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.

Green tea and kombucha characterization: Phenolic composition, antioxidant capacity and enzymatic inhibition potential.

The present study aimed to carry out the physical-chemical, antioxidant, and enzymatic characterization of green tea and kombucha. It was observed that kombucha had lower pH, higher acidity, and solids content compared to green tea. As for the concentration of total phenolic compounds by the Folin Ciocalteu method, there was no significant difference between the beverages. In the antioxidant analysis by the DPPH assay, it was observed that both green tea and kombucha presented significant antioxidant capacity. In the TBARS analysis with the pH of the beverages neutralized, both showed a significant reduction in lipid peroxidation; however, kombucha exhibited pro-oxidant activity when evaluated in its natural form by this method. The beverages also showed significant inhibitory activity of the α-glucosidase enzyme, however, green tea presented superior inhibitory potential.

Uliginosin B, a Possible New Analgesic Drug, Acts by Modulating the Adenosinergic System.

Uliginosin B (ULI) is a natural acylphloroglucinol that has been proposed as a new molecular scaffold for developing analgesic and antidepressant drugs. Its effects seem to be due to its ability to increase monoamines in the synaptic cleft by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive effect of uliginosin B. The selective adenosine A1 receptor antagonist DPCPX and the selective A2A antagonist ZM 241385 prevented the effect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole) or adenosine deaminase (EHNA) did not affect the ULI effect. On the other hand, its effect was completely prevented by an inhibitor of ecto-5'-nucleotidase (AMPCP). This finding was confirmed ex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A1 and A2A receptors and the modulation of ecto-5'-nucleotidase activity contribute to the antinociceptive effect of ULI.

Paediatric anti-N-methyl-D-aspartate receptor encephalitis: The first Italian multicenter case series.

BACKGROUND: Given the rarity of this condition, especially in children, there is a paucity of large reported paediatric case series of anti-N-methyl-d-aspartate receptor encephalitis. METHODS: To contribute to define the features of this condition, we describe retrospectively a new nationwide case series of 20 children (50% females), referred by 13 Italian centres. RESULTS: Mean age at onset was 8 years (range 3-17). Prodromal symptoms were reported in 31.6%; onset was with neurological symptoms in 70%, and with behavioural/psychiatric disturbances in 30%. Most patients developed a severe clinical picture (90%), and 41% experienced medical complications; children 12-18 years old seemed to be more severe and symptomatic than younger patients. All children received first-line immune therapy; second-line treatment was administered to 45%. Relapses occurred in 15%. At last follow-up (mean 23.9 months, range 5-82), 85% patients had mRS 0-1; this rate was higher among older patients, and in those receiving first immune therapy within 1 month. CONCLUSIONS: Our case series confirms a symptomatologic core of paediatric anti-N-methyl-d-aspartate receptor encephalitis, even though displaying some distinctive features that may be explained by a specific genetic background or by the limited number of patients. The growing incidence of this condition, the relative age-dependent variability of its manifestations, the availability of immunotherapy and the possible better outcome with early treatment impose a high index of clinical suspicion be maintained. In the absence of data suggesting other specific etiologies, paediatricians should consider this diagnosis for children presenting with neurological and/or behavioural or psychiatric disturbances, regardless of age and gender.

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital.

BACKGROUND: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. OBJECTIVE: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. METHODS: This retrospective study was based on information obtained from patients' records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC). All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. RESULTS: The study population consisted of 100 patients who were mostly male (51%) with ages ranging between 21 and 40 years (42%), from the countryside (59%), in the chronic phase (95%), with high-risk prognostic factors (40%); the prognosis of high risk was not associated with complete hematologic response or complete cytogenetic response, but correlated to complete molecular response or major molecular response. Reticulin condensation was associated with complete hematologic response and complete cytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. The high adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. CONCLUSION: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC). All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51%) with ages rangingbetween 21 and 40 years (42%), from the countryside (59%), in the chronic phase (95%), with high-riskprognostic factors (40%); the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications. .

CD8+ NK cells are predominant in chimpanzees, characterized by high NCR expression and cytokine production, and preserved in chronic HIV-1 infection.

