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1.
Braz. j. med. biol. res ; 55: e12381, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403908

ABSTRACT

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

2.
Braz. j. med. biol. res ; 54(2): e10107, 2021. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1142578

ABSTRACT

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.


Subject(s)
Animals , Male , Rabbits , Brain/drug effects , Brain/enzymology , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/pharmacology , Antidepressive Agents/pharmacology , Astrocytes , Glycogen Synthase Kinase 3 , Disease Models, Animal , Glial Fibrillary Acidic Protein , Histone Deacetylases
3.
Braz. j. med. biol. res ; 54(9): e10700, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249336

ABSTRACT

It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 μg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1β and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.


Subject(s)
Humans , Female , Burns/drug therapy , Sapotaceae , Proline , Keratinocytes , Plant Leaves , Methanol
4.
Braz. j. med. biol. res ; 52(2): e7773, 2019. tab, graf
Article in English | LILACS | ID: biblio-984030

ABSTRACT

The aim of this study was to evaluate the therapeutic effects of ultrasound (US)-mediated phonophoresis alone or in association with diclofenac diethylammonium (DCF) administered topically in animal models of inflammation. A pre-clinical, prospective, and randomized experimental study of quantitative and qualitative nature was carried out. Phonophoresis was performed using a therapeutic ultrasound apparatus in two distinct models of acute inflammation. Edema was induced by an intraplantar injection of carrageenan and measured by plethysmography. The Hargreaves test was used to evaluate the antinociceptive activity and investigate the action of phonophoresis on tumor necrosis factor (TNF)-α production. A histological analysis with hematoxylin-eosin was used to evaluate tissue repair, and the expression of COX-2 was determined by immunohistochemical analysis. At the peak of inflammatory activity (3 h), treatment with US, US+DCF, and DCF significantly reduced edema formation compared to the control group. Treatment with US+DCF was more effective than treatment with US alone at both analyzed times. In the analysis of the antinociceptive activity, the treatments significantly increased the latency time in response to the thermal stimulus. Histopathological analysis revealed a reduction of the inflammatory infiltrates and immunohistochemistry demonstrated that the association was effective in reducing COX-2 expression compared to the control group. The association of DCF with US produced anti-inflammatory and antinociceptive effects in rat models of inflammation, which may be associated with inhibition of COX-2 and TNF-α production.


Subject(s)
Animals , Male , Rats , Phonophoresis , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diclofenac/administration & dosage , Analgesics/administration & dosage , Inflammation/drug therapy , Anti-Inflammatory Agents/administration & dosage , Ultrasonic Therapy/methods , Random Allocation , Prospective Studies , Administration, Topical , Tumor Necrosis Factor-alpha , Rats, Wistar , Disease Models, Animal , Inflammation/physiopathology , Inflammation/pathology
5.
Braz. j. med. biol. res ; 44(2): 173-181, Feb. 2011. ilus
Article in English | LILACS | ID: lil-573654

ABSTRACT

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.


Subject(s)
Animals , Male , Mice , Rats , Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Lovastatin/therapeutic use , Pain/drug therapy , Carrageenan , Edema/chemically induced , Pain Measurement/drug effects , Rats, Wistar
6.
Braz. j. med. biol. res ; 40(1): 127-134, Jan. 2007. tab
Article in English | LILACS | ID: lil-439675

