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Biomedical subjects

K Ehrlich

Publications and source records attributed to K Ehrlich.

At least 19 recordsLinked to original sources
PubMed2001

Pluraflavins, potent antitumor antibiotics from Saccharothrix sp. DSM 12931.

The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931. The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations. The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-gamma-pyrone ring system. Pluraflavin E has a carboxyl group in this position. Pluraflavin A has a reactive dimethyl epoxide side chain at position 2 of the anthraquinone-gamma-pyrone aglycon, which may explain the high activity of the antibiotic. The outstanding biological characteristic of pluraflavin A is its powerful, organ-dependent cytostatic action: the IC50 in the colon carcinoma proliferation assay is in the subnanomolar range.

Actinomycetales↗
PubMed1999

Selective cyclo-oxygenase-2 inhibitors aggravate ischaemia-reperfusion injury in the rat stomach.

1. Effects of indomethacin, the selective cyclo-oxygenase (COX)-2 inhibitors NS-398 and DFU, and dexamethasone on gastric damage induced by 30 min ischaemia followed by 60 min reperfusion (I-R) were investigated in rats. Modulation of gastric levels of COX-1 and COX-2 mRNA by I-R was evaluated using Northern blot and reverse transcription-polymerase chain reaction. 2. I-R-induced gastric damage was dose-dependently aggravated by administration of indomethacin (1 - 10 mg kg(-1)), NS-398 (0.4 - 4 mg kg(-1)) or DFU (0.02 - 2 mg kg(-1)) as assessed macroscopically and histologically. 3. Likewise, administration of dexamethasone (1 mg kg(-1)) significantly increased I-R damage. 4. Low doses of 16, 16-dimethyl-prostaglandin(PG)E(2), that did not protect against ethanol-induced mucosal damage, reversed the effects of the selective COX-2 inhibitors, indomethacin and dexamethasone. 5. I-R had no effect on gastric COX-1 mRNA levels but increased COX-2 mRNA levels in a time-dependent manner. Dexamethasone inhibited the I-R-induced expression of COX-2 mRNA. 6. I-R was not associated with a measurable increase in gastric mucosal formation of 6-keto-PGF(1alpha) and PGE(2). PG formation was substantially inhibited by indomethacin (10 mg kg(-1)) but was not significantly reduced by NS-398 (4 mg kg(-1)), DFU (2 mg kg(-1)) or dexamethasone (1 mg kg(-1)). 7. The findings indicate that selective COX-2 inhibitors and dexamethasone markedly enhance gastric damage induced by I-R. Thus, whereas COX-2 has no essential role in the maintenance of gastric mucosal integrity under basal conditions, COX-2 is rapidly induced in a pro-ulcerogenic setting and contributes to mucosal defence by minimizing injury. This suggests that in certain situations selective COX-2 inhibitors may have gastrotoxic effects.

Animals↗
PubMed1998

Back pain in primary care. Patient characteristics, content of initial visit, and short-term outcomes.

STUDY DESIGN: Prospective study of patients making primary care visits for back pain. OBJECTIVE: To examine the content of primary care visits for back pain in patients with little interference of pain with activities at the visit and 1 month later; high interference of pain with activities at the visit but not 1 month later; and high interference of pain with activities, both at the visit and 1 month later. SUMMARY OF BACKGROUND DATA: Advice about resumption of activities may be therapeutic for patients with back pain, but little is known about the extent to which primary care providers assess and respond to limitation of activities in patients. METHODS: Audiotapes of primary care visits for back pain were coded for content. Patients indicated their goals for the visit and completed measures of pain and the pain's interference with activities, just before the visit and 1 month later. RESULTS: In most visits, providers did not assess functional limitations related to pain and did not discuss how to resume normal activities, although this was a highly rated goal for most patients. Providers did not appear to assess or respond to patients differently according to how much pain interfered with their activities. However, in patients with high interference of pain with activities, there was more discussion of limitation of activities and how to return to usual activities among those who improved than there was among those who did not improve during the next month. CONCLUSIONS: Although back pain frequently is associated with limitation of activity, pain's interference with activities is assessed inconsistently in primary care visits.

Activities of Daily Living↗
PubMed1998

Selective cyclo-oxygenase-2 inhibitors and their influence on the protective effect of a mild irritant in the rat stomach.

