Search PubMed⌕ Search

Biomedical subjects

J Albrecht

Publications and source records attributed to J Albrecht.

At least 109 records · Page 6Linked to original sources
PubMed1993

Changes of the Na/K ATPase activity in the cerebral cortical microvessels of rat after single intraperitoneal administration of mercuric chloride: histochemical demonstration with light and electron microscopy.

Since inorganic mercury salts only poorly penetrate the cerebral microvascular endothelial cells comprising the blood-brain barrier (BBB), their neurotoxicity may be predicted to result from interference with BBB transport enzymes. In the present study, we tested the effect of mercuric chloride (HgCl2) on Na+/K+ ATPase activity, a key enzyme involved in the ion transport in and out of the brain. Routine histochemical staining in conjunction with light and electron microscopy was used to evaluate the changes in the Na+/K+ ATPase activity in cerebral cortical microvessels of rats who received a single intraperitoneal injection of 6 mg/kg HgCl2. At 1 h after HgCl2 administration, light microscopy revealed uniform reduction of the Na+/K+ ATPase reaction in all cortical layers. Electron microscopy confirmed the enzyme reaction to be very weak to completely absent in both the luminal and abluminal endothelial cell membranes, and the luminal plasmalemma showed invaginations and pinocytic vesicles indicative of changes in its transport functions. The enzyme inhibition coincided with, and was likely to contribute to, profound perivascular swelling, involving mainly the astrocytic endfeet. The enzyme activity showed a partial recovery 18 h after HgCl2 treatment, mainly in cortical layers II and III. After 5 days, the recovery of the enzyme activity appeared complete as observed by light and electron microscopy. The recovery of the microvascular Na+/K+ ATPase coincided with the appearance of a strongly positive Na+/K+ ATPase reaction in the adjacent astrocytic processes and with the diminution of perivascular swelling.

Animals↗
PubMed1993

The two catalytic components of the 2-oxoglutarate dehydrogenase complex in rat cerebral synaptic and nonsynaptic mitochondria: comparison of the response to in vitro treatment with ammonia, hyperammonemia, and hepatic encephalopathy.

The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i.p. administration of ammonium acetate on the two components of the multienzyme 2-oxoglutarate dehydrogenase complex (OGDH): 2-oxoglutarate decarboxylase (E1) and lipoamide dehydrogenase (E3), were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to E1 the response to ammonium ions in vitro (3 mM NH4Cl) was observed in nonsynaptic mitochondria only and was manifested by a 21% decrease of Vmax and a 35% decrease of Km for 2-oxoglutarate (2-OG). By contrast, both in vivo conditions primarily affected the synaptic mitochondrial E1: TAA-induced HE produced an 84% increase of Vmax and a 38% increase of Km for 2-OG. Hyperammonemia elevated Vmax of E1 by 110% and Km for 2-OG by 30%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 35% increase of Vmax and a 30% increase of Km for 2-OG of E1. Both in vivo conditions produced a 20% increase of E3 activity in synaptic mitochondria, but no effect at all in nonsynaptic mitochondria. The preferential sensitivity of E1 to ammonium chloride in vitro in nonsynaptic mitochondria and hyperammonemic conditions in vivo in synaptic mitochondria may play a crucial role in the compartmentation of OGDH responses under analogous conditions. These results confirm the intrinsic differences between the OGDH properties in the synaptic and nonsynaptic brain compartments.

Acetates↗
PubMed1993

Changes in the cytoplasmic (lactate dehydrogenase) and plasma membrane (acetylcholinesterase) marker enzymes in the synaptic and nonsynaptic mitochondria derived from rats with moderate hyperammonemia.

