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Biomedical subjects

M Lanza

Publications and source records attributed to M Lanza.

At least 19 recordsLinked to original sources

Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis.

BACKGROUND: The conjugate of doxorubicin with lactosaminated human albumin has the potential of increasing the doxorubicin efficacy in the treatment of hepatocellular carcinomas expressing the asialoglycoprotein receptor. However, coupled doxorubicin also accumulates in the liver, which might damage hepatocytes. AIMS: To verify whether coupled doxorubicin impairs liver function in rats with liver fibrosis and cirrhosis. METHODS: Coupled doxorubicin was administered using the same schedule which exerted an antineoplastic effect on rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g). Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning. Liver samples were studied histologically. Serum parameters of liver function and viability were determined. RESULTS: In normal rats, administration of coupled doxorubicin neither caused microscopic changes of hepatocytes nor modified serum liver parameters. In rats with fibrosis/cirrhosis, although a selective doxorubicin accumulation within the liver followed coupled doxorubicin administration, the drug did not have a detrimental effect on the histology of the liver and, among serum liver tests, only alanine aminotransferase and aspartate aminotransferase levels were moderately modified. CONCLUSIONS: Coupled doxorubicin can be administered to rats with liver fibrosis/cirrhosis without inducing a severe liver damage. If further studies will confirm the efficacy and safety of this compound, coupled doxorubicin therapy may open a new perspective in the treatment of hepatocellular carcinoma.

Animals↗

[Nearly total thyroidectomy: versus total thyroidectomy: our experience].

AIM: Generally, the classification of thyroidectomy as benign pathology is: multinodular toxic goitre, simple goitre, toxic adenoma, Base-dow disease, Hashimoto's tyroiditis Subtotal thyroidectomy provides for the removal of the gland except for a bilateral residue of about 6-10 g, near total thyroidectomy provides for the near total removal of the gland except for a residue inferior to 5 grams. Near total thyroidectomy has taken the place of the subtotal thyroidectomy. METHODS: In two years, in our institute, there have been exeuted: 96 near total thyrodectomies, 96 total thyroidetomies, 8 lobectomies ad two revues for recurrencies. RESULTS: In 2 cases there have been haemorrhagies after nearly total thyroidetomy. Only in 1 case we practiced tracheotomy for follicular carcinoma infiltering thiroidic cartilage. In 2 cases treated with nearly total thyroidetomy and in 4 cases treated with total thyroidetomy, there has been temporary hypoparathyroidism. In no case treared wih nearly total thyroidetomy and in 2 cases treated with total thyroidetomy, there has been permanent hypo-parathyroidism. In 5 cases treated with total thyroidetomy and in no case treated with nearly total thyroidetomy, there has been, monolateral, temporary paralysis of the inferior laryngeal nerve that solved in 6 months for 3 patients and in 2 months for 2 patients. CONCLUSIONS: There has not been permanent paralysis of the mono or bilateral inferior laryngeal nerve. Even if the surgical approach to the benign disease is now orientated to the total thyroidectomy, a more conservative surgery is, in our opinion, justified when a malignant pathology is excluded and considering also the low effect of recurrencies and hypothyroidism.

Adolescent↗

Can we utilize photorefractive keratectomy to improve visual acuity in adult amblyopic eyes?

PURPOSE: To report the results of photorefractive keratectomy (PRK) in adult amblyopic patients. DESIGN: Noncomparative case series. PARTICIPANTS: Thirty-eight amblyopic eyes of 36 adult patients who had undergone PRK ranging from -14.63 diopters (D) to +3.75 D (mean, -6.38+/-4.10) were analyzed. METHODS: Preoperative and postoperative (1, 3, and 6 months) refractions and measurements of the best spectacle-corrected visual acuity (BSCVA) were reviewed. Statistical evaluation was performed using a paired Student's t test. MAIN OUTCOME MEASURES: Best-corrected visual acuity before and after PRK. RESULTS: Before PRK, BSCVA ranged between 0.2 and 0.7 lines (mean, 0.60+/-0.13). One month after PRK, BSCVA ranged between 0.2 and 1.2 lines (mean, 0.77+/-0.24), with a significant difference (P = 3x10(-5)). Three months after PRK, BSCVA ranged between 0.15 and 1.15 lines (mean, 0.84+/-0.23), with a significant difference (P = 5x10(-7)). Six months after PRK, BSCVA ranged between 0.25 and 1.3 lines (mean, 0.88+/-0.25), with a significant difference (P = 8x10(-8)). CONCLUSIONS: Our study does not imply that refractive surgery should or may be performed in young children but, rather, that adults wishing to undergo refractive surgery may undertake such procedures despite an amblyopic eye thought to be refractory to visual rehabilitation by conventional methods, such as spectacles and contact lenses.

Adult↗

Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier.

