Study of in vitro and in vivo extraction of kavalactones of pharmaceutical form containing ground plant drug (Piper methysticum G. Forster)

An evaluation of the extraction of pharmacological markers (kavalactones) of the plant species Piper methysticum (kava-kava) was conducted. Capsules containing ground kava-kava were submitted to an in vitro method using a controlled dissolution system where the extractive mediums were a solution of 0.1M HCl, phosphate buffered solution (pH = 6.8) and distilled water, at 30 and 60 min, and in vivo that was based on the pylorus ligation method in rats. In the in vitro system starting from 6 capsules (3 g) containing the kava-kava powder, the following extractive concentrations of kavalactones were obtained: HCl (30 min.) = 0.93% (27.9 mg), HCl (60 min.) = 1.1% (33 mg), buff. (30 min) = 2.8% (84 mg), buff. (60 min.) = 0.7% (21 mg), water (30 min.) = 0.71% (21.3 mg) and water (60 min.) = 2.6% (78 mg), while in the in vivo method, 1 and 2 h after administration of 500 mg of the kava-kava powder through gavage, the extractive concentrations of total kavalactones were: 1h = 1.31% (6.55 mg) and 2h = 1.41 % (7.05 mg). In the in vitro system a slight difference was observed among the solutions, which were not statistically significant, and the same occurred with the in vivo experiment, although at the time of 2 h after administration it proved more effective in the extraction of kavalactones by the gastric juice, but below the dose recommended for therapeutic use.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Study of in vitro and in vivo extraction of kavalactones of pharmaceutical form containing ground plant drug (Piper methysticum G. Forster)

An evaluation of the extraction of pharmacological markers (kavalactones) of the plant species Piper methysticum (kava-kava) was conducted. Capsules containing ground kava-kava were submitted to an in vitro method using a controlled dissolution system where the extractive mediums were a solution of 0.1M HCl, phosphate buffered solution (pH = 6.8) and distilled water, at 30 and 60 min, and in vivo that was based on the pylorus ligation method in rats. In the in vitro system starting from 6 capsules (3 g) containing the kava-kava powder, the following extractive concentrations of kavalactones were obtained: HCl (30 min.) = 0.93% (27.9 mg), HCl (60 min.) = 1.1% (33 mg), buff. (30 min) = 2.8% (84 mg), buff. (60 min.) = 0.7% (21 mg), water (30 min.) = 0.71% (21.3 mg) and water (60 min.) = 2.6% (78 mg), while in the in vivo method, 1 and 2 h after administration of 500 mg of the kava-kava powder through gavage, the extractive concentrations of total kavalactones were: 1h = 1.31% (6.55 mg) and 2h = 1.41 % (7.05 mg). In the in vitro system a slight difference was observed among the solutions, which were not statistically significant, and the same occurred with the in vivo experiment, although at the time of 2 h after administration it proved more effective in the extraction of kavalactones by the gastric juice, but below the dose recommended for therapeutic use.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Study of in vitro and in vivo extraction of kavalactones of pharmaceutical form containing ground plant drug (Piper methysticum G. Forster)

An evaluation of the extraction of pharmacological markers (kavalactones) of the plant species Piper methysticum (kava-kava) was conducted. Capsules containing ground kava-kava were submitted to an in vitro method using a controlled dissolution system where the extractive mediums were a solution of 0.1M HCl, phosphate buffered solution (pH = 6.8) and distilled water, at 30 and 60 min, and in vivo that was based on the pylorus ligation method in rats. In the in vitro system starting from 6 capsules (3 g) containing the kava-kava powder, the following extractive concentrations of kavalactones were obtained: HCl (30 min.) = 0.93% (27.9 mg), HCl (60 min.) = 1.1% (33 mg), buff. (30 min) = 2.8% (84 mg), buff. (60 min.) = 0.7% (21 mg), water (30 min.) = 0.71% (21.3 mg) and water (60 min.) = 2.6% (78 mg), while in the in vivo method, 1 and 2 h after administration of 500 mg of the kava-kava powder through gavage, the extractive concentrations of total kavalactones were: 1h = 1.31% (6.55 mg) and 2h = 1.41 % (7.05 mg). In the in vitro system a slight difference was observed among the solutions, which were not statistically significant, and the same occurred with the in vivo experiment, although at the time of 2 h after administration it proved more effective in the extraction of kavalactones by the gastric juice, but below the dose recommended for therapeutic use.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Polímeros impressos com íons: fundamentos, estratégias de preparo e aplicações em química analítica

Chemical imprinting technology has been widely used as a valuable tool in selective recognition of a given target analyte (molecule or metal ion), yielding a notable advance in the development of new analytical protocols. Since their discovery, molecularly imprinted polymers (MIPs) have been extensively studied with excellent reviews published. However, studies involving ion imprinted polymers (IIPs), in which metal ions are recognized in the presence of closely related inorganic ions, remain scarce. Thus, this review involved a survey of different synthetic approaches for preparing ion imprinted adsorbents and their application for the development of solid phase extraction methods, metal ion sensors (electrodes and optodes) and selective membranes

