Effects of parenteral nutrition supplemented with beta-hydroxy-beta-methylbutyrate on gut-associated lymphoid tissue and morphology in mice.

BACKGROUND: Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice. METHODS: Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine. RESULTS: Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression. CONCLUSION: HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN.

Efficacy of Pharmacotherapy for Seasonal Influenza in Young and Middle-aged Adults: A Systematic Review and Network Meta-analysis.

Objective Seasonal influenza affects healthcare demand. However, the efficacy of anti-influenza drugs, particularly among young patients at a low risk of complications, has rarely been evaluated. Therefore, we evaluated the efficacy of anti-influenza drugs against seasonal influenza in healthy young and middle-aged adults. Methods A systematic review and network meta-analysis were conducted. The Cochrane Central Register of Controlled Trials and Medical Literature Analysis and Retrieval System Online were searched for original articles reporting double-blind, randomized controlled trials published up to the end of July 2023. Clinical trials that tested the efficacy of anti-influenza drugs in young and middle-aged patients with seasonal influenza were also included. The primary outcome was time to fever alleviation. The efficacy and adverse effects of these treatments were estimated using a Bayesian hierarchical random-effects model and a Markov chain Monte Carlo simulation. Results In total, 24 articles with 34 treatments and 8,949 individuals were included. Oseltamivir (300 mg/day for 5 days) showed the largest reduction in time to fever alleviation by -19.1 [95% confidence interval (CI): -29.4, -10.7] h compared with a placebo. Baloxavir marboxil (40 mg/day) reduced the time to symptom alleviation by -28.2 (95% CI: -42.7, -13.7) h, and peramivir (300 mg/day) administered by intravenous infusion for 1 day reduced the time to resumption of usual activities by -43.5 (95% CI: -72.8, -14.2) h. Conclusion Several pharmaceutical treatments were able to reduce the recovery time for fever and symptom alleviation and resumption of usual activities in young and middle-aged adults with seasonal influenza without increasing the risk of complications.

Effect of a Community-Based Program to Accelerate Referral to Physicians for Individuals at High-Risk of Lifestyle-Related Diseases: A Cluster Randomized Trial.

AIM: A cluster randomized trial was conducted within 43 Japanese municipalities (21 intervention and 22 usual care) to examine whether the standardized health counseling for individuals at high cardiovascular risk screened at community sites accelerates clinic visits to strengthen the primary health care system. METHODS: Among high-risk individuals aged 40-74 years screened by health checkups, 8,977 and 6,733 were allocated to the intervention and usual care groups, respectively, who were not under medical treatment but had high levels of blood pressure (systolic/diastolic ≥ 160/100 mmHg), hemoglobin A1c or glucose (≥ 7.0% or corresponding glucose levels), LDL-cholesterol (≥ 180 mg/dL for men), and/or proteinuria of ≥ 2+. The intervention was performed from May 2014 to March 2016 under a standardized health counseling program based on the health belief model primarily by public health nurses. The usual care group was provided with local counseling protocols. RESULTS: The cumulative proportions of clinic visits for 12 months after health checkups were 58.1% (95% confidence interval, 57.0%, 59.3%) versus 44.5% (43.2%, 45.8%), with the probability ratio of clinic visits between the groups being 1.46 (1.24, 1.72). The between-group differences between the baseline and 1-year surveys were -1.50 (-2.59, -0.41) mmHg for diastolic blood pressure in the hypertension category, -0.30% (-0.53%, -0.07%) for HbA1c in the diabetes category, -0.37 (-0.48, -0.27) mmol/L for LDL-cholesterol in the dyslipidemia category, and none for proteinuria. CONCLUSION: Standardized health counseling for high-risk individuals accelerated clinic visits, with larger reductions in blood pressure, HbA1c, and LDL-cholesterol levels. The nationwide use of counseling after health checkups for high-risk individuals could help in controlling risk factors and in preventing lifestyle-related diseases.

Early biomarkers for kidney injury in heat-related illness patients: a prospective observational study at Japanese Self-Defense Force Fuji Hospital.

