Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

COX-2 Inhibitors for Cancer Treatment in Dogs

Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2) whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID) and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

Use of Medicines Among a Brazilian Elderly Sample: A Cross-sectional Study

Background: The use of multiple medicines is very frequent among the elderly, allowing them to perceive more often adverse side effects from drugs and present undesirable drug interactions.Methods: This article presents a cross-sectional survey about the use of medicines among 300 elderly Brazilians, equally divided into institutionalized and community-dwelling groups.Results: The average daily intake of medicines is 3.2 among institutionalized elderly, a higher (p < 0.001) number when compared with community-dwelling elderly, who takes an average of 1.8 medicines daily. The most commonly used medications are antihypertensives (58.0%), diuretics (23.0%), nonsteroidal anti-inflammatory drugs (22.7%), supplements (21.7%), antidiabetics (16.3%), and antiulcerants (14.0%). Antiulcerants, diuretics, supplements, and central nervous system drugs are more frequently used by institutionalized than by community-dwelling elderly.Conclusion: In this Brazilian elderly sample, the most widely used medicines were antihypertensives, diuretics, and nonsteroidal anti-inflammatory drugs, and institutionalized used more medications than community-dwelling elderly. Copyright (C) 2011, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.

Prótese intra-ocular de resina acrílica em cães e gatos

Foram atendidos no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Unesp - Campus de Botucatu, 11 animais (oito cães e três gatos), com alterações oftálmicas unilaterais graves que levaram à perda total da função ocular (protrusão de globo com injúria nervosa e estrutural, perfurações de córnea com perda de conteúdo intra-ocular e endoftalmites, entre outras). Os animais, com idades entre dois meses e 10 anos, foram submetidos à evisceração e posterior inclusão de esfera de resina acrílica (metilmetacrilato) na capa córneo-escleral ou escleral. As esferas foram previamente confeccionadas e esterilizadas por autoclavagem. No pós-operatório foram utilizados antiinflamatórios e antibioticoterapia tópica combinada ou não a sistêmica. O período de observação variou de 2 meses a 3 anos e os aspectos avaliados foram secreção ocular, blefarospasmo, sinais de desconforto e estética. Obtiveram-se resultados satisfatórios em oito casos. Concluiu-se que a resina acrílica pode ser uma alternativa para uso como inclusão em cavidade anoftálmica.

Lipoperoxidation and cyclooxygenase enzyme inhibitory piperidine alkaloids from Cassia spectabilis green fruits

Phytochernical work in the search for bioactive metabolites from the methanolic extract of Senna spectabilis green fruits led to the isolation of a new piperidine alkaloid, (+)-3-O-feruloylcassine (1), in addition to the known (-)-spectaline (2) and (-)-3-O-acetylspectaline (3). The isolates were submitted to in vitro evaluation of lipoperoxidation (LPO) and cyclooxygenase enzymes (COX-1 and -2) inhibitory properties and showed moderate antioxidant activities (40-70%) at 100 ppm when compared to commercial standards BHT and vitamin E and moderate inhibition of COX-1 (ca. 40%) and marginal inhibition of COX-2 enzymes (< 10%) at 100 ppm when compared to nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, rofecoxib, and celecoxib, respectively.

Pharmacological modulation of allergic inflammation in the rat airways and association with mast cell heterogeneity

Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15 min) protein exudation in different airway tissues, as determined by Evans blue staining. This was associated with marked mast cell degranulation determined by histological examination, with there being no difference between mucosal and connective tissue mast cells. A 5-day administration regimen with compound 48/80 selectively depleted connective tissue mast cell (Positive to berberine staining) without modifying ovalbumin-induced plasma protein extravasation. Treatment of rats with dexamethasone (1 mg/kg, - 12 h) or nor-dihydroguaiaretic acid (30 mg/kg i.p., - 30 min) significantly reduced ovalbumin-induced protein extravasation and preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., - 30 min) exerted no effect on either parameter. In conclusion, we propose the mucosal mast cell as a target cell responsible at least partly for the inhibitory actions of known anti-inflammatory drugs. We suggest an involvement of endogenous leukotriene(s), but not prostanoid(s), in mucosal mast cell activation/degranulation. (C) 2001 Published by Elsevier B.V. B.V.

Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCI/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCI/EtOH-induced gastriculcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p < 0.000 1). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p < 0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p < 0.0001), increased pH values and promoted reduced acid output (p < 0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p > 0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action. (c) 2004 Elsevier GmbH. All rights reserved.

