Plasma concentration and clinical effect in imipramine treatment of childhood enuresis.

The relationship between steady-state plasma concentraton and clinical effect of imipramine in the treatment of nocturnal enuresis was studied in 22 hospitalised children. After 1 week on placebo the children were given imipramine in a fixed dose of about 1 mg/kg for 3 weeks. The enuresis frequency decreased significantly from the placebo to the first week on imipramine, but then no further improvement was observed. There was a significant correlation between steady-state plasma concentration of desipramine or imipramine + desipramine and the reduction in enuresis frequency during imipramine treatment. The optimum effect was obtained when steady-state levels of imipramine + desipramine were above 60 microgram/L; i.e. the effective concentration in enuresis is 3 to 4 times lower than in antidepressive therapy. Dose- and weight-corrected, steady-state plasma concentration of imipramine and desipramine were not significantly different from those previously observed in younger adults. In 1 child, a transient rise in imipramine and desipramine concentration was seen during a period with fever and bacterial infection.

Supply chain and marketing of sea grapes, Caulerpa racemosa (Forsskål) J. Agardh (Chlorophyta: Caulerpaceae) in Fiji, Samoa and Tonga.

This report describes for the first time the supply chain of Caulerpa racemosa in three Pacific Island countries. The harvesting and marketing of C. racemosa are important subsistence activities for villagers in Fiji and Samoa, less so in Tonga. At least 150 harvesters are involved in Fiji, some 100 in Samoa and only a handful in Tonga. The annual combined crop is of some 123 t valued at around US$266,492. In Fiji, it is projected that supply does not meet local demand and there is a potential export market that is currently operating at a pilot project level. In Samoa, the supply is considered adequate for the current market. In Tonga, harvesting is carried out by a few families and supplies a niche market in that country. The possibilities of field cultivation of Caulerpa have been explored but, at present, with only limited success in Samoa. The supply chain is simple in all three countries, and only in Fiji are middlemen involved in the distribution process. The limitations for marketing include the fact that only a few sites supply most of the crop in all the three countries, that all sites need to be conserved through sustainable harvesting methods, the short shelf life of the crop and a lack of information on the carrying capacity of harvest sites. Caulerpa remains a crop that fulfils a niche market but has the potential to be scaled up for additional livelihood development in the future.

[Chemical properties of plasma fibrinogens and fibrins from normal and cobalt-treated rabbits]. / Untersuchungen über einige chemische Eigenschaften von Plasma-fibrinogenen und -fibrinen normaler und kobaltbehandelter Kaninchen

The sulfitolysis products of fibrinogens from normal and cobalt-treated rabbits (5 mg Co2+/kg b.w.) were resolved by ion exchange chromatography on CM-cellulose columns. The elution patterns of both fibrinogens showed a distinct heterogeneity of gamma-chains. Furthermore, a gamma-chain derivative from cobalt fibrinogen could be distinguished electrophoretically from the corresponding one of normal fibrinogen because of its reduced electrophoretic mobility. Normal and cobalt fibrinogen did not differ from each other in their N-terminal (Val2 Ala2 Tyr2) and C-terminal (Pro1-2 Val4-5) amino acid compositions related to a subunit structure of A alpha 2 B beta 2 gamma 2, and their carbohydrate contents - neutral hexoses 1,21% (1,26%), N-acetyl hexosamines 1,16% (1,05%), N-acetyl neuraminic acid 1,19% (1, 13%), values for cobalt fibrinogen in parentheses. The main amounts of carbohydrates are bound to gamma- and B beta-chains, The BrCn cleavage products from cobalt fibrinogen and its gamma- and B beta-chains showed other electrophoretic properties than the corresponding derivatives from normal fibrinogen. But BrCN split products of A alpha-chains of both fibrinogens were electrophoretically very similar. Spectrographic investigations of the S-sulfoderivates demonstrated a diminution of the absorption maximum near 282mn of gamma and B beta derivatives of cobalt fibrinogen. A alpha-chains of both fibrinogens were not different from each other. Using autoradiography the highest 58Co binding could be found in the gamma-chain with a reduced electrophoretic migration velocity, whereas B beta-and gamma-chains with unchanged electrophoretic mobility bound only small amounts. A alpha-chains of cobalt fibrinogens were apparently not loaded with 58Co. gamma-chain and alpha-chain cross-links could be observed in normal fibrins stabilized by factor XII, however, in cobalt fibrins a gamma-dimer formation was demonstrable without participation of gamma-chains with reduced electrophoretic mobility. A distinct alpha-chain cross-link could not be demonstrated either. From these and other investigations on molecular weights of both fibrinogens it was assumed that earlier observed changes of physicochemical properties and biological behaviour of cobalt fibrinogen might result from a complex binding of cobalt ions on specific structures of the fibrinogen molecule.

