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PubMed2006

[Changes of protein kinase C for the proliferation of retinal pigment epithelium cells induced by subretinal fluid].

OBJECTIVE: To study the effects of subretinal fluid (SRF) on the proliferation of retinal pigment epithelium (RPE) cells and on the activation and translocation of protein kinase C (PKC); to investigate the relationship between the proliferation and the changes of PKC in the RPE cells; and to study the effect of PKC inhibitor. METHODS: RPE cells were harvested to measure the PKC activity in cytoplasm and cellular membrane after being treated with subretinal fluid (SRF) obtained from PVR patients with different degrees (B grade and C), PKC specific activator PMA (positive control) or normal vitreous. RPE cells cultured with DMEM culture medium only were used as the negative controls. PKC activity in cytoplasm and cellular membrane was measured with radioactive isotope (32)P label method. For further study, the PKC specific inhibitor N, N-dimethyl was used to pretreat the RPE cells before the administration of SRF, PMA or normal vitreous, and then the activity of PKC was observed and recorded. (3)H-TdR was used to measure the proliferation of RPE cells with or without the activation and translocation. RESULTS: SRF and PMA could promote the proliferation of RPE cells and activate PKC in the cytoplasm of RPE cells, and then promoted the PKC translocated from the cytoplasm to cellular membrane. The peak of PRC on the cell membrane appeared later in cells treated with SRF when compared with those treated with PMA. The appearance of peak of PKC in cells treated with SRF from grade B PVR was later than those treated with SRF from grade C PVR, the stimulating effect on the proliferation of RPE cells by the SRF B was also less than those from the SRF C. No activation of PKC and increased proliferation were observed in RPE cells treated with normal vitreous or DMEM culture medium. Pre-treatment with PKC inhibitor could block the PKC-activating effects and proliferation-stimulating effects of SRF and PMA on the RPE cells, therefore no significant difference could be detected between different groups. CONCLUSION: SRF can promote the proliferation of RPE cells and induce the activation and translocation of PKC in RPE cells. PKC is involved in the process of the proliferation of RPE cells. The PKC inhibitor could block this process.

Adult↗
PubMedDate not supplied

[90Y-ibritumomab tiuxetan in patients with follicular lymphoma relapsing or refractory to rituximab].

Radioimmunotherapy is a new antineoplastic treatment modality combining the effects of irradiation and monoclonal antibodies. 90Y-ibritumomab tiuxetan is a monoclonal antibody directed against the CD20 antigen to which a radioactive isotope of yttrium is attached, used for treating follicular lymphomas (FL). Using this compound we treated 8 patients with FL relapsing or refractory to combinations of rituximab and chemotherapy. Severe neutropenia developed in 5, and severe thrombocytopenia and anemia in 3 patients. Serious infections developed in 2 patients, one died. Six patients responded to treatment, 4 are still in remission after a median follow-up of 15 months, 2 died of lymphoma. Best response was achieved in low-risk patients with a low tumor burden. 90Y-ibritumomab tiuxetan is an effective treatment for FL with significant hematological toxicity and a high price.

Adult↗
PubMedDate not supplied

Recent progress in target therapy in colorectal cancer.

Monoclonal antibodies are a new class of agents targeting at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can cany substances, such as radioactive isotopes, toxins and antineoplastic agents, to the targeted cells. Two of them, cetuximab (Erbitux) and bevacizumab (Avastin), seem to have acquired a significant role in the management of patients with radically resected and advanced colorectal carcinoma. Cetuximab plus irinotecan has been approved as second-line therapy in irinotecan-resistant colorectal cancer patients; bevacizumab plus 5FU/LV has resulted in higher response and longer survival than 5FU/LV alone in first line metastatic colorectal cancer; its combination with oxaliplatin has recently doubled results. The superior therapeutic efficacy of these molecular targeting agents over traditional chemotherapy has been shown by the survival benefit achieved by patients with advanced or recurrent cancers. Although the precise molecular mechanism by which these agents produce or enhance an antitumour effect, alone or in combination with anticancer drugs, is unknown, the specific inhibition of target genes critically involved in tumour progression and metastasis is clear. Further studies to determine which patient groups and anticancer drugs are more appropriate for combination therapy with these agents are needed. All the most important data obtained through recent studies are discussed, emphasizing their mechanisms of action, safety profiles and clinical applications.

