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1.
Purinergic Signal ; 17(2): 247-254, 2021 06.
Article in English | MEDLINE | ID: mdl-33548045

ABSTRACT

6-Hydroxydopamine (6-OHDA) is the most used toxin in experimental Parkinson's disease (PD) models. 6-OHDA shows high affinity for the dopamine transporter and once inside the neuron, it accumulates and undergoes non-enzymatic auto-oxidation, promoting reactive oxygen species (ROS) formation and selective damage of catecholaminergic neurons. In this way, our group has established a 6-OHDA in vitro protocol with rat striatal slices as a rapid and effective model for screening of new drugs with protective effects against PD. We have shown that co-incubation with guanosine (GUO, 100 µM) prevented the 6-OHDA-induced damage in striatal slices. As the exact GUO mechanism of action remains unknown, the aim of this study was to investigate if adenosine A1 (A1R) and/or A2A receptors (A2AR) are involved on GUO protective effects on striatal slices. Pre-incubation with DPCPX, an A1R antagonist prevented guanosine effects on 6-OHDA-induced ROS formation and mitochondrial membrane potential depolarization, while CCPA, an A1R agonist, did not alter GUO effects. Regarding A2AR, the antagonist SCH58261 had similar protective effect as GUO in ROS formation and mitochondrial membrane potential. Additionally, SCH58261 did not affect GUO protective effects. The A2AR agonist CGS21680, although, completely blocked GUO effects. Finally, the A1R antagonist DPCPX, and the A2AR agonist CGS21680 also abolished the preventive guanosine effect on 6-OHDA-induced ATP levels decrease. These results reinforce previous evidence for a putative interaction of GUO with A1R-A2AR heteromer as its molecular target and clearly indicate a dependence on adenosine receptors modulation to GUO protective effect.


Subject(s)
Guanosine/pharmacology , Mitochondrial Diseases/prevention & control , Neostriatum/metabolism , Neuroprotective Agents/pharmacology , Oxidopamine/toxicity , Receptor, Adenosine A1/drug effects , Receptor, Adenosine A2A/drug effects , Respiratory Burst/drug effects , Adenosine A1 Receptor Antagonists/pharmacology , Animals , Drug Evaluation, Preclinical , In Vitro Techniques , Male , Membrane Potential, Mitochondrial/drug effects , Neostriatum/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Xanthines/therapeutic use
2.
Purinergic Signal ; 16(3): 379-387, 2020 09.
Article in English | MEDLINE | ID: mdl-32725400

ABSTRACT

Parkinson's disease (PD) signs and symptoms regularly include tremor. Interestingly, the nucleoside guanosine (GUO) has already proven to be effective in reducing reserpine-induced tremulous jaw movements (TJMs) in rodent models, thus becoming a promising antiparkinsonian drug. Here, we aimed at revealing the mechanism behind GUO antiparkinsonian efficacy by assessing the role of adenosine A1 and A2A receptors (A1R and A2AR) on GUO-mediated anti-tremor effects in the reserpinized mouse model of PD. Reserpinized mice showed elevated reactive oxygen species (ROS) production and cellular membrane damage in striatal slices assessed ex vivo and GUO treatment reversed ROS production. Interestingly, while the simultaneous administration of sub-effective doses of GUO (5 mg/kg) and SCH58261 (0.01 mg/kg), an A2AR antagonist, precluded reserpine-induced TJMs, these were ineffective on reverting ROS production in ex vivo experiments. Importantly, GUO was able to reduce TJM and ROS production in reserpinized mouse lacking the A2AR, thus suggesting an A2AR-independent mechanism of GUO-mediated effects. Conversely, the administration of DPCPX (0.75 mg/kg), an A1R antagonist, completely abolished both GUO-mediated anti-tremor effects and blockade of ROS production. Overall, these results indicated that GUO anti-tremor and antioxidant effects in reserpinized mice were A1R dependent but A2AR independent, thus suggesting a differential participation of adenosine receptors in GUO-mediated effects.


Subject(s)
Guanosine/therapeutic use , Parkinson Disease, Secondary/metabolism , Receptor, Adenosine A1/metabolism , Receptor, Adenosine A2A/metabolism , Tremor/metabolism , Adenosine A1 Receptor Antagonists/pharmacology , Adenosine A2 Receptor Antagonists , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Guanosine/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/drug therapy , Reactive Oxygen Species/metabolism , Tremor/chemically induced , Tremor/drug therapy , Xanthines/pharmacology
3.
Braz. j. biol ; 80(2): 393-404, Apr.-June 2020. tab
Article in English | LILACS | ID: biblio-1132371

