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1.
Radiographics ; 36(6): 1888-1910, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27726741

RESUMO

Infection of the musculoskeletal system can be associated with high mortality and morbidity if not promptly and accurately diagnosed. These infections are generally diagnosed and managed clinically; however, clinical and laboratory findings sometimes lack sensitivity and specificity, and a definite diagnosis may not be possible. In uncertain situations, imaging is frequently performed to confirm the diagnosis, evaluate the extent of the disease, and aid in treatment planning. In particular, cross-sectional imaging, including computed tomography and magnetic resonance imaging, provides detailed anatomic information in the evaluation of soft tissues due to their inherent high spatial and contrast resolution. Imaging findings of soft-tissue infections can be nonspecific and can have different appearances depending on the depth and anatomic extent of tissue involvement. Although many imaging features of infectious disease can overlap with noninfectious processes, imaging can help establish the diagnosis when combined with the clinical history and laboratory findings. Radiologists should be familiar with the spectrum of imaging findings of soft-tissue infections to better aid the referring physician in managing these patients. The aim of this article is to review the spectrum of soft-tissue infections using a systematic anatomic compartment approach. We discuss the clinical features of soft-tissue infections, their imaging findings with emphasis on cross-sectional imaging, their potential mimics, and clinical management. ©RSNA, 2016.


Assuntos
Celulite (Flegmão)/diagnóstico por imagem , Erros de Diagnóstico/prevenção & controle , Fasciite Necrosante/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Infecções dos Tecidos Moles/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Aumento da Imagem/métodos , Imagem Multimodal/métodos , Posicionamento do Paciente/métodos
2.
Radiographics ; 36(2): 481-96, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26963458

RESUMO

The combination of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) for dual-modality imaging (PET/CT) plays a key role in the diagnosis and staging of FDG-avid malignancies. FDG uptake by the tumor cells offers an opportunity to detect cancer in organs that appear normal at anatomic imaging and to differentiate viable tumor from posttreatment effects. Quantification of FDG uptake has multiple clinical applications, including cancer diagnosis and staging. Dedicated FDG PET/CT-based visual and quantitative criteria have been developed to evaluate treatment response. Furthermore, the level of tumor FDG uptake reflects the biologic aggressiveness of the tumor, predicting the risk of metastasis and recurrence. FDG uptake can be measured with qualitative, semiquantitative, and quantitative methods. Qualitative or visual assessment of PET/CT images is the most common clinical approach for describing the level of FDG uptake. Standardized uptake value (SUV) is the most commonly used semiquantitative tool for measuring FDG uptake. SUV can be measured as maximum, mean, or peak SUV and may be normalized by using whole or lean body weight. SUV measurements provide the basis for quantitative response criteria; however, SUVs have not been widely adopted as diagnostic thresholds for discriminating malignant and benign lesions. Volumetric FDG uptake measurements such as metabolic tumor volume and total lesion glycolysis have shown substantial promise in providing accurate tumor assessment. SUV measurement and other quantification techniques can be affected by many technical, physical, and biologic factors. Familiarity with FDG uptake quantification approaches and their pitfalls is essential for clinical practice and research.


Assuntos
Radioisótopos de Flúor/análise , Fluordesoxiglucose F18/análise , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/análise , Fatores de Confusão Epidemiológicos , Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18/farmacocinética , Glicólise , Humanos , Estadiamento de Neoplasias/métodos , Neoplasias/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Compostos Radiofarmacêuticos/farmacocinética , Padrões de Referência , Reprodutibilidade dos Testes , Distribuição Tecidual
3.
Expert Rev Respir Med ; 10(3): 317-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26822467

RESUMO

Positron emission tomography/computed tomography (PET/CT) is an important imaging tool for management of lung cancer and can be utilized in diagnosis, staging, restaging, treatment planning and evaluating treatment response. In the past decade PET/CT has proven to be beneficial for the prediction of prognosis and outcome. PET findings before and after treatment, the quantitative PET parameters such as standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as well as delayed PET/CT imaging can be used to determine patient prognosis and outcome. Other tracers such as hypoxia and proliferation marker tracers may be used for prognostication. The prognostic factors derived from PET/CT imaging help early development of risk-adapted treatment strategies, which provides cost-effective treatment and leads to improved patient management. Here, we discuss findings of studies related to application of PET/CT in lung cancer as well as some technical updates on quantitative PET/CT in lung cancer.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Meios de Contraste , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos , Fatores de Risco , Resultado do Tratamento , Carga Tumoral
4.
Epilepsy Res ; 101(3): 217-27, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22578701

