Lutzomyia longipalpis salivary gland homogenate impairs cytokine production and costimulatory molecule expression on human monocytes and dendritic cells

In this report, we describe an investigation of the effects of Lutzomyia longipalpis sand fly salivary gland homogenates (SGH) on cytokine production and expression of costimulatory molecules on human monocytes, macrophages (Ms), and dendritic cells (DCs). SGH of L. longipalpis induced an increase in interleukin-6 (IL-6), IL-8 and IL-12p40 production but a decrease in tumor necrosis factor alpha and IL-10 production by lipopolysaccharida (LPS)-stimulated monocytes. We also examined the expression of costimulatory molecules on the surface of monocytes, Ms, and DCs. Whereas SGH affected the expression of these molecules on monocytes and Ms, it had little effect on these molecules on DCs. However, when DCs were generated from human monocytes in the presence of SGH, SGH inhibited the expression of costimulatory molecules. In addition, a decrease in the maturation of DCs induced by CD40L was observed in the presence of SGH. Finally, preincubating SGH with human sera containing anti-SGH-specific antibodies abolished the effects of SGH on cytokine production by LPS-stimulated monocytes.     

Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review

Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti‐apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.     

THE PROTECTIVE ACTION OF A SPECIFIC ENZYME AGAINST TYPE III PNEUMOCOCCUS INFECTION IN MICE

The bacterial enzyme which decomposes the purified capsular polysaccharide of Type III Pneumococcus in vitro also destroys the capsules of the living organisms growing in media and in the animal body. Potent preparations of this same enzyme protect mice against infection with virulent Type III Pneumococcus. The protective action is type-specific. The protective activity of the specific enzyme is destroyed by heat (70°C. for 10 minutes). The enzyme remains in an effective concentration 24 to 48 hours after its injection into normal mice. The enzyme has been found to exert a favorable influence on the outcome of an infection already established at the time of treatment. A definite relationship has been found to exist between the activity of the enzyme in vitro and its protective power in the animal body. The mechanism of the protective action is discussed with special reference to the relation between the decapsulation of the bacteria by the enzyme and the phagocytic response of the host.     

Melanoma: Diagnosis,Staging, and Treatment. Consensus group recommendations

The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.     

Relative contribution of different l-arginine sources to the substrate supply of endothelial nitric oxide synthase

In certain cases of endothelial dysfunction l-arginine becomes rate-limiting for NO synthesis in spite of sufficiently high plasma concentrations of the amino acid. To better understand this phenomenon, we investigated routes of substrate supply to endothelial nitric oxide synthase (eNOS). Our previous data with human umbilical vein (HUVEC) and EA.hy.926 endothelial cells demonstrated that eNOS can obtain its substrate from the conversion of l-citrulline to l-arginine and from protein breakdown. In the present study, we determined the quantitative contribution of proteasomal and lysosomal protein degradation and investigated to what extent extracellular peptides and l-citrulline can provide substrate to eNOS. The RFL-6 reporter cell assay was used to measure eNOS activity in human EA.hy926 endothelial cells. Individual proteasome and lysosome inhibition reduced eNOS activity in EA.hy926 cells only slightly. However, the combined inhibition had a pronounced reducing effect. eNOS activity was fully restored by supplementing either l-citrulline or l-arginine-containing dipeptides. Histidine prevented the restoration of eNOS activity by the dipeptide, suggesting that a transporter accepting both, peptides and histidine, mediates the uptake of the extracellular peptide. In fact, the peptide and histidine transporter PHT1 was expressed in EA.hy926 cells and HUVECs (qRT/PCR). Our study thus demonstrates that l-citrulline and l-arginine-containing peptides derived from either intracellular protein breakdown or from the extracellular space seem to be good substrate sources for eNOS.     

Subjective dysphagia in older care home residents: A cross-sectional,multi-centre point prevalence measurement

Background

Dysphagia has been found to be strongly associated with aspiration pneumonia in frail older people. Aspiration pneumonia is causing high hospitalization rates, morbidity, and often death. Better insight in the prevalence of (subjective) dysphagia in frail older people may improve its early recognition and treatment.

Objective

First, to assess the prevalence of subjective dysphagia in care home residents in the Netherlands. Second, to assess the associations of subjective dysphagia with potential risk factors of dysphagia.

Design

Retrospective data-analysis of a cross-sectional, multi-centre point prevalence measurement.

Setting

119 care homes in the Netherlands.

Participants

Data of 8119 care home residents aged 65 years or older were included and analyzed.

Methods

Subjective dysphagia was assessed by a resident's response to a dichotomous question with regard to experiencing swallowing problems. If a resident was not able to respond (e.g. residents with dementia or aphasia), the question was answered by the ward care provider, or the resident's file was consulted for registered swallowing complaints and/or dysphagia. Several residents’ data were collected: gender, age, (number of) diseases, the presence of malnutrition, the Care Dependency Scale score, and the body mass index.

Results

Subjective dysphagia was found in 751 (9%) residents. A final model for subjective dysphagia after multivariate backward stepwise regression analysis revealed eight significant variables: age (B −0.022), Care Dependency Scale score (B −0.985), ‘malnutrition’ (OR 1.58; 95% CI 1.31–1.90), ‘comorbidity’ (OR 1.07; 95% CI 1.01–1.14), and the disease clusters ‘dementia’ (OR 0.55; 95% CI 0.45–0.66), ‘nervous system disorder’ (OR 1.55; 95% CI 1.20–1.99), ‘cardiovascular disease’ (OR 0.81; 95% CI 0.67–0.99) and ‘cerebrovascular disease/hemiparesis’ (OR 1.74; 95% CI 1.45–2.10).

Conclusion

It seems justified to conclude that subjective dysphagia is a relevant care problem in older care home residents in the Netherlands. Care Dependency Scale score, ‘malnutrition’, and the disease clusters ‘dementia’, ‘nervous system disorder’, and ‘cerebrovascular disease/hemiparesis’ were associated with the presence of subjective dysphagia in this study. Age, ‘comorbidity’ and ‘cardiovascular disease’ showed very small influence.     

Echoendoscopic ultrasound/fine needle aspiration of an hepatic cystadenoma

The diagnosis of hepatic cystadenoma is difficult with the conventional radiologic imaging. When these hepatobiliary cystic tumors are located in the left liver, Echoendoscopic ultrasound/Fine needle aspiration can help in the diagnosis by showing high levels of cystic CEA and CA 19-9 in a mucinous fluid. Definitive histological evaluation is assessed by the examination of the operative specimen.