[Electrophoretic patterns of differently prepared fibrinogen subunits in sodium dodecyl sulfate containing polyacrylamide gels]. / Elektrophoresemuster unterschiedlich präparierter Fibrinogen-untereinheiten in dodezylsulfathaltigen Polyakrylamidgelen.

The electrophoretic behaviour of mercapto, carboxamidomethyl, carboxymethyl and thiosulfonic acid derivatives of rabbit fibrinogen subunits was investigated electrophoretically in sodium dodecyl sulfate containing polyacrylamide gels. Comparing carboxymethyl, carboxamidomethyl and thiosulfonic acid derivatives with the corresponding mercapto subunits divergent electrophoretic patterns were observed. Especially, the position of the Bbeta-chain was strongly dependent on the method of preparation. Similar results were obtained from investigating electrophoretic mobilities of albumin with differently substituted SH-groups after reduction with mercaptoethanol.

[Review: hemorrhagic diathesis resulting from acute exposure to ionizing radiation]. / Ubersicht: Hämorrhagische Diathese als Folge einer akuten Einwirkung von ionisierenden Strahlen.

The symptoms of the acute radiopathy are chiefly characterized by a severe blood coagulation disorder. The main results and problems of research work on this haemorrhagic diathesis are shortly reviewed.

[Changes in the cholinesterase activity and glucose concentration in the blood induced by paraoxon in rabbits immunized against paraoxon]. / Veränderungen der Cholinesteraseaktivitäten und der Glukosekonzentration im Blut durch Paraoxon bei gegen Paraoxon immunisierten Kaninchen.

The immunization of rabbits with a paraoxon-HSA-conjugate resulted in an antibody response with titres of 1:25000 to 1:100000 of antisera dilution and average affinity constants K0 of 10(6) M-1 and heterogeneity indices of 0.8 to 0.9 calculated by means of the Sips equation. The serum cholinesterases and the erythrocyte acetylcholinesterase in immunized rabbits were protected against a stronger inhibition by parenteral application of paraoxon. An increase of blood glucose after paraoxon application to immunized rabbits could not be observed but was detectable in unimmunized animals.

[Some problems in standardization of fructosamine tests]. / Zu einigen Problemen bei der Standardisierung des Fructosamin-Tests.

The degree of nonenzymatic glycation of serum proteins was estimated in 500 nondiabetic subjects and in 124 Type 2 diabetic out-patients. The values were evaluated in relation to a DMF calibration curve, a secondary glycated protein standard and to serum protein concentrations. Neglecting the evaluation with respect to the protein concentration 0.4% of the samples from nondiabetics and 9% from diabetic patients would have been incorrectly interpreted. The fructosamine values from nondiabetic subjects showed a Gaussian distribution. The use of secondary protein standards is a premise to a widespread application of the fructosamine assay in diabetic care. The calibration of such secondary glycated protein standards results in some problems when using DMF protein mixtures as primary standards, because albumin preparations from the same or different suppliers gave variable standardization curves.

[Production and characterization of antisera against O,O-diethyl-O-(p-nitrophenyl)-phosphate (paraoxon)]. / Erzeugung und Charakterisierung von Antiseren gegen O,O-Diäthyl-O-(p-nitrophenyl)-phosphat (Paraoxon).

Methods for the production of antibodies against Paraoxon in rabbits are described. The highest-titre antisera were produced with conjugates containing a succinyl spacer group with a degree of derivatisation between 8 and 12 haptens per albumin molecule. The antibody response was tested by immunoprecipitation in agar gel with a hapten-rabbit-albumin-complex and by a radioimmunoassay. The synthesis of 125I labelled tracers is reported. The most potent antisera bound 50% of the radioactive tracer after 1:10(5) dilution and showed apparent affinity constants of 10(6) to 10(7) M-1 for Paraoxon. Compared to Paraoxon these antisera possessed cross reactivities with Parathion of 8.8 to 13.8%, with Methylparathion of 0.35 to 0.82%, and with Dimethoat of 0.0006 to 0.0012%.

