gamma-Aminobutyric acid and taurine release in the striatum of the rat during hypoglycemic coma, studied by microdialysis

Extracellular levels of striatal gamma-aminobutyric acid (GABA) and taurine were monitored during insulin-induced hypoglycemia using microdialysis. At the onset of isoelectricity in the electroencephalogram (EEG), a transient 5-fold increase in the levels of GABA occurred. Taurine levels increased 5 min following the onset of isoelectricity and continued to increase during the entire isoelectric period. The results demonstrate that events associated with the onset of isoelectricity during hypoglycemia trigger an increase in extracellular concentrations of GABA and taurine. The discrepancy in time-course of these changes may reflect differences in compartmentation, function and metabolism of the two amino acids.     

Renovaskuläre Hypertonie

Zusammenfassung In der vorliegenden Untersuchung wurde das postoperative Blutdruckverhalten bei 35 Patienten mit renovaskulärer Hypertonie untersucht: 17 Patienten mit fibromuskulärer Dysplasie (FMD) und 18 mit arteriosklerotischen Gefäßwandveränderungen (ASS).Patienten mit FMD waren im Mittel jünger (31,8 Jahre), zeigten eine kürzere Hypertonieanamnese (1,8 Jahre) und waren prävalent weiblich (82%), während Patienten mit ASS deutlich älter waren (48,2 Jahre), eine längere Hypertoniedauer (2,6 Jahre) zeigten und bevorzugt männlich (78%) waren.In beiden Gruppen zeigte das intravenöse Pyelogramm einen vergleichbar hohen Anteil positiver Befunde (FMD=64%, ASS=61%).Postoperativ waren in der Gruppe mit FMD 47% (n=8) geheilt, 47% (n=8) gebessert und nur 6% (n=1) der Patienten geringgradig gebessert. Die vergleichbaren Werte für die Gruppe mit ASS betrugen 28, 55 und 17%. Für das Gesamtkollektiv war folglich ein guter Operationserfolg (geheilt und gebessert) in 88,5% der Fälle zu beobachten. Patienten mit ASS und postoperativ nur geringgradiger Besserung (n=3) zeigten eine auffallend lange Hypertonieanamnese (7,0±1,4 Jahre).Bei allen Patienten wurde präoperativ die seitengetrennte Bestimmung der Renin-Aktivität (PRA) im Nierenvenenblut durchgeführt und aus den Werten die PRA-Quotienten (PRA betroffene/nicht betroffene Seite) errechnet. Bei 27 Patienten wurde die Bestimmung 15 und 30 min nach intravenöser Stimulation mit 40 mg Furosemid wiederholt. PRA-Quotienten von 1,5 wurden als signifikant bezeichnet.Bei 31 Patienten mit einseitiger renovaskulärer Hypertonie wurde die Höhe des PRA-Quotienten zum postoperativen Blutdruckverhalten korreliert. Dabei zeigte sich zwischen der Gruppe der postoperativ Geheilten und der der postoperativ Gebesserten kein signifikanter Unterschied im mittleren PRA-Quotienten. Ferner ließen sich für das Gesamtkollektiv der 31 Patienten mit einseitiger renovaskulärer Hypertonie unter Ausgangs- und Stimulationsbedingungen keine signifikanten Korrelationen zwischen Höhe der PRA-Quotienten und postoperativem Blutdruckabfall ermitteln.Unsere Ergebnisse unterstützen nicht die weit verbreitete Ansicht, daß sich die seitengetrennte Bestimmung der PRA im Nierenvenenblut als Parameter für den zu erwartenden Operationserfolg bei Patienten mit einseitiger renovaskulärer Hypertonie eignet. Die Methode kann deshalb nach unserer Ansicht nicht mehr als obligater Bestandteile der präoperativen Diagnostik der renovaskulären Hypertonie empfohlen werden.     

