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Biomedical subjects

H Jung

Publications and source records attributed to H Jung.

At least 19 recordsLinked to original sources
PubMed1992

Clinical pharmacokinetics of albendazole in patients with brain cysticercosis.

Albendazole pharmacokinetics were studied in eight patients who were receiving albendazole in doses of 15 mg/kg per day for 8 days as treatment of brain cysticercosis. Albendazole was not detected in plasma, but its main metabolite albendazole sulphoxide could be measured. Maximum plasma levels for albendazole sulphoxide ranged from 0.45 to 2.96 micrograms/mL. The half-life of albendazole sulphoxide was between 10 and 15 hours. A double peak was found in three patients. Mean residence time values were from 14 to 20 hours. Plasma levels of albendazole sulphoxide at the steady state showed great intraindividual variability. The results suggest that albendazole can be administered twice daily rather than three times as is currently done.

Administration, Oral↗
PubMed1992

Light and lithium effects in the rat retina: modification by the PAF antagonist BN 52021.

We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400-450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina.

Analysis of Variance↗
PubMed1992

A long-term survey of morphine in cancer pain patients.

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.

Analgesics↗
PubMed1992

[Therapy for symptomatic pain in advanced breast cancer].

From 1983-1989, 106 patients with breast cancer were treated in our pain management unit on 6767 treatment days. Pain was caused by bone metastasis in 73% of patients. Neuropathic pain was reported by 32% of the patients. In all but four of these patients, new tumour growth was diagnosed. Patients were treated according to WHO analgesic guidelines with non-opioids on 16% of the days, non-opioids in combination with weak opioids on 36% and with strong opioids on 38% (orally 90%, parenterally 4% of the days). Due to the prevalence of bone pain non-steroidal antiinflammatory drugs were given on 56% of the days. The high incidence of neuropathic pain led to frequent use of co-analgesics (antidepressants 17%, anticonvulsants 12%, steroids 12% of the days). Adjuvant therapy for symptoms other than pain was given on 86% of the days. Whilst 92% of patients reported more than moderate pain on admission, 45% obtained complete pain relief beginning from the first days of treatment. On 92% of the days, patients described their pain as moderate or less. Side effects were treated symptomatically and played a minor role in a reason to change therapy.

Adult↗
PubMed1992

Effect of thermotolerance and step-down heating on thermal radiosensitization in CHO cells.

Chinese hamster ovary cells were exposed to single or fractionated heat treatments followed by irradiation on ice with graded doses of X-rays. The dose-response curves obtained were fitted by the linear-quadratic equation -ln(S/S0) = alpha D + beta D2 and analysed in terms of TER10%, alpha and beta. Thermal enhancement ratio, TER10%, was reduced when heat sensitivity was lowered either by chronic (pretreatment 40 degrees C, 16 h) or acute (43 degrees C, 45 min-37 degrees C, 10 h) thermotolerance, but was enhanced after step-down heating (43-40 degrees C or 45-40 degrees C). It could be shown that thermal radiosensitization, as expressed by TER10%, is modified by thermotolerance or step-down heating only to the extent to which cellular survival is modified by the corresponding pretreatments. However, the relative change of alpha and beta was found to be different for thermotolerance and step-down heating. For thermotolerant cells the values for alpha and beta were reduced by about the same factor, whereas step-down heating caused an increase in both parameters, which was greater for alpha than for beta. Data analysis showed that the modification of thermal radiosensitization by thermotolerance can be interpreted as if the cells were heated at the given temperature for a shorter time, whereas after step-down heating the cells responded as if they were exposed to a higher temperature prior to irradiation.

Animals↗
PubMed1992

Kinetics of depopulation, repopulation and host cell infiltration in the rhabdomyosarcoma R1H after 14 MeV neutron irradiation.

The kinetics of depopulation and repopulation of the solid transplantable rhabdomyosarcoma R1H in the rat was studied following irradiation with 5 Gy of 14 MeV neutrons. Several parameters were sequentially measured over a time period of 4 weeks after irradiation: the tumour volume was assessed by in situ caliper measurements; the numerical density of tumour cells was obtained by morphometry; the clonogenic fraction of tumour cells was derived from in vitro colony assay; and the numerical ratio of host to tumour cells was determined by flow cytometry. From these primary parameters the number of clonogenic tumour cells, non-clonogenic tumour cells, and nucleated host cells per tumour, as well as their variation with time, were derived. The results were compared with two sets of data obtained previously for the same tumour exposed to 15 Gy of 200 kVp X-rays. Survival of tumour cells was reduced to 5.5 +/- 0.5% by 5 Gy neutrons and to 4.5 +/- 0.5% by 15 Gy X-rays, i.e. an RBE of close to 3. There was a lag period before the onset of repopulation (4.9 +/- 0.4 days and 4.9 +/- 0.5 days, respectively), followed by a high initial rate of repopulation corresponding to a doubling time of 2.0 +/- 0.2 days for neutrons and 2.1 +/- 0.2 days for X-rays. The rate of depopulation was significantly different for the two treatment modalities; the halving time for the number of non-clonogenic tumour cells was 11 +/- 4 days for neutrons and 2.8 +/- 0.5 days for X-rays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nitro group orientation, reduction potential, and direct-acting mutagenicity of nitro-polycyclic aromatic hydrocarbons.

