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Biomedical subjects

H Lehmann

Publications and source records attributed to H Lehmann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Immunocytochemical localization of GABA immunoreactivity in dentate granule cells of normal and kindled rats.

In order to identify lasting alterations in gamma-aminobutyric acid (GABA) neurons in the kindling model of epilepsy, immunocytochemical techniques were used to quantify the number of GABA-immunoreactive (IR) neurons in different regions of the hippocampal formation (HCF) of amygdala-kindled rats, 40 days after the last fully kindled seizure. A new, highly specific monoclonal GABA antibody was used for these experiments. Unexpectedly, the antibody not only stained neurons in CA1, CA3, and hilus, but also intensively stained granule cells (GCs) in the dentate gyrus (DG) of both kindled rats and non-kindled controls, indicating that GCs may be capable of synthesizing GABA. Comparison with a polyclonal GABA and a glutamate decarboxylase antibody showed that staining of GCs with the monoclonal GABA antibody was much more intense. The number of GABA-IR cells that were counted in different regions of the HCF, including the DG, did not differ significantly between kindled rats and controls, which does not support the hypothesis of loss of hippocampal GABAergic neurons to explain the permanency of kindled epileptogenesis.

Anesthesia↗
PubMed1996

Kindling induces a lasting, regionally selective increase of kynurenic acid in the nucleus accumbens.

We determined endogenous kynurenic acid in nine brain regions and plasma of amygdala-kindled rats at different intervals (24 h or 50 days) after the last fully kindled seizure. Data obtained were compared with age-matched electrode-implanted and non-implanted control groups. Kindling induced a lasting increase in kynurenate in nucleus accumbens, whereas no significant alterations were seen in hippocampus, cerebral cortex, olfactory bulb, striatum, thalamus, tectum, cerebellum, pons/medulla, or plasma. The regionally selective alteration in the nucleus accumbens is in line with previous studies indicating that this brain region functions as a modulatory interface between the limbic and motor systems and may be critically involved in seizure propagation in the kindling model of temporal lobe epilepsy. The increased levels of the endogenous glutamate antagonist kynurenate in nucleus accumbens may be interpreted as a compensatory change to reduce enhanced excitation in this brain region.

Amygdala↗
PubMed1996

The cost effectiveness of oral rehydration therapy for U.S. children with acute diarrhea.

Diarrheal disease is a common cause of morbidity among U.S. children under five years of age and exerts a heavy burden on the health care system. Oral rehydration therapy (ORT), a simple, inexpensive treatment modality that can prevent most diarrhea-related complications, is grossly underutilized in the United States. Using a decision-analysis model, this article describes the financial burden of childhood diarrhea in the United States for children under five years of age and discusses the substantial economic benefits of ORT programs. If fully implemented, such programs would save our health care system close to $1 billion annually.

Acute Disease↗
PubMed1996

L-deprenyl (selegiline) exerts anticonvulsant effects against different seizure types in mice.

L-Deprenyl (selegiline), a selective inhibitor of monoamine oxidase type B, has recently been shown to exert anticonvulsant and antiepileptogenic effects in the kindling model of partial (focal) epilepsy. In the present study, we examined if L-deprenyl exerts anticonvulsant effects in standard rodent models of generalized seizures. In addition to anticonvulsant activity, behavioral effects induced by L-deprenyl were monitored closely. To assess the stereoselectivity of anticonvulsant and behavioral effects of deprenyl, the D-enantiomer was included in the studies. Furthermore, the antiepileptic drug phenobarbital was used for comparison. The following tests were performed in mice: 1) the threshold for tonic electroconvulsions; 2) the maximal electroshock seizure test with fixed supramaximal (suprathreshold) stimulation; 3) the threshold for myoclonic, clonic and tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ); 4) the s.c. PTZ seizure test, with a fixed dose of PTZ (80 microgram/kg) for seizure induction; 5) the rotarod and chimney tests for determination of motor impairment. Furthermore, animals were observed in cage and open field for stereotyped behavior and other behavioral abnormalities. L-Deprenyl, tested at doses of 1 to 40 microgram/kg i.p., significantly increased myoclonic and clonic PTZ thresholds and the threshold for tonic electroconvulsions, whereas D-deprenyl was either ineffective or exhibited a lower anticonvulsant potency than L-deprenyl. Both drugs were ineffective in the maximal electroshock seizure and s.c. PTZ seizure tests. In contrast to the higher anticonvulsant potency of L-deprenyl in seizure threshold tests, D-deprenyl was more potent than L-deprenyl to induce behavioral abnormalities, such as hyperlocomotion. The data indicate that L-deprenyl exerts anticonvulsant activity against different seizure types. This anticonvulsant activity and the previously reported neuroprotective and cognition-enhancing action of L-deprenyl offer a unique combination of drug effects which might be of clinical benefit in patients with epilepsy.

