Mechanical pre-treatment (MPT) - revitalised by MBR process.

Since the mid-nineties membrane bioreactor (MBR) technology has been introduced to municipal wastewater treatment in Europe. The first MBR plants went into operation performing a conventional mechanical pre-treatment (MPT) without any advanced treatment units. After a short operation period, clogging caused by fibrous substances and hence module sludging was observed. Thus, MPT was upgraded introducing sieves. Several investigations had been carried out to determine the removal efficiency of different sieve units and entire MPT systems. Meanwhile experiences from long-term operation at different MBR sites indicate dependencies between different MPT units, especially between the aerated grit chamber/grease trap and the subsequent sieve unit. Usually the sieve is the final MPT unit and its performance depends on the performance of the upstream MPT units. This report describes and discusses results from a research project at MBR Kaarst-Nordkanal in Germany conducted in 2008 to 2010 by the Water Board of River Erft and the Department of Sanitary and Environmental Engineering. Main focus is addressed for the parameters SS (settable solids) and grease. One major experience is the confirmation of relevant interactions between the grit chamber and the downstream sieve unit. Stable operation of the grit chamber and grease trap is essential to achieve a constantly high removal performance of the sieve unit and therefore the entire MPT stage. In turn, negative impacts on the grit chamber performance from the return flow concept have to be avoided. Finally, it is shown that the appropriate two-dimensional sieve gap size should not go beyond 1 mm when operating hollow fibre membranes.

Considerations on the design and financial feasibility of full-scale membrane bioreactors for municipal applications.

Based on the practical experience in design and operation of three full-scale membrane bioreactors (MBR) for municipal wastewater treatment that were commissioned since 1999, an overview on the different design concepts that were applied to the three MBR plants is given. The investment costs and the energy consumption of the MBRs and conventional activated sludge (CAS) plants (with and without tertiary treatment) in the Erft river region are compared. It is found that the specific investment costs of the MBR plants are lower than those of comparable CAS with tertiary treatment. A comparison of the specific energy demand of MBRs and conventional WWTPs is given. The structure of the MBRs actual operational costs is analysed. It can be seen that energy consumption is only responsible for one quarter to one third of all operational expenses. Based on a rough design and empirical cost data, a cost comparison of a full-scale MBR and a CAS is carried out. In this example the CAS employs a sand filtration and a disinfection in order to achieve comparable effluent quality. The influence of membrane lifetime on life cycle cost is assessed.

Strategies for chemical cleaning in large scale membrane bioreactors.

Systematically testing alternative cleaning agents and cleaning procedures on a large scale municipal membrane bioreactor, the Erftverband optimized the cleaning strategies and refined the original cleaning procedures for the hollow fiber membranes in use. A time-consuming, intensive ex-situ membrane cleaning twice a year was initially the regular routine. By introducing the effective means of cleaning in place in use today, which employs several acidic and oxidative/alkaline cleaning steps, intensive membrane cleaning could be delayed for years. An overview and an assessment of various cleaning strategies for large scale plants are given.

Pharmacokinetic determinants of dynamic differences among three benzodiazepine hypnotics. Flurazepam, temazepam, and triazolam.

Healthy adult volunteers (n = 52) received single oral doses of flurazepam hydrochloride (15 mg), temazepam (15 mg), triazolam (0.25 mg), or placebo in a parallel, double-blind study. Sedative effects were greatest with triazolam, followed next by temazepam; peak effects closely coincided with peak plasma concentrations. Differential recovery from sedation corresponded in part to differences in mean elimination halflife, although sedative effects returned to baseline before plasma drug concentrations became undetectable. Sedation following flurazepam administration was less intense than with triazolam and temazepam. When tested at three hours after dosing, none of the active treatments impaired learning of a 16-item word list. However, at 24 hours, triazolam recipients could not recall a significant fraction of what was learned. Thus, dynamic differences among three benzodiazepine hypnotics may be partly explained by kinetic differences, as well as, we should caution, by possible "clinical inequivalence" in dosage.

