BACKGROUND: The surfactant specific proteins, SP-B and SP-C are believed to be important regulators of the surfactant function and homeostasis. Since acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults, and since abnormalities in the surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-B and SP-C. METHODS: Sprague-Dawley rats were given 5 mg/kg of an intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and were sacrificed at different time periods. RESULTS: 1. The SP-B mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 26.1% and 50%, respectively(P<0.01, P<0.001). 2. The SP-B mRNA levels 24 hours after the 3.5 mg/kg thiourea treatment was reduced by 9.8% and 12.5%, respectively. 3. The SP-C mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 38.7% and 53.6%, respectively(P<0.01, P<0.001). 4. The SP-C mRNA level 6 hours after the 3.5 mg/kg thiourea treatment was reduced by 22.8%(P<0.05). CONCLUSION: These results indicate that the differential regulation of the hydrophobic surfactant proteins in vivo is evident, and suggest that the hydrophobic surfactant proteins might be differentially regulated during lung injury at different time periods without altering the lung wet to dry ratios. The mechanism of these alternations at the different time periods and the different kinds of etiology remain to be determined.
Animals ; Gene Expression* ; Homeostasis ; Lung ; Lung Injury ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Salmonella enteritidis ; Thiourea*

The objectives of this study were to develop optimal analytic methods for detecting urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) and thiocarbamide simultaneously and to evaluate the usefulness of these metabolites to a biological exposure index (BEI) for carbon disulfide (CS2) exposure. For this experiment, synthesized TTCA and thiocarbamide were used. The synthesized TTCA was identified by infrared spectrophotometer, nuclear magnetic resonance spectrometer and thin layer chromatography. The recovery rates of both metabolites were calculated to find the optimum analytical method. The amounts of urinary TTCA and thiocarbamide were measured by using an ultraviolet detector connected to high performance liquid chromatography (HPLC) after the administration of CS2 (350, 700 mg/kg) into Sprague-Dawley rats intraperitoneally. The maximum absorbance wave lengths for TTCA and thiocarbamide were 272 and 236 nm, respectively. Ethyl acetate extraction with NaCl as a salting-out reagent was used as a simultaneous extraction method for these metabolites. HPLC conditions for these metabolites included using a NH2 column, 50 mM KH2PO4: acetonitrile (85:15) and pH 3. Excreted amounts of urinary TTCA and thiocarbamide were increased significantly following CS2 administration. TTCA, which was already adopted as a BEI for CS2 by the American Conference of Governmental Industrial Hygienists (ACGIH), seems to be a more useful BEI for CS2 exposure than thiocarbamide. However further studies are needed to increase analytical efficiency before thiocarbamide can be adopted as a BEI and to apply this analytic method for simultaneous analysis of these metabolites in workers exposed to CS2.
Animal ; Carbon Disulfide/pharmacology* ; Environmental Exposure* ; Rats ; Rats, Sprague-Dawley ; Thiazoles/urine* ; Thiourea/urine* ; Urea/urine*

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.
Action Potentials ; Animals ; Calcium/metabolism* ; Mice ; Myocytes, Cardiac/metabolism* ; Sodium/metabolism* ; Sodium-Calcium Exchanger ; Thiourea/pharmacology*

