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Biomedical subjects

H Hänel

Publications and source records attributed to H Hänel.

At least 19 recordsLinked to original sources
PubMed2003

Epidemiology, clinical manifestations and diagnosis of zoonotic cestode infections: an update.

This paper reviews the literature on zoonotic cestode infections with specific reference to the years 1999-2003. The sources and prevalence of various zoonotic tapeworm infections caused by adult and larval stages of the genera Taenia, Echinococcus, Diphyllobothrium, Hymenolepis and Dipylidium continue to be an important cause of morbidity and mortality, not only in most underdeveloped countries but also in industrialized countries, particularly in rural areas or among immigrant groups from endemic areas. The review gives a detailed report on recent molecular epidemiological studies on the taxonomy and phylogenetic variations in Echinococcus granulosus, immunological tests and imaging techniques used in epidemiological surveys and clinical investigations of important adult and larval tapeworm infections of animals and humans. Larval stages or metacestodes of Taenia solium, Echinococcus spp. and pseudophyllidean tapeworms (Spirometra syn. Diphyllobothrium spp.) may reside in various tissues of their intermediate hosts, including humans. In particular, Cysticercus cellulosae (T. solium) and the larvae of E. granulosus, and E. multilocularis, which are predominantly located in the liver, lungs and central nervous system forming various types of cysts, lead to a complex of systemic diseases such as cysticercosis, cystic echinococcosis and alveolar echinococcosis, respectively. Relatively rare clinical manifestations are seen in the muscles, subcutaneous tissue, spleen, kidneys, bones and body cavities.

Animal Diseases↗
PubMed2003

Nitroheterocyclic drugs with broad spectrum activity.

The group of biologically active nitroheterocyclic compounds includes various 5- and 2-nitroimidazoles and 5-nitrofurans, which can be used as therapeutic agents against a variety of protozoan and bacterial (anaerobic) infections of humans and animals. The current status in the the treatment of giardiasis, trichomoniasis, balantidiasis, histomoniasis, and amebiasis (including infections due to opportunistic amebas) is presented. The most relevant drugs (benznidazole, furazolidone, metronidazole, misonidazole, nifurtimox, nimorazole, nitazoxanide, ornidazole, secnidazole, and tinidazole) are characterized with regard to their chemical, chemotherapeutic, toxicological, pharmacokinetic, and pharmacological properties, including the mechanism of action and resistance in certain parasitic protozoa.

Animals↗
PubMed1995

Modification of cisplatin-induced renal p-aminohippurate uptake alteration and lipid peroxidation by thiols, Ginkgo biloba extract, deferoxamine and torbafylline.

To determine whether inhibition of lipid peroxidation modifies cisplatin-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplatin-induced lipid peroxidation and PAH accumulation changes in rat renal cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of either glutathione, N-acetylcysteine, the iron chelator deferoxamine, Ginkgo biloba extract or the xanthine derivate torbafylline. Lipid peroxidation monitored as the production of malondialdehyde (MDA) was stimulated by increasing cisplatin concentrations in a dose-related manner. At a cisplatin concentration of 1.0 mg/ml, MDA production was twofold compared to controls (0.69 +/- 0.06 vs. 1.36 +/- 0.07 nmol/mg; p < 0.05). In turn, cisplatin decreased PAH uptake of kidney slices dose-dependently from 13.3 +/- 1.3 to 2.6 +/- 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplatin concentration of 1.0 mg/ml, none of them prevented the decline of cisplatin-induced PAH uptake. Of the agents tested, deferoxamine proved to be the most effective antioxidant, completely inhibiting cisplatin-induced lipid peroxidation but in contrast preventing the decrease in PAH uptake only at a cisplatin concentration of 0.3 mg/ml. No strict association between lipid peroxidation and decline of PAH uptake was found, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.

Acetylcysteine↗
PubMed1994

Effects of rilopirox on rabbit blastocysts in a protein-free in vitro culture under different culture conditions.

The effect of rilopirox (Hoe 351, CAS 104153-37-9) on rabbit blastocysts in vitro was studied. Blastocysts of day 6 post coitum were cultured in Ham's F 10 medium supplemented with polyvinylpyrrolidone using different concentrations of rilopirox with and without serum proteins. In culture conditions without serum proteins there were no differences in the growth rates of the blastocysts after 24 h of culture in the presence of 1 microgram/ml of rilopirox. However, 5 micrograms/ml of rilopirox resulted in a significant reduction of the mean growth rate as well as in a serious morphological damage of the treated blastocysts. Purified human serum albumin could partly prevent this toxic effect, while complete human serum and foetal calf serum did not show this characteristic. Analyses of the protein synthesis of the blastocysts treated with rilopirox by two-dimensional gel electrophoresis and subsequent fluorography did not show any differences in comparison to the untreated controls, despite of obvious morphological alterations.

