Effects of Intravenous Lidocaine on Quality of Recovery After Laparoscopic Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to assess the effects of pre and intraoperative lidocaine infusion on short-term recovery quality after laparoscopic bariatric surgeries. In the search across MEDLINE, Embase, and Cochrane databases, we considered randomized controlled trials comparing intravenous lidocaine vs placebo (saline) for patients with obesity undergoing laparoscopic bariatric surgery. Seven studies (640 patients) were included. The lidocaine group had a significantly higher recovery quality score, a lower morphine consumption, and a notably reduced rate of nausea and vomiting compared with the placebo group. Additionally, Lidocaine infusion was associated with a shorter hospital stay, while no significant difference was observed in the time to bowel function recovery between both groups. In conclusion, lidocaine infusion before and during laparoscopic bariatric surgery contributes to an enhanced quality of recovery.

Arbovirus surveillance on the Mexico-USA border: West Nile virus identification in various species of field mosquitoes.

West Nile virus (WNV) has been documented in human and/or mosquito samples near the border with Mexico in El Paso, Texas, and Doña Ana County, New Mexico. However, on the Mexican side of the border, particularly in the State of Chihuahua, no such cases of WNV-infected mosquitoes have been documented. We tested 367 mosquitoes of four species (Culex quinquefasciatus, Cx. tarsalis, Aedes aegypti, and Aedes (Ochlerotatus) epactius) and found a high rate of WNV-positivity, including the first record of Ae. (Ochlerotatus) epactius infection with WNV. These results call for intensifying WNV surveillance efforts on the border between the United States and Mexico, with particular emphasis on vector control and monitoring of the species included in this study.

Design of a flexible cell-based assay for the evaluation of heat shock protein 70 expression modulators.

Heat shock protein 70 (Hsp70) is a chaperone protein that helps protect against cellular stress, a function that may be co-opted to fight human diseases. In particular, the upregulation of Hsp70 can suppress the neurotoxicity of misfolded proteins, suggesting possible therapeutic strategies in neurodegenerative diseases. Alternatively, in cancer cells where high levels of Hsp70 inhibit both intrinsic and extrinsic apoptotic pathways, a reduction in Hsp70 levels may induce apoptosis. To evaluate and identify, in a single assay format, small molecules that induce or inhibit endogenous Hsp70, we have designed and optimized a microtiter assay that relies on whole-cell immunodetection of Hsp70. The assay utilizes a minimal number of neuronal or cancer cells, yet is sufficiently sensitive and reproducible to permit quantitative determinations. We further validated the assay using a panel of Hsp70 modulators. In conclusion, we have developed an assay that is fast, robust, and cost efficient. As such, it can be implemented in most research laboratories. The assay should greatly improve the speed at which novel Hsp70 inducers and inhibitors of expression can be identified and evaluated.

The yeast Hsp110, Sse1p, exhibits high-affinity peptide binding.

Hsp110s are divergent relatives of Hsp70 chaperones that hydrolyze ATP. Hsp110s serve as Hsp70 nucleotide exchange factors and act directly to maintain polypeptide solubility. To date, the impact of peptide binding on Hsp110 ATPase activity is unknown and an Hsp110/peptide affinity has not been measured. We now report on a peptide that binds to the yeast Hsp110, Sse1p, with a K(D) of approximately 2 nM. Surprisingly, the binding of this peptide fails to stimulate Sse1p ATP hydrolysis. Moreover, an Hsp70-binding peptide is unable to associate with Sse1p, suggesting that Hsp70s and Hsp110s possess partially distinct peptide recognition motifs.

Design of a fluorescence polarization assay platform for the study of human Hsp70.

The 70kDa heat shock proteins (Hsp70) are molecular chaperones that assist in folding of newly synthesized polypeptides, refolding or denaturation of misfolded proteins, and translocation of proteins across biological membranes. In addition, Hsp70 play regulatory roles in signal transduction, cell cycle, and apoptosis. Here, we present a novel assay platform based on fluorescence polarization that is suitable for investigating the yet elusive molecular mechanics of human Hsp70 allosteric regulation.

High-throughput screening fluorescence polarization assay for tumor-specific Hsp90.

