Effectiveness of the short-term use of Cimicifuga racemosa in the endothelial function of postmenopausal women: a double-blind, randomized, controlled trial.

Objective: This study aimed to assess the effects of daily use of Cimicifuga racemosa on endothelial function through flow-mediated dilation of the brachial artery, when used for 28 days by healthy postmenopausal women.Methods: The double-blind, randomized, placebo-controlled study included two groups of postmenopausal women (n = 31 each). The subjects were clinically assessed and flow-mediated dilation of the brachial artery was measured before and after 28 days of treatment. Patients received dry extract corresponding to 160 mg C. racemosa (extract with 4 mg of triterpene glycosides) or placebo.Results: Mean age, time since menopause, and body mass index in the two groups were similar. The measurements of flow-mediated dilation of the brachial artery, pre and post treatment, respectively, showed a significant increase in patients who used C. racemosa (p = 0.006), unlike patients who used placebo, who did not present changes in the outcome of flow-mediated dilation of the brachial artery after 28 days of use (p ≥ 0.05). When comparing the number of women in both groups who showed an increase in flow-mediated dilation, a significant difference was found in the measurements of the treated group after the use of the medication (p = 0.018).Conclusions: Daily use of 160 mg C. racemosa extract by postmenopausal women for 28 days beneficially influences endothelial function by promoting elasticity of the brachial artery.

Capsaicin and Its Role in Chronic Diseases.

A significant number of experimental and clinical studies published in peer-reviewed journals have demonstrated promising pharmacological properties of capsaicin in relieving signs and symptoms of non-communicable diseases (chronic diseases). This chapter provides an overview made from basic and clinical research studies of the potential therapeutic effects of capsaicin, loaded in different application forms, such as solution and cream, on chronic diseases (e.g. arthritis, chronic pain, functional gastrointestinal disorders and cancer). In addition to the anti-inflammatory and analgesic properties of capsaicin largely recognized via, mainly, interaction with the TRPV1, the effects of capsaicin on different cell signalling pathways will be further discussed here. The analgesic, anti-inflammatory or apoptotic effects of capsaicin show promising results in arthritis, neuropathic pain, gastrointestinal disorders or cancer, since evidence demonstrates that the oral or local application of capsaicin reduce inflammation and pain in rheumatoid arthritis, promotes gastric protection against ulcer and induces apoptosis of the tumour cells. Sadly, these results have been paralleled by conflicting studies, which indicate that high concentrations of capsaicin are likely to evoke deleterious effects, thus suggesting that capsaicin activates different pathways at different concentrations in both human and rodent tissues. Thus, to establish effective capsaicin doses for chronic conditions, which can be benefited from capsaicin therapeutic effects, is a real challenge that must be pursued.

The relevance of kinin B1 receptor upregulation in a mouse model of colitis.

BACKGROUND AND PURPOSE: Kinins are implicated in many pathophysiological conditions, and recent evidence has suggested their involvement in colitis. This study assessed the role of the kinin B1 receptors in a mouse model of colitis. EXPERIMENTAL APPROACH: Colitis was induced in mice by 2,4,6-trinitrobenzene sulphonic acid (TNBS), and tissue damage and myeloperoxidase activity were assessed. B1 receptor induction was analysed by organ bath studies, binding assay and reverse transcription PCR. KEY RESULTS: TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of colon B1 receptor-mediated contraction, with the maximal response observed at 72 h. The upregulation of the B1 receptor at this time point was also confirmed by means of binding studies. B1 receptor mRNA levels were elevated as early as 6 h after colitis induction and remained high for up to 48 h. TNBS-evoked tissue damage and neutrophil influx were reduced by the selective B1 receptor antagonist SSR240612, and in B1 receptor knockout mice. In vivo treatment with inhibitors of protein synthesis, nuclear factor-kappaB activation, inducible nitric oxide synthase (iNOS) or tumour necrosis factor alpha (TNFalpha) significantly reduced B1 receptor agonist-induced contraction. Similar results were observed in iNOS and TNF receptor 1-knockout mice. CONCLUSIONS AND IMPLICATIONS: These results provide convincing evidence on the role of B1 receptors in the pathogenesis of colitis. Therefore, the blockade of kinin B1 receptors might represent a new therapeutic option for treating inflammatory bowel diseases.

Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice.

BACKGROUND AND PURPOSE: We investigated the mechanisms underlying the pruritogenic response induced by trypsin in mice, to assess the relevance of neurogenic inflammation components in this response. EXPERIMENTAL APPROACH: Itching was induced by an intradermal injection of trypsin in the mouse neck. The animals were observed for 40 min and their scratching behaviour was quantified. KEY RESULTS: Trypsin-induced itching was blocked by the lima bean trypsin inhibitor, the selective proteinase-activated receptor-2 (PAR-2) antagonist FSLLRY and PAR-2 receptor desensitization. An important involvement of mast cells was observed, as chronic pretreatment with the mast cell degranulator compound 48/80 or the mast cell stabilizer disodium cromoglycate prevented scratching. Also, trypsin response was inhibited by the selective COX-2 inhibitor celecoxib and by the selective kinin B2 (FR173657) and B1 (SSR240612) receptor antagonists. Moreover, an essential role for the mediators of neurogenic inflammation was established, as the selective NK1 (FK888), NK3 (SR142801) and calcitonin gene-related peptide (CGRP(8-37) fragment) receptor antagonists inhibited trypsin-induced itching. Similarly, blockade of transient receptor potential vanilloid 1 (TRPV1) receptors by the selective TRPV1 receptor antagonist SB366791, or by genetic deletion of TRPV1 receptor reduced this behaviour in mice. C-fibre desensitization showed a very similar result. CONCLUSIONS AND IMPLICATIONS: Trypsin intradermal injection proved to be a reproducible model for the study of itching and the involvement of PAR-2 receptors. Also, trypsin-induced itching seems to be widely dependent on neurogenic inflammation, with a role for TRPV1 receptors. In addition, several other mediators located in the sensory nerves and skin also seem to contribute to this process.