ABSTRACT

Abstract This paper reports the in vitro antiproliferative effects, antiprotozoal, anti-herpes and antimicrobial activities of 32 organic extracts of 14 marine sponges and 14 corals collected in northeast Brazilian coast. The ethanolic extracts of the sponges Amphimedon compressa and Tedania ignis, and the acetone extract of Dysidea sp. showed relevant results concerning the antiproliferative effects against A549, HCT-8, and PC-3 cell lines by sulforhodamine B assay, but also low specificity. Concerning the antiprotozoal screening, the ethanolic extract of Amphimedon compressa and the acetone and ethanolic extracts of Dysidea sp. were the most active against Leishmania amazonensis and Trypanosoma cruzi expressing β-galactosidase in THP-1 cells. In the preliminary anti-HSV-1 (KOS strain) screening, the ethanolic extracts of the sponges Amphimedon compressa, Haliclona sp. and Chondrosia collectrix inhibited viral replication by more than 50%. The most promising anti-herpes results were observed for the ethanolic extract of Haliclona sp. showing high selective indices against HSV-1, KOS and 29R strains (SI> 50 and >79, respectively), and HSV-2, 333 strain (IS>108). The results of the antibacterial screening indicated that only the ethanolic extract of Amphimedon compressa exhibited a weak activity against Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli by the disk diffusion method. In view of these results, the extracts of Amphimedon compressa, Tedania ignis and Dysidea sp. were selected for further studies aiming the isolation and identification of the bioactive compounds with antiproliferative and/or antiprotozoal activities. The relevant anti-herpes activity of the ethanolic extract of Haliclona sp. also deserves special attention, and will be further investigated.


Resumo Este artigo reporta as atividades in vitro antiproliferativa, atiprotozoárica, anti-herpética e antimicrobiana de 32 extratos orgânicos provenientes de 14 esponjas marinhas e 14 corais coletados no litoral nordestino brasileiro. Os extratos etanólicos das esponjas Amphimedon compressa e Tedania ignis, e o extrato acetônico de Dysidea sp. demonstraram resultados promissores em relação aos efeitos antiproliferativos frente as linhagens celulares A549, HCT-8, PC-3 pelo método da sulforrodamina B, mas sem especificidade. Em relação à atividade antiprotozárica, os extratos etanólico de Amphimedon compressa e acetônico e etanólico de Dysidea sp. apresentaram atividade contra Leishmania amazonensis e Trypanosoma cruzi através do método de expressão de β-galactosidase em células THP-1. Na investigação preliminar de atividade antiviral frente ao vírus Herpes simplex tipo 1 (cepa KOS), os extratos etanólicos das esponjas Amphimedon compressa, Haliclona sp. e Chondrosia collectrix inibiram mais de 50% da replicação viral. O extrato etanólico da esponja Haliclona sp. demonstrou resultados promissores para atividade anti-herpética com altos índices de seletividade para as cepas KOS (IS >50) e 29R (IS>79) frente ao VHS-1 e cepa 333 (IS>108) frente ao VHS-2. O extrato etanólico da esponja Amphimedon compressa exibiu uma pequena atividade contra Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli pelo método de difusão em disco. De acordo com os resultados apresentados, os extratos das esponjas Amphimedon compressa, Tedania ignis e Dysidea sp. serão selecionados para futuros estudos de isolamento e identificação dos compostos bioativos para as atividades antiproliferativa e antiprozoárica. O extrato etanólico de Haliclona sp. será investigado por possuir atividade relevante anti-herpética.


Subject(s)
Animals , Porifera , Brazil , Plant Extracts , Enterococcus faecalis , Anti-Bacterial Agents
4.
Braz J Biol ; 80(2): 393-404, 2020.
Article in English | MEDLINE | ID: mdl-31389485

ABSTRACT

This paper reports the in vitro antiproliferative effects, antiprotozoal, anti-herpes and antimicrobial activities of 32 organic extracts of 14 marine sponges and 14 corals collected in northeast Brazilian coast. The ethanolic extracts of the sponges Amphimedon compressa and Tedania ignis, and the acetone extract of Dysidea sp. showed relevant results concerning the antiproliferative effects against A549, HCT-8, and PC-3 cell lines by sulforhodamine B assay, but also low specificity. Concerning the antiprotozoal screening, the ethanolic extract of Amphimedon compressa and the acetone and ethanolic extracts of Dysidea sp. were the most active against Leishmania amazonensis and Trypanosoma cruzi expressing ß-galactosidase in THP-1 cells. In the preliminary anti-HSV-1 (KOS strain) screening, the ethanolic extracts of the sponges Amphimedon compressa, Haliclona sp. and Chondrosia collectrix inhibited viral replication by more than 50%. The most promising anti-herpes results were observed for the ethanolic extract of Haliclona sp. showing high selective indices against HSV-1, KOS and 29R strains (SI> 50 and >79, respectively), and HSV-2, 333 strain (IS>108). The results of the antibacterial screening indicated that only the ethanolic extract of Amphimedon compressa exhibited a weak activity against Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli by the disk diffusion method. In view of these results, the extracts of Amphimedon compressa, Tedania ignis and Dysidea sp. were selected for further studies aiming the isolation and identification of the bioactive compounds with antiproliferative and/or antiprotozoal activities. The relevant anti-herpes activity of the ethanolic extract of Haliclona sp. also deserves special attention, and will be further investigated.