Cognitive effects of beta-adrenergic antagonists after single doses: pharmacokinetics and pharmacodynamics of propranolol, atenolol, lorazepam, and placebo.

The behavioral effects of two beta-adrenergic receptor antagonists, selected to represent differing lipophilicity, were evaluated in a double-blind, single-dose, parallel-group study. A group of 55 healthy volunteers (mean age, 28 years) received single oral doses of placebo, atenolol (50 mg), propranolol (40 mg), or lorazepam (2 mg). Plasma drug concentrations, self-ratings of sedation and mood, observer ratings of sedation, and performance on the Digit Symbol Substitution Test (DSST) were assessed at multiple times during 24 hours after drug administration. Information acquisition and recall were tested at 3 and 24 hours after drug administration. Lorazepam significantly increased sedation and fatigue, impaired DSST performance, and impaired memory. The time course of these changes was highly consistent with plasma lorazepam concentrations. In contrast, atenolol and propranolol produced at most small changes in self-ratings and observer ratings and did not alter DSST performance or memory. Under experimental conditions that are sensitive to the depressant effects of a typical benzodiazepine, single doses of atenolol and propranolol produced no meaningful changes, compared with placebo.

Androgen levels and female social dominance in Lemur catta.

Morphological and behavioural traits which improve agonistic power are subject to intrasexual selection and, at the proximate level, are influenced by circulating androgens. Because intrasexual selection in mammals is more intense among males, they typically dominate females. Female social dominance is therefore unexpected and, indeed, rare. Ring-tailed lemurs (Lemur catta) are sexually monomorphic primates in which all adult females dominate all males. The goal of our study was to test the prediction that female dominance in this species is associated with high androgen levels. Using two captive groups, we collected data on agonistic behaviour and non-invasively assessed their androgen concentrations in faeces and saliva by enzyme immunoassay. We found that adult female L. catta do not have higher androgen levels than males. However, during the mating season there was a twofold increase in both the androgen levels and conflict rates among females. This seasonal increase in their androgen levels was probably not due to a general increase in ovarian hormone production because those females showing the strongest signs of follicular development tended to have low androgen concentrations. At the individual level neither the individual aggression rates nor the proportion of same-sexed individuals dominated were correlated with their androgen levels. We conclude that female dominance in ring-tailed lemurs is neither based on physical superiority nor on high androgen levels and that it is equally important to study male subordination and prenatal brain priming effects for a complete understanding of this phenomenon.

Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway.

Noradrenergic systems are integrally involved in the release of growth hormone (GH) from the anterior pituitary gland and in regulating the activity of hypothalamic growth hormone-releasing hormone (GHRH) neurones. GH secretagogues act at both the pituitary and the hypothalamus to facilitate the release of GH. In male rats, using the induction of Fos protein as an indicator of neuronal activation, we examined whether neurones in the brainstem, the main noradrenergic input to the hypothalamus, were activated by systemic administration of peptide and non-peptide GH secretagogues. In addition, we examined the effects of chronic central noradrenaline depletion upon GH secretagogue-induced activation of the arcuate nucleus. Systemic injection of the GH secretagogues, GHRP-6 and MK-0677 induced Fos protein expression in a population of area postrema cells, but less than 10% of these cells were noradrenergic. Depletion of hypothalamic noradrenaline by the specific neurotoxin, 5-ADMP, did not alter GH secretagogue-induced activation of Fos protein in the arcuate nucleus compared to vehicle-treated controls. We conclude that the central actions of GH secretagogues involve the activation of non-noradrenergic cells in the area postrema and that GH secretagogue-induced activation of the arcuate nucleus occurs independently of noradrenergic tone.

Validity of self-reports of caffeine use.

