Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats

The Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem contributes to blood pressure regulation. Activation of this pathway might be involved in the central nervous system mechanisms of hypertension. The aim of the present study was to determine whether baroreflex control of heart rate is altered by inhibition of Rho-kinase in the NTS. Adenovirus vectors encoding dominant-negative Rho-kinase or beta-galactosidase were transfected into the nucleus tractus solitarii of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Baroreflex control of heart rate was examined by changing arterial pressure with an intravenous infusion of phenylephrine or sodium nitroprusside. The maximum gain of baroreflex control of heart rate was attenuated in SHR compared with WKY before the gene transfer. Transfection of adenovirus vectors encoding dominant-negative Rho-kinase significantly augmented the maximum gain in both WKY and SHR. The extent of this augmentation, however, was greater in SHR than in WKY. After treatment with metoprolol, the maximum gain was significantly decreased in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase, but not in nontransfected rats. In contrast, after treatment with atropine, the maximum gain was greater in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase compared with nontransfected rats, although it was decreased in both groups. These results suggest that inhibition of Rho-kinase in the NTS augments baroreflex control of heart rate, in both WKY and SHR, probably because of a cardiac sympathoinhibitory effect.     

A study on clinical features of Mycobacterium kansasii pulmonary disease in women

OBJECTIVES: To clarify clinical features of M. kansasii pulmonary disease in women. METHODS: We performed a retrospective analysis of M. kansasii pulmonary disease in women compairing with that in men. We focused on 8 female cases of M. kansasii pulmonary disease during the past 7 years from June 1998 to August 2005. RESULTS: The cases of M. kansasii pulmonary disease in women have increased in the latter few years. The mean age of female cases was higher than that of male cases, 65.6 and 53.1 years old, respectively. The number of female cases with smoking history was lower than that of male cases, 37.5% and 90.0%, respectively. Two female cases had underlying pulmonary diseases, as compared with 10 male cases, 25.0% and 33.3%, respectively. The radiological findings in female cases included 2 cavitary opacities, 1 infiltrative opacity and 5 nodular, bronchiectatic opacities, as compared with 27 cavitary opacities, 1 infiltrative opacity, 1 solitary nodular opacity and 1 nodular, bronchiectatic opacity in male cases. MAC was also detected in 2 female cases, who presented with nodular, bronchiectatic opacities. On the other hand, there were 6 female cases, in which no other NTM was detected. 3 cases showed cavitary or infiltrative opacities, which improved with the following 3 tuberculous drugs INH, RFP, and EB (HRE), while others showed nodular, bronchiectatic opacities, in which 2 cases showed radiological exacerbations without any treatment and another one revealed an improvement with HRE. CONCLUSIONS: M. kansasii pulmonary disease in women tends to be identified in elderly who smoke less and have no underlying pulmonary diseases, and most of radiological findings in female cases revealed nodular, bronchiectatic opacities. Summing up all these findings, clinical features of M. kansasii pulmonary disease in women was considered to resemble that of MAC infection, and it was speculated that the increase of M. kansasii pulmonary disease in women has some relationship with that of MAC infection in middle or lingular lobe. However, it was confirmed that some cases of M. kansasii pulmonary disease in women might primarily present with nodular, bronchiectatic lesions, regardless of MAC infection.     

Association of physical activities of daily living with the incidence of certified need of care in the long-term care insurance system of Japan: the ROAD study

Background

The present study aimed to investigate association of physical activities of daily living with the incidence of certified need of care in the national long-term care insurance (LTCI) system in elderly Japanese population-based cohorts.

Methods

Of the 3,040 participants in the baseline examination, we enrolled 1,773 (699 men, 1,074 women) aged 65 years or older who were not certified as in need of care-level elderly at baseline. Participants were followed during an average of 4.0 years for incident certification of need of care in the LTCI system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used assess function. Associated factors in the baseline examination with the occurrence were determined by multivariate Cox proportional hazards regression analysis. Receiver operating characteristic curve analysis was performed to evaluate cut-off values for discriminating between the occurrence and the non-occurrence group.

