Biomedical subjects

R Ientile

Publications and source records attributed to R Ientile.

At least 19 recordsLinked to original sources

PubMed2006

Relationship between metabolic syndrome and platelet responsiveness to leptin in overweight and obese patients.

OBJECTIVE: To verify whether platelet responsiveness to leptin is associated with metabolic syndrome risk factors. DESIGN: Cross-sectional study. SUBJECTS: We studied 169 consecutive patients, mean age=43.6+/-9.9 years, with overweight (N=57) or obesity (N=112). MEASUREMENTS: Cluster analysis was used to generate three clusters based on platelet responsiveness to increasing doses of leptin. Profiles of metabolic syndrome risk factors of the three clusters were compared by discriminant analysis. RESULTS: Platelet responsiveness to leptin was absent in cluster 1, whereas cluster 3 had the greatest platelet aggregation response to leptin pre-incubation. Plasma leptin levels significantly decreased from cluster 1 to cluster 3 in both gender. Patients in cluster 2 had an intermediate profile of leptin responsiveness. Highest body mass index (BMI) values were more frequent in non-responders, whereas the prevalence of high waist circumference, as well as hypertriglyceridemia and hypertension, increased with increasing responsiveness to leptin from cluster 1 to cluster 3. Pattern of metabolic syndrome risk factors qualified as group specific in 69.0% of the cluster 1, 54.9% of the cluster 2 and 55.8% of the cluster 3. Circulating leptin, waist circumference, plasma triglycerides and BMI defined distinctive patterns of metabolic syndrome risk factors in the clusters. CONCLUSIONS: In overweight and obese outpatients, metabolic syndrome risk factors parallel to some extent platelet responsiveness to leptin. Such a correlation involves plasma leptin levels, waist circumference, plasma triglycerides and BMI, and may contribute to the excess risk of cardiovascular events in overweight and obese patients.

Adult↗

PubMed2006

Increased transglutaminase activity was associated with IL-6 release in cultured human gingival fibroblasts exposed to dental cast alloys.

Molecular mechanisms underlying gingival and periodontal inflammation caused by dental alloys are still poorly understood. Recently, it has been demonstrated that tissue transglutaminase can be involved in inflammatory cell response. The aim of this study was to evaluate effects of exposure to orthodontic materials on transglutaminase in cultured human gingival fibroblasts. The incubation with Ni-Ti heat-activated (T3) or Ni-Ti super-elastic (T4), and with Ni-Cr-Co (T2) alloys produced respectively 2.5-fold and 8-fold increases in IL-6 release compared with control cultures. Transglutaminase activity was significantly increased in cells exposed to T3 and T4 alloys (about 170% of control; p < 0.05), where it was mainly localized close to inner part of cell membrane. The exposure to T3 and T4 specimens significantly up-regulated also tTG expression compared with control cultures. These data first show an association between IL-6 release and tissue transglutaminase increases, suggesting that TGase-mediated reactions may play a major role in periodontal inflammation.

Cell Line↗

PubMed2006

Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes.

A moderate increase of total homocysteine (tHcy) plasma levels seems to increase cardiovascular disease (CVD) risk in Type 2 diabetic subjects, but its relationship with diabetes and insulin-resistance is still controversial. We examined whether mild hyperhomocysteinemia and its major genetic determinant would cluster with the metabolic syndrome (MS) in Type 2 diabetes. One hundred Type 2 diabetic subjects with and without MS were enrolled in the study. Fasting tHcy, vitamin B12, and folate plasma levels, insulin-resistance [assessed by homeostasis model assessment, (HOMAIR)] and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype were assessed in all the participants. Geometric mean tHcy concentration and the prevalence of mild hyperhomocysteinemia, as commonly defined by tHcy >/=15 micromol/l, were comparable in diabetic subjects with and without MS, even after adjustment for age, sex, vitamin B12, folate and creatinine levels. In both groups, the MTHFR C677T genotype distribution was not significantly different from the Hardy-Weinberg equilibrium, with a TT homozygous frequency of 21% in subjects with and 18% in those without the syndrome (p=ns). tHcy plasma levels and the degree of insulin-resistance did not differ across MTHFR genotypes in both groups, even after multivariable adjustment. Overall, tHcy significantly correlated with creatinine (r=0.25; p=0.009) and trygliceride concentrations (r=0.24; p=0.02), but not with HOMAIR. At multivariate analysis, only creatinine was significantly correlated with tHcy levels (beta=0.42; p=0.001). In conclusion, hyperhomocysteinemia and the common C677T variant of MTHFR gene are not associated with MS in Type 2 diabetic subjects.

