Blood-brain glucose transfer: repression in chronic hyperglycemia.

Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

Reduced reciprocal inhibition is seen only in spastic limbs in patients with neurolathyrism.

If reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity as has been suggested in several studies, the inhibition is expected to be impaired in spastic, but not in normal muscles. Patients with neurolathyrism offer a possibility of testing this prediction since the spastic symptoms in these patients are restricted to the lower extremities only. Three patients with neurolathyrism were tested. Their data were compared with 15 age-matched healthy subjects. All patients showed signs of spasticity in the legs. Two patients had normal voluntary muscle force in the lower extremities and one had decreased force. No clinical abnormalities were found in the upper extremities. Reciprocal inhibition between ankle dorsiflexor and plantarflexor muscles was absent in all patients, whereas the inhibition between wrist extensor and flexor muscles was present and of normal size and latency. These findings are consistent with the hypothesis that reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity.

Apical sodium-sugar transport in pulmonary epithelium in situ.

The presence of an apical sodium-coupled transport system for D-glucose in lung alveolar epithelial cells has been demonstrated in lungs instilled with Ringer's fluid and perfused with either blood or Ringer's fluid (Basset et al. (1987) J. Physiol. 384, 325-345). The direction of transport is from alveoli towards interstitium. The characteristics of the system were evaluated in similar preparations by use of sugar analogues such as alpha-methyl-glucopyranoside, 2-deoxyglucose, 3-O-methylglucose and L-glucose. The main finding was the presence of a transport system for alpha-methylglucopyranoside and 2-deoxyglucose in the apical cell membrane. This system was unaffected by phloretin. Both alpha-methylglucopyranoside and 2-deoxyglucose transports were inhibited by phloridzin and by the presence of glucose (10(-2) mol.l-1). Competition was demonstrated between D-glucose and alpha-methylglucopyranoside or 2-deoxyglucose, but not for 3-O-methylglucose or L-glucose. 3-O-Methylglucose was cleared as slowly as L-glucose. The results comply partly with those known from intestinal epithelium and kidney proximal tubular epithelium, but the handling of 3-O-methylglucose was different. The relative transport rates of Na+ and glucose are compatible with a Na+: glucose coupling ratio larger than one.

Electrical resistance of a capillary endothelium.

The electrical resistance of consecutive segments of capillaries has been determined by a method in which the microvessels were treated as a leaky, infinite cable. A two-dimensional analytical model to describe the potential field in response to intracapillary current injection was formulated. The model allowed determination of the electrical resistance from four sets of data: the capillary radius, the capillary length constant, the length constant in the mesentery perpendicular to the capillary, and the relative potential drop across the capillary wall. Of particular importance were the mesothelial membranes covering the mesenteric capillaries with resistances several times higher than that of the capillary endothelium. 27 frog mesenteric capillaries were characterized. The average resistance of the endothelium was 1.85 omega cm2, which compares well with earlier determinations of the ionic permeability of such capillaries. However, heterogeneity with respect to resistance was observed, that of 10 arterial capillaries being 3.0 omega cm2 as compared with 0.95 omega cm2 for 17 mid- and venous capillaries. The average in situ length constant was 99 micrometers for the arterial capillaries and 57 micrometers for the mid- and venous capillaries. It is likely that the ions that carry the current must move paracellularly, through junctions that are leaky to small solutes.

The permeability of single capillaries to potassium ions.

