COMPARAÇÃO MICROBIOLÓGICA ENTRE MEMBRANAS AMNIÓTICAS HUMANAS COLETADAS EM PARTOS VAGINAIS E CESARIANAS – PROJETO PILOTO

Objective: The amniotic membrane, a thin membrane, may be used as a temporary cover on deep burns. The objective of this study is to identify the differences regarding bacterial contamination between membranes of vaginal and cesarean deliveries, as well as to assess the possibility of the clinical use of stored membranes.Methods: Twelve membranes were obtained from women submitted to vaginal and cesarean deliveries at the Obstetric Center of Hospital de Clínicas de Porto Alegre. Each amniotic membrane was stored in five different flasks containing a physiological solution. Samples were obtained from these flasks for analysis on days 1, 7, 14, 21 and 28. These samples were tested for bacterial contamination, analyzing its relation to time of storage and type of delivery. This is a pilot study with a transversal design.Results: The comparison between types of delivery yielded a relative risk of contamination in vaginal delivery (RR) of 2.67 (95% CI: 1.09-6.52) and no significance (P = 0.08). No contamination was found on day 1 flasks.Conclusion: All membranes derived from vaginal deliveries ended up showing bacterial contamination during the storage period, which lead to a theoretical unavailability for its use on Amniotic Membrane Banks.Objetivo: A membrana amniótica, uma membrana fina, pode ser utilizada como cobertura temporária em queimaduras profundas. O objetivo deste estudo é o de verificar as possíveis diferenças quanto à contaminação bacteriana entre as membranas de partos cesáreo e vaginal, assim como avaliar a viabilidade ou não do uso clínico-cirúrgico da membrana armazenada.Métodos: Foram coletadas 12 membranas amnióticas de mulheres submetidas a parto cesáreo e vaginal no Centro Obstétrico do HCPA. Cada membrana amniótica foi armazenada em cinco frascos diferentes contendo soro fisiológico, dos quais foram obtidas amostras para análise no momento da coleta e nos dias 7, 14, 21 e 28. Essas amostras foram testadas quanto à contaminação bacteriana, analisando sua relação com o tempo de armazenamento e com o tipo de parto realizado. O estudo é um piloto e tem um delineamento transversal. Resultados: A comparação entre os tipos de parto mostrou um risco relativo (RR) de 2,67 de contaminação no parto vaginal em relação à cesariana (IC de 95%: 1,09 a 6,52), P = 0,08. Não foi verificada contaminação em nenhum dos frascos no momento da coleta. Conclusão: Todas as membranas coletadas de parto vaginal apresentaram crescimento bacteriano no processo de estocagem, levando à sua inviabilidade teórica para uso em Bancos de Membrana Amniótica

Keratinocyte Growth Factor Induces Gene Expression Signature Associated with Suppression of Malignant Phenotype of Cutaneous Squamous Carcinoma Cells

Keratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin. The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs (n = 6) than in normal skin samples (n = 6). Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF. KGF did not stimulate SCC cell proliferation, but it reduced invasion of SCC cells through collagen. Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes, including genes with tumor suppressing properties (SPRY4, DUSP4, DUSP6, LRIG1, PHLDA1). KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes, including genes associated with tumor progression (MMP13, MATN2, CXCL10, and IGFBP3). Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2. Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression. These results provide evidence, that KGF does not promote progression of cutaneous SCC, but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells, as compared to normal keratinocytes

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Adiponectin inhibits neutrophil phagocytosis of Escherichia coli by inhibition of PKB and ERK 1/2 MAPK signalling and Mac-1 activation

Full length adiponectin is a potent immune modulatory adipokine, impacting upon the actions of several immune cells. Neutrophil oxidative burst has been shown to decrease in response to adiponectin, and we speculated that it could have other effects on neutrophil function. Here we report that adiponectin reduces the phagocytic ability of human neutrophils, decreasing significantly the ingestion of opsonised E. coli by these cells in whole blood (p<0.05) and as isolated neutrophils (p<0.05). We then determined the mechanisms involved. We observed that the activation of Mac-1, the receptor engaged in complement-mediated phagocytosis, was decreased by adiponectin in response to E. coli stimulation. Moreover, treatment of neutrophils with adiponectin prior to incubation with E. coli significantly inhibited signalling through the PI3K/PKB and ERK 1/2 pathways, with a parallel reduction of F-actin content. Studies with pharmacological inhibitors showed that inhibition of PI3K/PKB, but not ERK 1/2 signalling was able to prevent the activation of Mac-1. In conclusion, we propose that adiponectin negatively affects neutrophil phagocytosis, reducing the uptake of E. coli and inhibiting Mac-1 activation, the latter by blockade of the PI3K/PKB signal pathway

Gastroparesis

Gastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence of a mechanical obstruction of the stomach, resulting in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching and bloating. Gastroparesis is now recognized as part of a broader spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation. The overlap between upper gastrointestinal symptoms makes the distinction between gastroparesis and other disorders, such as functional dyspepsia, challenging. Thus, a confirmed diagnosis of gastroparesis requires measurement of delayed gastric emptying via an appropriate test, such as gastric scintigraphy or breath testing. Gastroparesis can have idiopathic, diabetic, iatrogenic, post-surgical or post-viral aetiologies. The management of gastroparesis involves: correcting fluid, electrolyte and nutritional deficiencies; identifying and treating the cause of delayed gastric emptying (for example, diabetes mellitus); and suppressing or eliminating symptoms with pharmacological agents as first-line therapies. Several novel pharmacologic agents and interventions are currently in the pipeline and show promise to help tailor individualized therapy for patients with gastroparesis