The relationship between self-reports of caffeine ingestion on two occasions and measured plasma concentrations of caffeine and its major metabolites was examined. A subject population [25 men and 25 women, age 20-45 years (mean: 28.7 yr)] that was enrolled in a benzodiazepine pharmacokinetic study underwent general medical screening on two occasions, each including detailed caffeine histories. Before beginning their scheduled study, plasma samples were obtained and evaluated by HPLC for caffeine, paraxanthine, theophylline, and theobromine. These values were compared with estimates of caffeine consumption in mg/day generated from both histories. There was no significant difference between plasma levels of caffeine, metabolites, or caffeine plus metabolites for categories corresponding to reports of low, intermediate or high caffeine use. A self-reported caffeine consumption of greater than 300 mg/day (high) did correlate, however, with a significant smoking history. The authors conclude that self-reports of caffeine ingestion do not accurately reflect acute exposure, and that if caffeine use is of importance in a given setting, reports should be confirmed by biochemical means.

Pharmacokinetics and pharmacodynamics of diphenhydramine 25 mg in young and elderly volunteers.

Thirty-seven young and elderly male and female volunteers 21 to 76 years of age received a single 25-mg oral dose of diphenhydramine or matching placebo in a double-blind, randomized, two-way crossover study. Plasma diphenhydramine concentrations, self-ratings of sedation, mood, and autonomic effects, performance on the digit-symbol substitution test (DSST), and heart rate were determined for 24 hours after administration. Information acquisition and recall were tested at 2.5 and 24 hours after administration. Age and gender did not significantly influence diphenhydramine peak plasma concentration, time of peak concentration, elimination half-life, area under the plasma concentration curve, or apparent oral clearance. Effects on psychomotor performance, sedation, mood, and memory did not differ between diphenhydramine and placebo in either group. Thus, the pharmacokinetics of single 25-mg oral doses of diphenhydramine are not influenced by age or gender. This dose of diphenhydramine produces essentially undetectable pharmacodynamic effects in both the young and elderly.

Electron microscopy and microcalorimetry of the postnatal rat heart (Rattus norvegicus).

The interplay of ultrastructure and tissue metabolism was examined in neonatal, infant and adult rat hearts by electron microscopy and microcalorimetry. Morphometry was used to determine parameters of oxygen diffusion capacity (distance between capillaries and mitochondria, capillary surface density) and oxidative metabolic capacity (mitochondrial volume fraction). Thin slices and large samples of living tissue were examined calorimetrically to quantify aerobic metabolism and ischemia tolerance, respectively. After birth, rat hearts grow in parallel to body mass and show characteristics of cellular hypertrophy. Capillary surface density increases from neonatal to infant rats, and decreases to an intermediate value in adult rats. The distance between capillaries and mitochondria shows no significant changes throughout postnatal development. Mitochondrial volume fraction increases continuously until adulthood. The specific aerobic tissue metabolic rate is higher in the neonatal than in the infant and adult rat. However, the ischemic decline in metabolic rate is much slower in the neonatal rat, reflecting an elevated hypoxia tolerance. In conclusion, the neonatal rat heart exhibits a high metabolic rate despite a low mitochondrial volume fraction. The subsequent structural rearrangements can be interpreted as long-term adaptations to the increased postnatal workload and may contribute to the progressive loss of hypoxia tolerance.

Specific antigen of murine erythroblasts.

A new antigan has been revealed by means of antisera against Rauscher virus in mice with Rauscher virus-induced leukemia. This antigen appears to be different from both Rauscher type-specific antigen and MULV-gs-1 (p-30), as shown by studies of electrophoretic mobility and immunochemical specificity. Except in leukemic mice it was also found in low levels in both serum and spleen extracts of healthy mice of a number of strains. Furthermore, this antigen was regularly demonstrated by immunofluorescence on the surface of erythroblasts, but not on the surface of erythrocytes, lymphocytes, polymorphonuclear cells and thymocytes, and was shown to be different from fetal hemoglobin. Therefore, it is referred to as antigen of erythroblasts (Ag-Eb), which seems to represent a surface marker for a certain differentiation stage of erythroid cells.

Ultrastructural localisation of alpha-fetoprotin (AFP) in regenerating mouse liver poisoned with CCL4. 1. Reexpression of AFP in differentiated hepatocytes.

