Anti-Inflammatory and Antioxidant Effects of the Indole-Derived N-Salicyloyltryptamine on Peritonitis and Joint Disability Induced by Carrageenan in Rodents.

Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats. Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO2 -) and thiobarbituric acid reactive species (TBARS) levels were determined. Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis. Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms.

α-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain.

Medical reports indicate a prevalence of pain in 50% of patients with cancer. In this context, this article investigated the antinociceptive activity of α-PHE using in vivo Sarcoma-180-induced hypernociception in mice to detail its mechanism(s) of antinociception under different conditions of treatment and tumor progression. Firsty, in vitro cytotoxic action was assessed using melanoma B-16/F-10 and S-180 murine cells and colorimetric MTT assays. For in vivo studies, acute treatment with α-PHE (6.25, 12.5, 25 and 50 mg/kg orally by gavage) was performed on the 1st day after S-180 inoculation. Subacute treatments were performed for 8 days starting on the next day (early protocol) or on day 8 after S-180 inoculation (late protocol). For all procedures, mechanical nociceptive evaluations were carried out by von Frey's technique in the subaxillary region peritumoral tissue (direct nociception) and in right legs of S-180-bearing mice (indirect nociception). α-PHE showed in vitro cytotoxic action on B-16/F-10 and S-180 (CI50 values of 436.0 and 217.9 µg/mL), inhibition of in vivo tumor growth (ranging from 47.3 to 82.7%) and decreased direct (peritumoral tissue in subaxillary region) and indirect (right leg) mechanical nociception in Sarcoma 180-bearing mice with early and advanced tumors under acute or subacute conditions of treatment especially at doses of 25 and 50 mg/kg. It improved serum levels of GSH as well as diminished systemic lipid peroxidation, blood cytokines (interleukin-1ß, -4, -6, and tumor necrosis factor-α). Such outcomes highlight α-PHE as a promising lead compound that combines antinociceptive and antineoplasic properties. Its structural simplicity make it a cost-effective alternative, justifying further mechanistic investigations and the development of pharmaceutical formulations. Moreover, the protocols developed and standardized here make it possible to use Sarcoma-180 hypernociception model to evaluate the capacity of new antinociceptive molecules under conditions of cancer-related allodynia.

Technological development of microemulsions with perspectives for pain treatment: a patent review.

INTRODUCTION: Microemulsions are thermodynamically stable translucent systems widely used for systemic delivery of drugs. The present study is the first to analyze the biotechnological potential of microemulsion systems for therapeutic purposes, through transdermal route, for pain treatment. AREAS COVERED: Patents were searched in the World Intellectual Property Organization (WIPO), European Patent Office (Espacenet), United States Patent and Trademark Office (USPTO) and National Institute of Intellectual Property (INPI). The inclusion criteria were published patents containing the keywords; 'microemulsion' and 'transdermal' in their title or abstract. 208 patents were found. However, only those patents which mentioned in their abstract or in their description the use of microemulsion system (object of invention) for pain treatment were selected. Were excluded duplicate patents and those that did not report pharmacological use of MEs specifically for pain treatment. Thus, sixteen patents were selected and described in the present study. EXPERT OPINION: Patents were found that focused specifically on the development process of microemulsion systems, the inclusion of essential oils in microemulsions, which place microemulsions as delivery systems for NSAIDs and other substances, as well as microemulsions for transdermal administration. These studies reinforce the therapeutic applicability of MEs in the treatment of acute and chronic pain.

Effects of isopulegol in acute nociception in mice: Possible involvement of muscarinic receptors, opioid system and l-arginine/NO/cGMP pathway.