This paper reports a description of methods for determining the diffusional permeability to potassium ions of single capillaries in the frog mesentery. By means of micropipettes, injections or infusions were delivered into a single capillary. The subsequent concentration variations in and about the capillary were followed with K(+)-sensitive microelectrodes. A theoretical analysis is provided which give a quantitative frame of reference for evaluating the observed time-concentration curves in terms of capillary permeability. The advantage of single capillary studies is that the surface area through which diffusion occurs is known as is the concentration difference across the capillary membrane. Three different techniques are: (a) the "single injection" method which represents an application of the indicator diffusion technique where a high-K(+) bolus is injected into a single capillary; (b) the "sack" method which determines the rate of K(+) disappearance from within and immediately outside an occluded capillary segment, after a brief increase in intracapillary K(+) concentration; and (c) the "interstitial diffusion" method which records time and spatial distribution of K(+) in the interstitial space after a step-change in intracapillary K(+) concentration. The methods gave an average potassium permeability of the capillary membrane of 67x10(-5) cm s(-1) (SD: 23, n=26) at room temperature. These figures are clearly higher than those previously reported in mammalian capillary studies using whole-organ techniques. In terms of the pappenheimer pore model, this estimate of capillary permeability is consistent with the behavior of a membrane with a thickness of 1.0 mum which possesses equivalent pores with a radius of 110 A, a fractional pore area of 0.3 percent, and a pore density of 8 mum(-2).

Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP).

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.

Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier disease subjects.

Tangier disease (TD) is an inherited disorder of lipid metabolism characterized by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl ester accumulation and reduced cholesterol excretion in response to HDL apolipoproteins. Molecular defects in the ATP binding cassette transporter 1 (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role in the translocation of cholesterol across the plasma membrane, and defective ABCA1 causes cholesterol storage in TD cells. Not only cholesterol efflux, but also phospholipid efflux was shown to be impaired in TD cells. By use of thin layer chromatography, high performance liquid chromatography and time-of-flight secondary ion mass spectrometry, we characterized the cellular phospholipid content in fibroblasts from three homozygous TD patients. The cellular content of the major phospholipids was not found to be significantly altered in TD fibroblasts. However, the two phospholipids cardiolipin and lysocardiolipin, which make up minute amounts in normal cells, were at least 3-5-fold enriched in fibroblasts from TD subjects. A structurally closely related phospholipid (lysobisphosphatidic acid) has recently been shown to be enriched in Niemann-Pick type C, another lipid storage disorder. Altogether these data may indicate that the role of these phospholipids is a regulatory one rather than that of a bulk mediator of cholesterol solubilization in sterol trafficking and efflux.

Growth of colorectal carcinoma cells: regulation in vitro by gastrin, pentagastrin and the gastrin-receptor antagonist proglumide.

The growth-regulating effects of pentagastrin, gastrin and the gastrin-receptor antagonist proglumide were investigated in three established cell lines derived from human colorectal carcinomas in vitro and after transplantation into nude mice. In vitro a significant increase of cell growth in the SW 403 cell line incubated with pentagastrin or gastrin was observed. In the Lovo cell line this effect was only detected after synchronization of cell growth. Pentagastrin and gastrin had no effect on the growth of the Ls 174 T cell line. Proglumide reduced cell proliferation in all three cell lines as well as in the L929S cell line derived from fibroblasts, which served as control. After transplantation into nude mice all tumor cell lines increased, Lovo and Ls 174 T as undifferentiated tumor, SW 403 as differentiated. Pentagastrin increased and proglumide decreased growth in SW 403 tumors, whereas no effect was observed on Ls 174 T and Lovo tumors. We therefore conclude that growth of some colorectal carcinomas is regulated by gastrin, but that the effect of proglumide is unspecific rather than related to blockage of gastrin receptors. The growth-regulating effect of gastrin could be due to tumor differentiation.

Electrical resistance of brain microvascular endothelium.

A newly developed technique for determination of the electrical resistance of the capillary wall was applied to microvessels at the surface of the frog brain. Current was injected into a capillary or venule via a microelectrode and the ensuing intravascular potential profile away from the current source was determined with a second microelectrode placed at various positions along the capillary. The membrane resistance was calculated according to the theory for leaky cables used in determinations of axon membrane resistance. The average resistance was 1870 omega . cm2. Since the surface vessels of the frog brain are devoid of glial investment but otherwise similar to brain parenchymal vessels, the results prove that the endothelium is the site of the blood-brain barrier. The electrical resistance is similar to that of a 'tight' epithelium.

Neurophysiological studies in malignant disease with particular reference to involvement of peripheral nerves.