The AFP-synthesizing cells were identified by ultrastructural localization of the antigen in regenerating liver of adult mice after CCl4 poisoning. An indirect immunoperoxidase method with rabbit anti-mouse AFP and peroxidase conjugates of anti-rabbit IgG or their Fab' was used. Good preservation of AFP and tissue structure, and sufficient permeability for the conjugates were obtained after 20' prefixation of small liver specimens in 8% formaldehyde -0.05% glutaraldehyde followed by 16 h fixation in 8% formaldehyde. The intracellular localization of AFP observed in the light microscope in most cases corresponded to its synthesis and secretion. It was found in two cell types, both concentrated mainly in the perinecrotic zones and constituting only a small part of the whole cell population. Most of the AFP-producing cells were normal differentiated hepatocytes without any structural signs of damage. A few smaller cells with active AFP synthesis were present in some animals. By their ultrastructure they resembled the oval cells found during chemical hepatocarcinogenesis in rats.

Oval cell proliferation in early stages of hepatocarcinogenesis in simian virus 40 large T transgenic mice.

In transgenic mice bearing the Simian Virus 40 large T antigen under the control of the human antithrombin III regulatory sequences, a stepwise progression toward hepatocellular carcinoma is observed. We have used two monoclonal antibodies (A6 and G7) developed against a surface antigen expressed in oval cells from dipin-treated mice, to analyze the emergence of such preneoplastic populations in the livers of antithrombin III Simian Virus 40 T transgenic mice. We show that a unique population of small heterogeneous epithelial cells, which probably corresponds to oval and/or transitional cells according to their morphological features, consistently appears at approximately the 10th week after birth and proliferates thereafter. This oval cell-like population stained positively for A6 and G7 monoclonal antibodies. Furthermore, different subpopulations usually recognized as possible precursors of carcinoma cells including hyperplastic foci and neoplastic nodules as well as carcinoma cells, were also positive for A6 but not G7 monoclonal antibodies. Stimulation of cell proliferation by partial hepatectomy performed at the time of emergence of the oval-like cells resulted in a rapid increase in the number of oval/transitional A6-positive cells. Our findings support the view that a common mechanism may be involved in the development of carcinomas that are induced by chemical carcinogens and in transgenic mice expressing a potent oncogene under the control of a hepatic specific promoter. In addition, our findings demonstrate a specific precursor-product relationship between the appearance of the oval/transitional cells and the development of neoplastic hepatocytes in this transgenic model.

Sensitivity to triazolam in the elderly.

BACKGROUND: Elderly persons frequently appear to be sensitive to the effects of many drugs that depress the central nervous system. We studied the effect of age on the pharmacokinetics and pharmacodynamics of the benzodiazepine hypnotic agent triazolam, now the most frequently prescribed hypnotic drug in the United States. METHODS: Twenty-six healthy young subjects (mean age, 30 years) and 21 healthy elderly subjects (mean age, 69 years) participated in a four-way crossover study. After a single-blind adaptation trial with placebo, each subject received, in random order and in double-blind fashion, single doses of placebo, 0.125 mg of triazolam, and 0.25 mg of triazolam. For 24 hours after the administration of each of the three study medications, plasma triazolam levels were determined and psychomotor performance, memory, and degree of sedation were assessed. RESULTS: Plasma triazolam concentrations increased in proportion to the dose, but the elderly subjects had higher plasma concentrations due to reduced clearance of the drug. The degree of sedation as rated by an observer and the reduction in the subjects' performance on the digit-symbol substitution test were both greater in the elderly than in the young subjects after they were given the same doses. The relation of the plasma triazolam concentration to the degree of impairment was similar for the two groups. As part of the study, information was presented 1 1/2 hours after the administration of the drugs; the subjects' ability to recall the information 24 hours later was impaired by both doses of triazolam, and the percent decrease was similar in the young and elderly groups. CONCLUSIONS: Triazolam caused a greater degree of sedation and greater impairment of psychomotor performance in healthy elderly persons than in young persons who received the same dose. These effects resulted from reduced clearance and higher plasma concentrations of triazolam rather than from an increased intrinsic sensitivity to the drug. On the basis of these results, the dosage of triazolam for elderly persons should be reduced on average by 50 percent.

