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G Yadid

Publications and source records attributed to G Yadid.

8 recordsLinked to original sources
PubMed1992

Preferential release of epinephrine by glycine from adrenal chromaffin cells.

Isolated adrenal chromaffin cells were used as a model for the release of catecholamines from adrenergic nerve endings. In this study we used an HPLC technique to determine the effects of acetylcholine and glycine on norepinephrine and epinephrine release. The amount of catecholamine released in response to glycine was 22% less than that released by acetylcholine. However, while the norepinephrine-to-epinephrine ratio was 1.6 after stimulation with acetylcholine, it was 0.6 after stimulation with glycine. This suggests that glycine preferentially affects epinephrine secretion as compared to acetylcholine, which preferentially releases norepinephrine. This differential effect could be of physiological importance considering our recent demonstration of a functional high-affinity chloride-gated glycine receptor on adrenal chromaffin cells.

Acetylcholine↗
PubMed1992

Methylprednisolone does not decrease eicosanoid concentrations or edema in brain tissue or improve neurologic outcome after head trauma in rats.

Methylprednisolone was recently reported to significantly improve motor and sensory function after acute spinal cord injury in patients. Our study was designed to determine whether methylprednisolone exerts a beneficial effect after head injury. Diethyl ether-anesthetized rats were assigned to receive surgery with no cranial impact and no methylprednisolone (group A, n = 13); surgery with no cranial impact and intraperitoneal methylprednisolone (greater than or equal to 60 mg/kg) (group B, n = 8); surgery with cranial impact and no methylprednisolone (group C, n = 8, and group E, n = 8); or surgery with cranial impact and methylprednisolone (greater than or equal to 60 mg/kg) (group D, n = 15, and group F, n = 13). Neurologic severity score was determined at 1, 2, 4, and 24 h (when appropriate) after injury, and brain tissue eicosanoid levels and cerebral edema were determined when the animals were killed (4 h after injury in groups C and D and 24 h after injury in groups E and F). Treatment with methylprednisolone did not improve neurologic severity score or edema formation and did not alter brain tissue levels of prostaglandin E2, thromboxane B2, or 6-keto-prostaglandin F1 alpha at any time period. The authors conclude that methylprednisolone does not exert a beneficial effect on brain tissue edema or functional activity after cranial impact in rats.

Animals↗
PubMed1991

Effects of the glycine prodrug milacemide (2-N-pentylaminoacetamide) on catecholamine secretion from isolated adrenal medulla chromaffin cells.

1. Milacemide (2-n-pentylaminoacetamide) is a glycine prodrug which readily crosses the blood brain barrier and increases brain glycine and glycineamide. In vitro and in vivo studies, with numerous tissues, including adrenal chromaffin cells, have clearly shown that the formation of the latter metabolites is exclusively mediated by monoamine oxidase B for which milacemide is a substrate. 2. Milacemide, glycineamide and glycine caused a time- and dose-dependent release of catecholamines from bovine isolated chromaffin cells. 3. Milacemide (10(-4) M) induced catecholamine release was roughly 30% of that initiated by acetylcholine (10(-4) M), the natural secretagogue. 4. The combined effects of milacemide (10(-4) M) and acetycholine (10(-4) M) on catecholamine secretion from chromaffin cells is additive, suggesting that milacemide does not act through the normal nicotinic receptor release mechanism. 5. The release of catecholamines from chromaffin cells in response to milacemide (10(-4) M) was partially inhibited by the selective MAO-B inhibitors (-)-deprenyl (10(-7) M) and AGN 1135 (10(-6) M). This indicates that the MAO-B derived metabolites, glycineamide and glycine, contribute to the secretion of catecholamines as does milacemide itself. 6. It is apparent that release of catecholamines by glycine is mediated by its uptake into the cells since [3H]-glycine uptake and catecholamine release showed a highly significant correlation (r = 0.96).

Acetamides↗
PubMed1990

Protective effect of MK801 in experimental brain injury.

The effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK801, was studied in a model of closed head injury in rats. Head trauma (HT) was induced over the left cerebral hemisphere by a calibrated weight-drop device. One or 3 h later, MK801 in saline was given i.p. in a single bolus of either 1, 3, or 10 mg/kg. The rats were killed at 4, 24, or 48 h after HT. Cortical tissue samples were taken from the injured zone and from the corresponding region of the contralateral hemisphere and analyzed for specific gravity (SG) by linear gradient columns. The neurological status of the traumatized rats was evaluated by a neurological severity score (NSS) 1 h after trauma and just before death. Pathological evaluation, based on size and severity of the lesion, was performed 24 and 48 h after HT on control and MK801-treated rats. A dose of 3 mg/kg MK801 given 1 h after trauma effectively prevented the reduction in tissue SG only at 24 h. The NSS could not be evaluated at 24 h after trauma because of the sedating effect of the drug. At 48 h posttrauma, however, the drug significantly improved the neurological state of the rats. No significant difference was found in the pathological score between treated and untreated rats. The results demonstrate neuroprotective properties of MK801, as expressed in two different variables--reduced edema formation and improved neurological recovery after HT. These findings support existing evidence that pharmacological intervention with NMDA receptor antagonist after head injury may be of clinical value in the management of head-injured patients.