HIV-1 infection in humans results in an early and progressive NK cell dysfunction and an accumulation of an "anergic" CD56- CD16+ NK subset, which is characterised by low natural cytotoxicity receptor expression and low cytokine producing capacity. In contrast to humans, chimpanzee NK cells do not display a distinguishable CD56(bright) and CD56(dim) subset but, as shown here, could be subdivided into functionally different CD8+ and CD8- subsets. The CD8+ NK cells expressed significantly higher levels of triggering receptors including NKp46 and, upon in vitro activation, produced more IFN-gamma, TNF-alpha and CD107 than their CD8- counterparts. In addition, chimpanzee CD8- NK cells had relatively high levels of HLA-DR expression, suggestive of an activated state. Killing inhibitory receptors were expressed only at low levels; however, upon in vitro stimulation, they were up-regulated in CD8+ but not in CD8- NK cells and were functionally capable of inhibiting NKp30-triggered killing. In contrast to HIV-1-infected humans, infected chimpanzees maintained their dominant CD8+ NK cell population, with high expression of natural cytotoxicity receptors.

Aids no Brasil: uma epidemia em transformação / Aids in Brazil: an epidemic diseases in transformation

O quadro da AIDS no Brasil evidencia uma epidemia que tem sofrido transformações na sua evolução e distribuição geográfica. O presente estudo teve como objetivo descrever o atual perfil epidemiológico da AIDS no Brasil. Trata-se de uma análise retrospectiva, descritiva e observacional dos casos de AIDS notificados ao Minitério da Saúde, no período de 1980 a 2007. No início da epidemia, os casos de AIDS se concentravam nas grandes cidades do Sul e Sudeste, em indivíduos jovens do sexo masculino com nível sócio econômico elevado e considerados de grupo de risco. Atualmente, o perfil epidemiológico da AIDS está passando por grandes transformações. A epidemia está vançando para as regiões Norte e Nordeste, em indivíduos com idade acima de 50 anos, em ambos os sexos. A AIDS passou a atingir as mulheres, principalmente na faixa etária reprodutiva, o que pode acarretar aumenta da transmissão vertical do HIV, de mãe para filho. Observa-se um número maior de casos de AIDS em indivíduos heterosexuais e estabilização do número de casos em homosexuais. É imperativo que toda a sociedade em geral participe ativamente das campanhas de prevenção e conscientização da população para a vulnerabilidade de todos frente ao risco de contrair AIDS.

IFN-alpha-mediated increase in cytolytic activity of maturing NK cell upon exposure to HSV-infected myelomonocytes.

Impaired control of chronic pathogen replication may be associated to alterations of NK-cell function. Whether mechanisms underlying this dysfunction involve perturbations of differentiating NK cells is still unknown. We studied an "in vitro" model of differentiation from CD34(+)Lin(-) precursors growing only myelomonocytes and maturing NK cells and where myelomonocytes could be suitably infected with HSV, HIV, or vaccinia. Cultures were evaluated by cytofluorometry and cytotoxicity assays for perturbations in differentiating NK cells. Increased expression of natural cytotoxicity receptors on maturing NK cells with increased cytolytic activity was observed with HSV-1 infection, and with vaccinia while no modulation of NK-cell phenotype nor cytotoxic activity were evident with an ssRNA lentivirus (HIV-1). In the presence of constant IL-12 and IL-15 concentrations, the observed effect did not require cell contact, involved IFN-alpha and was not reproduced by the addition of TLR9 agonist, nor blocked by TLR9 antagonists. Virus replication at sites of NK-cell precursor development may have different outcomes depending on the interaction between invading viruses and maturing NK cells. Thus, NK-cell precursors may be involved in the immune response to dsDNA viruses and possibly contribute to efficient control of virus infection.

Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients.

Hepatitis C virus (HCV) readily establishes high-level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV-specific CD8+ CTL to clear viral replication. Virus-induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus-specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV-infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL-10 and normal concentrations of IFN-gamma upon cell-mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL-10 production could contribute, once NK cells localize in the liver, to a NK-DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control.

Molecular and functional characterization of NKG2D, NKp80, and NKG2C triggering NK cell receptors in rhesus and cynomolgus macaques: monitoring of NK cell function during simian HIV infection.

