Dissociated cell culture of rat cerebral cortical neurons in serum-free, conditioned media: GABA-immunopositive neurons.

The gamma-aminobutyric acid (GABA)ergic properties of embryonic (E15d) rat cortical neurons were studied in dissociated serum-free culture by immunohistochemical methods. GABA-like immunoreactivity was found in a subpopulation of neurons from the first day onwards. The number of GABA-positive neurons reached mature values (10.5-12.6%) within the first week, while their morphological differentiation was not found to be fully completed until the 11th day of culture and was characterized by several discrete developmental stages. First, GABA-positive neurons gained their mature complement of neurites at 3 days in vitro (DIV). Three days later somal maturation became evident, followed at least by the maturation of the neuritic arbor. Double-labelling studies revealed the coexpression of GABA and tyrosine hydroxylase within the same cells. The similarities of relative number, morphology, time course of development and biochemistry of cultured GABAergic neurons compared with those in situ suggest that the applied culture system is a useful model to investigate several aspects of GABAergic neurotransmission at the cellular level.     

Die dopplersonographische Bestimmung der maximalen Blutströmungsgeschwindigkeit in der Diagnostik peripherer arterieller Verschlußkrankheiten bei Diabetes mellitus

Summary Seventy-five diabetic and 40 nondiabetic subjects who where suffering from peripheral vascular disease were studied in order to determine whether the degree of the severity of their disease can be better calculated by Doppler ultrasound examinations of the peak velocity than by the systolic pressure of the peripheral bloodstream. In 46 examinations of normal controls the mean value of the peak velocity was 13.3±3.3 cm/s with a standard deviation of 15.4%±13.2% on one day and 16.1%±15.9% on different days. Considering patients with or without diabetes mellitus the velocity was significantly decreased in correlation to an increasing degree of severity of the vascular disease (P<0.001); however, the decrease was lower in diabetic than in nondiabetic subjects (6.9±2.8 vs 4.6±6.2,P<0.05). The systolic pressure hardly decreased, but remained higher in all stages of peripheral vascular disease of diabetics than in the nondiabetic subject (P<0.05 toP<0.005). There was a significant decrease of the systolic pressure only in diabetic subjects with the most advanced degree of the disease, i.e. stage IV (P<0.05).It is concluded from this study that Doppler ultrasound measurements of the peak velocity of the peripheral bloodstream are a useful parameter to calculate the degree of severity of the peripheral vascular disease. In addition, it is concluded than peak velocity is an even better prognostic indicator of peripheral vascular disease than is measurement of the systolic blood pressure at the feet.

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Abkürzungen AVK periphere arterielle Verschlußkrankheit - USDI Ultraschall-Doppler-Index - MSBG maximale Blutströmungsgeschwindigkeit - HFV Herzfrequenzvariation     

Nitratbehandlung

Organic nitrates are used for the treatment of angina pectoris symptoms, acute coronary syndrome and for acute and chronic heart insufficiency. In spite of the proven effectiveness of organic nitrates for acute cases, long-term therapy is limited by to the development of tolerance. Recent animal experiments, as well as clinical data, show that an endothelial dysfunction is also induced, a disquieting point, especially considering the negative prognostic impact of endothelial dysfunction. Due to these side effects, the published guidelines of the American Heart Association and the American College of Physicians do not recommend the use of long-term nitrates, such as mono- and dinitrate, for the treatment of stable angina pectoris. Rather, if good left ventricular function is present the calcium antagonist amlodipine should be used. In cases of appreciably reduced left ventricular function, there is a current discussion, based on the recently published A-HeFT study, as to whether a combination therapy with organic nitrates and the effective arteriole dilator hydralazine is beneficial for patients with severe heart insufficiency.     

Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4- triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities

Some 2-methyl-3-triazole-substituted-4(3H)-quinazolinones 3a-f were prepared and tested for their H1- and H2-antihistaminic activities. In addition these compounds are central nervous system depressants and anticonvulsants. 3e shows highly significant decrease of locomotor activity.     