ABSTRACT

The antinociceptive effects of a lectin (LEC) isolated from the marine alga Amansia multifida were determined in Swiss mice. The LEC (1, 5, and 10 mg/kg) inhibited acetic acid-induced abdominal writhings in a dose-dependent manner after intraperitoneal or oral administration. A partial but significant inhibition of writhings was observed after the combination of LEC (10 mg/kg) with avidin (1 mg/kg), a potent inhibitor of the hemmaglutinant activity of the lectin. However, total writhing inhibition was demonstrable in the group of mice treated with LEC plus mannose (1 mg/kg), as compared to LEC alone or to control groups. Furthermore, avidin and mainly mannose also play a role in antinociception, somehow facilitating the interaction of LEC with its active cell sites. In the formalin test, although both phases of the response were significantly inhibited, the effect of LEC was predominant during phase 2, causing inhibition of licking time that ranged from 48 to 88 percent after oral (5 and 10 mg/kg) and intraperitoneal (1 to 5 mg/kg) administration. As is the case with morphine, the effect of LEC (2 mg/kg) was reversed by naloxone (2 mg/kg), indicating the involvement of the opioid system. LEC was also effective in the hot-plate test, producing inhibitory responses to the thermal stimulus, and its effects were blocked by naloxone. In the pentobarbital-induced sleeping time, although LEC did not alter the onset of sleep significantly, it increased the time of sleep within the same dose range compared to control. These results show that LEC presents antinociceptive effects of both central and peripheral origin, possibly involving the participation of the opioid system.


Subject(s)
Animals , Male , Female , Mice , Rhodophyta/chemistry , Analgesics/pharmacology , Plant Lectins/pharmacology , Analgesics/isolation & purification , Pain Measurement , Plant Extracts/pharmacology , Plant Lectins/isolation & purification
7.
Braz. j. med. biol. res ; 37(12): 1839-1846, Dec. 2004. ilus, tab
Article in English | LILACS | ID: lil-388052

ABSTRACT

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20 percent aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47 percent increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70 percent) and DA (50 and 36 percent) levels. On the other hand, increases were seen in 5-HIAA (146 and 153 percent) and 5-HT (59 and 86 percent) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129 percent) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61 percent). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.


Subject(s)
Animals , Male , Rats , Catecholamines/metabolism , Central Nervous System Depressants/pharmacology , Corpus Striatum/drug effects , Ethanol/pharmacology , Hippocampus/drug effects , Central Nervous System Depressants/administration & dosage , Corpus Striatum/metabolism , Dopamine/metabolism , Ethanol/administration & dosage , Hippocampus/metabolism , Norepinephrine/metabolism , Rats, Wistar , Serotonin/metabolism , Time Factors
8.
Braz. j. med. biol. res ; 37(7): 1071-1079, July 2004. graf
Article in English | LILACS | ID: lil-360926

ABSTRACT

Bryothamnion seaforthii, a red alga common to the Northeastern coast of Brazil, was used to prepare the protein fraction F0/60 by ammonium sulfate precipitation. The chromatography of F0/60 on DEAE-Sephadel column resulted in two lectin fractions, PI and PII, which have antinociceptive properties in rodents. We determined the antinociceptive activity of the PII fraction and of a carbohydrate-containing fraction (CF) in mice. The CF was prepared from the dried algae, after digestion with 100 mM sodium acetate, pH 6.0, containing 5 mM cysteine, EDTA and 0.4 percent papain, at 60ºC. A 10 percent cetylpyridinium chloride was added to the filtrate, and the precipitate was dissolved with 2 M NaCl:ethanol (100:15, v/v) followed by the carbohydrate precipitation with ethanol. The final precipitate, in acetone, was dried at 25ºC. The PII fraction markedly inhibited acetic acid-induced abdominal writhing after ip administration (control: 27.1 ± 2.20; PII 0.1 mg/kg: 5.5 ± 1.85; 1 mg/kg: 1.6 ± 0.72 writhes/20 min) and after oral administration (control: 32.0 ± 3.32; PII 0.1 mg/kg: 13.1 ± 2.50; 1 mg/kg: 9.4 ± 3.96 writhes/20 min). PII was also effective against both phases of pain induced by 1 percent formalin (control, ip: 48.2 ± 2.40 and 27.7 ± 2.56 s; PII: 1 mg/kg, ip: 34.3 ± 5.13 and 5.6 ± 2.14 s; control, po: 44.5 ± 3.52 and 25.6 ± 2.39 s; PII 5 mg/kg, po: 26.5 ± 4.67 and 15.3 ± 3.54 s for the 1st and 2nd phases, respectively) and in the hot-plate test. The CF (ip) also displayed significant antinociceptive properties in all tests but at higher doses (1 and 5 mg/kg, ip and po). Thus, CF at the dose of 5 mg/kg significantly inhibited writhes (ip: 7.1 ± 2.47 and po: 14.5 ± 2.40 writhes/20 min) as well as the 1st (po: 19.6 ± 1.74 s) and 2nd (po: 7.1 ± 2.24 s) phases of the formalin test compared to controls ip and po. The antinociceptive effects of both the PII and CF in the formalin and hot-plate tests were prevented at least partially by pretreatment with the opioid receptor antagonist naloxone (2 mg/kg, sc). Moreover, both fractions retained antinociceptive activity in the acetic acid-induced writhing test following heating, a procedure which abolished the hemagglutinating activity of the fraction, presumably due to lectins also present. Finally, both fractions also prolonged the barbiturate-induced sleeping time...