BACKGROUND: Since heatstroke-induced acute kidney injury (AKI) can progress to chronic kidney disease, it would be useful to detect heatstroke-induced AKI and severe heat-related illness in the early phase. We studied the epidemiology of heat-related illness among patients in the Japanese Ground Self-Defense Force and evaluated the relationship between heat-related illness severity and early urinary biomarkers for AKI. METHODS: We enrolled patients who were diagnosed with heat-related illness at the Self-Defense Force Fuji Hospital from 1 May to 30 September 2020. We compared the urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin levels according to the severity of heat-related illness as defined by positive scores for the Japanese Association of Acute Medicine Heatstroke Working Group (JAAM-HS-WG) criteria (0, mild; 1, moderate; ≥2, severe). RESULTS: Of the 44 patients, kidney injury, defined as serum creatinine (sCr) ≥1.2 mg/dL, was seen in 9 (20.5%) patients. Urinary NAG, NGAL and L-FABP levels were significantly higher in the ≥2 JAAM-HS-WG criteria group than in the 0 group. Furthermore, urinary L-FABP levels were positively correlated with sCr levels. In contrast, the urinary KIM-1 levels showed the best correlation with serum cystatin C (sCysC) among these biomarkers. CONCLUSIONS: We conclude even mild to moderate heatstroke could lead to AKI. Urinary L-FABP is useful for detecting heatstroke-induced AKI and patients with severe heat-related illness requiring immediate treatment. Urinary KIM-1 may detect heatstroke-induced AKI in terms of sCysC, although it was not related to the severity of heat-related illness.

Prehabilitation Ameliorates Gut Ischemia Reperfusion Injury in Mice.

INTRODUCTION: We previously demonstrated that prehabilitation by running on a treadmill leads to improved survival after gut ischemia reperfusion (I/R) in mice. The purpose of this research was to examine whether prehabilitation attenuates inflammatory responses after gut I/R in mice. MATERIALS AND METHODS: Male C57BL/6J mice (n = 92) were assigned to the sedentary (n = 46) or the exercise (n = 46) group. The exercise group ran on a treadmill for 4 wk, while the sedentary mice did not exercise. After the 4-week pretreatment, all mice underwent gut I/R and the blood, urine, small intestine, lung, liver, and gastrocnemius were harvested prior to ischemia or at 0, 3, 6, or 24 h after reperfusion. Histologically demonstrated organ damage, cytokine levels in the blood, gut and gastrocnemius, myeloperoxidase activity in the gut, 8-hydroxy-2'-deoxyguanosine levels in urine and the gut, and adenosine triphosphate (ATP) and ATP + ADP + adenosine monophosphate levels in the gut and gastrocnemius were evaluated. RESULTS: The treadmill exercise reduced gut and lung injuries at 3 h and liver injury at 6 h after reperfusion. Running on the treadmill also decreased proinflammatory cytokine levels in the blood at 6 h, gut at 3 h and gastrocnemius at 6 h after reperfusion, myeloperoxidase activity in the gut prior to ischemia, and 6 h after reperfusion and the urinary 8-hydroxy-2'-deoxyguanosine level at 24 h after reperfusion, while ATP levels in exercised mice prior to ischemia and 3 h after reperfusion were increased in the intestine as compared to the levels in sedentary mice. CONCLUSIONS: Prehabilitation with treadmill exercise reduces inflammatory responses after gut I/R and may exert protective actions against gut I/R.

Lipid Compositions of Total Parenteral Nutrition Affect Gut Peyer's Patches and Morphology in Mice.

