Effect of vitamin E in gastric mucosal injury induced by ischaemia-reperfusion in nitric oxide-depleted rats

BACKGROUND: Neutrophil infiltration and lipid peroxide accumulation are involved in reperfusion-induced gastric mucosal injury in nitric oxide-depleted rats. AIM: To assess the effect of vitamin E on this injury. METHODS: After ischaemia-reperfusion, the total area of erosions, lipid peroxide contents in gastric mucosa, and gastric neutrophil accumulation were compared between nitric oxide-depleted rats with deficient, normal, and increased vitamin E intake over 8 weeks. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. RESULTS: The total area of erosions was significantly increased in the vitamin E-deficient group compared with the sufficient-intake and vitamin-supplemented groups. Both thiobarbituric acid-reactive substances and myeloperoxidase activity also were significantly increased in the vitamin E-deficient group compared with others. The total area of erosions closely paralleled the increases in both thiobarbituric acid-reactive substances and myeloperoxidase activity. CONCLUSION: These results indicate that the inhibition of lipid peroxidation and interference with neutrophil infiltration by vitamin E may be responsible for its cytoprotective effect in ischaemia-reperfusion.     

Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient

Objectives

A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC.

Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia

Objectives

To assess the relationship between superior vena cava (SVC) flow and short-term outcome in infants with perinatal asphyxia.

Methods

Infants in sequence born after more than 35 weeks of gestation who had been hospitalized at the NICU and normal neonatal wards of Wakayama Medical University between May 2005 and September 2010 were recruited for this observational cohort study. The study eligibility criterion was the presence of perinatal asphyxia, as evidenced by abnormal fetal heart rate monitoring and an Apgar score of 7 or less at 1 min or need for resuscitation using positive pressure ventilation. SVC flow was measured in the first three days of life by Doppler echocardiography as described by Kluckow and Evans. Short-term outcome was defined as poor if MRI demonstrated bilateral lesions of the basal ganglia and thalamus and/or multicystic encephalomalacia due to hypoxic ischemia.

Results

In the head cooling group, SVC flow in infants with a good outcome was lower than that in infants with a poor outcome at 12 h (36.9 ± 7.7 vs 113.4 ± 42.4 ml/kg/min (p = 0.01)), 24 h (75.2 ± 25.3 vs 155.6 ± 45.7 ml/kg/min (p = 0.03)), and 48 h (92.5 ± 34.2 vs 161.1 ± 46.7 ml/kg/min (p = 0.04)) after birth. SVC flow decreased promptly after introduction of head cooling in infants who had a good outcome, whereas it increased gradually after head cooling in those who had a poor outcome.

Conclusion

We speculate that regulation of brain circulation is disrupted in infants with asphyxia who show a poor outcome.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Association study between catechol-O-methyltransferase polymorphisms and uterine leiomyomas in a Japanese population

PURPOSE: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. METHODS: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. CONCLUSION: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.     

Fetal intraventricular bleeding possibly due to maternal vitamin K deficiency

We report a rare case of fetal intraventricular bleeding possibly due to maternal vitamin K deficiency. A 20-year-old woman was admitted to our hospital due to impending premature delivery and loss of dietary intake at 28 weeks of gestation. Her blood examination showed metabolic alkalosis, prolonged prothrombin time, and extremely high level of plasma des-gamma-carboxyprothrombin (protein induced by vitamin K absence, PIVKA-II). Intraventricular hemorrhage was demonstrated by ultrasonography 6 days after admission. She delivered a 2,288-gram girl infant at 40 weeks of gestation. Cranial computerized tomography and magnetic resonance images obtained postnatally demonstrated a reduced cerebral parenchyma adjacent to the interior side of the right lateral ventricle and the deficit of left cerebellum. The infant's head control was insufficient and central impaired hearing was noted at 6 months of life.