Cytotoxic effects of Chartergellus communis wasp venom peptide against melanoma cells.

Cancer is a huge public health problem being one of the main causes of death globally. Specifically, melanoma is one of the most threatening cancer types due to the metastatic capacity, treatment resistance and mortality rates. It is evident the urgent need for research on new agents with pharmacological potential for cancer treatment, in order to develop new cancer therapeutic strategies and overcome drug resistance. The present work investigated the anti-tumoral potential of Chartergellus-CP1 peptide, isolated from Chartergellus communis wasp venom on human melanoma cell lines with different pigmentation degrees, namely the amelanotic cell line A375 and pigmented cell line MNT-1. Chartergellus-CP1 induced selective cytotoxicity to melanoma cell lines when compared to the lower induced cytotoxicity towards to nontumorigenic keratinocytes. Chartergellus-CP1 peptide induced apoptosis in both melanoma cell lines, cell cycle impairment in amelanotic A375 cells and intracellular ROS increase in pigmented MNT-1 cells. The amelanotic A375 cell line showed higher sensitivity to the peptide than the pigmented cell line MNT-1. From our knowledge, this is the first study reporting the cytotoxic effects of Chartergellus-CP1 on melanoma cells.

Is Shoulder Imbalance a Useful Parameter in the Screening of Idiopathic Scoliosis? A Preliminary Study.

Objective The present study aims to analyze the use of shoulder imbalance as a parameter for scoliosis screening as well as its relationship with other parameters of physical examination. Methods This study assesses a smartphone application that analyzes several parameters of the physical examination in adolescent idiopathic scoliosis. Medical and non-medical examiners applied the screening tool in students in a public school and in a private sports club. After data collection, interobserver correlation was done to verify shoulder imbalance and to compare shoulder imbalance with Adam's bending test and with trunk rotation. Results Eighty-nine participants were examined, 18 of whom were women and 71 of whom were men. Two subjects were excluded from the analysis. The mean age of subjects from the public school was 11.30 years and, for those from the sports club, it was 11.92 years. The examiners had poor-to-slight interobserver concordance on shoulder asymmetry in the anterior and posterior view. No significant statistical correlation was found between shoulder asymmetry and positive Adam's forward bending test. Conclusion Our preliminary study shows that the shoulder asymmetry has a poor correlation with the Adam's forward bending test and measuring trunk rotation using a scoliometer. Therefore, the use of shoulder imbalance might not be useful for idiopathic scoliosis screening. Level of Evidence III; Diagnostic Study.

Is Shoulder Imbalance a Useful Parameter in the Screening of Idiopathic Scoliosis? A Preliminary Study / O desequilíbrio do ombro é um parâmetro útil na triagem da escoliose idiopática? Um estudo preliminar

Abstract Objective The present study aims to analyze the use of shoulder imbalance as a parameter for scoliosis screening as well as its relationship with other parameters of physical examination. Methods This study assesses a smartphone application that analyzes several parameters of the physical examination in adolescent idiopathic scoliosis. Medical and non-medical examiners applied the screening tool in students in a public school and in a private sports club. After data collection, interobserver correlation was done to verify shoulder imbalance and to compare shoulder imbalance with Adam's bending test and with trunk rotation. Results Eighty-nine participants were examined, 18 of whom were women and 71 of whom were men. Two subjects were excluded from the analysis. The mean age of subjects from the public school was 11.30 years and, for those from the sports club, it was 11.92 years. The examiners had poor-to-slight interobserver concordance on shoulder asymmetry in the anterior and posterior view. No significant statistical correlation was found between shoulder asymmetry and positive Adam's forward bending test. Conclusion Our preliminary study shows that the shoulder asymmetry has a poor correlation with the Adam's forward bending test and measuring trunk rotation using a scoliometer. Therefore, the use of shoulder imbalance might not be useful for idiopathic scoliosis screening. Level of Evidence III; Diagnostic Study