Subject(s)
Porifera , Animals , Anti-Bacterial Agents , Brazil , Enterococcus faecalis , Plant Extracts
5.
Arch. Clin. Psychiatry (Impr.) ; 46(1): 1-4, Jan.-Feb. 2019. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-991618

ABSTRACT

Abstract Objective To describe the development of weCope, a Portuguese mobile app for people with schizophrenia. Methods The development of weCope followed 4 stages: I-102 people with psychotic disorders completed an online questionnaire; II-a multidisciplinary focus group was conducted among five mental health professionals; III-we developed the app; IV-9 participants used weCope during 8 weeks to assess its efficiency. Results weCope targets coping with voices, problem solving, goals setting and stress management, and results indicated that: weCope improved symptoms, sense of recovery and personal and social functioning; 59% of the participants were willing to download an application for illness self-management; professionals revealed some concerns about mHealth but enhanced the high importance to develop these apps; usability testing revealed that 89% considered weCope useful for illness self-management. However, the more years with mental illness, the less importance is given to a mobile application for this purpose. Discussion weCope was developed through a comprehensive development process and may contribute to a subjective perception of the patient's better well-being and health condition.

6.
Photochem Photobiol Sci ; 16(2): 238-245, 2017 02 15.
Article in English | MEDLINE | ID: mdl-28009887

ABSTRACT

Crepis japonica (L.) D.C. (Asteraceae), a weed with antioxidant, antiallergenic, antiviral and antitumor properties displays both medicinal properties and nutritional value. This study aims to assess the effects of a supplementation of blue light and UV-A radiation on the growth, leaf anatomical structure and phenolic profile of the aerial parts of Crepis japonica. Plants were grown under two light treatments: W (control - white light), W + B (white light supplemented with blue light) and W + UV-A (white light supplemented with UV-A radiation). We recorded the length, width, and weight of fresh and dry leaves, the thickness of the epidermis and mesophyll, and stomata density. The phenolic profiles of the aqueous extracts of the aerial parts were analyzed by HPLC-DAD. There was an increase in the leaf size, stomatal density, and phenolic production, and a thickening of the mesophyll and epidermis. UV-A radiation increased the phenolic production more than blue light. Blue light and UV-A radiation both improved the production of caffeic acid by about 6 and 3 times, respectively, in comparison to control. This compound was first reported as a constituent of the extract from the aerial parts together with caftaric acid. UV-A also promoted the production of chlorogenic acid (about 1.5 times in comparison to the control). We observed that the morphological and chemical parameters of C. japonica are modified in response to blue light and UV-A radiation, which can be used as tools in the cultivation of this species in order to improve its medicinal properties and nutritional value.


Subject(s)
Crepis/radiation effects , Light , Ultraviolet Rays , Chlorogenic Acid/chemistry , Chlorogenic Acid/isolation & purification , Chlorogenic Acid/metabolism , Chromatography, High Pressure Liquid , Crepis/chemistry , Crepis/metabolism , Phenols/chemistry , Phenols/isolation & purification , Phenols/metabolism , Plant Components, Aerial/chemistry , Plant Components, Aerial/metabolism , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Leaves/metabolism , Plant Leaves/radiation effects
7.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1467306

ABSTRACT

Abstract This paper reports the in vitro antiproliferative effects, antiprotozoal, anti-herpes and antimicrobial activities of 32 organic extracts of 14 marine sponges and 14 corals collected in northeast Brazilian coast. The ethanolic extracts of the sponges Amphimedon compressa and Tedania ignis, and the acetone extract of Dysidea sp. showed relevant results concerning the antiproliferative effects against A549, HCT-8, and PC-3 cell lines by sulforhodamine B assay, but also low specificity. Concerning the antiprotozoal screening, the ethanolic extract of Amphimedon compressa and the acetone and ethanolic extracts of Dysidea sp. were the most active against Leishmania amazonensis and Trypanosoma cruzi expressing -galactosidase in THP-1 cells. In the preliminary anti-HSV-1 (KOS strain) screening, the ethanolic extracts of the sponges Amphimedon compressa, Haliclona sp. and Chondrosia collectrix inhibited viral replication by more than 50%. The most promising anti-herpes results were observed for the ethanolic extract of Haliclona sp. showing high selective indices against HSV-1, KOS and 29R strains (SI> 50 and >79, respectively), and HSV-2, 333 strain (IS>108). The results of the antibacterial screening indicated that only the ethanolic extract of Amphimedon compressa exhibited a weak activity against Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli by the disk diffusion method. In view of these results, the extracts of Amphimedon compressa, Tedania ignis and Dysidea sp. were selected for further studies aiming the isolation and identification of the bioactive compounds with antiproliferative and/or antiprotozoal activities. The relevant anti-herpes activity of the ethanolic extract of Haliclona sp. also deserves special attention, and will be further investigated.


