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Influence of Soy Lecithin Administration on Hypercholesterolemia

Recent studies suggest that lecithin-rich diet can modify cholesterol homeostasis and hepatic lipoprotein metabolism. Considering the phytotherapeutic impact of lecithin, this work hypothesizes that lecithin administration in hypercholesterolemic patients may reduce cholesterol concentrations by increasing biliary secretion. Total cholesterol and LDL were evaluated after soy lecithin administration in hypercholesterolemic patients. One soy lecithin capsule (500 mg/RP-Sherer) was administrated daily. One-two months before the treatment beginning, blood samples were collected for total lipids and cholesterol fractions analysis. The results showed a reduction of 40.66% and 42.00% in total cholesterol and of 42.05% and 56.15% in LDL cholesterol after treatment for one and two months, respectively. A significant reduction in total cholesterol and LDL-cholesterol concentrations was observed during the first month of treatment, suggesting that the administration of soy lecithin daily may be used as a supplemental treatment in hypercholesterolemia.

XPD c.934G > A polymorphism of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation.

Antioxidant capacity total in non-melanoma skin cancer and its relationship with food consumption of antioxidant nutrients

The non-melanoma skin cancer is the most common cancer and accounts for more than half of the diagnoses of cancer, and basal cell carcinoma (BCC), the most frequent cutaneous neoplasm, corresponding to 70-80% of cutaneous tumors. Oxidative stress is an important trigger for skin carcinogenesis. Thus, it is important to evaluate oxidative stress, in order to discern effective therapeutic strategies able to stop it or attenuate it, thereby prevent the installation of non-melanoma skin cancer. Cross-sectional study with controls, involving 84 individuals of both sexes aged between 38-84 years, divided into two groups: control group of healthy people(n = 24) and the case group included individuals who presented non-melanoma skin and they have undergoing surgery (n = 60). The blood samples of the individuals were obtained for evaluation of biomarkers of oxidative stress (F2-isoprostane, nitrite, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity). The usual dietary intake and nutritional status of the subjects were evaluated. The significance level for this study was 5%. Patients in the case group had higher serum concentrations of biomarkers of oxidative stress, F2-isoprostane concentrations were significantly higher compared to controls. The results showed high rates of overweight and obesity in the case and control groups. The dietary concentrations of antioxidant minerals zinc, copper and selenium in the case group were significantly lower compared to controls. The correlation between markers of oxidative stress and dietary concentrations of antioxidant nutrients showed the influence of food intake of vitamins A and E in reducing oxidative stress, since these nutrients behave as important antioxidants, acting as sweepers of RL, by removing of the body the negative effects on the redox balance of the skin. We emphasize the importance of adopting healthy eating habits that optimize the consumption of antioxidant nutrients as a strategy to prevent oxidative damage to the skin.

Do Genetic Polymorphisms Modulate Response Rate and Toxicity of Cisplatin Associated With Radiotherapy in Laryngeal Squamous Cell Carcinoma? A Case Report

AbstractCisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality. Case presentation: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.

High 15-F2t-Isoprostane Levels in Patients with a Previous History of Nonmelanoma Skin Cancer: The Effects of Supplementary Antioxidant Therapy.

Background. Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. Materials and Methods. In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo (n = 34) and the other (n = 26) receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. Results. In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15-F2t-isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15-F2t-isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers. Conclusion. Patients with history of NMSC had significantly high 15-F2t-isoprostane plasma levels; supplementation did not result in significant reduction of oxidative stress biomarkers. This trial was registered with ClinicalTrials.gov (ID NCT02248584).

Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

GSTP1 c.313A>G, XPD c.934G>A, XPF c.2505T>C and CASP9 c.-1339A>G Polymorphisms and Severity of Vomiting in Head and Neck Cancer Patients treated with Cisplatin Chemoradiation

Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.−93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.‐1191A>G and c.‐1168G>T, CASP9 c.‐1339A>G, CASP8 c.‐937_‐932delAGTAAG, FAS c.‐1378G>A and c.‐671A>G, and FASL c.‐157‐687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT. Ondansetron and dexamethasone were administered as anti‐emetic therapy. Patients with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC, and CASP9 c.‐1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in DNA repair pathway, is capable of modulating emesis in HNSCC patients under CDDP chemoradiation and may be used for selecting patients who should receive pre‐emptive anti‐emetic therapy.

