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Aim: The impact of glycaemic control on fracture risk is controversial, which may be due to the possible presence of hypoglycaemia. The aim of this study was to separately investigate the impacts of severe hypoglycaemia and poor glycaemic control on fracture risk in people with type 2 diabetes. Methods: Overall, 4706 Japanese participants (2755 men and 1951 postmenopausal women) with type 2 diabetes (mean age 66 years) were followed prospectively (a median of 5.3 years; follow‐up rate, 97.6%), and were stratified by severe hypoglycaemia status and glycaemic control. The primary outcome was fractures at any anatomic site. Results: Fractures occurred in 662 participants (249 men and 413 women). The age‐ and sex‐adjusted incidence rates (expressed per 1000 person‐years) were: 71.2 (multiple episodes of severe hypoglycaemia), 43.1 (one episode), 25.2 [HbA1c < 53 mmol/mol (< 7%) without severe hypoglycaemia], 28.7 [HbA1c 53 to < 64 mmol/mol (7% to < 8%) without severe hypoglycaemia], 27.7 [HbA1c 64 to < 75 mmol/mol (8% to < 9%) without severe hypoglycaemia] and 40.5 [HbA1c ≥ 75 mmol/mol (≥ 9%) without severe hypoglycaemia]. Multivariate‐adjusted hazard ratios (95% confidence intervals) for fractures were 2.24 (1.56, 3.21) in those with multiple episodes of severe hypoglycaemia, and 1.42 (1.04, 1.95) in those with HbA1c ≥ 75 mmol/mol (≥ 9%) without severe hypoglycaemia, compared with those with HbA1c < 53 mmol/mol (< 7%) without severe hypoglycaemia. Conclusions: Both severe hypoglycaemia and poor glycaemic control were significantly related to an increased risk of fracture in people with type 2 diabetes, although severe hypoglycaemia conferred a stronger risk. What's new?: Bone fractures are common among older persons with type 2 diabetes. The impact of glycaemic control on fracture risk is controversial, and may be confounded by the possible presence of hypoglycaemia.Severe hypoglycaemia and poor glycaemic control [HbA1c ≥ 75 mmol/mol (≥ 9%)] were separately related to an increased risk of fracture in people with type 2 diabetes. Recurrent severe hypoglycaemia was strongly associated with fracture risk.This study highlights the importance of glycaemic control to prevent fractures, not only via an HbA1c < 75 mmol/mol (< 9%) but also by avoidance of severe hypoglycaemia. [ABSTRACT FROM AUTHOR]

Background Simultaneous use of proton pump inhibitors ( PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug ( NSAID)-induced small bowel injury. Aim To investigate whether polymorphisms of the cytochrome P450 2C19 gene ( CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole. Methods Study participants included 55 healthy Japanese volunteers, who participated in the PPI- NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group. Results In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury. Conclusions The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole. [ABSTRACT FROM AUTHOR]

The C242T polymorphism of p22 phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi-squared test revealed that the T-allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate-adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72–1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS-7 cells cotransfected with Nox4 and p22 phox of each genotype. The superoxide-producing activity in those cells expressing p22 phox with the T allele was not significantly different from that in cells expressing p22 phox with the C allele. The present results suggest that the p22 phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan. [ABSTRACT FROM AUTHOR]

Transient forebrain ischemia causes selective induction of ΔFosB, an AP-1 (activator protein-1) subunit, in cells within the ventricle wall or those in the dentate gyrus in the rat brain prior to neurogenesis, followed by induction of nestin, a marker for neuronal precursor cells, or galectin-1, a β-galactoside sugar-binding lectin. The adenovirus-mediated expression of FosB or ΔFosB induced expression of nestin, glial fibrillary acidic protein and galectin-1 in rat embryonic cortical cells. ΔFosB-expressing cells exhibited a significantly higher survival and proliferation after the withdrawal of B27 supplement than the control or FosB-expressing cells. The decline in the ΔFosB expression in the survivors enhanced the MAP2 expression. The expression of ΔFosB in cells within the ventricle wall of the rat brain also resulted in an elevated expression of nestin. We therefore conclude that ΔFosB can promote the proliferation of quiescent neuronal precursor cells, thus enhancing neurogenesis after transient forebrain ischemia.Cell Death and Differentiation (2005) 12, 1078–1096. doi:10.1038/sj.cdd.4401648; published online 29 April 2005 [ABSTRACT FROM AUTHOR]

Liquid diet (LD) is known to be protective against indomethacin-induced enteropathy, which is thought to be associated with ischemic change. We tested the hypothesis that the solid component of diet modulates small intestinal blood flow (SIBF) following indomethacin administration. In the first experiment, male Wistar rats were divided into 18-hr-fasted and normal diet groups. Indomethacin (20 mg/kg) or vehicle was administered intracolonically. SIBF was measured on both the mesenteric and antimesenteric sides of the intestine, using the hydrogen gas clearance method. In the second experiment, rats were given LD alone or LD with increasing concentration of soluble/insoluble fiber for seven days. The baseline SIBF was significantly higher in the groups with normal diet and LD with fiber than in the fasting and LD groups. Following indomethacin administration, SIBF gradually decreased in the groups with normal diet and LD with insoluble fiber, while neither liquid diet nor fasting reduced SIBF. There was no difference in SIBF between the mesenteric and antimesenteric sides of the intestine in any group. Our findings suggest that solid components of diet increase basal SIBF and decrease SIBF following indomethacin administration. [ABSTRACT FROM AUTHOR]