Heat shock protein 90 (Hsp90) is a molecular chaperone that has emerged as an important target in cancer and several other diseases, such as neurodegenerative diseases, nerve injuries, inflammation, and infection. Discovery of novel agents that inhibit Hsp90 and have druglike properties is therefore a major focus in several academic and industrial laboratories. In this study, the authors describe the development and optimization in a 384-well format of a novel assay for the identification of Hsp90 inhibitors using fluorescence polarization, which measures competitive binding of red-shifted fluorescently labeled geldanamycin (GM-cy3B) to Hsp90 found in the NCI-N417 small-cell lung carcinoma cells. The authors demonstrate that GMcy3B binds with high affinity and specificity to cellular Hsp90. The assay results in excellent signal-to-noise ratios (>10) and Z' values (>0.75) at tracer concentrations greater than 4 nM and 1 microg/well of total NCI-N417 protein, indicating a robust assay. It also equilibrates after 5 h of incubation at room temperature and remains stable for up to 24 h. Furthermore, it is a simple mix-and-read format that is cost-effective and uses only low amounts of fluorophore and cell lysates. A study using more than 15,000 compounds from the National Institutes of Health Molecular Libraries Screening Center Network was performed to validate its performance in a high-throughput screening format.

Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer.

The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compounds, we have discovered that small-cell lung carcinoma is a distinctive cellular system in which apoptosis is mainly regulated by Hsp90. Unlike the well-characterized antiapoptotic chaperone Hsp70, Hsp90 is not a general inhibitor of apoptosis, but it assumes this role in systems such as small-cell lung carcinoma, in which apoptosis is uniquely dependent on and effected through the intrinsic pathway, without involvement of caspase elements upstream of mitochondria or alternate pathways that are not apoptosome-channeled. These results provide important evidence for a transformation-specific interplay between chaperones in regulating apoptosis in malignant cells.

Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies.

Neurodegeneration, a result of multiple dysregulatory events, is a lengthy multistep process manifested by accrual of mutant variants and abnormal expression, posttranslational modification, and processing of certain proteins. Accumulation of these dysregulated processes requires a mechanism that maintains their functional stability and allows the evolution of the neurodegenerative phenotype. In malignant cells, the capacity to buffer transformation has been attributed to heat-shock protein 90 (Hsp90). Although normal proteins seem to require limited assistance from the chaperone, their aberrant counterparts seem to be highly dependent on Hsp90. Whereas enhanced Hsp90 affinity for mutated or functionally deregulated client proteins has been observed for several oncoproteins, it is unknown whether Hsp90 plays a similar role for neuronal proteins and thus maintains and facilitates the transformed phenotype in neurodegenerative diseases. Tauopathies are neurodegenerative diseases characterized by aberrant phosphorylation and/or expression of Tau protein, leading to a time-dependent accumulation of Tau aggregates and subsequent neuronal death. Here, we show that the stability of p35, a neuronal protein that activates cyclin-dependent protein kinase 5 through complex formation leading to aberrant Tau phosphorylation, and that of mutant but not WT Tau protein is maintained in tauopathies by Hsp90. Inhibition of Hsp90 in cellular and mouse models of tauopathies leads to a reduction of the pathogenic activity of these proteins and results in elimination of aggregated Tau. The results identify important roles played by Hsp90 in maintaining and facilitating the degenerative phenotype in these diseases and provide a common principle governing cancer and neurodegenerative diseases.

Synthesis of a red-shifted fluorescence polarization probe for Hsp90.

The synthesis of a red-shifted cy3B-GM ligand and its evaluation as a fluorescence polarization probe for Hsp90 is presented.

Synthesis of Hsp90 dimerization modulators.

The synthesis and evaluation of several chemical modulators of heat shock protein 90 (Hsp90) dimerization is presented. These agents may represent useful tools to study the importance of N-terminal dimerization and also to determine subunit interface(s) in Hsp90.

Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90.

Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and, thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. The study identifies water soluble derivatives (>5 mM in PBS pH 7.4) of nanomolar potency (IC(50) approximately 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenografted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors.

Evaluation of 8-arylsulfanyl, 8-arylsulfoxyl, and 8-arylsulfonyl adenine derivatives as inhibitors of the heat shock protein 90.

Hsp90 is a chaperone protein with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Currently there is an increasing interest in developing inhibitors of this protein as anticancer therapeutics. One of such inhibitors, the purine-scaffold class, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of 8-arylsulfanyl, -sulfoxyl, and -sulfonyl adenine members of the purine class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. Our results suggest that 8-arylsulfanyl adenine derivatives are good inhibitors of chaperone activity, whereas oxidation of the sulfides to sulfoxides or sulfones leads to compounds of decreased activity. The study identifies derivative 11v as the most potent Hsp90 inhibitor of the purine-scaffold series published to date (EC(50) = 30 nM), and also as the compound of this class with highest selectivity for tumor vs normal cell Hsp90 (700 to 3000-fold). Most rewardingly, this work has allowed for the identification of Hsp90 inhibitors with selective affinities for Hsp90-client protein complexes, derivatives that may represent useful pharmacological tools in dissecting Hsp90-regulated processes.

