Hyponatremia as an independent prognostic factor in patients with terminal cancer.

PURPOSE: Hyponatremia is a common and associated with poor clinical outcome in cancer patients. But little is known regarding hyponatremia in terminal cancer patients. The purpose of this study is to investigate the prognostic role of the hyponatremia in terminal cancer patients. METHODS: A retrospective observational study was conducted between January 2010 and December 2012 in a tertiary hospital palliative care unit. Medical records were collected from hospitalized patients who were eligible for obtaining serum sodium level. Hyponatremia was defined as serum sodium <136 mEq/L. And we classified patients into three groups; eunatremia (sodium 136-145 mEq/L), mild to moderate hyponatremia (sodium 126-135 mEq/L), and severe hyponatremia (sodium ≤125 mEq/L). Univariate and multivariate Cox regression analyses were performed to determine factors affecting survival time. RESULTS: Of the 576 patients, hyponatremia was present in 367 individuals (63.7 %). In the univariate analysis, serum CRP, PPS, and sodium ≤125 mEq/L were associated with survival time (HR = 1.22; p < 0.001, HR = 0.69; p < 0.001, HR = 1.91; p < 0.001). In the multivariate analysis, serum CRP, PPS, sodium 126-135 mEq/L, and sodium ≤125 mEq/L were associated with survival time (HR = 1.16; p < 0.001, HR = 0.70; p < 0.001, HR = 1.19; p = 0.048, HR = 1.75; p < 0.001). CONCLUSIONS: Hyponatremia is an independent prognostic factor in terminal cancer patients and careful clinical concern is needed. In the future, large prospective study is warranted in terminal cancer patients.

Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons.

BACKGROUND: Proanthocyanidin is a polyphenolic bioflavonoid with known antioxidant activity. Some flavonoids have a modulatory effect on [Ca²âº]i. Although proanthocyanidin extract from blueberries reportedly affects Ca²âº buffering capacity, there are no reports on the effects of proanthocyanidin on glutamate-induced [Ca²âº]i or cell death. In the present study, the effects of grape seed proanthocyanidin extract (GSPE) on glutamate-induced excitotoxicity was investigated through calcium signals and nitric oxide (NO) in cultured rat hippocampal neurons. RESULTS: Pretreatment with GSPE (0.3-10 µg/ml) for 5 min inhibited the [Ca²âº]i increase normally induced by treatment with glutamate (100 µM) for 1 min, in a concentration-dependent manner. Pretreatment with GSPE (6 µg/ml) for 5 min significantly decreased the [Ca²âº]i increase normally induced by two ionotropic glutamate receptor agonists, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). GSPE further decreased AMPA-induced response in the presence of 1 µM nimodipine. However, GSPE did not affect the 50 mM K+-induced increase in [Ca²âº]i. GSPE significantly decreased the metabotropic glutamate receptor agonist (RS)-3,5-Dihydroxyphenylglycine-induced increase in [Ca²âº]i, but it did not affect caffeine-induced response. GSPE (0.3-6 µg/ml) significantly inhibited synaptically induced [Ca²âº]i spikes by 0.1 mM [Mg²âº]o. In addition, pretreatment with GSPE (6 µg/ml) for 5 min inhibited 0.1 mM [Mg²âº]o- and glutamate-induced formation of NO. Treatment with GSPE (6 µg/ml) significantly inhibited 0.1 mM [Mg²âº]o- and oxygen glucose deprivation-induced neuronal cell death. CONCLUSIONS: All these data suggest that GSPE inhibits 0.1 mM [Mg²âº]o- and oxygen glucose deprivation-induced neurotoxicity through inhibition of calcium signals and NO formation in cultured rat hippocampal neurons.

Impaction of an intrathoracic kidney acted as a shield against herniation of the abdominal viscera in a case of right congenital diaphragmatic hernia.

We describe a case of an intrathoracic kidney combined with right congenital diaphragmatic hernia (CDH) that was diagnosed at 32 weeks of gestation. Although it has been well established that a right CDH shows a poorer outcome than a left CDH, our present case showed a good outcome because there was no herniation of other abdominal viscera, except for the right kidney. Our findings in this case indicate that impaction of the intrathoracic kidney may act as a 'shield' against further herniation of other abdominal viscera into the thoracic cavity.

Effects of PI3Kγ overexpression in the hippocampus on synaptic plasticity and spatial learning.