Resumo Este artigo reporta as atividades in vitro antiproliferativa, atiprotozoárica, anti-herpética e antimicrobiana de 32 extratos orgânicos provenientes de 14 esponjas marinhas e 14 corais coletados no litoral nordestino brasileiro. Os extratos etanólicos das esponjas Amphimedon compressa e Tedania ignis, e o extrato acetônico de Dysidea sp. demonstraram resultados promissores em relação aos efeitos antiproliferativos frente as linhagens celulares A549, HCT-8, PC-3 pelo método da sulforrodamina B, mas sem especificidade. Em relação à atividade antiprotozárica, os extratos etanólico de Amphimedon compressa e acetônico e etanólico de Dysidea sp. apresentaram atividade contra Leishmania amazonensis e Trypanosoma cruzi através do método de expressão de -galactosidase em células THP-1. Na investigação preliminar de atividade antiviral frente ao vírus Herpes simplex tipo 1 (cepa KOS), os extratos etanólicos das esponjas Amphimedon compressa, Haliclona sp. e Chondrosia collectrix inibiram mais de 50% da replicação viral. O extrato etanólico da esponja Haliclona sp. demonstrou resultados promissores para atividade anti-herpética com altos índices de seletividade para as cepas KOS (IS >50) e 29R (IS>79) frente ao VHS-1 e cepa 333 (IS>108) frente ao VHS-2. O extrato etanólico da esponja Amphimedon compressa exibiu uma pequena atividade contra Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli pelo método de difusão em disco. De acordo com os resultados apresentados, os extratos das esponjas Amphimedon compressa, Tedania ignis e Dysidea sp. serão selecionados para futuros estudos de isolamento e identificação dos compostos bioativos para as atividades antiproliferativa e antiprozoárica. O extrato etanólico de Haliclona sp. será investigado por possuir atividade relevante anti-herpética.

8.
Neurotox Res ; 27(2): 118-28, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25367806

ABSTRACT

The search for new therapeutic strategies through modulation of glutamatergic transmission using effective neuroprotective agents is essential. Glutamatergic excitotoxicity is a major factor common to neurodegenerative diseases and in acute events such as cerebral ischemia, traumatic brain injury and epilepsy. We have previously demonstrated that N-methyl-D-aspartate (NMDA) preconditioning in mice showed 50 % of protection against seizures and full protection against damage to neuronal tissue induced by quinolinic acid (QA). In this study, cellular and molecular mechanisms involved on NMDA preconditioning and neuroprotection were investigated in mice treated with NMDA 24 h before QA insult. Calcium uptake and D-aspartate release from hippocampal slices obtained from mice treated with NMDA plus QA and not displaying seizures (protected mice) were similar to control (saline) or NMDA preconditioned mice. Increased calcium uptake and glutamate release is evidenced in unprotected (convulsed) mice as well as QA control, demonstrating that calcium and glutamate are involved in NMDA-induced preconditioning. Increased glutamate release evoked by QA was blocked by MK-801, whereas increased calcium uptake was abolished by voltage-dependent calcium channels inhibitors, but not MK-801. NMDA preconditioning is effective in normalizing the deregulation of glutamate transport and calcium homeostasis evoked by QA due to aberrant NMDA receptors activation that culminates in seizures and hippocampal cells damage.


Subject(s)
Calcium/metabolism , Excitatory Amino Acid Agonists/pharmacology , Glutamic Acid/metabolism , Hippocampus/drug effects , Homeostasis/drug effects , N-Methylaspartate/pharmacology , Animals , D-Aspartic Acid/metabolism , Excitatory Amino Acid Agonists/administration & dosage , Hippocampus/metabolism , Male , Mice , N-Methylaspartate/administration & dosage , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Quinolinic Acid/administration & dosage , Seizures/chemically induced , Seizures/metabolism
9.
Peptides ; 30(10): 1914-20, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19616051

