Arthrospira (Spirulina) platensis Attenuates Dextran Sulfate Sodium-induced Colitis in Mice by Suppressing Key Pro-inflammatory Cytokines.

Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions: SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.

The Wound Healing Property of N-Methyl-(2S,4R)-trans-4-Hydroxy-L-Proline from Sideroxylon obtusifolium is Related to its Anti-Inflammatory and Antioxidant Actions.

Wound healing involves the interaction of blood cells, proteins, proteases, growth factors, and extracellular matrix components. Inflammation is one of the first events occurring during this process. Previously, we showed that the N-Methyl-(2S,4R)-trans-4-Hydroxy-L-Proline (NMP) from Sideroxylon obtusifolium leaves (a Brazilian medicinal species) presents an anti-inflammatory action. Considering inflammation as an important event in the wound healing process, the objectives were to investigate the topical effects of the NMP gel on a mice wound-induced model. Male Swiss mice were divided into 4 groups: Sham (surgical procedure only), Control (gel-base treated), and 3% or 10% NMP gel-treated groups. Measurements of wound areas and microscopic analyses (HE [hematoxylin-eosin] and PSR [picrosirius red] stainings) were carried out, at the 7th and 12th, days after the wound induction. Furthermore, immunohistochemical assays for iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) and biochemical measurements for TBARS (thiobarbituric acid reactive substances), GSH (glutathione), and myeloperoxidase (MPO) were also performed, at the second day after the wound induction. The work showed that NMP decreases the wound areas, after topical application, relatively to the Sham and Control groups. In addition, microscopic alterations were reduced and collagen deposition was increased, at the 7th and 12th days, in the 10% NMP group. While iNOS and COX-2 immunostainings and GSH contents increased, in relation to the Sham and Control groups, TBARS and MPO decreased. Altogether, the results showed NMP to improve the wound healing process, by upregulating iNOS and COX-2 activities, reducing lipid peroxidation and MPO activity, and increasing GSH contents. In addition, NMP certainly contributes to the increased collagen deposition. These data may stimulate translational studies dealing with the possible use of NMP from Sideroxylon obtusifolium or from other sources for the management of wound healing.

Himatanthus drasticus: a chemical and pharmacological review of this medicinal species, commonly found in the Brazilian Northeastern region

ABSTRACT In order to compile the empirical use, as well as the chemical, pharmacological and biological aspects of Himatanthus drasticus (Mart.) Plumel, Apocynaceae, a review was carried out by searching PubMed, Google Scholar, Scientific Electronic Online Library, Web of Science, Science Direct, Scopus and Cochrane. For that, works in English, Spanish and Portuguese, preclinical studies and revisions, addressing chemical, pharmacological, biological properties and popular uses, from 1994 to 2017, were used. The therapeutic potential of the "milk-of-janaguba" (a mixture of the latex with water) became widely known for the treatment of neoplasias, mainly lung and lymphatic cancer types, in the 1970s. The available literature presents works related to the anti-inflammatory, antinociceptive, antitumor and gastroprotective properties of the latex from bark and leaves of H. drasticus. In addition, this review presents some of our own results with the triterpene-rich fraction from H. drasticus, attempting to clarify its action mechanisms at the molecular level. The antinociceptive and anti-inflammatory activities of H. drasticus are probably associated with inhibitions of inflammatory mediators, as TNF-alpha, iNOS, COX-2 and NF-kB. Most importantly, a triterpene-rich fraction also inhibited HDAC activity, and compounds with this activity have been considered as therapeutic agents with antitumor activity. In conclusion, although the literature shows several works on species of the Himatanthus genus, including H. drasticus, dealing with some bioactive compounds as triterpenes, translational studies focusing upon the clinical uses of this medicinal species are still in great need.

Justicia pectoralis, a coumarin medicinal plant have potential for the development of antiasthmatic drugs?

