Biomedical subjects

L A Wetmore

Publications and source records attributed to L A Wetmore.

10 recordsLinked to original sources

PubMed2000

Antiproliferative effects of compounds derived from plants of Northeast Brazil.

Ten compounds derived from plants indigenous to Northeast Brazil were examined for antiproliferative effects on human cells in vitro. The effects of these phytochemicals on cell growth were determined by the MTT microtitre assay with 3-day continuous drug exposure. Three human cell lines were used: CEM leukaemia, SW1573 lung tumour and CCD922 normal skin fibroblasts. Four active compounds were found with IC(50) values less than 10 microg/mL in the two cancer cell lines. Oncocalyxones A and C, both 1,4-anthracenediones from Auxemma oncocalyx (Boraginaceae), showed cytotoxicity with mean IC(50) values of 0.8-2, 7-8 and 12-13 microg/mL against CEM, SW1573 and CCD922, respectively. One diterpene and one flavonoid, both from Egletes viscosa (Compositae), were also active. 12-Acetoxy-hawtriwaic acid lactone was cytotoxic with mean IC(50) values of 6, 10 and 10 microg/mL, respectively. 4,5-Dihydroxy-3,3,7, 8-tetramethoxy flavone (ternatin) was only growth-inhibitory with mean IC(50) values of 2, 1 and 10 microg/mL, respectively. These four most active compounds were examined further for their effects on DNA integrity and on DNA synthesis. All but ternatin caused substantial DNA damage and marked inhibition of 5-bromo-2'-deoxyuridine incorporation within 24 h. This study demonstrated the antiproliferative activity of four novel phytochemicals, three of which are DNA-reactive and inhibit DNA synthesis. Further studies are warranted to evaluate these compounds for antitumour potential.

Anthraquinones↗

PubMed2000

Epidural analgesia in veterinary critical care.

Epidural analgesia has minimal systemic effects and is a useful technique for relieving pain in critical care patients. Before administration, patients must be thoroughly assessed to identify any preexisting conditions that preclude the safe use of this technique. Analgesia can be achieved by administration of local anesthetics, opioids, alpha 2 agonists, or a combination of these analgesic agents. Concurrent administration of more than one drug allows the synergistic interaction of these agents and generally improves the level of analgesia achieved, lengthens the duration of action, and lowers the dose of each drug required to achieve analgesia. Complications of epidural techniques are infrequent and include both iatrogenic and idiopathic problems, most of which have no permanent sequelae. This review provides a detailed description of the epidural analgesia technique and lists multiple sources of specialized supplies necessary for either single injection or epidural catheter placement. It also provides direction for monitoring the critical care patient with an epidural catheter.

Analgesia, Epidural↗

PubMed1999

Tamoxifen inhibits particulate-associated protein kinase C activity, and sensitises cultured human glioblastoma cells not to etoposide but to gamma-radiation and BCNU.

We investigated the potential mechanisms of tamoxifen cytotoxicity in the U-373, U-138, and U-87 human glioblastoma cell lines, namely interference with protein kinase C (PKC) activity, the oestrogen receptor, and/or the production of transforming growth factor beta 1 (TGF-beta 1). We further examined the effects of tamoxifen on the cytotoxicity exerted by gamma-radiation, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and etoposide in this cell line panel. Thus, the cells were treated for 4 days with tamoxifen, gamma-radiation, purified recombinant human TGF-beta 1 (rhTGF-beta 1), BCNU, or etoposide, either alone or at certain combinations. Cellular responses were evaluated with the sulphorhodamine B assay, as well as by multiple drug effect analysis, and related to PKC activities in particulate and cellular fractions; cellular oestrogen receptor contents; and the influence of rhTGF-beta 1 on cell growth. Tamoxifen inhibited cell proliferation as well as the phosphorylation capacity of the particulate, but not of the cytosolic fractions dose-dependently, at comparable kinetics, and at IC50 values of approximately 15 microM. At these concentrations, tamoxifen acted synergistically with gamma-radiation (4- to 6-fold) and additively with BCNU (approximately 2-fold), but did not affect etoposide cytotoxicity. The cells were negative to immunostaining for the oestrogen receptor, and rhRGF-beta 1 did not influence their growth up to 100 nm. Our data suggest that tamoxifen can sensitise cultured glioblastoma cells not to etoposide but to gamma-radiation and BCNU, possibly through interference with membrane PKC, supporting its evaluation in experimental protocols for primary malignant gliomas.