Resumo Objetivo O objetivo deste estudo é analisar o uso da assimetria de ombros como parâmetro para a triagem de escoliose e sua relação a outros parâmetros do exame físico. Métodos Este estudo avalia um aplicativo para smartphone que analisa diversos parâmetros do exame físico de adolescentes com escoliose idiopática. Examinadores médicos e não médicos utilizaram o instrumento de triagem em alunos de uma escola pública e de um clube esportivo privado. Após a coleta de dados, a correlação interobservador foi determinada para verificar a assimetria de ombros e compará-la ao teste de inclinação de Adam e à medição da rotação do tronco. Resultados Oitenta e nove participantes foram examinados, sendo 18 do sexo feminino e 71 do sexo masculino. Dois indivíduos foram excluídos da análise. A média de idade dos participantes da escola pública foi de 11,30 anos e do clube esportivo, 11,92 anos. Os examinadores apresentaram concordância interobservador baixa a branda quanto à assimetria de ombros em incidência anterior e posterior. Não houve correlação estatística significativa entre a assimetria de ombros e o resultado positivo no teste de inclinação do tronco de Adam. Conclusão Nosso estudo preliminar mostra que a assimetria de ombros tem baixa correlação com o teste de inclinação de Adam e assim como com a medição de rotação do tronco com escoliômetro. Portanto, o uso da assimetria de ombros pode não ser útil na triagem da escoliose idiopática. Nível de Evidência III; Estudo Diagnóstico

Clinical characteristics and laboratory parameters associated with the risk of severe COVID-19 in patients from two hospitals in Northeast Brazil.

BACKGROUND: Although most coronavirus disease 2019 (COVID-19) infections are mild, some patients have severe clinical conditions requiring hospitalization. Data on the severity of COVID-19 in Brazil are scarce and are limited to public databases. This study aimed to investigate the clinical and laboratory factors associated with the severity of COVID-19 in a cohort of hospitalized adults from two hospitals in Northeast Brazil. METHODS: Patients over 18 years of age who were hospitalized between August 2020 and July 2021 with a confirmed diagnosis of COVID-19 were included. The patients were classified into two groups: moderate and severe. Clinical, laboratory and imaging parameters were collected and compared between the groups. A multivariate logistic regression model was used to determine the predictors of COVID-19 severity. RESULTS: This study included 495 patients (253 moderate and 242 severe). A total of 372 patients (75.2%) were between 18 and 65 years of age, and the majority were male (60.6%; n = 300). Patients with severe disease had higher levels of leukocytes, neutrophils, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, blood glucose, C-reactive protein, ferritin, D-dimer, aspartate aminotransferase, creatinine, and urea (p < 0.05). In multivariate logistic regression, the following variables were significant predictors of COVID-19 severity: leukocytes (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.12-5.06), international normalized ratio (INR) (OR 0.22, 95% CI 0.14-0.33), and urea (OR 4.03; 95% CI 2.21-7.35). CONCLUSIONS: The present study identified the clinical and laboratory factors associated with the severity of COVID-19 in hospitalized Brazilian individuals.

Antitumoral potential of Chartergellus-CP1 peptide from Chartergellus communis wasp venom in two different breast cancer cell lines (HR+ and triple-negative).

Breast cancer represents the most incident cancer in women. Surgery, chemotherapy, radiation therapy, and hormone therapy remain the main treatment for this type of cancer. However, increasing resistance to anti-cancer drugs through poor response for some types of breast cancer to treatments highlights the need to develop new therapeutic agents to fight the disease. In this study, we evaluated the anti-tumor potential of the Chartergellus-CP1 peptide isolated from the wasp venom of Chartergellus communis in human breast cancer cell lines MCF-7 (HR+) and MDA-MB-231 (triple-negative). Cells viability, morphology, cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis were assessed for both cell lines after exposure to Chartergellus-CP1 during 24 and 48 h. The results showed that Chartergellus-CP1 led to a significant increase of cells in the S phase in addition to a high generation of ROS (being more evident in the MCF-7 cell line) associated with apoptotic cell death. This work demonstrates, for the first time, the cytotoxic effects of Chatergellus-CP1 on human breast cancer cell lines including cell cycle profile, oxidative stress generation, and cell death mechanisms.