Previous studies have shown that isopulegol has anxiolytic, anticonvulsant, gastro-protective and antioxidant activities in rodents, but until now there are no studies showing activity of isopulegol in animal models of nociception and inflammation. The objective of this study was to evaluate the antinociceptive effect of isopulegol and to propose possible mechanisms involved in its effects observed in mice. Groups of male and female Swiss mice (20-35 g, n = 5-8) were used in this test under the authorization of Ethics Committee on Animal Experimentation (CEEA/UFPI N° 82/2014). In order to evaluate the antinociceptive activity of isopulegol, nociception was induced using formalin test, capsaicin and glutamate in hind paw licking model, followed by the investigation of the involvement of opioid mechanisms, K + ATP channels, muscarinic, L arginine-nitric oxide and cGMP. The oral administration of isopulegol showed antinociceptive effect in both phases of the formalin test at doses from 0.78 to 25 mg/kg (first phase) and 1.56-25 mg/kg (second phase) and also produced significant results before capsaicin test at doses from 1.56 to 12.5 mg/kg and glutamate test at doses from 3.12 to 6.25 mg/kg with a dose-dependent effect. The antinociception activity of isopulegol was inhibited in the presence of naloxone (2 mg / kg, ip), glibenclamide (3 mg/kg, ip), atropine (1 mg/kg, ip), l-arginine (600 mg/kg, ip) and methylene blue (20 mg/kg, ip). The results suggested that acute antinociceptive action of opioid isopulegol seems to be related to the K + ATP channels system, through the involvement of muscarinic receptors, inhibiting nitric oxide and cGMP.

Involvement of Cholinergic and Opioid System in γ-Terpinene-Mediated Antinociception.

The literature shows that the monoterpenes are great candidates for the development of new drugs for the treatment of various pathological processes, including painful conditions. The gamma terpinene (γ-TPN) is a monoterpene present in plant species that have multiple pharmacological properties and has structural similarity to antinociceptive monoterpenes, such as limonene and alpha-phellandrene. The γ-TPN molecular mass was evaluated by mass spectrometry and showed a pseudomolecular ion with m/z 137.0 Da. The animals did not present any signs of acute toxicity at 2 g/kg, p.o. γ-TPN (1.562 to 50 mg/kg, p.o.) showed an antinociceptive effect in the formalin, capsaicin, and glutamate tests. γ-TPN has antinociceptive action when administered by others routes in glutamate test. To eliminate a possible sedative effect of γ-TPN, the open field and rota-rod test were conducted and the γ-TPN did not show muscle relaxant activity or central depressant effect. To investigate the mechanisms of action, the animals were pretreated with naloxone, glibenclamide, atropine, mecamylamine, or L-arginine in the glutamate test. γ-TPN antinociception was inhibited in the presence of naloxone, glibenclamide, atropine, and mecamylamine. The results suggest that the γ-TPN (p.o.) produced antinociceptive effect in models of chemical nociception through the cholinergic and opioid systems involvement.

Interações fármaco-alimento/nutriente potenciais em pacientes pediátricos hospitalizados / Potential interactions between drugs and foods/nutrients in the pediatric unit

A alimentação e a administração de medicamentos são indispensáveis na rotina hospitalar, porém sua interação pode acarretar prejuízos ao estado nutricional ou ao tratamento farmacológico, principalmente em crianças, uma vez que possuem certas particularidades. Por isso, profissionais da saúde devem aumentar a atenção durante a administração de fármacos, sobretudo os enfermeiros, por estarem envolvidos diretamente nesse processo. O objetivo desse estudo foi investigar as possíveis interações entre medicamentos e alimentos/nutrientes na unidade de pediatria em um hospital piauiense. Tratou-se de um estudo descritivo, transversal, com abordagem quantitativa, realizado com 90 pacientes hospitalizados. A amostra apresentou prevalência do sexo masculino (55,6%) e uma média de idade de 62,76 meses (± 44,101). Os antimicrobianos tiveram uma frequência significativa, com 79 interações entre os medicamentos estudados, seguidos pelos corticoides com 22 ocorrências. Foram encontrados ainda, nove episódios de interações envolvendo os antiulcerosos. Entre os nutrientes, a vitamina B12 teve sua biodisponibilidade reduzida por muitos fármacos. Em suma, pode ser observado que as interações estão presentes na clínica pediátrica, e só o conhecimento pode minimizar prejuízos e/ou multiplicar os benefícios decorrentes das associações de medicamentos com alimentos. Assim, esse trabalho surge como um indicador de segurança do paciente, uma vez que identifica erros de medicação (interações entre prescrições médicas e a da equipe de nutrição).

