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1.
Braz. j. biol ; 83: e241164, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278551

ABSTRACT

Abstract Behavior is a useful trait for comparative studies that provide the comprehension of phylogenetic relationships among species. Here, we present a description of two spiny-rats species' behavioral repertoire, Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). The affiliative and agonistic behavioral patterns were sampled during a three-year study of captive populations of wild animals. Observational data were collected in two phases under different arrangements of individuals in groups. We also compare the behavioral traits of T. setosus and C. laticeps with the known behavioral patterns of Trinomys yonenagae. We add categories to the previous descriptions of T. setosus and a standard ethogram for C. laticeps. Trinomys setosus showed a visual and vocal display we called foot-trembling, which was not described in this form and function for other species studied until now. We discuss the differences in their sociality levels and similarities and differences among behavior patterns and repertoires.


Resumo O comportamento é uma característica útil para estudos comparativos que fornecem a compreensão das relações filogenéticas entre as espécies. Apresentamos aqui uma descrição do repertório comportamental de duas espécies de ratos-de-espinho Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). Os padrões comportamentais afiliativos e agonísticos foram amostrados durante um estudo de três anos em populações de animais silvestres em cativeiro. Os dados foram coletados em duas fases sob diferentes arranjos de indivíduos em grupos sociais. Comparamos as características comportamentais de T. setosus e C. laticeps com as da espécie mais conhecida, T. yonenagae. Adicionamos categorias às descrições anteriores de T. setosus, e um etograma padrão para C. laticeps. Trinomys setosus mostrou uma exibição visual e vocal que chamamos de saltitar, que não foi descrito nesta forma e função para outras espécies do gênero estudado até agora. Discutimos diferenças nos níveis de socialidade e similaridades e diferenças entre os padrões comportamentais e repertórios.


Subject(s)
Animals , Rats , Rodentia , Social Behavior , Phylogeny , Brazil , Animals, Wild
2.
Braz. j. biol ; 83: 1-17, 2023. tab, ilus, graf
Article in English | LILACS, VETINDEX | ID: biblio-1468832

ABSTRACT

Behavior is a useful trait for comparative studies that provide the comprehension of phylogenetic relationships among species. Here, we present a description of two spiny-rats species' behavioral repertoire, Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). The affiliative and agonistic behavioral patterns were sampled during a three-year study of captive populations of wild animals. Observational data were collected in two phases under different arrangements of individuals in groups. We also compare the behavioral traits of T. setosus and C. laticeps with the known behavioral patterns of Trinomys yonenagae. We add categories to the previous descriptions of T. setosus and a standard ethogram for C. laticeps. Trinomys setosus showed a visual and vocal display we called foot-trembling, which was not described in this form and function for other species studied until now. We discuss the differences in their sociality levels and similarities and differences among behavior patterns and repertoires.


O comportamento é uma característica útil para estudos comparativos que fornecem a compreensão das relações filogenéticas entre as espécies. Apresentamos aqui uma descrição do repertório comportamental de duas espécies de ratos-de-espinho Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). Os padrões comportamentais afiliativos e agonísticos foram amostrados durante um estudo de três anos em populações de animais silvestres em cativeiro. Os dados foram coletados em duas fases sob diferentes arranjos de indivíduos em grupos sociais. Comparamos as características comportamentais de T. setosus e C. laticeps com as da espécie mais conhecida, T. yonenagae. Adicionamos categorias às descrições anteriores de T. setosus, e um etograma padrão para C. laticeps. Trinomys setosus mostrou uma exibição visual e vocal que chamamos de saltitar, que não foi descrito nesta forma e função para outras espécies do gênero estudado até agora. Discutimos diferenças nos níveis de socialidade e similaridades e diferenças entre os padrões comportamentais e repertórios.


Subject(s)
Animals , Rats , Behavior, Animal , Rodentia
3.
Braz. j. biol ; 832023.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469048

ABSTRACT

Abstract Behavior is a useful trait for comparative studies that provide the comprehension of phylogenetic relationships among species. Here, we present a description of two spiny-rats species behavioral repertoire, Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). The affiliative and agonistic behavioral patterns were sampled during a three-year study of captive populations of wild animals. Observational data were collected in two phases under different arrangements of individuals in groups. We also compare the behavioral traits of T. setosus and C. laticeps with the known behavioral patterns of Trinomys yonenagae. We add categories to the previous descriptions of T. setosus and a standard ethogram for C. laticeps. Trinomys setosus showed a visual and vocal display we called foot-trembling, which was not described in this form and function for other species studied until now. We discuss the differences in their sociality levels and similarities and differences among behavior patterns and repertoires.