Subject(s)
Animals , Male , Female , Mice , Analgesics , Carbohydrates , Eukaryota , Pain Measurement , Plant Extracts
9.
Braz. j. med. biol. res ; 36(4): 503-509, Apr. 2003. tab, graf
Article in English | LILACS | ID: lil-331234

ABSTRACT

We studied the effects of ethanol on the levels of norepinephrine, dopamine, serotonin (5-HT) and their metabolites as well as on D1- and D2-like receptors in the rat striatum. Ethanol (2 or 4 g/kg, po) was administered daily by gavage to male Wistar rats and on the 7th day, 30 min or 48 h after drug administration, the striatum was dissected for biochemical assays. Monoamine and metabolite concentrations were measured by HPLC and D1- and D2-like receptor densities were determined by binding assays. Scatchard analyses showed decreases of 30 and 43 percent, respectively, in D1- and D2-like receptor densities and no change in dissociation constants (Kd) 48 h after the withdrawal of the dose of 4 g/kg. Ethanol, 2 g/kg, was effective only on the density of D2-like receptors but not on Kd of either receptor. Thirty minutes after the last ethanol injection (4 g/kg), decreases of D2 receptor density (45 percent) as well as of Kd values (34 percent) were detected. However, there was no significant effect on D1-like receptor density and a 46 percent decrease was observed in Kd. An increase in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), a decrease in norepinephrine, and no alteration in 5-HT levels were demonstrated after 48-h withdrawal of 4 g/kg ethanol. Similar effects were observed in dopamine and DOPAC levels 30 min after drug administration. No alteration in norepinephrine concentration and a decrease in 5-HT levels were seen 30 min after ethanol (4 g/kg) administration. Our findings indicate the involvement of the monoaminergic system in the responses to ethanol


Subject(s)
Humans , Male , Rats , Corpus Striatum , Receptors, Dopamine D1 , Receptors, Dopamine D2 , Biogenic Monoamines , Central Nervous System Depressants , Chromatography, High Pressure Liquid , Corpus Striatum , Dopamine , Ethanol , Norepinephrine , Rats, Wistar , Receptors, Dopamine D1 , Receptors, Dopamine D2 , Serotonin
10.
Braz. j. med. biol. res ; 35(8): 927-930, Aug. 2002. ilus, graf
Article in English | LILACS | ID: lil-325539

ABSTRACT

Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native to the Brazilian northeast where it is known as "pau-branco". We investigated the ability of the water soluble fraction isolated from the heartwood of A. oncocalyx to inhibit sea urchin egg development. This fraction contains about 80 percent oncocalyxone A (quinone fraction), a compound known to possess strong cytotoxic and antitumor activities. In fact, the quinone fraction inhibited cleavage in a dose-dependent manner [IC50 of 18.4 (12.4-27.2) æg/ml, N = 6], and destroyed the embryos in the blastula stage [IC50 of 16.2 (13.7-19.2) æg/ml, N = 6]. We suggest that this activity is due to the presence of oncocalyxone A. In fact, these quinones present in A. oncocalyx extract have strong toxicity related to their antimitotic activity