Animals↗
PubMed1996

Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys.

The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in the ratio 5:4:1 was investigated for its chronic toxicity in rats. For comparison the individual drugs ASA and NAPAP as well as the double combination ASA+NAPAP were tested in equipotent doses. 20 male and 20 female rats per group (Chbb:THOM/SPF) received doses of 50, 100 and 200 mg/kg of the combination ASA+NAPAP+caffeine, 45 and 180 mg/kg of the combination ASA+NAPAP, and 50 and 200 mg/kg of the individual drugs ASA or NAPAP over a period of 6 months. The daily dose was splitted into two parts and administered 3 h apart. The rats were single housed under standardized conditions with free access to food and drinking water. Plasma concentrations were measured in four additional animals of all high dose groups after the last dosing at seven time points. Besides the usual routine toxicological investigations the kidneys of five females per group were investigated by transmission electron microscopy. All investigations were performed according to GLP regulations. All animals behaved unobtrusively throughout the study with only minor impairment of general conditions in some animals of all ASA, ASA+NAPAP+caffeine and the high dose NAPAP groups. Dose related mortality was observed in the groups receiving ASA alone or in combination, partly with rales and tonic convulsions immediately prior to death. Body weight gain was decreased in males but not in females of the ASA+NAPAP+ caffeine and ASA groups. No consistent drug- and dose-dependent changes in hematological, clinico-chemical or urinanalytical parameters were observed, except for a slight increase in excretion of epithelial cells in both genders of the ASA groups. Plasma drug level monitoring demonstrated that the pharmacokinetics of ASA were not altered by co-administration of caffeine or NAPAP or vice versa. In males, maximum plasma concentrations (Cmax) and areas under the curve (AUC) for ASA and NAPAP tended to be slightly lower than in females. The plasma concentrations reached in the study represent a low multiple (2.2-7.9) of therapeutic plasma levels. Therefore, the results reported in the study can be considered representative for normal therapeutic use of the analgesic combination ASA+NAPAP+caffeine. Gastric erosions in the ASA and ASA+NAPAP+caffeine groups, increased kidney weights in females given 200 mg/kg ASA+NAPAP+caffeine, and dose-dependently increased liver weights in females given 200 mg/kg ASA and decreased liver weights in males at 100 and 200 mg/kg ASA-NAPAP+caffeine were the only consistent drug-induced changes observed at necropsy. Except for the above mentioned ulcer, all histopathological findings were iatrogenic or spontaneous lesions. The kidneys demonstrated initial stages of age-associated nephropathy at comparable incidence and severity in all groups including controls. Semi-thin section evaluation and transmission electron microscopy showed only minor changes. Taking all tubular and vascular changes together (total mean), the animals of the NAPAP group were slightly more affected than those of the other groups. Summing up it can be concluded that the nephrotoxic potential of the combination ASA+NAPAP+caffeine, if existing at all, was marginal even after prolonged administration, and that it does not exceed that of the monosubstances when given at pharmacologically equipotent doses and clinically relevant exposures.

Acetaminophen↗
PubMed1995

Effects of the enantiomers of (+/-)-HA-966 on dopamine neurons: an electrophysiological study of a chiral molecule.