Resumo O comportamento é uma característica útil para estudos comparativos que fornecem a compreensão das relações filogenéticas entre as espécies. Apresentamos aqui uma descrição do repertório comportamental de duas espécies de ratos-de-espinho Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). Os padrões comportamentais afiliativos e agonísticos foram amostrados durante um estudo de três anos em populações de animais silvestres em cativeiro. Os dados foram coletados em duas fases sob diferentes arranjos de indivíduos em grupos sociais. Comparamos as características comportamentais de T. setosus e C. laticeps com as da espécie mais conhecida, T. yonenagae. Adicionamos categorias às descrições anteriores de T. setosus, e um etograma padrão para C. laticeps. Trinomys setosus mostrou uma exibição visual e vocal que chamamos de saltitar, que não foi descrito nesta forma e função para outras espécies do gênero estudado até agora. Discutimos diferenças nos níveis de socialidade e similaridades e diferenças entre os padrões comportamentais e repertórios.

4.
J Hosp Infect ; 123: 92-99, 2022 May.
Article in English | MEDLINE | ID: mdl-35217130

ABSTRACT

BACKGROUND: Decisions to isolate patients at risk of having coronavirus disease 2019 (COVID-19) in the emergency department (ED) must be rapid and accurate to ensure prompt treatment and maintain patient flow whilst minimising nosocomial spread. Reverse transcription polymerase chain reaction (RT-PCR) assays are too slow to achieve this, and near-patient testing is being used increasingly to facilitate triage. The ID NOW severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) assay is an isothermal nucleic acid amplification near-patient test which targets the RNA-dependent RNA-polymerase gene. AIM: To assess the diagnostic performance of ID NOW as a COVID-19 triage tool for medical admissions from the ED of a large acute hospital. METHODS: All adult acute medical admissions from the ED between 31st March and 31st July 2021 with valid ID NOW and RT-PCR results were included. The diagnostic accuracy of ID NOW [sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)] was calculated against the laboratory reference standard. Discrepant results were explored further using cycle threshold values and clinical data. FINDINGS: Two percent (124/6050) of medical admissions were SARS-CoV-2 positive on RT-PCR. Compared with PCR, ID NOW had sensitivity and specificity of 83.1% [95% confidence interval (CI) 75.4-88.7] and 99.5% (95% CI 99.3-99.6), respectively. PPV and NPV were 76.9% (95% CI 69.0-83.2) and 99.6% (95% CI 99.5-99.8), respectively. The median time from arrival in the ED to ID NOW result was 59 min. CONCLUSION: ID NOW provides a rapid and reliable adjunct for the safe triage of patients with COVID-19, and can work effectively when integrated into an ED triage algorithm.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/diagnosis , COVID-19 Testing , Humans , RNA , SARS-CoV-2/genetics , Sensitivity and Specificity , Triage
5.
Braz J Biol ; 83: e241164, 2021.
Article in English | MEDLINE | ID: mdl-34231655

ABSTRACT

Behavior is a useful trait for comparative studies that provide the comprehension of phylogenetic relationships among species. Here, we present a description of two spiny-rats species' behavioral repertoire, Clyomys laticeps and Trinomys setosus (Rodentia: Echimyidae). The affiliative and agonistic behavioral patterns were sampled during a three-year study of captive populations of wild animals. Observational data were collected in two phases under different arrangements of individuals in groups. We also compare the behavioral traits of T. setosus and C. laticeps with the known behavioral patterns of Trinomys yonenagae. We add categories to the previous descriptions of T. setosus and a standard ethogram for C. laticeps. Trinomys setosus showed a visual and vocal display we called foot-trembling, which was not described in this form and function for other species studied until now. We discuss the differences in their sociality levels and similarities and differences among behavior patterns and repertoires.


Subject(s)
Rodentia , Social Behavior , Animals , Animals, Wild , Brazil , Phylogeny , Rats
6.
Dis Esophagus ; 25(3): 209-13, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21899655

ABSTRACT

Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.


