Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 ± 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 ± 8.64 to 39.14 ± 6.77 mmHg) and alveolar air (from 92.97 ± 2.14 to 63.91 ± 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 ± 42.01 to 84.34 ± 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 ± 0.34 to 0.33 ± 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 ± 1.71 to 60.76 ± 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 ± 1.22 to 23.15 ± 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 ± 1.36 to 37.61 ± 12.79 mmHg), as also did the calculated alveolar (from 56.38 ± 22.47 to 178.09 ± 37.46 mL) and physiological (from 0.37 ± 0.05 to 0.75 ± 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution induced by hypocapnic bronchoconstriction.

Biphasic modulation of insulin receptor substrate-1 during goitrogenesis

Insulin receptor substrate-1 (IRS-1) is the main intracellular substrate for both insulin and insulin-like growth factor I (IGF-I) receptors and is critical for cell mitogenesis. Thyrotropin is able to induce thyroid cell proliferation through the cyclic AMP intracellular cascade; however, the presence of either insulin or IGF-I is required for the mitogenic effect of thyroid-stimulating hormone (TSH) to occur. The aim of the present study was to determine whether thyroid IRS-1 content is modulated by TSH in vivo. Strikingly, hypothyroid goitrous rats, which have chronically high serum TSH levels (control, C = 2.31 ± 0.28; methimazole (MMI) 21d = 51.02 ± 6.02 ng/mL, N = 12 rats), when treated with 0.03% MMI in drinking water for 21 days, showed significantly reduced thyroid IRS-1 mRNA content. Since goiter was already established in these animals by MMI for 21 days, we also evaluated IRS-1 expression during goitrogenesis. Animals treated with MMI for different periods of time showed a progressive increase in thyroid weight (C = 22.18 ± 1.21; MMI 5d = 32.83 ± 1.48; MMI 7d = 31.1 ± 3.25; MMI 10d = 33.8 ± 1.25; MMI 14d = 45.5 ± 2.56; MMI 18d = 53.0 ± 3.01; MMI 21d = 61.9 ± 3.92 mg, N = 9-15 animals per group) and serum TSH levels (C = 1.57 ± 0.2; MMI 5d = 9.95 ± 0.74; MMI 7d = 10.38 ± 0.84; MMI 10d = 17.72 ± 1.47; MMI 14d = 25.65 ± 1.23; MMI 18d = 35.38 ± 3.69; MMI 21d = 31.3 ± 2.7 ng/mL, N = 9-15 animals per group). Thyroid IRS-1 mRNA expression increased progressively during goitrogenesis, being significantly higher by the 14th day of MMI treatment, and then started to decline, reaching the lowest values by the 21st day, when a significant reduction was detected. In the liver of these animals, however, a significant decrease of IRS-1 mRNA was detected after 14 days of MMI treatment, a mechanism probably involved in the insulin resistance that occurs in hypothyroidism. The increase in IRS-1 expression during goitrogenesis may represent an important event associated with the increased rate of cell mitosis promoted by TSH and indicates that insulin and IGF-I are important co-mitogenic factors in vivo, possibly acting through the activation of IRS-1.

Expression of TERT in precancerous gastric lesions compared to gastric cancer

The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46% of IM, 50% of GU, and 79% of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38% of IM, 39% of GU, and 55% of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.

The efficacy of moxifloxacin-based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of randomized clinical trials

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitroand in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pyloritreatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

Avaliação físico-química de filés de tilápia (Oreochromis niloticus) submetidos à sanitização

No presente trabalho foi avaliado o efeito dos agentes sanificantes dicloroisocianurato de sódio na concentração de 3 a 3,5 mg.L-1 (T1), dicloroisocianurato de sódio associado ao ultra-som (T2), ozônio na concentração de 3 a 3,5 mg.L-1 (T3), ozônio associado ao ultra-som (T4) e controle (T5) sobre a composição centesimal, perfil de ácidos graxos (AG), teor de colesterol e índice de peróxido de filés de tilápia. Os tratamentos afetaram (p < 0,05) a composição centesimal. Os filés foram tratados por imersão, durante 20 minutos, em soluções que apresentavam pH 6,0 e temperatura de 5 °C. Os sanificantes causaram uma perda de água e aumentaram a concentração de proteínas no filé, tendo esse fato sido notado mais acentuadamente no T3 (77,16% de umidade e 19,73% de proteína) quando comparado ao T5 (78,60% de umidade e 18,71% de proteína). Foi demonstrada diferença significativa (p < 0,05) na fração lipídica para ácidos graxos saturados (AGS), ácidos graxos monoinsaturados (AGM) e ácidos graxos polinsaturados (AGP) entre os tratamentos propostos. Os AGS apresentaram diferença entre os T3, T4 e T5, com as respectivas médias 37, 33,50 e 36,30%. Os T1 e T2 (34,90 e 34,80%) não diferiram entre si, mas foram diferentes dos T3, T4 e T5 (39,30, 36,30 e 39,10%) para AGM. O T3 foi o que mais preservou a fração AGM. Os AGP não apresentaram diferença entre os T1 e T2 (23 e 22,50%) e os grupos T3, T4 e T5 (18,30, 20,40 e 17,70%) diferiram entre si, tendo o T1 apresentado as maiores médias. Obteve-se uma redução mais acentuada do nível de colesterol no grupo T2 (43,94 mg.100 g-1) quando comparado com T5 (54,77 mg.100 g-1). Os teores médios de peróxido encontrados nos filés submetidos aos tratamentos não revelaram diferença estatística segundo análise de variância (p > 0,05), apesar dos valores serem bastante diferentes, apresentando uma variação de 6,07 a 39,57 meq.kg-1.

Changes in the physicochemical and microbiological properties of frozen araça pulp during storage

Araça belongs to the Myrtaceae family and is popularly known as araçá-comum, araçá-azedo, or araçá-do-campo. Frozen fruit pulp is of great importance for the food industry, which can produce it at the time of harvest, store it, and use it according to the demand of the consumer market and/or as an ingredient in the formulation of products such as yogurt, candies, and ice creams among others. The aim of this study was to evaluate the physical, chemical, and microbiological stability of frozen araça pulp during 12 months of frozen storage. It was observed that the levels of moisture (90.55-88.75%), ash (0.34-0.26%) total soluble sugars (7.11-6.62%), sucrose (3.55-1.39%), soluble pectin (0.24-0.23%), total pectin (0.5-0.46%), pH (3.82-2.31%), organic acids (698.12-122.25 µg.g-1 citric acid), and phenolic compounds (6.22-0.00 mg GAE.100 g-1) decreased during storage, whereas the levels of protein (0.61-0.83%), lipids (0.14-0.38%), total carbohydrates (8.36-9.78%), calorific value (37.14-45.86 kcal.100 g-1), reducing sugars (3.51-5.21%), soluble solids (5.17-6.0%), total antioxidant capacity (6.89-35.13%), and color parameters (L*49.75-50.67; a*0.79-1.82 and b*22.5-25.19) increased over the one-year storage period. According to the chemical and microbiological parameters assessed, the product can be stored for 12 months without loss of quality with addition of citric acid as a preservative.