Lamella separators in the upgrading of a large urban sewage treatment plant.

Wupperverband is using lamella separators for the upgrading of its Kohlfurth sewage treatment plant that is currently in progress. The lamellae positioned at the outlet of the biological treatment stage already remove part of the biomass in the activation basin and prevent it from reaching the final clarification stage. This preliminary separation system reduces solids concentration in the biological treatment system without negative impact on final clarification and therefore also lowers the basin capacity needed, with positive effects on costs. This article gives an overview of the separation performance achieved.

Therapeutic use of the natriuretic peptide ularitide in acute renal failure.

BACKGROUND: Ularitide is a member of the natriuretic peptide family. This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide. Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously. Its main action sites are the glomerulum, inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate, and the tubular system inhibiting Na(+)-reabsorption. In initial uncontrolled clinical trials, this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure. METHODS: We conducted a double-blind, placebo-controlled, multicenter, dose-finding trial recruiting 176 patients randomized into 4 different Ularitide doses groups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5. The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours. FINDINGS: The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)). INTERPRETATION: In summary, the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol. Further prospective clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure.

Properties of a 3-methylcholanthrene-inducible phenol UDP-glucuronosyltransferase from rat liver.

Functional and molecular probes are described which are useful to identify a 3-methylcholanthrene-inducible phenol UDP-glucuronosyltransferase (GTMC) from rat liver. Two different procedures for isolation of GTMC were compared, method 1 utilizing DEAE-Sepharose chromatography or method 2, chromatofocusing. Method 2 appeared to be superior in separating different isoenzymes. Subsequently the enzyme was purified by affinity chromatography on UDP-hexanolamine Sepharose. With both methods a protein was purified with a subunit Mr of 55,000, catalyzing glucuronidation of a variety of planar phenols and, in particular, of benzo(a)pyrene-3,6-quinol to its mono- and diglucuronide. Antibodies to GTMC recognized a polypeptide with a subunit Mr of 55,000 as the major 3-methylcholanthrene-inducible isoenzyme in rat liver microsomes. The described functional and molecular probes may help to differentiate GTMC from similar isoenzymes conjugating planar phenols and to elucidate its regulation and biological function.

Regioselectivity of rat liver microsomal UDP-glucuronosyltransferase activities toward phenols of benzo(a)pyrene and dibenz(a,h)anthracene.

Inducibility of rat liver microsomal UDP-glucuronosyltransferase was investigated with regard to the substrate structure using 3-, 6-, 7-, 8-, and 9-hydroxybenzo(a)pyrene, all seven phenols of dibenz(a,h)anthracene, 3-hydroxybenz(a)anthracene, and 3-hydroxyfluoranthene as substrates. Glucuronide formation of the majority of the planar phenols was preferentially inducible by 3-methylcholanthrene (4- to 8-fold, group 1). However, glucuronidation of 8-hydroxybenzo(a)pyrene, 3-hydroxybenz(a)anthracene, and 3-hydroxydibenz(a,h)anthracene was markedly inducible by phenobarbital (3- to 8-fold, group 2). Glucuronidation of 9-hydroxybenzo(a)pyrene and 3-hydroxyfluoranthene was only moderately induced by the two inducers (less than 2-fold, group 3). Glucuronidation was also determined with purified phenol UDP-glucuronosyltransferase from 3-methylcholanthrene-treated rats. A close correlation (r = 0.95) was observed between purification factors (ratio of enzyme activities in purified enzyme and microsomes) and induction factors (ratio of microsomal enzyme activities from 3-methylcholanthrene-treated rats and untreated controls). Interestingly, differences in size and shape of group 1 and 2 substrates could be recognized. Group 1 substrates were shorter (less than 1.3 nm) and broader (greater than 1.1 nm) than group 2 substrates when viewed from the hydroxy group, along the axis of the C-O bond, to the plane of the polycyclic aromatic hydrocarbon, suggesting a distinct geometry of the binding site of the 3-methylcholanthrene-inducible phenol UDP-glucuronosyltransferase.

Species differences of glucuronidation and sulfation in relation to hepatocarcinogenesis.