Subject(s)
Autoimmune Diseases/epidemiology , Esophageal Achalasia/epidemiology , Esophageal Achalasia/immunology , Adult , Age Factors , Canada/epidemiology , Confidence Intervals , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Female , Humans , Hypothyroidism/epidemiology , Lupus Erythematosus, Systemic/epidemiology , Male , Middle Aged , Odds Ratio , Prevalence , Retrospective Studies , Sjogren's Syndrome/epidemiology , Uveitis/epidemiology
7.
Am J Cardiol ; 85(5): 658-60, A10, 2000 Mar 01.
Article in English | MEDLINE | ID: mdl-11078286

ABSTRACT

Eighteen patients with heart failure were studied to clarify whether angiotensin-converting enzyme inhibitor treatment improves excess ventilation during exercise. Treatment with angiotensin-converting enzyme inhibitors had a beneficial effect on excess ventilation during exercise, without significant improvement in exercise capacity in patients with moderate congestive heart failure.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Cardiomyopathy, Dilated/complications , Enalapril/pharmacology , Heart Failure/drug therapy , Imidazoles/pharmacology , Imidazolidines , Pulmonary Ventilation/drug effects , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Enalapril/therapeutic use , Exercise Test , Exercise Tolerance/drug effects , Heart Failure/etiology , Humans , Imidazoles/therapeutic use , Middle Aged , Time Factors
8.
Bioorg Med Chem Lett ; 10(6): 531-4, 2000 Mar 20.
Article in English | MEDLINE | ID: mdl-10741547

ABSTRACT

The activity of a novel series of peptidomimetic hematoregulatory compounds, designed based on a pharmacophore model inferred from the structure activity relationships of a peptide SK&F 107647 (1), is reported. These compounds induce a hematopoietic synergistic factor (HSF) which in turn modulates host defense. The compounds may represent novel therapeutic agents in the area of hematoregulation.


Subject(s)
Cardiovascular Agents/chemical synthesis , Chemokines, CXC , Intercellular Signaling Peptides and Proteins , Oligopeptides/pharmacology , Amino Acids/chemistry , Animals , Candidiasis/drug therapy , Cardiovascular Agents/pharmacology , Cardiovascular Agents/therapeutic use , Cell Line , Chemokine CXCL1 , Chemotactic Factors/metabolism , Drug Design , Granulocyte Colony-Stimulating Factor/biosynthesis , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Growth Substances/metabolism , Macrophage Colony-Stimulating Factor/biosynthesis , Mice , Oligopeptides/chemistry , Receptors, Drug/chemistry , Receptors, Drug/drug effects
9.
Biol Pharm Bull ; 22(7): 698-702, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10443465

ABSTRACT

Effects of the administration of a water-soluble prodrug of vitamin E on doxorubicine (DXR)-induced lethal and oxidative toxicity in mice were studied. The prodrug used was d-alpha-tocopheryl N,N-dimethylaminoacetate hydrochloride (TDMA). It was intravenously administered to animals 2 h prior to an intraperitoneal administration of DXR (15 mg/kg). The single preadministration of the prodrug (10-50 mg/kg equivalent for d-alpha-tocopherol) delayed the DXR-induced death and the ameliorative effect was TDMA-dose dependent. The extent of total lipid peroxidation of the heart and liver was assessed by 2-thiobarbituric acid reactant substance levels. DXR significantly accelerated lipid peroxidation in the liver but not in the heart. The elevation of liver lipid peroxide was significantly suppressed to a normal range by a single preadministration of TDMA (50 mg/kg equivalent for d-alpha-tocopherol). TDMA did not significantly affect the antitumor activity of DXR in mice inoculated with L1210 leukemia cells.


Subject(s)
Antineoplastic Agents/toxicity , Doxorubicin/toxicity , Glycine/analogs & derivatives , Prodrugs/pharmacology , Vitamin E/analogs & derivatives , Vitamin E/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Doxorubicin/therapeutic use , Drug Therapy, Combination , Glycine/pharmacology , Glycine/therapeutic use , Leukemia L1210 , Lipid Peroxidation/drug effects , Male , Mice , Prodrugs/therapeutic use , Protective Agents/pharmacology , Solubility , Vitamin E/therapeutic use , Water
10.
Ann Nucl Med ; 13(2): 127-32, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10355959