ABSTRACT Justicia pectoralis Jacq., Acanthaceae, is a medicinal plant found Central America. In the Northeast of Brazil, it is popularly known as "chambá" being extensively used in homemade preparations for the treatment of cough, bronchitis and asthma. The species is part of a public phytotherapy program in Brazil entitled "Farmácias Vivas", National Record of Plants of Interest to the National Health System and the National Formulary of Herbal medicines. This paper aims to critically review the available scientific literature regarding the health promoting effects of J. pectoralis var. stenophylla. The traditional uses, phytochemistry, pharmacological activities, toxicology, quality control and potential interactions with conventional drugs were included in the present review. Botanical, chemical and pharmacognostical studies stablished several parameters useful for quality control of plant drug, extracts and phytomedicine from aerial parts of J. pectoralis using as markers two bioactive coumarins. A wide range of evidence have demonstrated the anti-inflammatory, anti-nociceptive, anti-spasmodic, smooth muscle relaxant and anxiolytic effects of J. pectoralis and its chemical constituents. Pilot clinical studies showed the efficacy of a syrup preparation of J. pectoralis in the treatment of mild and moderate asthma. The pharmacological potential make these medicinal plants good candidates for the development of new phytomedicine for the treatment of asthma. However, a strong collaboration to bridge the gap between preclinical and clinical study is still necessary for the development of an effective medicine from J. pectoralis.

The anti-inflammatory effects of N-methyl-(2S,4R)-trans-4-hydroxy-l-proline from Syderoxylon obtusifolium are related to its inhibition of TNF-alpha and inflammatory enzymes.

BACKGROUND: Sideroxylon obtusifolium (Roem. & Schult.) T.D. Penn., Sapotaceae family, is a medicinal species native to the Brazilian Northeastern region. The plant is popularly used as an anti-inflammatory and hypoglycemic. PURPOSE: To evaluate the anti-inflammatory properties of the N-methyl-(2S,4R)-trans-4-hydroxy-l-proline (NMP) from S. obtusifolium leaves in models of inflammation and to clarify its action mechanisms. METHODS: Male Swiss mice were distributed intocontrols and groups treated with NMP (25, 50 and 100mg/kg, p.o.), indomethacin or morphine (reference drugs). The animals were subjected to the formalin, carrageenan-induced edema and peritonitis tests. Furthermore, peritoneal lavage and slices from edematous paws were used for histological and immunohistochemical (iNOS, TNF-alpha, COX-2 and NF-kB) assays. RESULTS: Decreases in licking time, in the 1st and mainly in the 2nd phases of the formalin test, were shown after NMP treatments. In addition, decreases (around 50%) in paw edema were noticed at the 3rd h. The HE staining of paw slices demonstrated a complete reversion of the increased PMN cell numberafter NMP treatment. Similarly, decreases higher than 70% were also demonstrated in PMN cells, in the peritoneal fluid. Furthermore, NMP significantly decreased iNOS, TNF-alpha, COX-2 and NF-kB immunoreactivities. CONCLUSIONS: We showed that S. obtusifolium presents a potent anti-inflammatory activity, due to the presence of the N-methyl-(2S,4R)-trans-4-hydroxy-l-proline(NMP) in the plant extract. This action is related to the inhibition by NMP of TNF-alpha and inflammatory enzymes.

Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson's Disease.

Pentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson's disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO), untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg) groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations), histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS) studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT) were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD.

Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson's Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties.

Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson's disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were observed not only in the CA1 and CA3 subfields of the hippocampus, but also in the temporal cortex. In conclusion, we showed that VA partly reversed the behavioral, neurochemical, histological, and immunohistochemical alterations observed in the untreated 6-OHDA-lesioned animals. These effects are probably related to the drug anti-inflammatory activity and strongly suggest that VA is a potential candidate to be included in translational studies for the treatment of neurodegenerative diseases as PD.

Antinociceptive Effect of the Essential Oil Obtained from the Leaves of Croton cordiifolius Baill. (Euphorbiaceae) in Mice.