Antineoplastic Agents↗

PubMed1999

Propofol: application in veterinary sedation and anesthesia.

Propofol can be used for sedation, induction of anesthesia, and maintenance of anesthesia in small animal patients. In all these situations recovery from its effects is typically rapid and smooth. The drug should be administered slowly, intravenously, to minimize the negative cardiac and respiratory effects seen after rapid bolus administration. The currently available formulations do not contain preservatives, and sterile technique should be strictly followed during its use. Propofol can be used for induction of anesthesia in patients with preexisting disease with minimal delays in recovery. It does not cause excitement at low doses so is also useful for sedation of patients undergoing nonpainful procedures such as radiological examination. This review focuses on the diverse clinical applications for propofol in a small animal practice including indications, recommendations, and contraindications as well as a discussion of the controversies that surround its use.

Anesthetics, Intravenous↗

PubMed1995

Influence of protein tyrosine phosphorylation on the expression of the c-myc oncogene in cancer of the large bowel.

We tested the potential impact of tyrosine phosphorylation on the expression of the c-myc gene in two colon cancer cell lines, HCT8 and SW837. We found that the protein tyrosine kinase inhibitor genistein causes a decrease in the abundance of c-myc RNA and an inhibition of proliferation with a similar dose response. Geldanamycin, a mechanistically different tyrosine kinase inhibitor, also causes a decrease in both the expression of c-myc RNA and proliferation. Genistein has also been found to inhibit topoisomerase II, but the topoisomerase II inhibitor novobiocin did not lower the expression of c-myc. The most likely interpretation is that inhibition of protein tyrosine kinase activity caused a decrease in c-myc expression in these cells. The impact of tyrosine phosphorylation on the expression of the c-myc gene is further supported by the finding that inhibition of phosphotyrosine phosphatase using orthovanadate causes an increase in the level of c-myc RNA. The effect of genistein on HCT8 cells is not dependent on the synthesis of new protein and does not involve an alteration in the stability of the message. Analysis of transcription in the c-myc gene reveals a more complicated picture with a decrease in initiation and an increase in elongation but no net change in transcription. We speculate that the genistein induced reduction in myc expression is the result of a posttranscriptional intranuclear event(s).

Benzoquinones↗

PubMed1993

Human lung expresses unique gamma-glutamyl transpeptidase transcripts.

gamma-Glutamyl transpeptidase (EC 2.3.2.2, gamma GT) is a membrane-bound ectoenzyme that plays an important role in the metabolism of glutathione. It is composed of two subunits, both of which are encoded by a common mRNA. We examined the expression of gamma GT in human lung tissue by Northern blot analysis and screening a cDNA library made from human lung poly(A)+ RNA. Our results show that there are two gamma GT mRNA populations in human lung tissue. We define these as group I (2.4 kb) and group II (approximately 1.2 kb) transcripts. In the present communication, we characterize the unique lung transcript. Sequence analysis of representative clones shows that group I transcripts are virtually identical to those previously isolated from liver and placenta but possess a unique 5' untranslated region. In marked contrast, group II transcripts appear to be human-lung-specific. Group II transcripts appear on Northern blots probed with full-length or 3'-biased gamma GT cDNA. Sequence analysis of group II clones shows them to be homologous with group I clones in the region that encodes the reading frame for the light chain; however, they possess a series of unique 5' untranslated regions, which suggests that they arise from lung-specific message processing. Additionally, approximately 50% of the isolated group II clones contain 34 nt substitutions compared with the "wild-type" gamma GT transcripts. These data indicate that human lung expresses unique gamma GT transcripts of unknown function as well as the classical form. The abundant group II transcripts may encode part of a heterodimer related to gamma GT or represent processed lung-specific pseudogenes.

Amino Acid Sequence↗

PubMed1991

Leukotriene receptor on U-937 cells: discriminatory responses to leukotrienes C4 and D4.

