Intraperitoneal actinomycosis in a cat.
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Actinomyces↗
Biomedical subjects
R Azuma
Publications and source records attributed to R Azuma.
Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in humans.
1. TAS-103, a novel condensed quinoline derivative, has been developed as an anticancer drug targeting topoisomerases I and II. 2. The purpose of the present study was to characterize the metabolism and urinary excretion of TAS-103 after the intravenous infusion of a single dose to patients in Phase I clinical trials. 3. Five metabolites were detected using high-performance liquid chromatography (HPLC) photodiode array and a precursor scan by liquid chromatography mass spectrometry mass spectrometry (LC/MS/MS). 4. Structures of the five metabolites were determined using the results of enzymatic hydrolysis and the analysis of production mass spectra obtained by LC/MS/MS, and by comparing HPLC retention times and UV, mass and production mass spectra of authentic standards. 5. The metabolites were identified as demethyl-TAS-103 glucuronide (DM-TAS-103-G), TAS-103 glucuronide (TAS-103-G), TAS-103 glucuronide N-oxide (NO-TAS-103-G), demethyl-TAS-103 (DM-TAS-103) and TAS-103 N-oxide (NO-TAS-103). 6. The mean total amount of TAS-103 and TAS-103-G in urine was only 6.03% of the dose, suggesting that urine is not the main elimination route. TAS-103 was extensively metabolized, and a small percentage of the parent drug (0.41%) was found in urine.
Aminoquinolines↗
First-pass of GTS-21 on canine gut wall and liver determined by portal-systemic concentration difference.
To clarify the cause of the canine individual variability of plasma concentration after oral administration of GTS-21 [(E)-3-(2,4-dimethoxybenzylidene)-3,4,5,6-tetra-hydro-2,3'-bipyridine dihydrochloride], we evaluated the absorption ratio (F(A)), intestinal availability (F(G)), and hepatic availability (F(H)). The bioavailability (F) was evaluated from the ratio of the area under the plasma concentration versus time curves after oral and intravenous administration. Three isoflurane anaesthetised dogs were fitted with an electromagnetic flow probe attached to the portal vein and cannulated through the portal and the femoral veins. After intraduodenal administration of GTS-21, both plasma concentrations were determined simultaneously. F(A) x F(G) was calculated from the portal-systemic concentration difference taking into consideration the blood-plasma partition ratio. F(A) was calculated from the residual drug contents of the small intestine. F(H) was calculated by dividing F by F(A) x F(G). The F values were 0.072, 0.021, and 0.037, indicating an individual variability of ca. threefold. The F(A) values were close to 1, and the F(G) values ranged from 0.449 to 0.461. Accordingly, the F(H) values were estimated at 0.170, 0.047, and 0.083. GTS-21 was completely absorbed but lost by first-pass effects of passage through the gut wall and liver. The first-pass effect of liver is larger than that of the gut wall, and dominates the individual variability in plasma concentration.
Animals↗
Reconfiguration of task-set: is it easier to switch to the weaker task?
Switching between two tasks afforded by the same stimuli results in slower reactions and more errors on the first stimulus after the task changes. This "switch cost" is reduced, but not usually eliminated, by the opportunity to prepare for a task switch. While there is agreement that this preparation effect indexes a control process performed before the stimulus, the "residual" cost has been attributed to several sources: to a control process essential for task-set reconfiguration that can be carried out only after the stimulus onset, to probabilistic failure to engage in preparation prior to the stimulus, and to two kinds of priming from previous trials: positive priming of the now-irrelevant task set and inhibition of the now-relevant task-set. The main evidence for the carry-over of inhibition is the observation that it is easier to switch from the stronger to the weaker of a pair of tasks afforded by the stimulus than vice versa. We survey available data on interactions between task switching and three manipulations of relative task strength: pre-experimental experience, stimulus-response compatibility, and intra-experimental practice. We conclude that it is far from universally true that it is easier to switch to the weaker task. Either inhibition of the stronger task-set is a strategy used only in the special case of extreme inequality in strength, or its consequences for later performance may be masked by slower post-stimulus control operations for more complex tasks. Inhibitory priming may also be stimulus specific.
Attention↗
The effect of repeat administration of GTS-21 on mixed-function oxidase activities in rat.