Animals↗
PubMed1991

Quantification of keratinolytic activity from Dermatophilus congolensis.

The bacterium Dermatophilus congolensis is the causative agent of pitted keratolysis, a skin disease. Infection occurs mainly in keratinized tissues and it is necessary for the organism to produce and excrete exoenzymes which are able to degrade keratin. We investigated the amount of keratinase liberated using Keratinazure as substrate and the fungal protease XI as standard. When compared with uninoculated samples, D. congolensis liberated significant amounts of keratinase during a 12-day incubation period with this substrate. An equivalent of 15 units of protease (keratinase) was produced by 10(7) colony-forming units of D. congolensis during a 12-day period at 37 degrees C. We consider the extracellular proteolytic activity of this bacterium to be responsible for keratinized tissues being the main sites of infection.

Actinomycetales↗
PubMed1991

Studies for the elucidation of the mode of action of the antimycotic hydroxypyridone compound, rilopirox.

Rilopirox is a synthetic, fungicidal antimycotic agent with hydrophobic characteristics. Its chemical name is 6-[4-(4-chlorophenoxy)-phenoxy-methyl]-1-hydroxy-4-methyl-2-pyridone and it has a molecular weight of 357.79. Rilopirox is very soluble in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) but poorly soluble in water. The amount of antimycotic agent remaining in the solution is dependent on the final concentration of the solvent and the amount of rilopirox used. Complexometric studies show that rilopirox has a high affinity for iron ions [unpubl. data]. Catalase, an iron-containing enzyme, is inhibited by the chelating agent rilopirox. Studies on yeast mitochondria and submitochondrial particles show that rilopirox inhibits the respiratory chain. Complex I (NADH-ubiquinone oxidoreductase) contains iron-sulfur proteins and is the main system which is inhibited.

Antifungal Agents↗
PubMed1991

Ciclopirox nail lacquer 8%: in vivo penetration into and through nails and in vitro effect on pig skin.

This report presents original methods to assess the bioavailability of an antifungal drug from a varnish preparation in finger nails. For the studies with human volunteers a ciclopirox 8% nail lacquer was used to determine its efficacy in the treatment of onychomycoses. In vivo studies were performed on the fingernails of healthy volunteers by determining the total amount of ciclopirox penetrated per milligram of nail and the partition of the drug in the plate of the nails (technically divided into four layers). Ciclopirox concentrations were evaluated by measuring the inhibition of Candida pseudotropicalis growth in vitro. The ciclopirox concentration after 30 days treatment was determined as 3.35 +/- 0.82 micrograms/mg nail material. This is a sufficient amount to kill the fungal pathogens. In addition, in vitro penetration experiments were carried out with excised pig skin. Lacquer formulations from 0.5 to 8% were used to inhibit the growth of Trichophyton mentagrophytes. Formulations from 2 to 8% led to a strong to total inhibition of the dermatophyte after 30 min treatment time.

Administration, Topical↗
PubMed1991

Ciclopiroxolamine cream 1%: in vitro and in vivo penetration into the stratum corneum.

Studies were conducted to assess the penetration of 1% ciclopiroxolamine cream, establishing the concentrations of the antimycotic compound in different layers of the stratum corneum with two skin models. Results of in vitro studies using skin from domestic pigs indicate that ciclopiroxolamine has the ability to penetrate fast into the epidermis, by inhibiting and killing inoculated Trichophyton mentagrophytes. In vivo investigation of the stratum corneum has been performed in healthy human volunteers by 20 strippings collected in four layers. Fungicidal concentrations of ciclopiroxolamine were determined after extraction from the strippings. These studies demonstrate that the concentrations reached levels which are sufficient to inhibit and kill pathogenic fungi.

Administration, Topical↗
PubMed1991

[Therapy of seborrheic eczema with an antifungal agent with an antiphlogistic effect].

