Influence of hormone release during acute stress upon plasma glucose and arterial pressure

Stress is a common factor in daily routine, and yet little attention is given to the possible changes and disturbances caused by stress upon homeostasis. Therefore, this study aims to evaluate blood pressure (BP) and blood glucose (BG) before and after acute stress simulation and to verify the influence of catecholamine secretion upon these parameters. Acute stress simulation was achieved by submitting fifteen volunteers to a ride on a free-fall simulator at an amusement park. The distance of the fall is approximately 69.5 m and the velocity reaches 94 kph. BG was determined before and after the stress situation and BP was checked before and after that condition. The result demonstrated that the volunteers who had previously mentioned being afraid of the ride had a significant increase in BG immediately after stress and tended to have a higher BP, indicating that psychological factors, such as fear and anxiety, are related to significant changes in the parameters under evaluation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary oxidative and nitrosative stress biomarkers in patients with head and neck

Cisplatin is a chemotherapeutic agent widely used in the treatment of several solid tumours. For patients with advanced head and neck squamous cell carcinoma in whom surgery is contraindicated, treatment with high-dose cisplatin administered every 21 days for 3 cycles concomitantly with conventional radiotherapy is recommended [1-3]. Its anticancer mechanism is mediated by DNA binding, which leads to the formation of inter-and intrastrand crosslinks and results in defective DNA templates, arrest of DNA synthesis and replication, DNA damage and, finally, cell death [4]. In addition, cisplatin accumulates in human cells (normal and tumour cells) resulting in enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which leads to mitochondrial damage and dysfunction [5,6]. In addition, there is a decrease in the antioxidant defence system mediated primarily by links formed between cisplatin and glutathione, which culminates in the depletion of glutathione [7]. The excessive generation of ROS and RNS damages biomolecules, resulting in lipid, protein and DNA/RNA oxidation and causing toxicities including nephrotoxicity, neurotoxicity, ototoxicity and hepatotoxicity [8-11]. The intensity of biomolecular damage can be determined by oxidative/nitrosative stress biomarkers. In this study, we used malondialdehyde (MDA) and lipid hydroperoxides, which are indicators of lipid peroxidation/oxidative stress biomarkers and nitrite, a nitrosative stress biomarker. Therefore, the aim of this study was to determine the effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary levels of MDA, lipid hydroperoxides and nitrite biomarkers in patients with head and neck11818386CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES

MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer.

BackgroundNo biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin.MethodsWe performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity.ResultsMiR-3168 (p = 1.98 × 10- 8), miR-4718 (p = 4.24 × 10- 5), and miR-6125 (p = 6.60 × 10- 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00-1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03-2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98-3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61-0.93) with sensitivity of 66.76 and specificity of 79.49.ConclusionsWe have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity

GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 ille105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal orValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the Ilelle genotype. In multivariate Cox analysis, patients with the GSTP/1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the Ilelle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP/1 ille105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT9FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2012/1807-

Influência do fumo na atividade da amilase salivar e na curva glicêmica Influence of smoking on salivary amylase activity and glycemic curve

OBJETIVO: Determinar a atividade da amilase salivar e a relação com a glicemia, antes e após a ingestão de carboidratos em fumantes e não fumantes, uma vez que in vitro a exposição da saliva à fumaça do cigarro induz à redução da atividade da amilase salivar e poderia influenciar na absorção dos carboidratos da dieta. MÉTODOS: Foram avaliados voluntários fumantes (n=10) e não fumantes (n=10). Realizou-se coletas da saliva antes e após o fumo e determinou-se a glicemia antes e após a ingestão de 72g de carboidratos. Para glicemia usaram-se tempos de 0, 15, 30, 60, 120 minutos. A determinação da atividade da amilase salivar foi realizada por meio de kits comerciais. A glicemia foi determinada utilizando o aparelho Glicomiter (Accu-Chek-Roche). As análises estatísticas foram realizadas no software Sigmastat, utilizou-se o método Teste t pareado (p<0,05). RESULTADOS: O aumento da glicemia aos 15, 30, 60 e 90 minutos foi de 3,9; 11,9; 34,8 e 22,7% para os não fumantes e 4,9; 6,5; 13,8 e 9,7% para os fumantes, respectivamente. No pico máximo de absorção tem-se uma glicemia de 21,0 % maior nos pacientes não fumantes. A atividade da amilase salivar antes e após alimentação apresentou-se 75,0% menor nos indivíduos fumantes. CONCLUSÃO: Estes resultados sugerem que o fumo inibe a amilase e influencia na diminuição da digestão/absorção de carboidratos, consequentemente na concentração de glicose sanguínea, reduzindo assim o aporte energético ingerido.<br>OBJECTIVE: The objective of this study was to determine salivary amylase activity and its relationship with glycemia before and after smokers and nonsmokers ingested carbohydrates. Since cigarette smoke reduces salivary amylase activity in vitro, it may affect dietary carbohydrate absorption. METHODS: Twenty volunteers participated in this study, 10 smokers and 10 nonsmokers. Samples of saliva were collected before and after the smokers had a cigarette and glycemia was determined before and after the ingestion of 72g of carbohydrates. Glycemia was measured 0, 15, 30, 60 and 120 minutes after carbohydrate intake. Salivary amylase activity was determined by commercial kits. Glycemia was determined by a glucometer (Accu-Chek-Roche). The paired t-test was used for the statistical analyses, done by the software Sigmastat, with p<0.05. RESULTS: Glycemia 15, 30, 60 and 90 minutes after carbohydrate intake rose 3.9%, 11.9%, 34.8% and 22.7% in nonsmokers and 4.9%, 6.5%, 13.8% and 9.7% in smokers, respectively. The peak glucose absorption in nonsmokers was 21.0% greater than in smokers. Salivary amylase activity before and after eating was 75.0% smaller in smokers. CONCLUSION: These results suggest that smoking inhibits amylase and has a negative impact on the digestion/absorption of carbohydrates, consequently in blood glucose levels, thereby reducing the amount of energy absorbed