1. The effects of the non-selective cyclo-oxygenase (COX) inhibitor indomethacin and the selective COX-2 inhibitors, N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulphonamide (NS-398), 5-methanesulphonamido-6-(2,4-difluorothio-phenyl)-1-indan one (L-745,337) and 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone (DFU), on the protection induced by the mild irritant 20% ethanol were investigated in the rat stomach. 2. Instillation of 20% ethanol (1 ml, p.o.) effectively protected against gastric mucosal injury induced by subsequent instillation of 70% or 96% ethanol (1 ml, p.o.). 3. Oral administration of indomethacin (1.25-20 mg kg[-1]) dose-dependently counteracted the protective effect of 20% ethanol (ID50: 3.5 mg kg[-1]). 4. Likewise, NS-398 (0.1-1 mg kg[-1]), L-745,337 (0.2-2 mg kg[-1]) and DFU (0.02-0.2 mg kg[-1]) inhibited the protective effect of 20% ethanol in a dose-dependent manner with ID50 values of 0.3 mg kg(-1), 0.4 mg kg(-1) and 0.06 mg kg(-1), respectively. 5. Inhibition of mild irritant-induced protection was also found when NS-398 (1 mg kg[-1]) was administered s.c. or when 96% ethanol was used to damage the mucosa. 6. Pretreatment with 16,16-dimethyl-prostaglandin (PG)E2 at 4 ng kg(-1), a dose that did not protect against ethanol (70%)-induced mucosal damage when given alone, completely reversed the effect of the selective COX-2 inhibitors on the mild irritant-induced protection. 7. Pretreatment with dexamethasone (3 mg kg(-1), 24 and 2 h before instillation of 20% ethanol) did not affect the protective activity of the mild irritant, indicating that enzyme induction is not involved. 8. Indomethacin (20 mg kg(-1), p.o.) did not prevent the protection conferred by sodium salicylate (100 mg kg[-1]), dimercaprol (30 microg kg[-1]), iodoacetamide (50 mg kg[-1]) and lithium (20 mg kg[-1]). Likewise, the protective effect of these agents was not counteracted by NS-398 (1 mg kg(-1), p.o.). 9. Whereas indomethacin (20 mg kg(-1), p.o.) near-maximally inhibited gastric mucosal formation of PGE2, 6-keto-PGF1alpha and thromboxane (TX) B2 as well as platelet TXB2 release, the selective COX-2 inhibitors were ineffective. 10. The findings show that selective COX-2 inhibitors, although lacking in ulcerogenic activity, prevent the protection conferred by a mild irritant. Prostaglandis generated by a constitutive COX-2 could thus contribute to physiological functions involved in gastric homeostasis, although at present a non-COX-2-related mechanism underlying the effect of the selective COX-2 inhibitors tested on mild irritant-induced protection cannot be completely excluded.

16,16-Dimethylprostaglandin E2↗
PubMed1998

Peptidergic and cholinergic neurons and mediators in peptone-induced gastroprotection: role of cyclooxygenase-2.

This study investigates the neural pathways, mediators, and cyclooxygenase isoenzymes involved in the gastroprotection conferred by peptone in rats. Intragastric perfusion with 8% peptone protected against gross and histological damage induced by subsequent perfusion with 50% ethanol. The gastroprotective effect of peptone was near maximally inhibited by gastrin immunoneutralization, inactivation of capsaicin-sensitive afferent neurons, calcitonin gene-related peptide (CGRP) immunoneutralization, blockade of gastrin receptors, CGRP, bombesin/gastrin-releasing peptide (GRP), or somatostatin receptors, and by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester and was partially (46%) counteracted by atropine. Indomethacin and the selective cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated the peptone-induced protection. Dexamethasone was ineffective. These results indicate that protective effects of peptone involve endogenous gastrin and possibly somatostatin and are mediated by capsaicin-sensitive afferent, cholinergic, and bombesin/GRP neurons. CGRP, NO, and prostaglandins participate as essential mediators. The study provides evidence that prostaglandins derived from a constitutive cyclooxygenase-2 contribute to mucosal defense in the presence of ulcerogens and thus participate in homeostatic functions of the stomach.

Animals↗
PubMed1991

Flow cytometric analysis of Eimeria tenella sporozoite populations exposed to salinomycin sodium in vitro: a comparative study using light and electron microscopy and an in vitro sporozoite invasion-inhibition test.

Eimeria tenella sporozoites exposed to 100, 70, 60 and 50 micrograms salinomycin sodium (SAL)/ml medium 199 at 41 degrees C and then stained with propidium iodide/fluorescein diacetate were analysed by means of flow cytometry (FCM). After 20 min exposure, they showed dose-dependent alterations in their size and shape, i.e. ballooning of most cells, and enhanced intracellular esterase activity as compared with untreated controls. After longer exposure periods (40 and 70 min), inflated cells gradually changed into shrivelled or crumpled, nonviable ones, thereby showing a gradual decrease in esterase activity and a gradual loss of membrane integrity (RFA+). As compared with untreated controls, sporozoites treated with 10 micrograms SAL/ml showed negligible RFA+ values (0.4%-2%), whereas those exposed to 1 and 0.1 microgram SAL ml and to the solvent dimethylsulfoxide (DMSO, 1%) did not, even after 70 min exposure. Slight to severe structural changes manifesting as an extremely wavy surface (1 microgram SAL/ml), vacuolization of the cytoplasm, distension or destruction of the mitochondrion and rupture of cell membranes (10 micrograms SAL/ml) were seen not only at higher SAL concentrations but also (rarely) at lower ones. The ability of sporozoites to invade primary chick-kidney cells was significantly inhibited by 70, 60 and 50 micrograms SAL/ml. In general, there were close relationships between findings obtained using FCM, electron microscopy and an invasion-inhibition test. The results indicate that FCM is a reliable and sensitive technique for characterizing the parasiticidal effects on and the possible mode of action of drugs in free coccidian sporozoites.

