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Biomedical subjects

G Höfle

Publications and source records attributed to G Höfle.

At least 37 records · Page 2Linked to original sources
PubMed1997

Quinolones and their N-oxides as inhibitors of mitochondrial complexes I and III.

4(1H)-quinolones (2-alkyl- (1), 2-alkyl-3-methyl- (2), 2-methyl-3-alkyl- (3), 1-hydroxy-2-methyl-3-alkyl- (4) and 1-hydroxy-2-alkyl- (5)) with n-alkyl side chains varying from C5 to C17 have been synthesized and tested for biological activity in mitochondrial complexes. Whereas all quinolones were efficient inhibitors of electron transport in the cytochrome b/c1-complex from either beef heart or Rhodospirillum rubrum, in complex I from beef heart quinolones 1 and 2 only were highly active. In a Quantitative Structure-Activity Relationship (QSAR) inhibitory activity in the cytochrome b/c1-complexes could be correlated to the physicochemical parameters lipophilicity pi and/or to STERIMOL L. Maximal inhibitory potency was achieved at a carbon chain length of 12-14 A. Oxidant-induced reduction of cytochrome b established that some quinolones are inhibitors of the Qp rather than the Qn site.

Animals↗
PubMed1997

New onset hypertension after extracorporeal shock wave lithotripsy: age related incidence and prediction by intrarenal resistive index.

PURPOSE: In a recent study we found an increased resistive index immediately after extracorporeal shock wave lithotripsy (ESWL) in patients older than 60 years, which suggests renovascular disturbance. The present 26-month followup study was undertaken to investigate the relevance of elevated resistive index levels and the incidence of new onset hypertension. MATERIALS AND METHODS: Of the initial 76 patients 57, including 20 of the 23 at risk patients 60 or greater years, group 3), were followed for more than 26 +/- 6 months after ESWL. Followup included 2 resistive index measurements by Doppler ultrasound of the treated and the contralateral kidney, at least 2 blood pressure measurements 1 week apart and excretory urography as well as determination of plasma renin activity in 9 patients. RESULTS: With 1 exception, elevated resistive index levels and hypertension were observed exclusively in patients older than 60 years. In these patients the resistive index ranged between 0.65 and 0.86 (mean plus or minus standard deviation 0.74 +/- 0.05, normal less than 0.7). This increase in resistive index was statistically significant (p < 0.0001). Compared to the levels obtained immediately after ESWL, the resistive index continued to increase in all 9 patients older than 60 years who had hypertension (45%), whereas in the normotensive patients the resistive index was either stable or decreased. There was a strong positive correlation (0.903) between pathological resistive index levels and blood pressure. CONCLUSIONS: Patients older than 60 years are at risk for disturbances of renal perfusion as assessed by the resistive index, and 45% of these patients have new onset hypertension within 26 months of treatment.

Adolescent↗
PubMed1997

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up.

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.

Absorptiometry, Photon↗
PubMed1996

Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties.

An antifungal activity against Mucor hiemalis was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce90. The activity was excreted into the supernatant during the log and early stationary phase. When the adsorber resin XAD-16 was added to the culture, the active metabolites were quantitatively bound to the resin. The epothilons showed a high cytotoxicity for animal cells and mimic the biological effects of taxol (BOLLAG et al., Cancer Res. 55: 2325 approximately 2333, 1995).

Animals↗
PubMed1995

Endocrine ophthalmopathy in a patient under continuous immunosuppressive therapy after cardiac transplantation.

We present the case of a female patient who has been on immunosuppressive therapy consisting of cyclosporin A and prednisolone for 9 years because of heterotopic (auxiliary) heart transplantation in 1984. In 1992 the patient developed Graves' disease followed by endocrine ophthalmopathy class IV 1 year later. To our knowledge this is the first report on Graves' disease with subsequent severe endocrine ophthalmopathy in a patient under immunosuppressive treatment with cyclosporin A and prednisolone in doses that effectively prevent heart transplant rejection. Prednisolone, which is used as a first line treatment of endocrine ophthalmopathy, and cyclosporin A, both inhibit T cell function. However, in this patient they were not effective in preventing the development of Graves' disease with subsequent endocrine ophthalmopathy, both of which are autoimmune diseases.