Antibodies, Monoclonal↗
PubMed2006

[Radioiodine treatment of benign thyroid diseases].

Radioiodine treatment of benign thyroid disease has a 60 year history. Among the radioactive isotopes (131)-I can be used successfully. This method has been spread at different rate over the world. Radioiodine is used in Hungary since 1959, however, incidence of this type of therapy does not reach an optimal proportion. The aim of therapy is to decrease the function and/or the volume of thyroid gland. This study considers the reasons of radioiodine treatment in Graves' disease and in different forms of autonomously functioning nodular thyroid disorders, moreover, in cases of compressive euthyroid multinodular goiter when the thyroid volume is to be diminished. There are controversies in terms of indications of radioiodine treatment, however, contraindications are generally well accepted. Sometimes radioiodine therapy could exert an unfavourable effect on ophthalmopathy but this can be prevented with steroids. In cases of suitable administration of thyrostatic treatment before (131)-I therapy the outcome of which does not change significantly though propylthiouracil has really some radioprotection effect. Excellent cure rate can be reached in Graves' disease with radioiodine but hypothyroidism after the treatment may be frequent. In cases of autonomously functioning nodular thyroid disorders (i.e., toxic uninodular or multinodular goiter) cure rate is as high as in Graves' disease but the incidence of thyroid hypofunction is much lower. Thyrotoxic crisis after the treatment is extremely rare. In some cases thyroiditis can be observed after (131)-I therapy but this condition can be easily managed. Thyroid radioiodine uptake and the effectiveness of (131)-I can be increased with the administration of recombinant human thyrotropin in cases of euthyroid multinodular goiter. Recently radioiodine is recommended to young patients having Graves' disease (over 15 years) in special cases. The risk of malignancy after isotope therapy is not significant. Radioiodine treatment of benign thyroid disorders is a simple, safe and cost-effective method, the propagation of which can be suggested.

Contraindications↗
PubMed1991

Normalization of protein synthesis in dystrophic neurons of cerebral cortex in rats after hypoxia, opening of the blood-brain barrier and treatment with organospecific RNA.

The possibility of normalization of protein synthesis intensity was explored in dystrophic neurons and in the total brain cortex of rats after acute hypoxic hypoxia. We avoided transplantation of embryonic nervous tissue (ENT) into the rat brain, as we did before, as well as operations and brain damages in opening of the blood-brain barrier (BBB) caused by hypoxia and intramuscular injections of organo (brain)-specific RNA. As shown by the autoradiographic and biochemical methods using radioactive isotopes (3H-leucine), hypoxia causes a statistically significant reduction in the intensity of protein synthesis which increases and becomes normalized after injection of brain-specific RNA into femoral muscles of animals. Thus, it is possible to normalize hypoxia-inhibited compensation-restoration processes in the brain cortex of animals and, probably, the function of the higher nervous activity using the new simple and harmless biological method. The data presented are of priority significance and important both for development of a number of fundamental biological problems and for medicine since the described method permits the treatment of some serious nervous and mental diseases in humans.

Animals↗
PubMed1991

[Studies on microleakage of three kinds of dental restorative materials].

In this article we studied the microleakage of three kinds of dental restorative materials by using 131I label compounds and 3H label compounds. The results revealed that the radioactive isotope reverse diffusion method has the advantages of which it is quantitative and sensitive. It is an acceptable and feasible measuring method. Under the condition described in this article, microleakage phenomenon exists in all the test materials and the margin sealing ability of EB composite resins is superior to the others.

Composite Resins↗
PubMed1991

[Immunoscintigraphy with monoclonal antibody Tc99m BW 431/26 in the diagnosis of colorectal carcinoma].

BACKGROUND: The use of monoclonal antibodies against tumoral antigens marked with radioactive isotopes is the basis of immunoscintigraphy. The specificity of the technique is high owing to its intrinsic characteristics. METHODS: 40 patients with colorectal cancer who were awaiting surgery were evaluated by immunoscintigraphy. The group consisted of 34 primary diseases and 7 recurrences. Two days before surgery the specific monoclonal antibody BW 431/26 (Behringwerke, FRG) labeled with 99mTc was injected and scintigraphic images were obtained 4 and 24 hours after its administration. RESULTS: The following results were found after a comparison of the data with those from other diagnostic procedures and surgical findings: in primary disease, sensitivity (S) was 59% and accuracy (A) was 56% (these rates increased to 82% and 75%, respectively, when rectal tumors were excluded). For hepatic metastases, S was 44% and A was 85%. In the recurrence group the results were: 4 true positives, 2 false negatives (in the rectum), and one false positive. CONCLUSIONS: These results confirm the validity of immunoscintigraphy in patients with colorectal carcinoma. This test may supplement the information of other diagnostic tests, particularly when these have more limitations as it is the case for recurrences.