Attention has been paid to the thiocarbanilide derivative and the authors synthesized some new compounds of thiocarbanilides for experimental studies on tuberculosis and leprosy. The series of newly synthesized chemical compounds of thiocarbanilides were studied for comparision with the already known antimycobacterial agents; INH, PAS, Streptomycin and D. D. S. The strains of Mycobacterium tubercubsis (H37 Rv, Ravenel, and B. C. G.) and Mycobacterium phlei were used for the in vitro experiments. In the in vivo experiments, the strain of Mycobacterium tuberculosis var. bovis (Ravenel) was employed. The strain of Mycobacterium leprae murium (Hawaiian strain) was used for the murine leprosy experiments. The experimental animals for the in vivo tests were white mice (CFW strain) and these were extensively employed in tuberculosis and leprosy as well. Sixteen cases of Various types of human leprosy, were treated with one of the newly synthesized thiocarbanilides (L-4). Among the newly synthesized chemical compounds of thiocarbanilides studied for their antituberculous and antimurine leprosy activity in vitro and in vivo experiments, two compounds were shown to be suppressive agents for those infections without significant toxicity. These two compounds were named tentatively as L-1 and L-4. 1) LD50 of L-1 was 1,054 mg/kg and that of L-4 was 1,028 mg/kg, while the LD50 of INH was 650 mg/kg and PAS was 4,000mg/kg orally in the experimental animals. 2) L-1 and L-4 showed remarkable suppressive activity in vitro using solid media with 100r/ml. concentration. These data were parallel to 1r/ml. of INH and 50r/ml. of PAS. The inferiority of L-1 and L-4 to INH and PAS in vitro studies might have been due to the water insolubility of these compounds while INH and PAS were readily soluble in water. 3) In vivo experiments with L-1 showed a much-more superior antituberculous effect than was found with INH and PAS. 4) A method of grading the bacterial count in a homogenized tissue suspension of visceral organs (lungs, liver, spleen and kidneys) using the simple technique of the Gaffky scale was accurate and time saving technique in screening the results of the chemotherapeutic agents in tuberculosis. 5) Among the newly synthesized compounds L-4 showed the most remarkable suppressive effect on murine leprosy. The suppressive results were similar to those of INH. 6) The method of measuring the size and the weight of leproma at the inoculated site was simple and is an adequate screening test for chemotherapeutic effect in murine leprosy. 7) In the trials with human leprosy 16 cases of various types, using L-4, the effectiveness in clinical as well as in bacteriological improvement was remarkable. a) After L-4 treatment decrease in bactriologica1 indices and remarkable clinical improvement after a relative1y short period of treatment were observed. b) L-4, up to the maximum daily dose of 500 mg, can be safely administered orally to the patients without any significant side reactions. c) L-4 could be used with remarkable clinical improvement for the patients in lepra reactions.
Adult ; Animals ; Comparative Study ; Erythema Nodosum/drug therapy ; Female ; Human ; Leprosy/*drug therapy ; Male ; Mice ; Thiourea/*therapeutic use

AIMTo get some novel potent compounds with NOS inhibitory activity, a series of new compounds of isothioureas derived from 1,2,3,4-tetrahydroisoquinoline were synthesized.

METHODS1,2, 3,4-Tetrahydroisoquinol-2-yl was introduced into the structure of isothioureas, the NOS inhibitory activity of the new compounds synthesized were measured.

RESULTS AND CONCLUSIONTwenty-two isothiourea derivatives of [alkyl(or aryl) imino] (1,2,3,4-tetrahydroisoquinol-2-yl) methyl alkyl thioethers (I) and S-alkyl-1-phenyl-3-[4-(1,2,3,4-tetrahydroisoquinol-2-yl) methane] phenyl isothioureas (II) were synthesized from thioureas by S-alkylation with alkyl halides, and their structures were identified by IR, 1H NMR, MS and elemental analysis. The preliminary biological test showed that the part of type I (1-9 and 1-13) had higher NOS inhibitory activity than that the control aminoguanidine (AG), but the type II had weak ability to inhibit NOS.

Molecular Structure ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Stereoisomerism ; Tetrahydroisoquinolines ; chemistry ; Thiourea ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology

Animals ; Disease Models, Animal ; Liver ; parasitology ; Mice ; Mice, Inbred BALB C ; Schistosomiasis japonica ; immunology ; Thiourea ; analogs & derivatives ; pharmacology

AIMTo synthesize a series of 2-arylimino-4-thiazolidone derivatives and 2-imidazolino [2,3-b]-4-thiazolidone in order to get some novel potent compounds with nitric oxide synthases (NOS) inhibitory activity.

METHODSThe target compounds were prepared by reaction of N-chloroacetyl-1,2,3,4-tetrahydroisoquinoline or N-chloroacetylphthalimide with substituted thioureas, their NOS inhibitory activity were measured.

RESULTS AND CONCLUSIONThe 15 new compounds were synthesized and most of the reaction yields were over 65%. The structures of new compounds were identified by IR, 1H NMR, MS and elemental analyses. Bioassay indicated that, most of 15 new compounds synthesized had confirmed bioactivities inhibition against NOS.