[Plasma fibrinogen in female patients with genital cancer and its early stage]. / Untersuchungen über das Plasmafibrinogen bei Patientinnen mit Karzinom des Genitalsystems und seine Vorstufen.

Changes of plasma fibrinogen derivates in 54 female patients suffering from carcinomas of the genital system (36 with cervix carcinoma, 9 with ovarian carcinomas, 7 with carcinomas of the corpus uteri, 1 woman with a vulva and 1 patient with vaginal carcinoma) and 6 females with cervical intraepithelial neoplasia were investigated. It was shown, that the fibrinogen content and the concentration of soluble fibrin monomer complexes in blood plasma depend on the extension of the clinically diagnosed tumor. Furthermore, differently degraded fibrinogens were demonstrated to exist in the blood circulation. The extent of fibrinogenolysis did not correlate with the clinically diagnosed tumor stage.

[Alpha 1-globulin levels in patients with cancer of the genital tract]. / alpha 1-Globulin-Spiegel bei Patientinnen mit Karzinomen des Genitaltraktes.

Electrophoretical investigations of plasma protein patterns in 59 patients suffering from carcinomas of the genital system provide some evidence, that the alpha 1-globulin fraction amounts to only 2% in 25% and less than 2% of total plasma protein in 19% of the examined persons. The normal range of alpha 1-globulin is 2 to 4%. Low alpha 1-globulin values are mainly the result of a diminished alpha 1-antitrypsin level.

[Isolation of an alpha-globulin from rabbit serum responsible for a cobalt(II) ion-induced change in conformation of fibrinogen]. / Isolierung eines alpha-Globulins aus Kaninchesnserum, das für eine durch Kobalt(II)-Ionen induzierte Konformationsänderung des Fibrinogens verantwortlich ist.

A change in conformation of fibrinogen, caused by cobaltous ions after parenteral application or incubation of plasma, is dependent on the presence of species specific plasma proteins. These proteins, which can be found only in some animals, have not yet been identified. An glycoprotein, responsible for the cobalt effect, was isolated from rabbit serum. It migrates immunoelectrophoretically as an alpha-globulin. In the SDS electrophoresis it was shown to migrate in front of albumin. The actions of this protein, induced by cobaltous ions, could be inhibited by complexing and SH groups alkylating compounds.

[Qualitative changes in plasma fibrinogen in irradiated rabbits]. / Untersuchungen zu qualitativen Veränderungen des Plasmafibrinogens röntgenbestrahlter Kaninchen.

Plasma fibrinogens of sublethally irradiated rabbits (8 Gy X-ray irradiation) were isolated by affinity chromatography on fibrin monomer Sepharose and characterised by polyacrylamide gel electrophoresis with sodium dodecylsulfate before and after reduction with 2-mercaptoethanol. Only a small increase of fibrinogen degradation was mainly observed in early phases after irradiation. Fibrin monomer complexes were precipitated together with fibrinogen by 2,5 mol beta-alanine/l. The content of monomer complexes in the precipitate was estimated using Sepharose 6B gel chromatography. Evidence for an increased formation of monomers in the blood could not be obtained. Therefore, proteolytic changes of fibrinogen do not play a role for inducing a hemorrhagic disorder after sublethal X-ray irradiation in rabbits.

The nonenzymatic glycation of proteins and nucleic acids, their importance for the development of diabetic complications, possible molecular basis of aging and autoimmunological processes.

The formation of nonenzymatic glycation products of proteins and nucleic acids appears to be a link between chronic hyperglycaemia and long-term diabetic complications and special forms of aging during normoglycaemia. The major effects of extended glycation include cross-linking of glycated proteins, attachment of soluble proteins to extracellular glycated matrices, conformational changes of proteins followed by altered functions and immunogenicity, and abnormalities in nucleic acid functions.

ATPase and acetylcholinesterase activities in erythrocyte membranes after incubation with glucose and in streptozotocin diabetic rats.