INTRODUCTION: Although parenteral nutrition (PN) is the only option for providing adequate nutrition to patients who cannot tolerate oral ingestion, it severely impairs intestinal barrier function in terms of morphology and immunity. While addition of either soybean oil (SO) or fish oil (FO) to PN partially reverses these defects, the effects of the oil composition (FO/SO ratio) on morphology and gut-associated lymphoid tissues (GALT) have yet to be elucidated. We focused on the effects of the FO/SO ratio in PN on the number of lymphocytes in Peyer's patches, immunoglobulin A levels, and intestinal structures. METHODS: Male ICR mice (n = 61) were randomized into five groups; oral nutrition (Chow, n = 14) and four groups receiving PN without oral nutrition. PN solutions contained fat emulsions with the following FO:SO ratios: 0:1 (SO, n = 12), 1:11.5 (11.5FSO, n = 17),1:2 (1:2FSO, n = 13) and 1:0 (FO, n = 5). All mice underwent jugular vein catheter insertion. The PN groups were given isocaloric and isonitrogenous nutritional support with 20% of total calories from fat emulsions with equivalent fat delivery in 11.9 g/kg/d. After 5 d of each feeding, Peyer's patches lymphocytes were isolated from the small intestine, counted and analyzed with flowcytometry for determination of their phenotypes (αßTCR+, γδTCR+, CD4+, CD8+ and B cells). Villus height and crypt depth of the jejunum and ileum were evaluated with hematoxylin-eosin staining. Immunoglobulin A levels in the intestinal washings were also determined. RESULTS: Numbers of total lymphocytes and B lymphocytes in PP were increased in the 1:2 FSO-PN but neither in the 1:11.5 FSO nor the FO group, as compared to the SO group. There were no marked differences among the groups in numbers neither of total T cells nor in any of T cell phenotypes determined. The 1:2 FSO group showed significantly greater villus height and crypt depth than the SO group. IgA levels did not differ significantly among the four PN groups. CONCLUSIONS: The PN with 1:2 FSO (FO:SO = 1:2) maintained lymphocyte numbers in PP and intestinal villus morphology at levels nearly the same as those obtained with chow feeding. An appropriate ratio of FO to SO in PN is expected to prevent immunological impairment and morphological atrophy of the gut associated with lack of oral nutrition.

Evaluation of public health nurse-led health counseling programs for the prevention of cardiovascular diseases in Amagasaki City, Japan.

OBJECTIVE: We evaluated whether Amagasaki health counseling programs led by public health nurses (PHNs) are contribute to improving cardiovascular disease (CVD) risk factors and CVD mortality among adult residents. DESIGN AND SAMPLE: This cross-sectional study used a before-and-after comparative design. We evaluated data from health checkups and mortality before and after Amagasaki health promotion programs. MEASUREMENTS: Population levels of CVD risk factors body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting blood glucose, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, Triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, γ-glut amyl trans peptidase (γ-GTP), serum creatinine, estimated glomerular filtration rate (eGFR) were compared between 2008 and 2012 when the intervention with the Amagasaki health counseling program started from 2008. In addition, standardized mortality ratio (SMR) of acute myocardial infarction (AMI) were compared between 2003-2007 and 2008-2012. RESULTS: Mean value of most CVD risk factors improved and the SMR for AMI declined, which could be attributable in part to the effort of intensive health education and counseling.

Heat acclimation ameliorated heat stress-induced acute kidney injury and prevented changes in kidney macrophages and fibrosis.

Heatstroke can cause acute kidney injury (AKI), which reportedly progresses to chronic kidney disease. Kidney macrophages may be involved in such injury. Although heat acclimation (HA) provides thermal resilience, its renoprotective effect and mechanism remain unclear. To investigate heat stress-induced kidney injuries in mice and the mitigating effect of HA on them, male C57/BL6J mice were exposed to heat stress (40°C, 1 h) with or without 5-day HA (38°C, 3 h/day) prior to heat stress. Heat stress damaged kidney proximal tubules with an elevation of urinary kidney injury molecule-1. Kidney fibrosis was observed on day 7 and correlated with urinary kidney injury molecule-1 levels on day 3. Kidney resident macrophages decreased on day 1, whereas the number of infiltrating macrophages in the kidney did not change. Both subsets of macrophages polarized to the proinflammatory M1 phenotype on day 1; however, they polarized to the anti-inflammatory M2 phenotype on day 7. HA significantly ameliorated heat stress-induced proximal tubular damage and kidney fibrosis. HA substantially increased heat shock protein 70 expression in the tubules before heat stress and reduced the elevation of cleaved caspase-3 expression after heat stress. HA also induced heat shock protein 70 expression of resident macrophages and prevented heat stress-induced changes in both subsets of kidney macrophages. These results provide pathophysiological data supporting the renoprotective effect of HA. Further studies are needed to confirm that HA can prevent kidney damage due to heat stress in humans.NEW & NOTEWORTHY Heat stress could induce acute kidney injury. Although heat acclimation (HA) reportedly provides thermal tolerance, its effect on heat stress-induced kidney damage remains unclear. This study showed that 5-day HA ameliorates mouse kidney tubular damage and subsequent fibrosis caused by heat stress. It also demonstrated that HA enhances intracellular heat shock protein 70 expression in tubular cells and prevents a decrease in kidney resident macrophages, which explains the renoprotective effect of HA.

