Bradykinin-induced release of PGI2 from aortic endothelial cell lines: responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase.

1. Bradykinin (100 nM) triggers release of nitric oxide and prostacyclin from both AG07680A and AG04762 bovine cultured aortic endothelial cells. The exposure of these cells to bradykinin is in each case associated with a striking rise in intracellular calcium ion concentration. 2. Exposure of AG07680A cells to 250 nM ionomycin was followed also by a significant release of prostacyclin, whereas 250 nM ionomycin had no capacity to stimulate release of prostacyclin from AG04762 cells. 3. There was a similar concentration-dependent increase in intracellular calcium ion concentration on exposure of AG07680A and AG04762 cells to ionomycin. 4. Exposure of AG04762 cells for 10 min to staurosporine produced a concentration-dependent inhibition (IC50 = 107 +/- 14 nM) in bradykinin-stimulated prostacyclin release. There was no similar inhibitory effect of staurosporine in AG07680A cells. 5. Bradykinin (10 nM) triggered release of nitric oxide from both AG07680A and AG04762 cells, and the effect was not inhibited by 500 nM staurosporine. There was a similar ionomycin-dependent release of nitric oxide from both cell types. 6. These results identify a common pathway for bradykinin-dependent nitric oxide release from both AG07680A and AG04762 cells, involving increases in intracellular calcium ion concentration. In contrast, the bradykinin-dependent release of prostacyclin may involve one of two pathways (involving an increase in intracellular calcium or activation of a staurosporine-sensitive kinase), and the two pathways are selectively exploited in AG07680A and AG04762 cells, respectively.     

Rational diagnosis and treatment in unclassified arthritis: how clinical data may guide requests for Lyme serology and antibiotic treatment.

To improve the appropriateness and efficiency of diagnostic serological tests and subsequent antibiotic treatment, clinical data from 102 patients with unclassified arthritis were analysed to investigate whether the presence of positive IgG antibodies to Borrelia burgdorferi could be predicted. The clinical data were blindly ranked from 1 to 4 (1, Lyme arthritis unlikely; 4, Lyme arthritis very likely). Antibodies to B burgdorferi were positive in nine of 102 patients (9%). Six of 15 (40%) patients with rank numbers 3 and 4 were positive for antibodies to B burgdorferi, in contrast with only three of 87 (3%) patients with rank numbers 1 and 2. The likelihood ratio of positive Lyme serology for patients ranked 3 and 4 was 12.0, for patients ranked 2 to 4, 4.5, and for patients with arthritis of the knee, 3.0. These likelihood ratios were associated with a post-test probability of 55, 30, and 20% respectively. The clinical history in patients with unclassified arthritis can largely predict the presence of antibodies to B burgdorferi. The absolute value of a likelihood ratio can be a contributing factor in deciding to request tests for antibodies to B burgdorferi in patients with unclassified arthritis.     

Differential distribution of N-acetylaspartylglutamate and N-acetylaspartate immunoreactivities in rat forebrain

Summary Contradictory immunohistochemical data have been reported on the localization of N-acetylaspartylglutamate in the rat forebrain, using different carbodiimide fixation protocols and antibody purification methods. In one case, N-acetylaspartylglutamate immunoreactivity was observed in apparent interneurons throughout all allocortical and isocortical regions, suggesting possible colocalization with GABA. In another case, strong immunoreactivity was observed in numerous pyramidal cells in neocortex and hippocampus, suggesting colocalization with glutamate or aspartate. Reconciling these disparate findings is crucial to understanding the role of N-acetylaspartylglutamate in nervous system function. Antibodies to N-acetylaspartylglutamate and a structurally related molecule, N-acetylaspartate, were purified in stages, and their cross-reactivities with protein conjugates of N-acetylaspartylglutamate and N-acetylaspartate were monitored at each stage by solidphase immunoassay. Reduction of the cross-reactivity of the anti-N-acetylaspartylglutamate antibodies to N-acetylaspartateprotein conjugates to about 1% eliminated significant staining of most pyramidal neurons in the rat forebrain. Utilizing highly purified antibodies, the distributions of N-acetylaspartylglutamate and N-acetylaspartate were examined in several major telencephalic and diencephalic regions of the rat, and were found to be distinct. N-acetylaspartylglutamate-immunoreactivity was observed in specific neuronal populations, including many groups thought to use GABA as a neurotransmitter. Among these were the globus pallidus, ventral pallidum, entopeducular nucleus, thalamic reticular nucleus, and scattered non-pyramidal neurons in all layers of isocortex and allocortex. N-acetylaspartate-immunoreactivity was more broadly distributed than N-acetylaspartylglutamate-immunoreactivity in the rat forebrain, appearing strongest in many pyramidal neurons. Although N-acetylaspartate-immunoreactivity was found in most neurons, it exhibited a great range of intensities between different neuronal types.     

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. Repeated testing from an electrode placed chronically in the motor cortex showed a shift from vibrissa to forelimb within hours after facial nerve transection. These comparatively quick changes in motor cortex representation pattern suggest that synaptic relations between motor cortex and somatic musculature are continually reshaped in adult mammals.     

Severe herpetic keratitis. I: Prevalence of visual impairment in a clinic population.