ABSTRACT

A tetradentate chelating agent constituting of an iminodiacetic acid group and a nitrogen atom of pyridine, N-(2-pyridylmethyl)iminodiacetic acid (PMIDA), was coordinated with 99mTc and evaluated as a renal functional agent. The complex of PMIDA with 99mTc was prepared by using a stannous chloride solution as a reducing agent. The chelating efficiency was analyzed by thin layer chromatography and electrophoresis. Chelation with 99mTc resulted in a single radiochemical product. Biological studies were performed in mice and rats. 99mTc-PMIDA was removed from the circulation solely by the kidneys. Clearance of 99mTc-PMIDA from the blood and the kidneys was as rapid as that of 99mTc-diethylenetriaminepentaacetic acid. The rate of blood clearance was unaffected by the administration of probenecid (a test for tubular secretion by the weak-acid mechanism), so that the glomerular filtration rate could be estimated by measuring its clearance from the blood. The results in animals with myohemoglobinuric acute renal failure suggested that 99mTc-PMIDA might be a useful renal function radiopharmaceutical.


Subject(s)
Acute Kidney Injury/diagnostic imaging , Imino Acids , Kidney/diagnostic imaging , Organotechnetium Compounds , Radiopharmaceuticals , Acute Kidney Injury/metabolism , Acute Kidney Injury/physiopathology , Animals , Chelating Agents , Chromatography, Thin Layer , Electrophoresis , Glomerular Filtration Rate , Hydroxamic Acids , Imino Acids/chemical synthesis , Imino Acids/chemistry , Imino Acids/pharmacokinetics , Isothiocyanates , Kidney/metabolism , Kidney/physiopathology , Mice , Mice, Inbred ICR , Organotechnetium Compounds/chemical synthesis , Organotechnetium Compounds/chemistry , Organotechnetium Compounds/pharmacokinetics , Pentetic Acid/analogs & derivatives , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Rats , Technetium/chemistry
11.
Heart ; 81(5): 523-7, 1999 May.
Article in English | MEDLINE | ID: mdl-10212172

ABSTRACT

OBJECTIVE: To determine whether dobutamine stress echocardiography can predict the improvement of left ventricular systolic function in patients with dilated cardiomyopathy (DCM). METHODS: Myocardial contractile reserve, as assessed by dobutamine stress echocardiography, was determined in 18 patients with DCM (mean (SD) age 53 (13) years, left ventricular ejection fraction (LVEF) 28 (10)%) and compared with changes in LVEF during a follow up period of 15 (8) months. The LVEF and regional left ventricular wall motion score (0, normal to 4, dyskinesis) of 12 segments in short axis and four chamber views were analysed before and after dobutamine infusion (5-20 microg/kg/min). RESULTS: During a follow up period of 15 (8) months, a significant improvement in LVEF (> 20%) was found in seven patients but not in the remaining 11. Baseline haemodynamic findings were similar in both groups. Patients with an improvement in follow up LVEF showed a greater change in wall motion score from baseline during dobutamine infusion than patients with no improvement (at rest, 1.7 (0.4) v 1.9 (0.2), NS; dobutamine 10 microg/kg/min, 0.6 (0.4) v 1.2 (0.4), p < 0.05). The percentage change in LVEF during dobutamine infusion was also significantly greater in patients who showed improvement than in those who did not. The change in LVEF during the follow up period (follow up LVEF/baseline LVEF) correlated well with the change in LVEF during dobutamine stress (LVEF at rest/LVEF at dobutamine 10 microg/kg/min; r = 0.74, p < 0.001). CONCLUSIONS: Changes in left ventricular systolic performance during low dose dobutamine stress echocardiography are a useful marker to predict the outcome of left ventricular systolic function in patients with DCM.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Cardiotonic Agents , Dobutamine , Ventricular Dysfunction, Left/diagnosis , Adult , Cardiomyopathy, Dilated/diagnostic imaging , Echocardiography , Exercise Test , Female , Follow-Up Studies , Heart/diagnostic imaging , Humans , Male , Middle Aged , Prognosis , Regression Analysis , Tomography, Emission-Computed, Single-Photon , Ventricular Dysfunction, Left/physiopathology
12.
Chem Pharm Bull (Tokyo) ; 47(3): 413-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10212390

ABSTRACT

Conjugates of 2-aminooxyethyliminodiacetic acid with estrone, testosterone, epiandrosterone, 17-alpha-hydroxy-progesterone and progesterone were synthesized and their complexes with Tc-99m were successfully prepared in good yields, which indicated the agent to be promising for metal-labeling of biomolecules and related substances containing one or more carbonyl groups. The biodistribution and scintigraphic studies in mice bearing Ehrlich tumor and mammary tumor showed that the radioactivity accumulated considerably in the tumor tissues, but the tumor images were somewhat obscured.


