Investigation of an outbreak of chikungunya in Malegaon Municipal areas of Nasik district, Maharashtra (India) and its control

BACKGROUND & OBJECTIVES: An outbreak of chikungunya fever occurred in Malegaon town of Nasik district of Maharashtra state, India during February and March 2006. A total of 4530 fever cases were reported during this period including 1781 cases which were admitted in different hospitals of the town. An entomological and epidemiological investigation was carried out in the affected villages during the outbreak to study the possible causes of the outbreak and to isolate the virus responsible. METHODS: Entomological evaluation was done as per WHO guidelines. Sera samples were collected by venipuncture from clinically suspected chikungunya patients in hospitals and also during house-to-house survey in affected villages. IgM antibodies to dengue virus were detected using IgM capture ELISA (PANBIO) and by "Haemagglutination inhibition test" for detection of antibodies against Chikungunya virus. Acute sera samples were inoculated in cell lines for virus isolation. The isolates were confirmed by RT-PCR. RESULTS: On investigation, it was found that water storage containers like cement tanks, plastic containers or earthen pots placed in front of the individual houses were the potential breeding sites for Aedes aegypti. Entomological survey carried out in the most affected areas revealed high Aedes indices. House, container and breteau indices were found to be 27.2, 16.19 and 35.1, respectively. Out of the 13 acute sera samples collected, virus was isolated in 10 samples. The isolates were confirmed by RT-PCR and sequencing using primers from nsP1 gene of Chikungunya virus (CHIKV, Accession No. EF077609, EF077610). Of the 17 convalescent sera tested, significant level of HI antibodies to CHIKV was detected in five samples. One sample was positive for IgM antibodies against dengue virus. Based on clinico-epidemiological features and laboratory findings, the illness was confirmed to be of chikungunya viral disease. CONCLUSION: Control measures targeting the vector population and personal protective measures against the mosquito bites were instituted. Extensive IEC campaign with the involvement of community and religious leaders helped in containment of the disease.     

Discovery, structure-activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase

A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease.     

Combination therapy of Ifenprodil with Piroxicam may be an effective therapeutic intervention in cerebral stroke: A hypothesis

Owing to the intricate and multifaceted pathology of cerebral stroke, multiple drug therapy had long been suggested for effective stroke treatment. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. In this context, we hypothesize the combination effect of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b selective NMDAR antagonist in animal model of cerebral ischemia. A few past studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil administered in singlet against cerebral ischemia in animal model, hence we hypothesized that by using Piroxicam and Ifenprodil in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics of Piroxicam with Ifenprodil which has been proved to have neuroprotective, anticonvulsant and antinociceptive effects and has potentials for the treatment of several neuropsychiatric disorders, such as Parkinson's disease alcoholism and drug addiction.     

An in-silico strategy to explore neuroprotection by quercetin in cerebral ischemia: a novel hypothesis based on inhibition of matrix metalloproteinase (MMPs) and acid sensing ion channel 1a (ASIC1a)

Cerebral ischemia are caused by acute interruption of the brain arterial blood supply, typically by a thrombus or embolus, leading to neuronal insult and the remainder damage are caused by blood vessel rupture, leading to hemorrhage. Acidosis and matrix metalloproteinase activation are the central and prominent metabolic feature of ischemic brain. The combined inhibition of MMPs and ASIC1a channels can offer a new therapeutic approach in cerebral stroke management. Moreover, the combined inhibition of MMPs and ASIC1a with flavonoids remains unknown against neuroprotection in animal models of cerebral ischemia. Flavonoids are believed to act as health-promoting substances and some of them have antioxidant and anti-inflammatory properties. Therefore, the target of the present study was in-silico evaluation of the neuroprotective efficacy of quercetin in rat model of focal cerebral ischemia/reperfusion (I/R) injury and efforts were made to analyze its inhibitory effects on MMPs activation and ASIC1a channels mediated downstream survival/damage mechanisms. Thus on the basis of our in-silico studies we hypothesize that quercetin can be a neuroprotective agent in rat model of focal cerebral ischemia/reperfusion (I/R) injury due to its inhibitory effects on MMPs activation and ASIC1a channels mediated downstream survival/damage mechanisms.     

Diuretics induced uremia and nonrecovery of renal function in a patient with acute renal failure caused by sepsis

Sepsis is a clinical syndrome related to severe infection and is characterized by systemic inflammation and injury to multiple organs and functional systems. Sepsis is one of the main causes of acute renal failure (ARF). Diuretics are frequently administered during ARF. However, there is scant evidence that diuretics provide any benefit to the patients with ARF. This case report highlights the occurrence of uremia and nonrecovery of renal function after administration of diuretics in a patient with ARF caused by sepsis. It is suggested that physicians should be cautious in prescribing diuretics to patients with ARF due to septicemia. Diuretics cause uremia and may lead to false diagnosis of chronic renal failure and nonrecovery of renal function. The patient may unnecessarily require prolonged dialysis.     

Injuries to the tibiofibular syndesmosis

The management of injury to the distal tibiofibular syndesmosis remains controversial in the treatment of ankle fractures. Operative fixation usually involves the insertion of a metallic diastasis screw. There are a variety of options for the position and characterisation of the screw, the type of cortical fixation, and whether the screw should be removed prior to weight-bearing. This paper reviews the relevant anatomy, the clinical and radiological diagnosis and the mechanism of trauma and alternative methods of treatment for injuries to the syndesmosis.     

Summarizing activity limitations in children with chronic illnesses living in the community: a measurement study of scales using supplemented interRAI items

Background  

To test the validity and reliability of scales intended to measure activity limitations faced by children with chronic illnesses living in the community. The scales were based on information provided by caregivers to service program personnel almost exclusively trained as social workers. The items used to measure activity limitations were interRAI items supplemented so that they were more applicable to activity limitations in children with chronic illnesses. In addition, these analyses may shed light on the possibility of gathering functional information that can span the life course as well as spanning different care settings.     

Cytogenetics of childhood T-cell leukemia

The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.