Immune modulation: Role of the inflammatory cytokine cascade in the failing human heart

Recent studies have determined that expression of inflammatory mediators, such as cytokines and chemokines, is an important factor in the development and progression of heart failure (HF). These inflammatory mediators are expressed in response to various myocardial insults, including myocardial ischemia, viral infection, and toxins, and appear to have a detrimental effect on cardiac function and prognosis in HF patients. Our previous reports have shown activation of inflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), in the myocardium and peripheral monocytes in patients with HF. Indeed, sustained increases in cytokines, including TNF-α and its receptor, lead to monocyte phenotype transition, myocytic apoptosis, and activation of matrix metalloproteinase. This in turn modifies the interstitial matrix, augmenting further ventricular remodeling. Thus, in view of the emerging importance of TNF-α in the pathogenesis of HF, we review the effects of TNF-α on the physiology of the heart and the development of clinical strategies to target the inflammatory cytokine cascade.     

A lipoprotein lipase activator,NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether the lipoprotein lipase activator NO-1886 had an effect on the prevention of atherosclerosis in aged rats which undergo exercise. Exercise for 3 months did not affect plasma lipids but decreased the accumulation of visceral fat in 2-year-old rats (aged rat). Exercise also resulted in an elevation of plasma lipid peroxide (LPO) levels and impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in aged rats. On the other hand, NO-1886 decreased plasma triglycerides and increased HDL cholesterol and suppressed the elevation of plasma LPO levels caused by exercise. Furthermore, NO-1886 prevented impaired endothelium-dependent relaxation caused by exercise. In summary, the results of our study indicate that exercise may cause impaired endothelium-dependent relaxation by elevation of LPO in aged rats, and that NO-1886 prevents this impaired endothelium-dependent relaxation of aorta by reducing plasma triglycerides, elevating HDL cholesterol, and suppressing the elevation of plasma LPO caused by exercise.     

The role of physical therapists in introducing assistive products for the home-bound elderly disabled

[Purpose] This study explored the roles of physical therapists (PTs) in introducing assistive products, which are essential for living securely and stably at home, and examined how PTs can fulfill these roles more efficiently and effectively. [Subjects and Methods] A questionnaire on introducing assistive products was administered to PTs working at randomly selected hospitals, health-care facilities for the elderly requiring long-term care, home-visit nursing stations, and other such facilities and to PTs providing physical therapy directly to the home-bound elderly disabled. The subjects of the study were 77 PTs who returned valid responses. [Results] For awareness of systems for assistive product’s introduction, PTs were more aware of the system based on the Long-Term Care (LTC) Insurance Act than the system based on the Act on Welfare for the Home-Bound Elderly Disabled. For PTs handling assistive product’s introduction for the home-bound elderly disabled, approximately 91% of the respondents answered that they had handled some cases of assistive product’s introduction, and PTs with longer clinical experience had handled more assistive product’s introduction cases. [Conclusion] The results demonstrated that PTs understand the work involved in introducing assistive products work well and that they handle it. The results, however, also suggested that educational and operational improvements are urgently required for PTs introducing assistive products essential for the lives of the home-bound elderly disabled.Key words: Assistive products, Physical therapists, Home-bound elderly disabled     

Induction of cyclooxygenase protein and stimulation of prostaglandin E2 release by epidermal growth factor in cultured guinea pig gastric mucous cells

The present study was undertaken to investigate whether epidermal growth factor (EGF) could stimulate prostaglandin E₂ release, and if so, by what mechanism EGF would exert such an effect in gastric mucosal cells. In cultured guinea pig gastric mucous cells, EGF dosedependently stimulated prostaglandin E₂ release, with maximal stimulation observed at 10 ng/ml. EGF stimulated an increase in cyclooxygenase activity, which was reduced by protein synthesis inhibitor, actinomycin D, and cycloheximide. EGF also stimulated the enzyme protein synthesis estimated by Western blot analysis, whereas EGF did not stimulate phospholipase A₂ activity. These results suggest that such an effect of EGF onde novo synthesis of cyclooxygenase protein and prostaglandin E₂ release may be involved at least in part in the mechanism of EGF-induced local regulation of gastric mucosal integrity.     