Subject(s)
Imino Acids/chemistry , Radiopharmaceuticals/chemical synthesis , Steroids/chemistry , Technetium/chemistry , Animals , Carcinoma, Ehrlich Tumor/diagnostic imaging , Female , Isotope Labeling , Male , Mammary Neoplasms, Experimental/diagnostic imaging , Mice , Mice, Inbred ICR , Quality Control , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution
13.
Biol Pharm Bull ; 22(2): 172-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10077437

ABSTRACT

The N,N-dimethylglycine esters of menahydroquinone-4 (1-mono, 1; 4-mono, 2; 1,4-bis, 3) were established in previous reports as prodrugs that could achieve the systemic bioreductive activation-independent delivery of menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4), in rat. The present study was undertaken to investigate if the prodrugs could undergo cleavage to parent drug (MKH) by a human tissues enzyme catalyzed hydrolytic pathway, the mechanism of the prodrugs for vitamin K-dependent carboxylation in human liver and their action in the warfarin poisoned human liver. The hydrolysis of the esters was shown to be catalyzed by esterases located in human liver but not in human plasma. The susceptibility of the esters to undergo human liver esterase hydrolysis was affected by the esterified position: 1>2>3. By using a human liver microsomal test system, the stimulation of vitamin K-dependent carboxylation with the prodrugs was determined. The prodrug could stimulate the carboxylation activity in the absence of dithiothreitol, an artificial activator of the reductive activation pathway of MK-4. The carboxylation activity of the prodrug was strongly inhibited in the presence of eserine, an esterase inhibitor. The prodrug could also stimulate the carboxylase under warfarin-poisoned conditions, where the vitamin K cycle was strongly inhibited. The results confirmed that the prodrug could generate MKH in human liver (active site), and that the resultant MKH could act as a cofactor for the carboxylase without reductive activation processes of MK-4 to MKH. Such bioreductive activation-independent vitamin K-dependent carboxylation characteristic of the prodrug leads to enhanced pharmacological efficacy in the treatment of hypoprothrombinaemia induced in patients with coumarin and cephalosporin therapies.


Subject(s)
Hydroquinones/pharmacokinetics , Microsomes, Liver/enzymology , Prodrugs/pharmacology , Vitamin K 2/analogs & derivatives , Vitamin K/analogs & derivatives , Warfarin/poisoning , Biotransformation , Carboxylic Acids/metabolism , Enzyme Inhibitors/pharmacology , Esterases/antagonists & inhibitors , Humans , Hydrolysis , Hydroquinones/blood , Microsomes, Liver/drug effects , Oxidation-Reduction , Vitamin K/blood , Vitamin K/pharmacokinetics
14.
Ann Nucl Med ; 13(6): 407-13, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10656275

ABSTRACT

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value.


Subject(s)
Antibodies, Monoclonal , Carcinoembryonic Antigen/immunology , Radioimmunodetection/methods , Stomach Neoplasms/diagnostic imaging , Technetium/pharmacokinetics , Animals , Antibodies, Monoclonal/pharmacokinetics , Gamma Cameras , Humans , Mice , Mice, Nude , Recombinant Fusion Proteins/pharmacokinetics , Tissue Distribution , Transplantation, Heterologous , Tumor Cells, Cultured
15.
Biol Pharm Bull ; 22(12): 1347-54, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10746168