Adult↗

PubMed2005

Effects of magnesium sulphate on leptin-dependent platelet aggregation: an ex vivo study.

Magnesium sulphate has well known antiplatelet properties. Its effect on leptin-dependent platelet aggregation has not been studied previously. Thus, we performed this ex vivo study to investigate whether magnesium sulphate is able to inhibit leptin-dependent aggregation of human platelets. We obtained platelet rich plasma (PRP) from venous blood samples of 16 healthy male volunteers, and we measured ADP-induced platelet aggregation in the presence of leptin alone (5-500 ng/mL) or leptin and magnesium sulphate (0.25-8 mM). Platelet pre-incubation with leptin led to a significant and dose-dependent increase in ADP-induced platelet aggregation. Magnesium sulphate was able to inhibit the pro-aggregating effect of leptin in a dose-dependent manner. The inhibitory effect was apparent at 1 mM of magnesium sulphate concentration (% maximal aggregation=38.1 +/- 12.2) and reached its maximum at 8 mM (% maximal aggregation=20.0 +/- 7.8). Our results demonstrate that leptin-dependent platelet aggregation is inhibited by magnesium sulphate in a dose-dependent manner. It seems conceivable that the blocking of hydrolysis of phosphoinositide and of intracellular calcium mobilization by magnesium sulphate may be involved in these findings.

Adenosine Diphosphate↗

PubMed2004

Glutamate-evoked redox state alterations are involved in tissue transglutaminase upregulation in primary astrocyte cultures.

The aim of this study was to evaluate the involvement of oxidative stress in glutamate-evoked transglutaminase (TGase) upregulation in astrocyte cultures (14 DIV). A 24 h exposure to glutamate caused a dose-dependent depletion of glutathione intracellular content and increased the ROS production in cell cultures. These effects were receptor-mediated, as demonstrated by inhibition with GYKI 52466. The pre-incubation with glutathione ethyl ester or cysteamine recovered oxidative status and was effective in significantly reducing glutamate-increased tissue TGase. These data suggest that tissue TGase upregulation may be part of a biochemical response to oxidative stress induced by a prolonged exposure of astrocyte cultures to glutamate.

Animals↗

PubMed2004

Tissue transglutaminase was up-regulated by EGF-retinoid interplay in epithelial carcinoma cells.

Retinoids have been shown the most powerful inducers of transglutaminase activity, a well known marker of differentiation. In this work, we tested the effects of all-trans retinoic acid and EGF, used alone or in combination, on transglutaminase activity in a squamous, epithelial carcinoma cell line, HEp-2. We demonstrated that nanomolar EGF further enhances transglutaminase activity previously induced by all-trans retinoic acid. Confocal laser scanning microscopy revealed functional changes in transglutaminase activity localisation, at first restricted to the outermost region of cytosol, then diffused both in the membrane region and extracellular space. RT-PCR showed the presence of mRNA transcripts of different transglutaminases (1, 2, 3). Transglutaminase 2 expression was increased by either all-trans retinoic acid or EGF, and further up-regulated by the simultaneous addition of both substances. These effects were confirmed by Western blotting with transglutaminase 2 specific antibody. The results obtained by combined use of retinoic acid and EGF suggest that transglutaminase activity and expression are differently regulated, and that EGF-signalling can be involved in differentiation of epithelial carcinoma cells induced by retinoids.

Carcinoma, Squamous Cell↗

PubMed2004

Excitotoxic and post-ischemic neurodegeneration: Involvement of transglutaminases.

Neurodegeneration induced by excitotoxicity is a common feature in various neurological disorders. This pathological condition is caused by prolonged stimulation of glutamate receptor subtypes, followed by both intracellular Ca2+ overload and activation of specific genes, resulting in synthesis of enzymes involved in cell stress response. Using experimental in vitro models of excitotoxicity, we demonstrated that glutamate exposure up-regulated tissue transglutaminase in primary cultures of both cerebellar granule cells and astrocytes. These changes were consequent to receptor-mediated Ca2+ influx, as demonstrated by the inhibition with selective antagonists, MK-801 and GYKI 52466. Early increases in different transglutaminase isoforms were also observed in global cerebral ischemia, which closely resembles neuronal damage caused by NMDA receptor activation. These findings agree with a postulated role for transglutaminases in molecular mechanisms of several neurodegenerative diseases. Indeed, increased cross-linking reactions could be of pathologic relevance, as part of biochemical changes observed in neurological disorders.