Modifiable factors for the length of life with disability before death: mortality retrospective study in Japan

BACKGROUND: Past studies have measured and described the length of life with disability before death, but there has been no study of the relationship between modifiable lifestyle factors and duration of disability. OBJECTIVE: To examine whether there are modifiable factors influencing the length of life with disability before death. METHODS: The study was designed as a retrospective observation of the deceased who had earlier been enrolled in a prospective cohort study.During the follow-up period (1996-1999), we documented 781 deaths among those who were 70-79 years of age at the baseline survey in 1994 (n=10,216). In 2000, we interviewed family members of the deceased about the duration of the subjects' disability before death (n=655). RESULTS: The median duration of disability before death was approximately 6 months. Both higher Body Mass Index (BMI) and shorter time spent walking were significantly associated with an increased risk of long-term disability (more than 6 months). The odds ratios of long-term disability were 1.3 in those with BMI 20-25 and 2.1 in those with BMI>25, compared with BMI<20. The odds ratios of long-term disability were 1.3 in those walking for 0.5-0.9 h/day and 1.7 in those walking for <0.5 h/day, compared with those walking for >1.0 h/day. These relationships were unchanged after stratification for causes of death. CONCLUSION: Weight control and walking in later life may shorten the length of life with disability before death.     

Mucin and differentiation in Epstein-Barr virus-associated gastric carcinoma

BACKGROUND/AIMS: Epstein-Barr virus (EBV) is present in roughly 1 in 10 cases of gastric carcinoma, particularly in undifferentiated adenocarcinomas. To clarify the histological developmental processes in EBV-associated gastric carcinoma, we investigated the presence of EBV infection, changes in the degree of differentiation within lesions, and mucin phenotypes of gastric carcinomas. METHODOLOGY: We had already examined 124 gastric carcinomas using in situ hybridization for EBV-encoded small RNA1 (EBER-1) and 12 lesions were EBER-1-positive. From these lesions we selected 8 carcinomas positive for EBER-1, and then chose 16 EBER-1-negative carcinomas as controls. Hematoxylin and eosin (H&E) stained specimens were examined for changes in histological type within each lesion. Mucin phenotypes of the specimens were determined using human gastric mucin (HGM), MUC2 and CD10 immunostaining. RESULTS: Of the EBER-1-positive lesions, 50% exhibited the gastric type mucin phenotype, whereas only 19% of the EBER-1-negative lesions were of the gastric phenotype. Changes in the histological type were seen within 75% of the EBER-1-positive lesions and within 62.5% of the EBER-1-negative lesions. CONCLUSIONS: The gastric mucin phenotype tended to be more common in the EBV-associated gastric carcinomas. The influence of EBV infection on the change in the histological type within the lesion was considered to be slight.     

A case of pulmonary nocardiosis with Nocardia beijingensis

A 60-year-old woman seen at the National Hospital Organization Nagasaki Medical Center of Neurology with a cough and abnormal chest radiography was found in CT to have interstitial shadows in the bilateral lower lung fields. She was diagnosed with interstitial pneumonia and treated with steroids. Treatment was effective, and the predonisolone dosage was gradually tapered. When dosage was 17.5 mg/day, her chest Xray showed exacerbation. Cyclophosphamide at 50mg/day was added, and chest radiography improved. Two months later, her chest radiography showed infiltration with cavities in the left lung field. Although several antibiotics (sulbactam/cefoperazone, levofloxacin) were administered, no improvement was seen. Sputa on hospital day 60 showed the presence of gram-positive branched rods, identified as Nocardia beijingensis. We administered sulfamethoxazole/trimethoprim, meropenem and levofloxacin together, and shadows improved. With recurrent aggravation of interstitial pneumonia, however, new cavity shadows occurred in the bilateral lung due to Aspergillus fumigatus. Shadows worsened and she died of respiratory failure. Testing for pulmonary nocardiosis should be added to differential diagnosis procedures as an opportunistic infection in immune-compromised hosts.