Association between chronic musculoskeletal pain and executive function in community-dwelling older adults.

BACKGROUND: We examined the association of chronic musculoskeletal pain with executive function in community-dwelling older adults. METHOD: This cross-sectional study recruited 234 community-dwelling older adults in Japan (mean age: 72.7, women: 62.8%). Chronic musculoskeletal pain was defined as having moderate or more severe pain lasting ≥ 3 months. Executive function was assessed using the Digit Symbol Substitution Test (DSST), Trail Making Test (TMT) parts A and B, Letter Verbal Fluency Test (LVFT) and Category Verbal Fluency Test (CVFT). RESULTS: Prevalence of chronic musculoskeletal pain was 19% (n = 44). In the univariate analysis, the DSST and CVFT scores were significantly lower in the chronic musculoskeletal pain group than in the control group (DSST: chronic musculoskeletal pain group vs. control group, 40.2 vs. 45.4, respectively, p < 0.05; CVFT: 13.7 vs. 15.6, respectively, p < 0.05), whereas the TMT parts A and B and LVFT scores were not. The multivariate linear regression models adjusted for covariates showed that the chronic musculoskeletal pain group had significantly lower DSST (adjusted ß = -0.13, p < 0.05) and CVFT scores (adjusted ß = -0.17, p < 0.05) than the control group. CONCLUSION: Chronic musculoskeletal pain may interfere with the elements of executive function, processing speed and semantic fluency, in community-dwelling older adults. The association of chronic musculoskeletal pain with executive function requires further investigation. SIGNIFICANCE: Our results suggest an association between moderate-severe chronic musculoskeletal pain and impairments of semantic fluency and processing speed in community-dwelling older adults.

Expression of a constitutively active phosphatidylinositol 3-kinase induces process formation in rat PC12 cells. Use of Cre/loxP recombination system.

It has been shown that inhibition of phosphatidylinositol (PI) 3-kinase blocks neurite outgrowth of PC12 cells stimulated with nerve growth factor. To further assess the role of PI 3-kinase, the active form of PI 3-kinase was expressed in PC12 cells by the adenovirus mediated introduction of a site-specific recombinase, Cre. After expression of the active PI 3-kinase, elevation of the levels of PI 3,4-diphosphate and PI 3,4,5-trisphosphate as well as formation of neurite-like processes was observed. The process formation was inhibited by wortmannin, a selective inhibitor of PI 3-kinase, which suggests that a high activity of PI 3-kinase was responsible for the formation of these processes. The processes lacked accumulation of F-actin and GAP43 at the growth cone, which suggests that the processes were incomplete compared with neurites. Instead, the bundling of microtubules was enhanced, which suggests that organization of the microtubules might be driving the process of elongation in the cells expressing the active PI 3-kinase. Induction of active PI 3-kinase resulted in activation of Jun N-terminal kinase but not of mitogen-activated protein kinase or protein kinase B/Rac protein kinase/Akt. These results suggest that PI 3-kinase is involved in neurite outgrowth in PC12 cells and that activation of Jun N-terminal kinase cascade may be involved in the cell response.

Purification and characterization of the phosphatidylinositol-3,4,5-trisphosphate phosphatase in bovine thymus.

Using phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] prepared from phosphatidylinositol 4,5-bisphosphate and inositolphospholipid 3-kinase, we identified in bovine thymus extracts the enzyme activity which catalyzed dephosphorylation of PtdIns(3,4,5)P3, to produce phosphatidylinositol biphosphate. Since bovine thymus exhibited the highest level of activity among tissues screened, we tried to purify this enzyme PtdINs(3,4,5)P3 phosphatase from bovine thymus. After sequential chromatographies using S-Sepharose, heparin-Sepharose, blue Sepharose, and Toyopearl HW55, the enzyme was purified 1875-fold with a yield of 10%. SDS/PAGE analysis revealed that a 120-kDA protein band copurified with the enzyme activity. The apparent molecular mass of the active protein was 120 kDa on size-exclusion chromatography, suggesting that the 120-kDa band on SDS/PAGE is the PtdIns(3,4,5)P3 phosphatase. Since PtdIns(3,4,5)P3 phosphatase seemed to be the only activity that metabolized PtdIns(3,4,5)P3, and the enzyme did not hydrolyze phosphatidylinositol 4,5-biphosphate, the enzyme may play a critical role in the inositolphospholipid 3-kinase signalling.