Animals↗

PubMed2004

Identifying pathways involved in leptin-dependent aggregation of human platelets.

OBJECTIVE: To investigate the role of phospholipase C (PLC), phospholipase A(2) (PLA(2)), calcium, and protein kinase C (PKC) in mediating leptin-enhanced aggregation of human platelets. DESIGN: In vitro, ex vivo study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy. SUBJECTS: In total, 14 healthy normal-weight male (age 31.4+/-1.9 y; body mass index 22.7+/-0.6 kg/m2) subjects. MEASUREMENTS: Adenosine diphosphate-(ADP-) induced platelet aggregation and platelet free calcium were measured after incubation of platelets with leptin alone (5-500 ng/ml), or leptin (50 and 100 ng/ml) in combination with anti-human leptin receptor long form antibody (anti-ObRb-Ab, 1:800-1:100 dilutions), PLC inhibitor U73122 (3.125-25 microM), PLA(2) inhibitor AACOCF3 (1.25-10 microM), or PKC inhibitor Ro31-8220 (1.25-10 microM). RESULTS: Platelet stimulation with leptin leads to a significant and dose-dependent increase in ADP-induced platelet aggregation and platelet free calcium concentrations. Leptin effects on both platelet aggregation and calcium mobilization were completely abated by the co-incubation with leptin and anti-ObRb-Ab. Leptin-induced platelet aggregation was dose-dependently inhibited by U73122, AACOCF3, or Ro31-8220. The effect of leptin on intracellular calcium was inhibited in a dose-dependent manner by incubation with U73122 and AACOCF3, but not with Ro31-8220. CONCLUSIONS: Our study confirms that leptin is able to enhance ADP-induced aggregation of human platelets, and raise the possibility that PLC, PKC, PLA(2), and calcium could play a relevant role in mediating the proaggregating action of leptin.

Adenosine Diphosphate↗

PubMed2004

Correlates of total homocysteine plasma concentration in type 2 diabetes.

BACKGROUND: Although well-defined in the general population, correlates of total homocysteine (tHcy) plasma concentration have not been sufficiently evaluated in diabetes. We investigated factors potentially associated with tHcy concentration in a cohort of type 2 diabetic subjects. MATERIALS AND METHODS: The common methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism, fasting tHcy, vitamin B12 and folate plasma levels were assessed in 312 diabetic subjects, whose clinical, metabolic and lifestyle information was also available. RESULTS: The MTHFR genotype distribution was comparable to the Hardy-Weinberg equilibrium, with an overall TT homozygous frequency of 22%. Fasting tHcy concentration was significantly higher in men than in women (P < 0.001). Multivariate-adjusted tHcy concentration was significantly different across the quartiles of age (P < 0.001), folate (P = 0.01), vitamin B12 (P = 0.03), creatinine concentrations (P = 0.001) and smoking (P = 0.02). Overall, significant trends were noted for creatinine clearance (P for trend = 0.02) and systolic blood pressure (BP) (unadjusted P for trend = 0.01), whereas no differences were noted according to BMI, diastolic BP, presence of hypertension, and diabetes-related variables, such as diabetes duration, fasting glucose and glycated haemoglobin concentrations, current treatment and diabetes long-term complications. Total homocysteine levels significantly correlated with age, systolic BP, vitamin B12, creatinine and creatinine clearance, but only age, creatinine, folate and vitamin B12 levels were independently associated with tHcy concentration in stepwise regression analysis. CONCLUSIONS: Age, creatinine, folate, vitamin B12, and to a minor extent, sex, smoking, TT genotype and systolic BP were significantly associated with Hcy plasma concentration in type 2 diabetes, whereas no significant associations were noted with diabetes-related variables.

Adult↗

PubMed2004

Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia.

Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic polymorphisms andor inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298 allele was significantly higher in patients (30.5% vs 19.4%, p < 0.05). Significant differences between the two groups were also found for the frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p < 0.01) and AC1298 (46.3% in cases vs 26.6% in controls, p < 0.01). Other genotype frequencies did not show any statistically significant differences. Haplotype frequencies significantly differed between the two groups. The CT677/AC1298 diplotype was significantly more frequent in epileptic patients than in controls (32.6% vs 18.4%, p < 0.05). Patients treated with enzyme-inducing antiepileptic drugs, having this diplotype and concomitant low folate concentration (i.e., < 3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than normal values (27.1 +/- 2.44 micromol/L, p < 0.001). This increase, however, was lower than that observed in folate-deficient patients with diplotype TT677/AA1298 (41.3 +/- 3.41 micromol/L, p < 0.001). Indeed, these two diplotypes could be regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the CC677/AA1298 diplotype was significantly more frequent in controls (p < 0.01), suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR polymorphisms should be examined when assessing genetic risk factors of hyperhomocysteinemia in epilepsy.

Adolescent↗

PubMed2003

Cystamine inhibits transglutaminase and caspase-3 cleavage in glutamate-exposed astroglial cells.

Although the precise role of transglutaminase in cell death is unknown, several findings demonstrate that tissue transglutaminase selectively accumulates in cells undergoing apoptosis both in vivo and in vitro. Calcium-dependent transglutaminase reactions are also implicated in several neurodegenerative diseases, including alterations in the release of excitatory amino acids. One prevalent theme in cell damage induced by excitotoxic stimuli in different regions of the CNS is that apoptosis may be executed by intracellular caspase proteases. Furthermore, the presence of functional ion channel-gated receptors in glial cells suggests that also astrocytes can be susceptible to glutamate's toxic effects. In this study, we demonstrated that prolonged exposure to glutamate (100 microM) of cultured astrocytes caused an increase in the expression of tissue transglutaminase (tTG). This effect was prevented by preincubation with GYKI 52466, an antagonist of AMPA/KA receptors. Glutamate exposure also promoted an increase in caspase-3 compared with control cultures. Confocal laser microscopy analysis demonstrated the presence of activated caspase-3 in the cytoplasm as well as in the nucleus. The inhibition of TG-catalyzed reactions by cystamine (1 mM) blocked the activation pathway of caspase-3, with an evident reduction of enzyme cleavage. These results suggest that glutamate increased both TG and caspase-3 in astroglial cells early in the excitotoxin-induced events.

Animals↗

PubMed2003

Glutamate-induced increases in transglutaminase activity in primary cultures of astroglial cells.

Glutamate exposure of astroglial cells caused ligand-gated channel receptor activation, associated with excitotoxic cell response. We investigated the effects of 24 h glutamate exposure on transglutaminase in astrocytes primary cultures at 7, 14, and 21 days in vitro (DIV). Increases in enzyme activity were observed as a function of cell differentiation stage in glutamate-treated cultures. These effects were significantly reduced when GYKI 52466, an AMPA/KA receptors inhibitor, was added to the culture medium prior to incubation with glutamate. Microscopy observation on transglutaminase-mediated, fluorescent dansylcadaverine incorporation in living cells was consistent with these results. Western blotting analysis with monoclonal antibody showed that glutamate also up-regulated tissue transglutaminase expression, which reached the highest values in 14 DIV cultures. Confocal laser scanning microscopy analysis of immunostained astroglial cells showed a mainly cytoplasmic localisation of the enzyme both in control and treated cultures; nevertheless, counterstaining with the nuclear dye acridine orange demonstrated the presence of tissue transglutaminase also into the nucleus of glutamate-exposed and 21 DIV cells. The increases in enzyme expression and localisation in the nucleus of glutamate-treated astroglial cells may be part of biochemical alterations induced by excitotoxic stimulus.

Animals↗

PubMed2003

Excitotoxin-induced changes in transglutaminase during differentiation of cerebellar granule cells.

Excitotoxicity induced by NMDA receptor stimulation is able to increase the activity of many enzymes involved in neuronal cell death. Primary cultures of rat cerebellar granule cells were used to elucidate the role of transglutaminase reaction in the excitotoxic cell response, and to evaluate the role of glutamate receptors in cell survival and degeneration. Granule neurons, maintained in vitro for two weeks, were exposed to NMDA at different stages of differentiation. Following NMDA receptor activation, increases in transglutaminase activity were observed in cell cultures. The levels of enzyme activity were higher in cells at 5 days in vitro than in those at 8-9 or 13-14 days in vitro. Moreover, NMDA exposure up-regulated tTG expression in neurons as young as 5 days in vitro. These cultures also exhibited morphological changes with clear apoptotic features. Results obtained demonstrate that susceptibility of granule cells to excitotoxicity depends on the developmental stage of neurons.