Croton cordiifolius Baill. is a shrub known as "quebra-faca" and is used to treat inflammation, pain, wounds, and gastrointestinal disturbances in the semiarid region in the northeast of Brazil. In an ethnobotanical survey in the state of Pernambuco, "quebra-faca" use was cited in 33% of the interviews. Thus, we decided to evaluate the antinociceptive effects of the essential oil from C. cordiifolius (CcEO). Chemical analysis by gas chromatography-mass spectrometry revealed 1,8-cineole (25.09%) and α-phellandrene (15.43%) as major constituents. Antinociceptive activity was evaluated using murine models of chemically induced pain (writhing induced by acetic acid, formalin, capsaicin, and glutamate tests). Opioid and central nervous systems (CNS) involvement were also investigated. Regarding antinociceptive activity, CcEO (50 and 100 mg/kg) reduced the number of writhing responses induced by acetic acid and decreased the licking times in both phases of the formalin test. CcEO also was evaluated in capsaicin- and glutamate-induced nociception. While no effect was observed in the capsaicin test, CcEO (100 mg/kg) was effective in the glutamate test. Naloxone, an opioid antagonist, did not affect the antinociceptive activity of CcEO in writhing test. In conclusion, the antinociceptive effect of CcEO could be explained, at least in part, by inhibition of the glutamatergic system.

Avaliação da saúde bucal de crianças de escolas públicas, em cidade do Nordeste do Brasil / Oral health evaluation of children from public schools in a city of Northeastern Brazil

Objetivo: Avaliação da saúde bucal em crianças na cidadede Juazeiro mdo Norte Ceará. Materiais e Métodos: Apresença de Streptococcus mutans (SM) na saliva foidetectada com DENTALCULT II e a contagem expressa emunidades formadoras de colônias por mililitro (UFC/mL). Paraa frequência de escovação, uso do fio dental, utilização doflúor, visitas ao dentista e história familiar utilizaram-sequestionários. Resultados: Observou-se que 47% dascrianças encontravam-se em péssimas condições de saúdebucal e 64% apresentaram 107 UFC/mL de saliva. A maioriaapresentou (81%) referente a alto risco de cárie. Nosquestionários aplicados, 50% das mães afirmaram que ascrianças já haviam ido ao dentista, 25% recebido algum tipode tratamento, 58% alguma instrução sobre higiene oral e98% escovavam os dentes, pelo menos uma vez ao dia.Apenas 10% utilizavam fio dental, 46% já fizeram uso doflúor e 90% mostraram uma história de cárie na família.Conclusões: Este estudo teve como finalidade conhecer osfatores de desenvolvimento da cárie, contribuindo para amelhoria das condições de vida da população infantil efornecendo subsídios para políticas públicas de saúde bucal,adequadas às necessidades desta faixa etária...

Objective: This study evaluated 178 children from Juazeirodo Norte, Brazil, for the presence of Streptococcus mutans(SM). Methods: The DentalCult II kit was used, and the SMcounting expressed as colony forming units per 1 mL ofsaliva (CFU/mL). In order to analyze the teeth brushingfrequency, use of dental floss, fluoride, dentist appointmentsand family dental history, a questionnaire was applied to thechildren’s parents. Results: The data showed that 47%presented poor oral health conditions; 64% showed 107 CFU/mL saliva of S. mutans, and the majority (81%) were at highrisk for dental caries. According to the mothers, 50% visitedthe dentist, 25% received treatment, 58% received someinformation on oral hygiene, and 98% brushed their teeth atleast once a day. Dental floss was used by 10%, and 46%utilized fluoride. The great majority (90%) had a family historyof caries. Conclusion: The importance of this study lies in theknowledge of factors related to the onset and etiology ofcaries in childhood. Moreover, it could be used bygovernmental programs as a guide for oral health planningoriented to the needs of that population...

Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses.