RESUMO

Citalopram is a selective serotonin reuptake inhibitor (SSRI), widely used in the treatment of depressive disorders. It has been shown that citalopram affects seizure susceptibility. Although the exact mechanism of these effects are not yet fully understood, recent data suggest that 5HT(3) receptors and nitric oxide (NO) might participate in the central effects of SSRIs. In this study in a mouse model of clonic seizure induced by pentylenetetrazole we investigated whether 5-HT(3) receptors are involved in the effects of citalopram on seizure threshold. In our experiments, citalopram at lower doses (0.5 and 1mg/kg, i.p) significantly increased the seizure threshold and at higher doses (≥25mg/kg) showed proconvulsive effects. Moreover, mCPBG (a 5-HT(3) receptor agonist) at low and non-effective doses augmented while non-effective doses of tropisetron prevented the anticonvulsive properties of citalopram. On the other hand, Low doses of nitric oxide synthase inhibitors l-NAME and 7-NI alone or in combination with lower doses of 5-HT(3) receptor agonist enhanced the anticonvulsive property of citalopram, while l-arginine (NO precursor) alone or in combination with tropisetron blocked the protective effect of citalopram. In summary, our findings demonstrate that 5-HT(3) receptor mediates the anticonvulsant properties of low doses of citalopram, whereas it seems that the proconvulsive effect is mostly mediated through the NO pathway and can be totally blocked by NOS inhibitors. This could propose a new approach toward finding the mechanism of citalopram activity, curtailing the adverse effects of citalopram and perhaps managing the convulsions as a vicious consequence of citalopram overdose.


Assuntos
Anticonvulsivantes/uso terapêutico , Citalopram/uso terapêutico , Óxido Nítrico/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Biguanidas/farmacologia , Citalopram/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Masculino , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Pentilenotetrazol/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/metabolismo , Agonistas do Receptor de Serotonina/farmacologia
5.
Pediatr Radiol ; 42(4): 481-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22218736

RESUMO

We report the use of susceptibility-weighted imaging (SWI) in detection of red nucleus (rubral) degeneration and atrophy in children with hypertrophic olivary degeneration (HOD) after posterior fossa tumor resection. The use of this modality for this particular application has not been previously described. Detection of red nucleus changes seems to be facilitated by the contrast mechanism of SWI over conventional MRI sequences. SWI can be considered in the evaluation of these patients and in the future might provide a means for further classification of patients with HOD and related symptomatology.


Assuntos
Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/cirurgia , Imageamento por Ressonância Magnética/métodos , Núcleo Olivar/patologia , Núcleo Rubro/patologia , Adolescente , Humanos , Hipertrofia/patologia , Masculino , Complicações Pós-Operatórias , Resultado do Tratamento
6.
PET Clin ; 7(2): 139-50, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27157232

RESUMO

A number of diagnostic tests is often necessary to differentiate aseptic loosening from periprosthetic infection in most clinical settings. The accuracy of [(18)F]Fluorodeoxyglucose examined with positron emission tomography imaging (FDG PET) in diagnosing periprosthetic infection has been determined by a number of investigations. In general, Images are considered positive for infection if they demonstrate increased FDG activity at the bone-prosthesis interface of the prostheses. Based on the large number of reports in the literature the sensitivity and specificity for FDG PET are about 85-90%. The overall accuracy of this non-invasive imaging modality is superior to the other existing imaging techniques. Therefore, FDG PET appears a very promising and accurate diagnosing tool for distinguishing septic from aseptic painful hip prostheses.