Dimethyl sulfoxide (DMSO)-differentiated U-937 cells develop cell surface receptors for leukotrienes that, when stimulated, initiate a transient increase in intracellular calcium concentration [( Ca2+]i). We investigated the calcium transient that occurs after addition of leukotriene C4 (LTC4) to determine whether it occurs due to 1) the bioconversion of LTC4 to leukotriene D4 (LTD4), which then acts at the LTD4 receptor; 2) the direct action of LTC4 at the LTD4 receptor; or 3) the action of LTC4 at a receptor selective for LTC4. Bioconversion of [3H]LTC4 to [3H]LTD4 was inhibited by 98% when DMSO-differentiated U-937 cells were incubated with 10 mM AT-125 compared with control cells. The dose-response curve for LTC4, with [Ca2+]i as the index of response, was parallel to that for LTD4 but was significantly (P less than 0.0001) shifted 1.6 +/- 0.11 log units to the right. AT-125 did not change the response to LTD4 but the LTC4 dose-response curve was shifted on additional 1.7 logo units to the right. The antagonists SKF 104353 (1 microM) and LY 171883 (10 microM) shifted the dose-response curve for LTD4 3.0 +/- 0.23 and 2.5 +/- 0.23 log units, respectively, to the right and completely inhibited the change in [Ca2+]i due to LTC4 in the presence of 10 mM AT-125. Molecular modeling studies demonstrated a striking difference in the spatial configuration of LTC4 and LTD4, likely accounting for the ability of cell surface receptors to discriminate between the effects of these two molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗

PubMed1987

Effect of intravenous administration of dextrose or lactated Ringer's solution on seizure development in dogs after cervical myelography with metrizamide.

The effect of fluid (5% dextrose in water or lactated Ringer's solution) administered intravenously on the development of seizures after cervical myelography with metrizamide was studied in 10 dogs. In a crossover experimental design, 8 dogs were used twice. Urine output was measured during the second part of the study to determine whether diuresis was a factor affecting seizure development. Dogs given 5% dextrose in water had significantly (P less than 0.05) fewer seizures than did dogs given lactated Ringer's solution. This was attributed to an increase in CSF glucose concentration and was not associated with diuresis.

Animals↗

PubMed1987

Mixed venous oxygen tension as an estimate of cardiac output in anesthetized horses.

The relationship between mixed venous O2 tension and cardiac output was studied in six anesthetized horses breathing 100% O2. Cardiac output, O2 consumption, mean arterial pressure, heart rate, and arterial and venous blood gases were measured after administration of xylazine or dobutamine to horses in lateral, sternal, and dorsal recumbencies. After approximately 3 hours, Escherichia coli endotoxin was administered while horses were in dorsal recumbency, and all measurements were repeated. Relationships between cardiac index (CI) and PVO2, heart rate, mean arterial pressure, jugular PVO2, and PVO2 of blood from a superficial limb vein were evaluated by linear regression analysis. Mean arterial pressure was significantly (P less than 0.05) correlated with CI in horses in all positions and after endotoxin administration. However, data points were poorly grouped. Heart rate and CI were significantly correlated in horses in all positions, but not after endotoxin administration. Correlations between jugular PVO2 and PVO2 of blood from a superficial limb vein were not significant in horses in sternal recumbency, and PVO2 of blood from a superficial limb vein was not significantly correlated with CI in horses in lateral recumbency. There was a significant and tight correlation between PVO2 and CI in horses in all positions and after endotoxin administration.

Anesthesia, General↗

PubMedDate not supplied

Oncocalyxones A and C, 1,4-anthracenediones from Auxemma oncocalyx: comparison with anticancer 1,9-anthracenediones.

Oncocalyxones A and C are 1,4-anthracenediones isolated from Auxemma oncocalyx (Boraginaceae) that have been shown to be cytotoxic to tumor cells in vitro. The present study compared the cytotoxicity of these compounds with that of two conventional anticancer agents doxorubicin and mitoxantrone, both 1,9-anthracenediones, in a panel of human tumor cell lines. The effect on cell growth was examined using an MTT microtiter assay in two leukemia lines, five solid tumor lines of different histological origin, and two multidrug-resistant sublines of a lung tumor line. The oncocalyxones showed much lower potency than the 1,9-anthracenediones, but were similarly more cytotoxic to leukemia cells compared to solid tumor lines. However, in the multidrug-resistant cells with 10 to 500 times decreased sensitivity to doxorubicin, the cytotoxicity of oncocalyxones A and C was only modestly reduced by about twofold, 1,4-Anthracenediones may be a promising novel class of chemotherapeutic agents effective against multidrug resistant tumors.

Anthraquinones↗