Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

Effects on Behaviour and EEG of Single Chain Phospholipases A2 from Snake and Bee Venoms Injected into Rat Brain: Search for a Functional Antagonism

Abstract: Three phospholipase A₂ (PLA₂s), OS₁ and OS₁ purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA₂ were injected to rats by the intracerebroventricular route. OS₁ showed no sign of neurotoxicity at doses at which OS₂ and bee venom PLA₂ produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA₂s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS₂-induced disturbances. Blockers of L-type Ca²⁺ channels and K⁺ channel openers were also without effect. The toxicity of OS₂ and bee venom PLA₂ is probably due to their initial specific binding to their neuronal receptor sites.     

Hepatitis C associated with Guillain-Barré syndrome

ABSTRACT— Hepatitis C is frequently associated with immune-mediated diseases, such as cryoglobulinemia. Guillain-Barré syndrome is an acute demyelinating neuropathy of probable immune pathogenesis. We describe two patients with Guillain-Barré syndrome, and associated chronic hepatitis C, the second one previously treated with interferon. The link between both conditions may be hepatitis C being the trigger of this immune polyneuropathy. Guillain-Barré syndrome should be added to the list of conditions associated with hepatitis C.     

Hyperreactio luteinalis in a normal pregnancy: Sonographic and MRI findings

A case of hyperreactio luteinalis in an otherwise normal pregnancy is reported. Ascites was present, but no peritoneal implants or adenopathy were seen. Findings that would have suggested the correct diagnosis are the symmetrical and bilateral pattern of the mass, as well as the rather uniform size of the loculi, which were 1 to 3 cm in diameter.     

Ascending cluster pinning of the humerus inserted through the deltoid tuberosity

Summary Goal of Surgery Stable internal fixation of extraarticular proximal humeral fractures. Indications Extraarticular fractures angulated more than 30° which can be reduced closely or through a small incision. Epiphysiolysis. Fracture-dislocation of the humeral head. Contraindications Pathological fractures. Four part fractures. Segmental fractures of the humerus. Positioning and Anaesthesia Supine; the affected shoulder overhanging the edge of the table and supported by a radiolucent board. General or regional anaesthesia. Surgical Technique Closed pinning of two part and certain three part fractures of the proximal humerus being displaced, unstable, and mainly at the metaphyseal level. Introduction of Kirschner wires through a diaphyseal window and advancement into the proximal fragments after reduction which is controlled by image intensification. Postoperative Management Temporary immobilization in a sling. Passive and active assisted movements after a few days. Active movements after 2 weeks. Removal of wires after 3 months. Possible Complications Fracture of the humerus at the site of the cortical window. Injury to the radial nerve. Results 32 patients, mean age 49 years, 30 two part fractures and 2 three part fractures. Number of Kirschner wires used: 3 to 6, mean 4. Two out of 3 patients complained of pain at the site of wire insertion. All fractures consolidated. No avascular necrosis nor infection. Complications: Partial loss of internal fixation in 3 patients. One fracture of the humeral shaft. Sympathetic reflex dystrophy in 3 patients. Half of the patients had a normal range of motion. Time of follow-up: 6 to 24 (mean 10) months. Division of Orthopaedics and Traumatology, Purpan Hospital, Toulouse, France.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.     

Définition et évolution du statut nutritionnel au cours d'une greffe osseuse allogénique (15 malades): Rôle de la nutrition parentérale et de l'apport azoté

Our work concerned 15 patients (9 males, 6 females) with a mean age of 29.5 years, having a hematologic malignant disease and undergoing allogenic bone marrow transplantation.We studied :

1. The metabolic disorders induced by the conditioning regimen (chemotherapy and total body irradiation) pregraft accompanying cytolysis (day −7, −5, −2).

2. The corrective effect of a total parenteral nutrition introduced 2 days before the transplantation and pursued during 30 days post-graft (day −2 to day 30).

3. The interest of a high calorie intake (BEE × 2) and, after randomisation, of a variable nitrogen intake (24% of the total calorie intake for group A [8 patients] and 14% for group B [7 patients]). The patient characteristics of these two groups were closely comparable. Urinary parameters were studied daily (3-methylhistidine, cratinine, nitrogen) and blood parameters weekly (transferrin, pre-albumin, albumin, retinol binding protein).

We observed globally :

-- An excellent result of the nutritional support without significant weight loss;

-- protein catabolism stopped with a recovery of synthesis of RBP after day 7 and pre-albumin from day 7;

-- a decrease in muscle catabolism.

The randomized study showed :

-- a significant difference in nitrogen excretion between group A and group B;

-- earlier and better protein synthesis recovery in group A, particularly with regard to RBP and pre-albumin.

In conclusion, we recommend for the patients undergoing bone marrow transplantation :

-- nutritional support should be introduced before the conditioning regimen;

-- a high calorie intake (BEE × 2) with a nitrogen intake between 14% and 24% of the total calorie intake;

-- cyclic parenteral nutrition should be pursued during the second and third month post-graft.

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

Aspects of three dimensional reconstruction for a multi ring positron tomography

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Effect of temperature on the transcription by bacteriophage T3-induced RNA polymerase

Bacteriophage T3-induced RNA polymerase is rapidly inactivated at 42°C. Addition of T3 DNA delays this process for 30 s and reduces the rate with which the enzyme activity is lsot indicating that a labile binary complex between T3 DNA and polymerase must have been formed. The ternary complex between T3-specific RNA polymerase, T3 DNA, and nascent RNA chains obtained when the enzyme is incubated with T3 DNA, GTP, ATP, and UTP is stable to heat (42°C) and only slowly inactivated by polyvinyl sulfate. The optimal temperature for the formation of polyanionresistant ternary complexes is 30°C while the elongation of T3 RNA chains proceeds fastest at 38°C.