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Biomedical subjects

J C Agharanya

Publications and source records attributed to J C Agharanya.

8 recordsLinked to original sources

The effect of a nutritionally-balanced cassava (Manihot esculenta Crantz) diet on endocrine function using the dog as a model. 2. Thyroid.

Growing dogs were divided into three groups and were fed on nutritionally-balanced diets. Control dogs were fed on a rice diet, the cassava (gari) group ate a diet in which gari provided the carbohydrate source, while the rice + cyanide group consumed the rice diet to which hydrocyanic acid (equivalent to that present in gari) was added. Each group consumed its diet for 14 weeks, during which plasma thiocyanate concentration and total serum triiodothyronine (T3) were monitored. At the end of the experiment the concentrations of the plasma free amino acids phenylalanine and tyrosine, the thyroid weights and histology were determined. While plasma thiocyanate remained undetectable in control dogs, animals consuming both gari and rice + cyanide generated significant amounts. In the control dogs and the gari group, total serum T3 increased 40 and 38.8% respectively from the basal level by the end of the period (P less than 0.02). In contrast there was a decrease in T3 by 36% in the dogs fed on rice + cyanide (P less than 0.05). This group also showed significant thyroid enlargement and a histological picture consistent with parenchymatous goitre, whereas the gari group was essentially normal. The relatively low mean thyroid weight, the rise in total serum T3 level and the normal histological appearance of the gland indicate that dogs that consumed the gari diet were essentially normal with respect to their thyroid function, in spite of their high blood thiocyanate content. In contrast, dogs that consumed rice with cyanide suffered from hypothyroidism and goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modulation of insulin activity by hydrochloride salts.

The influence of hydrochloride salts of various amino acids and other drugs on the activity of exogenously administered insulin was studied in the rat. Insulin activity was assessed in terms of insulin's effects on lowering of blood glucose and nonesterified fatty acids (NEFA), release of adrenaline (epinephrine) from the adrenal medulla, and the elevation of urinary catecholamines. Insulin alone produced a 60-70% fall in blood glucose and NEFA, 70% depletion of adrenal epinephrine, a 10-fold increase in urinary epinephrine, and a 2-fold elevation of adrenal dopamine. Concurrent administration of hydrochloride salts completely abolished all clinical manifestations that usually accompany insulin injection. Serum glucose and NEFA remained unchanged, the fall in adrenal epinephrine was blocked, and the increase in urinary catecholamines was abolished. These data suggest that certain hydrochloride salts possess an anti-insulin property. They decrease tissue responsiveness to insulin, thus rendering its action ineffective. The implication of these findings on the treatment of diabetic subjects requiring insulin therapy is discussed.

Amino Acids↗

Studies on the mechanism by which tyrosine raises urinary catecholamines.

The source of urinary catecholamines and the mechanisms by which tyrosine administration raises these compounds were investigated in rats. Adrenalectomy blocked the tyrosine-induced rise in urinary epinephrine but not dopamine or norepinephrine. Following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), the tyrosine-induced increase in urinary norepinephrine was diminished, but epinephrine and dopamine responses were unaffected. Cardiac norepinephrine, which is normally unchanged following tyrosine administration, became significantly elevated in 6-OHDA-pretreated animals. At the doses used in this study, tyrosine had no effect on the uptake or metabolic clearance of circulating catecholamines. We conclude that tyrosine augments the synthesis of the three catecholamines in sympathoadrenal cells by increasing the extent to which tyrosine hydroxylase is saturated with its amino acid substrate. Moreover, the effects of tyrosine on peripheral catecholamine synthesis may be enhanced under conditions of increased sympathetic activity.

Adrenal Glands↗

Elevation of urinary catecholamines and their metabolites following tyrosine administration in humans.

A single oral dose of tyrosine (100 or 150 mg/kg) caused significant increases in urinary levels of norepinephrine (NE), epinephrine (E), dopamine (DA), 3-methoxy-4-hydroxyphenylglycol (MHPG), vanilmandelic acid (VMA), and homovanillic acid (HVA) during the first 2 hr after its ingestion; water administration failed to produce such changes. The temporal patterns of these increases paralleled those of previously described increases in plasma tyrosine. Since urinary catecholamines derive from peripheral sources, while the catecholamine metabolites in urine may reflect both CNS and peripheral catecholamine turnover, these findings indicate that tyrosine administration may accelerate catecholamine synthesis in and release from cells throughout the human body. Tyrosine may thus constitute a useful agent for treating central or peripheral disorders associated with insufficient release of catecholamines.

Adolescent↗

Changes in catecholamine excretion after short-term tyrosine ingestion in normally fed human subjects.

The effects of ingesting the aromatic amino acid L-tyrosine on excretion of unconjugated catecholamines (dopamine, norepinephrine, and epinephrine) and tyrosine were studied. (Tyrosine is the circulating precursor for the catecholamines, but only a small fraction of the tyrosine in the body is utilized for catecholamine synthesis.) In 10 of 11 normal volunteer subjects, ingestion of 100 mg/kg tyrosine (in three divided doses, preceding each meal, between 8 AM and 5 PM) for 1 day increased the 24-h excretions of total catecholamines by 25%. Only 0.42% of the tyrosine dose was excreted unchanged, but this was sufficient to increase urinary tyrosine by 138%. Both tyrosine and catecholamine excretions varied diurnally; 60% or more of the total output occurred during the day. Since urinary catecholamines reflect molecules synthesized outside the central nervous system, these findings indicate that tyrosine administration can accelerate catecholamine synthesis in the human sympathoadrenal system, probably by enhancing saturation of tyrosine hydroxylase. Therefore, tyrosine may be useful therapeutically in diseases characterized by peripheral catecholamine deficiencies.

Adolescent↗

Tyrosine loading enhances catecholamine excretion by rats.

Tyrosine administration to rats causes dose-related increases in urinary catecholamine levels without reducing tissue catecholamines. Pretreatment with carbidopa, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, reduces basal urinary catecholamine levels and blocks of urinary catecholamine increases caused by tyrosine administration or cold exposure. DOPA excretion, which is usually undetectable by our methods, becomes significant after carbidopa, and rises a further four-fold when rats are also given tyrosine. These observations suggest that tyrosine availability can affect both catecholamine synthesis in and release from the sympathoadrenal apparatus.

Adrenal Glands↗

Clinical usefulness of ELISA technique in the assessment of thyroid function.

The clinical usefulness of Enzyme-linked Immunosorbent analysis (ELISA) for the assay of triiodothyronine (T3), thyroxine (T4) and T4 Uptake was studied in groups of clinically defined subjects. The following ranges of values were obtained in the normal control subjects: T3: 1.1-2.9 nmol/1; T4: 61.8-144 nmol/l; T4-Uptake: 0.7-1.34 and Free Thyroxine Index (FTI): 52.8-136. The diagnostic sensitivity of the technique was found to be reasonably good: showing good discrimination between hypothyroid, hyperthyroid and euthyroid subjects. Free thyroxine Index provided the best consistent correlation with the clinical states of the subjects particularly in subjects with altered binding protein levels. Several advantages offered by ELISA technique over radiochemical methods such as freedom from radiation hazards, non-requirement of specialized laboratories with expensive equipment and cheaper reagents with relatively longer shelf lives, make this procedure particularly suitable for use in small laboratories.

Adult↗