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Biomedical subjects

K Winckler

Publications and source records attributed to K Winckler.

At least 19 recordsLinked to original sources
PubMed1998

Influence of body mass, age, and maturation on specific oxygen consumption in a freshwater cichlid fish, Cichlasoma nigrofasciatum (Günther, 1869).

The oxygen consumption of a freshwater convict cichlid (Cichlasoma nigrofasciatum) was determined throughout the fish development from age 74 days to 403 days, covering the period before and after maturation. The specific oxygen consumption decreases with increasing age. The decrease in metabolic rate appears rather in distinct phases. A small increase in the average specific metabolic rate (mainly from the bigger fish) around age 200 days suggests an involvement of internal changes in the fish during a transition period from "young" state to "mature" state. The relationship between the specific oxygen consumption and body mass is determined by maturation and age. Before reaching maturation (before age 200 days) the correlation between specific oxygen consumption and body mass is negative for "young" fish of the same age. After age 200 days, no correlation between both parameters could be found. We suggest from this study that both factors "age" and "size" of the organism have to be considered for determining the metabolism, especially in fish. This study indicates that even in fish, which retain a continuous growing capability until they die, the decrease in the specific oxygen consumption is related to the aging process.

Aging↗
PubMed1998

Potential influence of increased sub-lethal UV-A irradiation on aquatic food production (Aquaculture).

In the tropics organisms have permanently adapted to deal with extremely high intensities of light, temperature and other environmental factors. Especially in coastal environments and fish farmings conditions can easily reach and exceed the tolerance limits of an organism. The UV-A band has been shown to be a potent modulator of light induced effects and general physiological functions in organisms. The biological endpoints and underlying mechanisms still have to be investigated. Our experiments were carried out with the easy to handle sub-tropical Convict-Cichlid fish (Cichlasoma nigrofasciatum) as a model organism. In our studies we observed that constant sub-lethal UV-A irradiation had a significant effect on the general metabolism and on the sensitivity towards other environmental stress factors in this fish. We found that, in addition to the depression of the general metabolism, sub-lethal UV-A irradiation in combination with elevated environmental temperature had a deleterious effect on the population. The threshold temperature for a sudden increase in mortality of the fish receiving the additional sub-lethal UV-A irradiation was 32 degree C. The fish were grown and adapted at 27-29 degrees C. A total of 78% of the fish receiving an additional UV-A irradiation died by high temperature stress while the reference population remained at a normal level (3%). The metabolic rate (MR) of the UV-A survivors during temperature stress was less than half the average value obtained in the reference population. After the environmental temperature returned below the apparent upper tolerance limit for this fish, the MR of UV-A population gradually increased to normal. Apparently a constant elevated sub-lethal dose of UV-A leads to the destabilization of an organism, making it more sensitive for other environmental stress factors. These observations seem to be important considerations in fish farming in the tropical and subtropical regions.

Animals↗
PubMed1996

Combined effects of constant sublethal UVA irradiation and elevated temperature on the survival and general metabolism of the convict-cichlid fish, Cichlasoma nigrofasciatum.

In a previous study we observed that a constant sublethal UVA (320-400 nm) irradiation had a significant effect on the general metabolism in the Convict-cichlid fish (Cichlasoma nigrofasciatum) [Winckler, K. and Fidhiany, L. (1996) J. Photochem. Photobiol. B. Biol. (In press)]. In the present study we show that sublethal UVA irradiation in combination with elevated environmental temperature has a deleterious effect on the same population. The threshold temperature for a sudden increase in mortality of fish receiving an additional sublethal UVA irradiation was 32 degrees C. Prior to the increased mortality, the fish started to avoid the UV light source when the water temperature increased to 31.5 degrees C. Mortality decreased when the temperature declined below 31.5 degrees C. As soon as the temperature changed to normal (adapted) condition (27-29 degrees C) mortality returned to normal levels. In contrast, no changes of fish behavior or mortality were observed at elevated temperature in the nonirradiated reference population. The percentages of fish surviving the high temperature stress were 21.9% for the UVA population and 96.8% for the reference population. The specific oxygen consumption (SOC, average +/- SD) of the survivors from the UVA population during temperature stress was 0.21 +/- 0.05 mg O2 h-1 g body weight (BW)-1, while it was 0.54 +/- 0.11 mg O2 h-1 g BW-1 in the reference population. After the environmental temperature returned below the apparent upper temperature tolerance limit, the oxygen consumption of the UVA population gradually normalized. The SOC measured at different temperature levels--after after the fish passed the temperature stress--showed no significant differences between the UVA population and its reference at 23, 25, 27 and 29 degrees C. However, the SOC at 31 degrees C was significantly (P < 0.05) lower than reference, while at 33 degrees C it was higher (P < 0.10).

