Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

[Clinical course of cytomegalovirus infection in adults]. / Klinik der Zytomegalie-Infektion des Erwachsenen.

Between 1972 and 1984 73 patients with acute cytomegalovirus infection have been monitored. In 55 patients case history did not reveal any former disease. In 18 patients the cytomegalovirus infection was a sequela of cardiac surgery ("postperfusion syndrome"), transplantation or underlying malignant disease. After a prodromal stage which comprised unspecific symptoms in most cases various organ manifestations were noted in the course of disease. Typical cases presented hepatitis, myocarditis, Guillain-Barré syndrome with or without thrombocytopenia and (or) lympho-monocytosis. The organ symptoms were varying in degree and resolved completely within 4 to 12 weeks. Only one female patient died from congestive heart failure due to myocarditis after one year.

[Aseptic necrosis of the femoral head in lymphogranulomatosis and chronic myeloic leukemia treated intermittently with cytostatic agents and steroids (author's transl)]. / Aseptische Hüftkopfnekrosen bei Lymphogranulomatose und chronisch-myeloischer Leukämie unter intermittierender Steroid-und Cytostatica-Therapie.

Four male patients with the age from 31--43 years with lymphogranulomatosis and a 23 year old patient with chronic myeloic leukemia developed aseptic necrosis of the femoral head 15 to 69 months after treatment with a combination of cytostatic substances and steroids. In a patient who received maximal prednisone applications aseptic necrosis of the humeral head has been observed also. With increasing life expectancy asceptic bone necrosis due to treatment can appear as a late complication. The early recognition is important. The advancing of this irreversible bone destruction and the associated morbidity can be avoided by immediate cessation of the steroid application. Conservative treatment is indicated.

[Modification of the plasmatic blood coagulation system by normal and leukemic leukocytes]. / Die Beeinflussung des plasmatischen Gerinnungssystems durch normale und leukämische Leukozyten.

Homogenates of leukocytes of normal persons and of patients with acute and chronic leukemias have a weak tissue factor activity. The recalcification time is prolonged and the prothrombin consumption decreased, however, upon addition of these cell homogenates to the test mixture. The inhibition of the clotting is due to an antithrombin activity in the leukocytes. Massive cell destruction in chronic leukemias does not lead to a consumption coagulopathy. In acute leukemias a consumption coagulopathy following cell destruction is not uncommon.

The radioimmunological determination of glibenclamide and its metabolites in serum.

This report describes a sensitive and specific radio-immunological method for determining serum levels of the oral anti-diabetic agent 1-(p-[2-(5-chloro-2-methoxy-benzamido)-ethyl]-benzensulfonyl)-3-cyclohexylurea (glibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after a single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide.

[Clinical and diagnostical aspects of acute cytomegalovirus infections in previously healthy adults (author's transl)]. / Klinik und Diagnostik der akuten Cytomegalie-Infektion bei primär gesunden Erwachsenen

The clinical symptoms of floride Cytomegalovirus infections of 18 previously healthy adults are reported. Fever was generally observed. In most cases myocarditis or hepatitis could be identified. Two of our patients died of on severe myocarditis. In 3 patients Guillain-Barré-syndrome was observed. Only in few of our cases the clinical picture was characterized by mononucleosis with systemic swelling of lymphonodes and thrombocytopenia or by pneumonia. Other symptoms were found quite seldom. The diagnosis of cytomegalovirus infection could be ascertained by: 1. detection of cytomegalovirus IgM antibody titers of greater 1:64, 2. a four fold increase in the titer of complement fixing antibodies, 3. Virus isolation from urine.

[Guillain Barré- polyneuroradiculitis and Fisher-syndrome in cytomegalovirus infections (author's transl)]. / Polyneuroradikulitis Guillain Barré- und Fisher-Syndrom bei akuter Cytomegalie-Infektion

In seven patients suffering from polyneuroradiculitis of the Guillain-Barré type and one case of Fisher syndrome, a cytomegalovirus infection was found. The elevation of the virus-specific IgM-antibodies was confirmed in all cases. The clinical course was severe and acute with respiratory disturbances, but complete remission occurred within 1-4 months. The complement fixing antibodies were highest during the first week of illness, so that further elevations could not be demonstrated, therefore making the IgM-antibody method of special importance. The role of cytomegalovirus infections in polyneuroradiculitis is also discussed.

[Elimination kinetics of phenprocoumon (Marcumar) in liver cirrhosis and after premedication with phenobarbital]. / Eliminationskinetik von Phenprocoumon (Marcumar) bei Leberzirrhose und nach Vorbehandlung mit Phenobarbital

In this paper are presented the results of a study on the elimination kinetics of phenprocoumon in patients concomitantly treated with phenprocoumon and phenobarbital as well as in patients with bioptically proved hepatic cirrhosis. The pre-treatment of the patients with phenobarbital (3 X 100 mg), 4 days before phenprocoumon was started, resulted in an accelerated elimination of phenprocoumon. The biological half-life of phenprocoumon was reduced from 150 to 70 hrs when compared to normal controls, and the elimination constant was found to increase to 9,96 X 10(-3). Phenobarbital at plasma concentrations achieved by usual therapeutical dosage schedules of the drug does not interfere with the protein binding of phenprocoumon as could be shown by equilibrium dialysis. Phenobarbital, therefore, does not accelerate the elimination of phenprocoumon. The inducing effect of phenobarbital on the drug metabolizing enzyme system in the liver results in more rapid biotransformation of phenprocoumon. In patients with bioptically proved hepatic cirrhosis, the elimination kinetics did not differ from the results obtained in normal controls.

Pharmacokinetics of phenprocoumon in man investigated using a gas chromatographic method of drug analysis.

A gas chromatographic method for the determination of phenprocoumon (Marcumar) in serum and urine is described, which facilitates accurate values down to 0.5 mug phenprocoumon/ml serum. After the i.v. administration of 20 mg phenprocoumon in a single dose to 4 healthy volunteers the following pharmacokinetic data were obtained: After the initial fast decrease (phase 1) of the serum level of phenprocoumon, probably due to the distribution into the different compartments is followed by a subsequent slower fall (phase 2) which occurs with a serum half-life of 157 h. The apparent distribution volume was 6.51. Analysis of the urine demonstrated that 90% of the excreted phenprocoumon detected was in the glucuronide form.

[Hydroxylation of glibenclamide by liver biopsy specimens]. / Hydroxylierung von Glibenclamid durch Leberpunktionszylinder

A method for measuring hydroxylation rates of the oral antidiabetic agent glibenclamide (Euglucon) by liver biopsy specimens is described. After incubation of the material in a buffer system, containing glibenclamide-14-C, the supernatant is extracted with organic solvent. The extract is condensed and the radioactivity of the spots after thin-layer chromatography is measured. A linear relationship between incubation time and hydroxylation rates could be demonstrated. Equal amounts of the two metabolites, 4-trans- and 3-cis-hydroxy-cyclohexyl-glibenclamide were formed.