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Biomedical subjects

R Godfrey

Publications and source records attributed to R Godfrey.

31 records · Page 2Linked to original sources
PubMed1991

A chromatographic and spectroscopic study of photodegraded metronidazole in aqueous solution.

Preparative reversed-phase HPLC has been used to isolate a yellow photodegradation (2) product from aqueous metronidazole (1) solutions buffered with citrate:phosphate. Compound 2 can be further degraded into colorless materials by light, heat, or the addition of the nonaqueous solvents. These products have been characterized by UV, IR, proton NMR, mass spectroscopy, and melting point determination. It is proposed that the initial yellow degradation product (2) is an "excimer ion-pair" formed by the stabilization of 1 in its first electronic excited state by the citrate molecule.

Chromatography, High Pressure Liquid↗
PubMed1991

Studies on the stability of trimelamol, a carbinolamine-containing antitumor drug.

The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.

Chromatography, High Pressure Liquid↗
PubMed1990

p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes.

The clone MO15 which codes for a 40 kd protein (p40MO15) with 40% amino acid identity to the human cdc2 protein kinase has been isolated from a Xenopus cDNA library using a synthetic oligonucleotide probe. MO15 mRNA is accumulated during oogenesis, becomes de-adenylated during meiotic maturation, and is degraded after the mid-blastula-transition stage of embryogenesis. Translation of p40MO15 is restricted to non-mature oocytes. Specific inhibition of p40MO15 synthesis in stage VI oocytes by antisense oligonucleotide depletion of MO15 mRNA increases the rate of progesterone induced H1 kinase activation and oocyte maturation. This effect can be reversed by subsequent injection of synthetic MO15 mRNA. These results suggest that p40MO15 is involved in negatively regulating meiosis.

Amino Acid Sequence↗
PubMed1990

Effect of fibreoptic bronchoscopy on pulmonary function.

Several studies have shown that after fibreoptic bronchoscopy there may be a deterioration in lung function but it is not known whether this is due to the premedication, the topical anaesthetic, or the obstruction produced by the bronchoscope. The effects of each part of the procedure on spirometric measurements were studied in patients with lung disease and in normal non-smokers. Measurements were made after premedication (papaveretum and atropine) in seven patients and after topical anaesthesia of the bronchial tree (340 mg lignocaine) with and without the bronchoscope in the trachea in 21 patients and 10 control subjects. Premedication had no effect. In the normal subjects lignocaine produced significant falls in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and peak inspiratory flow (PIF), and insertion of the bronchoscope caused further falls that were also significant. In the patients, however, although anaesthesia produced significant falls in FEV1, FVC, PEF, and PIF of similar magnitude to those found in the normal subjects, there was no further important decrease when the bronchoscope was inserted. It is concluded that the major effect of bronchoscopy on lung function is due to topical lignocaine in the airways, and in patients with lung disease (excluding asthma or a central obstructing carcinoma) the insertion of the bronchoscope causes little additional obstruction.

Administration, Topical↗
PubMed1989

Carcinoid tumors of the gastrointestinal tract: a 44-year experience.

We retrospectively studied 112 patients treated for gastrointestinal carcinoid tumors between 1942 and 1986. The three most common sites were jejunum-ileum (27%), rectum (27%), and appendix (21%), followed by colon (12%), duodenum (9%), and stomach (4%). Seventy-five percent of patients had localized disease, primarily in the rectum and appendix. Colon and small bowel tumors were often manifested with metastatic disease. Complete surgical excision of all localized disease was curative in 94% of patients. Corrected five- and ten-year survival rates were 90% and 58%, respectively, in cases of localized disease, whereas in stage III disease, the rates were 46% and less than 30%, respectively. All patients with liver metastasis died within 25 months. A second malignancy, most often adenocarcinoma of the colon, occurred in 25% of patients. Carcinoid syndrome was found in 6% of patients. The best survival rates were noted for appendiceal and rectal carcinoids, and the worst for colon and stomach carcinoids.

Actuarial Analysis↗
PubMed1987

SK&F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid.

The effects of SK&F 86002 [5-(4-pyridyl)-6 (4-fluorophenyl)-2,3-dihydroimidazo (2,1-b) thiazole] on the generation of eicosanoids in vitro and on inflammatory responses in vivo are described and compared to other non-steroidal anti-inflammatory drugs. SK&F 86002 inhibited prostaglandin H2 (PGH2) synthase activity (IC50 120 microM) as well as prostanoid production by rat basophilic leukemia (RBL-1) cells (IC50 70 microM) and its sonicate (IC50 100 microM) and human monocytes (IC50 1 microM). In addition, SK&F 86002 inhibited the generation of dihydroxyeicosatetraenoic acid (diHETE) and 5-hydroxyeicosatetraenoic acid (5-HETE) by a high speed supernatant fraction of RBL-1 cells (IC50 10 microM). Cellular production of 5-lipoxygenase products was inhibited by SK&F 86002 as measured by leukotriene B4 (LTB4) generation from human neutrophils (IC50 20 microM), leukotriene C4 (LTC4) generation by human monocytes (IC50 20 microM), and 5-HETE production by RBL-1 cells (IC50 40 microM). The in vivo profile of anti-inflammatory activity of SK&F 86002 supports the dual inhibition of arachidonate metabolism as indicated by its activity in inflammation models that are insensitive to selective cyclooxygenase inhibitors. The responses of arachidonic-acid-induced edema in the mouse ear and rat paw, as well as the cell infiltration induced by carrageenan in the mouse peritoneum and by arachidonic acid in the rat air pouch, were inhibited by SK&F 86002 and phenidone but not by the selective cyclooxygenase inhibitors naproxen and indomethacin.

Animals↗