Role of metformin in experimentally-induced inflammatory bowel disease

En el presente trabajo, se ha estudiado la metformina, un derivado del antidiabético biguanida, para evaluar su efecto sobre una enfermedad inflamatoria intestinal inducida experimentalmente. Para inducir la enfermedad se utilizaron dos métodos: ácido 2, 4-dinitro-bencenosulfónico (DNBS) y ácido acético en ratas. El tratamiento con metformina (200 mg/kg, bid, vía oral) y ácido 5-aminosalicílico (5-ASA, estándar 100 mg/kg, vía intrarrectal) durante tres días permitió prevenir de forma significativa la pérdida de peso corporal (14,16±0,63; 9,8±0,51, p<0,05) y reducir el índice de daño macroscópico (1,33±0,45; 1,12±0,24, p<0,01), respectivamente en comparación con el grupo de control tratado con DNBS (6,66± 0,23). En ambos modelos se midieron igualmente otros parámetros: cambios de peso del colon, malondialdehido (MDA), mieloperoxidasa (MPO), superóxido dismutasa (SOD), óxido nítrico (NO) y degranulación de mastocitos. El tratamiento con metformina redujo significativamente los cambios de peso del colon, el índice de daño macroscópico, la peroxidación lipídica, el óxido nítrico (NO) y la degranulación de mastocitos en ambos modelos, sugiriendo una reducción significativa de la severidad de la inflamación en ratas.In the present study, metformin, a biguanide derivative of antidiabetic was studied for evaluating its effect against experimentally- induced infl ammatory bowel disease. The disease was induced by two methods: 2, 4 dinitrobenzenesulphonic acid (DNBS) and acetic acid in rats. Treatment with metformin (200mg/kg, bid, orally) and 5-aminosalicylic acid (5-ASA, standard 100mg/kg, intrarectally), for three days showed signifi cant prevention in body weight loss (14.16±0.63; 9.8±0.51, p<0.05) and reduction in macroscopic damage score (1.33± 0.45; 1.12± 0.24, p<0.01) respectively when compared with the DNBS treated control group (6.66± 0.23). Other parameters —colon weight changes, malondialdehyde (MDA), myeloperoxidase (MPO), super oxide dismutase(SOD), nitric oxide (NO) and mast cell degranulation— were also measured in both the models. Metformin treatment signifi cantly reduced colon weight changes, macroscopic damage score, lipid peroxidation, nitric oxide (NO) and mast cell degranulation levels in both the models suggesting signifi cant reduction in the severity of inflammation in rats

Natural DNA Uptake by Escherichia coli

Escherichia coli has homologues of the competence genes other species use for DNA uptake and processing, but natural competence and transformation have never been detected. Although we previously showed that these genes are induced by the competence regulator Sxy as in other gamma-proteobacteria, no conditions are known that naturally induce sxy expression. We have now tested whether the competence gene homologues encode a functional DNA uptake machinery and whether DNA uptake leads to recombination, by investigating the effects of plasmid-borne sxy expression on natural competence in a wide variety of E. coli strains. High- and low-level sxy expression alone did not induce transformation in any of the strains tested, despite varying the transforming DNA, its concentration, and the incubation conditions used. Direct measurements of uptake of radiolabelled DNA were below the limit of detection, however transformants were readily detected when recombination functions were provided by the lambda Red recombinase. This is the first demonstration that E. coli sxy expression can induce natural DNA uptake and that E. coli's competence genes do encode a functional uptake machinery. However, the amount of transformation cells undergo is limited both by low levels of DNA uptake and by inefficient DNA processing/recombination

Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera

Vertebrate studies show neuroligins and neurexins are binding partners in a trans-synaptic cell adhesion complex, implicated in human autism and mental retardation disorders. Here we report a genetic analysis of homologous proteins in the honey bee. As in humans, the honeybee has five large (31-246 kb, up to 12 exons each) neuroligin genes, three of which are tightly clustered. RNA analysis of the neuroligin-3 gene reveals five alternatively spliced transcripts, generated through alternative use of exons encoding the cholinesterase-like domain. Whereas vertebrates have three neurexins the bee has just one gene named neurexin I (400 kb, 28 exons). However alternative isoforms of bee neurexin I are generated by differential use of 12 splice sites, mostly located in regions encoding LNS subdomains. Some of the splice variants of bee neurexin I resemble the vertebrate alpha- and beta-neurexins, albeit in vertebrates these forms are generated by alternative promoters. Novel splicing variations in the 3' region generate transcripts encoding alternative trans-membrane and PDZ domains. Another 3' splicing variation predicts soluble neurexin I isoforms. Neurexin I and neuroligin expression was found in brain tissue, with expression present throughout development, and in most cases significantly up-regulated in adults. Transcripts of neurexin I and one neuroligin tested were abundant in mushroom bodies, a higher order processing centre in the bee brain. We show neuroligins and neurexins comprise a highly conserved molecular system with likely similar functional roles in insects as vertebrates, and with scope in the honeybee to generate substantial functional diversity through alternative splicing. Our study provides important prerequisite data for using the bee as a model for vertebrate synaptic development.Australian National University PhD Scholarship Award to Sunita Biswas

