Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study

We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n = 8), thalamocapsular hemorrhage (n = 6), or pure thalamic stroke (n = 7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit. These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment. Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia.     

Pioglitazone hydrochloride inhibits cholesterol absorption and lowers plasma cholesterol concentrations in cholesterol-fed rats.

Diabetes is associated with altered cholesterol metabolism that may contribute to cardiovascular complications. Treatment of rats with pioglitazone hydrochloride, a novel antidiabetic compound that improves the general response of target cells to insulin, significantly lowered cholesterol levels in rats fed a hypercholesterolemic diet and produced a significant reduction in cholesterol absorption. Drug treatment was ineffective in rats that were not given dietary cholesterol. To determine whether these effects of pioglitazone hydrochloride might be related to the known ability of this compound to improve the response to circulating insulin, similar studies were conducted in streptozocin-induced diabetic rats with and without insulin replacement. Diabetic rats absorbed a greater percentage of dietary cholesterol than control rats. Treatment of insulin-deficient diabetic rats with pioglitazone alone did not affect cholesterol absorption; however, the combination of insulin and pioglitazone was synergistic to lower absorption of cholesterol and circulating cholesterol and triglycerides. Treatment of either normal rats or diabetic rats receiving insulin with pioglitazone hydrochloride produced a twofold decrease in the ratio of total cholesterol to high-density lipoprotein cholesterol. These results suggest that treatments that improve insulin sensitivity may also have a positive impact on coronary artery disease associated with diabetes.     

Exercise increases the circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in normal individuals.

Recently two peptides consisting of amino acids (aa) 1 to 30 and 31 to 67 of the N-terminus of the 126 aa prohormone of atrial natriuretic factor (proANF), as well as atrial natriuretic factor (ANF, aa 99 to 126; C-terminus), were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in humans as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentrations of the N-terminus and C-terminus of the ANF prohormone in normal persons, 12 healthy individuals (mean age 45 +/- 2 years) were evaluated before, for 2 hours after, and during bicycle exercise at a work loads of 25, 50, 75, 100, 125, 150, and 175 W. Both the N- and C-terminus of the ANF prohormone were released simultaneously with graded exercise in direct proportion to the intensity of the work load, measured objectively via maximal oxygen consumption (VO2max), respiratory quotient, and heart rate. Both the N-terminus and C-terminus of the ANF prohormone had strong positive correlations (p less than 0.001) with blood pressure, heart rate, VO2max, and respiratory quotient. Following exercise, the C-terminus returned to preexercise levels within 30 minutes, while the N-terminus remained significantly elevated at 30 and 60 minutes postexercise, reflecting the longer half-life of the N-terminus in the circulation.     

Heel reconstruction with an iliac osteocutaneous free flap in a child

We report a case of heel reconstruction in a 13-month-old child in one stage. An iliac crest osteomyocutaneous free flap based on the deep circumflex vessels was transferred using microsurgical techniques. The apophysis of the os calcis was replaced with a portion of the iliac epiphysis to allow normal growth of the heel. At age 2 years, the patient is walking normally and wearing regular shoes of equal size. Gait analysis reveals normal ambulation.     

Bronchial blood flow and microvascular permeability in the pathophysiology of asthma

Bronchial smooth muscle contraction is not the only causative factor of airway narrowing in asthma. Other components, such as mucosal and submucosal oedema and mucosal inflammation, also intervene in the processes leading to bronchial obstruction. Re-analyzing the role of the tracheo-bronchial circulation is therefore necessary, since participation of the latter, through modification of bronchial blood flow and/or alteration of microvascular permeability, very likely modifies mucosal thickness of the bronchial wall and/or clearance of bronchoactive substances from the airways. This also implies that more attention should be paid on the vascular actions of compounds which are either currently prescribed or under development for future treatment of asthma.     