Hidroxiapatia sintética pura, hidroxiapatia sintética associada ao colágeno e hidroxiapatia sintética associada ao lipossoma como substitutos ósseos em defeitos provocados na tíbia de cäes: aspectos da osteointegraçäo à microscopia de luz transmitida / Pure synthetic hydroxyapatite, collagen associated synthetic hydroxyapatite and liposome associated synthetic hydroxyapatite as a bone substitute for defects in bone healing of dogs: transmited light microscopy osteointegration aspects

Utilizaram-se 40 cäes clinicamente sadios com o objetivo de avaliar histologicamente o efeito da hidroxipatita sintética pura (HAP-91), da HAP-91 associada ao colágeno (COL.HAP-91) e da HAP-91 associada ao lipossoma (INT.HAP-91) como substitutos ósseos em defeitos provocados na tíbia dos animais. Após protocolo anestésico, o procedimento cirúrgico constou de incisäo na face medial e no terço proximal da tíbia esquerda, com retirada de um fragmento ósseo com cerca de 10 x 6mm de tamanho. Os animais foram separados em quatro grupos de 10 cada. No grupo 1 a falha óssea foi preenchida com HAP-91, no grupo 2 com COL.HAP-91 e no grupo 3 com INT.HAP-91. O grupo quatro näo recebeu tratamento. Dois animais de cada grupo foram sacrificados nos dias 8, 30, 60, 120 e 180 de pós-operatório para coleta de material para histopatologia. Aos oito dias observou-se neoformaçäo óssea no grupo-controle e ao redor do implante nos grupos tratados com HAP-91 e INT.HAP-91. Aos 30 dias, notou-se preenchimento do defeito nos mesmos grupos, fato näo observado no grupo COL.HAP-91. Conclui-se que a cicatrizaçäo óssea ocorreu nos grupos controle e tratados com HAP-91 e INT.HAP-91, mais precoce neste último grupo. Nos animais tratados com COL.HAP-91 näo houve cicatrizaçäo completa

Hidroxiapatita sintética pura, hidroxiapatita sintética associada ao colágeno e hidroxiapatita sintética associada ao lipossoma como substitutos ósseos em defeitos provocados na tíbia de cães: aspectos da osteointegração à microscopia de luz transmitida

The objective of this work was to evaluate histologically the synthetic hydroxyapatite (HAP-91), associated to collagen (COL.HAP-91) and associated to liposome (INT.HAP-91), as bone substitutes. Fourty clinically healthy dogs were studied. After a conventional anaesthesic protocol, the surgical procedure consisted of skin incision on medial surface in the left tibial third middle. A bone fragment of 10 × 6mm in size was retreated in all animals, which were divided into four groups with 10 animals each. Group one was treated with HAP-91, group two with COL.HAP-91, group three with INT.HAP-91, group four did not receive any treatment and was used as a control. Histological material was collected after humane sacrifice of two animals from each group in 8, 30, 60, 120 180 days after surgery. By the 8th day, bone neoformation in control group and around the implant in groups treated with HAP-91 and INT.HAP-91 was observed. On the 30th day, the defect was filled up completely in the same groups, result which was not observed in COL.HAP-91 group. Bone repair was complete in control group, HAP-91 group and INT.HAP-91 group (most premature), but in animals treated with COL.HAP-91 complete regeneration was not observed.

Utilizaram-se 40 cães clinicamente sadios com o objetivo de avaliar histologicamente o efeito da hidroxiapatita sintética pura (HAP-91), da HAP-91 associada ao colágeno (COL.HAP-91) e da HAP-91 associada ao lipossoma (INT.HAP-91) como substitutos ósseos em defeitos provocados na tíbia dos animais. Após protocolo anestésico, o procedimento cirúrgico constou de incisão na face medial e no terço proximal da tíbia esquerda, com retirada de um fragmento ósseo com cerca de 10 × 6mm de tamanho. Os animais foram separados em quatro grupos de 10 cada. No grupo 1 a falha óssea foi preenchida com HAP-91, no grupo 2 com COL.HAP-91 e no grupo 3 com INT.HAP-91. O grupo quatro não recebeu tratamento. Dois animais de cada grupo foram sacrificados nos dias 8, 30, 60, 120 e 180 de pós-operatório para coleta de material para histopatologia. Aos oito dias observou-se neoformação óssea no grupo-controle e ao redor do implante nos grupos tratados com HAP-91 e INT.HAP-91. Aos 30 dias, notou-se preenchimento do defeito nos mesmos grupos, fato não observado no grupo COL.HAP-91. Conclui-se que a cicatrização óssea ocorreu nos grupos controle e tratados com HAP- 91 e INT.HAP-91, mais precoce neste último grupo. Nos animais tratados com COL.HAP-91 não houve cicatrização completa.