In the present study, we evaluated omega-3 polyunsaturated fatty acid (PUFA) (consisting of 20:5n-3 and 22:6n-3) properties on inflammation and nociception. Among the in vivo tests, writhing, formalin, and hot plate tests were conducted in mice, and carrageenan-induced paw edema, peritonitis, and Hargreaves tests were performed in rats. Following the carrageenan-induced edema, immunohistochemistry for tumor necrosis factor-α (TNF-α) was also carried out. We found that omega-3 PUFA treatment significantly decreased acetic acid-induced abdominal contortions as well as the first and second phases of the formalin test, which were reversed by naloxone. The carrageenan-induced rat paw edema was significantly reduced, along with neutrophil migration to the peritoneal cavity in the omega-3 PUFA treatment. In addition, there was a decrease in TNF-α immunostained cells in the inflamed paw with the omega-3 treatment compared with no omega-3. Withdrawal threshold in response to the thermal stimulation was significantly increased by the omega-3 treatment in the Hargreaves and hot plate tests. The in vitro studies (myeloperoxidase, lactate dehydrogenase, MTT cell viability and lipid peroxidation assays) were performed in human neutrophils. These studies showed that omega-3 treatment significantly decreased myeloperoxidase release, presented no cytotoxicity, and did not alter lipid peroxidation. Our study suggests that omega-3 PUFA anti-inflammatory and antinociceptive actions may involve inhibition of cyclooxygenases and microglial activation, leading to a reduced release of proinflammatory cytokines such as TNF-α, among other factors. The omega-3 PUFAs are potential candidates used alone or in combination with conventional nonsteroidal anti-inflammatory drugs, for the treatment of diseases where inflammation plays an important role.

Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties.

Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA + SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.

Chalcones from Myracrodruon urundeuva are efficacious in guinea pig ovalbumin-induced allergic conjunctivitis

The objective of the study was to verify the effects of dimeric chalcones (urundeuvines A, B, and C) from Myracrodruon urundeuva Allemão, Anacardiaceae (a Brazilian anti-inflammatory species), on an allergic conjunctivitis model. Male guinea-pigs were sensitized with two intraperitoneal injections of ovalbumin (10 μg dissolved in 0.5 mL saline and emulsified in 0.5 mL Freund's adjuvant), at days 0 and 7. At day 24, the animals were submitted to an ocular instillation (right eyes) with ovalbumin. At the next day, the animals were treated with chalcones (0.5 mg, three times a day for 7 days), 0.1 percent fluormetalone acetate (0.05 mg, as the reference drug) or saline. After anesthesia of the animals, enucleations of their corneas and conjunctivas were carried out for morphometric and histological analyses, at days 1, 3 and 7. Their radical scavenging activity and action on myeloperoxidase were also determined. We demonstrated that chalcones from M. urundeuva stem barks presented anti-inflammatory and antioxidant effects, and drastically inhibited the MPO activity, pointing them as candidates for the treatment of allergic conjunctivitis and other inflammatory conditions.

B vitamins attenuate haloperidol-induced orofacial dyskinesia in rats: possible involvement of antioxidant mechanisms.

Tardive dyskinesia (TD) is a serious motor disorder related to antipsychotic therapy, whose pathophysiology is associated to oxidative stress. Treatments that maintain antipsychotic efficacy while reducing TD risk are awaited. Haloperidol (HAL), a typical antipsychotic, is used as a putative murine model of TD. Here, we evaluated the protective role of vitamins B1, B6, and B12 alone or in combination (vitamin B cocktail) in preventing the HAL-induced orofacial dyskinesia (OD), based on their antioxidant properties. HAL (1 mg/kg) administered intraperitoneally to Wistar rats for 21 days caused OD and increased catalepsy time. The daily administration of B vitamins (B1 : B6 : B12 at 60 : 60 : 0.6 mg/kg) alone or the vitamin B cocktail, along with HAL, prevented the development of OD. Catalepsy time reduced in all groups treated with B vitamins, but to a lesser extent than OD. The participation of oxidative stress was assessed by the determination of reduced glutathione (GSH) levels and lipid peroxide formation in the striatum. HAL significantly decreased GSH levels and enhanced lipid peroxidation, whereas B1, B12, and vitamin B cocktail prevented the decrease in GSH levels. All groups treated with B vitamins presented a decrease in lipid peroxide formation. The data suggest a promising role for B vitamins in the prevention of OD.