Clinical characteristics and laboratory parameters associated with the risk of severe COVID-19 in patients from two hospitals in Northeast Brazil

ABSTRACT Background: Although most coronavirus disease 2019 (COVID-19) infections are mild, some patients have severe clinical conditions requiring hospitalization. Data on the severity of COVID-19 in Brazil are scarce and are limited to public databases. This study aimed to investigate the clinical and laboratory factors associated with the severity of COVID-19 in a cohort of hospitalized adults from two hospitals in Northeast Brazil. Methods: Patients over 18 years of age who were hospitalized between August 2020 and July 2021 with a confirmed diagnosis of COVID-19 were included. The patients were classified into two groups: moderate and severe. Clinical, laboratory and imaging parameters were collected and compared between the groups. A multivariate logistic regression model was used to determine the predictors of COVID-19 severity. Results: This study included 495 patients (253 moderate and 242 severe). A total of 372 patients (75.2%) were between 18 and 65 years of age, and the majority were male (60.6%; n = 300). Patients with severe disease had higher levels of leukocytes, neutrophils, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, blood glucose, C-reactive protein, ferritin, D-dimer, aspartate aminotransferase, creatinine, and urea (p < 0.05). In multivariate logistic regression, the following variables were significant predictors of COVID-19 severity: leukocytes (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.12-5.06), international normalized ratio (INR) (OR 0.22, 95% CI 0.14-0.33), and urea (OR 4.03; 95% CI 2.21-7.35). Conclusions: The present study identified the clinical and laboratory factors associated with the severity of COVID-19 in hospitalized Brazilian individuals.

Antiseizure potential of peptides from the venom of social wasp Chartergellus communis against chemically-induced seizures.

Epilepsy is one of the most common neurological diseases in the world. The objective of this research was to investigate a new peptide from the venom of the social wasp Chartergellus communis useful to the study or pharmacotherapy of epilepsy. The wasps were collected, and their venom was extracted. Afterward, the steps of fractionation, sequencing, and identification were carried out to obtain four peptides. These molecules were synthesized for behavioral evaluation tests and electroencephalographic assays to determine their antiseizure potential (induction of acute seizures using the chemical compounds, pentylenetetrazole - PTZ, and pilocarpine - PILO) and analysis of neuropharmacological profile (general spontaneous activity and alteration in motor coordination). Chartergellus-CP1 (i.c.v. - 3.0 µg/animal) caused beneficial alterations in some of the parameters evaluated in both models: PTZ (latency and duration of maximum seizures) and PILO (latency and duration of, and protection against, maximum seizures, and reduction of the median of the seizure scores. When evaluated in 3 doses in the seizure model induced by PILO, the dose of 3.0 µg/animal protected the animals against seizures, with an estimated ED50 of 1.49 µg/animal. Electroencephalographic evaluation of Chartergellus-CP1 showed an improvement in latency, quantity, and percentage of protection against generalized electroencephalographic seizures in the PILO model. Further, Chartergellus-CP1 did not cause adverse effects on general spontaneous activity and motor coordination of animals. This study demonstrated how compounds isolated from wasps' venom may be important resources in the search for new drugs. Such compounds can be considered valuable therapeutic and biotechnological tools for the study and future treatment of epileptic disorders. In this context, a peptide that is potentially useful for epilepsy pharmacotherapy was identified in the venom of C. communis.

Animal venoms: therapeutic tools for tackling Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation. With long-term use, conventional treatments can become inefficient, often triggering possible side effects. Considering these drawbacks, drug discovery constantly turns to nature as a source of efficient therapeutics. Thus, this review explores animal venoms as a rich source of bioactive compounds with potent neuropharmacological profiles for the development of effective adjuvant treatments with fewer side effects, ultimately aiming for the neuroprotection of dopaminergic neurons and the symptomatic relief of PD.

Characterization of two peptides isolated from the venom of social wasp Chartergellus communis (Hymenoptera: Vespidae): Influence of multiple alanine residues and C-terminal amidation on biological effects.

Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified: Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH2 (1836.3Da). Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC50=142.6µM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) induced hyperalgesia in mice. On the other hand, Communis (10nmol/animal) was able to induce edema but did not present hemolytic or hyperalgesic activity. Although both peptides have similarities in linear structures, we demonstrated the distinct biological effects of Communis and Communis-AAAA. This is the first study with Chartegellus communis venom, and both Communis and Communis-AAAA are unpublished peptides.

