Effect of MCI-2016 (bifemelane hydrochloride) on cerebral ischemia following ligation of both common carotid arteries in Mongolian gerbils

Cerebral protective effect of MCI-2016 and influence of age on survival time in the cerebral ischemic model induced by bilateral-carotid-arterial ligation in male Mongolian gerbils were studied. Of all animals (6 to 40 weeks old), the mean survival time of the immature group (6 to 7 weeks) was long (3.6 hr), but variable, and that of the 10 to 40 weeks group was relatively stable (1.9-2.4 hr), but that of the older group (30-40 weeks) inclined to be reduced. Effects of drugs on this model were studied in 10 to 15 weeks old male Mongolian gerbils. The mean survival time in the control groups was 2.3-2.4 hr. After a single administration of MCI-2016 at doses of 25 mg/kg, i.p., and 100 mg/kg, p.o., the mean survival time were 8.1 and 6.4 hr, respectively. In these cases, some animals survived over 12 hr, while no animals surviving over 12 hr were observed in the control group. In this model, animals showed severe neurological symptoms. This, however, tended to be depressed by the administration of MCI-2016 at a dose of 25 mg/kg, i.p., which was observed early after ligation. A cerebral metabolic activator, Ca-hopantenate, slightly increased the survival time at a dose of 100 mg/kg, i.p., and a cerebral vasodilator, ifenprodil, was not effective. Subsequently, consecutive administration of MCI-2016 at a dose of 25 and 50 mg/kg, p.o., was more effective than a single administration of MCI-2016 at each dose. The mechanism for the cerebral protective effect of MCI-2016 was discussed.     

LANGERHANS CELLS AMONG BILE DUCT EPITHELIAL CELLS IN CHRONIC LIVER DISEASE

Langerhans cells were found among bile duct epithelial cells in a biopsy specimen from a patient with chronic liver disease showing cholangitic features. The bile duct was 90 μm In diameter and surrounded with mononuclear cell infiltration. Under the electron microscope, the cell had a clear cytoplasm and contained a deeply indented nucleus, a centriole, well-developed Golgi complexes and many rod-shaped bodies (Birbeck granules).     

Changes of pancreatic exocrine function after major resection of the pancreas in dogs.

Changes of an exocrine function after major resection of the canine pancreas were observed by pancreozymin-secretin test and the results were compared with an endocrine function examined by glucose tolerance test. The exocrine function of the remnant pancreas revealed characteristic changes according to the resection rate of the pancreas: 1) After removal of 50 to 70 per cent of the entire pancreas, diabetes did not develop and the exocrine function of the remnant pancreas was well maintained. 2) After 70 to 90 per cent pancreatectomy, diabetes developed six weeks or more later and the exocrine function of the remnant pancreas per body weight decreased slightly. The degree of disturbance of the exocrine function in the diabetic dogs was greater than that in the non-diabetic group, but the exocrine function per the remnant pancreas weight increased and it was greater than normal level even in the diabetic dogs. The hypersecretory state of the exocrine pancreas after surgery was verified. 3) After 90 per cent or greater resection of the pancreas, diabetes occurred immediately and disturbance of the exocrine function was remarkable. Hypersecretory state did not appear. 4) Both the endocrine and exocrine functions after major pancreatic resection were found to be related to the resection rate, but there were significant differences in the reserve capacity of the endocrine and exocrine pancreas.     

Induction of CD4+ regulatory T cells by TPA in mice: contra-suppression by CD8+ T cells

Among the eight inbred mouse strains employed in our preceding report, 12-O-tetradecanoylphorbol 13-acetate (TPA) painting alone induced CD4+ regulatory T (Tr) cells in four strains (e.g., C3H/He) at 6-8 weeks of age, but not in the remaining strains (e.g., C57BL/6, BALB/c). In the present study, the effect of growth from 4-14 weeks on delayed-type hypersensitivity (DTH) response was investigated in three inbred murine strains, C3H/He (H-2k), C57BL/6 (H-2b) and BALB/c (H-2d) mice. In all strains older than 10 weeks, DTH response was suppressed exclusively by TPA painting. The defect of suppressive activity for DTH in several of the strains at 6-8 weeks of age was dependent on the presence of cells, which blocked regulatory cell activity at 6-8 weeks of age, but not at 10 weeks of age. The age-dependent difference in regulatory activity was caused by the presence of CD8+ contra-regulatory T (Tcr) cells. CD8+ contra-regulatory T cells are required to contact regulatory cells in order to block DTH suppressive activity. Adhesion molecules were of great importance in contra-suppression, as antibody treatment to LFA-1 or ICAM-1 blocked this activity. ICAM-1 expression on CD4 T cells greatly increased following growth in 10 week-BALB/c mice receiving TPA than 6-week-old mice, however, a slight increase in growth occurred in 6-to-10-week-old animals in which TPA was absent. The degree of increment in body weight was very similar in these inbred strains. Thymus involution in C3H/He mice was the earliest signal among these mice. This result may suggest that the period of differentiation and maturation of T cells in a first lymphoid tissue for the growth process differs in these three inbred strains. This study provides an interesting example of genetic control of maturation or proliferation of peripheral T cells.     