BACKGROUND: The hepatocyte receptor for asialoglycoproteins, which binds and internalises galactosyl terminating peptides, was found to be expressed also on the cells of the majority of hepatocarcinomas. AIMS: To verify whether doxorubicin coupling to lactosaminated albumin, a galactosyl terminating neoglycoprotein, produces selective drug accumulation in hepatocytes with reduced concentrations in extra-hepatic tissues, thus facilitating the use of the drug in hepatocarcinoma treatment. METHODS: Doxorubicin concentrations were measured in organs of mice injected with the free or coupled drug. RESULTS: In mice injected with the coupled drug, the ratios between doxorubicin concentrations in liver and those in heart, intestine, spleen and kidney were 8-14 times higher than in animals that received the same dose of the free drug. CONCLUSIONS: Due to the very efficient liver targeting of doxorubicin, the lactosaminated human albumin-doxorubicin conjugate appears to have the potential of improving the chemotherapy of hepatocellular carcinomas through the asialoglycoprotein receptor.

Animals↗

Citrus pulp and wheat straw silage as an ingredient in lamb diets: effects on growth and carcass and meat quality.

Twenty "Merinizzata Italiana" lambs were introduced to two experimental diets. Ten animals (five males and five females, control group) received the traditional diet that is supplied by farmers in southern Italy, which comprised of oat hay ad libitum and commercial concentrate. The second group (the same number of lambs, silage group) received citrus pulp and wheat straw silage ad libitum and 70% of the commercial concentrate supplied to the control group. The animals were slaughtered after 80 days of feeding and carcass and some meat quality parameters were measured. No differences were observed for live weight between treatments, and carcass weights were similar for the two diets, but with obvious differences between sexes. Animals on silage produced carcasses with a better muscular conformation and with a lower fatness score (P<0.05). Subcutaneous fat colour was influenced by sex, being lighter in the female carcasses (P<0.05). Dissection of different anatomical parts showed a higher percentage of lean and a lower proportion of fat in silage samples compared to control ones. Ultimate pH was highly affected by sex being higher in the samples from male lambs (P<0.01), but was unaffected by diet treatment. Diet tended to affect meat shear force value which was lower in the silage samples, although, samples from all the animals were extremely tender. Meat from silage samples had a higher water content (P<0.05). Overall, in our experimental conditions, the use of citrus pulp silage seemed to be economically convenient for producing animals with substantially unmodified carcass and meat quality characteristics.

Journal Article↗

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

Acanthosis Nigricans↗

111In platelet scintigraphy for the noninvasive detection of carotid plaque thrombosis.

BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. METHODS: We compared the performance of (111)In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at (111)In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Aged↗

Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons.

The effects of cholecystokinin sulfate octapeptide (CCK-8S) on [3H]gamma-aminobutyric acid (GABA) release have been studied in the anterior side of the rat nucleus accumbens on tissue punches exposed in superfusion to 30 mM KCl. CCK-8S in a concentration dependent manner (10-3000 nM) increased K+-evoked [3H]GABA release (EC50=192 nM). The increase caused by 1 microM CCK-8S ranged from 37% to 42%. CR 2945, (beta-[2-[[2-(8-azaspiro[4.5]dec-8-ylcarbonyl)-4,6-dimethylp henyl]-amino]-2-oxoethyl]-(R)-1-naphthalenepropanoic acid), a potent and selective nonpeptidergic CCK(B) antagonist, concentration-dependently blocked CCK-8S effect (IC50=2.16 nM). CCK-8S-induced increase in [3H]GABA overflow was completely blocked by 1 microM tetrodotoxin. Both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the N-methyl-D-aspartic acid (NMDA) receptor antagonist dizocilpine (MK-801) antagonized the CCK-8S effect. By contrast, (+)-bicuculline, a GABA(A) receptor antagonist, was completely ineffective. Phaclofen, a selective GABA(B) antagonist, increased K+-evoked [3H]GABA release but did not affect the facilitative effect of CCK-8S. Moreover, tetrodotoxin failed to block AMPA-evoked [3H]GABA release but completely prevented the effect of NMDA (Mg2+ free conditions). The data presented suggest that CCK(B) receptors modulating [3H]GABA release from anterior accumbal punches may not be present on GABAergic terminals but could be located on glutamatergic interneurons.

Animals↗

Polyethylene glycol as a means for reducing the impact of condensed tannins in carob pulp: effects on lamb growth performance and meat quality.