The supply of nutritious food and proper administration of drugs are essential activities in the hospital routine, but food-drug interactions can impair the nutritional or pharmacological treatment, especially in children, since they have certain peculiarities. Therefore, health professionals, especially nurses, who are directly involved in patient treatment, should increase attention during the administration of drugs. The aim of this study was to investigate the possible interactions between medicines and foods or nutrients in the pediatric unit of a hospital in Piauí. This was a descriptive, cross-sectional quantitative study of 90 hospitalized patients. The sample had a prevalence of males (55.6%) and a mean age of 62.76 months (+ 44.10). Antimicrobials had a significant frequency of interactions, with a total of 79 among the drugs studied, followed by corticosteroids with 22 occurrences. There were also nine episodes of interactions involving antiulcer drugs. Among the nutrients, vitamin B12 was reduced in bioavailability by many drugs. In short, it can be reported that interactions are present in the pediatric clinic, and only by being aware of them can we minimize losses and / or multiply the benefits of drug-food combinations. Thus, this study can serve as an indicator of patient safety, since it identifies medication errors (due to interactions between prescriptions and diet plans).

Identificação e análise dos fatores antinutricionais nas possíveis interações entre medicamentos e alimento/nutrientes em pacientes hospitalizados / Identification and analysis of antinutritional factors in possible interactions between medications and food/nutrients in hospitalized patients

Objective: To identify and analyze the presence of antinutritional factors in possible interactions between medications and foods/nutrients of the diets prescribed for patients of the Hospital Regional Justino Luz, in the city of Picos (PI) in order to suggest their likely mechanisms. Methods: The sample was made up of 120 medical records of hospitalized patients. The charts were analyzed to verify the presence or absence of interactions between medications and foods/nutrients of the diets prescribed to the patients at the Hospital Regional Justino Luz, emphasizing the action of antinutritional factors in these interactions. Results: Of the 189 medications prescribed, 128 (67.7%) had a possible interaction with food, totaling up 98 possible interactions between nutrients/foods and medications. Therefore, 20 (20.4%), 12 (12.2%) and 11 (11.2%) possible interactions were identified with captopril, acetylsalicylic acid and spironolactone, respectively, representing, in this order, the greatest frequencies of possible interactions among drugs and foods. A total of nine antinutritional factors were found in seven vegetable foods prescribed to inpatients, in which five (55.6%) were capable of interacting with the medications. Phytates and tannins had the largest quantity of possible interactions with drugs, each with 4 (26.7%) in a total of 15 interactions. The medications aluminum hydroxide, digoxin, and paracetamol attained greater probability of interaction with antinutrients, with 5 (33.3%), 3 (20%) and 3 (20%) interactions, respectively. Conclusion: Due to the large quantity of antinutritional factors capable of interacting with drugs prescribed for inpatients, the involvement of a multiprofessional team is indispensable so that these possible interactions between foods, antinutritional factors and drugs might be foreseen, detected, and resolved.

Identification and analysis of antinutritional factors in possible interactions between medications and food/nutrients in hospitalized patients.

OBJECTIVE: To identify and analyze the presence of antinutritional factors in possible interactions between medications and foods/ nutrients of the diets prescribed for patients of the Hospital Regional Justino Luz, in the city of Picos (PI) in order to suggest their likely mechanisms. METHODS: The sample was made up of 120 medical records of hospitalized patients. The charts were analyzed to verify the presence or absence of interactions between medications and foods/nutrients of the diets prescribed to the patients at the Hospital Regional Justino Luz, emphasizing the action of antinutritional factors in these interactions. RESULTS: Of the 189 medications prescribed, 128 (67.7%) had a possible interaction with food, totaling up 98 possible interactions between nutrients/foods and medications. Therefore, 20 (20.4%), 12 (12.2%) and 11 (11.2%) possible interactions were identified with captopril, acetylsalicylic acid and spironolactone, respectively, representing, in this order, the greatest frequencies of possible interactions among drugs and foods. A total of nine antinutritional factors were found in seven vegetable foods prescribed to inpatients, in which five (55.6%) were capable of interacting with the medications. Phytates and tannins had the largest quantity of possible interactions with drugs, each with 4 (26.7%) in a total of 15 interactions. The medications aluminum hydroxide, digoxin, and paracetamol attained greater probability of interaction with antinutrients, with 5 (33.3%), 3 (20%) and 3 (20%) interactions, respectively. CONCLUSION: Due to the large quantity of antinutritional factors capable of interacting with drugs prescribed for inpatients, the involvement of a multiprofessional team is indispensable so that these possible interactions between foods, antinutritional factors and drugs might be foreseen, detected, and resolved.

