Role of endothelium in hyperemia during cortical spreading depression (CSD) in the rat

The purpose of this study was to examine whether endothelium-mediated dilation is responsible for the cortical hyperemia that occurs during cortical spreading depression (CSD) in rats using three different approaches. The first approach taken was the acute pharmacological inhibition of the predominant endothelium-centered dilator systems, using indomethacin, a cyclooxygenase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and miconazole, a cytochrome P-450 epoxygenase inhibitor. The second approach used was the acute general pharmacological impairment of endothelial function by the intravascular administration of phorbol 12, 13-dibutyrate (PDBu). The third approach taken was the chronic impairment of endothelium-dependent dilator responses by diet in insulin resistant (IR) rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry. CSD was elicited by the topical application of potassium chloride. Pharmacological inhibition of endothelium-dependent dilator factors did not affect CSD. For example, with 20 mg/kg L-NAME, CBF peak of the first series of CSDs was 377 +/- 67% of baseline CBF. After drug administration, CBF peaks of the second and the third series of CSDs were 451 +/- 67% and 390 +/- 69% (n=5, P=n.s.), respectively. Control and IR animals and those treated with indomethacin, miconazole and PDBu showed similar results. We also calculated the area under the CBF curve to fully represent the extent of hyperemia during CSD. However, there were no significant differences in the CBF area with any treatment compared to control animals. Thus, our results provide strong evidence that endothelium-mediated mechanisms have minimal effects on the CSD-associated hyperemia.     

The anti-dementia drug FK960 stimulates glial glutamate release via a PKA pathway

The present study was conducted to understand the mechanism underlying the facilitatory action of FK960, an anti-dementia drug, on hippocampal neurotransmission. FK960 facilitated hippocampal neurotransmission in normal mice, and also in mice lacking the glial glutamate transporter, GLT-1 (glut-1(-/-)), but to a lesser extent. FK960 enhanced glutamate release from cultured hippocampal astrocytes from normal rats and mice, while the drug had no effect on the release from cultured rat hippocampal neurons. The glutamate release was still obtained with cultured hippocampal astrocytes from glut-1(-/-) mice, suggesting that the release is not due to GLT-1-mediated counter transport of glutamate. The FK960 action was inhibited by H-89, a selective inhibitor of cAMP-dependent protein kinase (PKA), bafilomycin A1, an inhibitor of vesicular transport, or BAPTA-AM, a chelator of intracellular Ca(2+). FK960 caused an increase in intracellular Ca(2+) concentrations by stored Ca(2+) release in cultured rat hippocampal astrocytes, and H-89 abolished the increase. Forskolin, a PKA activator, mimicked the effect of FK960 on intracellular Ca(2+) mobilizations. Taken together, it appears that FK960 stimulates glutamate release from astrocytes, likely as a result of raising intracellular Ca(2+) concentrations via a PKA pathway. The FK960 action would increase synaptic glutamate concentrations, in part responsible for the facilitation of hippocampal neurotransmission. The results of the present study may provide a new idea that agents targeting astrocytes could serve as anti-dementia drugs.     

Cirrhosis: modified caudate-right lobe ratio

PURPOSE: To determine whether a modified caudate-right lobe ratio (C/RL) with use of the right portal vein to set the lateral boundary (C/RL-r) is more accurate for diagnosing cirrhosis and evaluating its clinical severity than is the previously described C/RL with use of the main portal vein to set the lateral boundary (C/RL-m). MATERIALS AND METHODS: Two hundred thirty-six patients (121 with pathologically proved cirrhosis and 115 without history of chronic hepatic diseases) underwent magnetic resonance (MR) imaging. Two independent observers measured C/RL-r and compared it with C/RL-m. Results were compared by using receiver operating characteristic (ROC) curves and accuracy measures at various thresholds. RESULTS: The area below the ROC curve was greater for C/RL-r (0.797) than for C/RL-m (0.731; P =.040). By using a C/RL-r greater than 0.90, the sensitivity, specificity, and accuracy for the MR imaging diagnosis of cirrhosis were 71.7%, 77.4%, and 74.2%, respectively. The highest accuracy of the C/RL-m was 65.7%, when the C/RL-m was greater than 0.55. Interobserver agreement was statistically confirmed for both measurements by using kappa analysis. Significant differences were found among the three Child-Pugh classes by using C/RL-r (P =.0105) but not by using C/RL-m. CONCLUSION: C/RL-r is more accurate for diagnosing cirrhosis and evaluating its clinical severity than is C/RL-m.     

