Suppressive effects of methylthiouracil on polyphosphate-mediated vascular inflammatory responses.

Drug repositioning is used to discover drug candidates to treat human diseases, through the application of drugs or compounds that are approved for the treatment of other diseases. This method can significantly reduce the time required and cost of discovering new drug candidates for human diseases. Previous studies have reported pro-inflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of methylthiouracil (MTU), which is an antithyroid drug, and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behaviour of human neutrophils and vascular permeability were determined in PolyP-activated HUVECs and mice. MTU suppressed the PolyP-mediated vascular barrier permeability, up-regulation of inflammatory biomarkers, adhesion/migration of leucocytes, and activation and/or production of nuclear factor-κB, tumour necrosis factor-α and interleukin-6. Furthermore, MTU demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of MTU on various systemic inflammatory diseases, such as sepsis or septic shock.

[Preliminary study on Chinese herb induced apoptosis of thyrocytes in Graves' disease].

OBJECTIVE: To investigate the cellular and molecular mechanisms of some Chinese herbs on apoptosis of thyrocytes in Graves' disease. METHODS: Thirteen patients of Graves' disease were treated by anti-thyroid drugs and Chinese herbs were added in the therapeutic period for 2-10 weeks. Thyroid tissue of patient was sucked by percutaneous aspiration before and after adding Chinese herbs for observing the cellular morphology by fast red tablet staining, monitoring the cell apoptotic ratio by flow cytometry and terminal uridine deoxynucleotidyl end labelling (TUNEL) method to observe the effect of anti-thyroid drugs combined with Chinese herbs on Graves' disease. RESULTS: Compared with that treated with anti-thyroid drugs alone, after the combined therapy, the size of thyroid decreased significantly, P < 0.01. Typical apoptosis appearance, such as vacuolated cell, marginal nuclei, chromatin condensation and nuclear fragmentation, could be seen under light microscopy. The apoptotic rate before and after adding Chinese herbs was (2.11 +/- 1.78)% and (18.66 +/- 20.01)% respectively (P < 0.01). TUNEL positive cells were detectable for up to 2-20 weeks after Chinese herbal treatment. CONCLUSION: Some Chinese herbs could induce cell apoptosis when used in combination with antithyroid drugs in treating Graves' disease.

[Clinical investigation on treatment of integrated traditional and Western medicine in hyperthyroidism with leukocytopenia induced by sulfourea drugs].

OBJECTIVE: To seek for a safe and effective drug to treat hyperthyroidism. METHODS: Sixty cases of hyperthyroidism with leukocytopenia induced by sulfourea drugs were divided into treatment and control groups by 31 cases who were treated by traditional medicine Syndrome Differentiation and 29 cases who were treated by conventional western medicine alone respectively at random. They were estimated by total effective rate, major symptoms, WBC and immunological tests after four weeks. RESULTS: The total effective rate in the treatment group (96.8%) was more effective than that in the control group (86.2%, P < 0.05). The symptom recovery rate in the treatment group was better than that in the control group. The WBC in both were all increased, but in the treatment group, it was better than that in the control group (P < 0.05). The positive to negative rate of thyroglobulin antibody and thyromicrosome antibody in the treatment group was better than that in the control group (P < 0.01). CONCLUSIONS: It can not only improve the symptoms and immune function, but also increase WBC by using western medicine in combination with traditional medicine in treating hyperthyroidism.

[Immunity in children having had viral hepatitis A and been treated with various immunomodulators in the acute period]. / Sostoianie immuniteta u detei, perebolevshikh virusnym gepatitom A i lechennykh razlichnymi immunomoduliatorami v ostrom periode.

During the acute period of viral hepatitis A 51 children received saparal in the complex treatment while 84 children received metacil. It was established that convalescents of those receiving metacil showed less frequently residual phenomena, complications were absent, immunity indices normalized earlier. Saparal is recommended in mild and average severe forms of viral hepatitis A for 15-20 days showing advantages over metacil.

[Effect of 1-(chloromethyl)silatrane on biochemical indices in the tissue of experimental gastric ulcer]. / Vliianie 1-(khlormetil)silatrana na biokhimicheskie pokazateli tkani éksperimental'noi iazvy zheludka.