Neurological and neuromuscular disorders are frequent complications in patients with neoplasms and may involve the neuromuscular system, including motor and sensory nerve cell bodies, axons, myelin, neuromuscular transmission and muscle alone or in combination. Electrophysiological studies are of value in delineating the type, degree and extent of involvement, and may be of assistance in pointing towards the underlying cause: paraneoplastic factors, treatment with chemotherapy or radiation or metastatic infiltration. Though some electrophysiological features may be characteristic of certain syndromes, they rarely can stand alone but require clinical, pathological, radiological, and laboratory studies to obtain a diagnosis. Even in cases where such studies are obtained, a final diagnosis may only be ascertained during follow up, since the neuromuscular disorders frequently occur before the neoplasm is detected.

The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients.

OBJECTIVES: To measure the effect of baclofen on the transmission in different spinal pathways to soleus motoneurones in spastic multiple sclerosis patients. METHODS: Baclofen was administered orally in 14 and intrathecally in 8 patients. H(max)/M(max), presynaptic inhibition by biceps femoris tendon tap of femoral nerve stimulation, depression of the soleus H-reflex following previous activation of the Ia afferents from the soleus muscle (i.e. postactivation depression), disynaptic reciprocal Ia inhibition of the soleus H-reflex and the number of backpropagating action potentials in primary afferents, which may be a sign of presynaptic inhibition, were examined. RESULTS: Baclofen depressed the soleus H(max)/M(max) ratio significantly following oral and intrathecal baclofen. None of the two tests of presynaptic inhibition, or the postactivation depression or the disynaptic reciprocal Ia inhibition of the soleus H-reflex were affected by baclofen administration. Also the action potentials of the primary afferents were unchanged during baclofen administration. CONCLUSIONS: The antispastic effect of baclofen is not caused by an effect on the transmitter release from Ia afferents or on disynaptic reciprocal Ia inhibition. One possible explanation of the depression of the H-reflex by baclofen is suggested to be a direct depression of motoneuronal excitability.

The development and evaluation of an alcohol and drug prevention and treatment program for women and children. The AR-CARES program.

This study examined the evolution of the Arkansas Center for Addictions Research, Education, and Services (AR-CARES) over a 5-year period and evaluated its impact on women and children. The program was designed to provide comprehensive substance use prevention and treatment services to low-income pregnant and parenting women and their children. The program changed significantly over this time, based upon input from clients and staff, as well as in response to changing community resources. The evaluation suggests that the program had an impact on the substance use of study participants, birth outcomes, and the growth and development of children.

A comprehensive substance abuse treatment program for women and their children: an initial evaluation.

This article examines a comprehensive, residential substance abuse treatment program for women and their children. A majority of the 72 participants studied were African American single mothers, for whom crack/cocaine was the drug of choice. The women and their children were assessed repeatedly during treatment, and at 3, 6, and 12 months postdischarge. Program impact was estimated by comparing the outcomes of three groups that differed in the amount of treatment they received: early dropouts, late dropouts, and treatment graduates. Program graduates showed more positive outcomes than the nongraduate comparison groups in the areas of drug use and negative consequences of use, employment and self-sufficiency, and family interaction skills. Young children enrolled in treatment with their mothers were assessed using a developmental screening test, and older children with a measure of drug refusal skills. Results from both child measures suggest substantial improvement.

[Diagnosis of polyneuropathies]. / Diagnostik af polyneuropatier.

The accurate diagnosis of peripheral neuropathy is important with respect to the therapeutic possibilities and limitations, which are especially relevant in immune-mediated polyneuropathies. These polyneuropathies may be axonal or demyelinating and have an acute or chronic course, and they may be difficult to distinguish from non-treatable neuropathies on clinical grounds. Efforts have been made to establish clinical, neurophysiological, morphological, biochemical, immunological and molecular biological criteria to attain specific diagnosis. This has shown heterogeneity not only within the treatable neuropathies, which may have implications for the treatment. It has also been shown that hereditary or diabetic polyneuropathy may have features which respond to immunosuppressive treatment. Molecular biology studies have revealed markers for the diagnosis of hereditary neuropathy, and have in some instances also delineated the gene product.