Animals↗
PubMed1989

OKY-046 inhibits thromboxane synthesis with no effect on brain edema and neurological status in head traumatized rats.

Head trauma (HT) was induced in the left hemisphere of rats by a weight drop device. Edema was maximal 24 h after HT in the injured zone, and PGE2, TXB2 and 6-keto-PGF1 alpha were elevated in both the injured and remote areas. The effect of a specific thromboxane synthetase inhibitor, OKY-046, on the outcome of HT was studied. OKY-046, 100 mg/kg, was given to rats immediately and 8 h after HT. The neurological severity score (NSS) was evaluated at 1 h after HT, and at 24 h, just prior to sacrifice. Specific gravity (SG) of both hemispheres was measured after decapitation. Prostaglandins (PGs) were extracted from the site of injury and from the frontal lobes, remote from the injury, and assayed by RIA. Basal levels of PGE2 and 6-keto-PGF1 alpha were not reduced by the drug while basal TXB2 levels were lowered. However, the increased production due to HT of all PGs, was inhibited by OKY-046, especially that of TXB2. The ratio of TXB2/6-keto-PGF1 alpha, known to affect vascular tone, was reduced by OKY-046 treatment as a result of TXA2 synthesis inhibition. Still, no effect was found on the neurological outcome (as evaluated by the NSS), or on edema formation (expressed by reduced SG). Thus, based on the present findings increased TXA2 synthesis cannot be implicated in the pathophysiology of cerebral edema or dysfunction following HT.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Accumulation of calcium in the brain following head trauma.

Previous studies have reported accumulation of calcium (Ca) in brain tissue of injured or ischaemic experimental animals. In the present study, head trauma (HT) was induced in the left hemisphere of rats which were subsequently sacrificed 15 min, 1, 2, 4, 24 or 48 h later. Their brains were analysed for oedema formation by the determination of specific gravity (SG), using linear gradient columns, and water content, by dry to wet weight ratio. Total tissue Ca content was measured by atomic absorption spectroscopy. These values, in both the injured and contralateral hemispheres were compared with values obtained from sham-operated rats. Specific gravity of the contused hemisphere was lower than that of the contralateral hemisphere or sham and its water content was higher, at all time points studied. Calcium content was significantly higher in the contused grey matter at 1 h, and in the grey and white matter of both hemispheres at 24 and 48 h after HT. Statistical analysis revealed excellent correlation (cc = 0.65, p less than 0.001) between Ca levels and water content in the grey matter, whenever Ca concentrations were elevated (1, 24 and 48 h). These findings suggest that in the late phase of the post-HT period, Ca accumulation might play a role, along with other mediators, in the development of brain oedema after HT.

Animals↗
PubMed1989

Brain phospholipase A2 is activated after experimental closed head injury in the rat.

Head injury was induced in rats by a weight drop device, falling over the left hemisphere. The rats were killed at 15 min, 4 h, and 24 h after injury. Cortical slices were taken from the injured zone, from the corresponding region of the contralateral hemisphere, and from the frontal lobe of both hemispheres. These cortical slices were incubated in the presence of a fluorescent phospholipid analogue, 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)aminocaproylphosphatidylch oli ne (C6-NBD-PC) which is a substrate for phospholipase A2 (PLA2) in intact cells. The interaction of this substrate with cells produces only one fluorescent product, the fatty acid C6-NBD-FA, released from the 2-position of C6-NBD-PC. Thus, the level of C6-NBD-FA produced is a direct measure of PLA2 activity. Fifteen minutes after trauma, a 75% increase of PLA2 activity was found in the injured zone. At 4 h, the frontal lobe of the contused, left hemisphere had elevated PLA2 activity, as well as the injured zone (92 and 81%, respectively). At 24 h, PLA2 activity at the site of injury was 245% of sham. In the right, noninjured zone, no significant changes in PLA2 activity were noticed during the entire time course of the experiment. Prostaglandin E2 (PGE2) was extracted from the same cortical slices as those used for PLA2 activity measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