Toll-like receptors: Significance,ligands, signaling pathways,and functions in mammals

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.     

Migrating foreign body into the common carotid artery and internal jugular vein – A rare case

Ingested foreign bodies are a fairly common otorhinolaryngological emergencies encountered in Malaysia. The vast majority of these foreign bodies are fish bones which most commonly are impacted at the level of the cricopharynx. Rarely, however, a foreign body may migrate extraluminally and may even extrude subcutaneously. We report a rare occurrence where a fish bone not only migrated extraluminally, it was found to have migrated into the common carotid artery and the internal jugular vein and required surgical removal.     

11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics

In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues. We show that 11beta-HSD1, but not 11beta-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum. In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11beta-HSD inhibitor carbenoxolone (100 mg three times per day) improved verbal fluency (P < 0.01) after 4 weeks in 10 healthy elderly men (aged 55-75 y) and improved verbal memory (P < 0.01) after 6 weeks in 12 patients with type 2 diabetes (52-70 y). Although carbenoxolone has been reported to enhance hepatic insulin sensitivity in short-term studies, there were no changes in glycemic control or serum lipid profile, nor was plasma cortisol altered. 11beta-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline.     

The effects of preexisting depression on cerebrovascular health outcomes in geriatric continuing care

BACKGROUND: Previous studies have investigated depression as the cause and outcome of vascular deficit in elderly persons. METHODS: The authors wanted to determine whether baseline depression is predictive of subsequent cardiovascular events in very elderly persons residing in a continuing care retirement community (n = 181). RESULTS: Controlling for demographic factors, both depression and the number of cardiovascular risk factors (CVRFs) at baseline were strongly predictive of stroke, whereas only CVRFs strongly predicted myocardial infarctions. Depression accounted for 12% of the variance in stroke incidence, beyond the contribution of CVRFs. Path analysis indicated that depression was also a partial moderator of the effect of CVRFs. CONCLUSIONS: In support of the vascular depression hypothesis, the study findings indicate that, for the oldest old, depression may be a strong predictor of future stroke. The presence of depression in elderly patients should alert physicians to carefully investigate other stroke risk factors and to integrate depression into an overall intervention regimen for reducing patients' risks for stroke.     

Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?

There is currently intense research interest in the properties of HMG-CoA reductase inhibitors (statins) beyond their well-documented lipid-lowering action. Studies have consistently demonstrated that administration of statin therapy decreases levels of the inflammatory marker C-reactive protein (CRP), a marker associated with an increased risk of cardiovascular events. This effect appears to be independent of the extent of reduction in total or LDL-cholesterol. Statins also appear to improve endothelial dysfunction by increasing endothelium-dependent vasodilatation. There is also evidence that statins inhibit fibrin formation and thrombus development, an effect that which would be clinically beneficial following plaque fissure or rupture. Early preclinical and clinical evidence suggests that there are quantitative differences between statin regimens in terms of their cholesterol-independent properties. Trials comparing equipotent doses of different statins, based on lipid-lowering efficacy, have not reported any differences in cholesterol-independent properties. However, the current evidence base indicates that more aggressive statin regimens are associated with an enhanced anti-inflammatory effect. Intensive lipid-lowering using statin therapy generates a greater reduction in mortality than standard lipid management, and it is possible that enhanced cholesterol-independent effects may account for some of this excess benefit.     

Endoscopic management of pancreatic pseudocysts and walled-off pancreatic necrosis: A two-decade experience

Aim

To determine long-term outcome of endoscopic management of pancreatic pseudocyst/walled-off pancreatic necrosis (WOPN) without necrosectomy.

Methods

One-hundred and sixty-five pancreatic pseudocysts/WOPN managed endoscopically over a period of 22 years were analyzed retrospectively for technical success, complications, and recurrence.

Results

Symptomatic 118 males and 47 females with mean age of 35.8 years were included. Alcohol was the most common etiology (41.2 %). Transmural endoscopic drainage was done in 144 patients, while 21 patients underwent transpapillary drainage. All the patients were subjected to contrast computed tomography (CT) abdomen or routine/Doppler ultrasound. Endoscopic ultrasound was done in last 11 patients. One or two double pigtail 7 Fr stents were placed when clear watery fluid came out from cyst (130 patients, 78.8 %), and nasocystic drainage (NCD) tubes were placed in addition to two 7 Fr stents when there were frank pus, thick dark fluid, or solid components inside the cyst (35 patients). All these patients settled on this treatment. Thirty-three of 35 patients of WOPN could be managed endoscopically without necrosectomy. Complications occurred in 9.2 % of pseudocysts and 40 % of WOPN. Thirty-five patients were followed up for more than 5 years (3 patients more than 10 years), and 130 patients were followed up for up to 5 years. Recurrence occurred in 8.1 % of pseudocysts and 5.7 % of WOPN.

Conclusion

Majority of pancreatic pseudocysts/WOPN can be managed with endoscopic drainage without necrosectomy with high success, low complication, and recurrence rates.