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M Wiese

Publications and source records attributed to M Wiese.

At least 19 recordsLinked to original sources
PubMed1992

A time hierarchy-based model for kinetics of drug disposition and its use in quantitative structure-activity relationships.

By using the time hierarchy of the processes determining the fate of drugs in biosystems (absorption, transport, distribution, protein binding, and elimination), a one-compartment open model is formulated at a subcellular level for the disposition phase of pharmacokinetics. The resulting disposition function describes the kinetics of the intracellular disposition of drugs as determined by their hydrophobicity, acidity or basicity, affinity to proteins, and rate parameters of elimination. Structure-activity relationships, based on the function with incorporated extrathermodynamic relations, fit the literature data well (fixed-time bioactivity-hydrophobicity profiles, kinetics of microbial degradation of organic compounds, and kinetics of analgesic effects of fentanyl derivatives in rats). Application of the approach, creating a basis for the construction of model-based quantitative structure-time-activity relationship, to biosystems of varying complexity is discussed.

Animals↗
PubMed1991

Interaction of prostaglandin E1 with alpha-cyclodextrin in aqueous systems: stability of the inclusion complex.

Prostavasin, an inclusion complex of prostaglandin E1 (PGE1) with alpha-cyclodextrin (alpha-CD), is used in the therapy of thrombosis. Nuclear magnetic resonance measurements have been made to study the interaction of PGE1 with alpha-CD. The observed interaction (chemical shift) and the derived dissociation constant prove that only weak interaction forces are operative and that complete dissociation occurs upon dilution.

Alprostadil↗
PubMed1991

Pyrimethamin-resistant Plasmodium falciparum lack cross-resistance to methotrexate and 2,4-diamino-5-(substituted benzyl) pyrimidines.

Methotrexate resistance induced in cultured Plasmodium falciparum depends on an altered dihydrofolate reductase with decreased affinity for methotrexate as well as for pyrimethamine. In contrast, pyrimethamine-resistant field isolates of P. falciparum lack cross-resistance to methotrexate and 2,4-diamino-5-(substituted benzyl) pyrimidines. The structure of the latter class was optimized by the use of trimethoprim as a lead and the substitution of methoxy groups at the benzyl ring by 3-(4'-aminophenyl-4-sulfonylphenylamino)propoxy or by (4'-aminophenyl-4-sulfonylphenyl)methoxy, which resulted in antimalarials of high potency. The efficiency of these newly designed 2,4-diamino-5-(substituted benzyl) pyrimidines was confirmed by their strong inhibitory effect on plasmodial dihydrofolate reductase as well as by in vitro screening against drug-sensitive and -resistant strains of P. falciparum.

Animals↗
PubMed1991

A kinetic description of the fate of chemicals in biosystems.

A simple kinetic description of the fate of low-molecular-weight compounds in biosystems was derived using the mass action law. Michaelis-Menten kinetics of enzymatic reactions was considered with respect to its two boundary cases, namely first- and zero-order kinetics. Absorption, membrane accumulation, non-covalent protein binding, biotransformation, and excretion have been included in the model, with only the last two steps being considered as time-dependent on the pertinent time scale of hours and days. This time hierarchy allowed for simplification of the resulting expression. In accordance with the results of uptake experiments and contrary to previous approaches, transport of organic molecules into the cell was not considered as the rate-limiting step. The decisive compound properties were found to be hydrophobicity and the intrinsic rate parameters of biotransformation and excretion. The model was applied to the elucidation of the dependence of the observed biotransformation rate parameters on hydrophobicity. The resulting equations are consistent with literature data.

Biotransformation↗
PubMed1991

Long-term persistence of hepatitis C virus antibodies in a single source outbreak.

The occurrence of antibodies to hepatitis C virus (HCV) was investigated in 81 patients who developed hepatitis non-A, non-B (HNANB) after parenteral administration of contaminated immunoglobulin to prevent Rh sensitization. Sera from 74 of the 81 patients (89.9%) were anti-HCV positive at either 6-12 months or 9-10 years after administration of immunoglobulin. Sera were not available from any patients at either of the times: however, 52 of 56 sera (92.9%) were anti-HCV positive 6-12 months after use of immunoglobulin, and anti-HCV was present in 45 of 65 sera (69.2%) 9-10 years after immunoglobulin treatment. Of the latter, only two of 13 (15.4%) sera from patients who recovered from hepatitis were anti-HCV positive, whereas 43 of 52 patients (82.7%) with chronic disease were anti-HCV positive. The ELISA using a recombinant antigen was found a good detector as marker for a HCV infection because 90% of patients infected by a common source became anti-HCV positive. However, 10 years after infection most patients who did not develop chronic disease no longer had detectable antibodies.