Relationship between Health Counselor Characteristics and Counseling Impact on Individuals at High-Risk for Lifestyle-Related Disease: Sub-Analysis of the J-HARP Cluster-Randomized Controlled Trial.

Early diagnosis and treatment are necessary to prevent lifestyle-related diseases among high-risk individuals. This study aimed to examine the impact of counselor characteristics on clinic visits among individuals at high risk for lifestyle-related diseases. A total of 8975 patients aged 40 to 74 years with lifestyle-related comorbidities, who underwent an annual health checkup and received health counseling, were included in this study. Data intervention timing, mode of counseling, number of counseling sessions, and explanation methods were collected. We assessed the impact of counselor characteristics, including profession (public health nurse, clinical nurse, and nutritionist), age, and years of counseling experience, on counseling outcomes. The probability ratios (95% confidence intervals) of clinic visits were 1.22 (1.11-1.35) for public health nurses and 1.04 (0.90-1.20) for nurses compared with nutritionists. After adjustment for participant and counselor characteristics and initial timing, mode, and number of counseling sessions, the corresponding probability ratios (95% confidence intervals) were 1.16 (1.05-1.29) and 1.12 (0.95-1.31), respectively. Counselor age and years of experience did not influence clinic visits of the target population. Public health nurses were more effective in increasing clinic visits among the target population owing to their profession-specific knowledge, skills, and experience.

Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age.

OBJECTIVE: this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities. METHODS: we examined a prospective cohort of 20,373 men and 26,247 women aged 40-80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40-102 years was analysed. FINDINGS: during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7-8 health lifestyle points was 46.8 (45.6-48.1) and 51.3 (50.0-52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P < 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories. CONCLUSION: adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one's lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.

Influence of a Low-Carbohydrate High-Fat Diet on Peritoneal Inflammation, Cancer-Associated Lymphocytes, and Survival in a Murine Carcinomatous Peritonitis Model.

BACKGROUND: Low-carbohydrate high-fat diets (LCHFDs) are thought to be beneficial for metabolic support in patients with advanced cancer. However, whether LCHFDs affect the progression of carcinomatous peritonitis (CP) remains unclear. Our study examined the influence of a lard-based LCHFD on host immunity and survival in a murine CP model. METHODS: Mice were fed either a normal diet (ND) or an LCHFD ad libitum. On day 7, Panc02 cancer cells were inoculated intraperitoneally. Mice were killed on days 7, 21, and 35, and cytokine levels in the peritoneal fluid, as well as the number and phenotypes of peritoneal, splenic, and tumor-infiltrating lymphocytes were measured. Survival studies were performed with both ad libitum and isocaloric feeding in other sets of mice. RESULTS: The levels of all cytokines significantly increased in the LCHFD group compared with those in the ND group on day 21. The tumor necrosis factor α and interleukin-10 levels were higher in the LCHFD group than in the ND group on day 35. In the LCHFD group, the regulatory T-cell (Treg) number was significantly higher in the peritoneal cavity and tumor. The survival times were worse in the LCHFD group than in the ND group. CONCLUSION: The ad libitum, lard-based LCHFD feeding of CP mice increases the peritoneal cytokine levels, which may reduce splenic, anticancer lymphocytes and increase the number of Tregs in the peritoneal cavity and tumor. The detrimental effects of LCHFD are linked to dietary composition rather than overfeeding.