Caffeine and CSC, adenosine A2A antagonists, offer neuroprotection against 6-OHDA-induced neurotoxicity in rat mesencephalic cells.

In this study, the cytoprotective effects of caffeine (CAF) and 8-(3-chlorostyryl)-caffeine (CSC), A(2A) receptor antagonists, were tested against 6-OHDA-induced cytotoxicity, in rat mesencephalic cells. Both drugs significantly increased the number of viable cells, after their exposure to 6-OHDA, as measured by the MTT assay. While nitrite levels in the cells were drastically increased by 6-OHDA, their concentrations were brought toward normality after CAF or CSC, indicating that both drugs block 6-OHDA-induced oxidative stress which leads to free radicals generation. A complete blockade of 6-OHDA-induced lipid peroxidation, considered as a major source of DNA damage, was observed after cells treatment with CAF or CSC. 6-OHDA decreased the number of normal cells while increasing the number of apoptotic cells. In the CAF plus 6-OHDA group, a significant recover in the number of viable cells and a decrease in the number of apoptotic cells were seen, as compared to the group treated with 6-OHDA alone. A similar effect was observed after cells exposure to CSC in the presence of 6-OHDA. Unexpectedly, while a significant lower number of activated microglia was observed after cells exposure to CAF plus 6-OHDA, this was not the case after cells exposure to CSC under the same conditions. While CAF lowered the percentage of reactive astrocytes increased by 6-OHDA, CSC presented no effect. The effects of these drugs were also examined on the releases of myeloperoxidase (MPO), an inflammatory marker, and lactate dehydrogenase (LDH), a marker for cytotoxicity, in human neutrophils, in vitro. CSC and CAF (0.1, 1 and 10 microg/ml) produced inhibitions of the MPO release from PMA-stimulated cells, ranging from 45 to 83%. In addition, CSC and CAF (5, 50 and 100 microg/ml) did not show any cytotoxicity in the range of concentrations used, as determined by the LDH assay. All together, our results showed a strong neuroptrotection afforded by caffeine or CSC, on rat mesencephalic cells exposed to 6-OHDA. Furthermore, CSC and caffeine actions, inhibiting MPO as well as LDH releases, would contribute to their possible benefit in the treatment of neurodegenerative diseases, including DP. These effects are partially due to the ability of these A(2A) antagonists to decrease the cells free radicals production and oxidative stress, that are major components of 6-OHDA-induced cytotoxicity.

Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action.

The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K(+) channels (K(ATP) channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-L-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K(ATP) channel opening, and antioxidant properties.

Reações adversas causadas por fármacos que atuam no sistema nervoso: análise de registros de um centro de farmacovigilância do Brasil / Adverse reaction caused by drugs acting in nervous system: records analysis of a farmacovigilance center in Brazil