ABSTRACT

With the aim of overcoming the delivery problems (water-solubility and bioreductive activation problems) of phyllohydroquinone (PKH), an active form of phylloquinone (PK, vitamin K1), the N,N-dimethylglycine esters of phyllohydroquinone (1-mono, 1; 4-mono, 2; and 1,4-bis, 3) have been synthesized and assessed in vitro as a prodrug for the systemic bioreductive activation-independent delivery of PKH. The hydrochloride salts of the esters were found to be quite soluble in water. Hydrolysis of the esters in rat liver S9 fraction, rat plasma and phosphate buffer, pH 7.4, at 37 degrees C, was kinetically studied in the presence and absence of an esterase inhibitor. The hydrolysis was catalyzed by esterases located in rat liver and rat plasma and quantitatively yielded PKH. The enzymatic cleavage and the vitamin K-dependent carboxylation activity of the esters in the rat liver microsome preparation at pH 7.2 and 25 degrees C were studied. The regeneration of PKH from the esters was catalyzed by carboxylesterases located in the rat liver microsome, and the order was as follows: 1 > 3 > 2. The carboxylation was stimulated by selected ester 1 in the absence of dithiothreitol, an activator of the vitamin K cycle. The carboxylation activity of 1 was strongly inhibited in the presence of eserine, a carboxylesterase inhibitor. Compound 1 could also stimulate carboxylase under warfarin-poisoning conditions, where the vitamin K cycle was strongly inhibited. These results indicated that these highly water-soluble and liver-esterase hydrolyzable ester derivatives of PKH are potential candidates for parenteral prodrugs which can thus achieve the systemic bioreductive activation-independent delivery of PKH.


Subject(s)
Microsomes, Liver/metabolism , Prodrugs/administration & dosage , Vitamin K 1/administration & dosage , Vitamin K/analogs & derivatives , Animals , Biotransformation , Drug Delivery Systems , Drug Interactions , Esterases/antagonists & inhibitors , Esters/chemistry , Esters/metabolism , Hydrolysis , Male , Microsomes, Liver/drug effects , Oxidation-Reduction , Prodrugs/pharmacology , Rats , Rats, Wistar , Solubility , Vitamin K/administration & dosage , Vitamin K/chemical synthesis , Vitamin K/metabolism , Vitamin K 1/pharmacology , Warfarin/poisoning
17.
J Cardiol ; 31 Suppl 1: 147-52; discussion 153, 1998.
Article in Japanese | MEDLINE | ID: mdl-9666410

ABSTRACT

A 32-year-old woman presented with a rare case of tricuspid valve endocarditis causing inflammatory reopening of the spontaneously closed ventricular septal defect (VSD), associated with aortic valve malformation. She was admitted to our hospital because of fever lasting 4 weeks. Severe aortic regurgitation was revealed by color Doppler echocardiography. Blood culture identified Microccus faecalis. Antibiotics were administered over 3 weeks, but serial echocardiography showed a developing vegetation in the right ventricle and left-to-right shunt flow. The diagnosis was infective endocarditis complicated by aortic ring abscess and interventricular septal fistula. Surgery performed on the 22nd hospitalized day found a vegetation of the tricuspid valve, a membranous type of VSD, and aortic valve malformation. Aortic valve replacement, patch closure of VSD, and tricuspid valvuloplasty achieved a successful outcome.


Subject(s)
Aortic Valve Insufficiency/congenital , Endocarditis, Bacterial/etiology , Heart Septal Defects, Ventricular/pathology , Tricuspid Valve , Adult , Aortic Valve/abnormalities , Aortic Valve Insufficiency/surgery , Echocardiography, Doppler, Color , Endocarditis, Bacterial/surgery , Female , Gram-Positive Bacterial Infections/etiology , Heart Septal Defects, Ventricular/complications , Humans , Micrococcus , Tricuspid Valve/surgery
18.
Pathol Int ; 48(3): 221-4, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9589491

ABSTRACT

An autopsy case of a 58-year-old woman with massive cardiac involvement of adult T cell leukemia/lymphoma (ATLL) is reported. She developed cardiac failure due to aortic and mitral regurgitation with cardiac infiltration of ATLL cells, and underwent replacement of both aortic and mitral valves. Studies of the cut-surfaces revealed diffuse thickening of the subendocardial wall of the left chamber with widespread whitish-brown tumor infiltrates. In the regions surrounding the replaced aortic and mitral valves there was also massive tumor cell infiltration. The tumor cells infiltrating the cardiac muscle wall were T cell in origin and exhibited Leu-3a (CD4)-positive immunoreaction. Ultrastructurally, tumor cells contained markedly indented nuclei and some were attached directly to the muscle cells. These findings suggest that this was an unusual form of ATLL with widespread involvement of the heart.