Aged↗
PubMed1990

Utility of fluoroimmunoassay in detecting luteinizing hormone surges in spontaneous and human menopausal gonadotropin-stimulated menstrual cycles.

Luteinizing hormone (LH) levels measured with radioimmunoassay and time-resolved fluoroimmunoassay (FIA) in 274 serum samples correlated highly, with a linear correlation coefficient of 0.934. Through the analysis of serial samples from 43 women undergoing human menopausal gonadotropin stimulation for in vitro fertilization or gamete intrafallopian transfer and seven patients monitored in spontaneous menstrual cycles for receipt of frozen embryos, we demonstrated the utility of FIA in the detection of the LH surge. This LH assay technique, which involves no radioactive isotopes, should facilitate the monitoring of ovulation induction patients in the office/ambulatory setting.

Female↗
PubMed1990

Interstitial brachytherapy.

In the last several years there has been a renewed interest in interstitial brachytherapy for the treatment of both newly diagnosed and recurrent malignant gliomas and solitary cerebral metastases. A variety of techniques are currently in use for the planning and stereotactic implantation of radioactive isotopes into these tumors. Although there seems to be strong evidence to support the use of this technique for recurrent malignant gliomas, further work is needed to confirm its efficacy in an adjuvant setting for treating of newly diagnosed tumors and to determine the effect of the addition of hyperthermia or chemotherapy on outcome.

Brachytherapy↗
PubMed1990

Metabolism of leukotriene B4 in isolated rat hepatocytes. Involvement of 2,4-dienoyl-coenzyme A reductase in leukotriene B4 metabolism.

Radiolabeled leukotriene (LT) B4 was incubated with isolated rat hepatocytes in order to assess the metabolism of this chemotactic leukotriene by the liver. At least eight radioactive metabolites were observed, three of which were previously identified as 20-hydroxy-, 20-carboxy-, and 18-carboxy-19,20-dinor-LTB4. A less lipophilic major metabolite (designated HIV) was purified by two reverse phase high performance liquid chromatography separations and was found to exhibit maximal UV absorbance at 269 nm with shoulders at 260 and 280 indicating the presence of a conjugated triene chromophore. Negative ion electron capture gas chromatography/mass spectrometry analysis of the pentafluorobenzyl ester, trimethylsilyl ether derivative of HIV, and positive ion electron ionization mass spectra of the methyl ester trimethylsilyl derivative were consistent with a structure of this metabolite being 16-carboxy-14,15-dihydro-17,18,19,20-tetranor-LTB3. The appearance of this metabolite supports the concept of further beta-oxidation of LTB4 to the carbon 16 which requires the action of 2,4-dienoyl-CoA reductase to remove the 14,15-double bond located two carbon atoms removed from the CoA thioester moiety. One minor metabolite was analyzed by negative ion continuous flow fast atom bombardment mass spectrometry which revealed an ion at m/z 444 which by high resolution mass spectrometry was shown to contain both nitrogen and sulfur. Tandem mass spectrometry suggested the presence of SO3- as well as other fragments corresponding to the amino acid taurine. Incubation of isolated rat hepatocytes with [14C]taurine as well as [3H]LTB4 revealed the incorporation of both radioactive isotopes into this metabolite. The data supported the identification of this metabolite as tauro-18-carboxy-19,20-dinor-LTB4. Amino acid conjugation of leukotrienes has not been previously reported and suggests that such intermediates might participate in enterohepatic circulation of LTB4 metabolites in the intact animal and thus serve as an alternative metabolic route for LTB4 elimination.

Animals↗
PubMed1990

Using different sorbents for the concentration of enteroviruses.