Molecular Structure ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship ; Thiazoles ; chemical synthesis ; chemistry ; pharmacology ; Thiourea ; analogs & derivatives

BACKGROUND: The surfactant protein A(SP-A) is important in the regulation of surfactant secretion, synthesis and recycling. Since the acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults and since abnormalities in surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-A. METHODS: Sprague-Dawley rats were given 5 mg/kg intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and sacrified at different time periods. RESULTS: 1) SP-A mRNA was significantly increased 67.0% in 6 hours and 73.4% in 24 hours after 5 mg/kg endotoxin treatment respectively(P<0.005, P<0.005). 2)SP-A mRNA was significantly decreased 32.9% in 24 hours after 3.5 mg/kg thiourea treatment(P<0.05). CONCLUSIONS: These results indicate that the differential regulation of surfactant protein A in vivo is evident and suggest that surfactant protein A might be differentially regulated during different kind of insults of lung injury at different time periods without altering lung wet to dry ratios.
Animals ; Gene Expression* ; Lung Injury ; Lung* ; Pulmonary Surfactant-Associated Protein A* ; Rats* ; Rats, Sprague-Dawley ; Recycling ; RNA, Messenger* ; Salmonella enteritidis ; Thiourea*

The thiourea derivatives, propylthiouracil and methimazole are in widespread use for the treatment of hyperthyroidism. The untoward side effects of these drugs are not infrequent and agranulocytosis is the most serious side effect them. We observed one case of methimazole induced agranulocytosis complicated by deep neck abscess. A 54-year-old woman was admitted because of fever, chilling and sore throat for 1 week. The symptom was developed after receiving methimazole 30mg daily day due to hyperthyroidism during last 3 months. Physical examination revealed hyperemic, enlarged tonsils and tender swelling of the right lower neck The peripheral blood total leukoeyte count was 1,500/mm' (absolute neutrophil count, ANC 9) and a peripheral blood smear revealed few neutrophil. The patient was administered G-CSF 2 mg/kg daily, and on the fifth day of hospitalization, fever subsided and ANC increased to 3,431. On the 11th day, fever developed again and the tenderness and swelling in both lower neck area were aggrevated. Computed tomography of the neck was performed, and revealed a large deep neck abscess. After pus aspiration and antibiotics therapy, the neck abscess was disappeared.
Abscess* ; Agranulocytosis* ; Anti-Bacterial Agents ; Female ; Fever ; Granulocyte Colony-Stimulating Factor ; Hospitalization ; Humans ; Hyperthyroidism ; Methimazole* ; Middle Aged ; Neck* ; Neutrophils ; Palatine Tonsil ; Pharyngitis ; Physical Examination ; Propylthiouracil ; Suppuration ; Thiourea

It has been documented that SPA0355 exerts anti-inflammatory effects via the inhibition of nuclear factor-kappaB activation. In present study, we investigated the inhibitory effects of SPA0355 on periodontitis in an animal model. Periodontitis was induced by ligation of the cervix of the 1st molar in the left mandible in rats. After ligature, the rats were randomly divided into four groups and topically applied with SPA0355 (0.5, 1, and 2%) or the vehicle alone once daily for 10 days. Body weight and food intake were measured daily throughout the experimental period. At day 10 post-ligature, the infiltration of inflammatory cells and distance of the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) in the distal area of ligatured tooth were estimated histopathologically. No changes in body weight or food intake were found between the control and SPA0355 groups. The degree of inflammation was decreased in all three SPA0355 application groups. A decrease CEJ-ABC distance was observed in the 0.5% and 1% SPA0355 groups. These results indicate that SPA0355 inhibits the infiltration of inflammatory cells and alveolar bone resorption and suggests its potential as a therapeutic agent for periodontitis.
Alveolar Bone Loss ; Animals ; Benzoxazines ; Body Weight ; Bone Resorption ; Cervix Uteri ; Eating ; Female ; Inflammation ; Ligation ; Mandible ; Models, Animal ; Molar ; Periodontitis ; Rats ; Thiourea ; Tooth ; Tooth Cervix