Enzyme activities of ATPases and acetylcholinesterase from isolated erythrocyte membranes (ghosts) were investigated before and after incubation with 50 mM glucose. Glucose incubation caused a time dependent loss of ATPase and acetylcholinesterase activities. Ghost enzyme activities in steptozotocin diabetic rats were found only insignificantly diminished.

Diminished adhesion of endothelial aortic cells on fibronectin and collagen layers after nonenzymatic glycation.

Adhesion of bovine endothelial cells on fibronectin and collagen before and after nonenzymatic glycation in vitro has been studied. Nonenzymatic glycation of these proteins reduced their ability to bind endothelial cells. Furthermore, nonenzymatically glycated fibronectin failed to bind to normal and nonenzymatically glycated gelatin and to fibrin. So gelatin and fibrin Sepharoses can be used to separate highly glycated fibronectins from fibronectins with a low degree of nonenzymatic glucose substitution. Sodium dodecylsulfate polyacrylamide gel electrophoresis did not demonstrate a covalent cross-link between nonenzymatically glycated fibronectins. These results present further evidences for the role of nonenzymatic glycation of proteins in the development of vascular complications in long-term diabetes and of atherosclerosis.

Complement component 3 (C3) genetics and diabetes mellitus.

Complement component 3 (C3) phenotype and allele frequencies were defined in 312 patients with type-1 diabetes (insulin-dependent diabetes mellitus), 256 patients with type-2 diabetes (non-insulin-dependent diabetes mellitus), 114 apparently non-diabetic first-degree relatives of type-1 diabetics, in 10 families (29 members) with a familial history of type-1 or type-2 diabetes, in 181 patients with coronary heart disease and 255 subjects with arterial hypertension. 512 blood donors served as controls. All persons investigated were Europeans. There is no evidence that genes linked to C3 influence susceptibility to type-1 and type-2 diabetes and to their late complications as well as to atherosclerosis and essential hypertension. The distribution of apolipoprotein E phenotypes in patients and controls was likewise not significantly different. The combined evaluation of data from linked genes (C3 and apo E) could not improve the results. Deductions of C3 as a genetic disease marker have to be interpreted with caution.

[What is the fructosamine test and what is its clinical significance?]. / Was ist der Fructosamin-Test, worin besteht seine klinische Bedeutung?

The clinical usefulness of the fructosamine assay is reviewed. Problems of external standardization are discussed and possibilities to circumvent these problems are considered.

Properties of in vitro nonenzymatically glycated plasma fibrinogens.

Nonenzymatic glycation of fibrinogen is species independent and depends only on the glucose concentration in the incubation mixture under selected in vitro conditions. An increased fibrin monomer aggregation in the presence of Ca2+ ions and a decreased proteolytic susceptibility of nonenzymatically glycated fibrinogens may favour the development of thrombophilic states. Blocking of lysine residues as well as restricted conformational changes induced by glucose attachment may be responsible for these effects. Fibrin stabilization by factor XIII is not impaired by nonenzymatic glycation of fibrinogen. Attachment of aortic endothelial cells to fibrin films from glycated fibrinogens is diminished. This phenomenon may be the result of blocked plasminogen activator binding sites in fibrin by nonenzymatic glycation. These effects may contribute in vivo to the accumulation of fibrin in those tissues most frequently affected by diabetic complications.

Complement component 3 (C 3) and diabetes mellitus.

Complement factor 3 (C3) phenotype and allele frequencies were defined in 312 patients with Type 1 diabetes (IDDM), 256 patients with Type 2 diabetes mellitus (NIDDM), 114 apparently healthy first-degree relatives of Type 1 diabetics, in 10 families (29 members) with a familial history of Type 1 or Type 2 diabetes, and 512 controls (blood donors). All persons investigated were Europeans. There is no evidence to suggest that genes linked to C3 influence susceptibility to Type 1 and Type 2 diabetes and to their late complications. C3 levels in blood plasma were found to be slightly elevated in both types of diabetes. But the C3 concentrations varied considerably within the groups. C3 split products were demonstrable in a high percentage in the blood plasma of freshly manifested Type 1 diabetic persons as well as in Type 1 diabetics with a duration of the disease of 1 to 3 years. C3 proteolysis could also be found in plasma of Type 2 diabetics (26%).