The effect of repeat administration of GTS-21 on hepatic microsomal enzymes was determined in rats administered the drug at levels of 3, 60 and 300 mg/kg/day for 7 days. Liver weight and cytochrome P450 (CYP) contents were not changed. Cytochrome b5 contents were increased at the mid and high doses of GTS-21, as the contents increased with increasing dose, but were unchanged at the low dose. Five selective activities of CYP isoforms, acetanilide hydroxylase (CYP1A2), tolbutamide hydroxylase (CYP2C6), dextromethorphan O-demethylase (CYP2D1), p-nitrophenol hydroxylase (CYP2E1) and erythromycin N-demethylase (CYP3A) were examined. Enzyme activities were changed only at the highest dose; the activity of CYP1A2 was increased by 71% and the activities of CYP2C6 and CYP2D1 were decreased by 37 and 19%, respectively. At low and mid doses of GTS-21, all activities were unchanged. These data indicate that GTS-21 is not a strong modulator of the mixed-function oxidase system.
Alzheimer Disease↗
Experimental actinomycosis caused by Actinomyces-like bacteria in mice and a sow.
The present experiment was performed to test the pathogenicity of Actinomyces-like bacteria in experimental animals and swine. Two rough (R) strains of Actinomyces-like bacteria isolated from a site of arthritis and from the tonsil in pigs were used as inocula. To investigate their susceptibility to Actinomyces-like bacteria, BALB/c, SS and ddY mice and guinea-pigs were inoculated intraperitoneally with the strains of Actinomyces-like bacteria. The ddY mice were used for the long-term observation of Actinomyces-like bacteria lesions and the mammary tissue of a sow was inoculated with Actinomyces-like bacteria isolated from swine tonsil. Macroscopic observation revealed many abscesses on the surfaces of the abdominal and/or thoracic organs in the mice, but not on those of the guinea-pigs. The sow developed firm nodules at the inoculation site in the mammary glands. Histopathologically, the lesions in the mice were characterized as actinomycotic abscesses in the early stage and as pus-forming granuloma (PFG) in the advanced stage; the lesions were accompanied by crystalloid particles. Actinomyces-like bacteria induced granulomatous mastitis in the sow, and the lesion was characterized as PFG. The characteristic actinomycotic lesions in swine mammary glands were reproduced by experimental infection.
Actinomyces↗
Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease.
1. GTS-21, a novel drug for Alzheimer's disease, is currently under clinical development. In the current study, the metabolism and disposition of GTS-21 have been evaluated in rat and dog after single oral and intravenous administration. 2. Following oral administration of [14C]GTS-21 to rat, radioactivity was primarily excreted in the faeces (67%) via the bile with possible enterohepatic circulation. Urinary excretion of radioactivity in rat and dog was 20 and 19% respectively. 3. GTS-21 was rapidly and extensively absorbed after oral administration and rapidly cleared from plasma. The maximum concentration ratio of GTS-21 to total radioactivity in plasma was low, indicating first-pass or pre-systemic biotransformation. 4. In rat, GTS-21 showed linear pharmacokinetics over doses ranging from 1 to 10 mg/kg with an absolute bioavailability of 23%. In dog, the absolute bioavailability was 27% at an oral dose of 3 mg/kg. 5. GTS-21 was O-demethylated to yield compounds that were then subject to glucuronidation. Three of the metabolites in rat urine were isolated and characterized as 4-OH-GTS-21, 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. The major urinary metabolites were 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. 6. In vitro chemical inhibition of cytochrome P450 in human liver microsomes indicated that CYPIA2 and CYP2E1 were the isoforms primarily responsible for the O-demethylation of GTS-21, with some contribution from CYP3A.
Alzheimer Disease↗
Effects of response type on coordinated responses during arm movement.
This paper reports some experimental results on the coordination of finger and vocal responses with passing through a target position in multijoint arm movement. In Experiment 1, we found that the difference in the timing of finger and vocal responses cannot be attributed entirely to efferent or representational effects. Instead, it appears to reflect the extent to which information about the internal stimuli generated by the arm movement are available to the centers controlling these different responses. That is, it is a compatibility effect. In Experiment 2, the case in which a finger response is made on the same side of the body as the moving arm was compared with the case in which it is made with the contralateral hand, which remains static. The interaction effect observed suggests that the pathways subserving coordinated responses are informationally encapsulated, so that information about arm movement is not shared between the neural centers controlling different coordinated responses.