The present study was conducted to evaluate the effects of the resolved enantiomers of (+/-)-1-1 hydroxy-3-aminopyrrolidone-2 ((+/-)-HA-966) on the electrophysiological properties of dopamine-containing neurons in the substantia nigra of the chloral hydrate anesthetized rat. Both (+)- and (-)-HA-966 produced a dose-dependent reduction in firing rate that eventually resulted in total cessation of spontaneous neuronal activity (ID50 = 5.7 and 57.8 mg/kg i.v., respectively). The inhibitory effects of both drugs were accompanied by a marked increase in the regularity of neuronal firing and a concomitant suppression of bursting activity. Although approximately 10-fold less potent than the (-) enantiomer, the inhibitory effects of (+)-HA-966 were completely antagonized by the centrally active, GABAB receptor antagonist, CGP-35348 (300 mg/kg i.v.). These data suggest that the complementary electrophysiological effects of the enantiomers of (+/-)-HA-966 on nigral dopamine neurons are mediated through a common mechanism of action possibly involving a novel interaction with GABAB receptors.

Animals↗
PubMed1994

Effects of NPC16377, a potent and selective sigma receptor ligand, on the activity of mesencephalic dopamine-containing neurons in the rat.

NPC16377 is a highly selective sigma receptor ligand with low affinity for other neurotransmitter receptors. Preclinical studies indicate that the drug exhibits a pharmacological profile similar to that previously ascribed to atypical antipsychotic drugs. In the present series of experiments, extracellular recording techniques were used to assess the acute effects of NPC16377 on the electrophysiological properties of mesencephalic dopamine-containing neurons in the rat. Systemic administration of NPC16377 produced marginal increases in the firing rate of these neurons but failed to fully reverse the inhibitory effects of the dopamine agonists apomorphine and d-amphetamine. Low doses of the drug potentiated the rate-decreasing effects of d-amphetamine in the substantia nigra but not in the ventral tegmental area. Some of these effects are similar to the actions of atypical antipsychotic drugs, while others appear to be unique to this compound and may involve a direct interaction with sigma sites.

Action Potentials↗
PubMed1994

PRE3, highly homologous to the human major histocompatibility complex-linked LMP2 (RING12) gene, codes for a yeast proteasome subunit necessary for the peptidylglutamyl-peptide hydrolyzing activity.

20S proteasomes are multifunctional proteinase complexes ubiquitous in eucaryotes. We have cloned the yeast PRE3 gene by complementation of the pre3-2 mutation, which leads to a defect in the peptidylglutamyl-peptide hydrolyzing activity of the 20S proteasome. The PRE3 gene, a beta-type member of the proteasomal gene family, is essential for cellular life and codes for a 193-amino acid proteasomal subunit with a predicted molecular mass of 21.2 kDa. The Pre3 protein shows striking homology to the human proteasome subunits Hs delta and Lmp2 (Ring12). Lmp2 is encoded in the major histocompatibility complex class II region implicating proteasomes in antigen processing.

Amino Acid Sequence↗
PubMed1994

Pathomorphological and biochemical alterations in Ehlers-Danlos-syndrome type IV.

We are reporting the morphological and biochemical data of a patient with the characteristic features of the Ehlers-Danlos-Syndrome Type IV (Sack-Barabas Type) who died acutely after an episode of recurrent ruptures of the bowel with subsequent septic peritonitis. Morphologically, the connective tissue of the vessel walls, the dermis and the connective tissue of internal organs, particularly that of liver and lung, showed a distinct hypoplasia of the collagenous scaffold. Collagen fibers were irregularly arranged which was also corroborated by ultrastructural examination of the collagen fibrils of the dermis and of intervertebral disc material. Immunohistochemically, a loss in the staining intensity for collagen III could be observed in all locations. In contrast, the localization of collagen I, IV, V and VI appeared normal, although with some reduced staining intensity which particularly held true for collagen I in the dermis and vessel wall. The biochemical content of collagen III in lung and liver tissue was significantly reduced when compared to control tissues. Accordingly, in the pool of newly synthesized collagen from skin fibroblasts, only minute amounts of collagen III could be found which was normally secreted and had a normal electrophoretic migration.

Cells, Cultured↗
PubMed1994

[Comparative electron microscopic studies on the localization of silicon in leaves of two different grass species].