Connective tissue growth factor in Alzheimer's disease

The chemical organization of excitatory axon terminals in the rat cerebellar cortex was examined by immunocytochemistry and in situ hybridization histochemistry of vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2). Chemical depletion of the inferior olivary complex neurons by 3-acetylpyridine treatment almost completely removed VGluT2 immunoreactivity from the molecular layer, leaving VGluT1 immunoreactivity apparently intact. On the other hand, neuronal deprivation of the cerebellar cortex by kainic acid injection induced a large loss of VGluT1 immunoreactivity in the molecular layer. In the cerebellar granular layer, both VGluT1 and VGluT2 immunoreactivities were found in mossy fiber terminals, and the two immunoreactivities were mostly colocalized in single-axon terminals. Signals for mRNA encoding VGluT2 were found in the inferior olivary complex, and those for VGluT1 and VGluT2 mRNAs were observed in most brainstem precerebellar nuclei sending mossy fibers, such as the pontine, pontine tegmental reticular, lateral reticular and external cuneate nuclei.These results indicate that climbing and parallel fibers selectively use VGluT2 and VGluT1, respectively, whereas mossy fibers apply both VGluT1 and VGluT2 together to accumulate glutamate into synaptic vesicles. Since climbing-fiber and parallel-fiber terminals are known to make depressing and facilitating synapses, respectively, VGluT1 and VGluT2 might have distinct properties associated with those synaptic characteristics. Thus, it would be the next interesting issue to determine whether mossy-fiber terminals co-expressing VGluT1 and VGluT2 show synaptic facilitation or depression.     

Vitamin B12 deficiency neurological syndromes: a clinical,MRI and electrodiagnostic study

BACKGROUND: Vegetarianism is an important cause of vitamin B12 deficiency, especially in countries like India. We managed 17 patients with neurological syndrome due to vitamin B12 deficiency in a tertiary care referral teaching hospital which caters to relatively affluent population. AIM: To evaluate neurophysiological and MRI changes in patients presenting with vitamin B12 deficiency neurological syndrome and interpret these is the light of reported autopsy findings. SETTING: Tertiary care referral teaching hospital. METHODS: Patients with vitamin B12 deficiency neurological syndrome diagnosed by low serum vitamin B12 and/or megaloblastic bone marrow were subjected to clinical evaluation and spinal MRI. The neurophysiological tests included nerve conduction studies, tibial somatosensory evoked potential (SEP), motor evoked potential (MEP) and visual evoked potential (VEP) studies. The recovery was defined on the basis of 6 months Barthel Index score into complete, partial or poor. RESULTS: There were 17 patients with vitamin B12 deficiency neurological syndrome, 3 were females and 12 lactovegetarian. The clinical syndrome was that of myelopathy in 8, myeloneuropathy in 5, dementia myelopathy in 3 and neuropathy in 1 patient. All the patients had impaired joint position and vibration sensation in the lower limbs and 4 had in upper limbs as well. Lower limbs were spastic in 13 and upper limbs in 2 patients. Spinal MRI revealed T2 hyperintensity in cervicodorsal region in 6 and cord atrophy in 3 patients. Sural nerve conduction was abnormal in 8 and peroneal conduction in 5 patients. In one patient all sensory nerve conductions were unrecordable but motor conductions were normal. Tibial SEP was abnormal in 12 out of 15 and lower limb MEP in 8 out of 12 patients. P100 latency of VEP was prolonged in 7 out of 13 patients. Right to left asymmetry was present in tibial SEP in 4 and VEP in 2 patients. At 6 months followup 2 patients improved completely, 7 partially and 3 had poor recovery. Clinical recovery correlated with MEP but not with SEP or MRI changes. CONCLUSION: The evoked potential and MRI changes in vitamin B12 deficiency neurological syndrome are consistent with focal demyelination of white matter in spinal cord and optic nerve. Myelopathic presentation is commoner and SEP is more frequently abnormal. The outcome at 6 months correlated with MEP changes.     

Psychosocial work characteristics and perceived control in relation to cardiovascular rewind at night

This study examined the effects of psychosocial work characteristics on cardiovascular rewind at night. Ambulatory 24-hr recordings of blood pressure (BP) and heart rate (HR) of 75 borderline hypertensive and 74 normotensive men were related to diary ratings of perceived control (PC) and to scores of psychological demand (P), control (C), and social support (S) at work determined by an occupational classification system. Multiplicative interaction terms for job strain (P x C), isostrain (P x C x S), and Job Strain x Perceived Control (P x C x PC) were calculated. The P x C x PC interaction predicted diastolic BP at night but not at work. A delayed latency to attain the lowest systolic BP during the night was found for jobs with high job strain and isostrain. Low perceived control and social support were associated with higher HR at work and at night. A logistic regression analysis indicated that the interaction between P x C x PC and the body mass index was independently associated with borderline hypertension.     