Adaptation, Physiological↗
PubMed1991

[Intrapleural catheter analgesia in patients with multiple rib fractures].

Patients with multiple rib fractures often suffer from severe pain that impairs their respiratory performance. The effect of interpleural administration of bupivacaine (20 ml 0.25% every 4 h) for pain management was evaluated in ten patients. The initial interpleural injection resulted in significant pain relief and improvement of arterial oxygen tension. Two patients needed additional i.v. injections of opioids (piritramide 15-22.5 mg/24 h). In one patient a small asymptomatic pneumothorax was observed following placement of the catheter, which resolved spontaneously. No other complications were reported. In an intraindividual comparison, bupivacaine alone and bupivacaine plus epinephrine 1:200,000 were compared with regard to pharmacokinetics of bupivacaine, analgesic effect, side effects, and respiratory performance. The addition of epinephrine yielded only minor advantages from a pharmacokinetic point of view (median peak concentration of bupivacaine 1.8 micrograms/ml vs 2.0 micrograms/ml for bupivacaine alone). The quality and duration of analgesia and the effects on respiration were not influenced by epinephrine. The heart rate was significantly higher and the blood pressure significantly lower when epinephrine was added to the solution. Nevertheless, these differences were too small to be of clinical importance. Even though maximum total plasma concentrations of bupivacaine above 2 micrograms/ml were found in some patients, there were no signs of CNS toxicity, most probably because of the increased protein binding of bupivacaine following trauma. Accordingly, the maximum free plasma concentrations in all patients were below the threshold level of 0.24 micron/ml. We therefore conclude tht interpleural administration of bupivacaine could be a valuable means of pain relief in patients with multiple rib fractures, providing no severe pulmonary contusions or concomitant injuries are present.

Adult↗
PubMed1989

Determination of the thalidomide analogues 2-(2,6-dioxopiperidine-3-yl)phthalimidine (EM 12), 2-(2,6-dioxopiperidine-4-yl)phthalimidine (EM 16) and their metabolites in biological samples.

A rapid and sensitive method for quantitative analysis of the thalidomide analogues EM 12 and EM 16 and their metabolites has been developed. Following an optional extraction, samples were analysed by reversed-phase high-performance liquid chromatography with ion depression. The recovery of the extraction procedures was 65-80%. The method has been applied to pharmacokinetic studies in small laboratory animals and in vitro model experiments.

Animals↗
PubMed1988

Reactions of the intracellular NADpool in the yeast S. cerevisiae after UV-C- or X-ray irradiation.

The reaction of the intracellular NADpool after irradiation of cells either with UV-C light or with X-rays was studied in four different strains of the yeast S. cerevisiae. We found neither in wildtype strains nor in radiation sensitive mutants remarkable changes in the NADpool within 2 h after irradiation. Preculture of cells in medium enriched with nicotinic acid, a precursor of NAD, influenced the intracellular NAD concentration only to a small extend in all strains, but enhanced the radiation resistance against UV-C significantly in one rad6 mutant strain. The uptake of NAD and NAC by all strains before and after irradiation with UV-C and X-ray was tested also. NAD generally is taken up by the cells to a very low extent before and after irradiation without irradiation-dose dependency. NAC is taken up by all strains before and after irradiation. Only the rad6 mutant exhibited an irradiation-dose dependent NAC-uptake after UV-C irradiation.

Kinetics↗
PubMed1988

Side effects in excimer corneal surgery. DNA damage as a result of 193 nm excimer laser radiation.