CONTEXTO: A morbimortalidade por uso de medicamentos é um grande problema de saúde. As reações adversas a medicamentos podem resultar em óbito, aumento de internações hospitalares e dos custos com a saúde. OBJETIVOS: Descrever e analisar as notificações de suspeitas de reações adversas causadas por medicamentos que atuam no sistema nervoso (RAM-SN), registradas no Centro de Farmacovigilância do Ceará, de janeiro de 1997 a março de 2008. MÉTODOS: As RAM-SN foram classificadas segundo os critérios da Organização Mundial da Saúde. Uma relação de causalidade entre o fármaco administrado e a reação adversa identificada foi realizada, bem como a análise da reação quanto à gravidade. RESULTADOS: Foram registradas 176 notificações de RAM-SN. A maioria (n = 145; 82,4 por cento) ocorreu no ambiente hospitalar. O principal notificador foi o farmacêutico. As RAM-SN foram classificadas como: possíveis (n = 110), prováveis (n = 37) e definidas (n = 17). Quanto à gravidade, foram consideradas: leves (n = 21), moderadas (n = 127), graves (n = 15) e fatais (n = 1). O caso fatal foi notificado por médico e envolveu medicamentos anestésicos. Geralmente, as reações adversas observadas foram causadas predominantemente por analgésicos, anestésicos e antiepilépticos. DISCUSSÃO: Os dados demonstram o valor potencial de se ter acesso a sistemas de farmacovigilância local para registrar possíveis riscos com o uso de fármacos.

BACKGROUND: The morbi-mortality by the use of medicines is a major health problem. The drug adverse reactions may result in death, increased hospitalizations and healthcare costs. OBJECTIVES: Describe and analyze reports of suspected adverse reactions caused by drugs that act on the nervous system (SN-ADR), registered in the database of the Pharmacovigilance Centre of Ceará, from January 1997 to March 2008. METHODS: All the NS-ADRs were classified according to criteria of the World Health Organization. The causality between the drug administered and the adverse reaction was established, as well as the analysis regarding to the severity of the reaction. RESULTS: The Centre recorded 176 notifications of RAM-SN. The most of the reactions occurred in the hospital. The main reporter was the pharmacist. All the RAM-SN were classified as possible (n = 110), probable (n = 37) and definite (n = 17). With regard to severity, the NS-ADRs were considered: light (n = 21), moderate (n = 127), serious (n = 15) and fatal (n = 1). The fatal case was reported by physician, and involved anesthetic drugs. In general the adverse reactions observed were caused predominantly by analgesics, anesthetics and antiepileptics. DISCUSSION: The data demonstrate the potential values of accessing to a local system of pharmacovigilance to report possible risks with the use of nervous system drugs.

Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica / Ecstasy (MDMA): pharmacological and toxic effects, mechanism of action and clinical management

CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase) é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável.

BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985 and 2007. RESULTS: There were still many unanswered questions regarding the pharmacology of ecstasy and the pathophysiology of its toxic effects. The fundamental mechanism of action is insufficient to explain all effects induced by the drug. The exact mechanism responsible for mediating the toxic effects of MDMA on 5-HT neurons remain to be elucidated. DISCUSSION: There is limited information in published literature about the underlying pharmacology and mechanism of action that could account for the neurotoxic and other phathophysiological effect of MDMA.

Biocompatibility evaluation of an antibiotic paste after pulpotomy in dogs

The purpose of this study was to evaluate by histological analysis, the biocompatibility of an antibiotic paste following treatment of pulpotomies in dogs. Four male adult dogs were used and their mandibular and maxilar premolars and molars (PM3; PM4; M1; PM4;M1) of both sides were submitted to pulpotomies. The antibiotic paste (CTZ) was prepared with chloramphenicol, tetracycline, zincoxide and eugenol. After 6, 8, 9 and 10 months post-pulpotomy the dogs were sacrificed. Histological analysis of the teeth revealed an intense inflammatory process in the coronal pulp at 6 months after pulpotomy, with inflammatory cells dispersed throughout the entireapical region in this period. This process became partially reduced at 8 and 9 months after pulpotomy, and totally disappeared by the end of the experiment, at 10 months. In conclusion, the endodontic treatment with this antibiotic paste seemed to be biocompatible under the present experimental conditions. However, further clinical studies are necessary to assure that this paste is safe for use in pulpotomies in children.