Animals↗

PubMed2003

Leptin-dependent platelet aggregation in healthy, overweight and obese subjects.

OBJECTIVE: To investigate the effects of leptin on platelet aggregation and platelet free calcium (Ca(2+)) concentrations, and the role of the long form of leptin receptor (ObRb) and the phospholipase C (PLC) in mediating leptin effects on platelet function. DESIGN: Cross-sectional, clinical study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy. SUBJECTS: A total of 19 healthy, 14 overweight, and 16 obese male subjects. MEASUREMENTS: ADP-induced platelet aggregation and platelet Ca(2+) were measured after incubation of platelet-rich plasma with leptin alone 5-200 ng/ml, leptin 200 ng/ml and anti-human leptin receptor long-form antibody (ObRb-Ab) 5-10 microl, or leptin 200 ng/ml and PLC inhibitor U73122 0.5-1 nmol/l. RESULTS: Platelet stimulation with leptin lead to a significant and dose-dependent increase in platelet aggregation in healthy subjects. This effect was blunted in overweight, and strongly reduced in obese subjects. Similarly, the incubation with leptin induced a significant and dose-dependent increase in platelet free calcium, which was blunted in overweight and obese patients. The effect of leptin on platelet aggregation and platelet Ca(2+) was completely abated by the anti-ObRb-Ab and the PLC inhibitor U73122. CONCLUSIONS: Leptin produces a dose-dependent enhancement of ADP-induced platelet aggregation in humans. Platelet aggregation response to leptin is blunted, but not completely abolished in overweight/obese subjects, thus suggesting that platelet may represent a site of leptin resistance in human obesity. Leptin increases platelet free calcium in a dose-dependent manner. The inhibition of PLC completely abates the effect of leptin on both platelet aggregation and Ca(2+) levels. These findings suggest that signaling pathway other than JAK-STAT tyrosine phosphorylation (ie PLC and calcium) may be involved in mediating the prothrombotic action of leptin.

Adenosine Diphosphate↗

PubMed2003

Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele.

BACKGROUND: The current study was designed to characterize the process of nitric oxide (NO) and peroxynitrite generation through the determination of nitrotyrosine concentration in the dilated veins of varicoceles in adolescents. METHODS: Ten adolescents with a median age of 13 years (range 12-17) affected by a left idiopathic varicocele (grade II and III) were studied. Whole blood samples were withdrawn from a peripheral vein at time of induction of anaesthesia, and from a dilated spermatic vein before ligation. Peripheral blood samples from five adolescents undergoing minor surgical procedures were used as controls. The nitrotyrosine concentration was evaluated by a sandwich enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-nitrotyrosine antibody and Western blot analysis. RESULTS: Plasma nitrotyrosine concentrations were significantly greater in the spermatic vein when compared with the peripheral vein (P = 0.031). Nitrotyrosine in plasma of controls did not show any significant difference in comparison with peripheral samples from varicocele patients. Western blot analysis confirmed the above data. CONCLUSIONS: In adolescents with a varicocele, there is an increase in nitrotyrosine concentration within the spermatic vein that can cause protein nitration and cytotoxicity via its reaction with various molecular targets. This could have repercussions on both sperm and testis function. We conclude that an oxidative stress status is present and should be considered as an indication for varicocele treatment in the adolescent.

Adolescent↗

PubMed2002

NMDA-evoked excitotoxicity increases tissue transglutaminase in cerebellar granule cells.

In neuronal cells, excessive activation of glutamate receptors causes excitotoxic damage culminating in apoptotic and necrotic cell death. The molecular mechanism of excitotoxicity has been associated with excessive Ca(2+) influx and overload, triggering biochemical events that lead to cell death and tissue degeneration. Following mild insults via NMDA-receptor activation, central neurons undergo several biochemical modifications recognizable as early events in apoptotic machinery.Tissue transglutaminase, the most ubiquitous among cell transglutaminases, catalyzes the Ca(2+)-dependent protein cross-linking probably associated with morphological changes in several neurodegenerative disorders. The possible involvement of this enzyme in excitotoxicity-mediated events was investigated in primary cultures of cerebellar granule cells exposed for 30 min to NMDA (100 microM) in Locke's buffer. Under these conditions time-dependent increases in transglutaminase activity were observed. Tissue transglutaminase expression reached the highest levels within 3-4 h of NMDA exposure. Similarly, high levels of incorporation of fluorescent substrates were observed in living cells. Confocal laser microscopy analysis showed that fluorescein-labelled structures were distributed within the cytoplasm and close to the membranes of NMDA-exposed cells. These effects were dependent on the Ca(2+) influx triggered by the excitotoxic stimulus. Morphological changes in NMDA-treated cells gave evidence of significant cell damage which appeared within 5-6 h of NMDA exposure. These results suggest that increases in tissue transglutaminase may be associated to the effects of NMDA-induced excitotoxicity. Therefore, it is reasonable to hypothesize that if tissue transglutaminase levels and activity are up-regulated under such conditions, the protein cross-linking could be likely involved in excitotoxic response.

Animals↗

PubMed2001

Neuroprotective effects of lamotrigine and remacemide on excitotoxicity induced by glutamate agonists in isolated chick retina.

The possible neuroprotective effects of two recently developed antiepileptic compounds, lamotrigine (LTG) and remacemide (REMA), against glutamate agonist-induced excitotoxicity have been investigated in the isolated chick embryo retina model. Retina segments from 15- or 16-day-old embryos were incubated in 1 ml of balanced salt solution, at 25 degrees C for 30 min, in the presence or absence of N-methyl-d-aspartate (NMDA), kainic acid (KA), or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (10 to 200 microM). LTG, REMA, and the active desglycinyl metabolite of REMA (d-REMA) (10-200 microM) were added separately 5 min before glutamate agonists. Retina damage was assessed after 24 h (i) by measuring LDH activity present in the medium, expressed as percentage of total retina LDH activity, and (ii) by histological analysis of retina specimens through scoring for the presence or absence of edema, necrosis, nuclear pyknosis, and cell layer damage. LTG, REMA, and d-REMA reduced LDH release produced by NMDA 58-70% in a dose-dependent manner, with d-REMA being the most potent (EC(50): d-REMA, 25.75 +/- 3.27 microM; REMA, 64.75 +/- 7.75 microM; LTG, 60.50 +/- 6.80 microM; P < 0.001). The drugs had less effect on the LDH release produced by AMPA and KA. Histological analysis confirmed these biochemical results, with all three compounds reducing edema and the number of necrotic and pyknotic nuclei in the ganglion layer. d-REMA provided almost complete protection of the ganglion cell layer against damage produced by NMDA. Combinations of d-REMA and LTG showed additive rather than potentiative effects against NMDA-induced cell injury. The present data provide pharmacological evidence that LTG, REMA, and d-REMA decrease glutamate agonist-induced excitotoxicity in isolated chick retina, findings that might have therapeutic implications for various neurological disorders.

Acetamides↗

PubMed2001

Leptin and norepinephrine plasma concentrations during glucose loading in normotensive and hypertensive obese women.

We performed this study to investigate whether changes in plasma glucose, insulin, and norepinephrine concentrations during an oral glucose tolerance test (OGTT) are associated with changes in plasma leptin levels in normotensive and hypertensive obese women. Plasma insulin, glucose, norepinephrine, and leptin concentrations were evaluated at the baseline and during OGTT in normotensive women (NT-Ob, N = 24, mean age 38.3+/-1.8 years, body mass index [BMI] 37.9+/-1.1 kg/m2) and hypertensive (HT-Ob, N = 25, mean age 37.7+/-1.9 years, BMI 39.4+/-1.3 kg/m2) obese women, and in a group of normal-weight women (controls, N = 20, mean age 38.3+/-1.3 years, BMI 23.1+/-0.4 kg/m2). The OGTT caused a significant increase in plasma leptin concentrations in both NT-Ob and HT-Ob groups, whereas no such change was detectable in control subjects. Area under curve (AUC) for plasma leptin showed a direct correlation with norepinephrine AUC in both NT-Ob (r = 0.73, P = .001) and HT-Ob (r = 0.74, P = .001) group, which was still detectable in multivariate analysis (P = .014 and P = .017, respectively). Our study confirms that glucose loading increases circulating leptin concentrations in obese women, and demonstrates the existance of an association between leptin and norepinephrine changes during OGTT in both normotensive and hypertensive obese women. We hypothesize that this association may reflect the lack of leptin suppression by catecholamines or a direct leptin-induced sympathoactivation. These findings suggest that leptin could be relevant in the regulation of blood pressure in obese women.

Adult↗