Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.     

Influence of norepinephrine and dopamine on cortical perfusion,EEG activity,extracellular glutamate,and brain edema in rats after controlled cortical impact injury

Following traumatic brain injury, catecholamines given to ameliorate cerebral perfusion may induce brain damage via cerebral arteriolar constriction and increased neuronal excitation. In the present study the acute effects of norepinephrine and dopamine on pericontusional cortical perfusion (rCBF), electroencephalographic (EEG) activity, extracellular glutamate, and brain edema were investigated in rats following controlled cortical impact injury (CCI). rCBF, cerebral perfusion pressure (CPP), EEG activity, and glutamate were determined before, during, and after infusing norepinephrine or dopamine, increasing MABP to 120 mm Hg for 90 min at 4 h after CCI. Control rats received physiological saline. At 8 h after CCI, hemispheric swelling and water content were determined gravimetrically. Following CCI, rCBF was significantly decreased. In parallel to elevating MABP and CPP, rCBF was significantly increased by norepinephrine and dopamine, being mostly pronounced with norepinephrine (+44% vs. +29%). In controls, rCBF remained diminished (-45%). EEG activity was significantly increased by norepinephrine and dopamine, while pericontusional glutamate was only elevated by norepinephrine (28 +/- 6 vs. 8 +/- 4 microM). Brain edema was not increased compared to control rats. Despite significantly increasing MABP and CPP to the same extent, norepinephrine and dopamine seem to differentially influence pericontusional cortical perfusion and glutamatergic transmission. In addition to the pressure-passive increase in CPP local cerebral effects seem to account for the sustained norepinephrine-induced increase in pericontusional cortical perfusion. The significantly elevated pericontusional glutamate concentrations in conjunction with the increased EEG activity suggest a sustained metabolically driven increase in cortical perfusion during norepinephrine infusion.     

Pseudotumor cerebri in a patient with Goldenhar's and Duane's syndromes

A 4-year-old boy presented with Goldenhar's syndrome, Duane's syndrome and bilateral papilledema. Magnetic resonance imaging of the brain was unremarkable. On lumbar puncture, the cerebrospinal fluid (CSF) pressure measured 36 cm H(2)O. CSF examination was normal. The diagnosis of pseudotumor cerebri was made, and treatment with acetazolamide was started. As the papilledema did not resolve, steroids were added to the treatment. Lumbar puncture was repeated after 1 month, and pressure was found to be 30 cm H(2)O. Because medical treatment was not effective in lowering the CSF pressure, optic nerve sheath fenestration was performed. Papilledema resolved over the next 2 months. To the best of our knowledge, this is the first case of Goldenhar's syndrome associated with pseudotumor cerebri.     

Ocular perfusion abnormalities in diabetes

PURPOSE: To review the role of ocular perfusion in the pathophysiology of diabetic retinopathy, one of the leading causes of irreversible blindness in the industrialized world. METHODS: We carried out a Medline search of the literature published in English or with English abstracts from 1966 to 2000 using various combinations of relevant key words. RESULTS: Hyperglycaemia leads to a wide variety of vascular abnormalities at the microvascular and macrovascular levels, including abnormal autoregulation. CONCLUSION: Three major aspects of ocular perfusion in diabetic retinopathy require additional investigation. Firstly, the precise mechanisms that link elevated glucose to dysfunction of retinal vascular cells need to be identified. Secondly, those factors that lead to both capillary dropout and to angiogenesis, twin processes that are linked to tissue hypoxia and lead to excess perfusion, increased risk of extravascular leakage and frank haemorrhage, must be carefully delineated. Finally, once specific knowledge of disease fundamentals has been amassed, tests of therapies to reverse or prevent these pathological processes can move forward.     

Do blind persons have a better sense of smell than normal sighted people?

Functional disorders of sense organs may intensify the remaining senses. It is presumed that blind persons do not only hear better and have an intensified tactile sense but also have a stronger sense of smell. Better hearing ability was demonstrated by auditory evoked potentials. We investigated the sense of smell of blind persons by subjective tests (Sniffin' sticks: threshold, discrimination and identification) and for the first time also by objective tests (olfactory evoked potentials and trigeminal evoked potentials) and compared the results with the smelling ability of normal sighted persons by pair matching. Moreover, the investigated persons judged their performance via a questionnaire. The subjective test showed neither differences in the peripheral function nor in the central function between both groups. The amplitudes and latencies of the evoked potentials of vanillin, carbon dioxide and hydrogen sulfide were also not different. Blind persons tried unasked to identify the smell given in the discrimination test and thought themselves to be better in smelling. For the first time the smelling ability of blind people was compared with normal sighted people by objective test methods. Neither with subjective nor with objective methods differences were found.