Adult↗
Immunohistochemical detection for Actinomyces sp. in swine tonsillar abscess and granulomatous mastitis.
The tonsils of eleven pigs and the mammary glands of a sow were used to investigate actinomycotic lesions due to Actinomyces sp. infection. At necropsy, there was no abnormality on these tonsils, on the other hand, numerous abscesses containing sulfur granules were found in the mammary. Histopathologically, the Actinomyces sp. lesions were noted as crypt abscesses in the tonsils and as pus-forming granulomas in the mammary glands. The microorganisms in both lesions were composed of bead-like cocci, bacillary cells and short, branching filaments, those cells being positive by the Gram's and Grocott's methods. Clubs were formed around the microbial clumps in these lesions. Immunohistochemically, there were cross-reactions between antibodies of Actinomyces sp. Chiba 101 (101) and swine actinomycetes of 7 species: A. bovis, A. hyovaginalis, A. israeli, A. naeslundii, A. pyogenes, A. suis) formerly Eubacterium suits) and A. viscosus. However it was possible to differentiate Actinomyces sp. 101 from them by absorption and dilution of the antiserum, then the microorganisms in the tonsillar crypt abscesses and the granulomatous mastitis were labelled with an immunoperoxidase technique using the absorbed Actinomyces sp. 101 antiserum. Thus, these immunolabelling properties are suggestive of the presence of 'A. suis' (Grässer) Franke 1973.
Abscess↗
The p2gag peptide, AEAMSQVTNTATIM, processed from HIV-1 Pr55gag was found to be a suicide inhibitor of HIV-1 protease.
The p2gag peptide (AEAMSQVTNTATIM) processed from HIV-1 Pr55gag by HIV-1 protease was identified as a suicide inhibitor of the enzyme (Ki = 30 microM and IC50 = 10 microM for the synthetic peptide substrate, succinyl-SQNYPIVQ), and potently inhibited the proteolytic cleavage of the viral precursor protein (Pr55gag) into functional structural units (p17gag and p24gag) in vitro. The nonapeptide (AEAMSQVTN) derived from N-terminus of the p2gag peptide exhibits a potent inhibitory action on HIV-1 protease, but the other peptides (AEAMSQ, AEAMSQV, AEAMSQVT, VTN and VTNTATIM) do not. It was determined by exclusion gel chromatography that HIV-1 protease after treatment of the synthetic p2gag peptide dissociated from the active dimeric form to an inactive monomeric form. The p2gag peptide and HIV-1 protease were also detected in HIV-1 viral particles using both matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI TOF-MS) and western immunoblot analyses. Taken together, these results suggest that the p2gag peptide is the inhibitor of preventing dimerization of HIV-1 protease and that the enzyme activity is completely suicide inhibited with the accumulated p2gag peptide producing by the processing of Pr55gag during viral maturation.
Dimerization↗
Interstitial deletion of 6q21-q23 associated with split hand.
We report on a 7-month-old boy with interstitial deletion of 6q21-q23 and split-hand defect. He died at 7 months. This is the fifth patient with distal limb anomaly associated with a rearrangement of 6q21 region, and supports previous suggestions that there may be candidate gene(s) for distal limb development in the 6q21 region.
Chromosome Deletion↗
Simultaneous determination of a novel anticancer drug, TAS-103, and its N-demethylated metabolite in monkey plasma by high-performance liquid chromatography using solid-phase extraction.
A simple and rapid method for the analysis of a novel anticancer drug, TAS-103, and its metabolite demethyl-TAS-103 in monkey plasma has been developed. This method is based on high-performance liquid chromatography with visible detection at 460 nm after solid-phase extraction with a Sep-Pak Vac PS-2 cartridge. The extraction recoveries of each compound, including the internal standard TAS-1-1018, were from 88 to 102%. The quantitation limit of each compound was 5.0 ng/ml in 0.5 ml of plasma. The coefficients of variation for each compound ranged from 0.9 to 4.9%, and relative errors for each compound ranged from -3.8 to 4.6%. Both compounds in monkey plasma were stable at -80 degrees C for 39 days and the extracts were stable at ambient temperature for 24 h. This method has been demonstrated to be useful for the pharmacokinetic study of TAS-103 in monkey plasma after intravenous administration.
