Diabetes-related changes in L-tryptophan-induced release of striatal biogenic amines.

In vivo voltammetry was used to measure the synaptic release of rat striatal dopamine and serotonin after the administration of the amino acid L-tryptophan to streptozocin-induced diabetic rats. Dopamine and serotonin release from rat striatum was studied at a short-term or acute (3-day) interval and a long-term or chronic (3- to 7-wk) interval after the induction of diabetes. The study was also done in age-, sex-, and food-matched controls. The findings show that L-tryptophan decreased dopamine release from rat striatum in nondiabetic rats. The decreased striatal dopamine release, after L-tryptophan administration, was exacerbated in acutely diabetic rats and further exacerbated in chronically diabetic rats. By contrast, rat striatal serotonin release predictably increased after L-tryptophan injection in nondiabetic rats. A further increased striatal serotonin release was seen in acutely diabetic rats. Chronically diabetic rats, however, responded to L-tryptophan with a dramatic and significant decrease in striatal serotonin release. The results show that in acutely diabetic and normal rats, L-tryptophan administration reduced striatal dopamine and increased striatal serotonin release, whereas in chronically diabetic rats, the release of both biogenic amines was decreased. The findings indicate that the progression of diabetes is associated with an impaired ability to release primary neurotransmitter biogenic amines.

Thyroid state and brain monoamine metabolism.

The rates at which rat brain synthesizes catecholamines and serotonin were estimated by measuring the accumulation of DOPA and 5-hydroxytryptophan (5-HTP) 45 min after ip administration of the decarboxylase inhibitor RO4-4602 (800 mg/kg BW). Following thyroparathy-roidectomy, hypothyroid rats showed a decreased accumulation of both precursor amino acids. On the other hand, hyperthyroidism (caused by administering 15 mug T4/100 g BW for 25 days) accelerated the accumulation of catecholamines and serotonin. The accumulation of 5-HTP correlated closely with brain tryptophan concentration in all treatment groups; DOPA accumulation, however, did not similarly correspond to brain tyrosine levels.

Serotonergic function in diabetic rats: psychotherapeutic implications.

Extracellular serotonin in striatum was studied in untreated streptozotocin-induced diabetic rats and in untreated nondiabetic rats that served as age-, food-, and sex-matched controls. Extracellular serotonin was studied under anesthesia in vivo and dynamically with voltammetry. The results showed that an early and significant increase in extracellular serotonin occurred in striatum in the untreated acutely (3 days) diabetic rat. In untreated long-term (3-7 weeks) diabetic rats, however, the increase in serotonin in extracellular fluid in striatum decreased and returned to normal. The findings show a change in serotonergic function in acutely diabetic rats. The serotonergic alteration may have psychotherapeutic implications.

Increased tryptophan hydroxylase activity in serotonergic nerve terminals spared by 5,7-dihydroxytryptamine.

Adult rats received intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) to destroy serotonin (5-HT)-containing nerve terminals throughout the brain. When the animals were killed 3 or 21 days later, we observed a marked decrease in 5-HT content in septum and hippocampus and a parallel decline in in vitro high affinity 5-HT uptake. 5-Hydroxyindoleacetic acid (5-HIAA) concentrations also were reduced but by a much smaller extent, resulting in significant increases in the ratio of 5-HIAA to 5-HT. These changes were accompanied by similar increases in the ratio of tryptophan hydroxylase (TPH) activity to 5-HT content. The relative increases in TPH activity resulted from two temporally distinct processes, the first of which appeared to be an activation that could be mimicked in vitro by Ca2+-dependent phosphorylation. We conclude that, after partial damage to 5-HT neurons, there is a compensatory increase in the synthesis and release of 5-HT from those terminals that remain.

Paradoxical short-term effects of cyproheptadine on insulin and glucagon release in the rat.

