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Biomedical subjects

O A Adegoke

Publications and source records attributed to O A Adegoke.

5 recordsLinked to original sources

Anabolic and catabolic mediators of intestinal protein turnover: a new experimental approach.

Studies on regulation of protein turnover in skeletal muscle have revealed the important contributions of protein synthesis and catabolism to tissue protein balance, and have identified a host of specific anabolic and catabolic stimuli and biochemical mechanisms that regulate these processes. This knowledge is critical to current efforts designed to promote anabolism and limit atrophy. Of the tissues with a potentially large contribution to whole-body amino acid metabolism, protein turnover of the intestine stands out as being poorly understood. The intestine is subject to complexities in regulation of its metabolism that are not apparent for other tissues. The study of intestinal protein turnover also entails some important technical challenges. We recently developed an in-situ experimental system for study of intestinal mucosal protein synthesis with the following unique features: multiple observations within an animal; controlled delivery of nutritional stimuli to the apical side, basolateral side, or both; and luminal delivery of tracer in a flooding dose for determination of protein synthesis. We have begun to use the system to test the specific roles of individual luminal nutrients in regulation of mucosal protein synthesis. We have also used protease gene expression as an index of potential regulation of catabolic pathways.

Animals↗

Luminal amino acids acutely decrease intestinal mucosal protein synthesis and protease mRNA in piglets.

Because parenteral feeding is associated with negative N balance and reduced rates of protein synthesis in intestinal mucosa, we hypothesized that luminal exposure to specific amino acids or energy fuels would stimulate intestinal protein synthesis. We studied the acute effects of luminal nutrients on mucosal protein synthesis in the absence of systemic influences. Multiple jejunal segments constructed in piglets deprived of food overnight (n = 6) were randomly assigned to luminal perfusion with saline, 30 mmol/L amino acid mixture with or without 50 mmol/L glucose, or 30 mmol/L glutamine for 90 min. Protein synthesis was then measured by luminal perfusion with L-[2,6-(3)H]-phenylalanine. Energy substrates (glucose, short-chain fatty acids or beta-hydroxybutyrate) had no effect on mucosal protein synthesis. Relative to saline, a 30 mmol/L amino acid mixture or 30 mmol/L glutamine suppressed mucosal protein synthesis by 20-25% (P < 0.05). On the basis of these surprising results, we speculated that a coordinate reduction of proteolytic processes would be required to maintain positive intestinal N balance. Although intestinal protein catabolism cannot be assessed directly, the 30 mmol/L amino acid mixture acutely suppressed mucosal levels of mRNA encoding ubiquitin, 14-kDa ubiquitin conjugating enzyme and the C9 subunit of the proteasome by 20-30% (P < 0.05), demonstrating the sensitivity of components of the ATP-ubiquitin proteolytic pathway to acute regulation by nutrients. The suppression of protein synthesis by luminal amino acids in the absorptive state might lower intestinal utilization of amino acids to ensure efficient allocation of absorbed nutrients to nonintestinal tissues.

Amino Acids↗

Jejunal mucosal protein synthesis: validation of luminal flooding dose method and effect of luminal osmolarity.

To validate a system to study acute regulation of protein synthesis in intestinal mucosa by luminal nutrients, we compared the fractional rate of protein synthesis (Ks) in jejunal mucosa using the intravenous flooding dose technique with the administration of a comparable concentration and specific activity of tracer in a luminal perfusate. Routes of tracer administration and surgery and perfusion trauma had no effect on mucosal Ks. Furthermore, four 10-cm jejunal segments (within a piglet) simultaneously but separately perfused with a luminal flooding dose had similar Ks values (mean, 43 +/- 2%/day; P > 0.05). Nutrient solutions perfused through four intestinal segments within an animal did not affect plasma levels of most amino acids or glucose. Because cellular hydration is important in regulating metabolism, the effects of physiological variation in luminal osmolarity were studied. Luminal osmolarities between 250 and 380 mosM did not affect mucosal Ks. The system described allows multiple comparisons within an animal and provides a robust model to study acute modulation of protein synthesis in intestinal mucosa by luminal stimuli.

Amino Acids↗

AIDS: awareness and blood handling practices of health care workers in Lagos, Nigeria.

A questionnaire survey of 260 health care workers from 13 randomly selected health care facilities was undertaken. Their knowledge, attitude, belief and blood handling practices regarding HIV/AIDS were enquired about. Virtually all (99.0%) respondents had heard about AIDS but only 57.0% had seen an AIDS patient before. Although 83.0% knew that AIDS is caused by a virus, a high proportion still confuses mode of transmission with causative agent. Deficient knowledge was exhibited when asked about groups of people who were at a higher risk of contracting HIV and AIDS: Only 54.6% and 51.5% identified homosexuals and i.v. drug users as being at a higher risk. Almost all (97.0%) of our respondents claimed to have been more careful in their blood handling practices since the emergence of AIDS, 68.5% wore gloves for all procedures involving handling of blood and 28.5% sometimes although as many as 30.4%, 40.4% and 18.1% do not wear gloves for cleaning up blood stained materials, nursing procedures and taking obstetric delivery respectively. It was evident from their responses that not all the health workers knew the correct method for disposing of used bloodstained instruments and left-over blood samples and neither were they all adhering to the safety guidelines recommended for handling these materials. Education of all health care workers in Nigeria on the Universal Precautions Guidelines issued by the Centers for Disease Control (CDC) in 1987 regarding blood, body fluids and contaminated instruments' handling precautions is urgently recommended.

Acquired Immunodeficiency Syndrome↗

Glucose tolerance during experimental tetanus toxicity in rabbits.

Tetanus was induced in rabbits by injection of high doses of purified tetanus toxin. After the induction of tetanus, the fasting blood glucose level was significantly elevated in the rabbits with tetanus--blood glucose level being 137.5 mg% compared with 114.8 mg% in controls. The Glucose tolerance showed the expected curve in control rabbits while in the rabbits with tetanus, there was a continuous rise in blood glucose levels even after 3 hours. Histological studies show degranulation of the beta cells of the pancreas in the tetanus rabbits. Thus, the high fasting blood sugar level and the diabetic pattern of Glucose tolerance observed in the tetanus animals are suggestive of reduced insulin production during tetanus, as part of the mechanism involved.

Animals↗