Analysis of Variance↗
PubMed1991

[Serological diagnosis of viral hepatitis].

The differentiation and classification of different types of viral hepatitis was essentially improved in the laboratory diagnosis by the direct determination of the virus in serum, viral antigens or their antibodies. Especially for the hepatitis B it is possible to recognize the infectivity by the serum marker HBeAg, the prognosis by seroconversion (HBeAg/HBeAb), the epidemiology, and vaccination prophylaxis, respectively. Without doubt, immunological marker have an increasing significance for prophylaxis, diagnosis, and therapy of viral hepatitis.

Diagnosis, Differential↗
PubMed1990

[Progress in the development of a detection test for parenteral non-A, non-B hepatitis--results of enzyme immunoassay for anti-hepatitis C virus].

After more than one decennium of international research work the doubtless identification of the causative agents of the non A-non B-hepatitis (NANBH) has not yet been successful. 1988, however, a viral genome of the parenteral NANBH could be isolated, on which basis an EIA was built up. By means of this anti-HCV-ELISA altogether 413 sera were tested. In 262 sera of 154 women of a NANBH-group with homogeneous source of infection (contaminated anti-D-immunoglobulin) in 74% positive reactions were the result. This and the extensive reproducibility of the test results in identical patients speak for the fact that the recombinant antigen underlying the test really belongs to the parenteral NANBH-group. In the group of the sporadic, however, only in one case a positive reaction was achieved, which supports the thesis of at least two parenteral causative agents of NANBH. The deep-freezing storage of patients' sera lasting up to 8 years did not lead to the failure of the test. The reasons for non-reactive tests were discussed.

Adult↗
PubMed1990

Effect of cyclodextrin derivatives on indomethacin stability in aqueous solution.

The effect of various cyclodextrins (CD) and cyclodextrin derivatives on indomethacin stability in phosphate buffer, pH 7.4, was investigated. The influence of CD-ring size, type of substituent, degree of substitution, substitution pattern, and influence of CD concentration were monitored. The indomethacin complex in solution was studied by 1H-NMR spectroscopy to develop a molecular inclusion model. The most favorable ring size for the stabilization of indomethacin was the beta-CD. The beta-CD derivatives inhibited the hydrolysis of indomethacin more effectively than the parent CD. Among the studied CD derivatives, those with lipophilic substituents, such as ethyl or methyl, were superior to those with hydrophilic substitutents. The more hydroxyl groups of the glucose moiety are substituted, the better is the stabilizing effect. Further, the p-chlorobenzoic part of the indomethacin molecule is included in the CD channel.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1989

[The relation of B- and non-A, non-B hepatitis virus--hepatitis B virus (HBV) DNA hybridization studies of the sera in non-A, non-B hepatitis].

Referring to informations of various international groups of investigators who regard the NANBH as HBV-variant the sera of 77 female patients with chronic NANBH and 28 acute phase sera of a NANBH serum bank were tested for HBV-DNA. The sera in question were such ones of a particularly well defined group of patients with unique parenteral source of infections. Though further ALAT attacks were observed, in none of the NANBH-sera HBV-DNA was proved as a sign of an active HBV-replication. This, like the absence of an immunity against the NANBH-virus after HBV-disease and the observed suppression of the HBV-DNA in NANBH-superinfection of HBV-carriers (virus interference), speaks against the hypothesis of a close genetic relationship between the two viruses.

Adult↗
PubMed1989

[Differential diagnosis of drug-induced liver damage. Problems and conclusions from the viewpoint of the clinician].

Our analysis showed that in of more than 80% of the patients admitted to the infection hospital because of suspicion of viral hepatitis there is also an anamnesis of one or several drugs. Among 2944 patients, admitted with being suspect of having viral hepatitis, there were 128 patients (adequate to 4.4%) with a drug-induced liver injury diagnosed in the result of all clinical, serological, histological and immunological findings. Inducing noxes were - in accordance to the frequency of ordination - ovulation inhibitors followed by Berlocombin, Ketazon, Depressan and Obsidan. In view of a clinic for infectious diseases it has to be pointed to the necessity of a high degree of security in the differential diagnosis of the drug-induced liver injury in relation to the viral hepatitis and one has to consider the great responsibility of the clinician. Often a decision may only be taken in close interdisciplinary collaboration of gastroenterologists, pathologists, epidemiologists and immunologists.