Ursodeoxycholic acid therapy in the treatment of biliary atresia.

The prognosis of operated biliary atresia in the cases with bile excretion chiefly depends upon the prevention of ascending cholangitis. An antibiotic is therefore intravenously administered during the early postoperative phase, but cannot be used over a long period. In the cases showing satisfactory bile excretion after operation, ascending cholangitis is rare because of rapid disappearance of jaundice. Regarding this, the authors prescribed ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day to 6 infants with biliary atresia for several weeks after operation, and then determined the effects of UDCA in improving jaundice and bile excretion. As a result, serum bilirubin and serum total bile acid (STBA) levels were decreased in 4 of the 6 infants. In the remaining 2 infants, their STBA levels showed no decrease, but were rather increased; these infants subsequently died of hepatic failure. These results suggested that UDCA is useful in the treatment of cholestasis associated with biliary atresia in the cases attaining postoperative bile excretion. It was also suggested that the treatment with UDCA should be stopped when the STBA levels increased after the beginning of the treatment. Therefore, it was thought that STBA levels measured during UDCA therapy could serve as a good indicator of the choleretic effect of UDCA.

Sulfated and nonsulfated bile acids in urine of patients with biliary atresia: analysis of bile acids by high-performance liquid chromatography.

To elucidate urinary bile acid patterns in patients with biliary atresia (BA), 15 sulfated and nonsulfated bile acids in urine were separately measured by high-performance liquid chromatography. This relatively simple technique for fluorescence detection utilizes the enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) to reveal urinary bile acid patterns. By this method, recovery rates of sulfated and nonsulfated bile acids in urine were satisfactory, and this analysis was shown to be applicable to clinical situations. In 10 patients with BA, the mean level of total bile acids in urine (23.35 +/- 18.51 mumol/day) was seven times higher than the mean level in eight normal infants (3.05 +/- 2.05 mumol/day). In the infants with BA, the mean level of total sulfated bile acids was about half of the total bile acid level. The main components of urinary nonsulfated bile acids in BA were glycocholic acid (6.21 +/- 5.55 mumol/day) and taurocholic acid (2.28 +/- 1.33 mumol/day), whereas the main components of the urinary sulfated bile acids were glycochenodeoxycholic acid (4.58 +/- 6.97 mumol/day) and taurochenodeoxycholic acid (3.67 +/- 3.54 mumol/day). Chenodeoxycholic acid, which is relatively toxic to the liver, may more easily be conjugated with sulfate and, hence, excreted into urine at a faster rate than cholic acid. Marked individual variations in urinary bile acid patterns were observed not only in BA patients but also in normal controls.

Investigation of serum bile acids; seven patients with Alagille syndrome.

To clarify whether an abnormal bile acid pattern has a role in the pathogenesis of Alagille syndrome, we compared serum bile acid patterns in seven with Alagille syndrome with those of patients with congenital biliary atresia (CBA), neonatal hepatitis (NH) and normal infants. Of the seven patients with Alagille syndrome, four patients were younger and three were older than 1 year. The mean total serum bile acid level in the infants was higher than in older subjects. There was a dissociation between the levels of serum total bile acid and bilirubin in three of the seven cases. The mean total bile acid levels in serum were in the following decreasing order: CBA, Alagille syndrome, NH and controls. The ratio of cholate to chenodeoxycholate in the younger patients with Alagille syndrome was significantly higher than CBA (P less than 0.001). However, no specific bile acid pattern was found in Alagille syndrome by high-performance liquid chromatography (HPLC).