Subject(s)
Animals , Anthraquinones , Boraginaceae , Ovum , Plant Extracts , Quinones , Anthraquinones , Antineoplastic Agents , DNA Damage , Quinones , Sea Urchins
11.
Braz. j. med. biol. res ; 35(6): 713-722, June 2002. ilus, tab
Article in English | LILACS | ID: lil-309509

ABSTRACT

We report the antinociceptive activity, determined by the writhing, formalin and hot-plate tests in mice, of crude (F0/60), lectin and carbohydrate fractions isolated by ammonium sulfate precipitation (0 to 60 percent) from Bryothamnion seaforthii and B. triquetrum, species of red algae. Not only fraction F0/60 but also lectins from both species significantly inhibited acetic acid-induced abdominal contractions after intraperitoneal or oral administrations. In the formalin test, lectins (1 and 5 mg/kg, ip, and 5 to 20 mg/kg, po) inhibited the 1st and 2nd phases (5 and 20 min, respectively), but the effect occurred predominantly on the 2nd phase. The effects of the lectins were totally or partially reversed by naloxone (2 mg/kg, sc) in the 1st and 2nd phases, respectively. Experiments performed with lectins in the absence and presence of avidin (1 mg/kg, ip) and D-mannose (1 mg/kg, ip) showed that avidin did not interfere with the effect of B. seaforthii lectin but partially reversed the effect of B. triquetrum lectin. D-Mannose completely reversed the effects of both species. F0/60 fractions from both algae significantly increased the latency time in response to thermal stimuli, and naloxone reversed antinociception, indicating the involvement of the opioid system in both the peripheral and central effects of the fractions. In the writhing test, the carbohydrate fractions were the most active, inhibiting the contractions by 71 and 79 percent (B. triquetrum) and by 46 and 69 percent (B. seaforthii) at doses of 1 and 5 mg/kg, ip, respectively. Sulfated carbohydrate fractions of B. seaforthii and B. triquetrum, containing only about 5 percent protein as contaminants, are probably responsible for the antinociceptive effects of these red algae


Subject(s)
Animals , Male , Mice , Female , Cattle , Analgesics , Carbohydrates , Lectins , Plants, Medicinal , Rhodophyta , Plant Extracts , Sulfates
12.
Braz. j. med. biol. res ; 29(5): 643-6, May 1996. tab
Article in English | LILACS | ID: lil-182549

ABSTRACT

The anti-inflammatory and analgesic activities of a water-soluble fraction (WSF), extracted with 0.1 M ammonium bicarbonate, pH 8.0, from shark cartilage were studied in several experimental mod-els. Orally administered WSF (1O mg/kg) caused 25.7 and 23.6 per cent inhibition of the paw edema produced in female Wistar rats (200-250 g) by carrageenan and dextran, respectively, after 3 h, as compared to controls. WSF administered orally had no effect on acetic acid-induced writhings in male Swiss mice (25-30 g) at the dose of 0.01 mg/kg, but caused 52.8 and 61.4 per cent inhibition at the doses of 0.1 and 0.5 mg/kg, respectively, compared to controls (No. of writhings/20 min, means ñ SEM: treated groups = 18.6 ñ 2.5, N = 12 and 15.2 ñ 1.4, N = 12, respectively; controls = 39.3 ñ 1.3, N = 77). In the formalin test (male Swiss mice, 25-30 g), orally administered WSF (0.5 and 1 mg/kg) caused 12.0 and 46.6 per cent inhibition of licking time, respectively, only in the 2nd phase (infiammatory) of the test (licking time, means ñ SEM: treated group = 18.3 ñ 4.4 sec, N = 7 and 11.1 ñ 3.4 sec, N = 13; controls = 20.8 ñ 2.4 sec, N = 44). The results suggest that a molecule of a protein nature in shark cartilage is probably responsible for the effects observed.