Subject(s)
Heart Neoplasms/pathology , Heart Valves , Leukemia-Lymphoma, Adult T-Cell/pathology , Myocardium , Biomarkers, Tumor/metabolism , Fatal Outcome , Female , Heart Neoplasms/metabolism , Humans , Immunohistochemistry , Leukemia-Lymphoma, Adult T-Cell/metabolism , Leukocyte Common Antigens/metabolism , Microscopy, Electron , Middle Aged
19.
Am J Cardiol ; 81(2): 137-40, 1998 Jan 15.
Article in English | MEDLINE | ID: mdl-9591894

ABSTRACT

The autonomic nervous system importantly regulates coronary arterial tone and vascular resistance. To evaluate a role of autonomic nervous activity and the effects of calcium antagonist in patients with vasospastic angina (VSA), 13 VSA patients with patent coronary arteries (58+/-8 years) and 8 normal subjects (58+/-12 years) were studied. Arterial pressure and electrocardiogram were continuously recorded with the patient in a supine position under controlled respiration (0.2 Hz). Low-frequency (LF) and high-frequency (HF) components of the beat-to-beat variabilities of systolic arterial pressure and RR interval were then estimated by autoregressive power spectral analysis. The LF power (normalized unit) of both systolic arterial pressure (0.53+/-0.17 vs 0.30+/-0.17, p < 0.01) and RR variabilities (0.51+/-0.20 vs 0.31+/-0.16, p < 0.05) in patients with VSA were greater than that in normal subjects. There was no significant difference in the HF power. Seven patients with VSA who were treated with diltiazem (60 to 200 mg/day) had normalized LF power (normalized unit) of both systolic arterial pressure (0.62+/-0.12 vs 0.33+/-0.16, p < 0.01) and RR variabilities (0.55+/-0.23 vs 0.36+/-0.14, p < 0.05), together with clinical improvement. An increased sympathetic vasomotor tone and cardiac sympathetic predominance may play an important role in patients with VSA. Diltiazem improves these sympathetic hyperactivities.


Subject(s)
Angina Pectoris, Variant/physiopathology , Blood Pressure/physiology , Calcium Channel Blockers/therapeutic use , Diltiazem/therapeutic use , Heart Rate/physiology , Heart/innervation , Sympathetic Nervous System/drug effects , Angina Pectoris, Variant/diagnosis , Angina Pectoris, Variant/drug therapy , Blood Pressure/drug effects , Blood Pressure Monitoring, Ambulatory , Data Interpretation, Statistical , Echocardiography , Electrocardiography, Ambulatory/drug effects , Female , Heart/physiopathology , Heart Rate/drug effects , Humans , Male , Middle Aged , Supine Position , Sympathetic Nervous System/physiopathology , Treatment Outcome
20.
Jpn Circ J ; 62(4): 249-54, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9583457

ABSTRACT

To detect a significant narrowing of the left anterior descending artery in patients with inferior/posterior myocardial infarction, 200 patients underwent standard exercise testing. Age, gender, and grade of stenosis of the left anterior descending artery were similar in 138 patients with inferior myocardial infarction and 62 with posterior myocardial infarction. In patients with left anterior descending artery stenosis, there were more lateral leads with ST-segment depression (1.8+/-1.0 vs 1.1+/-1.1; p<0.01) and fewer anterior leads with ST-segment depression (2.1+/-1.4 vs 2.9+/-1.4; p=0.02) in those with inferior myocardial infarction than in those with posterior myocardial infarction. Applying the criterion of exercise-induced ST-segment depression > or = 0.1 mV, sensitivities and specificities in detecting left anterior descending artery stenosis were 98% and 21% respectively in inferior myocardial infarction and 94% and 26% respectively in posterior myocardial infarction. In contrast, discriminant analysis revealed sensitivities and specificities of 77% and 91% respectively in inferior myocardial infarction and 71% and 81% respectively in posterior myocardial infarction using the variables related to severity of inducible ischemia and lateral and anterior lead ST-segment depression. These results indicate that a multivariate approach underscoring the site of myocardial infarction can help in identifying stenosis of the left anterior descending artery in patients with inferior/posterior myocardial infarction.


Subject(s)
Coronary Vessel Anomalies/diagnosis , Diagnostic Techniques and Procedures , Exercise Test , Myocardial Infarction/physiopathology , Adult , Aged , Aged, 80 and over , Coronary Vessel Anomalies/pathology , Coronary Vessel Anomalies/physiopathology , Female , Humans , Male , Middle Aged , Myocardial Infarction/pathology
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