Closed-loop feedback control of methohexital anesthesia by quantitative EEG analysis in humans

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital anesthesia in 13 volunteers. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Median frequency values from 2-3 Hz were chosen as the desired EEG level (set-point). In 11 volunteers, the feedback system succeeded in maintaining a satisfactory depth of anesthesia (i.e., unresponsiveness to verbal commands and tactile stimuli). During feedback control, 75% of all measured median frequency values were in the preset range of 2-3 Hz. This distribution of median frequency was obtained by applying random stimulation (six different acoustic and tactile stimuli) to the volunteers approximately every 1.5 min. The decrease of median frequency from baseline to anesthetic values was primarily induced by increasing the fractional power in the frequency band of 0.5-2 Hz from 12.6 +/- 4.5% (mean +/- SD) to 46.0 +/- 2.5%. The median time to recovery (as defined by opening eyes on command) after cessation of the feedback control period was 20.6 min (10.7-44.5 min) when median EEG frequency was 5.2 Hz (4.7-8.4 Hz). The average requirement of methohexital (mean +/- SD) during the 2 h was 1.02 +/- 0.16 g. It is concluded that pharmacokinetic-pharmacodynamic models of intravenous anesthetics established previously may be used to form a suitable background for model-based feedback control of anesthesia by quantitative EEG analysis. This approach gives a possible solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Effect of the calcium antagonist nimodipine on hemodynamics, gas exchange and endocrine parameters in opiate anesthesia

During opiate anesthesia (standardized dosage of fentanyl) for operation of cerebral aneurysms after subarachnoid hemorrhage, different hemodynamic, respiratory, metabolic, and endocrine parameters were determined before (1 in Fig. 1-4), after (6), and during consecutive stages of induced hypotension (systolic blood pressure 100 mmHg (2), 90 mmHg (3), 80 mmHg (4, 5) during an interval of 20 min), comparing two groups with different vasodilating drugs. In the first group (nimo/NNP in Figs. 2-4) a constant infusion of nimodipine was applied (1.2 micrograms/kg b.w. X min-1), while sodium nitroprusside (NNP) was added in small amounts as necessary to achieve the respective values of systolic blood pressure. In the second group (NNP in Figs. 2-4) induced hypotension was done with NNP alone (maximal dosage: 8 micrograms/kg X min-1). Each group consisted of 11 patients. Additional nimodipine (in the first group), a calcium antagonist commonly recommended for preventing vasospasm and consequent neurologic deficits after subarachnoid hemorrhage, not only reduced the need for NNP, a vasodilating drug with potential toxicity, by 70%-80% as compared to the second group (Table 1). In addition, the cardiovascular situation was more stable in patients with nimodipine infusion: rapid variations of blood pressure and heart rate as well as tachyphylaxis and rebound, typical for NNP-induced hypotension, were avoided. Nevertheless, comparing the hemodynamic data at fixed stages of hypotension, there were only minor differences between both groups (Fig. 2). Reduction of blood pressure was due to a decrease in vascular resistance and was accompanied by an increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total anatomic correction of interrupted aortic arch complex. Experience in 4 infants

In two cases of interrupted aortic arch (IAA) of type A, one associated with a ventricular septal defect (VSD) and one with an aortopulmonary window, and two of type B, both associated with a VSD, total anatomic repair was performed at respective ages of 6 months and 24, 8 and 3 days. All four operations were performed through a median sternotomy, using profound hypothermia and circulatory arrest. The repair included resection of the patent ductus arteriosus, direct end-to-side anastomosis of the descending to the ascending aorta and closure of the VSD or, in one case, of the aortopulmonary window. The two oldest infants (with type A IAA) survived. Reexamination two years postoperatively demonstrated good width of the aortic anastomosis with no gradient. In the child who had had an aortopulmonary window there was a proximal tight stenosis of the right pulmonary artery, which was corrected at reoperation. Total anatomic correction of IAA through an anterior approach is technically feasible and the aortic anastomosis seems to grow satisfactorily. The management of very sick neonates with IAA remains a great challenge.