Objectives: Silent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral blood flow (CBF) and metabolism are in dispute. The purpose of this study was to elucidate CBF and metabolism in patients with SBI in relation to symptomatic stroke.Methods: The patients underwent PET and were separated into three groups; control group (C group), with no lesions on CT (n=9, mean age 57), SBI group, with no neurological signs or history of stroke, but with ischaemic lesions on CT (n=9, mean age 63), and brain infarction group (BI group), with neurological deficits and compatible CT lesions in the area supplied by perforating arteries (n=19, mean age 56). Regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were measured by PET.Results: Mean values for CBF to the cerebral cortex and deep grey matter were lower in the SBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively) and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) than in the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively). Although mean CMRO2 of deep grey matter (2.36 (SD 0.52) ml/100 g/min) was significantly decreased in the SBI group compared with the C group (2.76 (SD 0.480), p<0.01), CMRO2 of the cortical area was as well preserved in the SBI patients (2.36 (SD 0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increase of mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively).Conclusions: Patients with SBI showed decreased CBF and CMRO2 in deep grey matter. On the other hand, decreased CBF with milder increased OEF, resulting in preserved CMRO2 in the cerebral cortex indicates the presence of occult misery perfusion, suggesting that patients with SBI have reduced cerebral perfusional reserves. [ABSTRACT FROM AUTHOR]

Objective: To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM).Research Design and Methods: A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16-2.71, 2.72-3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM.Results: In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14-2.85; P = 0.01).Conclusions: Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 20-year-old woman with recurring postprandial epigastric pain and vomiting. She was diagnosed with a pocket-type intraluminal duodenal diverticulum. It discusses the two-channel method of endoscopic canalization technique used to treat her considering her recurrent abdominal symptoms.

Background: Polyomavirus BK nephropathy (BKVN) is an important infectious complication in kidney transplant patients. Regular screening using polymerase chain reaction for BK virus DNA in plasma and urinary cytology is effective for early diagnosis of BKVN. However, methods of follow-up and therapeutic targets are not well described. Methods: Ten patients with BKVN who received biweekly urinary cytology and repeat biopsies after diagnosis were retrospectively studied. Histological remission of BKVN was determined when biopsy revealed negative SV40 large T-antigen (TAg) staining. Results of urinary cytology and repeat biopsy findings were compared. Results: Urinary decoy cells disappeared in 8 of 10 patients 55 ± 25 (range 13–79) days after index biopsies. In those cases, allograft function was preserved and the final serum creatinine level was 2.14 ± 1.19 (0.80–4.55) mg/dL after 962 ± 393 (325–1563) days of follow-up. Two cases with persistent urinary decoy cells shedding lost their graft 195 and 362 days later. Amongst 29 repeat biopsies, there were 13 TAg-positive and 16 negative biopsies. In 12 of 13 TAg-positive biopsies (92%), urinary decoy cells were still positive, whereas at the same time in 15 TAg-negative biopsies, decoy cells had already disappeared (94%). Conclusions: Cytology testing is advantageous because of its cost effectiveness. Clearance of decoy cells from urine was closely related to histological remission of BKVN, and may possibly be a therapeutic target in BKVN. [ABSTRACT FROM AUTHOR]

Abstract: Background: Once-daily extended-release tacrolimus (Tac-QD) has been shown to have equivalent efficacy and safety to the twice-daily formulation (Tac-BID) in kidney transplant patients. However, detailed comparison of allograft pathology found on a protocol biopsy (PB) in Tac-QD– versus Tac-BID–based regimens has not been described. Methods: We retrospectively investigated 119 de novo living donor kidney transplant patients treated with Tac-QD (n = 90) or Tac-BID (n = 29) and their 3- and 12-month PB results. Other immunosuppressive drugs administered included basiliximab, mycophenolate mofetil, and methylprednisolone. We evaluated daily doses and trough levels of Tac and serum creatinine levels, and compared pathologic findings. Results: Daily doses were higher in the Tac-QD group, but trough levels and serum creatinine levels were comparable. On 3- and 12-month PB, the frequency of subclinical rejection was similar between the groups, whereas interstitial fibrosis and tubular atrophy (IF/TA) were less common in the Tac-QD group at 12 months (42.2% vs 20.6%, P = .04). Univariate and multivariate logistic regression analyses revealed that allograft rejection (borderline changes or higher) was associated with IF/TA (odds ratio 4.09, 95% confidence interval 1.76–10.10, P = .001). The Tac-QD–based regimen showed a trend toward the absence of IF/TA but it did not reach statistical significance. Tubular vacuolization and arteriolar hyaline changes were also comparable in the two groups. Conclusions: We found a trend toward milder IF/TA, but no significant differences in kidney allograft pathology in patients who were administered Tac-QD– versus Tac-BID–based regimens at 12 months. The effects of Tac-QD on chronic allograft injury must be studied by longer observation. [Copyright &y& Elsevier]