a lack of awareness and poor ADR reporting practices. Efforts are required to enhance awareness and attitude toward pharmacovigilance and ADR reporting

Utilization study of antidiabetic agents in a teaching hospital of Sikkim and adherence to current standard treatment guidelines

Objective: Diabetes has gradually emerged as one of the most serious public health problems in our country. This underlines the need for timely disease detection and decisive therapeutic intervention. This prospective cross-sectional observational study aims at analyzing the utilization pattern of antidiabetic agents in a remote North-East Indian tertiary care teaching hospital in the perspective of current standard treatment guidelines. Materials and Methods: Diabetic patients receiving antidiabetic medication, both as outpatients and inpatients in our hospital over a period of 12 months (May 2013–May 2014), were included in this study. The data obtained were sorted and analyzed on the basis of gender, type of therapy, and hospital setting. Results: A total of 310 patients were included in the study. Metformin was the single most frequently prescribed antidiabetic agent (66.8%) followed by the sulfonylureas group (37.4%). Insulin was prescribed in 23.2% of the patients. Combination antidiabetic drug therapy (65.1%) was used more frequently than monotherapy (34.8%). The use of biguanides (P < 0.0001) and sulfonylureas (P = 0.02) in combination was significant as compared to their use as monotherapy. A total of 48% of all antidiabetic combinations used, comprised metformin and sulfonylureas (n = 96). Insulin use was significantly higher as monotherapy and in inpatients (P< 0.0001). The utilization of drugs from the National List of Essential Medicines was 51.2%, while 11% of antidiabetics were prescribed by generic name. Conclusion: The pattern of utilization largely conforms to the current standard treatment guidelines. Increased use of generic drugs is an area with scope for improvement

Isolated Hepatobiliary Involvement in an Infant with Langerhans Cell Histiocytosis: A Case Report with Review of Literature

Background: Langerhans cell histiocytosis (LCH) is a rare condition in which there is the proliferation of cells of the monocyte-dendritic cell lineage, including Langerhan's cells, with variable clinical manifestations and outcomes. Hepatic involvement is often seen as a part of multi-system LCH and is associated with a fulminant course. Isolated hepatobiliary involvement in LCH is rare. Clinical Description: We report an 11-month-old female infant presenting with prolonged fever associated with progressive jaundice, clay-colored stools, and a massive hepatomegaly. Liver biopsy showed CD1a and Langerin positivity. There was no other system involvement, and hence, the infant was diagnosed with a case of single-system LCH with isolated hepato-biliary LCH. Management and Outcome: A customized chemotherapeutic regimen was started with cytarabine and prednisolone. The patient has responded and there has been gradual improvement in the general clinical condition as well as the laboratory parameters. Conclusions: This case report creates the awareness of possible presentation of pediatric LCH with isolated liver involvement. A high index of suspicion, carefully customized chemotherapeutic regimen may help in the timely diagnosis and successful management