Results

All 17 items in the WOMAC function domain were significantly associated with the occurrence of certified need of care in the overall population. Cut-off values of the WOMAC function score that maximized the sum of sensitivity and specificity were around 4–6 in the overall population, in men, and in women. Multivariate Cox hazards regression analysis revealed that a WOMAC function score ≥4 was significantly associated with occurrence with the highest hazard ratio (HR) for occurrence after adjusting for confounders in the overall population (HR [95 % confidence interval (CI)] 2.54 [1.76–3.67]) and in women [HR (95 % CI) 3.13 (1.95–5.02)]. A WOMAC function score ≥5 was significantly associated with the highest HR for occurrence in men [HR (95 % CI) 1.88 (1.03–3.43)].

Conclusions

Physical dysfunction in daily living is a predictor of the occurrence of certified need of care. Elderly men with a WOMAC function score ≥5 and women with a score ≥4 should undergo early intervention programs to prevent subsequent deterioration.     

A comparative study of two types of sternal pins used for sternal closure: poly-l-lactide sternal pins versus uncalcined hydroxyapatite poly-l-lactide sternal pins

Bioabsorbable poly-l-lactide (PLLA) sternal pins are applied to reinforce sternal closure during cardiac surgery. However, these pins lack osteoconductivity. A new bioabsorbable sternal pin with osteoconductivity, made of uncalcined hydroxyapatite and poly-l-lactide (u-HA-PLLA) has been developed. This study was conducted to compare the two types of sternal pins in terms of sternal stability and healing after median sternotomy. Between October 2006 and January 2012, 105 patients underwent aortic surgery for aortic aneurysms or dissection via median sternotomy and sternal closure with sternal pins. Among these patients, 75 were followed for 12 months using serial computed tomography (CT). PLLA sternal pins were used in 30 patients (group A) and u-HA-PLLA sternal pins were used in 45 patients (group B). The incidence rates of transverse sternal dehiscence, anteroposterior displacement and complete sternal fusion were evaluated using CT. The cross-sectional cortical bone density area (CBDA) of the sternum around the sternal pins was examined to evaluate the osteoconductivity of the sternal pins. There were no significant differences between groups A and B in the sternal dehiscence rate (6.7 vs 4.4 %), sternal displacement rate (6.7 vs 2.2 %) or 12-month sternal fusion rate (63.3 vs 73.3 %). The CBDA around the sternal pins significantly increased between discharge and 12 months after surgery in group B (P < 0.001) but not in group A. These results show that u-HA-PLLA sternal pins exhibit certain osteoconductivity; however, both PLLA and u-HA-PLLA sternal pins provide comparable clinical outcomes regarding sternal stability and healing.     

Characterization of Neospora caninum Surface Protein NcSRS2 Based on Baculovirus Expression System and Its Application for Serodiagnosis of Neospora Infection

The baculovirus expression system has proved to be a useful tool for the production of recombinant proteins. Here we have characterized the Neospora caninum surface protein NcSRS2 produced by two types of the recombinant virus and also have developed an enzyme-linked immunosorbent assay (ELISA) using recombinant NcSRS2 for the serologic diagnosis of Neospora infection. Western blot analysis showed two major protein bands that were detectable in insect cells infected with each recombinant baculovirus, and a lower-molecular-weight protein was detected in culture supernatants from a cell infected with the recombinant virus lacking the hydrophobic C-terminal tail. Analysis of the N-terminal amino acids showed that the secreted NcSRS2 lacked 6 kDa of the N-terminal signal peptide. Moreover, the detergent-soluble protein of insect cells infected with the recombinant baculovirus expressing the full-length NcSRS2 gene was used to develop an ELISA system based on specificity and reactivity to antisera against Toxoplasma gondii, Hammondia heydorni, or N. caninum. Anti-N. caninum mouse, dog, and bovine sera recognized the recombinant NcSRS2 on Western blots. Furthermore, we have shown that the developed ELISA system consistently discriminates indirect fluorescent-antibody test (IFAT)-positive bovine sera against N. caninum from IFAT-negative sera. These results indicate that the ELISA using baculovirus-expressed NcSRS2 can be useful for effective and reliable serodiagnosis of N. caninum infection.