Agronomic performance of castor under different growing conditions / Desempenho agronômico de mamona sob diferentes condições de cultivo

Castor has emerged as an oilseed species capable of meeting the demand of the Brazilian market. Thus, there is a need for studies to evaluate the different growing conditions that this species can be cultivated in order to subsidize their production. The study aimed to evaluate the influence of different growing conditions on agronomic performance of seven castor bean cultivars grown in Savanna-Pantanal ecotone region. The trial was conducted at Universidade Estadual de Mato Grosso do Sul, Aquidauana Campus. Treatments consisted of seven castor bean cultivars (BRS Energia, IAC-2028, IAC-Guarani, BRS Nordestina, BRS Paraguaçu, IAC-80 and IAC-226) and three growing conditions (with weed control and without topdress nitrogen; with topdress nitrogen at 80 kg ha-1 and with weed control; without weed control and absence of topdress nitrogen) in two agricultural years (2011 and 2012), arranged in randomized block design with three replications in factorial arrangement (7 x 3 x 2). The following variables were evaluated: plant height, stem diameter, number of bunches, number of fruits and fruit yield. The cultivars BRS Energia, IAC 2028, IAC Guarani and BRS Paraguaçu obtained greater fruit yield. Topdress nitrogen and weed control provided to cultivars the highest stem diameter, number of bunches, number of fruits and fruit yield.

A mamona vem se destacando como uma espécie oleaginosa capaz de suprir a demanda do mercado brasileiro. Desta forma, existe a necessidade de pesquisas que avaliem as diferentes condições de cultivo que esta espécie possa ser cultivada, a fim de subsidiar sua produção. O objetivo do trabalho foi avaliar a influência de diferentes condições no desempenho agronômico de cultivares de mamona cultivada na região do ecótono Cerrado-Pantanal. O experimento foi conduzido na Universidade Estadual de Mato Grosso do Sul, Campus de Aquidauana. Os tratamentos consistiram de sete cultivares de mamona (BRS Energia, IAC-2028, IAC-Guarani, BRS Nordestina, BRS Paraguaçu, IAC-80 e IAC-226) e três condições de cultivo (com controle de plantas daninhas e sem adubação de cobertura com N; com adubação de 80 kg ha-1 de N e controle de plantas daninhas; sem controle das plantas daninhas e ausência de adubação de cobertura com N) em dois anos agrícolas (2011 and 2012), dispostos em delineamento de blocos ao acaso com três repetições, em esquema fatorial (7 x 3 x 2). Foram avaliadas as seguintes variáveis: altura de plantas, diâmetro do caule, número de cachos, número de frutos e produtividade de frutos. As cultivares BRS Energia, IAC 2028, IAC Guarani e BRS Paraguaçu obtiveram maior produtividade de frutos. A adubação nitrogenada em cobertura e o controle de plantas daninhas proporcionaram às cultivares maior diâmetro do colmo, número de cachos, número de frutos e produtividade de frutos.

Correlations and path analysis on oil content of castor genotypes / Correlações e análise de trilha sobre o teor de óleo de genótipos de mamona

With the aim of to evaluate the correlation and the direct and indirect effects of morphological descriptors on oil content of castor (Ricinus communis L.) genotypes, an experiment was conducted in the agricultural years 2010/2011 and 2011/2012 at Universidade Estadual de Mato Grosso do Sul ­ Unit of Aquidauana (UEMS/UUA). The experimental design used was randomized blocks with three replications. The treatments consisted of seven castor genotypes (BRS Energia, IAC-2028, IAC-Guarani, BRS Nordestina, BRS Paraguaçu, IAC-80 and IAC-226). The following descriptors were evaluated: plant height (PH), stem diameter (SD), number of bunches (NB), number of fruits (NF), mass of fruits (MF), mass of hundred seeds (MHS) and oil content (OC). Initially, it was determined the following genetic parameters: genotypic variance, environmental variance, coefficient of experimental variation, coefficient of genotypic variation, heritability, environmental correlations, phenotypic correlations and genetic correlations. The phenotypic correlations were deployed by path analysis in estimates of direct and indirect effects, and preceded the diagnosis of multicollinearity in explanatory variables and independent explanatory variables on the OC (primary dependent variable). The results indicated that the direct and indirect selection of genotypes with plant height, stem diameter, number of bunches and mass of hundred seeds is promising to select genotypes with high oil content in castor.