We report a prevalence study of the best visual acuity in the affected eye of 100 selected patients with herpetic keratitis seen during a two-year period. Sixty-two patients retained an acuity of 6/9 or better without requiring penetrating keratoplasty (PK). The prevalence of reduced visual acuity severe enough to warrant PK was 33%. Patients requiring PK for whom full clinical records were available suffered a mean of 6.8 episodes of keratitis. In this group of patients the vision of 18 fell from 6/6 to 6/60 over a mean period of 8.5 years. Once visual acuity was permanently reduced to 6/12, 78% of patients proceeded to lose vision to 6/60. Unilateral visual impairment occurs in at least a third of patients with severe herpetic keratitis. Once vision falls permanently to 6/12, the long-term prognosis for vision appears to be poor.     

慢性低氧大鼠肺动脉内皮素mRNA的表达及定位

目的：探讨慢性低氧大鼠肺动脉内皮素－1基因表达及分布。方法：采用生物素标记cRNA探针，对Wistar大鼠肺动脉进行原位杂交。结果：低氧1周组及低氧2周组大鼠大部分肺动脉内皮细胞ET－1mRNA表达呈阳性信号，而对照组大鼠仅极少数阳性信号（P＜0．01）；低氧1周组大鼠部分显示强阳性信号。低氧1周组及低氧2周组大鼠部分肺动脉平滑肌细胞呈现ET-1mRNA表达阳性信号，而对照组大鼠则无阳性信号表达（P＜0．01及0．05）。结论：慢性低氧对大鼠肺动脉ET－1分泌的影响是在基因转录水平进行，且主要细胞定位在肺动脉内皮细胞，此外还包括肺动脉平滑肌细胞。     

Kardiale Manifestationen der HIV-Infektion

Zusammenfassung. Die Infektion mit dem humanen Immundefizienzvirus (HIV) betrifft nicht nur das Immunsystem des menschlichen Organismus, sondern schließt vielmehr eine Reihe weiterer Organsysteme mit ein. Es wird angenommen, dass bei 5-15% der HIV-positiven Patienten kardiale Manifestationen auftreten. Zu den häufigsten HIV-assoziierten kardialen Manifestationen gehören der Perikarderguss und die chronisch aktive, fokale oder diffuse Myokarditis. Endokardiale Manifestationen bei HIV-positiven Patienten treten in Form der infektiösen Endokarditis und der nichtbakteriellen thrombotischen Endokarditis auf. In der Regel weisen HIV-assoziierte kardiale Manifestationen einen langsam progredienten Krankheitsverlauf auf. Komplikationen sind Folge eines langfristig unentdeckten Fortschreitens der Erkrankung, aber auch schnell progredienter Verlaufsformen. Aufgrund der Vielzahl HIV-assoziierter kardialer Manifestationen und deren möglicher Komplikationen ist daher neben der Früherkennung ein effektives diagnostisches und therapeutisches Vorgehen erforderlich. Seit Einführung der Proteaseinhibitoren in den 90er Jahren und der Anwendung der hochaktiven antiretroviralen Kombinationstherapie (HAART) konnten sowohl Mortalität als auch Morbidität der HIV-Infektion deutlich gesenkt werden. Die Auswirkungen der HAART auf das kardiovaskuläre System sind bisher nur in Ansätzen bekannt. Als Nebenwirkungen wurden metabolische Veränderungen in Form von Hyperlipoproteinämie und Insulinresistenz bei einer Vielzahl HIV-positiver Patienten beobachtet. Es kann davon ausgegangen werden, dass durch den Anstieg der kardiovaskulären Risikofaktoren unter der HAART in den nächsten Jahren eine erhöhte Rate kardialer Erkrankungen bei HIV-positiven Patienten auftreten wird. In dem vorliegenden Übersichtsartikel wird ein Überblick über die häufigsten kardialen Erkrankungen bei HIV-Infektionen gegeben. Zusätzlich werden Vorschläge zu Diagnostik und Therapie unterbreitet und eine Einschätzung über Veränderungen der HIV-assoziierten kardialen Manifestationen nach Einführung der HAART vorgenommen. Abstract. The human immunodeficiency virus (HIV) does not only affect the immune system. Other organs including the cardiovascular system are influenced by the HIV as well. Most common HIV-associated cardiac manifestations are pericardial effusion and chronic active, focal or diffuse myocarditis. In addition to peri- and myocardial disease, endocardiac manifestations occur as infective endocarditis and nonbacterial thrombotic endocarditis in HIV-infected patients. Although most of the cardiac manifestations associated with HIV-infection exhibit a slow progression, rapid courses may lead to fatal complications. Early screening of HIV-infected patients will identify the potentially fatal complications of HIV disease and permit efficient treatment. The use of highly active antiretroviral therapy (HAART) significantly reduced the mortality and morbidity of HIV-infected patients. However, the impact that HAART will have on the incidence and prevalence of cardiac complications in HIV-infected patients is still unknown. It can be predicted, that the long-term viral infection and the increase of cardiovascular risk factors by HAART will probably lead to an increased prevalence of HIV-infected individuals with cardiac complications in the next decade. The present review describes the most frequent HIV-associated cardiac manifestations including diagnostic and therapeutic perspectives.