The activities of the cytoplasmic and plasma membrane marker enzymes: lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), respectively, were measured in the cerebral homogenates, in the synaptic and nonsynaptic mitochondrial fractions, and in the postmitochondrial supernatants derived from rats in which a 3-d, moderately hyperammonemic condition (no more than 120% increases in blood ammonia) was produced by repeated administration of ammonium acetate (simple hyperammonemia, SHA) or a hepatotoxin, thioacetamide (TAA) (hepatic encephalopathy, HE). As measured in the homogenate and postmitochondrial supernatants, neither of the enzyme activities was affected by SHA or HE. SHA and HE increased the synaptic mitochondrial LDH activity by respectively 53 and 24%, but reduced this enzyme activity in nonsynaptic mitochondria by 19%. Both conditions stimulated the synaptic and nonsynaptic mitochondrial AChE activity by 30-40%. By contrast, the only significant change produced in these fractions by in vitro treatment with a toxic (3 mM) concentration of ammonium chloride was a slight decrease of LDH activity in nonsynaptic mitochondria and postmitochondrial supernatants. It is concluded that moderate hyperammonemia modifies subsequent separation of both cerebral classes of mitochondria from the cytosolic and plasma membrane components. This modification is likely to reflect subtle hyperammonemia-related changes in the physicochemical properties of the two mitochondrial classes and/or other subcellular components.

Acetylcholinesterase↗
PubMed1993

Improved purification of an (R)-oxynitrilase from Linum usitatissimum (flax) and investigation of the substrate range.

The purification of (R)-oxynitrilase (EC 4.1.2.10) from Linum usitatissimum (flax) has been improved considerably. The enzyme is obtained from seedlings in 60% yield by fractional salt precipitation followed by ion-exchange and hydrophobic-interaction chromatography. Final gel-permeation chromatography yields a protein with a specific activity of 53 units/mg at pH 4.1. The N-terminal sequence is reported and microheterogeneity demonstrated. The substrate range was investigated using (R)-oxynitrilase immobilized on Eupergit and t-butyl methyl ether as solvent. The addition of HCN to various aliphatic ketones and aldehydes is catalysed by the enzyme, while aromatic ketones are not converted. (R)-Butan-2-one cyanohydrin was synthesized on a preparative scale and the product characterized.

Aldehyde-Lyases↗
PubMed1992

The effect of ammonia and pH on brain gamma-glutamyl transpeptidase in young rats.

Acute hyperammonemia, induced by two consecutive injections of ammonium acetate (550 and 450 mg per kg b.wt.), decreased the activity of gamma-glutamyl transpeptidase (GGT) in most brain regions of 18- and 30-day-old rats. This decrease in the brain GGT activity was more pronounced in younger than in older rats. After the addition of NH4Cl to the incubation medium, the inhibitory action of NH4+ on this enzyme activity was also demonstrated in crude synaptosomal membranes at pH 7.4, but in a range of NH4+ concentrations many-times higher than those found in the plasma or brains of young hyperammonemic rats. Because similar concentrations of NH4+ stimulated the activity of the purified enzyme from rat kidney (mainly at pH 9.0), the inhibition of GGT activity in the young rat brain is probably mediated indirectly and not by a direct interaction of ammonia with the enzyme molecules.

Acetates↗
PubMed1992

Characteristics of large neutral amino acid-induced release of preloaded L-glutamine from rat cerebral capillaries in vitro: effects of ammonia, hepatic encephalopathy, and gamma-glutamyl transpeptidase inhibitors.