ABSTRACT

Neuropeptide S (NPS) and its receptor NPSR comprise a recently deorphaned G-protein-coupled receptor system. There is a body of evidence suggesting the involvement of NPS in wakefulness, anxiety, locomotor activity and oxidative stress damage. Considering that mood stabilizers block the stimulatory effect of psychostimulants in rodents, the present study aimed to investigate the effects of the pretreatment with lithium and valproate on the hyperlocomotion evoked by NPS. Another relevant action induced by lithium and valproate is the neuroprotection against oxidative stress. Thus, aiming to get further information about the mechanisms of action of NPS, herein we evaluated the effects of NPS, lithium and valproate, and the combination of them on oxidative stress damage. Behavioral studies revealed that the pretreatment with lithium (100 mg/kg, i.p.) and valproate (200 mg/kg, i.p.) prevented hyperlocomotion evoked by NPS 0.1 nmol. Importantly, the dose of valproate used in this study reduced mouse locomotion, although it did not reach the statistical significance. Biochemical analyses showed that lithium attenuated thiobarbituric reactive species (TBARS) formation in the striatum, cerebellum and hippocampus. NPS per se reduced TBARS levels only in the hippocampus. Valproate did not significantly affect TBARS levels in the brain. However, the combination of mood stabilizers and NPS blocked, instead of potentiate, the neuroprotective effects of each one. No relevant alterations were observed in carbonylated proteins after all treatments. Altogether, the present findings suggested that mainly the mood stabilizer lithium evoked antagonistic effects on the mediation of hyperlocomotion and protection against lipid peroxidation induced by NPS.


Subject(s)
Antipsychotic Agents , Behavior, Animal/drug effects , Lithium Compounds , Neuropeptides/metabolism , Animals , Anticonvulsants/metabolism , Anticonvulsants/pharmacology , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Humans , Lithium Compounds/metabolism , Lithium Compounds/pharmacology , Male , Mice , Motor Activity/drug effects , Receptors, G-Protein-Coupled , Thiobarbituric Acid Reactive Substances/metabolism , Valproic Acid/metabolism , Valproic Acid/pharmacology
10.
Braz J Med Biol Res ; 40(6): 831-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17581683

ABSTRACT

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.


Subject(s)
Anxiety Disorders/etiology , Avoidance Learning/physiology , Cecal Diseases/physiopathology , Depressive Disorder/etiology , Intestinal Obstruction/physiopathology , Intestinal Perforation/physiopathology , Shock, Septic/physiopathology , Animals , Anxiety Disorders/physiopathology , Depressive Disorder/physiopathology , Disease Models, Animal , Male , Maze Learning , Memory, Short-Term/physiology , Rats , Rats, Wistar , Shock, Septic/psychology , Swimming
11.
Braz. j. med. biol. res ; 40(6): 831-837, June 2007. graf
Article in English | LILACS | ID: lil-452677

ABSTRACT

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50 percent of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40 percent) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.


Subject(s)
Animals , Male , Rats , Anxiety Disorders/etiology , Avoidance Learning/physiology , Cecal Diseases/physiopathology , Depressive Disorder/etiology , Intestinal Obstruction/physiopathology , Intestinal Perforation/physiopathology , Shock, Septic/physiopathology , Anxiety Disorders/physiopathology , Disease Models, Animal , Depressive Disorder/physiopathology , Maze Learning , Memory, Short-Term/physiology , Rats, Wistar , Swimming , Shock, Septic/psychology
12.
Neuroscience ; 146(4): 1719-25, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17445991

ABSTRACT

Many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD), are caused by different mechanisms but may share a common pathway to neuronal injury as a result of the overstimulation of glutamate receptors. It has been suggested that this pathway can be involved in generation of cognitive deficits associated with normal aging. Previous studies performed in our laboratory have demonstrated that aged rats presented recognition memory deficits. The aim of the present study was to evaluate the effect of memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, on age-induced recognition memory deficits. Additionally, parameters of oxidative damage in cerebral regions related to memory formation were evaluated. In order to do that, male Wistar rats (24 months old) received daily injections of saline solution or memantine (20 mg/kg i.p.) during 21 days. The animals were submitted to a novel object recognition task 1 week after the last injection. Memantine-treated rats showed normal recognition memory while the saline group showed long-term recognition memory deficits. The results show that memantine is able to reverse age-induced recognition memory deficits. We also demonstrated that memantine reduced the oxidative damage to proteins in cortex and hippocampus, two important brain regions involved in memory formation. Thus, the present findings suggest that, at least in part, age-induced cognitive deficits are related to oxidative damage promoted by NMDA receptor overactivation.


Subject(s)
Aging/physiology , Excitatory Amino Acid Antagonists/therapeutic use , Memantine/therapeutic use , Memory Disorders/drug therapy , Animals , Behavior, Animal/drug effects , Exploratory Behavior/drug effects , Male , Memory Disorders/etiology , Protein Carbonylation/drug effects , Rats , Rats, Wistar , Statistics, Nonparametric , Time Factors
13.
Rev. cuba. med. mil ; 35(2)abr.-jun. 2006.
Article in Spanish | LILACS | ID: lil-450574