Adolescent↗
PubMed1989

Preparation and biological activity of new substituted antimalarial diaminodiphenylsulfones.

Starting from 4,4'-diamino-diphenylsulfone (DDS) as a lead structure, new 2-substituted analogues as well as new 2-substituted 4-alkylamino-4'-amino diphenylsulfones have been designed and synthetized in different ways. This has led to compounds the inhibitory activity of which against 7,8-dihydropteroic acid synthase of plasmodia and mycobacteria is clearly superior to that of sulfadoxine and in most cases to that of DDS. Of special interest is 4'-amino-4-n-propylamino-2-methyl-diphenylsulfone. Together with inhibitors of 7,8-dihydrofolate reductase in vitro and in vivo it possesses a marked synergistic inhibitory activity against plasmodia. In contrast to DDS in doses up to 200 mg/kg p.o. (cat) no methemoglobin formation is observed. The compound has been selected for further studies.

Animals↗
PubMed1989

Studies on 2,3,N,N'-substituted 4,4'-diaminodiphenylsulfones as potential antimalarial agents.

A series of new 4,4'-diaminodiphenylsulfones substituted at 2 and 3 position and also at primary amino group of the phenyl rings have been synthesized and evaluated for their antimalarial activity against Plasmodium berghei infection in mice. Some of these compounds were active and showed complete inhibition of parasitaemia which included 7a1-7a4, 7b3, 7b4 and 16a at 1 mg/kg i.p. for 4 days and 16a, at 0.3 mg/kg for 4 days. Some compounds tested for their synthetase inhibitory action in cell-free system isolated from P. berghei (7b1, 7b2 and 8b2) were found to be more active than diaminodiphenylsulphone. The difference in order of activity between these in vivo and in vitro tests may be due to differences in their pharmacokinetic properties.

Animals↗
PubMed1987

[Significance of viral hepatitis in a dialysis center for patients and health personnel--a 5-year review].

As a nosocomial infection the virus hepatitis is now as ever of importance in dialysis centres. In a 5-year study (1980-1985) in the dialysis centre of the County Hospital St. Georg Leipzig we found an annual incidence of 14 to 20% in patients and in 25 out of 26 members of the staff signs of an overcome infection could be proved. In these cases above all younger persons with an average age of 31 years were affected about 1.5 years after the beginning of work. For patients the entry into the transplant recipient register retarded by on an average 9.4 months, for patients already registered a transient reincorporation of 12.4 months was the result. Despite the active inoculation against the virus hepatitis B on account of the further existing endangering by the NANB hepatitis and possible inoculation eruptions in the immune-disturbed dialysis patients the observation of a strong hygiene regimen is necessary.

Hepatitis B↗
PubMed1987

A comparative analysis of the synergistic interaction between N1-phenylsulfanilamides and benzylpyrimidines using qsar techniques.

Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N1-phenylsulfonilamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pKa irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N1-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.

Benzyl Compounds↗
PubMed1987

[Typical recurrent disease behavior of NANB hepatitis. A computer-assisted analysis].

1013 ALAT-attacks--in addition to the frequent asymptomatic onset of the disease and the high tendency of chronicity a typical symptom of the non-A, non-B hepatitis--were statistically analysed on 333 patients (of these 216 with uniform parenteral source of infection). 52% of the patients showed a multiphasic course. The aim of the analysis was the exact mathematical description of the attack-behaviour and the discovery of presumed regularities. The investigation of the periodicity of the attacks showed a maxima of spectral density corresponding to a 7-day-rhythm. The trend function of the ALAT-amplitudes in the time-course was assessed as an exponential function. Between mono- and multiphasic ALAT-courses no significant differences existed concerning the clinical picture (icteric--anicteric--subclinical), but as regards the late prognosis the multiphasic courses exhibited highly-significantly more transitions into chronic hepatitis. From the time-serial analysis of the attacks can be deduced for practical application that the reliable detection of non-A, non-B hepatitis cannot be guaranteed with weekly screenings. Screenings at 2-day-intervals which take into consideration the attack-behaviour and the ascertained time of incubation are recommended.

Alanine Transaminase↗