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Biomedical subjects

J Kao

Publications and source records attributed to J Kao.

At least 73 records · Page 4Linked to original sources
PubMed1988

The spectrum of Escherichia coli--Bacteroides fragilis pathogenic synergy in an intraabdominal infection model.

Pathogenic synergy between Escherichia coli and Bacteroides fragilis was investigated in an intraabdominal infection model. Defined inocula of E. coli and B. fragilis, alone or in combination, were enmeshed within a fibrin clot and surgically implanted into the peritoneal cavity of rats. A spectrum of bacterial synergy ranging from synergistic abscess formation to synergistic lethality was demonstrated using this model. The type of synergy exhibited was dependent upon the initial E. coli inoculum. When combined with B. fragilis, high inocula of E. coli (greater than 10(8) cfu/clot) produced synergistic lethality while low inocula (2 x 10(2) to 2 x 10(7) cfu/clot) resulted in synergistic abscess formation. With respect to abscess formation, there was reciprocal synergy between E. coli and B. fragilis. Abscesses resulting from mixed inocula were larger and had significantly higher numbers of E. coli and B. fragilis than abscesses initiated by monomicrobial inocula. These studies define a clinically relevant model of bacterial interactions in the setting of intraabdominal infection and suggest that conclusions drawn from experimental models of bacterial synergy should consider the type of model examined, the strains of bacteria studied, and the number of bacteria inoculated.

Abscess↗
PubMed1988

Prevention of intra-abdominal abscesses with fibrinolytic agents.

Fibrin deposition during secondary peritonitis predisposes to abscess formation by protecting bacteria from host-defence mechanisms. To test the hypothesis that local fibrinolytic therapy can prevent the formation of intra-abdominal abscess, daily injections of the fibrinolytic enzymes trypsin and tissue plasminogen activator (t-PA) were administered intraperitoneally to Wistar rats inoculated intraperitoneally with infected fibrin clots. After 5 days, trypsin (1 mg/ml) had significantly (p less than 0.001) reduced abscess formation in animals inoculated with monomicrobial Bacteroides fragilis clots (20% versus 87%) or mixed Escherichia coli-B. fragilis clots (11% versus 91%). Bacteroides fragilis abscesses were also completely prevented with t-PA (0.25 mg/ml). The number of B. fragilis organisms present in residual abscesses in the trypsin-treated group was significantly (p less than 0.05) lower than in the control group (8.2 +/- 0.2, n = 7 versus 5.7 +/- 1.4, n = 4, log CFU/g abscess). In-vitro studies demonstrated that trypsin had no bactericidal effect on B. fragilis, suggesting enhanced clearance of bacteria. From these studies it appears that controlled fibrinolysis at operation may be a useful adjunct to surgery and systemic antibiotics in preventing abscess formation postoperatively.

Abdomen↗
PubMed1987

Skin absorption and cutaneous first pass metabolism of topical steroids: in vitro studies with mouse skin in organ culture.

Using mouse skin maintained in a permeability chamber-organ culture system, we have examined the percutaneous penetration and cutaneous fate of some selected steroids. At 16 hr after in vitro topical application (10 micrograms/2 cm2), the extent of permeation of the selected steroids was testosterone (65.13%) much greater than cortisol (18.1%) = estradiol (18.0%) greater than estrone (10.58%) much greater than estriol (2.45%). Permeation was accompanied by cutaneous first pass metabolism. In addition to water-soluble metabolites, other metabolites found in the perfusion medium from topical testosterone included 5 alpha-dihydrotestosterone, 5 alpha-androstanedione and androstenedione. Cortisone was identified as one of the metabolites of topical cortisol. For the estrogens, estradiol and estriol were metabolites of topical estrone, whereas estrone and estriol were metabolites of topical estradiol. The extent of cutaneous first pass metabolism of these selected steroids varies considerably. Estrone was metabolized extensively, but only limited metabolism of estradiol and cortisol was observed during their translocation through the skin. With testosterone, it was evident that an increase in the topically applied dose was accompanied by a decrease in the relative extent of both permeation and cutaneous first pass metabolism. However, cutaneous first pass metabolism of estriol was essentially negligible. These observations demonstrated that both diffusional and metabolic processes are important in the percutaneous fate of topical steroids. They also suggest that in future studies concerned with the absorption and bioavailability of topically applied chemicals, an assessment of the drug-metabolizing capabilities of the skin needs to be considered.

Administration, Cutaneous↗
PubMed1985

pH profile of the adsorption of nucleotides onto montmorillonite. I. Selected homoionic clays.