Comparative investigations were carried out to evaluate the efficiency of concentration (EC) of enteroviruses (poliovirus type 1 and simian rotavirus SA-11) using macroporous glass (brands MPG-1000 VGKh, USSR, and SO1, Czechoslovakia) and membrane filters (MF): (nitrocellulose PNTs 0.45, USSR, Millipore HAWP 0.45, USA, Synpor 0.45, Czechoslovakia as well as polycapromide MF Pall 0.2, FRG, and FMPA 0.55, USSR). To assess the sorption properties of filters, poliovirus preparations and rabbit serum gamma-globulin were labelled with radioactive isotopes. Nitrocellulose filters (Millipore and PNTs) proved to be superior in providing for 64-90% virus sorption and 20-24% protein sorption. Elution experiments using solutions of different chemical nature--protein solutions (triptosophosphate broth and beef extract), amino acid mixture (glycine + arginine), chaotropic salt (sodium trichloroacetate mixed with lysine)--showed that protein solutions better eluted rotavirus SA-11 from nitrocellulose filters and macroporous glass (MPG). The utilization of nitrocellulose filters and MPG as sorbents enables a 10-40-fold concentration of enteroviruses depending on the chosen eluent. Comparisons of EC values for rotavirus SA-11 obtained using porous glass MPS-1000 VGKh and SO1 indicated that MPS-1000 VGKh was superior both with respect to recovery efficiency (R) and concentration factor (CF).

Adsorption↗
PubMed1990

[Disorders of zinc transport through the ileal epithelium in vitamin A deficiency and ischemia].

By means of histochemical revealing of zinc and applying radioactive isotope 65Zn accumulation, absorption and distribution of cations of this metal in the mucous membrane of the iliac intestine have been studied in chicken, normal, at ischemia and at A-avitaminosis. An essential zinc-depositing ability is peculiar to coverings of mucus upon the intestine epithelium, and among intracellular components--to smooth endoplasmic reticulum. A-avitaminosis and especially ischemia result in increasing permeability of the apical part of the external membrane of epitheliocytes, in overloading of the latter with zinc cations, when they are introduced into the intestine, as well as in decreasing transepithelial transport of zinc. The changes mentioned are accompanied with certain disturbances in the barrier function of the intestinal epithelium.

Animals↗
PubMed1989

[Carbonic anhydrase and its function in ion transport in cultivated pigmented ciliary body epithelial cells].

The effect of inhibitors of the carbonic anhydrase on aqueous humor formation suggests that carbonic anhydrase has an important role in ion transport across the ciliary epithelium. We therefore investigated the role of carbonic anhydrase in Na+ and Cl- transport in cultured bovine pigmented ciliary epithelial cells (PE) using the radioactive isotopes 22Na and 36Cl. Our findings can be summarized as follows. (1) Na+ uptake into the cell occurs via an amiloride-sensitive Na+/H+ exchanger. (2) Cl- is transported into the cell in exchange for bicarbonate ions. (3) PE cells contain biochemical carbonic anhydrase activity. (4) Na+ uptake into NaCl-depleted cells is markedly stimulated by Cl-. This stimulation is HCO3- dependent and is completely blocked by amiloride and partly inhibited by the carbonic anhydrase inhibitor methazolamide. (5) A model is introduced for transport of NaCl in the ciliary epithelium: carbonic anhydrase is responsible for coupling of Na+/H+ exchange and Cl-/HCO3- countertransport. This model could explain the effect of carbonic anhydrase inhibitors on intraocular pressure.

Animals↗
PubMed1989

Synopsis of nuclear medicine.

The application of radionuclides to medical diagnosis and treatment has a relatively short history. The phenomenon of radioactivity was originally discovered by Henri Bacquerel in 1896, whereas Pierre and Marie Curie isolated the naturally occurring element radium in 1899. The use of radium in the treatment of malignant disease was first introduced at the turn of this century, and was established by 1920. It was not until 1938, however, that the discovery of nuclear fission made possible the subsequent development of the nuclear reactor, and the large-scale production of artificial radioactive nuclides. It was immediately realised that the latter opened up great possibilities in the medical field. The radioactive isotope was chemically indistinguishable from the stable isotopes of the element, and minute quantities of it in the body could be detected externally by virtue of the radiation they emitted; it could be used as a "tracer" to follow the metabolism of a substance throughout the body. The following synopsis is a brief attempt to introduce the Kenyan medical personnel into the scope of nuclear energy in medicine.

