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Biomedical subjects

N Weger

Publications and source records attributed to N Weger.

At least 37 records · Page 2Linked to original sources
PubMed1979

Nephrotoxicity of aminophenols: effects of 4-dimethylaminophenol on isolated rat kidney tubules.

In isolated rat kidney tubules DMAP was found to inhibit the gluconeogenesis from lactate, pyruvate, or dihydroxyacetone. The ratio DMAP/protein rather than the calculated concentration of DMAP determined the strength of the effect, 20--25 nmoles DMAP/mg protein inhibiting the rate of gluconeogenesis by about 50%. The inhibition was not reversible. Phenacetin, 4-aminophenol and 4-acetamidophenol were much less effective than DMAP in inhibiting gluconeogenesis in isolated rat kidney tubules. DMAP 14C-labeled in the ring was quickly bound to proteins in kidney tubules. A portion of DMAP which did not exceed about 4 nmoles/mg protein, was bound in compounds soluble in perchloric acid. From this portion tris-GS-DMAP was isolated. DMAP diminished the glutathione content of isolated rat kidney tubules. Reduced glutathione added before DMAP prevented the inhibition of gluconeogenesis and diminished the binding of DMAP to proteins. The binding of DMAP required oxygen and was inhibited by carbon monoxide or cyanide. Several enzymes from isolated kidney tubules were found to be inhibited by DMAP doses which inhibited gluconeogenesis. Large DMAP doses also diminished the sums of ATP + ADP + AMP as well as NAD + NADH and NADP + NADPH. This effect corresponded to an increase in nucleotide degradation products and to increased activity of extracellular LDH. The results indicate that the inhibition of gluconeogenesis by DMAP is not due to a specific effect on one enzyme or on membranes but to unspecific reactions with many substances.

Aminophenols↗
PubMed1979

Effects of 4-dimethylaminophenol and Co2EDTA on circulation, respiration, and blood homeostasis in dogs.

The effects of intravenously injected 4-dimethylaminophenol and Co2EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin. A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30--40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase. Co2EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co2EDTA. The side effects of Co2EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.

Acid-Base Equilibrium↗
PubMed1979

Therapeutic effects of the bis-pyridinium salts HGG-12, HGG-42, and atropine, benactyzine in organophosphate poisoning of dogs.

Therapeutic properties of various combinations of the bispyridinium salts HGG-12 and HGG-42 against soman and sarin poisoning were investigated in male beagles. Best therapeutic efficiency was shown by HGG-42 in a dosage of 30 muMol/kg. Also good effects were produced by the combination of both oximes in a low dosage of 3 muMol/kg for each one. In soman poisoning no significant reactivation of cholinesterase in serum or erythrocytes was observed.

Animals↗
PubMed1979

Circulation, respiration, and blood homeostasis in cyanide-poisoned dogs after treatment with 4-dimethylaminophenol or cobalt compounds.

The effects of intravenously injected 4-dimethylaminophenol-HCl (DMAP), Co2EDTA, and Co(histidine)2 on the survival rate and several physiological parameters were studied on dogs after acute intravenous poisoning with the double lethal dose of potassium cyanide. All dogs survived when the antidotes were administered 1 min after poisoning. When the therapy began 4 min after poisoning more dogs were rescued in the DMAP group than in the cobalt groups. DMAP, Co2EDTA, and Co(histidine)2 restored circulation and respiration of the surviving animals in a similar manner. The increase in the plasma concentrations of glucose and lactate was much higher in the Co2EDTA group than in the DMAP group. The injection of Co2EDTA produced a sharp rise in the lactate-to-pyruvate ratio. The lactate-to-pyruvate ratio stayed unchanged for some 15 min after injection of DMAP before also rising. The total dose of KCN (4 mg/kg) was bound to the ferrihemoglobin formed by DMAP. The arterial pO2 increase, caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin, was less when the cyanide could act on the tissues for a longer period of time before the therapy with DMAP began. DMAP is more appropriate for the therapy of cyanide poisoning than Co2EDTA, since the latter adds its inhibitory effects on the metabolism to those of cyanide.

Aminophenols↗
PubMed1977

[Antidotes in acute poisonings].

Inhalation of dexamethazone (Auxiloson) prohibits a toxic edema of the lungs after poisoning with irritants. Poisoning with methanol is to be treated with ethanol trisbuffer and tetrahydrofolic acid (Folsan). "Solvents" should be "bound" in paraffinum liquidum in order to prohibit their absorption. Poisoning with organophosphates is to be treated with high doses of atropine and with the reactivator obidoxime (Toxogonin). Cyanide poisoningis are to be treated with 4-dimethylamino-phenol (DMAP) and sodium thiosulfate. In methemoglobin-poisoning the reduction of ferrihemoglobin is accelerated when toluidine-blue is applied intravenously.