Heart and Stroke Foundation of Ontario (HSFO) high blood pressure strategy's hypertension management initiative study protocol

Background  

Achieving control of hypertension prevents target organ damage at both the micro and macrovascular level and is a highly cost effective means of lowering the risk for heart attack and stroke particularly in people with diabetes. Clinical trials demonstrate that blood pressure control can be achieved in a large proportion of people. Translating this knowledge into widespread practice is the focus of the Hypertension Management Initiative, which began in 2004 with the goal of improving the management of this chronic health condition by primary care providers and patients in the community.     

Microalbuminuria screening for patients having type 2 diabetes mellitus: who wants to participate?

BACKGROUND AND OBJECTIVES: "Difficult-to-recruit" patients are sometimes less compliant with their care, are more reluctant to seek medical attention and less likely to survive than their "easy-to-recruit" counterparts. They also tend to be excluded from clinical trials. The aim of this paper was to evaluate whether such differences extend to patients' willingness to be screened for diabetic nephropathy in a family practice setting. DESIGN: A cross-sectional study. SETTING: A Canadian university family practice unit. PATIENTS: Two hundred and forty-seven patients with type 2 (adult-onset) diabetes mellitus as identified by computer searches of patient records of approximately 12,000 patients in the family practice unit. INTERVENTION: A cross-sectional secondary preventive screening program obtained urine samples from all patients with type 2 diabetes mellitus, regardless of patients' willingness to participate. MAIN OUTCOME MEASURE: The prevalence of micro- and macroalbuminuria. RESULTS: Of the 247 patients identified, 186 (75%) easy-to-recruit enrollees agreed to participate in screening and 61 (25%) difficult-to-recruit non-enrollees initially declined to be screened. The non-enrollees were subsequently evaluated by their own family physicians as part of routine clinical care and the results were captured for analysis. Overall rates of albuminuria were similar in the easy- and difficult-to-recruit groups (31% versus 38%, p = 0.151). The main predictors of albuminuria were female sex (odds ratio [OR] = 2.1, p = 0.021), duration of diabetes in years (OR = 1.05, p = 0.023), current use of angiotensin-converting enzyme inhibitor (OR = 2.26, p = 0.008) and number of diabetic complications (OR = 1.45, p = 0.028). CONCLUSIONS: There is little difference in the prevalence of albuminuria related to patients' willingness to participate in a screening program. Therefore, there are no disproportionate gains for family practice researchers who aggressively seek difficult-to-recruit patients in this set ting. In contrast, primary care doctors should make every effort to ensure optimal care to diabetic patients regardless of a patient's initial hesitancy.     

Clinical characteristics of prostate cancer in elderly Japanese patients 80 years of age or older

OBJECTIVE: Prostate adenocarcinoma is predominantly a disease of elderly men. This study retrospectively examined prostate adenocarcinoma in Japanese patients 80 years of age or older to determine the natural history and prognosis of this malignancy in the elderly population. METHODS: The medical records of 593 patients were reviewed, with respect to age, histologic grade, clinical and pathological stage, treatment modality and clinical outcome. A variety of possible clinical factors were compared between patient groups > or = 80 and < 80 years old. RESULTS: No significant difference in clinical stage, tumor grade, and performance status (PS) was found between two age groups of patients with prostate cancer. A significant stage migration between pre-PSA era and PSA era was found only in the group < 80 years old. In the series of stage D2 cancer patients, while there was no significant difference in cause-specific and progression-free survival rates between the two groups, the younger group < 80 years old had a better marker response at 3 months from the start of endocrine therapy compared with the older group (P = 0.0048, chi2 analysis). CONCLUSION: These data suggest that patients > or = 80 years with prostate cancer present with similar histologic grade and disease stage as younger patients, although the younger group with stage D2 had a better marker response to endocrine therapy.     

Development of a method to identify persistent and blanchable redness by skin blotting in mice

Persistent and blanchable redness (PBR) is not currently included in category I pressure injury (PI), which is defined as non-blanchable redness (NBR). However, PBR progresses to PI in a clinical setting. Therefore, it should be clinically managed as category I PI, and a method to distinctly identify PBR is needed. This study aimed to examine whether PI-related biomarkers can distinguish PRB from transient redness (TR) and NBR using skin blotting. TR, PBR, and NBR models were established by the different conditions of dorsal skin compression. Redness observation and skin blotting were performed, and the skin tissue samples were subjected to histological and molecular biological analyses. The vascular endothelial growth factor (Vegf) b, heat shock protein (Hsp) 90aa1, tumour necrosis factor, interleukin (Il) 1b, and Il6 messenger ribonucleic acid levels were significantly different between the three models. The VEGF-A, VEGF-B, IL-1β, and IL-6 protein levels were different between the three models. Although the results of skin blot examinations were inconsistent with those of the expression analysis of tissue, HSP90α and IL-1β are suggested to be potential markers to distinguish PBR from TR and NBR.