ABSTRACT

Se aplicó una sistemática de estudio a los pacientes mayores de 60 años de edad operados de forma electiva por cirugía de mínimo acceso en el período comprendido entre junio de 2003 a mayo de 2004 en el Departamento de Cirugía Laparoscópica del Instituto Superior de Medicina Militar “Dr Luis Díaz Soto”, con el propósito de determinar las características clinicoquirúrgicas de estos pacientes. Se estudiaron 103 pacientes con edades entre 60 y 70 años; el 71,8 por ciento de ellos correspondió a mujeres de la raza blanca. Entre las enfermedades asociadas más frecuentes estuvo la hipertensión arterial (56 pacientes; 53,3 por ciento), el asma y las cardiopatías (19 pacientes; 18,4 por ciento respectivamente). La mayoría de los enfermos (75 pacientes; 72,8 por ciento) presentó un cuadro clínico caracterizado por dolor y trastornos dispépticos. El tiempo de evolución de los síntomas fue de varios años en 81 pacientes (78,6 por ciento). El examen de ultrasonido resultó el medio diagnóstico más eficaz, pues demostró la litiasis vesicular en 101 pacientes (98 por ciento). Se encontró un plastrón vesicular en 6 pacientes y en 10 colecistitis subaguda. El tiempo quirúrgico fue menor de 30 min, no aparecieron complicaciones posoperatorias y la estadía fue de 24 h promedio. Quedó demostrado que los pacientes de edad avanzada pueden disfrutar de los beneficios de la cirugía de mínimo acceso


Subject(s)
Male , Humans , Female , Aged , Digestive System Surgical Procedures , Laparoscopy , Elective Surgical Procedures
14.
Rev. cuba. med. mil ; 35(2)abr.-jun. 2006.
Article in Spanish | CUMED | ID: cum-29821

ABSTRACT

Se aplicó una sistemática de estudio a los pacientes mayores de 60 años de edad operados de forma electiva por cirugía de mínimo acceso en el período comprendido entre junio de 2003 a mayo de 2004 en el Departamento de Cirugía Laparoscópica del Instituto Superior de Medicina Militar “Dr Luis Díaz Soto”, con el propósito de determinar las características clinicoquirúrgicas de estos pacientes. Se estudiaron 103 pacientes con edades entre 60 y 70 años; el 71,8 por ciento de ellos correspondió a mujeres de la raza blanca. Entre las enfermedades asociadas más frecuentes estuvo la hipertensión arterial (56 pacientes; 53,3 por ciento), el asma y las cardiopatías (19 pacientes; 18,4 por ciento respectivamente). La mayoría de los enfermos (75 pacientes; 72,8 por ciento) presentó un cuadro clínico caracterizado por dolor y trastornos dispépticos. El tiempo de evolución de los síntomas fue de varios años en 81 pacientes (78,6 por ciento). El examen de ultrasonido resultó el medio diagnóstico más eficaz, pues demostró la litiasis vesicular en 101 pacientes (98 por ciento). Se encontró un plastrón vesicular en 6 pacientes y en 10 colecistitis subaguda. El tiempo quirúrgico fue menor de 30 min, no aparecieron complicaciones posoperatorias y la estadía fue de 24 h promedio. Quedó demostrado que los pacientes de edad avanzada pueden disfrutar de los beneficios de la cirugía de mínimo acceso(AU)


Subject(s)
Humans , Male , Female , Aged , Laparoscopy/methods , Digestive System Surgical Procedures , Elective Surgical Procedures
15.
Exp Toxicol Pathol ; 51(4-5): 299-303, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10445386

ABSTRACT

The role of monoamine oxidase (MAO) and cytochrome P450 (P450) in the oxidative deamination of primaquine by rat liver fractions was studied. Rat liver fractions including liver homogenate, mitochondria, microsomes and 100,000 g supematant fractions were prepared from a pool of rat livers and characterised using benzylamine as a probe for MAO activity and N,N-dimethylbenzamide as a probe for P450 N-dealkylation activity. Incubation of all fractions with primaquine yielded carboxyprimaquine as the only metabolite detectable by HPLC. The mitochondrial fraction, which contained MAO activity but not P450 activity, presented the highest Vmax/K(M) value for the formation of carboxyprimaquine (8.5 x 10(-6) dm3mg(-1)h(-1). A substantially lower Vmax/K(M) value (1.3 x 10(-6) dm3mg(-1)h(-1)) was obtained in the microsomal fraction, which contained P450 but not MAO activity. The liver homogenate fraction presented a similar value (1.8 x 10(-6) dm3mg(-1)h(-1), though it contained both enzyme systems. Incubations of all the fractions that presented MAO activity, in presence of the MAO inhibitor pargiline, resulted in a marked inhibition of primaquine oxidation. P450 inhibitor SKF 525-A effectively inhibited primaquine metabolism in the microsomal fraction but inhibition in the liver homogenate was less effective. The results are consistent with an important role for MAO in primaquine biotransformation, though clearly metabolism by P450 has a contribution role.


