Insulin resistance and endothelial dysfunction: Are epoxyeicosatrienoic acids the link?

Epoxyeicosatrienoic acids (EETs), the cytochrome P450 epoxygenase metabolites of arachidonic acid, are potent vasodilators and are believed to be the endothelium-derived hyperpolarizing factor in a number of vascular beds. In addition, EETs may play a role in the secretion and action of insulin and the metabolism of carbohydrates and lipids. Pharmacological manipulation of EETs may be a useful therapeutic approach for disease states such as hypertension, diabetes mellitus and the metabolic syndrome. EET mimetics and antagonists and drugs that increase EET synthesis or decrease their degradation are currently under investigation. The cellular mechanism of action of EETs appears to be complex and is being intensively studied by a number of investigators. In the present article, EET production, metabolism, isomerism and vasodilatory effects will be reviewed and potential mechanisms of action discussed. The role of EETs in insulin secretion and sensitivity and their implication in diabetes mellitus and the metabolic syndrome will also be reviewed. Drugs affecting EET bioavailability and action may be promising agents to use to treat hypertension/insulin resistance. The effects of these agents in experimental vascular disorders will also be discussed.     

Optimization and synthesis of silver nanoparticles using Isaria fumosorosea against human vector mosquitoes

The efficacy of silver generated larvicide with the help of entomopathogenic fungi, Isaria fumosorosea (Ifr) against major vector mosquitoes Culex quinquefasciatus and Aedes aegypti. The Ifr-silver nanoparticles (AgNPs) were characterized structurally and functionally using UV-visible spectrophotometer followed by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy and Fourier transform infrared (FTIR) spectra. The optimum pH (alkaline), temperature (30 °C) and agitation (150 rpm) for AgNP synthesis and its stability were confirmed through colour change. Ae. aegypti larvae (I–IV instars) were found highly susceptible to synthesized AgNPs than the larvae of Cx. quinquefasciatus. However, the mortality rate was indirectly proportional to the larval instar and the concentration. The lethal concentration that kills 50 % of the exposed larvae (LC₅₀) and lethal concentration that kills 90 % of the exposed larvae (LC₉₀) values of the tested concentration are 0.240, 0 0.075.337, 0.430, 0.652 and 1.219, 2.210, 2.453, 2.916; 0.065, 0.075, 0.098, 0.137 and 0.558, 0.709, 0.949, 1.278 ppm with respect to 0.03 to 1.00 ppm of Ifr-AgNPs against first, second, third and fourth instars of Cx. quinquefasciatus and Ae. aegypti, respectively. This is the first report for synthesis of AgNPs using Ifr against human vector mosquitoes. Hence, Ifr-AgNPs would be significantly used as a potent mosquito larvicide.     

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Acute kidney injury in critically ill children: Risk factors and outcomes

Background:

Acute kidney injury (AKI) is common in patients in the pediatric intensive care unit (PICU) and is associated with poor outcome. We conducted the present study to determine the incidence, risk factors and outcomes of AKI in the PICU.

Materials and Methods:

We collected data retrospectively from case records of children admitted to the PICU during one year. We defined and classified AKI according to modified pRIFLE criteria. We used multivariate logistic regression to determine risk factors of AKI and association of AKI with mortality and morbidity.

Results:

Of the 252 children included in the study, 103 (40.9%) children developed AKI. Of these 103 patients with AKI, 39 (37.9%) patients reached pRIFLE max of Risk, 37 (35.9%) patients reached Injury, and 27 (26.2%) had Failure. Mean Pediatric Risk of Mortality (PRISM III) score at admission was higher in patients with AKI than in controls (P < 0.001).     

Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population

Context:

Critically ill patients requiring mechanical ventilation frequently need sedatives and analgesics to facilitate their care. Dexmedetomidine, a short-acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic properties.

Aims:

The objective of this study was to evaluate the efficacy and safety of dexmedetomidine in comparison to propofol in the management of sedation for post-operative intensive care unit (ICU) patients, as a sedative agent.