7.
Eur J Pharmacol ; 666(1-3): 93-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21651904

RESUMO

After 60 years, lithium is still the mainstay in the treatment of mood disorders and widely used in clinic. In addition to its mood stabilizer effects, lithium also shows some anticonvulsant properties. Similar to lithium, agmatine also plays a protective role in the CNS against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on α(2)-adrenoceptors. So, we designed this study: 1) to investigate whether agmatine and lithium show an additive effect against clonic seizures induced by pentylenetetrazole; 2) to assess whether this additive effect is mediated through the α(2)-adrenoceptor or not. In our study, acute administration of a single effective dose of lithium chloride (30 mg/kg, i.p.) increased the seizure threshold. Pre-treatment with low and, per se, non-effective doses of agmatine (1 and 3mg/kg) potentiated a sub-effective dose of lithium (10mg/kg). Interestingly, the anticonvulsant effects of these effective combinations of lithium and agmatine were prevented by pre-treatment with low and non-effective doses of yohimbine [α(2)-adrenoceptor antagonist] (0.1 and 0.5mg/kg). On the other hand, clonidine [α(2)-adrenoceptor agonist] augmented the anticonvulsant effect of a sub-effective combination of lithium (5mg/kg i.p.) and agmatine (1mg/kg) at relatively low doses (0.1 and 0.25mg/kg). In summary, our findings demonstrate that agmatine and lithium chloride exhibit additive anticonvulsant properties which seem to be mediated through α(2)-adrenoceptor.


Assuntos
Agmatina/farmacologia , Anticonvulsivantes/farmacologia , Cloreto de Lítio/farmacologia , Pentilenotetrazol/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismo , Agmatina/farmacocinética , Agmatina/uso terapêutico , Animais , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Cloreto de Lítio/farmacocinética , Cloreto de Lítio/uso terapêutico , Masculino , Camundongos , Convulsões/tratamento farmacológico , Ioimbina/farmacologia
8.
Epilepsy Behav ; 21(2): 122-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21531632

RESUMO

Citalopram, a selective serotonin reuptake inhibitor (SSRI), is frequently used in the treatment of major depressive disorders. In addition to its antidepressant features, citalopram shows some anticonvulsive properties at lower doses, whereas higher doses, ingested in cases of suicide, have been associated with seizures. Moreover, some reports support the enhancing effect of morphine on different responses of SSRIs such as analgesic and anticonvulsant properties. Although the exact mechanisms of these additive effects are not yet fully understood, 5-HT(3) receptor has recently been shown to play an important role in the central effects of SSRIs and morphine. In this regard, we used a model of clonic seizures induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether morphine and citalopram exhibit additive anticonvulsant effects and, if so, whether this effect is mediated through modulation of 5-HT(3) receptors. In our study, citalopram at lower doses (0.5 and 1 mg/kg, ip) significantly increased the seizure threshold (P<0.01) and at a higher dose (50 mg/kg) had proconvulsive effects. Moreover, morphine at low and noneffective doses had additive effects on the anticonvulsive properties of citalopram. This additive effect was prevented by pretreatment with low and noneffective doses of tropisetron (a 5-HT(3) receptor antagonist) and augmented by 1-(m-chlorophenyl)-biguanide (mCPBG, a 5-HT(3) receptor agonist). Moreover, low doses of morphine (0.1 and 0.5 mg/kg) alone or in combination with potent doses of 5-HT(3) receptor agonist or antagonist could not alter the proconvulsive properties of citalopram at higher dose (50 mg/kg), ruling out the contribution of 5-HT(3) to this effect. In summary, our findings demonstrate that 5-HT(3) receptor mediates the additive anticonvulsant properties of morphine and low-dose citalopram. This could constitute a new approach to augmenting the efficacy and curtailing the adverse effects of citalopram.