Membrane fusion between retroviral particles: host-range extension and vaccine prospects

We have analyzed if different populations of retroviral particles carrying the viral and cellular receptors of membrane viruses, respectively, are able to specifically fuse with each other. Using the glycoprotein of human immunodeficiency virus type 1 and its cellular receptor complex, we demonstrate that interviral membrane fusion can, indeed, occur and that the resultant fused viral structures are able to infect cells and transduce a marker gene. On the one hand, these results have relevance for the development of vaccine strategies based on fusion-induced conformational epitopes on the viral glycoprotein. However, in addition to this potential practical application, the results obtained (which were extended to include analyses with the vesicular stomatitis virus G protein and its cellular receptor) have far-reaching implications for in vivo situations in which simultaneous infections with different membrane viruses can occur.     

A novel mutation in the neonatal region of the fibrillin (FBN)1 gene associated with a classical phenotype of Marfan syndrome (MfS). Mutations in brief no. 163. Online

Marfan Syndrome (MfS) is an autosomal dominant inherited connective tissue disorder with variable phenotypic expression of cardiovascular, skeletal and ocular manifestations. Cardiovascular complications, such as aortic aneurysm and dissection drastically reduce life expectancy of individuals with MfS, whereas preventive surgery substantially improves the prognosis of these patients. A number of mutations in the fibrillin 1 (FBN1) gene associated with MfS have been identified to date, demonstrating considerable molecular heterogeneity. One region, however, located around exon 24, exhibits a striking clustering of mutations, which are associated with a severe, socalled neonatal form of MfS. Here we report the first mutation (G2950A) in exon 24 of the neonatal region of the FBN1 gene, associated with a classic MfS phenotype. The mutation leads to the subsitution of valin by isoleucin (V984I), both uncharged amino acids, which only differ in a single methyl group. This defect was identified in a proband with cardiovascular manifestations of MfS by SSCP analysis of PCR-amplified genomic DNA, direct PCR sequencing and RFLP analysis. The substitution was neither detected in the unaffected 4-year old daughter of the proband, nor in 3 of his healthy family members nor in 108 allels from control individuals, suggesting that this mutation is causative for MfS in the patient. Since no other family member of the proband is affected by MfS, the defect described is sporadic. In summary, we identified a novel defect in exon 24 of the neonatal region of the FBN1 gene in a patient with a classic phenotype of MfS, suggesting that conservative substitutions in this region may lead to a less severe phenotype of the disease. This finding further demonstrates the remarkable phenotypic heterogeneity associated with FBN1 mutations and stresses the significance of modifying genes and individual alterations in protein function for the pheontypic expression of the disease.     

Transcutaneous electrical nerve stimulation (TENS) increases survival of ischaemic musculocutaneous flaps

The effect of transcutaneous electrical nerve stimulation (TENS) on the survival of a dorsal musculocutaneous flap was studied in the rat. Postoperative TENS treatment significantly increased the flap survival area in groups of rats receiving different modes of TENS. The flap survival area was up to 95% in the TENS-treated groups compared with 33-45% in the control groups. Repeated (3 days) high intensity (20 mA), high-frequency (80 Hz) TENS applied segmentally at the base of the flap was shown to be the most effective treatment in increasing the flap survival. Preoperative TENS did not increase flap survival area compared with untreated controls. It is concluded that postoperative TENS treatment markedly increases the experimental flap survival area and may be of clinical value for treatment of local ischaemia.     

Therapeutic activity of leflunomide in acute and chronic relapsing experimental allergic encephalomyelitis

We examined the therapeutic effect of leflunomide in the two models of acute and chronic relapsing EAE in Lewis rats. In the first model, sensitization of adult rats with guinea pig spinal cord resulted in an acute clinical episode of severe EAE, and by day 15 all animals died. Treatment of these sensitized Lewis rats with leflunomide was most effective in delaying and reducing the onset of clinical symptoms and mortality was prevented. The protection afforded by leflunomide was long-lasting and no subsequent relapse has been observed. In the second model of chronic relapsing EAE, aged Lewis rats (6–8 months old) were immunized with rabbit myelin basic protein, and all untreated animals developed a disease with up to three relapses. The second and third episodes were both milder and shorter in duration than the first. All animals treated with leflunomide survived the first attack, which was also delayed, in comparison to untreated controls, and relapses did not occur. Inhibition of pathological signs and prevention of relapses were observed even when leflunomide treatment was started after the first appearance of clinical symptoms of chronic relapsing EAE.