Extreme fenestration of the basilar artery associated with cleft palate,nasopharyngeal mature teratoma,and hypophyseal duplication

The authors present the case of a newborn girl with extreme fenestration of the basilar artery. This anomaly was found incidentally during MR imaging study for cleft palate and nasopharyngeal teratoma. Magnetic resonance angiography showed a totally duplicated basilar artery with connections at the proximal and distal ends of the artery, suggesting an extreme fenestration. Duplicated pituitary gland was also found on MR imaging.     

Moyamoya disease associated with an anterior inferior cerebellar artery arising from a persistent trigeminal artery

The authors present a case of moyamoya disease associated with a persistent trigeminal artery from which the anterior inferior cerebellar artery arose. We reviewed previously reported cases of moyamoya disease associated with persistent carotid-basilar arterial anastomosis and investigated the embryology of this rare arterial variation.     

Mechanism of anemia associated with autonomic dysfunction in rats

The aim of this study was to elucidate the mechanism of anemia associated with autonomic dysfunction in rats. Using 6-hydroxydopamine (6-OHDA)-treated sympathectomized rats, changes in systolic blood pressure, plasma catecholamine levels, hemograms, erythropoietin (EPO) secretion, and beta-adrenergic receptors on erythrocytes were monitored, and compared with desipramine- and 6-OHDA-treated, and control rats. In 6-OHDA-treated rats, systolic blood pressure and plasma catecholamine levels significantly decreased from 7 days after 6-OHDA administration, returning to the control values on day 28. Hemoglobin (Hb), hematocrit (Hct) and red blood cell (RBC) levels significantly decreased from day 14 to day 28, and reached normal values after day 35, but neither corpuscular constants nor white blood cell (WBC) levels changed after anemia occurred. Administration of desipramine 1 day before 6-OHDA injection prevented anemia. EPO levels did not elevate, even after bloodletting to load anemia, and the EPO circadian rhythm was irregular in 6-OHDA-treated rats. beta-adrenergic receptors measured using 125I-cyanopindolol (CYP) significantly decreased from day 7 to day 28, and reached normal values after day 35. These results suggest that irregular EPO secretion via disordered autonomic nerves may induce anemia in patients with autonomic disorders.     

Key factors influencing bowel function after ileal W-pouch anal anastomosis: A spectral analysis of W-pouch motor activity

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure–volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = −0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch. Received: May 6, 1999 / Accepted: May 30, 2000     

Thoracic Esophagectomy Combined with Pylorus-Preserving Pancreatoduodenectomy in a One-Stage Procedure: Report of a Case

(Received for publication on Oct. 12, 1998; accepted on July 13, 1999)     

Biallelic inactivation by somatic mutations of the MEN1 gene in sporadic parathyroid tumors.

We report three sporadic parathyroid tumors with biallelic inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene. Three parathyroid tumors had two somatic mutations (K119del and 864del8, 363insT and 1767delT, and 508del33 and W341X, respectively). The mutations in both alleles detected by long-range polymerase chain reaction and subcloning in three tumors would likely result in a nonfunctional menin protein in parathyroid glands. These results show that the MEN1 gene is inactivated not only by a combination of somatic mutations and loss of heterozygosity, but also by somatic double mutations located on different alleles. The results directly confirmed the participation of MEN1 in the tumorigenesis of sporadic parathyroid tumors.     

Convergence of posterior semicircular canal and saccular inputs in single vestibular nuclei neurons in cats

Convergence between posterior canal (PC) and saccular (SAC) inputs in single vestibular nuclei neurons was investigated in decerebrated cats. Postsynaptic potentials were recorded intracellularly after selective stimulation of the SAC and PC nerves. Stimulation of either the SAC or PC nerve orthodromically activated 143 vestibular nuclei neurons. Of these, 61 (43%) were antidromically activated by stimulation of the C1-C2 junction, 14 (10%) were antidromically activated by stimulation of the oculomotor or trochlear nucleus, and 14 (10%) were antidromically activated by stimulation of both the oculomotor or trochlear nucleus and the spinal cord. Fifty-four (38%) neurons were not activated by stimulation of either or both. We named these neurons vestibulospinal (VS), vestibulo-ocular (VO), vestibulooculo-spinal (VOS) and vestibular (V) neurons, respectively. Both PC and SAC inputs converged in 47 vestibular nuclei neurons (26 VS, 2 VO, 6 VOS and 13 V neurons). Of these, 19 received monosynaptic excitatory inputs from both nerves. This input pattern was frequently seen in VS neurons. Approximately half of the convergent VS neurons descended to the spinal cord through the lateral vestibulospinal tract. The remaining half and all the convergent VOS neurons descended to the spinal cord through the medial vestibulospinal tract. Most of the convergent neurons were located in the lateral nucleus or descending nucleus.