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961.
962.
Eric Peys Jan Vandenkerckhove Johan Van hemel Benedikt Sas 《Experimental and toxicologic pathology》2006,57(4):299-304
The artemisinin derivative beta-artemether, an anti-malarial, was evaluated for its toxicity and tolerability in a 2-week, multiple-dose study in dogs. Eight beagle dogs (4 females, 4 males) were given beta-artemether by oral gavage 3 times daily at 45 mg/kg/dosing (a total daily dose-level of 135 mg/kg) for 2 weeks. This beta-artemether dose regime was well tolerated. Body weight changes were normal although feed consumption during the treatment period reduced compared to that of the pre-trial period. Clinical signs were transient spells of soft to liquid feces. On completion of the treatment period, the animals were sacrificed and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and a complete light microscopic examination was performed on 43 selected tissues from 1 animal per sex, and on the liver, kidneys, thymus, mandibular lymph nodes and lungs of the three other animals per sex. Major findings were high liver weight and histopathologic findings of slight diffuse hepatocellular hypertrophy and distal tubular dilatation, together with flattened epithelium, in the kidneys. With the dose regime used in this trial beta-artemether produced no clinical or apparent histopathological signs of neurotoxicity in dogs. 相似文献
963.
C. -F. Ekerot Dr. B. Larson 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1979,36(2):201-217
Summary The spino-olivocerebellar paths ascending through the dorsal funiculi (DF-SOCPs) were studied by recording climbing fiber field potentials in the cerebellar cortex. Several DF-SOCPs were identified on the basis of their response latencies, peripheral inputs, and projection areas. The projection areas consist of eight sagittal zones on each side of the anterior lobe denoted a, x, b, C1, c2, c3, d1, and d2. The a and b zones, which are activated exclusively from hindlimb nerves (Oscarsson, 1969a) were not studied.The shortest response latencies in the x, c1, c3 and d2 zones indicate that these zones are activated by direct paths between the dorsal funiculus nuclei and the inferior olive. These zones also have long latency responses evoked through indirect paths. The direct paths are activated from the flexor reflex afferents and the indirect paths from distal cutaneous afferents. The x zone is activated from forelimb nerves only. The c1 and c3 zones and presumably also the d2 zone are activated from hindlimb and forelimb nerves and have a detailed somatotopical organization.The c2 and d1 zones have long latency responses evoked through indirect paths. Both zones are activated from distal cutaneous afferents. The c2 zone has no distinct somatotopical organization, whereas the d1 zone has largely separate forelimb and hindlimb areas. In contrast to all other zones, the c2 zone is activated not only from ipsilateral but also from contralateral nerves. 相似文献
964.
Prof. Dr. A. Helber G. Wambach W. Hummerich G. Bönner K. A. Meurer W. Kaufmann 《Journal of molecular medicine (Berlin, Germany)》1980,58(9):439-447
Summary In patients with grade I and II essential hypertension studied during sodium loading (Na+ excretion above 175 meq·d–1) we found a bimodal behaviour of aldosterone excretion and could distinguish two groups of patients: In the major part of essential hypertensives sodium loading led to a suppression of aldosterone excretion below 6 µg·d–1, which is the highest control value during sodium loading, with an average of 2.7±1.4 (SD) µg·d–1. Aldosterone excretion in a second group of patients was not suppressible below 6 µg·d–1 despite forced sodium loading; it resulted in an average value of 10.0±3.0 (SD) µg·d–1. During sodium deprivation or free sodium intake, aldosterone excretion in the first group of patients followed exactly the behaviour of normotensive controls, while in the second group of essential hypertensives the correlation of aldosterone excretion and log. Na excretion or log. Na+/K+ ratio in 24 h urine (r=–0.59) was far below the control value ofr=–0.87. Serum potassium concentration during sodium loading was significantly (p<0.001) lower (3.81±0.44 meq·l–1) in the essential hypertensives with non-suppressible aldosterone excretion compared to those with suppressible aldosterone excretion (4.26±0.37 meq·l–1). The blood pressure response to treatment with 200 mg spironolactone·d–1 was better (p<0.05) in patients with non-suppressible aldosterone excretion compared to the essential hypertensives with normal aldosterone regulation. The plasma renin activity of both groups of patients was not significantly different, however, a tendency prevailed towards lower PRA-values in the patient group with non-suppressible aldosterone excretion during sodium loading.With the technical help of Mrs. R. Schendschilorz and Mrs. G. Suckau 相似文献
965.
Prof. Dr. J. Köbberling A. Kerlin W. Creutzfeldt 《Journal of molecular medicine (Berlin, Germany)》1980,58(10):527-530
Summary Three oral glucose tolerance tests (oGTT) have been performed in 312 non-diabetic relatives of diabetics over a period of 10 years. In a second study 6 identical oGTT's have been performed at weekly intervals in 55 individuals. In this study the variance, calculated from the logarithmic values, increased in the following order: fasting (0.026), 1 h (0.035), 2 h (0.044) and 3 h values (0.047). The sum of the 1 h and 2 h values showed the lowest variance (0.024). No significant difference of the variances was found in the 43 individuals in whom both the long-term and the short-term studies have been performed. Thus, a great proportion of the total variance of glucose observed over longer periods only represents a random variation. This random variation is much higher than most other factors which might influence the result of an oGTT. A diagnosis based on a single oGTT is of only limited value.Supported by a grant from Deutsche Forschungsgemeinschaft (Ko 457/8) 相似文献
966.