Aminoquinolines↗
Incidence of tonsillar lesions caused by Tonsillophilus suis and Actinomyces sp infection in swine.
The tonsils of ten fattening pigs were compared with those of ten breeding sows to determine the relative incidence of Tonsillophilus suis and Actinomyces sp lesions. Macroscopic observation revealed mildly focal upheavals on the tonsillar mucosal surfaces of two of the breeding sows. In tonsillar slices from both pig groups, tiny nodules containing sulfur granules were found. Histopathologically, the T. suis and Actinomyces sp lesions were noted as tonsillar crypt abscesses in both pig groups, and granulomas due to T. suis were seen in the breeding sows. T. suis showed larger 'club-shaped' structures than Actinomyces sp, characterized as clubs showing a broom-like structure with degenerated central thalli. Breeding sows are known to have a higher incidence of tonsillar T. suis lesions than fattening pigs, and in this study, those fattening pigs showing greater propensity to infection by Actinomyces sp also showed a mixed infection with T. suis that produced the tonsillar crypt abscesses. In addition, it is known that in breeding sows, the T. suis lesion develops from a crypt abscess into a granuloma.
Actinomyces↗
Lymph node abscess due to Actinomyces viscosus in a cat.
In a four-year-old male cat, a subcutaneous phyma about 3.5 cm in diameter was surgically removed from the left inframandibular region. Histopathologically, the phyma was found to be the swollen medial retropharyngeal lymph node containing an actinomycotic abscess. The filamentous organisms in the abscess stained positively by the Gram's, Grocott's and periodic acid-Schiff methods, and were negative by the Ziehl-Neelsen method. By the immunoperoxidase method, the organisms were specifically identified as Actinomyces viscosus serotype 2 by its antiserum absorbed with A. viscosus serotype 1 antigen.
Abscess↗
Simultaneous determination of GTS-21 and its metabolite in rat plasma by high-performance liquid chromatography using solid-phase extraction.
It has been suggested that GTS-21 can improve the learning deficits and inhibit the neuro-degeneration in patients with Alzheimer's disease. This paper describes a reversed-phase high-performance liquid chromatographic assay with visible detection at 405 nm for determination of GTS-21 and its metabolite, 4-hydroxy-GTS-21 in rat plasma. The method uses solid-phase extraction with a Bond Elut C18 column. A quantitation limit of 1.0 ng/ml was achieved using 0.5 ml of rat plasma. In the validation study, the coefficients of variation and the relative errors of each compound were less than 10%. Also freeze-thaw and storage stability were confirmed. This method has proved to be applicable to the pharmacokinetic study of GTS-21 in rats.
Animals↗
[A study of coping in middle-aged women with urinary incontinence].
The purpose of this study is to clarify the coping patterns of women with urinary incontinence (UI) who visited an incontinence special unit. Nineteen patients ranging from 42 to 86 in age were interviewed. When they had met the accidents or daily occurrences with UI, their attitudes toward UI were classified into six coping patterns. They were "managing of UI", "keeping UI in secret", "asking for medical treatment for UI", "asking for support", "accepting UI as a fact or being resigned to UI, and "avoiding the fact with UI". All these six coping patterns reflect their desire to keep themselves in normal status. They concentrated themselves on maintain the normalization so as to keep their self-esteem from the threat of UI.
Adaptation, Psychological↗
Assay of proteases from Actinomyces pyogenes isolated from pigs and cows by zymography.
Extracellular proteases of Actinomyces pyogenes were assayed by zymography on SDS-polyacrylamide gel with the concentrated culture supernatant of 7 isolates from pigs and cows. When gelatin was used as a substrate, three proteases with molecular weights of 69, 59 and 55 kilodalton (kDA) were detected in all the isolates from both the pigs and cows. In addition to these proteases, 108 and 102 kDa proteases were detected in the swine and bovine isolates respectively. No protease bands appeared, however, when the calcium ion was absent from the buffer solution of the zymography. When casein was used as a substrate, the bands of 69, 59 and 55 kDa proteases were present, but 108 and 102kDa proteases were not detected in any of the isolates. The activity of all proteases was completely inhibited by phenylmethyl-sulfonyl fluoride and diisopropyl fluorophosphate but not by other protease inhibitors. From this result, it seems likely that the five proteases produced by A, pyogenes, originating from pigs and cows, are serine proteases.
Actinomyces↗