Settings and Design:

Teaching hospital, A phase III, prospective, open, randomized and comparative.

Materials and Methods:

Thirty patients who were ambulatory and who required the post-operative mechanical ventilation or post-operative sedation were enrolled, in which 15 patients received Dexmedetomidine and remaining 15 patients received propofol. All these patients were treated for the period of 8 to 24 h.

Statistical Analysis Used:

Data were analyzed using Student''s t-test and Chi-square test. The value of P < 0.05 was considered as statistically significant.

Results:

Demographic data were comparable. Pulse rate, respiratory rate and blood pressure were comparable. Depth of sedation and extubation time were similar. To maintain analgesia throughout the study period, patients receiving propofol infusions required significantly more analgesics than patients receiving Dexmedetomidine.

Conclusions:

Dexmedetomidine appears to be a safe and acceptable ICU sedative agent when both the clinician''s and patient''s perspectives are considered.     

A chimeric T cell receptor with super-signaling properties

A key question yet to be resolved concerns the structure and function relationship of the TCR complex. How does antigen recognition by the TCR-alphabeta chains result in the activation of distinct signal transduction pathways by the CD3-gammadeltaepsilon/zeta complex? To investigate which part of the TCR-beta chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCR-beta chain with the corresponding TCR-gamma chain domains. We show here that hybridoma cells expressing a chimeric TCR-beta chain (betaIII) containing intracellular and transmembrane TCR-gamma amino acids, together with a wild-type TCR-alpha (alphawt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCR-alphawt/betawt chains. This super-signaling phenotype of the betaIII chain was observed in two different TCRs. One specific for an alloantigen (I-A(bm12)) and one for an autoantigen (I-A(b)/MOG(35-55)). We found that this chimeric alphawt/betaIII TCR had normal association with CD3-gammadeltaepsilon and zeta chains. To investigate the effect of the chimeric betaIII chain in transgenic T cells, we made MOG(35-55)-specific TCR transgenic mice expressing either the alphawt/betawt or chimeric alphawt/betaIII TCR. Similar to what was observed in hybridoma cells, transgenic alphawt/betaIII T cells showed a super-signaling phenotype upon antigenic stimulation. Further studies may help us understand the effect of increased TCR signaling on autoimmunity and may lead to the identification of signaling molecules that can be targeted to stop the progression of autoimmune disorders such as multiple sclerosis.     

Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi

Trypanosoma cruzi is an intracellular parasite that induces a strong Th1-type response and immunosuppression during the acute phase of infection. To study how the infection with T. cruzi would modulate the development of an autoimmune disease, we immunized C57BL/6 mice and IL-10 or iNOS knock-out mice of the same background with the encephalitogenic MOG 35-55 peptide and infected them with T. cruzi. Our results demonstrate that infection with T. cruzi completely prevents EAE development and furthermore induces complete and lasting remission in mice that were infected with this parasite after they had developed clinical EAE. Nitric oxide and IL-10 participate in triggering the mechanisms associated with EAE suppression by the infection. Decreased lymphoproliferation and increased frequencies of Annexin-positive cells and of T cells bearing CD95, CD95L or CTLA-4 were observed in the spleen from immunized/infected mice, as well as lower IL-2 and increased TGF-beta production in comparison with only immunized mice. Our results indicate that several effector and regulatory mechanisms of the immune response that arise during the acute phase of T. cruzi infection lastingly affect the expansion and/or effector functions of encephalitogenic cells, preventing the onset or inducing complete remission of EAE.     

Angiodysplasia of cardia of stomach--a case report

Angiodysplasia of gastrointestinal tract is still thought to be an entity of unknown aetiology. This lesion is most commonly observed in elderly patients presenting with severe and persistent iron deficiency anaemia, following occult blood loss or acute episodes of haematemesis. In the stomach antral vascular ectasia is the most common presentation. We report an autopsy case of vascular ectasia in the cardia of stomach in a young patient with clinical symptoms of anaemia as the presentation and an associated secondary hemosiderosis of liver.