We conducted an experiment to evaluate the effects that a diet containing condensed tannins with and without polyethylene glycol (PEG) has on lamb growth and meat quality. Twenty-three male Comisana lambs were introduced to the three experimental diets between 45 and 50 d of age. Eight were given a diet containing 56% of Ceratonia siliqua (carob) pulp (tannin group), another eight received the same diet with a supplement of 40 g of PEG for each kilogram of diet (PEG group), and the remaining seven lambs were given a conventional maize-based diet (maize group). Voluntary feed intake and live weights were measured until slaughter at 105 d of age, and digestibility measurements were undertaken toward the end of the feeding trial. Carcass yield, meat quality characteristics, and a taste panel evaluation were conducted. The tannin-based diet contained 2.5% condensed tannins (DM basis), and lambs given this diet had lower growth rates and poorer feed efficiencies (P < .01) compared with the other treatment groups. Daily gain was similar between the maize and PEG lambs, although the efficiency of feed conversion was highest in the maize group. The digestibility of DM, N, and fiber was reduced (P < .05) by the condensed tannins. Lambs fed the tannin diet had a lower carcass yield (P < .05) and had less fat (P < .05), and the meat had a higher ultimate pH (P < .01) than those given the PEG or maize diets. Condensed tannins affected meat color, which was lighter (L*) than meat from lambs given the PEG-containing diet (P < .01). Sensory evaluation showed that panelists preferred meat from lambs receiving PEG and maize treatments compared with those receiving the tannin diet, and this could be related to differences in meat ultimate pH and carcass fatness. These results show that condensed tannins from carob pulp are very detrimental to feed digestibility and lamb performance. Inclusion of 40 g of PEG/kg diet eliminated the effects of condensed tannins so that lamb performance and meat quality were similar to lambs given a maize-based diet.

Animal Feed↗

Changes in the permeability of the blood-brain barrier following sodium dodecyl sulphate administration in the rat.

The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvasculature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 microg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]alpha-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, Ki, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.

Animals↗

Characterization of a novel putative cognition enhancer mediating facilitation of glycine effect on strychnine-resistant sites coupled to NMDA receptor complex.

The effects of (S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxo-pentanoic acid ((S)CR 2249), a new chemical entity selected among a series of glutamic acid derivatives, were investigated on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline from rat hippocampal slices. (S)CR 2249 facilitated glycine-mediated reversion of kynurenate antagonism at strychnine-insensitive glycine receptors coupled to the NMDA receptor. The potency of glycine (EC50 = 21.5 microM +/- 4.2) was not significantly influenced by (S)CR 2249. Nevertheless, the efficacy of the glycine effect was enhanced in a concentration-dependent manner (3-10-30 microm) by (S)CR 2249. The interaction of (S)CR 2249 with NMDA receptors was also studied with binding experiments, in which we examined the effect of (S)CR 2249 on the modulation by glutamate, glycine and spermine of [3H]dizocilpine (MK-801) binding. (S)CR 2249, increased [3H]MK-801 binding in a concentration-dependent manner and we found positive cooperative interactions between glycine and (S)CR 2249, indicating that (S)CR 2249 probably acts at a separate allosteric site to increase NMDA receptor functionality.

Animals↗

Transport of alpha-tocopherol and its derivatives through erythrocyte membranes.

PURPOSE: To investigate the transport of alpha-tocopherol (T), tocopherol succinate (TS) and tocopherol succinate-3-glucose (a newly synthetized, less hydrophobic T ester; TSG) through bovine erythrocyte membranes. METHODS: Our experiments were carried out on erythrocytes (obtained from heparinized fresh bovine blood), because they represent a suitable model for investigations of membrane transport. RESULTS: T was shown to reside almost completely in the suspension medium, while the greater part of TS disappeared from the suspension medium and was mainly incorporated into erythrocyte membranes. In comparison with T, a larger amount of TSG was incorporated into erythrocyte membranes and taken up by cells; however the TSG intracellular accumulation was significantly lower than that observed with TS. Furthermore, the transport of TS and TSG was partially inhibited by p-chloromercuribenzenesulfonate (which inhibits monocarboxylate uptake; PCMBS) and by maltose (a competitive inhibitor of glucose transport) respectively, with a concomitant increase in drug membrane incorporation. No significant change in drug transport was observed in the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonate, a selective and irreversible blocker of band 3 protein (DIDS). CONCLUSIONS: Our results show 1) the existence of large differences in membrane incorporation of T, TS and TSG (very likely caused by differing abilities to fill spaces in the lipid bilayer) and 2) a specific contribution of the monocarboxylate transport protein and of the glucose transport protein in the cellular uptake of TS and TSG, respectively. A tempting suggestion is that the unique cytoprotective properties of TS may be related to the differences in the transmembrane mobility observed between T and its succinate ester. Furthermore, T conjugation to a monocarboxylate or glycoside moiety could provide suitable substrates for active membrane transport, thus appearing as a promising pharmaceutical strategy for the improved delivery of tocopherol derivatives.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.

The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics. CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.

Animals↗

Systemic cytokine administration can affect blood-brain barrier permeability in the rat.

The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium.