The role of glucuronidation and sulfation in the control of proximal and ultimate carcinogens is briefly reviewed. In accordance with the adopted practice of tumor risk assessment, data from two rodent species (rat, mouse) and man have been compared. Sulfate esters have been established as ultimate carcinogens in 2-acetylaminofluorene, safrole and estragole induced hepatocarcinogenesis. In interspecies comparisons the tumor incidence paralleled sulfotransferase activity (Miller and Miller 1981). Glucuronides are often stable transport forms of carcinogens and in this way determine their organ specificity, for example in 2-naphthylamine-induced bladder carcinogenesis and in colon carcinogenesis produced by 2',3-dimethyl-4-aminobiphenyl. In contrast to sulfotransferase activity certain UDP-glucuronyltransferase activities are differentially inducible by xenobiotics. A 3-methylcholanthrene-inducible phenol-glucuronyltransferase (GT1), present in rat, mouse and man, appears to be part of an adaptive program to detoxify aromatic hydrocarbons. After initiation of hepatocarcinogenesis permanent alterations of these enzymes occur; GT1 is markedly increased whereas sulfotransferase is decreased. Together with changes of other drug metabolizing enzymes these alterations often lead to toxin-resistance of initiated hepatocytes. This phenomenon may facilitate selective growth of initiated hepatocytes and may enhance the probability of multiple hits in their genome.

The role of conjugation reactions in detoxication.

The role of conjugating enzymes is best understood by looking at the interaction between phase I (mostly cytochromes P-450) and phase II (conjugation) enzymes of drug metabolism. A balance between phase I and II enzymes of detoxication largely determines the disposition to drug toxicity. Reactive electrophilic metabolites, generated by phase I enzymes, are often controlled by GSH-transferases, whereas nucleophilic metabolites such as phenols are controlled by UDP-glucuronosyltransferases (GT) and sulfotransferases. It is more and more recognized that the control of the more stable and more abundant nucleophiles is as important as the control of electrophiles, since the former can be readily converted to electrophiles. For example, phenols and quinols can undergo quinone/quinol redox-cycles with the generation of reactive oxygen species. In the case of benzo(a)pyrene-3,6-quinol toxicity can be prevented by glucuronidation. Conjugating enzymes consist of families of isoenzymes with distinct but overlapping substrate specificity. Rather than dealing with individual isoenzymes, adaptive programs are emphasized by which gene expression of a battery of phase I and II enzymes is turned on by certain types of inducing agents. Mechanistically best known is the program turned on by 3-methylcholanthrene-type inducers which includes enhanced synthesis of certain isoenzymes of cytochrome P-450, GT and probably GSH-transferase. The program may adapt the organism to efficiently detoxify and eliminate aromatic compounds such as benzo(a)pyrene. Evidence is presented that this program exists in both rodents and humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunochemical and functional characterization of UDP-glucuronosyltransferases from rat liver, intestine and kidney.

Glucuronidation of various substrates in hepatic, intestinal and renal microsomes of control, phenobarbital (PB), 3-methylcholanthrene (3MC) and Aroclor-1254 (A1254) pretreated rats was investigated. UDPGT activities tested could be divided in four groups on the basis of their tissue distribution and induction by PB or 3MC in liver microsomes. GT1 activities (1-naphthol, benzo(a)pyrene-3,6-quinol) are induced by 3MC in liver microsomes and are present in all tissues investigated. GT2 activities (morphine, 4-hydroxybipheynl) are induced by PB in liver microsomes and appear to be restricted to the liver and the intestine. UDPGT activity towards bilirubin, although induced by PB, can be detected in hepatic, intestinal and renal microsomes. UDPGT activity towards fenoterol is restricted to the liver and intestine and is not induced by PB, 3MC or A1254. The presence of inducible immunoreactive UDPGT isoenzymes in microsomes of liver, intestine and kidney of control and induced rats was demonstrated by immunoblot analysis using rabbit anti-rat liver-GT1 antibodies. Induction of both 54 and 56 kDa polypeptides in hepatitis, intestinal and renal microsomes by 3MC or A1254 was observed. Purification of UDPGT (1-naphthol as substrate) from intestinal microsomes to apparent homogeneity yielded a polypeptide with an apparent molecular weight of 54-56 kDa. The results indicate that 54 and 56 kDa UDPGT polypeptides are the major A1254 inducible isoenzymes in intestinal and renal microsomes. An increase in immunoreactive protein is correlated with a biochemically measurable increase in glucuronidation capacity for GT1 substrates.

Pituitary and adrenal hormones in patients after myocardial infarction under ergometer load.

The levels of human growth hormone (HGH), ACTH and cortisol in the plasma of 100 middle-aged men were measured by means of radioimmunoassay (12 patients in the phase of hospitalization after myocardial infarction, 47 patients in convalescence, 31 patients in post-convalescence, 10 healthy men). Twenty patients in the phase of convalescence and all patients in post-convalescence did exercises on bicycle ergometer with submaximal loading. Patients after myocardial infarction showed significantly lower basic levels of HGH than healthy persons, and the increase in the HGH level induced by exercise was significantly lower. The hormones ACTH and cortisol showed only slight differences. The secretion of the pituitary hormones, mainly HGH, seems to be altered in patients after myocardial infarction.

[Indirect blood pressure measurement with a two-probe-ultrasound system (author's transl)]. / Indirekte Blutdruckmessung mit einem Zwei-Sonden-Ultraschallsystem.