OncoLog Volume 39, Number 03 July-September 1994

Familial cancer syndromes a focus of cancer genetics research New test identifies Philadelphia chromosome-positive leukemiashttps://openworks.mdanderson.org/oncolog/1047/thumbnail.jp

An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor.

BackgroundWarthin tumors presenting concomitantly with a lymphoma is vanishingly rare with only 15 reported cases in English literature. Herein, we report an unusual initial presentation of a mantle cell lymphoma involving the lymphoid stroma of a Warthin tumor.Case presentationA seventy-seven year old otherwise healthy gentleman with a 50-pack year smoking history presents with a slowly enlarging left cheek mass. CT scan of the neck demonstrated a left parotid gland tumor measuring 3.4 cm in greatest dimension. He underwent a left superficial parotidectomy, with subsequent histopathologic examination revealing a Warthin tumor with extensive expansion of the lymphoid stroma. Flow cytometric, immunohistochemical, and cytogenetic studies of the stromal component of the tumor confirmed the presence of a mantle cell lymphoma. Clinical staging demonstrated stage IVa disease, and was considered to be at low to intermediate risk due to the slow growth of the parotid lesion. The patient is undergoing close follow up with repeat PET-CT scans at six months.ConclusionTo the best of our knowledge, this is the first well documented collision tumor between mantle cell lymphoma and a Warthin tumor. This case also brings to light the significance of thorough evaluation of the lymphoid component of Warthin tumor

Evaluation of the Clinical Efficacy of Potassium nitrate Desensitizing Mouthwash and a Toothpaste in the Treatment of Dentinal Hypersensitivity

Potassium Nitrate has been used as a desensitizing agent to treat dentinal hypersensitivity. The effectiveness of a potassium nitrate is evaluated both in the form of a toothpaste and a mouthwash in a clinical study. Thirty patients were assessed using evaporative stimuli and thermal stimuli and response was evaluated using Visual Analogue Scale at baseline, at 2 weeks and 4 weeks. The patients were divided into group I: fifteen patients who used toothpaste containing 5% potassium nitrate, sodium fluoride, xylitol and triclosan, group II: Fifteen patients who used mouthwash containing 3% potassium nitrate, sodium fluoride, xylitol and triclosan . The results of both the assessment methods indicated that potassium nitrate toothpaste as well as mouthwash showed statistically significant decrease in the sensitivity score on a Visual Analogue Scale. This was effective in reducing the symptoms of dentinal hypersensitivity when used either as toothpaste or as a mouthwash. But, there were no statistically significant differences between the groups, although both were effective in the treatment of hypersensitivity

Don’t turn your back on the symptoms of psychosis : a proof-of-principle, quasi-experimental public health trial to reduce the duration of untreated psychosis in Birmingham, UK

Background: Reducing the duration of untreated psychosis (DUP) is an aspiration of international guidelines for first episode psychosis; however, public health initiatives have met with mixed results. Systematic reviews suggest that greater focus on the sources of delay within care pathways, (which will vary between healthcare settings) is needed to achieve sustainable reductions in DUP (BJP 198: 256-263; 2011). Methods/Design: A quasi-experimental trial, comparing a targeted intervention area with a ‘detection as usual’ area in the same city. A proof-of–principle trial, no a priori assumptions are made regarding effect size; key outcome will be an estimate of the potential effect size for a definitive trial. DUP and number of new cases will be collected over an 18-month period in target and control areas and compared; historical data on DUP collected in both areas over the previous three years, will serve as a benchmark. The intervention will focus on reducing two significant DUP component delays within the overall care pathway: delays within the mental health service and help-seeking delay. Discussion: This pragmatic trial will be the first to target known delays within the care pathway for those with a first episode of psychosis. If successful, this will provide a generalizable methodology that can be implemented in a variety of healthcare contexts with differing sources of delay. Trial registration: http://www.controlled-trials.com/ISRCTN45058713 Keywords: Public mental health campaign, First-episode psychosis, Early detection, Duration of untreated psychosis, Youth mental healt

OncoLog Volume 40, Number 02, April-June 1995

Creative strategies key in fight against liver cancer Getting patients home and back to their routines more quickly Teaching physicians how to prevent cancerhttps://openworks.mdanderson.org/oncolog/1050/thumbnail.jp