Adult↗
PubMed1995

Chondramides A approximately D, new antifungal and cytostatic depsipeptides from Chondromyces crocatus (myxobacteria). Production, physico-chemical and biological properties.

Novel depsipeptides, named chondramides were produced at levels up to 4.3 mg/liter by several myxobacteria of the genus Chondromyces. The compounds are structurally closely related to jaspamide/jasplakinolide from marine sponges of the genus Jaspis. Initially the chondramides were detected in acetone extracts of the biomass of Chondromyces crocatus, strain Cm c2. So far, four structural variants could be characterized, the chondramides A approximately D. They inhibited the growth of a few yeasts and showed high cytostatic activity against cultivated human and animal cells.

Animals↗
PubMed1995

Gephyronic acid, a novel inhibitor of eukaryotic protein synthesis from Archangium gephyra (myxobacteria). Production, isolation, physico-chemical and biological properties, and mechanism of action.

A new antibiotic compound, gephyronic acid was isolated from the culture broth of the myxobacterium, Archangium gephyra strain Ar 3895. Up to 3 mg/liter was produced during the logarithmic and stationary growth phase. The compound is an aliphatic acid, which tends to form a hemiacetal. Both forms inhibited growth of yeasts and molds (MIC 1-25 micrograms/ml) and had a cytostatic effect on mammalian cell cultures (IC50 10-60 ng/ml). Gephyronic acid is a specific inhibitor of eukaryotic protein synthesis showing an IC50 of 1-2 x 10(-7) mol/liter in an in vitro translation assay.

Animals↗
PubMed1995

The tartrolons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum.

New antibiotics were isolated from the culture broth of the myxobacterium, Sorangium cellulosum, strain So ce 678. The antibiotics were active against Gram-positive bacteria and mammalian cells. They were named tartrolon A and B. Tartrolon B contains a boron atom. The boron binding region of tartrolon is identical with that of boromycin and aplasmomycin.

Anti-Bacterial Agents↗
PubMed1995

Disorazol A, an efficient inhibitor of eukaryotic organisms isolated from myxobacteria.

A new antibiotic, disorazol, was isolated from the culture broth of the myxobacterium, Sorangium cellulosum strain So ce 12. It is a macrocyclic compound containing two oxazole rings. The antibiotic acted against many fungi and mammalian cell cultures. The latter responded to extremely low doses (MIC 3-30 pg/ml). None of the tested bacteria and yeasts were inhibited.

Animals↗
PubMed1995

The ripostatins, novel inhibitors of eubacterial RNA polymerase isolated from myxobacteria.

A new antibiotic, ripostatin, was isolated from the culture supernatant of the myxobacterium, sorangium cellulosum strain So ce377. It is a macrocyclic lactone carbonic acid containing an unsubstituted phenyl ring in a side chain. The antibiotic acts especially on Staphylococcus aureus, but seems not to penetrate most bacteria. The MIC values are in the range of 1 microgram/ml. Ripostatin is an inhibitor of eubacterial RNA polymerase. It interferes with the initiation of RNA synthesis.

Anti-Bacterial Agents↗
PubMed1995

Chivosazol A, a new inhibitor of eukaryotic organisms isolated from myxobacteria.

A new antibiotic, chivosazol, was isolated from the culture broth of the myxobacterium Sorangium cellulosum strain So ce12. It is a macrocyclic ring with one oxazol ring and a glycosidically bound 6-deoxyglucose (quinovose) at C-11. The antibiotic shows antimicrobial activity against yeasts and filamentous fungi, and is especially potent against mammalian cells. It was not active against bacteria.

Animals↗
PubMed1995

Ratjadon: a new antifungal compound from Sorangium cellulosum (myxobacteria) production, physio-chemical and biological properties.

An antifungal activity, ratjadon, was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce360. The metabolite was quantitatively bound to the adsorber resin XAD-16, which was added to the medium at the beginning of the fermentation. The antibiotic spectrum was narrow, but some important phytopathogenic fungi, especially species of Oomycetes, were inhibited at very low concentrations.

Animals↗
PubMed1994

Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase.

