Ingestion of a moderate high‐sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon‐like peptide‐1 secretion

Aims/Introduction: Excessive intake of sucrose can cause severe health issues, such as diabetes mellitus. In animal studies, consumption of a high‐sucrose diet (SUC) has been shown to cause obesity, insulin resistance and glucose intolerance. However, several in vivo experiments have been carried out using diets with much higher sucrose contents (50–70% of the total calories) than are typically ingested by humans. In the present study, we examined the effects of a moderate SUC on glucose metabolism and the underlying mechanism. Materials and Methods: C57BL/6J mice received a SUC (38.5% sucrose), a high‐starch diet (ST) or a control diet for 5 weeks. We assessed glucose tolerance, incretin secretion and liver glucose metabolism. Results: An oral glucose tolerance test (OGTT) showed that plasma glucose levels in the early phase were significantly higher in SUC‐fed mice than in ST‐fed or control mice, with no change in plasma insulin levels at any stage. SUC‐fed mice showed a significant improvement in insulin sensitivity. Glucagon‐like peptide‐1 (GLP‐1) secretion 15 min after oral glucose administration was significantly lower in SUC‐fed mice than in ST‐fed or control mice. Hepatic glucokinase (GCK) activity was significantly reduced in SUC‐fed mice. During the OGTT, the accumulation of glycogen in the liver was suppressed in SUC‐fed mice in a time‐dependent manner. Conclusions: These results indicate that mice that consume a moderate SUC show glucose intolerance with a reduction in hepatic GCK activity and impairment in GLP‐1 secretion. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00208.x , 2012)     

Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines

Heme oxygenase-1 (HO-1) confers cytoprotection against oxidative stress. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism, which was classified into S (< 27 GT), M (27-32 GT), and L alleles (>/= 33 GT). Polymorphism in the HO-1 gene promoter was shown to be associated with susceptibility to pulmonary emphysema and restenosis after angioplasty. However, the biologic mechanism underlying these associations is still unclear. To examine this issue, we established lymphoblastoid cell lines (LCLs) from subjects possessing S/S or L/L genotypes. HO-1 mRNA expressions and HO activities induced by oxidative stress were significantly higher in LCLs with S/S than those with L/L. Furthermore, LCLs with S/S were significantly more resistant to oxidant-induced apoptosis than those with L/L. These findings suggested that the polymorphism of the HO-1 gene is associated with the strength of antiapoptotic effects of HO-1, resulting in an association with susceptibility to oxidative stress-mediated diseases.     

Dental status and mortality in institutionalized elderly people

Background:   Inadequate dentition for mastication is one of the major issues associated with systemic health for institutionalized elderly people, but its prognostic value and related deaths have not been fully examined.
Methods:   Four hundred and three patients aged 65 and older were recruited from nine nursing homes and were prospectively followed up for morbidity and mortality for 5 years in Japan. These patients were classified into three groups according to dental status: patients who had adequate dentition with natural teeth only or natural teeth with partial dentures (Group A); those who were edentulous but wearing full dentures (Group B); and those who had inadequate dentition without dentures (Group C).
Results:   Dental status was strongly related to age, cognitive function and activities of daily living. After allowing for confounding effects, the 2-year risk of mortality among those in Group C was 1.84 times that of Group A (95% confidence interval 1.01–3.36, P  = 0.047). Furthermore, the 5-year mortality rate in Group C was higher than that in Group A, whereas that was not significant with a hazard ratio of 1.30 (0.90–1.88, P  = 0.168). The main causes of death were respiratory infections, which explained 14.1% of all causes of death in Group A, 14.3% in Group B and 18.3% in Group C. Any associations between a specific cause of death and the different dental status did not reach a significant level.
Conclusion:   Inadequate dental status is associated with high overall mortality. Our findings suggest that systemic attention to dental status should be recommended in institutionalized elderly people.     

Etiology, pathogenesis and management of senile inflammatory pulmonary diseases]

We studied the etiology, pathogenesis and management of therapy-resistant inflammatory pulmonary diseases. First, to understand the pathogenesis of rhinovirus (RV) infection-induced exacerbation of bronchial asthma, we infected cultured human tracheal epithelial cells with RV. The epithelial cells produced a variety of proinflammatory cytokines, intercellular adhesion molecules (ICAM-1) and low-density lipoprotein receptor, and increased the permeability across the epithelial cells. These findings suggest that these factors and the increased permeability may cause airway inflammation, resulting in the exacerbation of asthma. Glucocorticoid and bafilomycin inhibited RV infection in the epithelial cells by reducing ICAM-1 expression and RV RNA entry from the acidic endosomes to the cytoplasm. Second, we revealed the mechanisms of aspiration pneumonia induced by silent aspiration in patients with cerebral infarction. We also developed a pharmacologic treatment for preventing aspiration pneumonia with amantadine, which stimulates the dopaminergic neurons; the angiotensin-converting enzyme inhibitors, which decrease substance P catabolism; and cilostazol, which inhibits platelet aggregation and induces cerebral vasodilation. Third, we demonstrated that exhaled carbon monoxide concentrations caused by heme oxygenase-1 upregulation, may be a useful noninvasive means of monitoring airway inflammation and of controlling elderly patients with bronchial asthma. Finally, we demonstrated that microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema caused by cigarette smoke in Japanese patients with chronic pulmonary emphysema.     

Cytomegalovirus infection during immunosuppressive therapy for diffuse parenchymal lung disease

Background and objective: Cytomegalovirus (CMV) infection is a life‐threatening condition in patients with diffuse parenchymal lung diseases (DPLDs), who are receiving immunosuppressive therapy. The aim of this study was to describe the clinical features of CMV infection and to propose a strategy for managing CMV infection in patients with DPLD who are receiving immunosuppressive therapy. Methods: A retrospective longitudinal observational study was performed on 69 patients with DPLDs (39 with acute/subacute onset, 30 with chronic onset) who were receiving immunosuppressive therapy and were positive for CMV pp65 antigen (CMV‐pp65Ag) in peripheral blood leukocytes (PBLs). Results: Clinical CMV disease and subclinical CMV antigenaemia developed in 23 and 46 patients, respectively. The cut‐off level of CMV‐pp65Ag indicating clinical CMV disease, as determined by receiver operator characteristic curve analysis, was 7.5 cells per 5 × 10⁴ PBLs. Multivariate analysis revealed that early CMV infection was associated with acute/subacute onset of underlying DPLD and with respiratory dysfunction at the commencement of immunosuppressive therapy. Multivariate analysis also suggested that the acute/subacute onset of underlying DPLD, a CMV‐pp65Ag titre of >7.5 cells per 5 × 10⁴ PBLs, and C‐reactive protein levels ≥10 mg/L indicated a poor prognosis. Conclusions: We recommend that CMV‐pp65Ag antigenaemia of >7.5 cells per 5 × 10⁴ PBLs in patients with DPLD should be treated with ganciclovir. Patients with lower levels of CMV‐pp65Ag antigenaemia should be closely monitored or treated with ganciclovir if the clinical findings suggest a poor prognosis.