Prostaglandin synthesis inhibitor affects humoral conditions and oxygen metabolism during normothermic cardiopulmonary bypass

We have reported that infusion of prostaglandin synthesis inhibitor (PGSI) reduced the severity of hypotension during normothermic cardiopulmonary bypass (CPB). In the present study, we investigated the effects of PGSI on humoral conditions and whole body oxygen metabolism during normothermic CPB conducted for 60 min in 8 adult goats. The PGSI group (n = 4) was administered 100 to 150 mg of flurbiprofen, a potent PGSI, before and during CPB, and the control group (n = 4) was administered noradrenaline (NA) to restore hypotension. The prostaglandin E2 (PGE2) and NA concentrations in the PGSI group were significantly lower than those of the control group (PGE2 8.8 +/- 1.0 versus 30.3 +/- 11.5 pg/ml, NA 431 +/- 197 versus 3847 +/- 2,153 pg/ml). The adrenaline concentration was not significantly different between the groups. The oxygen consumption and the oxygen extraction rate were not significantly different between the groups, but the blood lactate level in the PGSI group was lower than that of the control group (34.3 +/- 7.6 versus 43.7 +/- 3.8 mg/dl). In conclusion, PGSI improves humoral disorder and thus prevents inadequate tissue oxygen delivery.     

The immunohistochemical analysis of pendrin in the mouse inner ear

Pendred's syndrome (PS) is an autosomal recessive disorder characterized by deafness and goiter, which are caused by mutations in the Pendred's syndrome gene (PDS). PDS encodes a membrane protein named pendrin that is considered to act as an anion transporter. An expression pattern of the PDS ortholog (Pds) mRNA in the auditory and vestibular systems has been reported in mice, and the localization of pendrin has been reported recently. We generated antipeptide antibodies against human pendrin, and performed immunohistochemical analysis of mouse inner ears. We detected pendrin in the endolymphatic duct and sac, and the utricle, saccule, and external sulcus. In the endolymphatic duct and sac, the expression of pendrin was apparent at the apical membrane. In addition, we detected pendrin in the spiral ligament, Claudius cells, Deiter's cells, and the spiral ganglion of the cochlea. Our results are key to defining the role of pendrin in inner ear development and elucidating the pathogenic mechanisms underlying deafness in PS.     

Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat,an animal model of the metabolic syndrome

SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats.     

Isolation of microsatellite loci from the millipede, Brachycybe nodulosa Verhoeff

Brachycybe nodulosa is a fungivorous millipede that distributed in Japan and Korea. This species shows patchy distributions and the exclusive paternal care of eggs, and thus is an important subject for both conservation and evolutionary biology. Thirteen polymorphic microsatellite loci were newly isolated from the taxon. Moderate to high levels of polymorphism were observed, with numbers of alleles ranged from 2 to 10. The mean observed and expected heterozygosities ranged from 0.200 to 1.000 and 0.405 to 0.886, respectively. Two loci showed lower heterozygosities than the expectation under HWE. No linkage disequilibrium was detected for any pair of the loci. These new loci will be useful in conservation genetics and evolutionary ecology studies of this species.     

Cardiac Autonomic Nervous Function During Long-Term Nonpulsatile Left Heart Bypass

We investigated the changes in cardiac autonomic nervous activities during long-term nonpulsatile left heart bypass (NLHB) by analyzing heart rate variability. A pulsatile ventricular assist device was installed in 3 goats, and pulsatile left heart bypass (PLHB) was conducted for 2 weeks. Then, NLHB was maintained for the following 4 weeks. The segmental data of the R-R intervals (R-Rs) was analyzed by maximum entropy spectral analysis. Changes in evaluated parameters from the last week of PLHB to the 4th week of NLHB were as follows: the mean R-Rs increased from 511 ms to 692 ms; the coefficient of variation of R-R increased from 10.2 to 14.1%; the power of the low frequency band (LF) increased from 747 ms2 to 2,855 ms2; the power of the high frequency band (HF) increased from 512 ms2 to 1,270 ms2; and the ratio of LF to HF increased from 2.6 to 6.5. These results indicated that the cardiac autonomic nervous activity, both sympathetic and parasympathetic, increased during long-term NLHB.     

Medical care costs of patients with rheumatoid arthritis during the prebiologics period in Japan: a large prospective observational cohort study

Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan. The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004. Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed. The average outpatient cost gradually increased (+7.7% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004. Medications accounted for approximately 50% of total outpatient costs, which increased 29.6% during the 4 years. The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score. Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs (p < 0.001). Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan. Medical costs were higher with increasing RA disease activity and disability levels.