Elucidating the Function of Non catalytic Domains of Collagenases and Aggrecanases

Metalloproteinases that degrade extracellular matrix molecules play important roles in development and progression of various diseases. Among them, collagenases are unique as they have an ability to degrade triple helical interstitial collagens into 3/4 and 1/4 fragments, a crucial step for collagenolysis in the tissue. Collagenases, consisting of a catalytic domain and a hemopexin domain, requires both domains for collagenolysis. The enzymes unwind triple helical collagen before they hydrolyze the peptide bonds. Aggrecanases are also multidomain metalloproteinases belonging to the ADAMTS family, and the noncatalytic ancillary domains also play an important role in recognition of aggrecan and their activities. Attenuation of collagenase and aggrecanase activities will be achieved by inhibitors or antibodies that interact directly with those noncatalytic ancillary domains (exosite inhibitors). Such molecules will be attractive for therapy as they will be highly selective because they are based on the unique mechanism of each proteinase.     

Impaired catecholamine secretion as a cause of diabetic autonomic neuropathy

Human and animal studies were performed to investigate the causes of diabetic autonomic neuropathy. Human diabetics, with and without autonomic neuropathy, were measured for plasma catecholamine response to insulin hypoglycemia and for urinary catecholamine excretion. In streptozotocin-diabetic rats, plasma catecholamine response and tissue catecholamine concentrations were measured at various stages of the disease. As the duration of the diabetic state lengthens in rats, there is a time-proportional stepwise decrease in plasma catecholamine response. This is similar to the clinical course observed in human diabetics, which also includes a reduction of catecholamine excretion after the appearance of autonomic neuropathy. After 6 weeks of diabetes, rat tissue is found to have an increased concentration of catecholamines; this may represent a compensatory reaction to the difficulties of secretion. At 13 weeks of diabetes, tissue catecholamine concentrations return to almost normal, when plasma responses have disappeared. These results suggest that the impaired secretion of catecholamines in diabetics may be a cause of diabetic autonomic neuropathy.     

Nonepisodic angioedema with eosinophilia: a report of two cases and a review of the literature

We report two young female patients who developed sudden-onset nonpitting edema in both hands and lower legs in early autumn with no significant previous or family history. One of these patients showed arthralgia in both wrists and ankles. The clinical symptoms improved without treatment, and they were diagnosed as having nonepisodic angioedema with eosinophilia (NEAE) based on laboratory investigations and the lack of recurrence. The clinical picture of this disease is often similar to that of rheumatologic disorders with tenosynovitis with regard to edema and pain in the distal portion of the extremities. When edema is seen in the bilateral hands and lower legs, particularly in young women, NEAE should be actively considered as a possible diagnosis.     

Stimulation of choleresis by insulin-like growth factor-I in rats

Insulin-like growth factor-I (IGF-I) is an endogenous growth factor which is mainly produced in the liver. The functions of IGF-I can be summarized as growth-promoting and insulin-like metabolic actions. In the present study, the effect of IGF-I on bile flow and bile acid secretion was investigated in rats. In normal rats bile flow was significantly increased by single exogenous administration of IGF-I, and by 1 week treatment of IGF-I, both bile flow and bile acid secretion were significantly increased. Moreover, to further understand the relationship between IGF-I and bile acid secretion, hypophysectomized rats were next used. We found that the decreases in bile flow and bile acid secretion observed in rats after hypophysectomy, as well as the decrease in the endogenous level of IGF-I in the blood, were partially reversed by 1 week exogenous IGF-I treatment. Overall, this study showed that IGF-I stimulates choleresis associated with an elevation of bile acid secretion in both normal and hypophysectomized rats when exogenously administered, suggesting the importance of IGF-I in the stimulation of choleresis in vivo.     