Com o objetivo de avaliar a correlação e os efeitos diretos e indiretos de caracteres morfológicos sobre o teor de óleo de genótipos de mamona (Ricinus communis L.), um experimento foi conduzido nos anos agrícolas 2010/2011 e 2011/2012 na Universidade Estadual de Mato Grosso do Sul, Unidade Universitária de Aquidauana (UEMS/UUA). O delineamento experimental utilizado foi o de blocos casualizados com três repetições. Os tratamentos consistiram de sete genótipos de mamona (BRS Energia, IAC-2028, IAC-Guarani, BRS Nordestina, BRS Paraguaçu, IAC-80 e IAC-226). Foram avaliados os descritores: altura da planta (PH), diâmetro do colmo (SD), número de cachos (NB), número de frutos (NF), massa de frutos (MF), massa de cem sementes (MHS) and teor de óleo (OC). Inicialmente foram determinados os seguintes parâmetros genéticos: variância genotípica, variância ambiental, coeficiente de variância experimental, coeficiente de variação genotípica, herdabilidade, correlações ambientais, correlações fenotípicas e correlações genotípicas. As correlações fenotípicas foram desdobradas pela análise de trilha em estimativas de efeitos diretos e indiretos, e procedeu-se ao diagnóstico da multicolinearidade das variáveis independentes explicativas sobre o OC (variável dependente principal). Os resultados indicam que a seleção direta e indireta de genótipos com altura da planta, diâmetro do colmo, número de cachos e massa de cem sementes são promissoras para se selecionar genótipos com maior teor de óleo em mamona.

Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools.

Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders.

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.(AU)

Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.

The effects of the Brazilian ant Dinoponera quadriceps venom on chemically induced seizure models.

Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5mg/kg) increased the time until the first seizure and the percentage of survival (155.4±27.7s/12.5%, p<0.05) compared to the control group (79.75±3.97s/0%), whereas endovenous treatment (0.1 and 0.5mg/kg) decreased the time until the first seizure (0.1mg/kg: 77.83±5.3s versus 101.0±3.3s in the control group; 0.5mg/kg: 74.43±3.9s versus 101.0±3.3s for the control group, p<0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the D. quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.

Involvement of the nitric oxide/cyclic guanylate monophosphate pathway in the pilocarpine-induced seizure model in mice.

The present study was designed to investigate the involvement of the nitric oxide (NO)/cyclic guanylate monophosphate pathway in pilocarpine-induced seizures in mice. Male Swiss mice (26-32 g) were used as the in vivo model. The following pharmacological tools were utilized: the non-selective NO synthase (NOS) inhibitor L-NAME (10 mg/kg, i.p.), a preferential inducible NOS (iNOS) inhibitor aminoguanidine (25 mg/kg, i.p.), a highly specific iNOS inhibitor 1400W (2.5 mg/kg, i.p.), the NO donor L-arginine (150 mg/kg, i.p.), and the soluble guanylyl cyclase inhibitor ODQ (10 mg/kg, i.p.). The animals were divided into groups (n = 8) and pretreated for 30 min before receiving pilocarpine (400 mg/kg, i.p.), while the control group received only pilocarpine. They were observed for 60 min to measure initial seizure latency, latency till death, and mortality. An administration of L-NAME or ODQ delayed the onset of initial seizure, increased latency till death, and produced a 25% survival rate. Aminoguanidine increased the initial seizure and latency until death, and administration of 1400W did not have an effect. Incremental increases of NO by L-arginine were capable of decreasing the seizure and death latency. These results support the idea that the constitutive NOS, probably neuronal NOS, followed by soluble guanylyl cyclase activation is involved in the convulsive responses caused by pilocarpine administration.