A two-probe-ultrasound system is described as an example of the indirect measurement of blood pressure. Possible errors of the indirect method as well as attempts of improvement are shown. To receive a separate detection of the systolic, respectively the diastolic pressure, one probe of the two-probe system is fixed to the arteria radialis, the other to the arteria brachialis. The determination of the "Nulkriterium" (coincidence of the pneumatic cuff pressure and the arterial pressure) can be performed either by the investigator or automatically. The measuring systems shows the following advantages: 1. Use of a more reliable "Nulkriterium" (measurement of hypotonic blood pressure values which could no longer be measured by means of the Riva-Rocci/Korotkoff-procedure; no auscultatoric gap appeared at about 20 000 single measurements). 2. No falsification of systolic values by suprasystolic noises (two-probe principle; measurement of the systolic blood pressure by means of a probe outside the region of the pneumatic cuff). 3. Errors which come up by the expectation of the investigator or by the reading of the manometer can be avoided dependent on the mode of the system. The automatic measurement (dynamical compression, selection of frequencies, electronic threshold, delayed ECG coincidence) led to no satisfactory results, especially referring to the diastolic values. Principle criteria, however, come up which should be fulfilled with the construction of an automatic system of indirect blood pressure measurement. A better automatic measurement may be expected, if instead of the "threshold principle" used here a signal analysis is performed by microprocessors. The example of an intraarterial measurement of blood pressure demonstrates the phenomenon of a "mock auscultatoric gap" because of the spontaneous variability of the arterial pressure decreasing for a short time faster than the pneumatic cuff pressure.

[Traffic noise and hypertension risk. Hypothalamus theory of essential hypertension. Second communication (author's transl)]. / Verkehrslärm und Hypertonie-Risiko. Hypothalamus-Theorie der essentiellen Hypertonie--2. Mitteilung.

In connection with the Bonn Study on Traffic Noise, 56 males with healthy cardiovascular systems were selected at random from two areas with different traffic noise conditions. The blood pressure was measured under the influence of a 5 minute standardized stressor and a 30 minute exposure to traffic noise. The 17 subjects with hereditary tendency to hypertension reacted significantly under the influence of both stressors with more marked rises in systolic and diastolic blood pressures than the 35 subjects who denied a hereditary tendency. On the other hand, the different residential areas did not affect the blood pressures obtained experimentally. The results support the hypothalamus theory of essential hypertension through the decisive etiological factors. At the same time they form the basis of a working hypothesis for a prospective study. According to this it is expected that males with a hereditary tendency to hypertension who have been exposed to traffic noise for several years will be more likely to develop hypertension.

Relationship between blood pressure reactions on an ergometric and an emotional stress test.

The relationship between blood pressure reactions on an ergometric and an emotional stress test was studied in a population of 62 normotensive subjects. Significant correlations for systolic (r = 0.34, p = 0.004) and diastolic ( r = 0.03, p = 0.01) blood pressure were found. It is concluded that 1) there is a individual-specific blood pressure reactivity, 2) Hypertension is closely related to the individual-specific systolic blood pressure reactivity for it is known that hypertensives exhibit stronger systolic blood pressure reactions on both stressors.

[On the reaction of finger pulse amplitude to noise (author's transl)]. / Zur Reaktion der Fingerpulsamplitude auf Belärmung.

1. Forty-three (30 male and 13 female) subjects were exposed to traffic noise of ca. 72dB. Their reactions concerning blood pressure, pulse pressure, finger pulse amplitude and radialis pulse amplitude, heart rate, breathing rate, and integrated EMG were analyzed. 2. Each of the circulatory parameters exhibited significant reactions in either direction in more than 40% of the subjects. The vasoconstrictive reaction in finger pulse amplitude was most outstanding. Moreover, pulse pressure, radioalis pulse amplitude and, heart rate also tended to decrease whereas diastolic blood pressure tended to increase. Breathing rate and EMG remained mainly unchanged. 3. Owing to the different direction of reactions the mean values of a sample can yield possible misleading information. Furthermore, it is suggested that the reaction of finger pulse amplitude should be related to the standard deviation of the prestimulus resting period instead of to the mean value of this period. 4. Male subjects react with a stronger decrease of heart rate than female subjects. Male subjects with higher diastolic casual blood pressure and heart rate values exhibit stronger decreases in finger pulse amplitude and heart rate. Older male subjects tend to react with an increase of heart rate. 5. Within the male subjects, the reaction of finger pulse amplitude correlated positively with the reactions of pulse pressure and heart rate, but not with the reaction of radialis pulse amplitude. The attempt to distinguish between vasoactive and pressure-dependent components in finger pulse amplitude means of radialis pulse amplitude failed, which is probably a consequence of artifacts in radialis pulse amplitude.