An involvement of innate immunity and of NK cells during the priming of adaptive immune responses has been recently suggested in normal and disease conditions such as HIV infection and acute myelogenous leukemia. The analysis of NK cell-triggering receptor expression has been so far restricted to only NKp46 and NKp30 in Macaca fascicularis. In this study, we extended the molecular and functional characterization to the various NK cell-triggering receptors using PBMC and to the in vitro-derived NK cell populations by cytofluorometry and by cytolytic activity assays. In addition, RT-PCR strategy, cDNA cloning/sequencing, and transient transfections were used to identify and characterize NKp80, NKG2D, CD94/NKG2C, and CD94/NKG2A in M. fascicularis and Macaca mulatta as well as in the signal transducing polypeptide DNAX-activating protein DAP-10. Both M. fascicularis and M. mulatta NK cells express NKp80, NKG2D, and NKG2C molecules, which displayed a high degree of sequence homology with their human counterpart. Analysis of NK cells in simian HIV-infected M. fascicularis revealed reduced surface expression of selected NK cell-triggering receptors associated with a decreased NK cell function only in some animals. Overall surface density of NK cell-triggering receptors on peripheral blood cells and their triggering function on NK cell populations derived in vitro was not decreased compared with uninfected animals. Thus, triggering NK cell receptor monitoring on macaque NK cells is possible and could provide a valuable tool for assessing NK cell function during experimental infections and for exploring possible differences in immune correlates of protection in humans compared with cynomolgus and rhesus macaques undergoing different vaccination strategies.

The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44).

Signals leading to NK cell triggering are primarily mediated by natural cytotoxicity receptors (NCR) upon binding to as-yet-undefined cell surface ligand(s) on normal hematopoietic cells, pathogen-infected cells or tumor cells. In this study we tried to determine whether the decreased NK cell cytolytic function that is observed in HIV-1-infected patients may be related to a decreased expression of NCR. In HIV-1-infected patients, freshly drawn, purified NK cells expressed significantly decreased surface densities of NKp46 and NKp30 NCR. The low surface density of NKp46, NKp30 and NKp44 was also confirmed in in-vitro-activated NK cell populations and NK cell clones derived from HIV-1 patients compared with uninfected donors. This defective NCR expression in HIV-1 patients was associated with a parallel decrease of NCR-mediated killing of different tumor target cells. Thus, the present study indicates that the defective expression of NCR represents at least one of the possible mechanisms leading to the impaired NK cell function in HIV-1 infection and it can contribute to explain the relatively high frequency of opportunistic tumors reported in cohorts of untreated patients before the occurrence of profound immunosuppression (<200 CD4(+) cells/mm(3)).

Low expression of inhibitory natural killer receptors in CD8 cytotoxic T lymphocytes in long-term non-progressor HIV-1-infected patients.

We investigated whether a different pattern of HLA-specific inhibitory natural killer receptor (iNKR) expression on peripheral blood mononuclear cells (PBMC) of long-term non-progressor (LTNP) patients explained their benign course of HIV-1 infection. The surface expression of p70, p140 and CD94/NKG2A in their CD3+CD8+ PBMC was comparable to that of uninfected donors. The lack of iNKR-mediated functional inhibition of HIV-1-specific cytotoxic T lymphocytes in vitro could provide an additional mechanism for the efficient control of virus spread in LTNP patients.

Estudo comparativo de antraciclicos na indução de cardiotoxicidade experimental: parâmetros eletro e ecocardiográficos, marcadores bioquímicos, alterações morfo-funcionais e abordagem farmacológica / Comparative study of anthracycline cardiotoxicity in experimental induction: electro and echocardiographic parameters, biochemical markers, morphological and functional changes and pharmacological approach

A cardiotoxicidade específica, que se desenvolve após doses cumulativas de antraciclinas, é o principal efeito limitante para o tratamento a longo prazo com estes agentes. Vários modelos animais reproduzindo as alterações morfológicas, bioquímicas e funcionais induzidas por doxorubicina, têm sido descritos e usados para testar novos análogos. Em estudos anteriores desenvolvemos um modelo de tratamento "in vivo" para estudo da cardiotoxicidade induzida por antracíclicos em ratos em que, consistentes e significativas alterações da função miocárdica puderam ser observadas e mensuradas em intervalo de tempo relativamente curto. O objetivo do presente estudo foi validar o modelo proposto para avaliação da cardiotoxicidade induzida por doxorubicina em ratos, usando a epirubicina (EPI), idarubicina (IDA) e mitoxantrona (MIT). Além de avaliar o potencial cardioprotetor da talidomida e pentoxifilina. Os parâmetros utilizados nesta avaliação foram: estudo eletro e ecocardiográfico; dosagem sérica dos marcadores bioquímicos (troponina T, CK-MB, LDH); curva ponderal; parâmetros hematológicos, índices cardíaco, hepático, esplênico e análise histopatológica...