UV radiation is known to cause actinic damage to the DNA. Excimer laser light, possibly used for keratorefractive surgery, should not produce this damage, as the penetration depth is far less than the diameter of a cell. However, photoreactivation experiments with yeast cells show a significant amount of DNA repair after excimer irradiation. The zone of influence of a small slitlike exposure has a diameter of 2 cm. Consequently, the limbus, the critical location of epithelial neoplasia, always lies within the sphere of actinic damage. Radiation damage is induced by secondary radiation rather than by direct interaction.

Cell Line↗
PubMed1988

Survival of Saccharomyces cerevisiae after treatment with the restriction endonuclease Alu I.

Treatment of yeast cells proficient in the repair of radiation damage (Saccharomyces cerevisiae) with the restriction endonuclease Alu I leads to a positive dose-effect relationship between inactivation level and enzyme concentration. The data suggest an uptake of the active restriction enzyme into the cells and a relationship between induction of DNA double-strand breaks and cell killing.

Chromosome Aberrations↗
PubMed1988

Pharmacokinetics and protein binding of bupivacaine in postoperative epidural analgesia.

We describe a method, which is both specific and rapid, for the measurement of bupivacaine concentrations in plasma using high-performance liquid chromatography. Bupivacaine plasma concentrations, pharmacokinetics and protein binding in the postoperative period were investigated in seven patients (58-77 years old) following hip surgery. Postoperative analgesia was achieved by epidural bolus injections of 25 mg bupivacaine 0.25% every 6 h. Sufficient pain relief without side-effects was obtained. Total (maximum 1.13 micrograms/ml) as well as free (maximum 0.1 microgram/ml) bupivacaine plasma concentrations remained below toxic threshold levels and no cumulation occurred. Increased protein binding in the postoperative period is reported, emphasizing the importance of measuring the free fraction in addition to the total plasma concentration. The free fraction decreased from 5.4% preoperatively to 2.7% in the postoperative period (P less than 0.05). Changes in plasma protein binding of bupivacaine and changes in plasma levels of the acute phase reactant alpha-1-acid glycoprotein were correlated (r = 0.8, P less than 0.05). Difficulties in interpreting the elimination parameters following epidural administration are discussed, leading to the conclusion that the derivation of dosage regimens from kinetic parameters following epidural administration is not warranted.

Aged↗
PubMed1987

Cyclophosphamide: interstrain differences in the production of mutagenic metabolites by S9-fractions from liver and kidney in different mutagenicity test systems in vitro and in the teratogenic response in vivo between CBA and C 57 BL mice.

The formation of mutagenic compounds from cyclophosphamide (CPA) by S9-fractions from liver (S9L) or kidney (S9K) of pregnant CBA and C 57 BL mice was investigated, using point mutations in Salmonella typhimurium (TA 1535) and the induction of sister chromatid exchanges (SCE) in human peripheral lymphocytes (HPL) or Chinese hamster ovary (CHO) cells as end points. In addition, the teratological response of CBA and C 57 BL mice to CPA on day 11 of pregnancy was analysed in vivo. The results are as follows: (1) S9L from CBA mice was more effective than S9L from C 57 BL mice in metabolizing CPA to products inducing mutations in Salmonella and SCEs in HPL and CHO cells. (2) S9L was more effective than S9K from both strains of mice. (3) In vivo pretreatment of mice with a single dose of CPA (20 mg/kg) reduced the in vitro metabolizing capacity of S9L and S9K significantly and led to the disappearance of the interstrain difference. (4) The embryolethal and teratogenic effects of CPA were stronger in C 57 BL than in CBA mice; the types of teratological effects were partially different in the two strains.

Animals↗
PubMed1984

Mutagenic activities of cyclophosphamide (NSC-26271) and its main metabolites in Salmonella typhimurium, human peripheral lymphocytes and Chinese hamster ovary cells.