Analysis of possible food/nutrient and drug interactions in hospitalized patients / Análise das possíveis interações entre medicamentos e alimento/nutrientes em pacientes hospitalizados

Objective: To evaluate the prescription in relation to the possible interactions between drugs and foods/nutrients of the diets of patients in the Hospital Regional Justino Luz in the municipality of Picos, Piauí, Brazil. Methods: The sample consisted of 60 medical records of patients admitted at the hospital. The records were analyzed according to the presence or absence of interactions between drugs and foods/nutrients of the prescribed diets. Results: Of the 82 drugs prescribed in all periods, there were 16 drugs (19.5%) with possible interaction with food, a total of 60 interactions between nutrient/food and medicine. Thus, 18 (30%), 10 (17%) and 8 (13%) possible interactions were identified with captopril (cardiovascular drug) with acetylsalicylic acid (anti-inflammatory) and spironolactone (diuretic), respectively representing the highest numbers of interactions among the classes of investigated drugs. It was also found that the total interactions between food/nutrients and drugs, 32 (53%) accounted for interactions with cardiovascular drugs, 13 (22%) with anti-inflammatory drugs, 11 (18%) with diuretic agents e 4 (7%) with drugs that act on the digestive tract. Conclusion: There was a high number of interactions between food/nutrients and medicines emphasizing the need for prior knowledge of these interactions as a way to avoid impairment in the treatment, longer hospital stays and/or damage to the nutritional status of the patients.

Objetivos: Avaliar as possíveis interações entre os medicamentos e os alimentos/nutrientes das dietas de pacientes do Hospital Regional Justino Luz do município de Picos, Piauí. Métodos: A amostra foi constituída por 60 prontuários médicos de pacientes internados analisados para verificar a presença ou não de interações entre os medicamentos e os alimentos/nutrientes das dietas prescritas. Resultados: Dos 82 medicamentos prescritos, em todos os períodos, havia 16 (19,5%) com possível interação com a alimentação, totalizando 60 interações entre nutriente/alimentos e medicamentos. Assim, foram identificadas 18 (30%), 10 (17%) e 8 (13%) possíveis interações com o captopril (droga cardiovascular), com o ácido acetilsalicílico (anti-inflamatório) e com a espironolactona (diurético), respectivamente, representando as maiores frequências de interações entre as classes farmacológicas investigadas. Detectou-se também que, do total das interações entre alimentos/nutrientes e medicamentos, 32 (53%) corresponderam a interações com drogas cardiovasculares; 13 (22%) com fármacos anti-inflamatórios, 11 (18%) com agentes diuréticos e 4 (7%) com fármacos que atuam sobre o trato digestório. Conclusão: Verificou-se um alto número de interações entre alimentos/nutrientes e medicamentos, reforçando a necessidade do conhecimento prévio dessas interações para que não haja prejuízo no tratamento, aumento do tempo de internação e/ou danos ao estado nutricional dos pacientes.

Analysis of possible food/nutrient and drug interactions in hospitalized patients.

OBJECTIVE: To evaluate the prescription in relation to the possible interactions between drugs and foods/nutrients in the diets of patients in the Hospital Regional Justino Luz in the municipality of Picos, Piauí, Brazil. METHODS: The sample consisted of 60 medical records of patients admitted at the hospital. The records were analyzed according to the presence or absence of interactions between drugs and foods/nutrients of the prescribed diets. RESULTS: Of the 82 drugs prescribed in all periods, there were 16 drugs (19.5%) with possible interaction with food, a total of 60 interactions between nutrient/food and medicine. Thus, 18 (30%), 10 (17%) and 8 (13%) possible interactions were identified with captopril (cardiovascular drug) with acetylsalicylic acid (anti-inflammatory) and spironolactone (diuretic), respectively representing the highest numbers of interactions among the classes of investigated drugs. It was also found that the total interactions between food/nutrients and drugs, 32 (53%) accounted for interactions with cardiovascular drugs, 13 (22%) with anti-inflammatory drugs, 11 (18%) with diuretic agents e 4 (7%) with drugs that act on the digestive tract. CONCLUSION: There was a high number of interactions between food/nutrients and medicines emphasizing the need for prior knowledge of these interactions as a way to avoid impairment in the treatment, longer hospital stays and/or damage to the nutritional status of the patients.