An alternative pathway of oleate beta-oxidation in Escherichia coli involving the hydrolysis of a dead end intermediate by a thioesterase.

The degradation of 2-trans,5-cis-tetradecadienoyl-CoA, a metabolite of oleic acid, by the purified complex of fatty acid oxidation from Escherichia coli was studied to determine how much of the metabolite is converted to 3,5-cis-tetradecadienoyl-CoA and thereby diverted from the classical, isomerase-dependent pathway of oleate beta-oxidation. Approximately 10% of the 2,5-intermediate was converted to the 3,5-isomer. When the latter compound was allowed to accumulate, it strongly inhibited the flux through the main pathway. Since Delta(3,5),Delta(2,4)-dienoyl-CoA isomerase was not detected in E. coli cells grown on oleate, the 3,5-intermediate cannot be metabolized via the reductase-dependent pathway. However, it was hydrolyzed by a thioesterase, which was most active with 3,5-cis-tetradecadienoyl-CoA as substrate and which was induced by growth of E. coli on oleate. An analysis of fatty acids present in the medium after growth of E. coli on oleate revealed the presence of 3,5-tetradecadienoate, which was not detected after cells were grown on palmitate or glucose. Altogether, these data prompt the conclusion that oleate is mostly degraded via the classical, isomerase-dependent pathway in E. coli but that a small amount of 2-trans,5-cis-tetradecadienoyl-CoA is diverted from the pathway via conversion to 3,5-cis-tetradecadienoyl-CoA by Delta(3),Delta(2)-enoyl-CoA isomerase. The 3,5-intermediate, which would strongly inhibit beta-oxidation if allowed to accumulate, is hydrolyzed, and the resultant 3,5-tetradecadienoate is excreted into the growth medium. This study provides evidence for the novel function of a thioesterase in beta-oxidation.

Rol de enfermeria en la utilizacion de proteina C activada durante el tratamiento del shock septico en pacientes politraumatizados / Rol of nursing in the use of Protein C during the treatment of the septic shock for multiple trauma

El estudio de cada nuevo tratamiento, droga, tecnica,disminuye notablemente los errores en la administración de medicamentos. Este estudio de caso demuestra la utilizacion de una nueva droga y el conocimiento que las enfermeras deben tener o investigar para asumir el cuidado de estos pacientes que muestran una clara posibilidad de mejorar mientras padecen shock septico (AU)

Rol de enfermeria en la utilizacion de proteina C activada durante el tratamiento del shock septico en pacientes politraumatizados / Rol of nursing in the use of Protein C during the treatment of the septic shock for multiple trauma

El estudio de cada nuevo tratamiento, droga, tecnica,disminuye notablemente los errores en la administración de medicamentos. Este estudio de caso demuestra la utilizacion de una nueva droga y el conocimiento que las enfermeras deben tener o investigar para asumir el cuidado de estos pacientes que muestran una clara posibilidad de mejorar mientras padecen shock septico

Presion intracraneana: monitorizacion de la Pic. cuidados de enfermeria / Intracranial pressure. Nursing care

La monitorizacion continua de la presion intracraneana (pic) es una de las tecnicas de mayor desarrollo en las patologias neurocríticas. Es una herramienta fundamental que el equipo de enfermeria a diario pone al alcance de los pacientes con neurotraumas, representando un desafio continuo dentro de la unidad de cuidados criticos. La elevacion de la pic es una causa frecuente de mortalidad o determinante de secuelas en los sobrevivientes (AU)

Presion intracraneana: monitorizacion de la Pic. cuidados de enfermeria / Intracranial pressure. Nursing care

La monitorizacion continua de la presion intracraneana (pic) es una de las tecnicas de mayor desarrollo en las patologias neurocríticas. Es una herramienta fundamental que el equipo de enfermeria a diario pone al alcance de los pacientes con neurotraumas, representando un desafio continuo dentro de la unidad de cuidados criticos. La elevacion de la pic es una causa frecuente de mortalidad o determinante de secuelas en los sobrevivientes