Amino acid transport through the blood-retinal and the blood-brain barrier

The mechanisms controlling amino acid transport across the blood-brain barrier are described. The possible existence of carrier systems for amino acids in the blood-retinal barrier (BRB) similar to the blood-brain barrier (BBB) was investigated in rats by the uptake index method. The results indicate similar carrier systems in the BRB and the BBB for all amino acids studied except taurine, where a saturable uptake was found in the retina but not in the brain. Taurine constitutes a major fraction of the pool of free amino acids, not only in the retina but also in the brain. The significance of these findings is discussed with respect to retinal physiology and cellular metabolism.     

Criminality and platelet monoamine oxidase activity in former juvenile delinquents as adults

Platelet monoamine oxidase (MAO) activity was estimated in 70 former delinquent boys and 40 controls now aged 38–46 years. Platelet MAO activity was compared with their early criminal behaviour (before the age of 15) and their late registered criminality from the age of 15). Mean platelet MAO activity in subjects with both early and late criminality was significantly lower than that in former delinquents without late criminality. There was no significant difference in mean platelet MAO activity between controls and delinquents with early but no late criminality. When delinquents with early criminality were divided into a low and a high MAO group, the relative risk to be registered for late criminality was about 3.1 times higher for the subjects in the low MAO group. Thus, individuals with low platelet MAO activity run an increased risk of continued criminal behaviour.     

Prostaglandin F2 alpha-isopropylester eye drops: effects in normal human eyes.

The effects of PGF2 alpha-isopropylester eye drops on intraocular pressure (IOP) and aqueous humour dynamics were investigated in healthy male volunteers. The other eye was treated with vehicle and used as a control. Special attention was also paid to adverse effects. Single and repeated doses were tested. There was a dose related effect on IOP. Significant reductions were observed 4, 8, and 12 hours after application of 1.0, 2.5, or 10 micrograms PGF2 alpha equivalents of the drug. With 10 micrograms the effect lasted 24 hours. An initial tendency towards an increase in IOP was observed for these doses. Repeated doses of 1.0 microgram daily or 0.5 microgram twice daily produced a significant and lasting IOP reduction of about 2 mmHg for 1-2 weeks. Aqueous humour production was not altered, and outflow facility was not significantly changed. There was a dose dependent hyperaemia with a maximum within 2 hours after application. A foreign body sensation, some pain, and photophobia were noted with increasing doses. A slight miosis of 1 mm was seen in three of six eyes treated with 10 micrograms. No signs of intraocular inflammation were recorded, but a slight increase in penetration of fluorescein into the anterior chamber was observed after 16 days of treatment.     

Perilesional neurochemical changes in focal epilepsies

Circumscribed cortical lesions are frequently encountered in patients with chronic focal epilepsies. However, the pathogenesis of seizures is poorly understood. To determine whether the perilesional cortex shows evidence for abnormal excitatory or inhibitory neurochemical activity, we immunohistochemically examined the distribution of the α₁ subunit of the GABA_A receptor (GABAR), the N-methyl-d-aspartate receptor subunit 1 (NR1), and glutamate decarboxylase (GAD) in 30 surgical specimens of neocortical epilepsy-associated lesions. These comprised 7 low-grade gliomas, 2 gangliogliomas, 2 dysembryoplastic neuroepithelial tumors, 4 glioneuronal malformations, 5 vascular malformations, and 10 glial or gliomesodermal scars. All specimens originated from patients with chronic pharmacoresistant epilepsy. In 73% of the cases there was a distinct difference in immunoreactivity for GABAR, GAD or NR1 between the perilesional zone and the normal cortex. With each of the markers there was reduced perilesional immunoreactivity in 30% of the specimens. Increased staining for GAD was seen in 17%, for GABAR in 7%, and for NR1 in 13% of the cases. The age at surgery, onset of seizures, epilepsy duration, and maximal seizure frequency did not differ significantly between patients with normal and those with altered perilesional immunoreactivity patterns. Although the perilesional changes for GAD, GABAR or NR1 were heterogeneous, they suggest a disturbed balance between excitatory and inhibitory synaptic transmission which may contribute to the pathogenesis of focal seizures. Received: 17 August 1995 / Revised, accepted: 6 October 1995     

Prognostic value of steroid receptor concentration and flow cytometrical DNA measurements in stage I-II endometrial carcinoma

In order to make a more individualized therapy possible in endometrial cancer we investigated the prognostic ability of steroid receptor concentration and the DNA content in individual cells as measured by flow cytometry. We found that although the steroid receptor concentration was a prognostic parameter, the DNA content proved to be a better parameter than all other known prognostic parameters in endometrial carcinomas stage I-II. Thus it was possible to divide the tumors into three groups; 1) diploid tumors with a relapse rate of 6%, 2) aneuploid tumors with a high estradiol receptor concentration and without myometrial invasion of more than the inner third, and with a relapse rate of 18%, 3) aneuploid tumors, poorly differentiated with a low estradiol receptor concentration or myometrial invasion and with a relapse rate of 44%.     