The effect of ten naturally occurring and two synthetic inhibitors of NADH:ubiquinone oxidoreductase (complex I) of bovine heart, Neurospora crassa and Escherichia coli and glucose:ubiquinone oxidoreductase (glucose dehydrogenase) of Gluconobacter oxidans was investigated. These inhibitors could be divided into two classes with regard to their specificity and mode of action. Class I inhibitors, including the naturally occurring piericidin A, annonin VI, phenalamid A2, aurachins A and B, thiangazole and the synthetic fenpyroximate, inhibit complex I from all three species in a partially competitive manner and glucose dehydrogenase in a competitive manner, both with regard to ubiquinone. Class II inhibitors including the naturally occurring rotenone, phenoxan, aureothin and the synthetic benzimidazole inhibit complex I from all species in an non-competitive manner, but have no effect on the glucose dehydrogenase. Myxalamid PI could not be classified as above because it inhibits only the mitochondrial complex I and in a competitive manner. All inhibitors affect the electron-transfer step from the high-potential iron-sulphur cluster to ubiquinone. Class I inhibitors appear to act directly at the ubiquinone-catalytic site which is related in complex I and glucose dehydrogenase.

Acetobacteraceae↗
PubMed1994

The soraphens: a family of novel antifungal compounds from Sorangium cellulosum (Myxobacteria). I. Soraphen A1 alpha: fermentation, isolation, biological properties.

An antifungal activity was detected in the culture broth of Sorangium cellulosum (Myxococcales), strain So ce26. The activity was excreted into the supernatant during the log and early stationary phase. The active substance was quantitatively bound to XAD absorber resin added to the medium at the beginning of the fermentation. The new secondary metabolite was called soraphen and is of special interest to plant disease control for its inhibitory activity against numerous phytopathogenic fungi.

Antifungal Agents↗
PubMed1994

Crocacin, a new electron transport inhibitor from Chondromyces crocatus (myxobacteria). Production, isolation, physico-chemical and biological properties.

Crocacin was isolated from the biomass of the myxobacterium Chondromyces crocatus, strain Cm c3. It inhibited the growth of a few Gram-positive bacteria and a wide spectrum of yeasts and molds. In beef heart submitochondrial particles, crocacin blocked the electron transport within the bc1-segment (complex III) and caused a red shift in the reduced spectrum of cytochrome b with a maximum at 569 nm.

Anti-Bacterial Agents↗
PubMed1993

Thiazolidine derivatives as source of free L-cysteine in rat tissue.

The present study demonstrates that a variety of thiazolidine-4-(R)-carboxylic acids (TDs) which are the products of reactions of L-cysteine (cys) with carbonyl compounds could serve as a "delivery" system for cys to the cell. Liberation of the amino acid can occur enzymatically as well as non-enzymatically. The two possibilities have been proven by identification of representative compounds. The most specific substrate for mitochondrial enzymatic oxidation was thiazolidine-4-carboxylic acid (CF), the product of the reaction of cys with formaldehyde, and the least metabolized TD was 2-methyl-thiazolidine-4-carboxylic acid (CA), the product of the reaction of cys with acetaldehyde. TDs formed from cys and different sugars were not metabolized at all in mitochondria. N-Formyl-L-cysteine (NFC) the intermediate product of mitochondrial metabolism of CF was ascertained by 1H-NMR spectroscopy whereas N-acetyl-L-cysteine (NAC), the predicted metabolite of CA, was not detected, possibly due to a fast turnover. The further enzymatic hydrolysis of NFC as well as NAC to free cys was demonstrated to take place in the cytoplasm. Non-enzymatic hydrolysis of TDs depended on the chemical nature of the substituents in the thiazolidine (Th) ring. The most stable compound was unsubstituted Th and the least stable were CGlu(D) and CA. Following non-enzymatic ring opening and hydrolysis, CA was converted to methyl-djenkolic acid, which equilibrates with CA. We have identified this new compound by 1H-NMR spectroscopy. TDs may cause both a decrease and an increase in the levels of SH-groups in mitochondria. In the case of the stable CF, which is metabolized only enzymatically, an increase in the levels of SH-groups in mitochondria was observed. This suggests that enzymatic control of the breakdown of TDs prevents overflowing of the cell with thiol groups. The latter seems to be induced by high concentrations of those TDs which are hydrolysed non-enzymatically. This process leads finally to a decrease in free SH-groups by different mechanisms. The findings demonstrate two different mechanisms by which TDs can provide cys to the cells. The biological and pharmacological consequences are discussed.

Animals↗