Disease-a-month: DM (Impact Factor: 0.95). 09/2011; 57(9):490-510. DOI: 10.1016/j.disamonth.2011.05.005
Article: Pathophysiology of diarrhoea[Show abstract] [Hide abstract]
ABSTRACT: The absorption and secretion of water and electrolytes throughout the gastrointestinal tract is a finely balanced, dynamic process and, when there is loss of this balance caused either by decreased absorption or increased secretion, diarrhoea results. Diarrhoea remains a major cause of morbidity and mortality worldwide, accounting for 3 million deaths per year in young children, and it is therefore important for those who care for children to have a clear understanding of the pathophysiology of diarrhoea. Diarrhoea can be considered to be either osmotic or secretory. Osmotic diarrhoea occurs when excessive osmotically active particles are present in the lumen, resulting in more fluid passively moving into the bowel lumen down the osmotic gradient. Secretory diarrhoea occurs when the bowel mucosa secretes excessive amounts of fluid into the gut lumen, either due to activation of a pathway by a toxin, or due to inherent abnormalities in the enterocytes. The management of acute diarrhoea is based on assessment of fluid balance of the child and rehydration. Oral rehydration with oral rehydration solution is extremely effective and has significantly reduced childhood mortality over the past 40 years. Chronic diarrhoea has a number of infective and non-infective causes, careful history and specific investigation and management in secondary or tertiary care is often necessary.Paediatrics and Child Health 10/2012; 22(10):443–447. DOI:10.1016/j.paed.2012.05.006
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ABSTRACT: Gut homeostasis results from complex neuro-immune interactions aimed at triggering stereotypical and specific programs of coordinated mucosal secretion and powerful motor propulsion. A prominent role in the regulation of this highly integrated network, comprising a variety of immune/inflammatory cells and the enteric nervous system, is played by purinergic mediators. The cells of the digestive tract are literally plunged into a "biological sea" of functionally active nucleotides and nucleosides, which carry out the critical task of driving regulatory interventions on cellular functions through the activation of P1 and P2 receptors. Intensive research efforts are being made to achieve an integrated view of the purinergic system, since it is emerging that the various components of purinergic pathways (i.e., enzymes, transporters, mediators and receptors) are mutually linked entities, deputed to finely modulating the magnitude and the duration of purinergic signaling, and that alterations occurring in this balanced network could be intimately involved in the pathophysiology of several gut disorders. This review article intends to provide a critical appraisal of current knowledge on the purinergic system role in the regulation of gastrointestinal functions, considering these pathways as a whole integrated network, which is capable of finely controlling the levels of bioactive nucleotides and nucleosides in the biophase of their respective receptors. Special attention is paid to the mechanisms through which alterations in the various compartments of the purinergic system could contribute to the pathophysiology of gut disorder, and to the possibility of counteracting such dysfunctions by means of pharmacological interventions on purinergic molecular targets.Pharmacology [?] Therapeutics 04/2013; 139(2). DOI:10.1016/j.pharmthera.2013.04.002 · 9.72 Impact Factor
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ABSTRACT: Osteoarthritis is the most common, multi component joint disease mainly characterized by destruction of articular cartilage which leads up to subchondral bone. Current treatment by NSAID's gives only symptomatic relief but semi-synthetic anthraquinone diacerein is novel chondroprotective agent intended for the treatment of osteoarthritis. Its active metabolite rhein inhibits the agents responsible for cartilage degradation. In the present study, stearic acid, long chain fatty acids, based solid lipid nanoparticles were prepared with enhanced oral bioavailability and lesser side effects. Diacerein loaded solid lipid nanoparticles were prepared by modified high shear homogenization with ultrasonication method using stearic acid as lipid. Pluronic F68 and soya lecithin was used as surfactant. Citric acid was added to give acidic environment to drug. Solid lipid nanoparticles were evaluated for different characterization parameters, in-vitro performance and in-vivo pharmacokinetics and anti-diarrhoeal study. Particle size of the diacerein loaded SLN was found in the range of 270 ± 2.1 to 510 ± 2.8 nm with zeta potential -13.78 ± 3.4 mV to -19.66 ± 2.1 mV. Maximum entrapment efficiency was achieved up to 88.1 ± 1.3%. Surface and solid state characterization by TEM, XRD and DSC revealed that all particles are spherical in shape and drug entrapped inside lipid was in amorphous state. In-vitro release was done by dialysis bag method in phosphate buffer (pH 5.8) which showed controlled and extended release profile up to 12 hr. In-vivo pharmacokinetic study reveals an increase in Area Under Curve from 26.68 ± 1.63 to 71.25 ± 1.25 hr μ g ml<SUP>-1</SUP>. Further diarrhoeal side effect of diacerein was also found to reduce up to 37% by lipid nanoparticles. These results suggest that diacerein loaded solid lipid nanoparticles can be prepared efficiently with stearic acid and produces controlled and prolonged drug release profile. The oral bioavailability was enhanced by around 2.7 times and with lesser diarrhoeal side effects. These all will leads to overall improvement in patient compliance for the treatment.Journal of Biomedical Nanotechnology 05/2013; 9(5-5):891-900. DOI:10.1166/jbn.2013.1580 · 5.34 Impact Factor
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