Growth factors and the thyroid: effects of treatment for hyper- and hypothyroidism on serum IGF-I and urinary epidermal growth factor concentrations

We investigated the impact of thyroid hormone levels on serum concentrations of IGF-I and urinary epidermal growth factor (EGF) in hyper- and hypothyroid patients before and during medical treatment. Serum IGF-I levels measured with radioreceptor-assay decreased in 12 hyperthyroid patients from 1.25 (1.02-1.80) to 1.02 (0.77-1.78) X 10(3) U/l (P less than 0.01), whereas a non-significant increase in 8 hypothyroid patients--from 1.14 (0.85-1.40) to 1.39 (1.08-1.80) X 10(3) U/l was recorded. Urinary EGF, measured with radioimmunoassay decreased in 10 hyperthyroid patients from 68.0 (38.0-122.9) to 40.9 (23.6-100.3) micrograms/g creatinine (P less than 0.001) and increased in 7 hypothyroid subjects from 23.8 (17.5-35.8) to 36.1 (24.7-60.1) micrograms/g creatinine (P less than 0.05). In hyperthyroidism, but not in hypothyroidism, the urinary excretion of creatinine changed significantly from 0.66 (0.26-1.21) to 1.52 (0.81-2.59) g/l (P less than 0.001) during treatment, thus affecting the EGF excretion values. However, a comparison of untreated hyperthyroid with untreated hypothyroid patients showed a highly significant difference in EGF excretion (P less than 0.001) despite a non-significant difference in creatinine excretion between the two groups. FT4 I concentrations correlated significantly (r = 0.83) (P less than 0.001) to EGF values in untreated hyper- and hypo-thyroid patients. Data from the present study thus conform with the view that the growth promoting effect of thyroid hormones involves a stimulated synthesis or release of classic growth factors.     

The value of C2 monitoring in stable renal allograft recipients on maintenance immunosuppression.

BACKGROUND: Cyclosporin A (CyA) is a drug with a narrow therapeutic window and highly variable pharmacokinetics. Therapeutic drug monitoring is essential and conventionally has been guided by trough levels (C0). Recent evidence indicates that a single blood concentration measurement 2 h after CyA administration (C2) is a more accurate predictor of drug exposure and clinical events than determination of C0. To date, limited prospective data are available with respect to risks and benefits of C2 monitoring in renal transplant recipients, and little experience exists with C2 monitoring in maintenance patients. METHODS: In 127 long-term renal allograft recipients, we determined C2 levels in addition to conventional C0 and observed clinical outcome over a period of 13.6 +/- 3.1 months. To determine the precision of monitoring, we repeatedly determined C0 and C2 levels in 46 stable patients without dose change. RESULTS: Clinical outcome was excellent (patient survival 100%, graft survival 97%), with only two borderline rejections, although C2 levels (564 +/- 186 ng/ml) were lower than recommended so far for maintenance patients. We found no significant differences in C2 levels between patients with rejection and CyA toxicity. Receiver operating characteristic (ROC) analysis showed no prediction for risk of rejection, toxicity or infection by C2 levels. Repeated determinations of both C0 and C2 levels in 46 patients revealed a high intra-patient variability. In these patients, the coefficient of variation for C2 was only marginally better compared with C0. CONCLUSIONS: We conclude that in maintenance patients, C2 concentrations between 500 and 600 ng/ml are well tolerated and provide effective and safe rejection prophylaxis. Although mean C2 levels do not seem to be helpful in identifying patients at risk for rejection, they may be useful to detect over-immunosuppression and to improve long-term allograft survival further by reducing CyA nephrotoxicity.     

False positive results of exercise tests with thallium myocardial scintigraphy]

The authors have examined supposed causes of positive Th-201 stress scintigraphy. Patients were divided into two groups according to the presence of exercise-induced transitory hypoperfusion or in absence of it. In both groups negative coronarograms were verified. Results of two groups were compared according to parameters of the left ventricle function, pulmonary pressure, to the presence of disorder of system stimulus-conduction (LBBB, RBBB), mitral prolapsus, foramen ovale apertum, anomalous coronary anatomy, level of load during exercise, body weight, heart volume-index. Significant difference was found in disorder of left ventricle motion, ejection fraction and in comprehensive value of left ventricle function (F1).