Japanese severity score for acute pancreatitis well predicts in-hospital mortality: a nationwide survey of 17,901 cases

Background

Early identification of severe cases of acute pancreatitis is necessary to reduce mortality. The Japanese severity score, which consists of nine prognostic factors, is reported to be useful for assessment of acute pancreatitis severity, but has not been validated by large-scale data.

Methods

Data on adult patients with acute pancreatitis were collected between July 1, 2010, and September 30, 2011, from a national administrative database covering 1,032 Japanese hospitals. In-hospital mortality was analyzed to evaluate the predictive value of the Japanese severity score.

Results

A total of 17,901 patients were included. Total in-hospital mortality was 2.6 %, and mortality rates of non-severe and severe acute pancreatitis were 1.1 and 7.0 %, respectively (P < 0.001). In multivariate analysis with adjustment for other baseline characteristics, the odds ratio for mortality significantly increased according to an increase in prognostic factor score. The odds ratio for mortality of computed tomography grade 3 was significantly higher than that of grade 1 (P < 0.001), but that of grade 2 was not (P = 0.149). In receiver operating characteristic curve analysis of the prognostic factor score for prediction of in-hospital mortality, the area under the curve was 0.798 (95 % confidence interval 0.775–0.821), and the optimum cutoff level of the prognostic factors was 2, in accordance with the definition of the current scoring system.

Conclusions

The prognostic factor score has good predictive value for in-hospital mortality of acute pancreatitis, and thus is useful for severity assessment of acute pancreatitis at the early stage of hospital admission.     

Recent trends in practice patterns and impact of corticosteroid use on pediatric Mycoplasma pneumoniae-related respiratory infections

Background

Mycoplasma pneumoniae is a major pathogen causing community-acquired pneumonia/bronchitis in children, and macrolide-resistant strains are increasing in East Asian countries. Recent practice patterns, especially for antibiotic selection, and benefits of corticosteroid treatment in pediatric Mycoplasma pneumoniae infections remain unclear.

Association between Grit Scales and adherence to regular hospital visits among Japanese patients with type 2 diabetes: Prospective observational study

This study examined the association between Grit Scales and adherence to a schedule of regular hospital visits among Japanese type 2 diabetes patients. Patients with type 2 diabetes who visited the outpatient clinic as new patients comprised the study’s participants. Self-administered Short Grit Scale data were obtained from 122 patients at the first consultation and were then observed for 1 year. As the results, 21 participants failed to attend the hospital. In a logistic regression analysis, the Grit Scale as a continuous variable was positively associated with adherence to regular clinical visits. Its odds ratio and 95% confidential interval was 9.68 and 2.87–32.65 (P = 0.0003). In conclusion, it is likely that the Grit Scale is closely associated with adherence to regular hospital visits among Japanese type 2 diabetes patients.     

Rarity of Severe Bleeding and Perforation in Endoscopic Ultrasound-Guided Fine Needle Aspiration for Submucosal Tumors

Background

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established procedure for the pathological diagnosis of gastrointestinal submucosal tumors (SMTs). Although bleeding and perforation are potentially severe complications of EUS-FNA, the incidences and severities of these complications have not yet been fully evaluated because of their relative rarity.

Aim

The purpose of this study was to evaluate the incidences and mortality of severe bleeding and perforation in patients who underwent EUS-FNA for SMTs.

Methods

The records of 1,135 consecutive patients who underwent EUS-FNA for SMTs at 219 hospitals, with low- to high-volume, were reviewed using a Japanese nationwide administrative database.

Results

Of the targeted lesions 73.5 % were located in the stomach, 13.4 % in the esophagus, 8.2 % in the duodenum, and 4.9 % at other sites. Five patients (0.44 %) experienced severe bleeding requiring red blood cell transfusion or endoscopic treatment, with none experiencing perforation. Only one patient (0.09 %) died in-hospital within 30 days of EUS-FNA (0.09 %), with death not associated with bleeding or perforation.

Conclusions

EUS-FNA is safe in evaluating SMTs, with low risks of bleeding and perforation.