The effect of adsorbed ions and pH on the adsorption of several purine and pyrimidine nucleotides on montmorillonite was studied. The cations used to prepare homoionic montmorillonite was Na+, Mn2+, Fe3+, Co2+, Ni+, Cu2+, and Zn2+. The nucleotides studied were 5'-,3'-, and 2'-AMP, and 5'-CMP in the pH range 2 through 12. The results show that preferential adsorption amongst nucleotides and similar molecules is dependent upon pH and the nature of the substituted metal cation in the clay. At neutral pH, it was observed that 5'-AMP was more strongly adsorbed than 2'AMP, 3'-AMP, and 5'-CMP. Cu2+ and Zn2+ clays showed enhanced adsorption of 5'-AMP compared to the other cation clays studied in the pH range 4-8. Below pH 4, the adsorption is attributed to cation and anion exchange adsorption mechanisms: above pH 4, anion exchange may also occur, but the adsorption (when it occurs) likely depends on a complexation mechanism occurring between metal cation in the clay exchange site the biomolecule. It is thus proposed that homoionic clays may have played a significant role in the concentration mechanism of biomonomers in the prebiotic environment, a prerequisite step necessary for the formation of biopolymers in the remaining steps leading to the origin of life.

Adenosine Monophosphate↗
PubMed1985

Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo[a]pyrene and testosterone.

Percutaneous absorption of chemicals is generally considered a diffusional process, with the rate-limiting barrier being the nonviable stratum corneum. Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in mammalian skin maintained as short-term organ cultures. Skin samples from mouse, rat, rabbit, guinea pig, marmoset, and man were examined. The results from studies with benzo[a]pyrene (BP) and testosterone showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous "first pass" metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and testosterone was highest in mouse skin, and significant species variations in the metabolite profiles were observed. Studies with mouse skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when KCN was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.

Administration, Topical↗
PubMed1985

Examination of adduct formation in vivo in the mouse between benzo(a)pyrene and DNA of skin and hemoglobin of red blood cells.

We are interested in devising techniques which will allow us to measure and quantitate exposure to chemical carcinogens and which eventually can be used in risk analysis with humans. Our recent research with HPLC/fluorescence has demonstrated that we can detect, identify, and quantitate the binding of benzo(a)pyrene (BaP) with DNA of mouse skin. The technique not only allows femtomole amounts of BaPDE associated with DNA isolated from a single mouse skin to be detected using conventional instrumentation, but also establishes the stereochemical origin of the adduct, and has been employed in the investigation reported here to estimate the concomitant binding of BaP to hemoglobin in vivo. The temporal existence of BaPDE/DNA adducts in mouse skin over a 5-week period showed that at 35 days after treatment, approximately 15% of the initial adducts were still detectable even though DNA turnover would predict that they should have been deleted from the genome. The concentration of the major covalently bound adduct, anti-BaPDE/deoxyguanosine, relative to the total BaPDE/DNA adduct population remained essentially constant during the 5-week period. It is known that topically applied BaP is absorbed, metabolized, and excreted by the mouse. Examination of hemoglobin of mouse RBCs 24 hr after BaP treatment revealed covalent adduct formation exclusively via anti-BaPDE. The dose response of adduct binding to hemoglobin and DNA appeared to be similar.

Animals↗
PubMed1984

An in vitro approach to studying cutaneous metabolism and disposition of topically applied xenobiotics.

The extent to which cutaneous metabolism may be involved in the penetration and fate of topically applied xenobiotics was examined by metabolically viable and structurally intact mouse skin in organ culture. Evidence that skin penetration of certain chemicals is coupled to cutaneous metabolism was based upon observations utilizing [14C]benzo[a]pyrene (BP). As judged by the recovery of radioactivity in the culture medium 24 hr after in vitro topical application of [14C]BP to the skin from both control and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced C3H mice, skin penetration of BP was higher in the induced tissue. All classes of metabolites of BP were found in the culture medium; water-soluble metabolites predominated and negligible amounts of unmetabolized BP were found. As shown by enzymatic hydrolysis of the medium, TCDD induction resulted in shifting the cutaneous metabolism of BP toward the synthesis of more water-soluble conjugates. Differences in the degree of covalent binding of BP, via diol epoxide intermediates to epidermal DNA, from control and induced tissues were observed. These differences may reflect a change in the pathways of metabolism as a consequence of TCDD induction. These results indicated that topically applied BP is metabolized by the skin during its passage through the skin; and the degree of percutaneous penetration and disposition of BP was dependent upon the metabolic status of the tissue. This suggests that cutaneous metabolism may play an important role in the translocation and subsequent physiological disposition of topically applied BP.

Administration, Topical↗
PubMed1984

Effect of ellagic and caffeic acids on covalent binding of benzo[a]pyrene to epidermal DNA of mouse skin in organ culture.

The covalent binding of the anti-diol epoxide of benzo[a]pyrene to cellular DNA of mouse skin in organ culture is affected by the presence of ellagic acid in the culture medium. At 10(-4) M, BaPDE /DNA formation is 40% less than that observed when no ellagic acid is present. Caffeic acid, a similar plant phenolic compound, demonstrates no inhibitory effect on BaPDE /formation. The plant phenolic acids do not drastically interfere with the metabolism of benzo[a]pyrene as shown by the BaP-metabolite profiles of the skin or of the culture medium.

