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M K Jones

Publications and source records attributed to M K Jones.

176 records · Page 10Linked to original sources

NSAIDs inhibit the activation of egr-1 gene in microvascular endothelial cells. A key to inhibition of angiogenesis?

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin (IND), ibuprofen and newer cyclooxygenase-2 selective NSAIDs (e.g. celecoxib) delay gastric ulcer healing partly through the inhibition of angiogenesis, but the molecular mechanisms involved are not fully elucidated. Effective angiogenesis is required for ulcer healing to supply oxygen and nutrients to the healing site. The early growth response factor (Egr-1) is a transcription factor, which is rapidly activated by a variety of extracellular signals or tissue injury and is important for angiogenesis to occur. This study aimed to determine whether indomethacin (IND) and/or the selective COX-2 inhibitor, NS-398, interfere with egr-1 gene expression in human microvascular endothelial cells (HMVEC) in response to vascular endothelial growth factor (VEGF) stimulation. HMVEC were treated with 0.5 mM IND or 100 microM NS-398 for 16 h, and then VEGF (10 ng/ml) or vehicle was added. Egr-1 mRNA and protein expression levels were determined by RT-PCR and Western-blotting, respectively. VEGF treatment caused a significant elevation of Egr-1 mRNA (261+/-21%, P<0.001) and protein expression (174+/-15%, P<0.01) vs. vehicle. IND pre-treatment significantly inhibited VEGF-induced Egr-1 mRNA expression by 29+/-4% (P<0.01) and protein expression by 41+/-8% (P<0.05). NS-398 inhibited VEGF-induced Egr-1 mRNA and protein expression by 23+/-3% and 35+/-4%, respectively (both P<0.01). Since transcriptional activation of egr-1 is responsible for expression of proteins involved in proliferation of endothelial cells essential for angiogenesis, these results provide a new mechanism for NSAIDs' interference with angiogenesis.

Anti-Inflammatory Agents, Non-Steroidal↗

Train? Who? Me!

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Hospital Bed Capacity, 500 and over↗

Ethanol metabolism in women taking oral contraceptives.

The relationship between oral contraceptives and ethanol metabolism in women was examined in a group of 40 female social drinkers between the ages of 21 and 30. Twenty women taking oral contraceptives and 20 women not taking oral contraceptives were given a moderate dose of ethanol (0.52 g/kg) during the menstrual, intermenstrual and premenstrual phases of the menstrual cycle. The group of women taking oral contraceptives demonstrated a significantly decreased ethanol elimination rate (105 mg/kg/hr) than the women not taking oral contraceptives (121 mg/kg/hr, p less than .005). Ethanol disappearance rate also was significantly decreased for women taking oral contraceptives (0.015%/hr) than women not taking them (0.019%/hr, p less than .001). These results were consistent across the three phases of the menstrual cycle and when body leanness was taken into consideration. The decreased rate of ethanol metabolism in women taking oral contraceptives is consistent with reports of other drugs having decreased metabolic rates in women taking birth control pills. These results suggest that women taking oral contraceptives should be cautioned concerning their possible interaction with ethanol, as well as other drugs.

Adult↗

Glycosylated serum albumin: an intermediate index of diabetic control.

Glycosylated hemoglobin (HbA1) is widely used as an index of glycemic control in diabetic patients. However, due to the long survival time of erythrocytes (120 days), it remains elevated for several weeks after improved control. Other plasma proteins are similarly glycosylated, and as glycosylated serum albumin (GSA) has a shorter half-life (20 days), it should detect glycemic changes earlier. Fasting blood glucose (FBG), GSA, and HbA1 were measured weekly in newly diagnosed diabetic patients (N = 12) for 8 wk after beginning treatment. After 4 wk, a similar fall in FBG and GSA levels, i.e., 72% and 58% respectively, was observed. In contrast, HbA1 fell significantly less (P less than 0.01), by only 39% of its initial value. By 8 wk there was no significant difference between the percentage reduction in the three indices of control. Therefore, GSA provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention and can be regarded as an intermediate index of diabetic control.

Blood Glucose↗

The clinical pharmacology of human insulin (Novo) in normal subjects.

Neutral regular human insulin (Novo) (derived from porcine insulin) and porcine insulin were administered by subcutaneous (s.c.) injection into the anterior abdominal wall in two different groups of six normal male subjects. The insulin dosage was 0.075 IU/kg body wt; diluting medium was used to obtain control values. In one group, somatostatin was administered by continuous intravenous infusion (100 micrograms/h) to inhibit pancreatic beta-cell secretion. The plasma glucose, C-peptide, and insulin (immunoreactive) responses to human insulin and porcine insulin were identical in the studies with and without somatostatin. Although the incremental plasma insulin values achieved with the two insulins were similar in the two studies, the hypoglycemic effect was accentuated in the presence of somatostatin, with a delayed recovery toward normoglycemia. The human insulin and porcine insulin were well tolerated in all subjects and there were no unwanted side effects.

Animals↗