Capsaicin-induced neuronal degeneration in the brain and retina of preweanling rats

Capsaicin is a neurotoxin known for its ability to cause degeneration of small unmyelinated primary sensory neurons in both spinal and cranial nerves. Although lower motor neurons do not degenerate following capsaicin treatment, the extent to which capsaicin may damage neurons in the brain has not been thoroughly evaluated. This study examines the effects of systemic capsaicin (50-150 mg/kg) on the central nervous system of 10-day-old rats. Rat pups were injected with capsaicin or the injection vehicle and sacrificed 6 hours-10 days later. Brains, spinal cords, and retinas were stained with cupric silver to label degenerating neurons. As previously reported for capsaicin-treated rats, degenerating nerve terminals were present in areas receiving primary afferent input: the spinal cord dorsal horn, spinal trigeminal nucleus, nucleus of the solitary tract, and area postrema. However, degenerating terminals were also present in areas not known to receive primary sensory innervation: the inferior olivary nucleus, sphenoid nucleus, medial and olivary pretectal nuclei, interpeduncular nucleus, interfascicular nucleus, caudal linear, dorsal, median, and paramedian raphe nuclei, supramammillary area, lateral habenula, ventrolateral geniculate nucleus, ventral reuniens nucleus, ventromedial hypothalamic nucleus, lateral hypothalamic and preoptic areas, suprachiasmatic nucleus, septohypothalamic nucleus, bed nucleus of the stria terminalis, lateral septal nucleus, accumbens shell, olfactory bulb, and retina. Some areas where capsaicin caused degeneration in rat pups do not appear to be capsaicin-sensitive in adult rats. Results indicate that (1) capsaicin's neurotoxicity is not limited to primary sensory neurons and (2) developmental factors may alter the capsaicin sensitivity of some neuronal projections within the brain.     

Immunohistochemical studies on colloid bodies (Civatte bodies) in oral lesions of discoid lupus erythematosus

Abstract – By electron microscopy colloid bodies have been shown to be derived from epithelial cells. It has been suggested, however, that connective tissue cells or components from the basement membrane zone contributed to the formation of colloid bodies. In order to examine these possibilities we stained oral lesions of discoid lupus erythematosus (DLE) with antibodies against intermediate filaments (keratin, vimentin), basement membrane components (laminin, collagen type IV) and fibronectin. IgM was used as a marker for colloid bodies. Colloid bodies were stained positive for keratin, whereas vimentin was never found in colloid bodies. Laminin and collagen type IV were occasionally seen in their periphery probably owing to adherence of basement membrane fragments during apoptosis. Fibronectin was frequently seen at the entire periphery of colloid bodies which may facilitate their elimination by macrophages. In conclusion, connective tissue cells or basement membrane components do not seem to contribute to the formation of colloid bodies in oral DLE.     

Enhanced transport in a therapeutic transdermal system

Ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. A variety of control membrane laminates were examined for swelling and adhesion strength following equilibration with ethanolic solutions to identify a mechanically stable control membrane laminate. In vitro skin permeation analysis of the control membrane laminate showed that ethanol flux was linearly related to the ethanol volume fraction. A reservoir-type therapeutic transdermal system incorporating ethanol was developed to provide constant release of drug and ethanol through skin for 24 h. In vitro ethanol skin permeation rates were constant for 24 h and adhesion was stable over 16 wk at 40°C using a transdermal reservoir device.     

The use of magnetic resonance imaging for the diagnosis of fetal intracranial anomalies

While fetal cranial sonography has been used for the sensitive detection of ventriculomegaly, ancillary imaging techniques may be needed for precise delineation of structural abnormalities. This report outlines the radiologic and clinical results using maternal magnetic resonance imaging (MRI) in ten patients with suspected fetal intracranial anomalies. Imaging was accomplished at 17–39 weeks gestational age, using spin-echo, a multislice technique with intramuscular morphine sulfate for sedation. In four cases, MRI significantly clarified the sonographic diagnosis, while in two cases the scan agreed with the sonographic findings. In one patient, MRI failed to image a lumbar meningomyelocele associated with the Chiari II malformation. In two patients with the Chiari II malformation, both sonography and MRI failed to delineate the anatomic pathology completely. Optimal imaging resolution was achieved in the third trimester. Four patients died in the perinatal period. All the surviving patients required shunting to treat intracranial hypertension; only two patients were meeting cognitive milestones. We conclude that due to the high incidence of multiple anomalies in the fetus with ventriculomegaly, precision in neuroradiological diagnosis is essential. MRI can be a useful adjunct to cranial sonography for the specific delineation of abnormalities of the fetal central nervous system.