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread genotoxic environmental pollutants. We have been interested in determining the structural and electronic features that may be useful in predicting the direct-acting mutagenic activity of nitro-PAHs in Salmonella typhimurium. In this study, a series of structurally related nitro-PAHs were used to determine the relationships among direct-acting mutagenicity, orientation of the nitro group, and reduction potential of the nitro group. The compounds consisted of isomeric mononitrated and dinitrated benzo[e]pyrenes, their derivatives, and other nitro-PAHs ranging from two to five aromatic-ring molecules in size. A general finding is that nitro-PAHs with their nitro substituent oriented perpendicular to the aromatic system exhibit either very weak or no direct-acting mutagenicity in S. typhimurium strains TA98 and TA100. However, if a nitro-PAH of this type has a relatively low first half-wave reduction potential, it may be direct-acting. Furthermore, a positive correlation between the first half-wave reduction potential and direct-acting mutagenicity is found only when the compounds are structurally similar. Consequently, the correlation cannot be made using nitro-PAHs with different molecular size. Nitro-PAHs having a perpendicular nitro orientation always have a higher (absolute value) first half-wave reduction potential than the isomer(s) with a parallel orientation. Perhaps due to electron-withdrawing by the second nitro group, dinitro-PAHs always have a lower first half-wave reduction potential than their mononitro analogues. These findings provide a useful molecular basis for interpreting and predicting the direct-acting mutagenicity of nitro-PAHs.

Benzo(a)pyrene↗
PubMed1991

Thermal radiosensitization in CHO cells by prior heating at 41-46 degrees C.

CHO cells were exposed to heat at temperatures ranging from 41 degrees C to 46 degrees C followed by irradiation on ice with graded doses of X-rays. The dose-response curves obtained were analysed in terms of D10%, D0 and Dq and thermal enhancement was expressed by the corresponding values TER10%, TEF and TEQ, respectively. TER10% and TEF were shown to increase linearly with heating time, the increase being steeper at higher temperatures. The dose-response curves were also analysed using the equation -ln(S/S0) = alpha D + beta D2; the values of alpha and beta obtained from curve-fitting were found to increase with heating time. For temperatures below 43 degrees C the relative increase in alpha was greater than that in beta; the Arrhenius activation energies were Ea = 890 kJ mol-1 for alpha and Ea = 1830 kJ mol-1 for beta. At temperatures exceeding 43 degrees C the relative increase of alpha and beta was similar and the corresponding activation energies were about the same (Ea approximately 700 kJ mol-1). The increase in the alpha-term was attributed to a depressed repair of double-strand breaks, whereas the increase of beta was assumed to be a consequence of an insufficient repair of base damage.

Animals↗
PubMed1991

Immunopathology of hepatitis B mediated membranous glomerulonephritis.

The study was undertaken to establish the clinical and immunological aspects of HBV-mediated membranous glomerulonephritis in children. Out of 54 children with membranous GN treated in the Children's Memorial Hospital 51 children (94.4%) had the disease related to HBV infection. The inhibitory effect of immune complexes: HBsAg-IgG and HBeAg-IgG, isolated from sera of these children on lymphocyte proliferation of blood donors was observed. This may partly explain the status of immune tolerance towards HBV in the infected children.

Adolescent↗
PubMed1991

A generalized concept for cell killing by heat. Effect of chronically induced thermotolerance.