Acute Disease↗
PubMed1977

Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate.

Cyanide in blood, plasma, and urine of dogs after administration of K14CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration. After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 micron cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 micron. Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 micron decreased the cyanide concentration in plasma and restored respiration, while cyanide was accumulated in red cells by formation of ferrihemoglobin cyanide. Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes. Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.

Animals↗
PubMed1977

Hematologic and immunologic studies in dogs given nitrogen mustard (hn3).

Hematologic and immunosuppressive effects of single doses of nitrogen mustard (HN3) were evaluated in 20 dogs. HN3 caused profound depression of peripheral blood counts in all animals. Recovery of total white blood cell counts in dogs surviving the acute gastrointestinal toxicity of HN3 was complete by day 15. Recovery of platelet and lymphocyte counts to initial levels took a more prolonged course. Granulopoietic progenitor cells (CFU-C) in the bone marrow were assayed by an in vitro culture system. Concentrations of CFU-C were markedly decreased one day after HN3-treatment, but showed at near-lethal doses rapid restoration to normal values within 4 to 7 days. Cellular immune function of HN3-treated dogs was impaired for prolonged periods as indicated by the reduced capacity of canine lymphocytes to proliferate in vitro in response to stimulation with mitogens. Humoral immune function was similarly affected as determined by the depressed and delayed antibody formation against an intravenous challenge with sheep red blood cell. In conclusion, our results suggest a different effect of HN3 on lymphoid and myeloid precursor cells.

Animals↗
PubMed1976

Therapeutic effects of HS-3, HS-6, benactyzine, and atropine in soman poisoning of dogs.

Investigations into the therapeutic properties of various combinations of the bispyridinium salts HS-3 and HS-6 and the cholinolytics atropine and benactyzine against soman poisoning in unanesthetized male beagles were performed. In our investigations we observed that: 1. The most effective protection against soman poisoning was attained if both oximes were applied early i.m. 6 min after intoxication together with the cholinolytics. 2. On the basis of clinical symptoms HS-6 proved to have a more intensive therapeutic effect than HS-3 upon early application. 3. If HS-3 was applied early after s.c. intoxication with low concentrations of soman (up to 3 LD50), a significant protection or reactivation effect on serium cholinesterase was measured. 4. When HS-3 was applied at the beginning of convulsions--generally 28 min after s.c. intoxication--it also raised the rate of surviving animals. 5. The maximal blood levels for HS-3 and HS-6 were measured 20-30 min after i.m. injection; the half-life values of HS-3 and HS-6 in plasma were 45-60 min.

Animals↗
PubMed1976

The effect of tris(2-chloroethyl)amine on human hemoglobin.

The reaction of tris(2-chloroethyl)amine (TCEA) with purified hemoglobin and its effect on properties of hemoglobin was studied using 14C-labeled TCEA. Hemoglobin remained soluble after binding as much as 4 TCEA per heme. In concentrations which did not denature hemoglobin TCEA reacted only with a small proportion of the free SH groups; blockade of the SH groups with PMB did not noticeably affect the binding of TCEA to hemoglobin. Hydrolysis by trypsin or chymotrypsin of hemoglobin which had reacted with TCEA yielded radioactive peptides besides not radioactive peptides and radioactive compounds not reacting with ninhydrin. The reaction with TCEA caused a change in electrophoretic mobility of hemoglobin and prevented its complete disintegration by PMB into subunits. After reaction with TCEA the affinity of hemoglobin for oxygen was strongly increased and the heme-heme interaction strongly diminished. The Bohr effect and the effect of 2,3-diphosphoglycerate on oxygen affinity remained unchanged. The effect of TCEA on the properties of hemoglobin points to specificity in its reaction with functional groups of hemoglobin.

Binding Sites↗
PubMed1975

Ferrihemoglobin and kidney lesions in rats produced by 4-aminophenol or 4-dimethylaminophenol.

4-Dimethylaminophenol hydrochloride (DMAP), 20mg/kg i.v., was found to oxidize in rats as much as 50% of the hemoglobin to ferrihemoglobin but did not cause kidney lesions. 4-Aminophenol hydrochloride, 400 mg/kg i.v., oxidized only 25% of the hemoglobin and produced large tubular necroses. In highly toxic doses only, e.g., twice the LD50, DMAP also produced tubular necroses.

Animals↗