Reposição de vitamina B12 reduz comportamento depressivo induzido em ratos jovens

Objetivos: Avaliar, em modelo animal, se a deplecao suave de vitamina B12, anterior ao desenvolvimento de anemia, induz a depressao; e se a suplementacao com vitamina B12 em animais jovens pode atuar como medida preventiva da depressao. Metodos: Foram utilizados ratos Wistar divididos em grupo controle (n=11) e grupo B12 (n=10). O grupo B12 recebeu suplementacao de vitamina B12 na agua de beber, ao longo de todo o estudo. Na fase 1, os animais dos dois grupos receberam por seis semanas dieta adicionada de pectina (50g/kg da racao), para induzir a deplecao de vitamina B12. Apos esse periodo, foi aplicado o Teste de Porsolt para inducao e avaliacao do estado depressivo. Foi realizado tambem um hemograma para pesquisa de anemia. Na fase 2 (com duracao de quatro semanas), a pectina foi removida da racao e os mesmos testes foram aplicados novamente no final do periodo. Resultados: Durante as duas fases do estudo o numero de hemacias, o hematocrito e a concentracao de hemoglobina mantiveram-se normais, ou seja, os ratos nao desenvolveram anemia. Os resultados do Teste de Nado Forcado ao final da fase 1 mostram que, em relacao ao grupo controle, o grupo suplementado apresentou tempo de desistencia menor (0,44±0,32 vs. 0,75±0,18 minutos, p=0,024) e tempo de natacao maior (4,64±0,27 vs. 4,32±0,28 minutos, p=0,013), indicando reducao do estado depressivo com a reposicao de vitamina B12. Na comparacao entre grupos no final da fase 2 nao houve diferenca significativa em nenhum dos componentes do Teste de Nado Forcado. Conclusoes: A deplecao suave de vitamina B12 na dieta, em nivel nao indutor de anemia, favoreceu o estado depressivo em ratos jovens, enquanto a sua suplementacao na situacao de deplecao reverteu esse quadro. Em condicoes de nutricao adequada, entretanto, a suplementacao dessa vitamina nao exerceu efeito sobre o estado depressivo. Estes resultados estimulam a realizacao de mais estudos que aprofundem a avaliacao das relacoes entre vitamina B12 e depressao em jovens. Alem disso, este estudo tambem abre perspectivas para um novo modelo experimental de depressao, induzida por deplecao de vitamina B12.

Efeito do consumo de erva-mate (Ilex paraguariensis) sobre o ganho de peso e a glicemia de jejum em ratos alimentados com uma dieta hiperlipídica

Objetivo: Avaliar o efeito do consumo de erva-mate sobre o ganho de peso e a glicemia de jejum em ratos alimentados com uma dieta hiperlipidica. Materiais e Metodos: Foram utilizados 14 ratos divididos em tres grupos. O primeiro grupo (n=4) foi alimentado com racao comercial para ratos, o segundo (n=5) recebeu dieta hiperlipidica e o terceiro (n=5) foi alimentado com dieta hiperlipidica acrescida de infusao de erva-mate, durante 24 dias. Durante o estudo foram monitorados o peso e o indice de Lee e ao final a glicemia de jejum. Resultados: Os ratos alimentados com dieta hiperlipidica contendo infusao de erva-mate apresentaram menor ganho de peso em relacao aos que consumiram apenas a racao hiperlipidica, nos tres periodos experimentais analisados (p=0,048, p=0,016 e p=0,048, respectivamente). Nao houve diferenca significativa em relacao ao indice de Lee entre os grupos. O consumo da erva-mate promoveu tendencia a menores niveis de glicemia de jejum em relacao ao grupo alimentado com dieta comercial (p=0,056) e ao grupo que recebeu dieta hiperlipidica (p=0,075). Conclusao: O consumo de erva-mate proporcionou menor ganho de peso em relacao aos ratos que foram alimentados apenas com racao hiperlipidica e tendencia a menores niveis de glicemia de jejum.

Influência do fumo na atividade da amilase salivar e na curva glicêmica

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.