Ceramide transfer protein function is essential for normal oxidative stress response and lifespan

Ceramide transfer protein (CERT) transfers ceramide from the endoplasmic reticulum to the Golgi complex, a process critical in synthesis and maintenance of normal levels of sphingolipids in mammalian cells. However, how its function is integrated into development and physiology of the animal is less clear. Here, we report the in vivo consequences of loss of functional CERT protein. We generated Drosophila melanogaster mutant flies lacking a functional CERT (Dcert) protein using chemical mutagenesis and a Western blot-based genetic screen. The mutant flies die early between days 10 and 30, whereas controls lived between 75 and 90 days. They display >70% decrease in ceramide phosphoethanolamine (the sphingomyelin analog in Drosophila) and ceramide. These changes resulted in increased plasma membrane fluidity that renders them susceptible to reactive oxygen species and results in enhanced oxidative damage to cellular proteins. Consequently, the flies showed reduced thermal tolerance that was exacerbated with aging and metabolic compromise such as decreasing ATP and increasing glucose levels, reminiscent of premature aging. Our studies demonstrate that maintenance of physiological levels of ceramide phosphoethanolamine by CERT in vivo is required to prevent oxidative damages to cellular components that are critical for viability and normal lifespan of the animal.     

An outbreak of Burkholderia cepacia associated with contamination of albuterol and nasal spray

BACKGROUND: Species within the Burkholderia cepacia complex (Bcc) can contaminate medications and disinfectants and cause severe pneumonia in critically ill patients or persons with cystic fibrosis. In March 2004, we investigated a hospital outbreak of Bcc possibly associated with a contaminated nasal spray. METHODS: We conducted a matched case-control study, environmental sampling, and observations of infection control practices. Case patients had infection or colonization with Bcc, and control patients had sputum culture not yielding Bcc. Isolates from patients and environmental samples were compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Bcc was recovered from sputum in 18 patients. Compared with matched control patients (n = 18), case patients were more likely to be receiving mechanical ventilation (p = 0.01), to have been hospitalized > 6 days (p = 0.01), and to have received antimicrobial treatment within 7 days before sputum collection (p = 0.03). Bcc was cultured from opened, but not unopened, multidose albuterol bottles, a nebulizer attached to a ventilator, and opened and unopened nasal spray bottles from contaminated lots. PFGE showed that isolates from albuterol samples and from patients were indistinguishable but unrelated to the nasal spray strain. Observations revealed improper aseptic techniques during respiratory therapy procedures and inadequate nebulizer cleaning. CONCLUSIONS: Despite a temporal association with use of a contaminated nasal spray, this outbreak was caused by extrinsic contamination of multidose albuterol used for nebulization treatments and lack of adherence to infection control precautions. Implementation and re-enforcement of infection control measures successfully terminated the outbreak.     

Outbreak of Acinetobacter spp septicemia in a neonatal ICU

An outbreak of Acinetobacter spp infection in the neonatal unit at Lok Nayak Hospital, New Delhi, India, is described. During a 6-month period, 68 strains of Acinetobacter baumannii were isolated from the blood and CSF of 47 neonates admitted to the intensive care unit. Diagnosis of clinically significant bacteremia was made in 36 patients. On environmental/personnel sampling, Acinetobacter spp isolates with similar antibiogram were recovered from intravenous catheter and washbasin. Control of the outbreak was possible only after strict infection control practices in the unit. It was concluded that any clinical multidrug resistant A. baumannii isolate can be a potential nosocomial outbreak strain.     

Loss of DLC1 is an independent prognostic factor in patients with oral squamous cell carcinoma