Animals↗
PubMed1983

Quantitation of cutaneous toxicity: an in vitro approach using skin organ culture.

A short-term (48 hr) organ culture system for maintaining metabolically viable and structurally intact mouse skin has been developed. With the culture system, the responses of skin to in vitro physical and chemical insults were assessed by histologic examination and selected biochemical measurements in an attempt to establish a quantitative basis for the evaluation of cutaneous toxicity in vitro. In studies with mouse skin in organ culture following either freeze-thaw treatment (physical insult) or a single in vitro topical application of tributyltin chloride (10 to 1000 nmole/cm2), deleterious morphologic changes were observed. The degree of cellular injury was reflected by inhibition of in vitro incorporation of [3H]thymidine and [14C]leucine into epidermal DNA and protein, respectively; there also was leakage of intracellular enzymes into the culture medium in a dose and time related manner. These biochemical parameters are sensitive indicators of cellular injury; as such they may offer a simple, sensitive, and quantitative measure for assessing cutaneous toxicity of chemicals in vitro.

Animals↗
PubMed1982

Two-dimensional technique to calculate the EM power deposition pattern in the human body.

A numerical procedure to calculate the electromagnetic (EM) power deposition in two-dimensional models of cross sections in the human body is described. The procedure involves obtaining X-ray images of cross sections of specific areas with computer axial tomographic scans and then solving the EM boundary value problem by using the method of moments. The formulation thus takes into account not only the spatial distribution of the different tissue types, but also the radiation characteristics of the typical EM source. Numerical results are given to illustrate the accuracy of the developed procedure. Special emphasis is placed on characterizing and analyzing the EM power deposition patterns obtained using the annular phased array system recently developed by BSD Medical Corporation for hyperthermia treatments.

Computers↗
PubMed1981

Induction of O-deethylase activity as an index to exposure to coal-derived products and trace environmental pollutants.

The metabolism of the synthetic substrate 7-ethoxyresorufin is a selective measure of the activity of cytochrome P-448 monooxygenase, the subset of cytochrome P-450-mediated enzymes preferentially induced by polycyclic aromatic hydrocarbons and related compounds. 7-Ethoxycoumarin metabolism, on the other hand, reflects total (nonselective) cytochrome P-450 monooxygenase activity. Either substrate yields a single, highly fluorescent product, amenable to direct, sensitive assay with the portable centrifugal analyzer. We used three assays with liver microsomes from C57/BL6 mice for the short-term bioassay of the dose-dependent effects of exposure to selected environmental toxins, including petroleums, polychlorinated biphenyls, and their oxidative degradation products.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1979

Metabolism of [14C]phenol by sheep, pig and rat.

1. Following an oral dose of [14C]phenol (12.5 or 25 mg/kg) to sheep, pig and rat, urinary elimination of radioactivity was rapid, 80-90% dose being excreted in the first 8 h. 2. In anaesthetized, ureter-cannulated rats, 70-80% of an intraduodenal dose was eliminated in 2 h; 2% dose was excreted as phenol conjugates in the urine within 10 min. 3. The major urinary metabolites from phenol (25 mg/kg) were phenylglucuronide and phenylsulphate. In the sheep, pig and rat, the glucuronide accounted for 49%, 83% and 42% respectively, of the total urinary metabolites and sulphate accounted for 32%, 1% and 55%. Conjugates of quinol were minor urinary metabolites (less than 7%) in all three species. 4. In sheep some 12% of the urinary metabolites was conjugated with phosphate; this metabolite was not found in rat or pig.

Animals↗
PubMed1979

Inaccuracy of the Clinitemp skin thermometer.

The Clinitemp Fever Detector (Clinitemp) is a newly marketed thermometer consisting of plasticencased thermophototropic esters of cholesterol that change color over a specific short-range of temperature. The manufacturer states that the instrument can identify fever by measuring skin temperature in children. On the basis of a patient's report of one inaccurate Clinitemp, we undertook to investigate the accuracy of this thermometer. One hundred fifty-two children presenting to the Children's Hospital Emergency Room had their temperature taken with two thermometers, an electronic thermometer that had been checked for accuracy with a National Bureau of Standards thermometer and the Clinitemp. Clinitemps, purchased over a two-month period from three pharmacies, were tested on different children. Thirteen of thirty children (43%) with fever (rectal temperature greater than or equal to 38.3 C (101 F) or oral temperature greater than or equal to (37.8 C) (100 F) identified by the electronic thermometer, were correctly classified as having fever using the Clinitemp. When fever was defined to include children with a rectal temperature greater than or equal to 38.0 C (100.5 F) or an oral temperature of greater than or equal to 37.4 C (99.5 F), the Clinitemp correctly identified 13 (32.5%) of 40 children with fever. There appears to be an appreciable risk that someone with a serious illness may delay seeking medical attention on the basis of a normal temperature as measured by the Clinitemp.

Adolescent↗