Japan Trial in High-Risk Individuals to Enhance Their Referral to Physicians (J-HARP)-A Nurse-Led, Community-Based Prevention Program of Lifestyle-Related Disease.

BACKGROUND: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. METHODS: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. RESULTS: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. CONCLUSIONS: We expect to provide scientific evidence on the effectiveness of health counselling.

Influences of Short-Term Fasting and Carbohydrate Supplementation on Gut Immunity and Mucosal Morphology in Mice.

BACKGROUND: Preoperative carbohydrate (CHO) supplementation has been recommended in enhanced recovery after surgery protocols. However, the effects of CHO supplementation on gut and systemic immunity are not well understood. METHODS: Mice (n = 60) were randomized to 1 of the following 5 groups: control (ad lib feeding), 12-hour fasting without CHO administration (fasting), and 12 hours of fasting with CHO administration at 2, 4, and 8 hours before sacrifice. Then, lymphocytes were isolated from gut-associated lymphoid tissue, that is, Peyer's patches, the intraepithelial space, and the lamina propria of the small intestine. These lymphocyte numbers and phenotypes were evaluated. IgA levels in respiratory and small-intestinal washings were determined by ELISA. Morphology, proliferation, and apoptosis of the intestinal epithelium were also evaluated histologically. RESULTS: Although there were no significant differences in IgA levels among the 5 groups, fasting decreased intraepithelial and lamina propria, but not Peyer's patches lymphocyte numbers. CHO at 2 hours prevented lymphocyte loss in intraepithelial, whereas CHO at 4 hours reversed lamina propria lymphocytes numbers. Percentages of lymphocyte phenotypes were similar in each site among the 5 groups. Fasting caused villous atrophy; however, CHO at 2 hours restored villous structure along with maintenance of epithelial cell proliferation rate. CONCLUSIONS: Only 12 hours of fasting causes marked gut-associated lymphoid tissue cell loss along with gut atrophy. However, CHO at 2 hours preserves gut immunity and morphology not completely but moderately.

Effects of semielemental diet containing whey peptides on Peyer's patch lymphocyte number, immunoglobulin A levels, and intestinal morphology in mice.

BACKGROUND: Enteral nutrition (EN) is the gold standard of nutritional therapy for critically ill or severely injured patients, because EN promotes gut and hepatic immunity, thereby preventing infectious complications as compared with parenteral nutrition. However, there are many EN formulas with different protein and fat contents. Their effects on gut-associated lymphoid tissue remain unclear. Recently, semielemental diets (SEDs) containing whey peptides as a nitrogen source have been found to be beneficial in patients with malabsorption or pancreatitis. Herein, we examined the influences of various dietary formulations on gut immunity to clarify the advantages of SEDs over elemental diets. METHODS: Forty-four male Institute of Cancer Research mice were randomized to four groups: chow (CH: n = 5), intragastric total parenteral nutrition (IG-TPN: n = 13), elemental diet (ED: n = 13), and SED (n = 13). The CH group received CH diet ad libitum, whereas the IG-TPN, ED (Elental, Ajinomoto, Japan), and SED (Peptino, Terumo, Japan) groups were given their respective diets for 5 day via gastrostomy. After 5 days, the mice were killed to obtain whole small intestines. Peyer's patch (PP) lymphocytes were harvested and counted. Their subpopulations were evaluated by flow cytometry. Immunoglobulin A (IgA) levels in intestinal and respiratory tract washings were measured with enzyme-linked immunosorbent assay. Villous height (VH) and crypt depth in the distal intestine were measured by light microscopy. RESULTS: SED increased the PP cell number and intestinal or respiratory IgA levels to those of CH mice, while ED partially restored these parameters. The IG-TPN group showed the lowest PP cell number and IgA levels among the four groups. VH was significantly greater in the CH than in the other groups. VH in the ED and SED groups also exceeded in the IG-TPN group, while being similar in these two groups. No significant crypt depth differences were observed among the four groups. CONCLUSIONS: SED administration can be recommended for patients unable tolerate complex enteral diets or a normal diet in terms of not only absorption and tolerability but also maintenance of gut immunity.