Animals↗
PubMed1987

Effect on aflatoxin production of competition between wild-type and mutant strains of Aspergillus parasiticus.

Co-cultivation of a strain of Aspergillus parasiticus, capable of making aflatoxins, with blocked mutant strains, capable of producing none or only a low level of aflatoxins, reduced the net yield of aflatoxins more than that expected based on spore recovery. Yields of aflatoxins were 8-fold less for a norsolorinic acid-producing strain, 14-fold less for an averantin-producing strain, 6-fold less for an averufin-producing strain, and 21-fold less for a versicolorin A-producing strain when co-cultured in equal amounts with a wild-type strain of Aspergillus parasiticus. Even when the wild-type strain was initially present in 100-fold excess, with two of the mutant strains, reduced aflatoxin production was still observed.

Aflatoxins↗
PubMed1985

Effect of phytate on aflatoxin formation by Aspergillus parasiticus grown on different grains.

Aflatoxin production by Aspergillus parasiticus on corn, soybean, and cottonseed in the absence or presence of added sodium phytate was examined. No variation in aflatoxin concentrations was found in raw, chemically sterilized, or autoclaved soybeans whereas a five-fold reduction in total aflatoxins was found in cottonseed after addition of 330 micrograms sodium phytate to 10 g of autoclaved material. However, phytate did not affect aflatoxin production on non-sterile cottonseeds, although in corn a slight inhibition was found. Extraction of raw soybeans with hexane allowed production of 20-fold more aflatoxins, but levels were still lower than those found on rice or corn. Part of this relative inhibition in soybeans may arise from a heat-unstable, polar solvent-soluble, dialyzable factor present in soybeans. Our results support the conclusion that phytate is not the factor in soy responsible for its relative resistance to aflatoxin formation.

Aflatoxins↗
PubMed1985

Biosynthetic relationship among aflatoxins B1, B2, M1, and M2.

Aflatoxins are a family of toxic, acetate-derived decaketides that arise biosynthetically through polyhydroxyanthraquinone intermediates. Most studies have assumed that aflatoxin B1 is the biosynthetic precursor of the other aflatoxins. We used a strain of Aspergillus flavus which accumulates aflatoxin B2 to investigate the later stages of aflatoxin biosynthesis. This strain produced aflatoxins B2 and M2 but no detectable aflatoxin B1 when grown over 12 days in a low-salt, defined growth medium containing asparagine. Addition of dichlorvos to this growth medium inhibited aflatoxin production with concomitant accumulation of versiconal hemiacetal acetate. When mycelial pellets were grown for 24, 48, and 72 h in growth medium and then transferred to a replacement medium, only aflatoxin B2 and M2 were recovered after 96 h of incubation. Addition of sterigmatocystin to the replacement medium led to the recovery of higher levels of aflatoxins B2 and M2 than were detected in control cultures, as well as to the formation of aflatoxins B1 and M1 and O-methylsterigmatocystin. These results support the hypothesis that aflatoxins B1 and B2 can arise independently via a branched pathway.

Aflatoxin B1↗
PubMed1984

Effect of phytate on aflatoxin formation by Aspergillus parasiticus and Aspergillus flavus in synthetic media.

The effect of phytate on the production of aflatoxins by Aspergillus parasiticus and Aspergillus flavus grown on synthetic media was examined. In the absence of pH control (initial pH 4.5-6.5) for A. parasiticus, phytate (14.3 mM) caused a six-fold decrease in aflatoxins in the medium and a ten-fold decrease in those retained by the mycelia. When the initial pH of the medium was adjusted to 4.5 no effect on aflatoxin production was observed. With A. flavus or A. parasiticus grown on media with a higher initial pH value (6 to 7), the presence of phytate in the media caused an increase in aflatoxin production. These results are inconsistent with previous studies which indicated that phytate depresses aflatoxin production by rendering zinc, a necessary co-factor for aflatoxin biosynthesis, unavailable to the mold.