The release of newly loaded L-[14C]glutamine (L-Gln) from rat cerebral cortical capillaries was stimulated by L-transport system substrates: tryptophan (TRY), leucine (leu), and nonlabeled L-Gln, respectively, by 32, 50, and 40% above the basal release resulting from superfusion with standard Krebs-Henseliet buffer. However, no stimulation was observed upon treatment with D-Gln or L-glutamate (L-Glu), which are not the L-system substrates, or with ammonium chloride. The stimulatory effect of TRY was temperature dependent but sodium independent, and was abolished in the presence of a sulfhydryl reagent N-ethylmaleimide (NEM). The results support the view that the L-Gln-stimulated uptake of large neutral amino acids (LNAA) across the blood-brain barrier involves the L-system mediated Gln-LNAA exchange. The TRY-stimulated Gln release was enhanced in vitro by simultaneous addition of ammonium chloride, and in capillaries derived from rats with acute hepatic encephalopathy (HE). These results confirm the role of Gln-LNAA exchange in the excessive accumulation of LNAA in brain observed in a variety of hyperammonemic conditions. Superfusion of L-Gln-loaded capillaries in a buffer containing gamma-glutamyl transpeptidase (GGT) inhibitors, serine borate (SB) or 6-diazo-5-oxo-L-norleucine (DON), increased the basal L-Gln release and made it irresponsive to subsequent treatment with TRY. However, the basal release was also increased by superfusion with serine alone or Leu, and this treatment abolished the subsequent effect of TRY as well. Moreover, DON stimulated L-Gln release from capillaries superfused in a standard way, and the effects of DON and TRY were additive. Hence, in the present conditions, SB and DON acted as L-system substrates rather than as GGT inhibitors. Taken together, the results do not support the concept that GGT mediates the Gln-LNAA exchange.

Amino Acids↗
PubMed1992

Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy.

The release of newly loaded [3H]GABA was studied in slices of different brain regions derived from rats in which acute hepatic encephalopathy (HE) was induced with a hepatotoxin thioacetamide. HE increased both spontaneous and high (50 mM) ammonium chloride-evoked GABA release in cerebral cortical slices by 38% and 50%, respectively. No effects of HE were noted in cerebellar or striatal slices. An increased release of GABA in the cerebral cortex may contribute to the endogenous benzodiazepine-mediated enhancement of GABAergic tone, which is thought to be partly responsible for the pathophysiological mechanism of HE.

Ammonium Chloride↗
PubMed1992

Progressive multifocal leukoencephalopathy in HIV-1-infected children.

OBJECTIVE: To describe the clinical and pathologic features of two HIV-1-infected children with progressive multifocal leukoencephalopathy (PML). DESIGN: Case report. SETTING: University-affiliated, public-health trust hospital. METHODS: Two HIV-1-infected children with PML are described. A 13-year-old girl, presumed to be congenitally infected with HIV-1, presented with dysarthria and paresthesias of the tongue and chin that evolved rapidly to dementia, muteness and severe spastic quadriparesis. The other patient, a 10-year-old boy who developed HIV-1 infection from a blood transfusion at the age of 3 years, presented with a facial palsy with subsequent development of right hemiparesis and aphasia. RESULTS: Brain biopsy in the first child and autopsy in the second confirmed the diagnosis of PML. In both patients, the CD4 T-lymphocyte count was less than 100 x 10(6)l at the time of neurological presentation. CONCLUSION: Despite seroepidemiological studies suggesting that the majority of individuals are infected with JC virus during childhood, PML is rare in children with impaired cell-mediated immunity. Our patients illustrate that PML is among the neurological complications of HIV-1 infection in children.

Adolescent↗
PubMed1992

Noradrenaline- and glutamate-induced taurine release from bulk isolated adult rat astrocytes.

The influence of noradrenaline and various agonists of glutamatergic receptors on preloaded [3H]taurine release from bulk isolated adult rat brain astrocytes was investigated by a superfusion technique. In the presence of 1 mM noradrenaline a stimulation of taurine release, resembling that observed in astroglial cultures, was preceded by an inhibition of the efflux, thus demonstrating different dynamics of noradrenaline-evoked taurine release from that observed with beta-agonists on cultured astroglia. Application of 1 mM glutamate and kainate produced stimulation of the release, while 1 mM N-methyl-D-aspartate (NMDA) and 1 mM NMDA together with 65 mM K+ had no effect on the [3H]taurine release. These data suggest the presence of kainate-sensitive and the absence of NMDA-sensitive glutamate receptors on bulk isolated astrocytes, which is consistent with previous observations on astrocytes in culture.