Assuntos
Anticonvulsivantes/uso terapêutico , Citalopram/uso terapêutico , Morfinanos/uso terapêutico , Receptores 5-HT3 de Serotonina/metabolismo , Convulsões/tratamento farmacológico , Análise de Variância , Animais , Biguanidas/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Indóis/farmacologia , Masculino , Camundongos , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Convulsões/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Tropizetrona
9.
Seizure ; 20(5): 409-13, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21377383

RESUMO

There are several lines of evidence that opioidergic and nitrergic systems could modulate the seizure threshold. We previously have shown that sildenafil had proconvulsant effects in a model of clonic seizure induced by pentylenetetrazole (PTZ) or bicuculline. In the present study, we examined whether the opioid system participates in the action of sildenafil on the PTZ-induced clonic seizures in mice. Sildenafil (1, 5, 10 and 20 mg/kg, i.p.) significantly decreased the seizure threshold in a dose-dependent manner, whereas morphine had both anticonvulsant and proconvulsant effects at low (0.5, 1, and 3 mg/kg, s.c.) and high (60 mg/kg, s.c.) doses. A sub-effective dose of sildenafil (5 mg/kg) combined with a dose of morphine (7.5 mg/kg) which was sub-effective for its proconvulsant effects significantly decreased the seizure threshold. Although naltrexone at 0.5 and 1 mg/kg had no effect on the seizure threshold, it significantly prevented both the proconvulsant effects of sildenafil as well as the anticonvulsant and proconvulsant effects of morphine on the PTZ-induced seizure thresholds. Our data suggested a role for opioidergic system in the proconvulsant effects of sildenafil on the PTZ-induced clonic seizures in mice.


Assuntos
Analgésicos Opioides/uso terapêutico , Morfina/uso terapêutico , Peptídeos Opioides/fisiologia , Pentilenotetrazol/toxicidade , Piperazinas/toxicidade , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Sulfonas/toxicidade , Analgésicos Opioides/toxicidade , Animais , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Camundongos , Morfina/toxicidade , Purinas/toxicidade , Convulsões/fisiopatologia , Citrato de Sildenafila
10.
PET Clin ; 6(4): 409-15, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27156875

RESUMO

Atherosclerotic plaque rupture is the leading cause of acute coronary syndrome. Molecular calcification represent as one of the early stages of plaque evolution has been hypothesized to play a potential role in atherosclerotic plaque instability and subsequent rupture. Several invasive and non-invasive structural imaging techniques have been utilized to diagnose atherosclerosis, but none of these methods are capable of detecting and quantifying molecular calcification. Fluorine-18-Sodium Fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) imaging allows detection and quantification of arterial molecular calcification in heart and across multiple vessels. In this review the authors discuss the feasibility, application and potential future of 18F-NaF-PET/CT in detecting molecular calcification and in defining the future risk of atherosclerotic plaque rupture in the affected vessels.

11.
PET Clin ; 6(4): 421-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27156877

RESUMO

Atherosclerosis is considered a chronic inflammatory disease, and thereafter the degree of this pathologic process is considered to be a major determinant in plaque stability and in forecasting future events. Over the past decade, (18)F-fluorodeoxyglucose PET/computed tomography has become a well-established imaging modality in evaluating various inflammatory disorders, and has been shown to be very useful in evaluating plaque activity in major arteries. This emerging noninvasive imaging modality has great potential in evaluating plaque vulnerability and in predicting the risk of future rupture and consequent thrombosis.

12.
Epilepsy Behav ; 19(4): 568-74, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20920846

RESUMO

Although morphine has an anticonvulsant effect in several animal models of seizures, its potential clinical application in epilepsy may be hindered by its adverse effects like opioid tolerance. The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice. We also examined whether administration of either lithium chloride (LiCl) or magnesium chloride (MgCl(2)) was able to prevent the probable tolerance. Our data demonstrated that the anticonvulsant effect of a potent dose of morphine (1mg/kg) was abolished in chronic morphine-treated mice (mice administered the same dose of morphine intraperitoneally twice daily for 4 days). Four days of pretreatment with low and noneffective doses of MgCl(2) (2 and 5mg/kg) and LiCl (5mg/kg) inhibited the development of tolerance to the anticonvulsant effect of morphine (1mg/kg, ip). Moreover, a single acute injection of the aforementioned agents at the same doses reversed the expression of tolerance to the anticonvulsant effects of morphine (1mg/kg, ip). Chronic 17-day treatment with LiCl (600 mg/L in drinking water) also inhibited the development of tolerance to the anticonvulsant effects of 1mg/kg morphine. These results demonstrate that the anticonvulsant effect of morphine is subject to tolerance after repeated administration. Both development and expression of tolerance are inhibited by either LiCl or MgCl(2). As both LiCl and MgCl(2) can modulate the function of N-methyl-d-aspartate (NMDA) receptors, we discuss how NMDA receptor functioning might be involved in the effects of LiCl and MgCl(2) on the development of tolerance to the anticonvulsant effect of morphine.