Aflatoxins↗
PubMed1980

A comparative study of proteoglycans from bovine lung, trachea, tracheal mucosa, and aorta.

Proteoglycans were isolated from bovine lung, trachea, tracheal mucosa, and aorta by dissociative extraction with 4M guanidinium hydrochloride. Fractionation of these tissue extracts by cesium chloride density centrifugation and gel chromatography allowed the isolation from each extract of a high molecular weight fraction consisting mainly of proteochondroitin sulfate and hyaluronic acid.

Animals↗
PubMed1980

Mammalian cell culture mutagenicity and carcinogenicity testing of dimethyl sulfoxide extracts of flame retardant-treated cotton fabrics.

Dimethyl sulfoxide extracts of flame retardant-treated cotton fabrics were tested for ability to mutate and transform mammalian cells in culture. Fabrics were treated with tetrakis(hydroxymethyl)phosphonium chloride (THPC) and tetrakis(hydroxymethyl)-phosphonium sulfate (THPS). Extracts were prepared at the precondensate stage of flame retardant processing and after ammonia neutralization (THPOH-NH3). Unconcentrated or 10-fold concentrated extracts were tested as 0.5 or 1% solutions in cell culture medium. All extracts were mutagenic to V79 hamster lung cells (conversion to ouabain resistance) with or without addition of rat liver microsomes (S9). Up to 84 mutant colonies per 10(6) surviving cells were found with THPS fabric extracts, whereas up to 113 were obtained with THPC fabric extracts. Extracts were also able to transform mammalian cells, as shown in two different assays. Transformation of BHK cells, as measured by colony formation in soft agar, increased more than 20-fold with THPC extracts, but less than 2-fold with THPS extracts. Both the THPC and THPS extracts induced 3T3 cell transformation with linear dose-response. The number of foci of transformed cells per 10(5) survivors was 10--100 times that in the solvent control. Greater numbers of transformed foci were obtained after treatment at the highest doses tested than after treatment with the positive control compounds, benzo[a]pyrene and N-methyl-N-nitro-N-nitrosoguanidine.

Animals↗
PubMed1980

Isolation and characterization of acylneuraminate cytidylyltransferase from frog liver.

Frog liver (Rana esculenta) is a rich source of acylneuraminate cytidylyltransferase. The soluble enzyme was purified 250-fold almost to purity with 25% yield and a specific activity of 9 mkat/kg protein (0.54 U/mg protein) using DEAE Sephadex and Sepharose 6B chromatography, followed by preparative polyacrylamide gel electrophoresis. The molecular weight of the cytidylyltransferase was determined to be 163 000 with the aid of Sepharose 6B chromatography and gel electrophoresis, with or without dodecyl sulphate or urea. No subunits were found. The isoelectric point of the enzyme is at pH 6. Optimum reaction rate was observed at pH 9, 37 degrees C, 50mM Mg2 or Ca2 and ImM mercaptoethanol. The Km values for N-acetylneuraminic acid, N-glycoloylneuraminic acid and CTP are 1.6mM, 2.3 mM and 0.6mM, respectively. O-Acetylated sialic acids are inactive with the cytidylyltransferase from frog liver. Enzyme activity can be inhibited by SH reagents and CMP (Ki = 0.5mM).

Animals↗
PubMed1980

Osmotic concentration of polypeptides from hemofiltrate of uremic patients.

Hemofiltrate from uremic patients was concentrated 15- to 40-fold by osmotic removal of water across a reverse osmosis membrane which retains salts and proteins. Salts and low molecular weight components were removed from the concentrate by partial dialysis using a highly impermeable cellulose membrane. Following this desalting step, 100- to 500-fold concentration could be achieved by evaporation at low pressure. The concentrate was fractionated on Sephadex G15 columns. Fractions were tested for their toxicity to human cells in culture. Fractions containing components with molecular weights greater than 700 daltons inhibited 3H-thymidine incorporation into the DNA of HeLa and skin fibroblast cells more than did low molecular weight peptides and an iso-osmolar control. Components eluting in the molecular weight range of angiotensin I and vitamin B-12 were most inhibitory. These studies show that hemofiltrate from uremic patients is a readily available source of toxic polypeptides. The osmotic concentration and gel chromatographic procedures described should make available large amounts of these molecules for further studies.

Animals↗
PubMed1979

Separation of six DNA bases by ion pair--reversed phase high pressure liquid chromatography.

An ion pair-reversed phase chromatography system is described which separates six of the bases normally found in prokaryotic and/or eukaryotic DNA from each other and from uracil, the characteristic base found in RNA. The effect of varying pH and the percentage of methanol in the column buffer is described. The addition of the ion-pairing reagent heptane sulfonate was shown to be necessary to achieve separation of all of these bases.

Base Composition↗