Animals↗
PubMed1991

Decreased potassium-stimulated release of [3H]D-aspartate from hippocampal slices distinguishes encephalopathy related to acute liver failure from that induced by simple hyperammonemia.

The calcium-dependent, high (65 mM) potassium-evoked release of the L-glutamate analogue [3H]D-aspartate (D-Asp) was measured in hippocampal slices derived from rats with (a) hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide, (b) hyperammonemia produced by i.p. administration of ammonium acetate, and (c) in normal slices preincubated for 30 min with 1 mM ammonium acetate. HE (variant a) inhibited the release by about 30%, which was interpreted to indicate depressed exocytosis of synaptic glutamate. This phenomenon is likely to lead to a decrease of glutamate-mediated neural excitation, which in turn could contribute to the neural inhibition typical of HE. By contrast, and in agreement with earlier reports, hyperammonemia (variant b) did not affect D-Asp release, whereas in vitro treatment of the slices with ammonium acetate (variant c) resulted in a 60% increase of the release. Hence, impairment of synaptic glutamate exocytosis is the phenomenon that distinguishes HE related to toxic liver failure from simple hyperammonemia. This result emphasizes the role of other factors than ammonia in the pathophysiological mechanism of HE.

Acetates↗
PubMed1991

Aluminum chloride stimulates the release of endogenous glutamate, taurine and adenosine from cultured rat cortical astrocytes.

Primary astrocyte cultures derived from neonatal rat cerebral cortex were treated for 5 min with 0.5 mM or 5.0 mM AlCl3, and the incubation medium was analyzed by HPLC for the content of released glutamate (Glu), taurine (Tau), serine (Ser) and the nucleoside adenosine (Ade). At 0.5 mM, AlCl3 stimulated Tau release to about 170% of basal levels, but did not affect the release of the other compounds. Treatment with 5.0 mM AlCl3 enhanced the release of Tau, Glu and Ade, to 800%, 1000% and 250%, respectively, but decreased the release of Ser to 70% compared to basal levels. The enhanced release of these neuroactive compounds from astrocytes may contribute to changes in neural transmission known to accompany exposure to aluminum.

Adenosine↗
PubMed1991

Aspartate aminotransferase, malate dehydrogenase, and pyruvate carboxylase activities in rat cerebral synaptic and nonsynaptic mitochondria: effects of in vitro treatment with ammonia, hyperammonemia and hepatic encephalopathy.

The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i.p. administration of ammonium acetate on the activity of the two malate-aspartate shuttle enzymes: aspartate aminotransferase (AAT), malate dehydrogenase (MDH), and on the pyruvate carboxylase (PC) activity were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to the shuttle enzymes the response to ammonium ions in vitro (3mM NH4Cl) was observed in nonsynaptic mitochondria only, and was manifested by a 27% decrease of AAT activity and a 16% decrease in MDH activity. By contrast, both in vivo conditions primarily affected the synaptic mitochondrial enzymes: TAA-induced HE produced a 26% decrease of synaptic mitochondrial AAT and a 50% decrease of synaptic mitochondrial MDH. Hyperammonemia inhibited synaptic mitochondrial AAT by 30% and synaptic mitochondrial MDH by 45%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 30% increase in the AAT activity, but no changes in MDH. All the experimental conditions affected the nonsynaptic mitochondria PC: ammonium chloride in vitro produced a 20% decrease, TAA-induced HE--a 30% decrease, whereas hyperammonemia inhibited the enzyme by 53%. The PC activity in synaptic mitochondria was very low (about 2% of that measured in nonsynaptic mitochondria), which is consistent with the primarily astrocytic localization of the enzyme.

Ammonia↗
PubMed1991

Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis.

Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond.

Adult↗
PubMed1991

Durable inhibition of rat cerebral capillary Na+/K(+)-ATPase after in vivo administration of mercuric chloride.