Subject(s)
Animals , Male , Mice , Female , Rats , Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cartilage , Sharks , Tissue Extracts/pharmacology , Administration, Oral , Carrageenan , Edema/chemically induced , Edema/drug therapy , Rats, Wistar
13.
Braz. j. med. biol. res ; 28(1): 113-9, Jan. 1995. tab, graf
Article in English | LILACS | ID: lil-153338

ABSTRACT

The effects of pimozide, mazindol and apomorphine on muscarinic receptors in homogenates of rat cerebral motor cortex were measured by binding assays, using 3H-N-methylscopolamine (3H-NMS) alone as ligand (for the measurement of M1- and M2-like receptors) or in the presence of carbachol or pirenzepine for determination of M1- and M2-like receptors, respectively. Female Wistar rats (150g) were treated daily for one week with pimozide, a dopaminergic antagonist (10 and 20 mg/Kg, po, by gavage), or with apomorphine (1mg/Kg,ip). In another ser of experiments, animals were treated with pimozide and 30 min later with mazindol (10 mg/Kg, po, by gavage) or apomorphine. The drugs were administered daily for one week. Controls received the same volume of saline. 3H-NMS binding was increased from the control value of 418 ñ 17 ñ 42 fmol/mg protein by administration of mazindol (10mg/Kg) but binding was reduced to 360 ñ 11 fmol/mg protein upon administration of pimozide (20mg/Kg) plus mazindol (10mg/Kg. Similarly 10 mg/ Kg pimozide reduced the increase in M1-like receptors caused by mazindol from 262 ñ to 220 ñ 20 fmol/mg protein. Although 20 mg/Kg pimozide alone produced a decrease in M1-plus M2-like receptors (from 418 ñ 17 to 348 ñ 22 fmol/mg protein), its action was preferentially on M2-like receptors, decreasing them from 148 ñ 10 to o ñ 15 fmol/mg protein in the control and treated groups, respectively. At the higher dose, 20 mg/Kg pimozide also inhibited the 3 H-NMS binding (M1-plus M2-like receptors) in the presence of apomorphine (263ñ25 vs 418 ñ 17 fmol/mg protein...


Subject(s)
Animals , Female , Rats , Apomorphine/pharmacology , Motor Cortex/physiology , Mazindol/pharmacology , Pimozide/pharmacology , Receptors, Muscarinic , Rats, Wistar , Receptors, Dopamine
14.
Cad. saúde pública ; 7(3): 396-408, jul.-set. 1991. tab, graf
Article in Portuguese | LILACS | ID: lil-397313

ABSTRACT

O presente trabalho teve por objetivo verificar a ocorrência de demência senil em amostra de pessoas de 65 e mais anos de idade residentes no Município de Fortaleza. Foram estudados 865 idosos, a partir do teste de Informação, Memória e Concentração, IMC (teste de Hachinski, modificado), que aborda aspectos concernentes à identificação da pessoa, à memória de fatos atuais e remotos e à concentração, determinando os estados demenciais em função do número e grau de respostas numa sequência programada e previamente testada quanto à sensibilidade e especificidade. Analisando-se os resultados quanto a idade, sexo e condição social, evidenciou-se uma prevalência de 8,4de demência senil no conjunto geral, com diferenças n†o significativa na faixa de 75 e mais anos de idade (9,3), comparada ao grupo de 65 a 74 anos (7,5). Os percentuais foram semelhantes para homens e mulheres: 8,7e 8,3, respectivamente. Quanto à condição social, foi verificado um aumento progressivo nas proporções de estados demenciais, desde 4,2para o estrato A/B (abastados), 6,9 para o grupo C (nível intermediário) e 10,3no nível D/E correspondente ao estrato de pessoas economicamente desprivilegiadas. Estes resultados, entretanto, dever†o ser vistos com certa reserva, dado o grau de recusa por ocasião das entrevistas, especialmente nos estratos A/B (19,3) e D/E (9,3)


