Analgesia and pain: Dual effect of dopamine on the peripheral nociceptive system is dependent on D2-or D1-like receptor activation.

In this study, a pharmacological approach, together with the paw pressure test, was used to investigate the role of dopamine and its receptors in the peripheral processing of the nociceptive response in mice. Initially, the administration of dopamine (5, 20, and 80 ng/paw) in the hind paw of male Swiss mice (30-40 g) promoted antinociceptive effects in a dose-dependent manner. This was considered a peripheral effect, as it did not produce changes in the nociceptive threshold of the contralateral paw. The D2, D3, and D4 dopamine receptor antagonists remoxipride (4 µg/paw), U99194 (16 µg/paw), and L-745,870 (16 µg/paw), respectively, reversed the dopamine-mediated antinociception in mice with PGE2-induced hyperalgesia. The D1 and D5 dopamine receptor antagonists SKF 83566 (2 µg/paw) and SCH 23390 (1.6 µg/paw), respectively, did not alter dopamine antinociception. In contrast, dopamine at higher doses (0.1, 1, and 10 µg/paw) caused hyperalgesia in the animals, and the D1 and D5 receptor antagonists reversed this pronociceptive effect (10 µg/paw), whereas the D2 receptor antagonist remoxipride did not. Our data suggest that dopamine has a dual effect that depends on the dose, as it causes peripheral antinociceptive effects at small doses via the activation of D2-like receptors and nociceptive effects at higher doses via the activation of D1-like receptors.

Ultrassonografia testicular no modo color Doppler∕ espectral e avaliação andrológica de garanhões tratados com gonadotrofina coriônica humana (hCG) em diferentes estações do ano / [Testicular ultrasonography in the doppler / spectral color mode and andrological evaluation of stallions treated with human corionic gonadotrofin (hCG) in different seasons of the year]

Utilizaram-se quatro garanhões nos meses de janeiro, abril, julho e outubro de 2016, em dois protocolos, em que: GI (n=4; 5mL de solução salina, i.v.) e GII (n=4; 5000UI de hCG, i.v.) e subdividiram-se esses protocolos em ciclos (C1 e C2), seguindo o esquema crossover, sendo: CI=animais 1 (GI) e 2 (GII), avaliados nos dias D1, D3 e D5, e animais 3 (GI) e 4 (GII), em D2, D4 e D6; CII= animais 1 (GII) e 2 (GI), em D1, D3, D5, e animais 3 (GII) e 4 (GI), em D2, D4 e D6. Realizou-se o tratamento em D1 e D2 de cada ciclo e a ultrassonografia testicular no modo color Doppler e Doppler espectral, uma hora antes de cada coleta de sêmen e imediatamente após. Avaliou-se: número de reflexo de Flehmen, de montas sem ereção, início da monta, tempo de reação à ereção e total da monta e análises de qualidade seminal. Estatisticamente foram utilizados os testes de qui-quadrado e ANOVA. Não houve diferenças estatísticas (P>0,05) entre os parâmetros analisados. Concluiu-se que uma única dose de 5000UI de hCG em garanhões não causou alterações significativas nos parâmetros avaliados em diferentes estações do ano.(AU)

Four stallions were used in January, April, July and October 2016 in two protocols: GI (n=4; 5ml saline, iv) and GII (n=4; 5000 hCG, iv), and these protocols were subdivided into cycles (C1 and C2) following the cross over scheme, as follows: CI=animal 1 (GI) and 2 (GII) evaluated on days D1, D3 and D5 and animal 3 (GI) and 4 (GII) at D 2, D 4 and D 6; CII=animal 1 (GII) and 2 (GI) at D1, D3, D5 and animal 3 (GII) and 4 (GI) at D2, D4 and D6. Treatment was performed on D1 and D2 of each cycle and testicular ultrasound in color Doppler and spectral Doppler mode, one hour before each semen collection and immediately after. We evaluated: Flehmen's reflex number, mounts without erection, start of the mount, reaction time to erection and total mount and seminal quality analyzes. Statistically, the Chi-square and ANOVA tests were used. There were no statistical differences (P>0.05) between the analyzed parameters. It was concluded that a single dose of 5000IU hCG in stallions did not cause significant changes in the parameters evaluated in different seasons of the year.(AU)

Association of estrogen receptor ß polymorphisms with posterior tibial tendon dysfunction.

Posterior tibial tendon (PTT) dysfunction is three times more common in females, and some patients may have a predisposition without a clinically evident cause, suggesting that individual characteristics play an important role in tendinopathy. The present study investigated the association of rs4986938 (+ 1730G > A; AluI RFLP) and rs1256049 (- 1082G > A; RsaI RFLP) single nucleotide polymorphisms (SNPs) of estrogen receptor-beta (ER-ß) gene with PTT dysfunction. A total of 400 participants were recruited. The PTT dysfunction group: these patients underwent surgery, with PTT tendinopathy confirmed by histopathology and magnetic resonance image (MRI). The control group was composed of participants with no clinical or MRI evidence of PTT dysfunction. Each group was composed of 100 postmenopausal women, 50 premenopausal women, and 50 men. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Concerning the ER-ß SNP rs4986938, there were significant differences in the frequencies of alleles between test and control groups of all the cases, only postmenopausal women and only men (p < 0.0001, p = 0.0016 and p = 0.0001). Considering the PTT dysfunction group and comparing postmenopausal women versus premenopausal women adding men, the analysis showed significant differences in the allelic distribution (p = 0.0450): the allele A in postmenopausal women is a risk factor. The ER-ß SNP rs1256049 did not show differences in the frequencies of alleles and genotypes between groups. The ER-ß SNP rs4986938, but not ER -ß SNPs rs1256049, may contribute to PTT insufficiency in the Brazilian population, with additional risk in postmenopausal women. Addition, in men the genetic factor could be more determinant.

ERα PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study.

BACKGROUND: Posterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-α) gene with PPT dysfunction. METHODS: A total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER-α gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER-α gene showed significant differences in the frequency of genotypes between control and test groups (p = 0.01; OR 95% 1.14 (0.55-2.33). CONCLUSIONS: The XbaI SNP in the ERα gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.

Origin of α and ß relaxations of Nafion.

Our experiments disentangle the low and high frequency dispersions in perfluorosulfonate ionomer solutions and membranes, providing a reasonable model for understanding these relaxations. Dielectric spectroscopy (DS) and small angle x-ray scattering (SAXS) measurements revealed that the dielectric relaxations observed at low (α relaxation) and high (ß relaxation) frequencies show typical features of the longitudinal and radial polarization, respectively, of rodlike polymeric aggregates. Such relaxations were attributed to counterion fluctuations in the vicinity of sulfonic acid groups, in resemblance with polyelectrolytes. Characteristic correlation lengths calculated from both DS and SAXS data are in good agreement adding further evidence to the proposed model. Such description provides insights for the understanding of the crossover from polyelectrolytes, dominated by charge repulsion, to ionomers, dominated by dipolar attraction.

Evidence of interaction between fluoxetine and isosorbide dinitrate on neuroleptic-induced catalepsy in mice.

Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors (SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to affect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, i.p.) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected i.p. 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74%) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62% attenuation). The combined drugs (FX + ID group), however, caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect on the raphe somatodendritic synapse, where inhibitory 5-HT1A autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.

Evidence of interaction between fluoxetine and isosorbide dinitrate on neuroleptic-induced catalepsy in mice

Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors(SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to effect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, ip) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected ip 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74 percent) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62 percent attenuation). The combined drugs (FX + ID group), however caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect oon the raphe somatodendritic synapse, where inhibitory 5-HT(1A) autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.