Numerous AIDS patients show the typical seborrheic eczema in a very prominent way. For this is an inflammatory disease, combination preparations were taken frequently which contain antimycotics and corticosteroids. We investigated 7 antimycotic compounds in 3 inflammatory models: amorolfin, ciclopiroxolamine (cic), fluconazole, ketoconazole, miconazole, naftifine, and rilopirox. In an in vitro model the inflammatory activity towards the 5-lipoxygenase was investigated. 1,000 mumol naftifine, 100 mumol ketoconazole, 50 mumol cic, and 10 mumol rilopirox inhibited 5-HETE by 90%. In a cell culture model only cic had a significant activity towards cyclo-oxygenase. In this model the inhibition of the prostaglandin E2 liberation by 1 mumol cic was 40%. In an in vivo model the anti-inflammatory activity on a mouse ear was investigated (arachidonic acid induced). In this model only cic showed a significant inhibition of inflammation (50%) at 1 mg/ear. These investigations show, that cic has a strong antiphlogistic activity. In an open clinical trial with 20 patients suffering from seborrheic eczema after 4 weeks on cic cream a strong inhibition of infiltration and flakiness had been observed. The antimycotic compound cic offers a possibility to treat inflammatory mycoses without using corticosteroid combinations. In a double blind clinical trial (tinea) where cic was compared with a cic/hydrocortisone combination no statistical differences were found.

Anti-Inflammatory Agents↗
PubMed1990

Experimental dermatophytosis in nude guinea pigs compared with infections in Pirbright White animals.

With this investigation we wanted to compare the suitability of two different strains of guinea pigs to evaluate topical antifungals after experimental Trichophyton mentagrophytes infection. The "hairless"-strain was compared with the hairy Pirbright White strain. The infection areas were treated with a skin retention test (application before infection) and two sets of therapy tests (application after infection). In the retention test the different antimycotic compounds led to better gradations. Also, in the two sets of therapy tests the gradations among the compounds were more clearly and more comparable to published results of clinical trials. In the histological investigations the infections in the "hairless" animals developed in a way which is known from dermatophytoses in human skin. In the Pirbright White strain, however, due to the adjacent hair roots, a marked inflammatory reaction of the tissue persisted for 3 weeks which is not observed on human skin of the trunk and extremities. We, therefore, consider the "hairless" strain of guinea pigs to be more suitable than hairy animals for the comparison of topical antimycotics.

Animals↗
PubMed1990

Rilopirox--a new hydroxypyridone antifungal with fungicidal properties.

Rilopirox, 6-[[p-chlorophenoxy)phenoxy]methyl]-1hydroxy-4-methyl-2(1H)-pyrido ne, is a new fungicidal antimycotic with very low water solubility. It was designed to meet the demand for an intravaginal antifungal with a long skin retention time and a strong killing effect on pathogenic yeasts. In addition, it inhibits all common fungal pathogens in the range 0.98 to 15.6 micrograms/ml. Fungicidal rates vis-à-vis Trichophyton mentagrophytes and Candida albicans under proliferative and non-proliferative conditions are higher than those achieved with common azole and allylamine antifungals. Rilopirox is affected by Fe3+ ions and high concentrations of human serum owing to its chelating activity. The peptone source is of utmost importance to the inhibitory activity of rilopirox whereas the pH value seems to be unimportant so long as it is within the range 5-8.5. Rilopirox appears to meet the demand for an intravaginal antifungal as a result of its very low water solubility of 50 ng/ml and its immediate fungicidal action even under non-proliferative conditions.

Animals↗
PubMed1989

Antimalarial activity of new floxacrine-related acridinedione derivatives: studies on blood schizontocidal action of potential candidates against P. berghei in mice and P. falciparum in vivo and in vitro.

Deoxyfloxacrine derivatives (1-hydrazone: S 83 0083; 1-imine: S 84 7277) and floxacrine derivatives (10-methoxy-floxacrine: L 84 7667; 1-imine: L 84 7693) selected from a series of newly synthesized 3-aryl-7-chloro-3,4-dihydro-1,9(2H,10H)-acridinediones were evaluated for blood schizontocidal activities in mice infected with asexual stages of various drug-resistant lines of P. berghei and in New World monkeys infected with blood schizonts of different chloroquine-resistant strains of P. falciparum. All compounds tested showed high activity against drug-resistant lines of P. berghei (ED50: 1.0-4.4 mg/kg x 5, per os) and were distinctly superior in their antimalarial potency to floxacrine. Compounds L 84 7667 and L 84 7693 proved to be highly active against the FCBR strain of P. falciparum in vitro (IC50: 0.73-1.78 nmol); they effected temporary clearance of parasitemias due to the Palo Alto strain of P. falciparum in squirrel monkeys at oral doses of 15 mg/kg given daily for 5 consecutive days. Compounds S 83 0083 and S 84 7277, showing moderate in vitro effects (12.9-24.8 nmol), cleared parasitemias of the FCBR strain of P. falciparum in owl monkeys at oral doses of 20 mg/kg (S 84 7277) given daily for 5 or 7 consecutive days (follow-up period, 17 and 30 days, respectively) or at doses of 20 mg/kg (x 4) (S 83 0083) followed by doses of 40 mg/kg (x 3) within a follow-up period of 30 days. These observations suggest that the range of doses required for the cure of established P. falciparum infections is probably too large to cover infections with strains of the least susceptibility and might evoke toxic reactions by the potential candidates tested.