The quality of green fodder can be diminished by lignifying and mineralizing the plant cell walls. In many grasses epidermal cell walls are penetrated with silica; those plants are extremely rough and sharp-edged and are not ingested by animals. The process of silicification of cell walls was studied comparatively in two grasses, the soft Perennial Ryegrass (Lolium perenne) and the rough Tufted Hair-grass (Deschampsia caespitosa). In Lolium only the epidermal cell walls of the leaf edges and the trichomes are penetrated with silica, whereas in Deschampsia silica could be demonstrated in the walls of all epidermal cells and of the trichomes. In addition, silica containing cells, the so called silica bodies, were found in Deschampsia leaves. Silica was detected using two analytical electron-microscopical techniques, the Electron-Energy-Loss-Spectroscopy (EELS) and the Electron-Spectroscopic-Imaging (ESI).

Animal Feed↗
PubMed1993

Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta.

Immunohistochemical studies of bone from individuals with osteogenesis imperfecta (OI) type II, OI type III, or OI type IV demonstrate a similar pattern, but varying extent, of the abnormal presence of interstitial collagens in bone matrix. OI type II bone had nests of cartilage with type II collagen, and significant type III collagen in the bone matrix. In OI types III and IV, type II collagen was present only in epiphyseal cartilage but bone still contained type III collagen. These findings resembled those in developing fetal bone indicating the "immature" nature of OI bone.

Adult↗
PubMed1993

Autoantibodies to cartilage collagens in relapsing polychondritis.

Relapsing polychondritis is a systemic disease associated with a destruction of cartilage in various parts of the body. Sera from six patients with relapsing polychondritis and one patient with microscopic polyarteritis nodosa as well as from six controls were analyzed by immunoblotting and ELISA. All patients had autoantibodies against native collagens II and IX. The serum from one patient showed a strong reaction with all three collagen chains of the high molecular weight fraction of collagen IX after denaturation; sera from four patients showed autoantibodies against alpha 2 (XI) and sera from three patients showed autoantibodies against the covalently cross-linked gamma component of collagen XI. The presence of autoantibodies against collagens II, IX, and XI, which form the major fibrillar scaffold in cartilage and mediate the interaction of collagen fibrils and proteoglycan, suggests that autoantibodies against cartilaginous collagen may play a crucial role in the pathogenesis of relapsing polychondritis and microscopic polyarteritis nodosa.

Adult↗
PubMed1993

Ultrastructural findings in soft tissues adjacent to titanium plates used in jaw fracture treatment.

The present study was conducted on biopsies from soft tissues overlying titanium miniplates that were used for the treatment of jaw fractures. The aim was to investigate the morphology of liberated titanium particles and cellular or ultrastructural changes in tissues adjacent to the miniplates. Conventional transmission electron microscope (TEM) images were used for ultrastructural investigation and identification of metal-dense particles. The presence of titanium was proved by an increase in the intensity of element-specific, inelastically scattered electrons from the primary beam. The results showed that 5-8 months after insertion of the plates and screws, there was weak cellular activity within the scar tissue overlying the plates without inflammatory cells. Most of the titanium particles were located extracellularly. The ultrastructural appearance of most of these particles suggested that titanium may be shaved off the plates or screws and may undergo cellular uptake and lysosomal degradation. The partially degraded titanium particles are then left in place after the phagocytic cells have been isolated by collagenous fibers and have finally perished.

Bone Plates↗
PubMed1993

[Osteogenesis imperfecta in childhood and adolescence].

BACKGROUND: 209 patients with osteogenesis imperfecta type I, III and IV were studied to provide data on the natural course of the disease until the end of the second decade. RESULTS: Weight and length at birth were normal in most cases of type I and IV, markedly reduced in type III. Fractures and deformities at birth were most frequent in type III. High fracture rates occurred in type III and IV up to 8-10 years of age. Skeletal deformities developed primarily in the lower extremities and the spine, again most frequently in type III. Radiological features were--besides osteopenia--Wormian bones of the skull, pseudoarthroses, deformity of the pelvis, popcorn epiphyses (most frequent in type III) and hyperplastic callus (most frequent in type IV). Longitudinal growth of patients with type I was in the lower normal range, while patients with type III and IV developed marked growth deficiency. Motor performance was not severely impaired in most cases of type I; however, all type III patients and 71% of type IV patients were confined to a wheelchair in later life. CONCLUSION: As defined, type I patients had a mild clinical course until early adulthood. Type III and IV represented a spectrum of severely affected patients. Although type IV patients were less affected at birth, their postnatal course in some respects resembled that of type III.

Activities of Daily Living↗