Aminoisobutyric Acids↗

Flavonoids as antioxidant agents: importance of their interaction with biomembranes.

Flavonoids, a group of phenolic compounds widely occurring in the plant kingdom, have been reported to possess strong antioxidant activity. In the present study, four flavonoids (quercetin, hesperetin, naringenin, rutin), chosen according to their structural characteristics, were tested in two different in vitro experimental models: (1) Fe(2+)-induced linoleate peroxidation (Fe(2+)-ILP), by detection of conjugated dienes; and (2) autooxidation of rat cerebral membranes (ARCM), by using thiobarbituric acid for assay of free malondialdehyde production. The results obtained were also interpreted in the light of flavonoid interactions, studied by differential scanning calorimetry, with dipalmitoylphosphatidylcholine (DPPC) vesicles as a biological membrane model. The antilipoperoxidant activity of the flavonoids tested can be classified as follows: rutin > hesperetin > quercetin > naringenin in the Fe(2+)-ILP test: quercetin > rutin > hesperetin > naringenin in the ARCM test. Quercetin, hesperetin, and naringenin interacted with DPPC liposomes causing different shifts, toward lower values, of the main transition peak temperature (Tm) typical for DPPC liposomes; however, no change in Tm of DPPC dispersion was observed in the presence of rutin. The hypothesis will be discussed that flavonoid capacity to modify membrane-dependent processes, such as free-radical-induced membrane lipoperoxidation, is related not only to their structural characteristics but also to their ability to interact with and penetrate the lipid bilayers.

Animals↗

Bleeding time and bleeding: an analysis of the relationship of the bleeding time test with parameters of surgical bleeding.

The bleeding time is currently the only clinically available comprehensive test to explore primary hemostasis. It is currently performed mostly as a screening procedure before surgery, to detect otherwise unknown defects in platelet-vessel wall interactions, but its use in this specific setting has been seriously questioned by recent reanalyses of previously published literature. We studied the relationship of the bleeding time from a standardized cutaneous incision with other parameters of bleeding derived from the analysis of the bleeding time curve and prospectively investigated possible correlations of these alternative parameters, as well as of the bleeding time, with a number of indices of actual bleeding during or after coronary bypass surgery. Four parameters (bleeding time, total bleeding, peak bleeding rate, and time to peak bleeding) were derived from the analysis of bleeding time curves measuring blood losses from a standardized cutaneous incision at 30-second intervals in 118 subjects. Parameters from the bleeding time curve were subsequently obtained in duplicate as a preoperative assessment in 40 patients with a negative bleeding history and no recent intake of non-steroidal anti-inflammatory drugs who were undergoing elective pure coronary bypass surgery performed by the same operator. These parameters were correlated in simple linear regression analysis with estimates of surgical bleeding (chest tube drainage, transfusion requirements, percentage of hematocrit, percentage of platelet level decrease, and times to hematocrit and platelet level nadir) and then, in multiple regression analysis, with indices of operation complexity (number of bypasses, total duration of the operation, and duration of the extracorporeal circulation). Bleeding time was significantly correlated, among parameters derived from the bleeding time curve, with total bleeding and peak bleeding rate, but not with time to peak bleeding. Bleeding time, total bleeding, and peak bleeding rate were similarly affected by acute interventions with intravenous aspirin (500 mg) and sublingual nitroglycerin (0.3 mg). None of these parameters, which were obtained in duplicate in each patient preoperatively, was significantly related to actual indices of bleeding at surgery. Thus, in patients with a negative history of bleeding and no recent intake of non-steroidal anti-inflammatory drugs, higher values for bleeding time and bleeding time-related parameters are not associated with higher indices of perioperative and postoperative bleeding at coronary bypass surgery. Therefore, we do not recommend the use of the test in this setting to predict perioperative or postoperative bleeding.

Aspirin↗

Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain.

1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 microliters/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.

Animals↗

Genetically epilepsy-prone rodents show some changes of ion levels in the brain.

In the present study the water and ion (Na+, K+, Ca2+, Fe3+, Se4+, Mg2+, Mn2+, Mn2, Se4+, Cu2+) content in the brain of genetically epilepsy-prone rats (GEPRs) and of 21-, 45-, and 60-day-old DBA/2 mice were determined, and compared with those measured in normal controls (Sprague-Dawley rats and Swiss mice), to verify whether the predisposition to audiogenic seizures (AGS) may be partially related to changes in the cerebral osmotic and ionic state. Our findings clearly evidenziate two points: a) a more complex shift in brain ionic balance (rather than a peculiar modification in the concentration of a single ion) seems very likely involved in AGS susceptibility; (b) brain Ca2+ and Se4+ amounts, together with the water content, appear to be really important factors to which a role in abnormal seizure predisposition may be attributed.

Acoustic Stimulation↗