It has been demonstrated in rats with experimental gastric ulcer that 1-(chloromethyl) silatrane intensifies the development of granulation-fibrous tissue and favours optimization of the ratio of collagens and glycosaminoglycans, the main connective tissue biopolymers. Furthermore, 1-(chloromethyl) silatrane produces a more pronounced effect on hexosamine-containing glycoproteins in the ulcer tissue as compared with methyluracil and oxyferriscorbon. At the same time, judging by the time course of sialoproteins, the antiulcerous drugs, methyluracil and oxyferriscorbon, are much more effective antiinflammatory agents than 1-(chloromethyl)silatrane.

[Experimental protective action of kanamycin, ampicillin and their combination with methyluracil and pyrogenal]. / Zashchitnoe deistvie kanamitsina, ampitsillina i ikh sochetaniia s metiluratsilom i pirogenalom v éksperimente.

Efficacy of kanamycin, ampicillin and their combinations with methyluracyl and pyrogenal in experimental Coli infections was studied. The antibiotics were administered an hour after the infection. Methyluracyl and pyrogenal were used according to 2 schemes. Scheme No. I: the drug is used daily for 7 days in increasing doses, the last dose is administered 24 hours before the infection. Scheme No. 2: the drug is used once at the moment of the infection. The methyluracyl doses were: 0.5, 1.0, 2.5 mg and 5 mg and 5 mg per a mouse during the following 4 days. The pyrrogenal doses were: 5, 10, 15, 25, 30 and 35 minimum pyrogenic doses. 5 mg of methyluracyl and 35 minimum pyrogenic doses of pyrogenal were used according to scheme No. 2. The most pronounced increase in the efficacy of kanamycin, ampicillin and their combination was observed in the animals treated simultaneously with methyluracyl and pyrogenal according to scheme No. 1. The efficacy of kanamycin and ampicillin increased 3 and 2.68 times respectively. ED50 of kanamycin and ampicillin used in combination in the animals treated with methyluracyl and pyrogenal was lowered 4 and 2.9 times respectively as compared to that in the animal groups treated only with the antibiotic combination and 21 and 15.2 times respectively when the antibiotics were used alone. Sanation of the animal organs was also rather successful. A single administration of methyluracyl and pyrogenal simultaneously with the infection (scheme No. 2) had a lower effect on the efficacy.

[Possibilities of preventing cardiotoxic complications in chemotherapy with carminomycin]. / Vozmozhnosti preduprezhdeniia kardiotoksicheskikh oslozhnenii pri khimioterapii karminomitsinom.

Carminomycin chemotherapy of the patients with malignant tumors is often complicated with cardiopathy which is sometimes assymptomic and registered only electrocardiographycally. Chemotherapy on the background of reparative regeneration stimulators from the series of synthetic pyrrimidine derivatives, such as methyluracyl for oral use and a soluble salt of methyluracyl for parenteral administration significantly decreased the rate of the cardiotoxic complications and promoted a decrease in their level. The use of methyluracyl and its soluble salt did not decrease the therapeutic effect of carminomycin. Methyluracyl and its soluble salt may be recommended for prophylaxis of cardiotoxic complications in chemotherapy of malignant tumors with carminomycin.

The increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter.

Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 mo and 69% within 1 yr of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive.

[Evaluation of the results of treatment of Graves' disease by synthetic antithyroid drugs]. / Evaluation des résultats du traitement de la maladie de Basedow par les anti-thyroïdiens de synthèse.

A study of 43 case records of Grave's disease followed up for at least two years after stopping treatment with synthetic antithyroid drugs, revealed 7 patients who did not relapse, 12 cases of rebound, (less than six months after stopping treatment), and 21 cases of recurrence (more than six months) of 10 cases (23%) had several recurrences. In relation to the 87 patients who formed this series, the cure rate after a single acute attack was only 50%. The good tolerance of antithyroid drugs, their almost complete efficacy, (2 failures out of 87 patients), indicate however that for a first attack they should be given for at least 18 months. Rebounds and recurrences suggest that radical treatment, mainly surgery, still have their place.