Assuntos
Anticonvulsivantes/uso terapêutico , Cloreto de Lítio/administração & dosagem , Cloreto de Magnésio/administração & dosagem , Morfina/uso terapêutico , Convulsões/tratamento farmacológico , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Tolerância a Medicamentos , Masculino , Camundongos , Pentilenotetrazol/efeitos adversos , Convulsões/induzido quimicamente , Fatores de Tempo
13.
Epilepsy Behav ; 18(3): 171-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20605531

RESUMO

Although lithium is still a mainstay in the treatment of bipolar disorder, its underlying mechanisms of action have not been completely elucidated. Several studies have shown that lithium can also modulate seizure susceptibility in a variety of models. In the present study, using a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice, we investigated whether there is any interaction between lithium and either calcium channel blockers (CCBs: nifedipine, verapamil, and diltiazem) or N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine and MK-801) in modulating seizure threshold. Acute lithium administration (5-100mg/kg, ip) significantly (P<0.01) increased seizure threshold. CCBs and NMDA receptor antagonists also exerted dose-dependent anticonvulsant effects on PTZ-induced seizures. Noneffective doses of CCBs (5mg/kg, ip), when combined with a noneffective dose of lithium (5mg/kg, ip), exerted significant anticonvulsant effects. Moreover, co-administration of a noneffective dose of either MK-801 (0.05mg/kg, ip) or ketamine (5mg/kg, ip) with a noneffective dose of lithium (5mg/kg, ip) significantly increased seizure threshold. Our findings demonstrate that lithium increases the clonic seizure threshold induced by PTZ in mice and interacts with either CCBs or NMDA receptor antagonists in exerting this effect, suggesting a role for Ca(2+) signaling in the anticonvulsant effects of lithium in the PTZ model of clonic seizures in mice.


Assuntos
Anticonvulsivantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Cloreto de Lítio/uso terapêutico , Convulsões/tratamento farmacológico , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Camundongos , Pentilenotetrazol , Convulsões/induzido quimicamente
14.
Epilepsy Res ; 91(1): 39-48, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20663644

RESUMO

Although morphine has anticonvulsant effect in several animal models of seizure, its potential clinical application in epilepsy may be hindered by its adverse effects like the phenomenon of opioid tolerance. The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a model of clonic seizure induced by pentylenetetrazole (PTZ) in male Swiss mice. We also examined whether N-methyl-d-aspartate (NMDA) receptor/nitrergic system blockage was able to prevent the probable tolerance. Our data demonstrated that anticonvulsant effects of a potent dose of morphine (1mg/kg) was abolished in chronic morphine-treated mice (with the same dose of morphine twice daily, 4 days, i.p.). Chronic pretreatment with low and non-effective doses of different NMDA antagonists ifenprodil (0.5mg/kg), MK-801 (0.05mg/kg) and ketamine (0.5mg/kg) as well as the non-selective nitric oxide (NO) synthase inhibitor l-NAME (2mg/kg) inhibited the development of tolerance to the anticonvulsant effect of morphine (1mg/kg). Moreover, a single acute injection of the above mentioned agents at the same doses reversed the expression of tolerance to the anticonvulsant effects of morphine (1mg/kg). These results demonstrate that anticonvulsant effect of morphine can be subject to tolerance after repeated administration. Both development and expression of tolerance are inhibited by NMDA receptor/nitrergic system blockage, suggesting a role for NMDA receptor/NO signaling in the development of tolerance to the anticonvulsant effect of morphine.


