The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

The metabolic activation of the heterocyclic food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by two human cytochrome P450 monoxygenases (P4501A1 and P4501A2) and two human N-acetyltransferases (NAT1 and NAT2) was investigated. Various combinations of these enzymes were functionally expressed in COS-1 cells. DNA adducts resulting from the activation of IQ were assayed quantitatively by the 32P-postlabeling procedure. The highest adduct frequency was observed in cells expressing both CYP1A2 and NAT2. CYP1A2 in combination with NAT1 was 3-6 times less active. When expressed alone these enzymes gave rise to low adduct frequencies. Experiments with N-acetyl-IQ as substrate suggest that NAT1 and NAT2 in addition to their known role in N-acetylation display arylhydroxamic acid N, O-acetyltransferase (AHAT) activity. Quantitative differences in adduct formation between IQ and N-acetyl-IQ indicated that metabolic activation of these arylamines preferentially occurs by P4501A2-catalyzed N-hydroxylation followed by O-acetylation mediated through NAT1 and/or NAT2. These data, in combination with the known genetic polymorphism of NAT2, may explain the clinical observation that the acetylation polymorphism constitutes a risk factor in the carcinogenic activation of environmental mutagens.     

Percutaneous needle trephination. Experience in 200 cases

Summary For many years percutaneous needle and classic burr-hole trephination with insertion of plastic catheters for external ventricular drainage are in use. The shortcomings of the conventional puncture needles were compensated for by the development of a modified instrument in recent years.In this prospective study we tried to define advantages and disadvantages of percutaneous ventriculostomy with this modified needle in a large number of patients. We treated and followed a total number of 200 patients with external ventricular drainage for various reasons (42% obstructive hydrocephalus, 27% haematocephalus, 11% malresorptive hydrocephalus, 11% elevated ICP and 9% infections). The ventriculostomy is performed — after percutaneous trepheication with a 1.5 mm drill and 1.2 mm needle under the local aesthesia as a bedside procedure. The modified blunt needle is provided with markings and a set screw which allows insertion to a prefixed depth and a sharp guide which is withdrawn after penetration of the dura. It is then bent rostrally and fixed by a plaster cast. The mean duration of drainage was 9 days (1–30 days). Mean operating time for the whole procedure including fixation and connection to the drainage system was 20 minutes. Overall complication rate was 13% (N=26). Two intracerebral haemorrhages (1%) occurred, of which one was caused by overdrainage. Five (3%) infections in primarily not infectious cases (N=182) were seen. Only one case of infection occurred without loosing of the needle on day 17. In 19 patients (10%) the needles had loosened. Fifteen times this complication was repaired in time and no infection occurred. The overall complication rate (13%) and the needle related risk of bleeding (0.5%) seem average. The true risk of infection with correct handling (0.5%) is very low despite the very long average duration of drainage. The main risk lies in the markedly high danger of loosening (10%), which entails a disproportionally high demand for nursing care. Nevertheless, we regard percutaneous needle trephination as the ventriculostomy method of choice because of its better practicability and low infection rate.     

RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.     

Einsatz einer Mischkultur in Acetat-Fermentationen

Bacterial cultures were selected from the native flora of liquid manure in order to metabolize liquid manure substances. The mixed culture used in the growth experiments is characterized by low growth rates when maximum degradation of acetate occurs. The biomass concentration reached 2.2 g/l.     

Microalbuminuria and nerve conduction velocity in type-I diabetics during conventional therapy and during continuous I.V. insulin infusion

Summary The objective of this study was to follow the development of microalbuminuria and nerve conduction velocity under continuous i.v. insulin therapy over a limited period of 4 months. For this purpose, 8 labile type I diabetics were selected (age 33±8 years, duration of diabetes 16±9 years) and treated conventionally with two insulin injections daily over 4 months. Afterwards, the same patients were treated with continuous i.v. insulin infusion and finally again with two injections daily over 4 months each. This procedure allowed each diabetic to serve as his own control. HbA₁, microalbuminuria, nerve conduction velocity and relative refractory period of the ulnar nerve were checked at montly intervals. During the continuous i.v. infusion over 4 months, blood sugar values were significantly lower, glucosuria had disappeared almost completely and the glycosylated hemoglobin had fallen to near normal values. The mean rate of albumin excretion was 16±5 μg/min at rest and 76±26 μg/min during exercise (normal: 3.9±0.4 and 4.8±1.2 μg/min, respectively) and did not change significantly. Nerve conduction velocity in the ulnar nerve rose significantly under i.v. insulin therapy from 47.9±0.6 m/sec to 52±0.6 m/sec. Similarly, the relative refractory period of the same nerve fell significantly from 3.7±0.2 to 1.9±0.1 msec (i.e. to within normal range). It is concluded that functional disturbances of peripheral nerve can regress by improved blood sugar control with continuous i.v. insulin infusion over 4 months. On the other hand, incipient microangiopathy measured as microalbuminuria remains unchanged over the same period of time. If an improvement is at all possible, considerably longer periods of euglycemia are likely to be necessary. Supported by Grant No. 3.964-0.80 from the Swiss National Science Foundation.