Common antigens of mouse oval and biliary epithelial cells. Expression on newly formed hepatocytes.

Two antigens - A6 and G7 - shared by mouse biliary epithelial and oval cells were revealed by monoclonal antibodies raised in rat immunized with oval-cell-enriched liver fraction. Oval cells were induced in CBA or F1 (CBA x C57BL6) mice by a combination of a single injection of the alkylating drug Dipin with partial hepatectomy. In normal liver A6 antigen was localized, using light and electron microscopy, in biliary epithelial cells of all ducts including Hering canals. Some bile ductal and Hering cells were A6-negative. Occasionally, A6 antigen was present in single hepatocytes forming the periportal ends of hepatic cords. In preneoplastic and tumorous liver A6 antigen was present in bile ductal and oval cells and in a fraction of newly formed hepatocytes and tumor cells. G7 antigen was revealed in normal, precancerous and tumorous liver in biliary epithelial and oval cells but not in hepatocytes. A6 and G7 antigens were not liver-specific: they were expressed in various normal organs and tissues, especially in epithelia. In studies of mouse liver lineages A6 antigen can be used as a common marker of biliary epithelial and oval cells and hepatocytes at certain stages of differentiation. G7 antigen is a marker of oval and biliary epithelial cells. There was a striking similarity in A6 antigen localization to that of human blood group antigens in normal liver and liver tumors. A6 antigen may thus provide a useful tool for the study of neoexpression of human blood group antigens in liver tumors.

Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse.

The A6 antigen--a surface-exposed component shared by mouse oval and biliary epithelial cells--was examined during prenatal development of mouse in order to elucidate its relation to liver progenitor cells. Immunohistochemical demonstration of the antigen was performed at the light and electron microscopy level beginning from the 9.5 day of gestation (26-28 somite pairs). Up to the 11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk sac and gut epithelium, while liver diverticulum and liver are A6-negative. In the liver epithelial lineages A6 antigen behaves as a strong and reliable marker of biliary epithelial cells where it is found beginning from their emergence on the 15th day of gestation. It was not revealed in immature hepatocytes beginning from the 16th day of gestation. However weak expression of the antigen was observed in hepatoblasts on 12-15 days of gestation possibly reflecting their ability to differentiate along either hepatocyte or biliary epithelial cell lineages. Surprisingly, A6 antigen turned out to be a peculiar marker of the crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen erythroblasts from A6 negative early hemopoietic cells of yolk sac origin. Moreover in the liver, A6 antigen probably distinguishes two waves of erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation onward while first extravascular erythroblasts appear in the liver on the 10th day of gestation. Both fetal and adult erythrocytes are A6-negative. In the process of organogenesis A6 antigen was revealed in various mouse fetal organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantable mouse hepatoblastoma: histologic, ultrastructural and immunohistochemical study.

Hepatoblastoma found adjacent to a liver cell adenoma in an aged (CBA x C57Bl/6)F1 male mouse was transplanted to the syngeneic host and passed through 30 generations. Histologically, tumours that grew on transplantation retained principal morphological features of the primary tumour. Transplanted tumours were negative for AFP and for antigen A6. This antigen in the normal mouse liver is found in epithelial cells lining bile ducts and ductules including the terminal Hering canals. Some of the Hering cells were consistently A6 negative under normal conditions, and the suggestion is made that these A6 negative cells might be the cells of hepatoblastoma origin.

[A method for determining the denominator in general practice--results of a pilot study]. / Eine Methode zur Bestimmung des Denominators in Allgemeinpraxen-Ergebnisse einer Pilotstudie.

In countries with fee for service billing and direct access to specialist care the general practitioner does not know key figures of the population he serves. As the role of general practice in health-service-research, quality assurance activities and the construction of sentinel-networks is becoming more important, valid methods to determine the denominator are needed. Results from five practices suggest that yearly contact groups should be used as a common denominator for general practice in our health care system. For certain groups of patients (e. g. the elderly > 60 yrs.) even quarterly contact groups can give sufficient information to forecast the yearly contact group.