PubMed Health⌕ Search

Biomedical subjects

T Nathan

Publications and source records attributed to T Nathan.

10 recordsLinked to original sources
PubMed2006

Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production.

Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.

Acidosis, Renal Tubular↗
PubMed2004

Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: It seems rational to perform endoscopic retrograde cholangiopancreatography (ERCP) if the probability of endoscopic therapy is high, but to carry out magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) first if this probability is moderate or low. The aim of the present study was to develop a model describing the probability of endoscopic therapy in patients without previous biliary imaging. PATIENTS AND METHODS: The development of the model was based on stepwise multiple logistic regression applied to 2470 prospectively registered first-time ERCP procedures. The model was evaluated by application to 442 prospectively registered first-time ERCP procedures entered in the database in the following 2 years. RESULTS: Predictors selected were: age, gender, p-amylase >/= 400 U/l, ln(s-bilirubin), ln(s-alkaline phosphatase), common bile duct (CBD) stone seen on transabdominal ultrasonography, gallbladder stone seen on transabdominal ultrasonography, interaction of dilated bile ducts seen on transabdominal ultrasonography with ln(s-bilirubin), and interaction between age and male gender. The area under the receiver operating characteristic (ROC) curve was 0.875 and there was good fit of the model. A test with a probability cutoff value of 80 % had a positive predictive value (PPV) of 92.8 %. Specificity was 87.1 % and, using this test, 52.4 % of patients would have been selected for primary ERCP. In the application cohort, the frequency of therapy was higher than in the development cohort. The area under the ROC curve was 78.7 %. When used in the evaluation cohort, with a cutoff probability of 80 %, the test had sensitivity 84.0 %, specificity 49.5 %, negative predictive value (NPV) 46.6 % and PPV 85.6 %. Of the patients, 76.7 % would have been selected for ERCP. This would have identified 85.5 % of individuals needing therapeutic ERCP without use first of MRCP or EUS. Test-positive cases constituted 90.3 % of stent insertions and 86.3 % of stone extractions. CONCLUSIONS: The model is useful for selection of patients for ERCP at our center.

Adolescent↗
PubMed1991

Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials.

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.

Animals↗
PubMed1991

Depression of the fast IPSP underlies paired-pulse facilitation in area CA1 of the rat hippocampus.

1. Intracellular recordings from CA1 pyramidal neurons in the rat hippocampal slice have been used to study synaptic transmission after maximal orthodromic stimulation of the Schaffer collateral-commissural fibers. Paired-pulse stimulation was used to investigate how the first (conditioning) stimulation influenced the response to the second (test) stimulation. 2. When the test stimulation was delivered up to approximately 4 s after the conditioning stimulation, the late phase of the excitatory postsynaptic synaptic potential (EPSP) was increased ("late-phase facilitation") whereas the fast (f-) and the slow (s-) inhibitory postsynaptic potentials (IPSPs) were depressed. 3. In terms of appearance and time course, facilitation of the intracellularly recorded EPSP was similar to that of the extracellularly recorded field EPSP in stratum radiatum. 4. The s-IPSP is not involved in facilitation of the EPSP. To show this, we counteracted the s-IPSP either by repolarizing the membrane potential to the resting level or by intracellularly injecting the quaternary lignocaine derivative QX 314. Facilitation of the late phase of the EPSP was unaffected by either procedure. 5. The conditioned response was modified in two ways when the stimulation was delivered at the equilibrium potential for the f-IPSP (Ef-IPSP) and the s-IPSP had been blocked by intracellular injection of QX 314. The amplitude of the EPSP was increased, and the repolarizing phase was delayed with an apparent depolarizing shift of Ef-IPSP. This effect was present at pulse intervals greater than 20 ms and was maximal after 150 ms. Facilitation could be detected at interpulse intervals of up to 4 s. 6. The gamma-aminobutyric acid-B (GABAB) agonist baclofen (1 microM) reduced late-phase facilitation by preferentially increasing the unconditioned response, such that this came to resemble a conditioned response in control medium. 7. The f-IPSP was isolated pharmacologically to investigate its role in the facilitation of the EPSP. This was done by blocking the s-IPSP with QX314 and the EPSP with a mixture of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovaleric acid (APV, 50 microM), and the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). An f-IPSP was then evoked by stimulating the interneurons directly. This potential could be blocked by the GABAA receptor antagonist bicuculline (20 microM), thereby confirming the successful isolation of GABAAergic transmission. 8. With paired-pulse stimulation, the amplitude of the conditioned f-IPSP was depressed.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1990

GABAB receptors play a major role in paired-pulse facilitation in area CA1 of the rat hippocampus.

Extracellular recordings of field potentials in area CA1 of the rat hippocampal slice have been used to investigate paired-pulse facilitation. Field potentials were evoked by maximal stimulation of the Schaffer collateral/commissural fibres. The height of the population spike (PS) in stratum pyramidale (str. pyr.) and the area under the field excitatory postsynaptic potential (EPSP) following the PS in the stratum radiatum (str. rad.) were quantified. These values were used to describe the time course of paired-pulse facilitation. Facilitation of the PS was maximal 50 ms after the conditioning pulse and was present over a period of about 500 ms. However, facilitation of the late area (LA) of the field EPSP was maximal afer 125 ms and had an overall duration of 1-2 s. The N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), had no effect on paired-pulse facilitation of either the LA or the PS. The gamma-aminobutyric acid-B (GABAB) agonist baclofen increased facilitation of the PS. This was mainly due to a reduction of the unconditioned response. Facilitation of the LA was reduced by both baclofen and the GABAB antagonist, 2-OH-saclofen. Baclofen increased the LA of the unconditioned response, while this was unaffected by 2-OH-saclofen. The LA of facilitated responses was decreased by 2-OH-saclofen while the effect of baclofen on these responses was more complex. Baclofen reduced the LA of maximally facilitated responses, while the LA of slightly facilitated responses was increased. The results show that different mechanisms are involved in the facilitation of the LA and the PS. Furthermore, activation of GABAB receptors makes a large contribution to paired-pulse facilitation of the field EPSP. It is also suggested that recording of extracellular fields in str. rad. in response to paired-pulse stimulation provides a simple electrophysiological model for testing the effect of agents which act at the GABAB receptor.

2-Amino-5-phosphonovalerate↗
PubMed1990

The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.

Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic.

Action Potentials↗
PubMed1986

[Apropos of Gilles de la Tourette's disease].

The observation of a young north african afflicted with a tic disorder suggests an underlying meaning in the apparently confused motoric discharges, thanks to psychodrama and to ethnopsychoanalytic consultations with the family. Thus, at a time when the Gilles de La Tourette syndrome is described as a neurological disorder, while recognizing the limited utility of chemotherapy, we believe that neurobiological studies, whatever their merit, do not exempt us from thinking about the specific psychopathology of tics and their evolving relationship with neurotic symptoms. That is, to go from motor discharge to the elaboration of conflicts.

Adolescent↗