Subject(s)
Antimalarials/metabolism , Cytochrome P-450 Enzyme System/metabolism , Liver/enzymology , Monoamine Oxidase/metabolism , Primaquine/metabolism , Animals , Cell Fractionation , Chromatography, High Pressure Liquid , Cytochrome P-450 Enzyme Inhibitors , Drug Combinations , Drugs, Chinese Herbal/pharmacology , Enzyme Inhibitors , Glycyrrhiza , Liver/ultrastructure , Male , Microsomes, Liver/enzymology , Mitochondria, Liver/enzymology , Monoamine Oxidase Inhibitors/pharmacology , Paeonia , Pargyline/pharmacology , Rats , Rats, Wistar
16.
Pharm Res ; 16(6): 949-55, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10397619

ABSTRACT

PURPOSE: Dipeptide derivatives of primaquine (PQ) with reduced oxidative deamination to the inactive metabolite carboxyprimaquine were synthesized and evaluated as a novel class of transmission-blocking antimalarials. METHODS; Antimalarial activity was studied using a model consisting of mefloquine-resistant Plasmodium berghei ANKA 25R/10, Balb C mice, and Anopheles stephensi mosquitoes. Metabolic studies were performed with rat liver homogenates, and the incubates were analyzed by HPLC. RESULTS: All dipeptide derivatives and glycyl-PQ completely inhibited the appearance of oocysts in the midguts of the mosquitoes at 15 mg/ kg, while N-acetylprimaquine was not active at this dose. However, none of the title compounds were able to block oocyst production at 3.75 mg/kg, in contrast with primaquine. Exception for sarc-gly-PQ, all remaining compounds prevented sporozoite formation in the salivary glands of mosquitoes at a dose of 3.75 mg/kg. Simultaneous hydrolysis to primaquine and gly-PQ ocurred with the following order of Vmax/Km: for primaquine formation. L-ala-gly-PQ > L-phe-gly-PQ > gly-gly-PQ; and for gly-PQ formation, L-phe-gly-PQ > L-ala-gly-PQ > gly-gly-PQ. In contrast, primaquine was not released from D-phe-gly-PQ, sarc-gly-PQ, and N-acetylprimaquine. Neither carboxyprimaquine nor 8-amino-6-methoxyquinoline were detected in any of the incubation mixtures. CONCLUSIONS: The title compounds prevent the development of the sporogonic cycle of Plasmodium berghei. Gametocytocidal activity is independent of the rate and pathway of primaquine formation. Acylation of the aliphatic side-chain effectively prevents the formation of carboxyprimaquine, but the presence of a terminal amino group appears to be essential for the gametocytocidal activity.


Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Liver/drug effects , Primaquine/analogs & derivatives , Primaquine/pharmacology , Acylation , Animals , Antimalarials/metabolism , Dipeptides/chemistry , Dipeptides/metabolism , Dipeptides/pharmacology , Liver/metabolism , Mice , Mice, Inbred BALB C , Plasmodium berghei/drug effects , Primaquine/metabolism , Rats , Rats, Sprague-Dawley
17.
Xenobiotica ; 29(4): 409-16, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10375009

ABSTRACT

1. The aim was to set out to establish the complete network of metabolites arising from the phenobarbital-treated rat liver microsomal oxidation of N,N-diethyl-m-toluamide (DEET). The products formed from DEET and all its subsequent metabolites were identified by HPLC retention times, UV spectroscopy, mass spectrometry and by comparison with authentic standards. 2. DEET (1a) produces three major metabolites, N-ethyl-m-toluamide (1b), N,N-diethyl-m-(hydroxymethyl)benzamide (2a) and N-ethyl-m-(hydroxymethyl)benzamide (2b), and, at low substrate concentrations or extended reaction times, two minor metabolites, toluamide (1c) and N,N-diethyl-m-formylbenzamide (3a). 1b and 2a are primary metabolites and their formation follows Michaelis-Menten-type kinetics. At low DEET concentrations, ring methyl group oxidation is favoured; at saturation concentrations, methyl group oxidation and N-deethylation proceed at similar rates. The rate of formation of 2b decreases with increasing DEET concentration; 2b is therefore a secondary metabolite of DEET and DEET acts as a competitive inhibitor of the metabolism of 1b and 2a. 3. Except for the primary amides, where N-dealkylation is impossible, metabolism of all subsequent compounds, 1b,c, 2a-c, 3a-c and 4a,b, involves an N-deethylation (NEt2 --> NHEt or NHEt --> NH2) competitive with a ring substituent oxidation (CH3 --> CH2OH, CH2OH --> CHO or CHO --> CO2H). Surprisingly, the aldehydes 3a-c are also reduced to the corresponding alcohols 2a-c (CHO --> CH2OH); CO inhibits the oxidative metabolism of 3a-c, but reduction to 2a-c continues uninhibited. 4. The outcomes of this work are that (1) previously unreported aldehydes 3b and 3c form part of the DEET network of metabolites, (2) the reduction of the aldehydes 3a-c has the potential to inhibit the formation of the more highly oxidized DEET metabolites, (3) amide hydrolysis was not observed for any substrate and (4) no evidence was obtained for N-(1-hydroxyethyl)amide intermediates.