Subject(s)
Dementia/epidemiology , Prevalence , Psychological Tests , Interviews as Topic , Sampling Studies , Social Conditions
15.
Braz. j. med. biol. res ; 24(1): 43-7, jan.-mar. 1991. tab
Article in English | LILACS | ID: lil-99579

ABSTRACT

The present paper describes the determination of muscarinic receptor number ([3H]-N-methylscopolamine binding) and acetylcholinesterase activity in six brain areas (pre-central gyrus, post-central gyrus, hippocampus, caudate nucleus,lentiform nucleus and substantia inominata) of demented patients (diagnosed by screening tests and neurological evaluation) and age-matched controls.These was a significant increase in muscarinic receptors in the hippocampus and substanctia inominata (171.2 and 359.4fmol/mg protein, respectively) of the demented group as compared with controls (123.9 and 219.0 fmol/mg protein, respectively). No changes were observed in pre-and post-central gyrus, while a tendency towards decreased binding was detected in the caudate nucleus and lentiform nucleus of the demented group. Lower acetylcholinesterase activity was also detected in the demented group in all areas studied although the differences were significant only in the post-central gyrus, caudate nucleus and substantia inominata which showed a 49.21 and 25% decrease in enzyme activity respectively. The results are discussed in terms of a compensatory mechanism of presynaptic deficiency such as that occurring in Parkinson's disease


Subject(s)
Aged , Humans , Male , Female , Acetylcholinesterase/metabolism , Brain/metabolism , Dementia/physiopathology , Receptors, Muscarinic/analysis , Aged, 80 and over , Binding Sites , Cerebral Cortex/pathology
16.
Braz. j. med. biol. res ; 22(8): 959-61, 1989. tab
Article in English | LILACS | ID: lil-77726

ABSTRACT

The effect of undernutrition on the ontogeny of muscarinic receptor density and acetylcholineasterase (AChE) activity was studied in the motor cerebral cortex homogenates of female Wistar rats aged 12-19 days, 2-3 months and 5-8 months. Experimental animals were fed a protein-calorie deficient diet. The dinding assays, using (3H)-N-methylscopolamine as a ligand, indicated a significant increase in muscarinic receptor density in the motor cortex of 5-8- monthes old control rats (36%) compared to neonatal controls. No increase was observed for undernourished rats at any of the ages studied. No significant difference was observbed in AChE activity at any age of either group studied


Subject(s)
Rats , Animals , Female , Acetylcholinesterase/metabolism , Cerebral Cortex/metabolism , Protein-Energy Malnutrition/metabolism , Receptors, Muscarinic/metabolism , Aging
17.
Rev. Med. Univ. Fed. Ceará ; 26/27(1/2): 55-7, 1986-7. tab
Article in English | LILACS | ID: lil-94719

ABSTRACT

The study was carried out with patients older than 65 (range 69 to 92 years old) living in a nursing home at the city of Fortaleza - Brazil. The patients were separated in two groups, control and demented according to neurological examination and screening tests. The demented patients were also submited to clinical and laboratory studies and the result compared with the control group at the same age interval


Subject(s)
Aged , Alzheimer Disease
18.
Braz. j. med. biol. res ; 20(6): 803-5, 1987. tab
Article in English | LILACS | ID: lil-77452

ABSTRACT

The effects of the aqueous extract of Astronium urundeuva Engl. on aspirin and restraint plus hustmine-induced ulceration in rats are described. The extract significantly inhibited aspirin-induced gastric lesions as well restraint plus histamine-induced ulceration in rats


Subject(s)
Rats , Animals , Plants, Medicinal , Peptic Ulcer/drug therapy , Gastric Acid , Aspirin , Histamine , Plant Extracts/therapeutic use , Rats, Inbred Strains , Restraint, Physical , Peptic Ulcer/etiology
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