Noradrenalin effectively rescues mice from blast lung injury caused by laser-induced shock waves.

BACKGROUND: Blast lung injuries (BLI) caused by blast waves are extremely critical in the prehospital setting, and hypotension is thought to be the main cause of death in such cases. The present study aimed to elucidate the pathophysiology of severe BLI using laser-induced shock wave (LISW) and identify the initial treatment. METHODS: The current investigation comprised two parts. For the validation study, mice were randomly allocated to groups that received a single shot of 1.2, 1.3, or 1.4 J/cm(2) LISW to both lungs. The survival rates, systolic blood pressure (sBP), heart rate (HR), peripheral oxyhemoglobin saturation (SpO2), and shock index were monitored for 60 min, and lung tissues were analyzed histopathologically. The study evaluated the effects of catecholamines as follows. Randomly assigned mice received 1.4 J/cm(2) LISW followed by the immediate intraperitoneal administration of dobutamine, noradrenalin, or normal saline. The primary outcome was the survival rate. Additionally, sBP, HR, SpO2, and the shock index were measured before and 5 and 10 min after LISW, and the cardiac output, left ventricular ejection fraction, and systemic vascular resistance (SVR) were determined before and 1 min after LISW. RESULTS: The triad of BLI (hypotension, bradycardia, and hypoxemia) was evident immediately after LISW. The survival rates worsened with increasing doses of LISW (100 % in 1.2 J/cm(2) vs. 60 % in 1.3 J/cm(2), 10 % in 1.4 J/cm(2)). The histopathological findings were compatible with those of human BLI. The survival rate in LISW high group (1.4 J/cm(2)) was highest in the group that received noradrenalin (100 %), with significantly elevated SVR values (from 565 to 1451 dyn s/min(5)). In contrast, the survival rates in the dobutamine and normal saline groups were 40 and 10 %, respectively, and the SVR values did not change significantly after LISW in either group. CONCLUSIONS: The main cause of death during the initial phase of severe BLI is hypotension due to the absence of peripheral vasoconstriction. Therefore, the immediate administration of noradrenalin may be an effective treatment during the initial phase of severe BLI.

Extent of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6-6.4.

AIMS/INTRODUCTION: Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. MATERIALS AND METHODS: The study participants were 482 men with an estimated visceral fat area of ≥100 cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual plasma glucose <200 mg/dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/dL, or casual plasma glucose ≥200 mg/dL. RESULTS: The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group (P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group. CONCLUSIONS: Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4-5% weight loss in those with HbA1c of 5.6-6.4%.

The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice.

BACKGROUND: Surgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed. MATERIAL AND METHODS: Male Institute of Cancer Research mice were randomly assigned to three dietary groups: ad libitum (AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined. RESULTS: Hepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group. CONCLUSIONS: DR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition.

An inverse U-shaped association of late and peak insulin levels during an oral glucose load with glucose intolerance in a Japanese population: a cross-sectional study.

The current study investigated the association of post-load insulin levels with glucose tolerance in a Japanese population. A total of 1450 Japanese employees who underwent a 75-g oral glucose tolerance test (OGTT) were included. Glucose tolerance was assessed by 120-min glucose levels during a 75-g OGTT. A penalized cubic regression spline model analysis revealed that the 60- and 120-min insulin levels, but not 0- or 30-min insulin levels, had an inverse U-shaped relationship to the 120-min glucose level. Furthermore, peak insulin level followed an inverse U shape in relation to the 120-min glucose level, whereas the peak of insulin appeared at a later point in time as the 120-min glucose level increased. These associations were similarly observed in both obese and non-obese subgroups, although obesity was associated with higher insulin levels. Peak insulin levels also demonstrated an inverse U shape in association with 0-min glucose levels and indices of ß cell function, assessed by the disposition index and the ß-cell function index. In conclusion, peak insulin levels followed an inverse U shape in relation to glucose intolerance in a Japanese population, whereas the impairment of glucose tolerance was associated with a delay in the time to reach peak insulin levels.