Subject(s)
DEET/pharmacology , Insect Repellents/pharmacology , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Animals , Dose-Response Relationship, Drug , Kinetics , Male , Rats , Rats, Wistar
18.
Rev. cuba. med. mil ; 28(1): 55-66, ene.-jun. 1999. tab, graf
Article in Spanish | CUMED | ID: cum-18126

ABSTRACT

Los traumatismos constituyen una afección grave e invalidante que en Cuba cobraron 5 450 fallecidos en 1997, la mayoría en sepsis generalizada y fallo orgánico multisistémico, la causa más común de muerte en estos pacientes, a pesar de los progresos en la antibioticoterapia y en las técnicas anestésicas y de reanimación. Motivado por esto se realizó una revisión de las alteraciones fisiológicas que estos producen, haciendo énfasis en su efecto inmunodepresor, diferenciando la respuesta inflamatoria al trauma de que se ha dado a llamar, en los pacientes más severos respuesta inmunohumoral hiperintensa y descontrolada o respuesta inflamatoria maligna. Se expuso el papel que desempeñan los mediadores de la inflamación en la misma, así como las formas de combatir la inmunodepresión. Se concluyó que la disminución de la respuesta inmune depués de traumatismo puede ser medida, prevenida y corregida o al menos modificada con medicamentos y apoyo nutricional suplementario(AU)


Subject(s)
Humans , Wounds and Injuries/immunology , Wounds and Injuries/metabolism , Immunity, Cellular , Antibody Formation
19.
Rev. cuba. med. mil ; 28(1): 55-66, ene.-abr. 1999.
Article in Spanish | LILACS | ID: lil-629177

ABSTRACT

Los traumatismos constituyen una afección grave e invalidante que en Cuba cobraron 5 450 fallecidos en 1997, la mayoría en sepsis generalizada y fallo orgánico multisistémico, la causa más común de muerte en estos pacientes, a pesar de los progresos en la antibioticoterapia y en las técnicas anestésicas y de reanimación. Motivado por esto se realizó una revisión de las alteraciones fisiológicas que estos producen, haciendo énfasis en su efecto inmunodepresor, diferenciando la respuesta inflamatoria al trauma de que se ha dado a llamar, en los pacientes más severos respuesta inmunohumoral hiperintensa y descontrolada o respuesta inflamatoria maligna. Se expuso el papel que desempeñan los mediadores de la inflamación en la misma, así como las formas de combatir la inmunodepresión. Se concluyó que la disminución de la respuesta inmune depués de traumatismo puede ser medida, prevenida y corregida o al menos modificada con medicamentos y apoyo nutricional suplementario.


Traumatisms are a severe and disabling affection that caused 5 450 deaths in Cuba, in 1997. Most of them resulted from generalized sepsis and multiple systems organ failure, the commonest cause of death in these patients, despite the progress attained in antibiotic therapy and in the anesthetic and reanimation techniques. A review of the physiological alterations they produce was made, making emphasis on their inmunodepressive effect and differentiating the inflamatory response to trauma known among the most severe patients as incontrolled and hypertensive immunohumoral response or malignant inflamatory response. The role played by the mediators of inflamation in itself, as well as the ways to fight immunodepression are approached. It was concluded tha the decrease of the post traumatic immune response may be measured, prevented and corrected, or at least modified with drugs and supplementary nutritional support.

20.
Rev. cuba. med. mil ; 27(1): 5-12, ene.-jun. 1998. tab
Article in Spanish | LILACS | ID: lil-223090

ABSTRACT

Se realizó un estudio prospectivo en 52 lesionados, y se estableció la correlación existente entre los valores de los índices predictivos utilizados y los resultados obtenidos en las fracciones protéicas estudiadas al ingreso, 3 y 7 días. Fueron aplicadas las siguientes pruebas estadísticas: medias, desviación estándar, minímo, máximo y prueba de correlación-regresión e hipótesis con una confiabilidad de 95 por ciento (alfa =0,05). El 38,5 por ciento de los lesionados correspondieron al rango entre 21 y 30 años de edad y predominó el sexo masculino (88,5 por ciento). Los accidentes del tránsito constituyeron la causa más frecuente de lesiones (38,5 por ciento); las lesiones ortopédicas fueron las de mayor incidencia (26,4 por ciento) y se encontraron complicaciones en el 38,4 por ciento de la muestra. Las proteínas totales, las albúminas y las globulinas gamma sufrieron disminución significativa a las 72 horas de ocurridas las lesiones, esta depresión se hizo más intensa en los fallecidos y se constató que existe correlación entre las variables estudiadas y los índices predictivos


Subject(s)
Humans , Male , Female , Albumins/metabolism , Globulins/metabolism , Prospective Studies , Proteins/metabolism , Injury Severity Score , Wounds and Injuries/metabolism
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