Chronic thermotolerance was induced in Chinese hamster ovary (CHO) cells by pretreatment at 40 degrees C for various times ranging from 15 min to 16 h. The thermotolerant cells were either exposed to single heat treatments at 43 degrees C or subjected to step-down heating consisting of a priming treatment at 43 degrees C for 90 min followed immediately by a graded test treatment at 40 degrees C. Data evaluation using a mathematical model published previously (H. Jung, Radiat. Res. 106, 56-72, 1986) showed that the rate constants p for the production of nonlethal lesions at 43 and 40 degrees C decreased by a factor of 20 with the duration of the thermotolerance-inducing pretreatment at 40 degrees C and approached exponentially (half-time 1.24 +/- 0.11 h) a minimum value. By contrast, the rate constants c for the conversion of nonlethal lesions into lethal events were not altered by the induction of thermotolerance; this applied to both c (43 degrees C) and c (40 degrees C). After transferring thermotolerant cells (pretreatment at 40 degrees C for 3 h) to 37 degrees C, the rate constants p increased exponentially with time (doubling time 25 +/- 5 h). Similar kinetics for the development and decay of chronic thermotolerance was shown to be applicable also to extended heating at 40 degrees C and to various data from the literature.

Acclimatization↗
PubMed1991

Radiotherapy of the rhabdomyosarcoma R1H of the rat: split-course versus continuous fractionation.

Fractionated split-course treatments were given with gaps of different length and the effects on tumor response was studied using the rhabdomyosarcoma R1H of the rat. Total doses of 68, 75 and 82 Gy were applied in 30 fractions (five fractions per week). After four weeks, that is after 20 fractions, treatment was interrupted for one or two weeks followed by another ten fractions. The results were compared to those of continuous treatment given in six consecutive weeks. Tumor response was quantified by TCD37% and net growth delay. The TCD37% increased with increasing duration of the gap. A mean repopulated dose of 0.72 Gy per day was obtained. This corresponds to a doubling time of tumor clonogens of 4.2 days during the gap, which is somewhat slower than the volume doubling time of unperturbed tumors (2.5 days) of the same size. The results obtained for the net growth delay support the results of the TCD37% data. It is concluded that a gap during fractionated radiotherapy leads to poorer results since the dose required for tumor control is enhanced and sparing of normal tissue can only be expected for early but not for late reacting tissues.

Animals↗
PubMed1990

L-carnitine metabolization and osmotic stress response in Escherichia coli.

Growth of Escherichia coli 044 K 74 in liquid medium of raised osmotic strength was stimulated by exogenous L-carnitine, crotonobetaine and gamma-butyrobetaine, respectively. L-Carnitine was accumulated within the cells in dependence on the salt concentration of the media. Osmotic stress during aerobic or anaerobic growth with glucose triggered the L-carnitine uptake in E. coli 044 K 74 whereas L-carnitine uptake by cells of this organism grown anaerobically on glycerol/fumarate was only slightly modified. Synthesis of the enzymes metabolizing L-carnitine to gamma-butyrobetaine in glycerol/fumarate growing bacteria was found to be completely repressed by high NaCl-concentrations. Together, these results indicate that most likely the L-carnitine metabolization sequence does not play a role in osmoregulation in E. coli 044 K 74.

Acyltransferases↗
PubMed1990

L-carnitine uptake by Escherichia coli.

The uptake of L-carnitine by Escherichia coli 044 K74 which is able to metabolize L-carnitine to gamma-butyrobetaine under anaerobic conditions was studied. The uptake system of E. coli was induced in the presence of L-carnitine or crotonobetaine. The optimum influx of L-carnitine was found to take place at 37 degrees C in phosphate buffer, pH 7.5. On the basis of the temperature dependence of the uptake rate an activation energy of 53.5 kJ/mol was estimated. The transport of L-carnitine was energy dependent. The kinetics of L-carnitine entry followed the Michaelis-Menten relationship yielding a Km value of 5.3 x 10(-4) M and a Vmax of 154 nmol/min.mg protein. The transport system showed considerable structural specificity for trimethylamine carboxylic molecules. The results suggest that E. coli possesses an inducible, active and carrier-mediated uptake system for L-carnitine.

2,4-Dinitrophenol↗
PubMed1990

Dexamethasone increases plasma levels of albendazole.

Therapy of neurocysticercosis with cysticidal drugs is frequently complicated by the exacerbation of symptoms that follows the inflammation triggered by the acute destruction of cysticerci. Treatment of such adverse reactions with dexamethasone is highly effective. However, it has been shown that dexamethasone lowers the plasma levels of praziquantel, thus reducing its cysticidal efficacy. We measured plasma levels of albendazole, another strong cysticidal drug, when dexamethasone was given simultaneously. We found that dexamethasone increased the plasma levels of albendazole by about 50% (P less than 0.002); hence, it seems that cysticercosis and the ensuing inflammation can be treated simultaneously with albendazole and dexamethasone without diminishing the efficacy of the cysticidal drug.

Adult↗