Previous studies have shown that a family of phosphoinositide 3-kinases (PI3Ks) plays pivotal roles in the brain; in particular, we previously reported that knockout of the γ isoform of PI3K (PI3Kγ) in mice impaired synaptic plasticity and reduced behavioral flexibility. To further examine the role of PI3Kγ in synaptic plasticity and hippocampus-dependent behavioral tasks we overexpressed p110γ, the catalytic subunit of PI3Kγ, in the hippocampal CA1 region. We found that the overexpression of p110γ impairs NMDA receptor-dependent long-term depression (LTD) and hippocampus-dependent spatial learning in the Morris water maze (MWM) task. In contrast, long-term potentiation (LTP) and contextual fear memory were not affected by p110γ overexpression. These results, together with the previous knockout study, suggest that a critical level of PI3Kγ in the hippocampus is required for successful induction of LTD and normal learning.

Effect of Food Deprivation on a Delayed Nonmatch-to-place T-maze Task.

Food deprivation can affect performance on difficult cognitive task, such as the delayed nonmatch-to-place T-maze task (DNMT). The importance of food deprivation on maintaining high motivation for DNMT task has been emphasized, but not many studies have investigated the optimal conditions for depriving rodents to maximize performance. Establishing appropriate conditions for food deprivation is necessary to maintain DNMT task motivation. We applied different conditions of food deprivation (1-h food restriction vs. 1.5-g food restriction; single caging vs. group caging) and measured body weight and the number of correct choices that 8-week-old C57BL/6J mice made during the DNMT task. The 1.5-g food restriction group maintained 76.0±0.6% of their initial body weight, but the final body weight of the 1-h food restriction condition group was reduced to 62.2±0.8% of their initial body weight. These results propose that 1.5-g food restriction condition is effective condition for maintaining both body weight and motivation to complete the DNMT task.

Mind bomb-1 is an essential modulator of long-term memory and synaptic plasticity via the Notch signaling pathway.

BACKGROUND: Notch signaling is well recognized as a key regulator of the neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-1 (Mib1) is an essential positive regulator in the Notch pathway, acting non-autonomously in the signal-sending cells. Therefore, genetic ablation of Mib1 in mature neuron would give valuable insight to understand the cell-to-cell interaction between neurons via Notch signaling for their proper function. RESULTS: Here we show that the inactivation of Mib1 in mature neurons in forebrain results in impaired hippocampal dependent spatial memory and contextual fear memory. Consistently, hippocampal slices from Mib1-deficient mice show impaired late-phase, but not early-phase, long-term potentiation and long-term depression without change in basal synaptic transmission at SC-CA1 synapses. CONCLUSIONS: These data suggest that Mib1-mediated Notch signaling is essential for long-lasting synaptic plasticity and memory formation in the rodent hippocampus.

Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease.

AIMS: The long-term prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFPEF) and coexistent chronic obstructive pulmonary disease (COPD) has not been previously investigated. The primary aim of this study was to determine whether the long-term prognosis of HFPEF patients with COPD differs from that of heart failure patients with reduced left ventricular ejection fraction (HFREF) and COPD. The secondary aim was to identify independent predictors of event-free survival in patients with HF and COPD. METHODS AND RESULTS: We investigated 184 patients with coexistent HF and COPD. Heart failure with preserved left ventricular ejection fraction was present in 98 cases (53%) and HFREF in the remaining 86 cases (47%). Mean follow-up time was 731±369 days. Cardiovascular/pulmonary hospitalization or mortality occurred in 71 patients (39%). No significant difference was observed between the two study groups in terms of event-free survival (P=0.457), but event-free survival was found to be independently associated with New York Heart Association (NYHA) class [III vs. I, hazard ratio (HR) 2.92, 95% confidence interval (CI) 1.09-7.82], Global initiative for chronic Obstructive Lung Disease (GOLD) stage (III vs. I, HR 3.20, 95% CI 1.33-7.68), systemic hypertension (SHT; HR 2.99, 95% CI 1.41-6.33), and pulmonary hypertension (PH; HR 4.35, 95% CI 1.95-9.68). CONCLUSION: In HF patients with coexisting COPD, cardiovascular and pulmonary event-free survival of HFPEF was found to be similar to that of HFREF over 3 years follow-up. Furthermore, severe NYHA class, severe GOLD stage, SHT, and PH were found to be independent predictors of event-free survival.