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

The aim of the present work was to compare colonic mucosa and plasmatic oxidative stress measured concomitantly and with different degrees of injury in rats with colitis induced by trinitrobenzene sulfonic acid. Three groups were studied: control group, colitis group, and colitis exacerbated by diclofenac. Enzymatic markers of colon injury showed enhanced activity in both groups with colitis. The colitis group treated with diclofenac presented higher colonic damage score than the other groups. In both groups with colitis, higher values of tert butyl hydroperoxide-initiated-chemiluminescence and thiobarbituric acid-reactive substances in tissue and decreased total radical-trapping antioxidant potential (TRAP) levels in plasma were found. In conclusion, independently of the degree of colonic mucosa injury and inflammation, oxidative stress in tissue occurs as a consequence of pro-oxidants increase, and is not explained by a reduction of antioxidant defenses. In both conditions, TRAP determination decreases in plasma, but not in tissue.

Efeitos de diferentes doses de tenoxicam sobre a medula espinhal e as meninges. Estudo experimental em caes

Background and Objectives. The analgesic actions of nonsteroidal anti-inflammatory drugs (NSAID) result from the inhibition of the peripheral synthesis of prostaglandins. In spite of the emphasis on the peripheral action, several studies have shown the potential central action of such drugs. In rats, NSAID doses insufficient to block pain when systemically administered were effective when intrathecally injected. This effect could be mediated by interaction with descending serotoninergic ways together with neurotransmission modulation of glycine or N-methyl-D-aspartate receptors. Our goal was to study the effect of different tenoxican doses in the histology of dogs spinal cord and meninges. Methods. Thirty two dogs (7 to 17 kg) were randomly distributed in four groups: G1 - Control with distilled water (DW); G2 - 2 mg tenoxican diluted in DW; G3 - 4 mg tenoxican diluted in DW; G4 - 10 mg tenoxican diluted in DW in a constant volume of 1 ml. Anesthesia was induced with etomidate and fentanyl and dural puncture was performed with a 25G spinal needle in interspace L6-7. Animals were observed for 72 hours and subsequently euthanized by electrocution. Lumbar and sacral spinal cord segments were removed for further histologic examination. Results. All animals were clinically normal during the observation period and there has been no histologic alteration of the nervous system and meninges. Conclusions. In our experimental model intrathecal tenoxican doses up to 10 mg have not triggered nervous tissue or meningeal injuries in dogs.

Síntese e modelagem molecular do novo derivado indolinônico como candidato a antiinflamatório COX-2 seletivo

Anti-inflammatory drugs are known to be the most widely-marketed drugs in the world, despite their serious side effects, mainly on the gastrointestinal tract. Thus, there are constant efforts to discover new prototypes with improved therapeutic activity and safety for the patient. Since the advent of the computational chemistry, the theoretical study of the physiological behavior of a new compound and hence an understanding of its supposed mechanism of action have been made a lot more accessible. Thus, molecule-receptor mathematical modeling was applied to compound I (1-(2,6-dichlorophenyl)indolin-2-one), to predict theoretically its ability to inhibit, selectively, the COX-2 isoform of prostaglandin endoperoxide synthase (PGHS-2), and the best positions to introduce chemical groups and to make molecular modifications.

Analgésicos Tópicos

Background and objectives: Pain treatment involves the usage of common and opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and adjuvant analgesics. Traditionally, these drugs are administered systemically or into the neuraxis. However, when analgesics are applied through these pathways, they are associated with significant side effects, which can hinder its use. Topical administration of analgesics is an alternative. The objective of this paper is to discuss topical analgesics, the mechanisms of action and clinical efficacy. Content: This is a review paper addressing the usage of the topical local anesthetics: capsaicin, clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids, discussing mechanism of action and effectiveness. Conclusions: Topical analgesics are promising as a strategy for pain treatment, as they are associated with lower incidence of side effects. The benefit of local anesthetics, NSAID's and capsaicin is well established. However, the efficacy of clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids is still questionable. Studies have shown that the multimodal approach is an alternative, but studies are needed to confirm this hypothesis. © 2012 Elsevier Editora Ltda.

Avaliação do perfil antiinflamatório e analgésico, e dos efeitos colaterais da administração oral de meloxicam em equinos: avaliação física, laboratorial e gastroscópica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Atividade gastroprotetora do óleo essencial de Citrus lemon (Rutaceae), de seus componentes principais Limoneno e β-pineno e do óleo essencial de Croton cajucara (Euphorbiaceae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da inibição da ativação plaquetária durante o desenvolvimento da doença periodontal em ratos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Farmacocinética pré-clínica do composto 1-(2,6-diclorofenil)indolin-2-ona (DICCIC), pró-fármaco de diclofenaco

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)