Avaliação hematológicas e bioquímicas do sangue de cães submetidas a pulpotomias com cimento de antibiótico / Hematological and biochemical evaluations of blood from dogs submitted to pulpotomies with an antibiotic sealer

Este estudo experimental avaliou os parâmetros hematológicos e bioquímicos no sangue de 7 cães machos e adultos, com peso variando de 11 a 20 kg, submetidos a pulpotomias dos dentes molares e pré-molares, utilizando-se o cimento de antibiótico composto de cloranfenicol, tetraciclina, óxido de zinco e eugenol, como obturador da câmara coronária. Foram selecionados 10 dentes hígidos de cada cão com boas condições gengivais e as pulpotomias foram realizadas sob anestesia geral. Coletou-se o sangue antes e 48 horas, 30, 60 e 90 dias após as pulpotomias, para as avaliações hematológicas e bioquímicas. Os resultados mostraram que, no exame hematológico, o único parâmetro alterado foi o referente à contagem de plaquetas cujos valores já eram reduzidos antes e após o tratamento endodôntico. O exame bioquímico manteve-se dentro dos valores de referência, no entanto, os valores médios referentes às bilirrubinas mostraram-se elevados, ao final do experimento. Concluiu-se que o uso do cimento de antibiótico, em pulpotomias realizadas em cães, parece ser destituído de efeitos tóxicos, seguindo-se a metodologia testada. Todavia, sua utilização em pulpotomias de dentes humanos decíduos, apesar de promissora, carece de maiores estudos clínicos.

The present work evaluated hematological and biochemical parameters in blood from seven male adult dogs (11 to 20 kg) submitted to molar and pre-molar pulpotomies with an antibiotic sealer. This sealer was prepared with chloramphenicol, tetracycline, zinc oxide and eugenol, and used for the obturation of the coronary pulp chamber. The pulpotomies were performed under general anesthesia, and the blood was collected before and 48 hours, 30, 60 and 90 days after that procedure, for hematological and biochemical evaluations. The hematological evaluation showed that the only altered parameter was that related to platelet count whose values were already reduced before and after the pulpar therapy. Similarly, the biochemical parameters were also maintained at normal levels, except for the bilirubin concentrations which were increased at the end of the experiment. The conclusion was that the use of the antibiotic sealer for pulpotomy, in dogs, seems to be devoid of toxicity under the experimental conditions. However, clinical studies are necessary for assuring the safety of the use of this sealer in pulpotomies in children.

Análise clínica e morfológica da conjuntivite alérgica induzida por ovalbumina e tratada com chalcona em cobaias / Clinical and morphologic analysis of allergic conjunctivitis induced by ovalbumin and treated with chalcona in guinea pigs

OBJETIVO: Verificar, do ponto de vista clínico e morfológico, o efeito da chalcona na conjuntivite alérgica induzida por ovalbumina em cobaias. MÉTODOS: Utilizaram-se 54 cobaias, albinos, machos pesando aproximadamente 400 g. Os animais foram sensibilizados por injeção intraperitoneal de ovalbumina suspensa em solução adjuvante completa de Freund. Posteriormente, a conjuntivite alérgica foi induzida por instilação de ovalbumina no saco conjuntival do olho direito. Os animais foram distribuídos em 3 grupos, conforme o tratamento proposto: chalcona, corticóide e salina. A avaliação clínica foi realizada com 5, 10 e 40 min, 7 e 24 h da indução e diariamente até o dia 7 da indução. A avaliação morfológica consistiu em avaliar edema, necrose, vascularização e exocitose nos dias 1, 3 e 7 da indução. RESULTADOS: Em todos os grupos a resposta inflamatória foi mais intensa 24 h após a indução. No grupo chalcona evidenciou-se menos sinais inflamatórios que no grupo salina. O grupo corticóide apresentou menos sinais inflamatórios quando comparados aos grupos chalcona e controle. A análise morfológica evidenciou-se que os grupos chalcona e corticóide apresentaram efeitos terapêuticos semelhantes. CONCLUSÃO: A chalcona teve efeito terapêutico na conjuntivite alérgica induzida por ovalbumina.