Deleted in liver cancer (DLC1), a Rho GTPase-activating protein, was observed to be differentially expressed in oral squamous cell carcinoma in comparison with normal tissues using tissue proteomics. In the current study, we investigated the clinical significance of loss of DLC1 expression in different stages of development of oral squamous cell carcinoma to determine its potential as a biomarker for oral dysplasia and prognosis of oral squamous cell carcinoma. Immunohistochemical analysis of DLC1 expression was carried out in oral squamous cell carcinoma patients (n=214), dysplasia (n=51), hyperplastic squamous mucosa (n=45), and histologically normal oral tissues (n=80), and correlated with clinicopathological parameters and disease prognosis over 91 months for oral squamous cell carcinomas. Loss of DLC1 expression was observed in oral squamous cell carcinoma (64%), oral dysplasia (31%), hyperplastic squamous mucosa (22%), and normal mucosa (16%). Significant loss of DLC1 expression was observed in oral squamous cell carcinomas as compared with dysplasia (P<0.001, odds ratio=3.8, 95% CI=2.0-7.3), suggesting it may be an important event involved in cancer progression. Among oral squamous cell carcinomas, the loss of DLC1 expression was significantly associated with poor prognosis (P=0.021, hazards ratio (HR)=1.8, 95% CI=1.1-2.9). Multivariate analysis revealed loss of DLC1 (P=0.023, HR=2.1, 95% CI=1.2-3.9) and histopathological grade (P=0.015, HR=1.7, 95% CI=1.1-2.7) to be independent predictors for disease-free survival in oral squamous cell carcinoma patients in comparison with known prognostic factors, viz. tumor stage, nodal status, and overall stage. Loss of DLC1 expression emerged as an important biomarker for predicting patients diagnosed with oral dysplasia at high risk of transformation upon future validation in longitudinal studies. Loss of DLC1 expression is a poor prognostic marker for oral squamous cell carcinoma patients.     

Chemotaxonomic Studies on Centella asiatica (L.) Urb. from Varied Phytogeographical Conditions of India for Its Industrial Prospection

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Centella asiatica (L.) Urb. (Apiaceae) with high commercial value is an important herb in traditional Indian...     

Incidence of Mallophaga on poultry in Dehradun (India).

The order of abundance of different mallophagan species on poultry birds in Dehradun (India) has been found to be Menopon gallinae greater than Menacanthus cornutus greater than Menacanthus stramineus greater than Goniocotes gallinae greater than Goniodes dissimilis greater than Lipeurus caponis greater than Lipeurus lawrensis tropicalis greater than Goniodes gigas. The intensity of these species upon 1249 birds has been recorded by coding system. The correlation between the monthly incidence of different species and environmental temperature as well as R.H. has been recorded. The degree of association between four most commonly occurring combinations has also been analysed.     

Percutaneous endoscopic colostomy of the left colon: a new technique for management of intractable constipation in children

BACKGROUND: The antegrade colonic enema is accepted as effective for management of intractable constipation in children when conventional bowel management has failed. This study describes experience with a new, minimally invasive technique, the distal antegrade colonic enema, which involves percutaneous endoscopic colostomy of the left colon. METHODS: Fifteen children with refractory constipation and soiling who had radiographic evidence of megarectum and/or distal colonic delay were selected for the procedure. The junction of the descending and the sigmoid colon was identified colonoscopically, and the percutaneous endoscopic colostomy tube, through which antegrade distal colonic enema are administered, was inserted. RESULTS: Fourteen children underwent distal percutaneous endoscopic colostomy insertion. The median time required for the procedure was 30 minutes (20-50 minutes). Excluding one child (technical difficulties with percutaneous endoscopic colostomy placement), median post-procedural hospital stay was 4 days (2-27 days). Thirteen children were no longer soiling, and improvement in quality of life was reported at 2 months' follow-up. At 6 months' follow-up, 90% of children were clean during intervals between enemas. All children evaluated at 12 months' follow-up remained clean. Median duration of follow-up was 12.5 months (2-51 months). CONCLUSIONS: The distal percutaneous endoscopic colostomy is a simple alternative to established methods for delivery of antegrade enemas. It is less invasive and on reversal leaves only minor scarring.     

Intestinal parasites in children with diarrhea in Delhi,India

The parasitic causes of diarrhea in children in Delhi were determined by the direct smear technique; stool specimens of 127 children were examined for intestinal parasites. In 59 cases (46.5%) intestinal helminths and protozoa were demonstrated. Ascaris lumbricoides was observed in 1 (0.8%) case, while Trichuris trichiura was the finding in 3 (2.4%). Protozoal parasites included Giardia intestinalis and Entamoeba histolytica in 14 (11%) cases each, Balantidium coli in 3 (2.4%) cases and Cryptosporidium spp in 24 (18.9%) patients. Mixed infection was not seen in any of the cases. Intestinal parasites may increase susceptibility to infection with other intestinal pathogens and therefore with the help of a simple technique, like direct fecal smear examination. rapid diagnosis can be made and specific therapy instituted.