The administration of cyproheptadine (25 mg/kg; i.p.) resulted in an increase of plasma insulin and glucagon (measured using 30 K antibody) 30, 60 and 120 min after injection to fasted rats. This dose of cyproheptadine also induced a hyperglycemia whereas a lower dose (5 mg/kg; i.p.), which did not alter plasma hormone levels, was associated with a hypoglycemia. Fed rats showed a reduction of plasma insulin with a similar elevation of blood glucose after cyproheptadine. Administration of an exogenous load of arginine resulted in increases of plasma insulin and glucagon of a greater magnitude than induced by cyproheptadine, however, cyproheptadine pretreatment (25 mg/kg) completely suppressed the pancreatic response to the amino acid, resulting in blood hormone levels similar to values seen after cyproheptadine administered alone. Cyproheptadine pretreatment also prevented the hyperinsulinemia and hypoglucagonemia resulting from glucose loading. alpha-Adrenergic receptor blockade (with phentolamine), beta adrenergic receptor blockade (with propranolol) and adrenodemedullation did not alter pancreatic responsiveness to the drug.

Studies on tryptophan accumulation in brain during methiothepin-induced enhancement of 5-hydroxyindole synthesis.

The elevation of brain tryptophan, 5-hydroxytryptophan and 5-hydroxyindoles (serotonin + 5-hydroxyindole acetic acid) that results from a tryptophan load is potentiated by prior administration of methiothepin, a serotonin receptor antagonist. Co-administration of valine with tryptophan attenuates these effects even in animals receiving methiothepin pretreatment. Administration of methiothepin and tryptophan to rats with widespread reduction of brain 5-hydroxyindole levels resulting from raphe lesions or 5,7-dihydroxytryptamine pretreatment still enabled brain tryptophan levels to rise considerably above the sum of increases found in animals receiving one or the other. Following transection of the spinal cord, the cranial portion still exhibited enhanced uptake of tryptophan and 5-hydroxyindole synthesis following methiothepin plus tryptophan treatment, however, both these events were absent in the caudal segment. Apparently, enhanced tryptophan uptake can proceed in the presence of minimal neuronal activity; however, when nerve impulse flow is eliminated, both 5-hydroxyindole synthesis and tryptophan uptake is impaired.

Simulation of breast carcinoma.

In Radiology Rounds, the authors presents a case history, mammogram, and discussion of causes of diseases simulating carcinoma of the breast. The patient is a 59-year-old female. The diagnosis is edema of the breast secondary to congestive heart failure, mimicking carcinoma.

CT and MRI of hepatic hemangioma.

UNLABELLED: Our patient exhibited typical characteristics of giant cavernous hemangioma by CT and MR, and was asymptomatic. We have concluded, therefore, that this did not represent a malignant lesion. In general, however, one must exhibit a reasonable degree of caution in applying this diagnosis, adhere strictly to the criteria described, and recognize the clinical setting of the patient. DIAGNOSIS: Giant cavernous hemangioma of the liver.

Radiographic assessment of traumatic rupture of the thoracic aorta.

The authors discuss the advantages and limitations of radiographic modalities in assessing traumatic rupture of the thoracic aorta (TRTA). TRTA is one of the most frequent causes of death from high-speed deceleration accidents and other blunt trauma sustained during motor vehicle accidents.

Radiology rounds: MRI of rotator cuff arthropathy.

Magnetic resonance imaging (MRI) has proved to be an excellent diagnostic tool in evaluating the musculoskeletal system. This article illustrates one particular facet of musculoskeletal MRI: investigation of the rotator cuff tendon complex.

Imaging of herpes simplex encephalitis.

The authors discuss computed tomography (CT) and magnetic resonance imaging (MRI) findings of herpes encephalitis as important adjuncts to the early diagnosis of this entity. The patient was a 42-year-old HIV-negative male who presented with a history of dizziness, headaches, and fever.

The radiologic diagnosis of quadriceps tendon rupture.

This paper reviews the pathophysiological mechanism of quadriceps tendon rupture and its diagnosis by means of medical imaging including radiography, sonography, and magnetic resonance imaging (MRI). MRI findings are emphasized.