967.
Allison DE Gourlay SG Koren E Miller RM Fox JA 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2002,16(1):63-70
Background and Objectives: Leucocyte β2 integrin adhesion receptors are hypothesised as a therapeutic target to modify immune responses to ischaemia-reperfusion injury that may be detrimental to recovery in a variety of disease states. Two phase I studies were designed to evaluate the pharmacokinetics, immunogenicity and safety of rhuMAb CD18, ahumanised monoclonal antibody F(ab’)2 fragment to the CD18 receptor, in normal healthy human volunteers. Study Design and Methods: The first study evaluated six escalating doses of rhuMAb CD18 (0.06, 0.12, 0.25, 0.5, 1.0, 2.0 mg/kg) in 36 subjects given two intravenous (IV) bolus injections 12 hours apart. In the second study, 16 subjects received IV doses of 1.0 and 2.0 mg/kg as a single dose or as two doses given 12 hours apart. Study endpoints were rhuMAb CD18 serum pharmacokinetics, change in white blood cell (WBC) count, and safety and tolerability. The two studies enrolled a total of 53 subjects. Results: Serum concentration-time profiles demonstrated a monophasic decline and were best characterised by a one-compartment pharmacokinetic model. At the doses administered, the volume of distribution approximated the serum volume (range of means: 42 to 58 ml/kg). The serum clearance decreased with increasing dose until becoming consistent at doses of 0.5 to 2.0 mg/kg (range of means: 3.1 to 5.0 ml/h/kg). At doses of 0.5 to 2.0 mg/kg, the mean elimination half-life ranged from 7.0 to 9.6 hours. WBC counts increased at doses of above 0.06 mg/kg, returning to within 20% of predose values by day 7. Antibodies to rhuMAb CD18 were not detected at day 28. Mild-to-moderate adverse events were observed in both the placebo and treated groups, and were limited to flu-like symptoms. One subject experienced a serious adverse event (febrile reaction) and recovered with minimal intervention. There was no evidence of an increase in infection in subjects who received rhuMAb CD18. Conclusions: Upon IV bolus administration, rhuMAb CD18 serum concentration-time data fit a one-compartment pharmacokinetic model. At doses of 0.5 to 2.0 mg/kg, the pharmacokinetics were linear and the half-life ranged from 7.0 to 9.6 hours with a volume of distribution that approximated the serum volume. No antibodies to rhuMAb CD18 were detected. A transient, dose-dependent increase in the WBC count was observed, consistent with the expected effect of rhuMAb CD18 on leucocyte demargination. No increase in infection was observed. rhuMAb CD18 administered by IV bolus was well tolerated, with the exception of one febrile reaction. 相似文献
968.
Summary Antigenic relationships of hexons of human adenovirus (Ad h) types 1, 2, 5 and 6 of subgenus C were studied with 61 monoclonal antibodies (MAbs) raised against human Ad h1, Ad h35 and bovine adenovirus 2. The reactivity pattern (RP) and the titers of the MAbs were determined in indirect ELISA. In previous experiments with hexons of different subgenera 49 MAbs displayed numerous different intertype specificities besides genus specific and type specific ones. With the four hexon types of subgenus C all MAbs gave identical RPs except the type specific ones. Data reveal the existence of a remarkable homogeneity in the antigenic structure among the hexon types of subgenus C defined by the presence of identical or closely related intertype specific epitopes on the surface of the hexons. The possible significance of the results in the experimental gene therapy is discussed. 相似文献
969.
Dr G. Jarry J. -P. Lefebvre S. Debray J. Perez 《Medical & biological engineering & computing》1993,31(2):157-164
Time-resolved tomography is performed in transillumination by using 527 nm picosecond pulses from a passively mode-locked
doubled Nd/glass laser and a streak camera to select photons according to their flight time. This work reports on the increase
in contrast of a time-resolved profile of a 2 mm radius opaque object embedded in a scattering medium, constituted of diluted
milk in a 30 mm thick cell. For spatial analysis, the emerging photons are detected through a 6 mm slit at the outlet face
of the cell. Transmission profiles obtained as a function of time show that the contrast is enhanced for the shortest flight
times, while the ‘shadow’ of the object is no longer detected after about 100 ps. Moreover, improvements in contrast are studied
for different configurations of the model, to analyse separately the role of collimated and scattered photons. It is expected
that such a tomographic method based on time-resolved absorption could be applied to imaging for more complex biological structures
in the red and near-infra-red range. 相似文献
970.
Vogt A 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1999,11(6):377-383
A breakthrough in platelet inhibition was achieved with the advent of antagonists of the glycoprotein (GP) IIb/IIIa receptors. These receptors are essential to platelet aggregation triggered by any of several different mechanisms. GP IIb/IIIa receptor antagonists, especially the monoclonal antibody abciximab, have been established as adjuncts to angioplasty in acute coronary syndromes. Conjunctive treatment with thrombolysis in myocardial infarction has been studied less extensively. GP IIb/IIIa receptor antagonists appear to be a feasible adjunct to thrombolysis. In particular, the use of abciximab in conjunction with reduced doses of thrombolytics is an attractive approach to achieve early coronary reperfusion with probably acceptable bleeding risk. The eventual role of this combined treatment can only be defined by the large-scale clinical trials that will be performed in the near future. 相似文献