Higher melatonin secretion is associated with lower leukocyte and platelet counts in the general elderly population: the HEIJO‐KYO cohort

Circulating white blood cell (WBC) and platelet (PLT) counts are widely available and inexpensive cellular biomarkers of systemic inflammation and have been associated with a risk of cardiovascular disease, cancer, and mortality. Melatonin may reduce systemic inflammation through its direct and indirect antioxidative effect; however, the associations of melatonin secretion with systemic inflammation remain unclear. In this cross‐sectional study on 1088 elderly individuals (mean age, 71.8 years), we measured overnight urinary 6‐sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin secretion and systemic inflammation, respectively. UME was naturally log‐transformed for linear regression models because of skewed distribution (median, 6.8 μg; interquartile range, 4.1–10.6 μg). Univariate models revealed that higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (P = 0.046 and 0.018). After adjusting for potential confounding factors significantly associated with WBC or PLT counts, higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (WBC: β, ?0.143; 95% confidence interval, ?0.267 to ?0.020; P = 0.023; PLT: β, ?6.786; 95% confidence interval, ?12.047 to ?1.525; P = 0.012). Furthermore, the adjusted mean differences in WBC and PLT counts between the lowest and highest UME tertile groups were 0.225 × 10⁹/L and 9.480 × 10⁹/L, respectively. In conclusion, melatonin secretion was significantly and inversely associated with WBC and PLT counts in the general elderly population. The associations were independent of several major causes of systemic inflammation, including aging, obesity, smoking, hypertension, diabetes, and physical inactivity.     

Trends in oral cancer mortality in Japan: 1950-1993

OBJECTIVES: To investigate trends in mortality rates of oral cancer patients in Japan between 1950 and 1993 by sex, age and cancer site, and compare the results with previous studies to determine whether there are any common characteristics of oral cancer patterns between Japan and European countries. MATERIAL AND METHODS: The mortality data obtained from the Japanese Vital Statistics were analyzed using the 5-year moving average method, and the mortality rates were adjusted to the 1990 world population by age and sex. Age-specific mortality rates were analyzed by birth cohort. RESULTS: The age-standardized mortality rates among the males increased from 1.14 per 100,000 person--years in 1952 to 1.84 in 1991, whereas the corresponding rate among females changed little over the same period. Cancer of the tongue was the most common cause of death in Japan among the five studied oral regions: lip, tongue, floor of the mouth, major salivary glands and oropharynx, males aged under 54 born in 1920 or later were found to have an increased risk of such disease. CONCLUSION: Further epidemiological investigations are necessary to clarify the etiology of oral cancer in Japan.     

Effects of intracerebroventricular (I.C.V.) administration of 5-hydroxytryptamine (5-HT) on hemodynamics in conscious spontaneously hypertensive rats (SHR): relation to sympathetic nervous system

Recently, the serotonergic nervous system has been receiving attention as part of the blood pressure regulating mechanism of the central nervous system, and it has been postulated that the system may participate in the pathogenesis of hypertension. The purpose of this experiment is to investigate the mechanism of hemodynamic change after i.c.v. administration of 5-HT in SHR and in normotensive Wistar Rats (WR). MATERIALS AND METHODS: Twenty-week-old male SHR (n = 11) and age-matched WR (n = 14) were used. On the day before the experiments, the unilateral carotid artery and jugular vein were cannulated. Also, a cannula was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. Experiments were performed under the conscious and minimum restrained state. Experiment I: After observation of resting mean arterial pressure (MAP) and heart rate (HR) for 20 minutes, 5-HT (5 micrograms/5 microliter saline) was administrated i.c.v., and MAP and HR were observed for 90 minutes. Then, 200 micrograms of phenoxybenzamine (POB) was given from the jugular cannula. Thirty minutes after the POB administration when MAP was stabilized, 5 micrograms of 5-HT was again given i.c.v., and MAP and HR were recorded for 30 minutes. Experiment II: Plasma norepinephrine (PNE) was measured before and 2 minutes after 5-HT i.c.v. administration. The control sample (1.5 ml) was withdrawn at least 30 minutes before the 5-HT injection, and immediately after the blood sampling, the same amount of blood which was obtained from the age-matched donor rat of the same strain was transfused. RESULTS: Experiment I: Resting MAP was 136.4 +/- 5.1 mmHg in SHR and 99.1 +/- 3.0 mmHg in WR. I.c.v. administration of 5-HT elicited consistent pressor response in SHR and in WR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology

Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus (PSORS1) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn-deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn-deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility.     

Effects of Sustained‐Release Beraprost in Patients With Primary Glomerular Disease or Nephrosclerosis: CASSIOPEIR Study Results

TRK‐100STP, a sustained‐release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK‐100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI₂ Derivative for Evaluating Improvement of Renal Function) was a randomized, double‐blind, placebo‐controlled study conducted at 160 sites in seven Asia‐Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK‐100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end‐stage renal disease. No significant differences were observed in composite endpoints between TRK‐100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK‐100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.     

The Prognostic Nutritional Index Predicts Long-term Outcomes of Gastric Cancer Patients Independent of Tumor Stage

Purpose

The aim of this study was to investigate the impact of the prognostic nutritional index (PNI) on the long-term outcomes in gastric cancer patients.

Methods

This study reviewed the medical records of 548 patients with gastric cancer who underwent gastrectomy. The PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm³). The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PNI. The multivariate analysis was performed to identify the prognostic factors.

Results

The mean PNI was significantly lower in patients with T3–T4 tumors (P < 0.001) and lymph node metastasis (P < 0.001) than in those without such factors. Patients who had a postoperative complication had a lower mean PNI than those without (P = 0.023). When the ROC curve analysis was performed, the optimal cutoff value of the PNI for predicting the 5-year survival was 48. In the multivariate analysis, a low PNI was an independent predictor for poor overall survival (P < 0.001). In the subgroup analysis, the overall and relapse-free survival rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III disease.

Conclusions

The PNI is a simple and useful marker for predicting the long-term outcomes of gastric cancer patients independent of the tumor stage. Based on our results, we suggest that the PNI should be included in the routine assessment of gastric cancer patients.     

Possibility of solving complex problems by recursive thinking

This study examined the ability in recursive thinking to solve problems. To think recursively is one of the most effective ways to break up large and complex problems into smaller ones. This study prepared two problems with the same tail recursion: The "Guess-the-Number game" and the "Hat puzzle (Wise men puzzle)." Because participants (N = 35) were not familiar with recursive thinking, they learned how to think recursively in the Guess-the-Number game. Then, we tested whether they could solve the Hat puzzle recursively. The results show that two-thirds of the participants could solve the problem recursively, even if the size of the problem increased. Furthermore, their solution times had differed between correct and incorrect answers. This suggests that the difference reflected a "saving" of effort for problem solving.