BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

Prevalence, clinical characteristics, quality of life, and prognosis of patients with congestive heart failure and isolated left ventricular diastolic dysfunction.

Prevalence of isolated left ventricular (LV) diastolic dysfunction has been reported to be as high as one-third of all heart failure (HF) cases, with an increasing prevalence in the elderly population. However, there is a paucity of prospective data about the prevalence and prognosis of isolated LV diastolic dysfunction in an unselected population of patients hospitalized with HF. Therefore, we prospectively evaluated 179 consecutive patients discharged from our hospital with HF to assess the prevalence of systolic versus diastolic LV dysfunction among patients hospitalized with HF and to compare their demographics, clinical features, self-perceived quality of life (QOL), and 6-month readmission rate and mortality. Among them, 133 (59% men, median age 74 years) showed in sinus rhythm and had no significant primary valvular disease. LV diastolic dysfunction was diagnosed on the basis of the European Study Group on Diastolic HF echocardiographic criteria. QOL was assessed at hospital discharge and 6-month follow-up visit using the Minnesota Living with HF questionnaire. Survival of patients with HF was compared with that of age- and sex-matched general population. In all, 29 patients (22%) had isolated LV diastolic dysfunction and 102 (78%) had prevalent LV systolic dysfunction (ie, LV ejection fraction 相似文献   

Minimum effective anesthetic concentration (MEAC) for sciatic nerve block: subgluteus and popliteal approaches

BACKGROUND: We tested the hypothesis that using a subgluteus approach to the sciatic nerve requires a lower concentration of mepivacaine to obtain complete anesthesia as compared with the popliteal approach. METHODS: With midazolam premedication (0.05 mg kg(-1) iv), 48 patients undergoing hallux valgus repair were randomly allocated to receive a sciatic nerve block using either a posterior popliteal (group Popliteal, n = 24) or subgluteus (group Subgluteus, n = 24) approach with 30 mL of local anesthetic injected after elicitation of plantar flexion of the foot with a current 相似文献   

Proline reduces brain cytochrome c oxidase: prevention by antioxidants

In the present study, we initially investigated the in vivo (acute and chronic) and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in rat cerebral cortex to test the hypothesis that proline might alter energy metabolism and that this alteration could be provoked by oxidative stress. The action of alpha-tocopherol and ascorbic acid on the effects produced by proline was also evaluated. For acute administration, 29- and 60-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously twice a day at 10h intervals from the 6(th) to the 28(th) day of age. Rats were sacrificed 12h (29(th)) or 31 days (60(th)) after the last injection. Results showed that acute administration of proline significantly diminished the activity of cytochrome c oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand, chronic hyperprolinemia reduced this complex activity only on day 29, but not on the 60(th) day of life. In another set of experiments, 22-day-old rats or 53-day-old rats were pretreated for 1 week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours after the last antioxidant injection, rats received a single injection of proline or saline and were killed 1h later. In parallel to chronic treatment, rats received a daily intraperitoneal injection of alpha-tocopherol and ascorbic acid from the 6(th) to the 28(th) day of life and were killed 12h after the last injection. Results showed that the pretreatment with alpha-tocopherol and ascorbic acid before acute proline administration or concomitant to chronic proline administration significantly prevented these effects. We also observed that proline (3.0 microM-1.0 mM) when added to the incubation medium (in vitro studies) did not alter cytochrome c oxidase activity. Data suggest that the inhibitory effect of proline on cytochrome c oxidase activity is possibly associated with oxidative stress and that this parameter may be involved in the brain dysfunction observed in hyperprolinemia.     

Parathyroid imaging. Use of dual isotope scintigraphy for the localization of adenomas before surgery.

Seventy-nine patients with primary hyperparathyroidism, whose average preoperative blood calcium level was 11.6 mg/dl, underwent thallium-technetium dual isotope scintigraphy of the thyroid and parathyroids. For patients who had surgery, the detection and localization rate of parathyroid disease or the sensitivity was low (0.53), but the positive predictive value for the location was high (0.80). Correct localization correlated positively with the weight of the tumor but not significantly with the parathyroid hormone blood level nor with the blood calcium level. Unprocessed data alone were sufficient to predict correctly the location in two thirds of the detected cases. Computer processing increased the sensitivity without decreasing the specificity. Those results, at variance with earlier published data but congruent with another more recent study, require a reevaluation of the role of this scintigraphic technique in the management of hyperparathyroidal patients.     

Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors

Insulin-like growth factor II (IGF-II) is a mitogen for manycell types and an important modulator of muscle growth and differentiation.IGF-II gene is prevalently expressed during prenatal developmentand its gene activity is regulated by genomic imprinting, inthat the allele inherited from the father is active and theallele inherited from the mother is inactive in most normaltissues. IGF-II expression is activated in several types ofhuman neoplasms and an alteration of IGF-II imprinting has beendescribed in Beckwith–Wiedemann syndrome and Wilms' tumour.Here we show that monoallelic expression of IGF-II gene is conservedin normal adult muscle tissue whereas two or more copies ofactive IGF-II alleles, arising by either relaxation of imprintingor duplication of the active allele, are found in 9 out of 11(82%) rhabdomyo-sarcomas retaining heterozygosity at 11p15,regardless of the histological subtype. Since IGF-II has beenindicated as an autocrine growth factor for rhabdomyosarcomacells, these findings strongly suggest that acquisition of adouble dosage of active IGF-II gene is an important step forthe initiation or progression of rhabdomyosarcoma tumorigenesis.Among different types of muscle tumors, relaxation of imprintingseems to arise prevalently in rhabdomyosarcomas, since we havedetected only one case of partial reactivation of the maternalIGF-II allele out of 7 lelomyosarcomas tested.     

Executive function impairments in children with attention-deficit hyperactivity disorder: do they differ between school and home environments?

OBJECTIVE: The primary purpose of this study was to compare parent and teacher reports of executive function (EF), as measured by the Behavior Rating Inventory of Executive Function (BRIEF), on a sample of children who had been diagnosed with attention-deficit hyperactivity disorder (ADHD). If differences were found, the secondary purpose was to explore these differences by determining which of the 8 BRIEF scales, each representing a different EF, would best predict symptoms of ADHD by the 2 proxy reporters. METHOD: We performed a secondary data analysis on the assessment information pertaining to 240 children, aged 5 to 15 years, accessing services at an urban Toronto psychiatric program specializing in ADHD. We compared parent and teacher ratings and applied logistical binary regressions to predict the probability of a child's meeting the criteria for clinically significant inattention and hyperactivity-impulsivity on the ADHD Rating Scale-IV. RESULTS: As expected, teachers reported more variety and severity of EF impairments than did parents. In addition, teachers used inhibition, organization of materials, and planning and organizing as predictors of ADHD symptoms, whereas parents relied predominantly on inhibition, working memory, and planning and organizing as the risk factors. CONCLUSION: Consistent with the current theory, EF impairments, particularly in inhibition, appear to underlie the behavioural manifestation of ADHD. However, parents and teachers do not always agree when reporting EF impairments at home and in school. Thus information from both types of informants is essential for understanding and treating children with this disorder.     

TNF alpha and Fas mediate tissue damage and functional outcome after traumatic brain injury in mice.

Tumor necrosis factor-alpha (TNFalpha) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNFalpha, Fas, or both (TNFalpha/Fas-/-), we hypothesized that TNFalpha and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNFalpha/Fas-/- mice had improved motor performance from 1 to 4 days (P<0.05), improved spatial memory acquisition at 8 to 14 days (P<0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P<0.05). Protection in TNFalpha/Fas-/- mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNFalpha before CCI, and TNFalpha-/- mice administered anti-Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice (P<0.05). Tumor necrosis factor-alpha/Fas-/- mice had decreased the numbers of cortical cells with plasmalemma damage at 6 h (P<0.05 versus WT), and reduced matrix metalloproteinase-9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNFalpha and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P<0.05 versus WT), suggesting that the beneficial effects of TNFalpha/Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNFalpha and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNFalpha/Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI.