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INTRODUCTION: Rassi score (NYHA functional class III/IV HF [5 points], cardiomegaly [5 points], contractions abnormalities [3 points], non-sustained ventricular tachycardia [3 points], low amplitude QRS [2 points] and male sex [2 points]) is used in the clinic for risk stratification due to cardiovascular death in patients with Chagas disease (P-CD). Whether this score has any role in identifying patients at risk of complex ventricular arrhythmias has not been determined. OBJECTIVE: Assess whether there is an association between Rassi score and the presence of potentially malignant complex ventricular arrhythmias in P-CD. METHODS: 79 P-CD (34 men, age 61±11 years-old), consecutively referred for 24h-Holter were divided into 2 groups: low risk Rassi score (57 P, 0-6 points) and medium-high risk (22 P, 7-20 points). The amount and complexity of ventricular arrhythmia (> 30/ h, ventricular tachycardia [VT]), LVEF, heart rate turbulence (HRT) indexes (turbulence onset [TO] and turbulence slope [TS]) and HRT category (0 [without disautonomy], 1 and/or 2 [presence of disautonomy]) were evaluated. RESULTS: Compared to P-CD with low risk score, those with medium-high risk had more ventricular arrhythmias, lower LVEF, worse HRT indexes and more HRT categories 1 and/or 2 (see table below). CONCLUSIONS: 1) P-CD and Rassi score of medium to high risk have a greater amount of ventricular arrhythmias; 2) These findings can be explained by the presence of greater degree of disautonomy, assessed by HRT, and by the lower LVEF; 3) Prospective studies are necessary to confirm these findings in clinical practice.

Assuntos

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Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Assuntos

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Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Assuntos

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This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Assuntos

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This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Assuntos

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The present study investigated the effect of thioperamide (THIO), an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM). We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure), the mice (n=10/group) were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL) immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms) compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA) followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL), indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL) microinjected into the cerebellum impaired emotional memory consolidation in mice.

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The present study investigated the effect of thioperamide (THIO), an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM). We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure), the mice (n=10/group) were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL) immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms) compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA) followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL), indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL) microinjected into the cerebellum impaired emotional memory consolidation in mice.

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This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Assuntos

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This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Assuntos

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Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have high density in the vermis and flocculus. Evidence indicates that the cerebellar vermis is involved in memory consolidation. Recently, we demonstrated that when histamine is microinjected into the cerebellar vermis it results in impaired emotional memory consolidation in mice that are submitted to the elevated plus maze (EPM). This study investigated whether histamine impairment was mediated by the H(1) or H(2) receptors. The cerebellar vermis of male mice (Swiss Albino) were implanted using a guide cannula. Three days after recovery, behavioral tests were performed in the EPM on two consecutive days (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL) or histamine (HA, 4.07 nmol/0.1 µl) was microinjected 5 min after pretreatment with the H(1) antagonist chlorpheniramine (CPA, 0.16 nmol/0.1µl) or SAL. In Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment with the H(2) antagonist ranitidine (RA, 2.85 nmol/0.1 µl) or SAL. Twenty-four hours later, the mice were re-exposed to the EPM (Trial 2) under the same experimental conditions but did not receive an injection. On both days, the test sessions were recorded to enable analysis of the behavioral measures. The decrease in open arm exploration (% entries and % time spent in the open arms) in Trial 2 relative to Trial 1 was used as a measure of learning and memory. The data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's tests. In Experiment 1, the Duncan's test indicated that the mice entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in Trial 2 after being microinjected with SAL+SAL, SAL+CPA and CPA+HA. However, the animals that received SAL+HA did not enter the open arms less frequently or spend less time in them, which was significantly different from the CPA+HA group. The results of Experiment 2 demonstrated that the %OAE and %OAT in Trial 2 were different from Trial 1 for the groups that were microinjected with SAL+SAL and SAL+RA. The animals that were microinjected with RA+HA or with SAL+HA did not show a reduction in %OAE. These results demonstrate that the animals treated with HA did not avoid the open arms less on retesting and indicated that CPA did not alter the behavior parameters but did revert the histamine-induced impairment of memory consolidation. Furthermore, the H(2) antagonist RA, at the dose used in this study, did not affect memory consolidation and failed to revert histamine-induced impairment.

Assuntos

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This study investigated the role of amygdala H(1) receptors in state-dependent memory deficits induced by l-histidine (LH). Tests using an elevated plus-maze (EPM) were performed on two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before each trial, mice were intraperitoneally (IP) injected with LH (500mg/kg). Two hours later, they were microinjected with the H(1) receptor antagonist, chlorpheniramine (CPA 0.016, 0.052, or 0.16 nmol/0.1µl), or saline (SAL) into the amygdala and submitted to the EPM. LH-CPA did not affect trial 1 performances in the EPM, which indicated that these drugs did not affect anxiety. Emotional memory, as revealed by a reduction in open arm exploration between both trials, was present in the SAL-SAL groups as well as in the SAL-CPA groups for the lower doses of CPA (0.016 and 0.052nmol). On the contrary, neither the LH-SAL group nor the LH-CPA groups exhibited this decrease in open arm activity between both trials, which reveals that LH impaired emotional memory. While intra-amygdalar CPA did not interact with LH effect, it impaired per se the emotional memory performances at the highest dose (0.16nmol). No significant changes were observed in the number of enclosed arm entries (EAE), an EPM index of general exploratory activity. These results may be attributed to a combined effect in the different nucleus of the amygdala. Taken together, these results suggest that the H(1) receptors in the amygdala are not implicated in anxiety-like behaviors but are involved in emotional states induced by the T1/T2 EPM protocol in mice.

Assuntos

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AIM: The purpose of this work is to investigate the effects of simvastatin on sciatic nerve regeneration in male Wistar Rats. MATERIALS AND METHODS: Forty animals were allocated into four groups: (1) control (C); (2) control+simvastatin (CS); (3) lesioned animals+sterile PBS (LC) and (4) lesioned animals+simvastatin (LS). Lesioned animals were submitted to crushing lesion of right sciatic nerve. Simvastatin (20mg/kg/day, i.p.) was administered for five days. Footprints were obtained weekly for evaluation of functional locomotor recovery by means of the Sciatic Function Index (SFI). Blood samples were obtained weekly for quantifying circulating leukocytes. Animals were sacrificed after 21 days for histological analyses of sciatic nerve and spleen. RESULTS: LS Animals presented increased SFI scores, decreased areas of oedema and mononuclear cell infiltration during Wallerian degeneration and nerve regeneration (7,14 and 21 days; P<0.05). Spleen weight and white pulp areas was increased in LC animals after 21 days. Increased numbers of circulating neutrophils were observed in simvastatin treated animals (CS e LS) at seven, 14 and 21 days, compared to non-treated groups (C and LC). CONCLUSION: The study suggests that simvastatin accelerates the morphological and functional recovery process of the peripheral nervous system interfering with innate and acquired immunity.

Assuntos

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The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean ± SEM; OAE: 4.0 ± 0.71, 4.80 ± 1.05; OAT: 40.55 ± 9.90, 51.55 ± 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 ± 0.73, 4.87 ± 0.66; OAT: 63.93 ± 11.72, 63.58 ± 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 ± 0.66, T2: 5.47 ± 1.05; T1: 63.58 ± 10.22; T2: 49.01 ± 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 ± 1.60, T2: 4.70 ± 1.04; T1: 51.55 ± 12.10, T2: 43.88 ± 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

Assuntos

RESUMO

The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean +/- SEM; OAE: 4.0 +/- 0.71, 4.80 +/- 1.05; OAT: 40.55 +/- 9.90, 51.55 +/- 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 +/- 0.73, 4.87 +/- 0.66; OAT: 63.93 +/- 11.72, 63.58 +/- 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 +/- 0.66, T2: 5.47 +/- 1.05; T1: 63.58 +/- 10.22; T2: 49.01 +/- 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 +/- 1.60, T2: 4.70 +/- 1.04; T1: 51.55 +/- 12.10, T2: 43.88 +/- 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

Assuntos