Acridines↗
PubMed1989

[The significance of yeasts in seborrheic eczema].

The high prevalence of seborrheic dermatitis in HIV-infected subjects has led to intensified the discussion of the etiopathogenesis of this dermatological disease. There is increasing controversy about the significance of Pityrosporum in seborrheic dermatitis. On the other hand, recent clinical and experimental data favor the role of intestinal candidiasis in seborrheic dermatitis: a high quantity of Candida in the feces of the affected patients, elevated phospholipase activity of the Candida sp. with special pathogenic relevance for mucosal adhesion and fast and long-lasting regression of seborrheic dermatitis after vigorous therapy with oral nystatin. Similar findings have been recorded in the seborrheic forms of psoriasis.

Candidiasis↗
PubMed1989

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 3rd communication: influence on host resistance to microorganisms, tumors and on experimental immune disorders.

To evaluate the influence of [2-(3-carboxy-1-probylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) on the host defense mechanisms, a number of experimental studies in different animal models were performed. The prophylactic treatment of NMRI mice with tiprotimod significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 and increased the resistance to the fungal infection to 180% in comparison to controls. In vitro the drug showed no direct fungistatic or fungicidal activity. In an experimental model of persistent systemic candidiasis Balb/c mice infected intravenously with Candida albicans were treated with the immunomodulator tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment of the mice after the infection resulted in a reduction of the infectious load and the abscess formation in kidney as well as in a decrease of numbers of yeasts in the urine. In the syngeneic B16 melanoma tumor model tiprotimod significantly prolonged the medium survival time and reduced the number of visuable metastases in the lungs even when applied after resection of the primary tumor graft. Tiprotimod also beneficially influenced the course of the disease in two murine graft-vs-host models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B cell mediated autoimmune disease with fatal outcome. The application of the drug in the induction phase mitigated the development of the diseases and prevented animals from dying.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1988

Evaluation of fungicidal action in vitro and in a skin model considering the influence of penetration kinetics of various standard antimycotics.

Ciclopiroxolamine (Loprox) was the first representative of hydroxpyridones to be developed as a topical antifungal. In the microtitration test and in a skin model using excised skin prices of slaughtered pigs, the fungistatic and fungicidal activity as well as the penetration kinetics of ciclopiroxolamine and ciclopirox were compared with those of the azole compounds bifonazole, clotrimazole, econazole, miconazole, oxiconazole, and tioconazole, and with other antimycotics such as naftifine, sulbentine, tolciclate, and tolnaftate. Clotrimazole had an in vitro inhibitory activity superior to that of the hydroxypyridone ciclopiroxolamine; the latter compound, however, exhibited faster penetration and higher inhibitory or fungicidal activity than the azoles and other antimycotics in the pig skin model. Studies of cream formulations with antimycotics at the bottom layer of the stratum corneum (close to the stratum granulosum) showed that ciclopiroxolamine cream had the most prominent inhibitory effect (93%) and the highest fungicidal activity (98%). The other antimycotics tested exhibited growth inhibition rates of 50% or less and lower fungicidal rates. Inoculated pig skin was treated with lacquer formulations to show that ciclopirox completely inhibited the growth of Trichophyton mentagrophytes, whereas the clotrimazole-treated samples allowed only 0.47% growth. The fungicidal activity of lacquer formulations was 99% for ciclopirox and around 90% for most of the azoles on the pig skin model. The necessity of models tackling the complex penetration kinetics in human skin was discussed.

Animals↗
PubMed1988

Effect of a killer toxin of yeast on eucaryotic systems.

The Saccharomyces cerevisiae killer toxin KT 28, which inhibits sensitive yeasts, was shown to have no effect on several pathogenic fungi or on the protozoan Trichomonas vaginalis. At concentrations of about 0.1 mg/ml, a partial inhibition of the skin pathogenic fungi Trichophyton rubrum and Microsporum canis was observed at pH 6.5. No pharmacological activity was detected in various tests with several animal organs.

Journal Article↗