Assuntos
Anticonvulsivantes/uso terapêutico , Tolerância a Medicamentos , Morfina/uso terapêutico , Óxido Nítrico/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Convulsões/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Masculino , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Pentilenotetrazol/toxicidade , Receptores de N-Metil-D-Aspartato/fisiologia , Convulsões/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
15.
Epilepsy Behav ; 18(3): 186-92, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20493779

RESUMO

After nearly 60years, lithium is still the mainstay in the treatment of mood disorders. In addition to its antimanic and antidepressant effects, lithium also has anticonvulsant properties. Similar to lithium, agmatine plays a protective role in the central nervous system against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on the L-arginine/nitric oxide pathway. This study was designed to investigate: (1) whether agmatine and lithium exert a synergistic effect against clonic seizures induced by pentylenetetrazole and (2) whether or not this synergistic effect is mediated through inhibition of the L-arginine/nitric oxide pathway. In our study, acute administration of a single potent dose of lithium chloride (30mg/kg ip) increased seizure threshold, whereas pretreatment with a low and independently noneffective dose of agmatine (3mg/kg) potentiated a subeffective dose of lithium (10mg/kg). N(G)-L-arginine methyl ester (L-NAME, nonspecific nitric oxide synthase inhibitor) at 1 and 5mg/kg and 7-nitroindazole (7-NI, preferential neuronal nitric oxide synthase inhibitor) at 15 and 30mg/kg augmented the anticonvulsant effect of the noneffective combination of lithium (10mg/kg ip) and agmatine (1mg/kg), whereas several doses (20 and 40mg/kg) of aminoguanidine (inducible nitric oxide synthase inhibitor) failed to alter the seizure threshold of the same combination. Furthermore, pretreatment with independently noneffective doses (30 and 60mg/kg) of L-arginine (substrate for nitric oxide synthase) inhibited the potentiating effect of agmatine (3mg/kg) on lithium (10mg/kg). Our findings demonstrate that agmatine and lithium chloride have synergistic anticonvulsant properties that may be mediated through the L-arginine/nitric oxide pathway. In addition, the role of constitutive nitric oxide synthase versus inducible nitric oxide synthase is prominent in this phenomenon.


Assuntos
Agmatina/uso terapêutico , Antidepressivos/uso terapêutico , Cloreto de Lítio/uso terapêutico , Convulsões/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Análise de Variância , Animais , Arginina/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Indazóis/farmacologia , Masculino , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Pentilenotetrazol , Convulsões/induzido quimicamente , Convulsões/metabolismo
16.
Epilepsy Res ; 89(2-3): 295-302, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20304610

RESUMO

Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of lithium is mediated via NO-cGMP pathway. Injection of a single effective dose of lithium chloride (25 mg/kg) intraperitoneally (i.p.) increased significantly the seizure threshold (P<0.01). The anticonvulsant properties of the effective dose of lithium were prevented by pre-treatment with the per se non-effective doses of L-ARG [the substrate for nitric oxide synthase; NOS] (30 and 50 mg/kg) or sildenafil [a phosphodiesterase 5 inhibitor] (10 and 20 mg/kg). L-NAME [a non-specific NOS inhibitor] (5, 15 and 30 mg/kg), 7-NI [a specific neural NOS inhibitor] (30 and 60 mg/kg) or MB [a guanylyl cyclase inhibitor] (0.5 and 1 mg/kg) augmented the anticonvulsant effect of a sub-effective dose of lithium (10 mg/kg, i.p.). Whereas several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of lithium. Our findings demonstrated that nitric oxide-cyclic GMP pathway could be involved in the anticonvulsant properties of the lithium chloride. In addition, the role of constitutive NOS versus inducible NOS is prominent in this phenomenon.


Assuntos
Anticonvulsivantes/farmacologia , GMP Cíclico/metabolismo , Cloreto de Lítio/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Arginina/administração & dosagem , Arginina/farmacologia , Convulsivantes , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacocinética , Indazóis/administração & dosagem , Indazóis/farmacologia , Injeções Intraperitoneais , Cloreto de Lítio/administração & dosagem , Masculino , Azul de Metileno/administração & dosagem , Azul de Metileno/farmacologia , Camundongos , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Pentilenotetrazol , Inibidores de Fosfodiesterase/administração & dosagem , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Purinas/administração & dosagem , Purinas/farmacologia , Convulsões/induzido quimicamente , Citrato de Sildenafila , Sulfonas/administração & dosagem , Sulfonas/farmacologia , Resultado do Tratamento
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