Cyclophosphamide (CPA) and its main metabolites were analyzed with respect to their mutagenic activities in Salmonella, human peripheral lymphocytes (PL), and Chinese hamster ovary (CHO) cells. In Salmonella, the compounds were activated with S9 mix from rat livers, which were unstimulated or stimulated with Aroclor 1254 or phenobarbital. For the enzyme inducers the following order of efficiency was found for all test compounds except carboxyphosphamide: phenobarbital greater than Aroclor 1254 greater than non-induced. The most potent mutagens in all 3 test systems were 4-OH-CPA, PAM and nor-HN2. S9 mix transforms 4-OH-CPA to strong mutagenic compounds in the Salmonella assay. All metabolites tested in the Salmonella assay were activated by S9 mix to higher mutagenic potential.

Animals↗
PubMed1983

Influence of secretin on the course of acute experimental pancreatitis in rats.

Inhibition of pancreatic secretion is a widely accepted therapeutical principle of acute pancreatitis. However, stimulation of water and bicarbonate secretion may be beneficial by washing out the ductular system in pancreatitis. Secretin (2 and 16 CU/kg body weight) or saline were given to rats at different time intervals after induction of sodium taurocholate pancreatitis. Pancreatic necrosis and edema were slightly more marked after secretin but secretin had no influence on the survival time and rate or enzymatic parameters. It is concluded that in the rat secretin-induced pancreatic secretion does not alter the course of acute pancreatitis.

Acute Disease↗
PubMed1983

Penetration of cefotaxime into the pancreas.

After intravenous injection of cefotaxime, higher pancreatic concentrations of the antibiotic were found in rats with experimental pancreatitis than in control animals. Also in human pancreatic pseudocysts, high and persistent concentrations of cefotaxime were found following intravenous injection. The results justify the use of cefotaxime in acute pancreatitis, whenever an antibiotic is indicated.

Animals↗
PubMed1983

Does PGE2 have a beneficial effect on acute experimental pancreatitis in the rat?

Prostaglandin E2 (PGE2) is known to have a cytoprotective effect on the gastric mucosa exposed to a variety of noxious agents. A cytoprotective effect on the pancreas in acute pancreatitis has been postulated, but available evidence is contradictory. Acute experimental pancreatitis was induced in 170 male Wistar rats by retrograde injection of 0.6 ml of 5% Na-taurocholate into the pancreatic duct. PGE2 (0.1 microgram/g rat) was given intraductally, intraperitoneally or subcutaneously before and after induction of pancreatitis. PGE2 had no effect on survival rate, enzyme levels in serum and ascites, or on morphologic damage to the pancreas.

Acute Disease↗
PubMed1982

Mutagenic, teratogenic and pharmacokinetic properties of cyclophosphamide and some of its deuterated derivatives.

To elucidate which metabolic pathway leads to the ultimate mutagenic and teratogenic metabolite of cyclophosphamide (CPA), the mutagenicity in vitro as well as the teratogenicity in vivo and the pharmacokinetics of CPA and several deuterated analogs (5,5-d2-CPA, 4,4-d2-CPA and 4,4-6,6-d4-CPA) were compared. 5,5-d2-CPA was less mutagenic (isotope effects between 1.7 and 12.3 were found for sister-chromatid exchanges and structural chromosomal aberrations in CHO cells and in the Ames test) and less teratogenic (deuterium isotope effect between 2 and 3) than CPA and the other deuterated analogs. Because the concentrations of 5,5-d2-CPA in pregnant mice and their embryos were equal to or even exceeded those of CPA and the other deuterated analogs, a particular metabolic pathway involving a fission of the C-D or C-H bond on the C-5 rather than the parent drug must be responsible for the isotope effect observed. It had previously been shown (Cox et al., 1976) that the 5,5-d2-CPA has a decreased anti-tumor activity in vivo (isotope effect 7-13) which was accompanied by a decreased formation of phosphoramide mustard and acrolein in vitro (isotope effect 5.3). Our results suggest that phosphoramide mustard is an important proximate metabolite of CPA with regard to the mutagenicity and teratogenicity of the drug. These results show for the first time that labeling of drugs with stable isotopes offers a promising approach to the study of the mechanism of the mutagenic and teratogenic actions of drugs.

Animals↗