Humans↗
PubMed1989

Ovine fetal coronary and cerebral vascular responses to forskolin.

The time related hemodynamic responses to forskolin-elicited increases in cAMP were studied in the near-term fetus. Catheters and electrodes were inserted into 6 fetal sheep to measure arterial, venous and thoracic pressures, electrocorticogram, and electrocardiogram. At gestational day 134, experiments were performed to determine the effect of forskolin infusion (400 micrograms/ml at 1.03 ml/min for 5 min) on fetal blood pressure, coronary and cerebral blood flow and resistance. Blood flow measurements were made using 15 microns microspheres labelled with radioactive isotopes during the control period and at 0, 5, 10, 15, and 45 min after forskolin infusion. Forskolin infusion was always initiated during a high-voltage electrocortical epoch and was given twice in each animal. In each case, forskolin caused electrocortical activity to change from high-voltage state to an intermediate voltage state. Blood pressure fell significantly by the end of the infusion period and returned to control levels 10 min later. Fetal heart rate and coronary blood flow were immediately elevated by forskolin (P less than 0.01) whereas cerebral blood flow did not increase until 5 min later (P less than 0.01). Cerebral blood flow was still elevated (P less than 0.05) 45 min after the end of forskolin infusion, whereas coronary blood flow had returned to control levels. Both cerebral and coronary vascular resistance fell significantly in response to forskolin infusion (P less than 0.01). This effect lasted at least 15 min and had returned to control levels 45 min after forskolin had been terminated.

Animals↗
PubMed1989

Toxicokinetics of cobalt and the problems of biological monitoring.

Toxicokinetics of cobalt was studied on rats by the method of radioactive isotopes using single or repeated administrations. Co was used in the form of sulphate in doses of 0.1 and 0.2 mg/kg administered by 4 different routes (intragastric, intraperitoneal, intratracheal, subcutaneous). Good absorption was established in the parenteral routes of administration, the regularities of absorption, retention in the internal organs and elimination of cobalt were determined and mathematically expressed. Clear dependence was established between the doses administered and the content in biomedia. The liver and the kidneys were found to be the organs of highest accumulation of cobalt. Elimination half-lives and the time of establishment of a constant level during long-term exposure were determined. It is proposed to carry out diagnostic examination in the course of a few hours after the work shift. Urine and blood are the test objects in which direct correlation has been established. Delayed elimination of cobalt from the organism under protracted exposure may be the essential cause of increased hazard for man, which conditions the necessity of determining maximum acceptable concentration for this substance.

Animals↗
PubMed1989

Studies on mucus biosynthesis in the gastrointestinal tract.

Mucin biosynthesis in the rat gastrointestinal tract was measured by following the incorporation of radioactive precursors, [3H] glucosamine, [3H] galactose and [3H] serine. The radioactive mucin was isolated by a combination of equilibrium centrifugation in a CsCl density gradient and gel-filtration or, by papain digestion and removal of digested peptides by dialysis. Radioactive precursors were incorporated into mucin by stomach, duodenum and colon in vivo and by stomach in organ culture in vitro. In the latter, incorporation was approximately 20-fold greater than in vivo, over 6 h. In all cases lower molecular weight non-mucin glycoprotein, of the same buoyant density as mucin, became radioactively labelled (non-dialysable) and usually accounted for the majority of the incorporated radioactivity. Acetylcholine, dibutyryl cAMP and secretin stimulated radioactive incorporation into both gastric mucin and non-mucin components with acetylcholine and dcAMP stimulating specifically [3H] glucosamine into gastric mucin. Using these conditions no stimulation of incorporation into gastric mucin of all three radioactive precursors could be obtained with topical PGE2. In some biosynthesis studies by others, methods used to precipitate radioactive mucins do not distinguish between mucin and lower sized material. This study points to the need for a reappraisal of existing methods using radioactive isotopes to study mucin biosynthesis.

Animals↗
PubMed1977

[The shaping of the margin in cast objects in oral rehabilitation].

Various preparations of margins in cast replacements as well as their insertion and finishing are studied and measured by means of radioactive isotopes. It was found, in particular, that the conventional preparation of cavity margins and the finishing of cast margins of tightly cemented cast replacements should be discontinued.

Cementation↗