Intraperitoneal administration of a single dose (6 mg/kg body wt.) of mercuric chloride led to a rapid and irreversible inhibition of Na+/K(+)-ATPase activity in rat cerebral capillaries. The activity measured at 1 h, 18 h and 5 days after injection was, respectively, 53, 44 and 26% of the control. By contrast, Mg(2+)-ATPase activity in the capillaries remained uninhibited throughout the observation period. Mercuric chloride administration did not affect either of the two enzyme activities in nerve endings, which is consistent with the inability of the compound to penetrate the blood-brain barrier. The mercuric-chloride-induced impairment of the capillary sodium pump may contribute to disturbances of ion homeostasis in the brain and thus to the neurophysiological abnormalities accompanying this exposure. Direct treatment of the isolated cerebral capillary preparations with mercuric chloride evoked a stronger inhibitory effect on Mg(2+)-ATPase (IC50 = 0.25 microM) than on Na+/K(+)-ATPase (IC50 = 5.0 microM). This result indicates that the effect in vivo may not have resulted from direct interaction of the compound with the latter enzyme.

Animals↗
PubMed1991

Decreased glucose utilization in discrete brain regions of rat in thioacetamide-induced hepatic encephalopathy as measured with [3H]-deoxyglucose.

To evaluate the possible contribution of bioenergetic failure in the particular brain regions to the pathomechanism of hepatic encephalopathy (HE), local cerebral metabolic rate for glucose (LCMRglue) was evaluated from [3H]-deoxyglucose uptake in frontal, visual and auditory cortex, striatum, cerebellum and medulla oblongata of rats with acute HE induced with a hepatotoxin--thioacetamide (TAA). HE caused a decrease of LCMRglue in all the regions studied. The strongest decrease (about 65%) was noted in hippocampus and cerebral cortex--the two regions rich in glutamatergic neurons. The results indicate a possible link between decreased energy metabolism and impaired excitatory, glutamatergic neurotransmission--the two factors whose contribution to HE has so far been implicated separately.

Animals↗
PubMed1991

Effects of acute hepatic encephalopathy and in vitro treatment with ammonia on glutamate oxidation in bulk-isolated astrocytes and mitochondria of the rat brain.

The metabolism of [1-14C] glutamate to 14CO2 and the glutamate dehydrogenase (GLDH) activity towards alpha-ketoglutarate (alpha-KG) formation were measured in bulk isolated astrocytes derived from control rats and rats with acute hepatic encephalopathy (HE) induced with thioacetamide. In addition, the effects of in vitro treatment of control and HE astrocytes and non-synaptic mitochondria with toxic (3mM) NH4Cl concentration were followed. [1-14C] glutamate oxidation measured as a whole was identical in control and HE astrocytes and was inhibited by ammonia to the same degree in either fraction. In the presence of a glutamate transamination inhibitor--3mM aminooxyacetic acid (AOA), when only the GLDH-mediated part (25% of total) of the glutamate oxidation remained active, the inhibitory effect of ammonia treatment was much more pronounced in HE astrocytes than in control astrocytes. The ability of non-synaptic mitochondria to utilize glutamate to CO2 was not changed in presence of 3mM NH4Cl, whereas a substantial decrease of CO2 production (about 80%) in both the control and HE preparations was observed in the presence of 3mM AOA. GLDH activity was not at all affected by either of the experimental conditions, both in astrocytes and purified non-synaptic mitochondria. Thus, the inhibition of glutamate oxidation in astrocytes by ammonia and the compounded inhibitory effect of HE, ammonia and AOA appeared to be located beyond the glutamate dehydrogenation step within the tricarboxylic acid cycle.

Ammonia↗
PubMed1990

[Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study].

The efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre double-blind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over a period of 60 days. 263 patients were included in this study, which was carried out in 8 centres in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. Treatment was discontinued in three of those cases.

Double-Blind Method↗