In vitro metabolism studies of erythraline, the major spiroalkaloid from Erythrina verna

Abstract\ud \ud Background\ud \ud Erythrina verna, popularly known as “mulungu”, is a Brazilian medicinal plant used to treat anxiety. Erythrina alkaloids have been described in several species of Erythrina, which have biological and therapeutic properties well known that include anxiolytic and sedative effects.\ud \ud \ud Methods\ud In this work, in vitro metabolism of erythraline (1), the major spirocyclic alkaloid of Erythrina verna, was studied in the pig cecum model and by biomimetic phase I reactions. The biomimetic reactions were performed with Jacobsen catalyst to produce oxidative metabolites and one metabolite was isolated and evaluated against cancer cells, as HL-60 (promyelocytic leukemia), SF-295 (Glioblastoma) and OVCAR-8 (ovarian carcinoma).\ud \ud \ud Results\ud Erythraline exhibited no metabolization by the pig microbiota and a main putative metabolite was formed in a biomimetic model using Jacobsen catalyst. This metabolite was isolated and identified as 8-oxo-erythraline (2). Finally, erythraline and the putative metabolite were tested in MTT model and both compounds showed no important cytotoxic activity against tumor cells.\ud \ud \ud Conclusions\ud The alkaloid erythraline was not metabolized by intestinal microbiota, but it was possible to identify its oxidative metabolite from biomimetic reactions. So these data are interesting and stimulate other studies involving this alkaloid, since it is present in phytomedicine products and there are not reported data about the metabolism of erythrina alkaloids.The authors gratefully acknowledge FAPESP (Process: 2010/07413-0, 2011/\ud 13281-2, 2012/18031-7), CAPES, CNPq (201691/2011-6) and INCT-if for financial\ud support. The authors also thanks Kurzen family (farmers) for the ceca supplying

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Evaluation of the in vitro metabolism of budlein A and correlates

A busca por novos fármacos inspirados em substâncias de origem natural é uma estratégia conhecida e há tempos utilizada. As lactonas sesquiterpênicas (LST) são um grupo de substâncias amplo e diverso com várias atividades farmacológicas descritas, e cuja característica estrutural determinante é a de um esqueleto principal contendo 15 átomos de carbono e um anel lactônico. O mecanismo de ação das LST está intrinsicamente relacionado com reações de adição do tipo Michael frente a biomoléculas, provocando alquilações. Há na literatura estudos aprofundados sobre a química medicinal das LST, entretanto pouco há sobre o metabolismo desse grupo de substâncias em ambientes fisiológicos. Neste sentido, este trabalho é focado no estudo do metabolismo e também das vias de fragmentação por eletrospray da budleína A, que possui estrutura química do tipo furanoeliangolido, e pertence à classe dos germacranolidos. Foram realizados ensaios in vitro utilizando-se os modelos de oxidação biomimética com metaloporfirina, microssomas hepáticos e metabolismo pela microbiota intestinal de ceco de porco (pig cecum model), sendo nos dois últimos testado também o correlato 4,5-dihidro-2\',3\'-epoxi-15-desoxigoyazensolido. O estudo de fragmentação também abordou a comparação entre budleína A e a centraterina - um estereoisômero que se diferencia apenas pela orientação da cadeia lateral ligada ao C-8 - em espectrômetros distintos e com suporte de métodos computacionais para cálculos de energia (Gaussian 03 em base B3LYP/6-31G(d)). Nos estudos de fragmentação observou-se a diferença de intensidade dos sinais para íons fragmento comuns às duas LST (m/z 275, 257 e 83), além da presença do íon fragmento de m/z 293 apenas para a budleína A, permitindo a diferenciação destes isômeros por meio de espectrometria de massas com ionização por eletrospray, sem a necessidade de ressonância de magnética nuclear. Os produtos de oxidação detectados na reação com metaloporfirinas acusaram a epoxidação na cadeia lateral envolvendo C-2\' e C-3\' com a formação de diastereoisômeros. No ensaio com microssomas não foram detectados produtos para a budleína A, enquanto que para a substância correlata observou-se a abertura do epóxido na cadeia lateral e adição de uma hidroxila, formando um diol vicinal. No modelo de ceco de porco observaram-se a formação de adutos de LST com o aminoácido cisteína, os quais foram posteriormente degradados pela ação da microbiota intenstinal, dando origem a diversos metabólitos compostos pela LST e partes de cisteína. Sendo assim, este trabalho lança bases para a maior compreensão do metabolismo de LST do tipo furanoeliangolido em modelos distintos e também contribui para os estudos de espectrometria de massas para este tipo de substância, além de descrever uma ferramenta analítica útil na diferenciação de dois estereoisômeros.The search for new drugs inspired on compounds from natural products is a wellknown strategy with several successful cases. Sesquiterpene lactones (STL) are a wide and diversified group of compounds which has already many pharmacological activities reported. Their fundamental moiety includes a skeleton containing 15 carbons and a lactone ring and the mechanism of action is related to Michael addition type reactions with biomolecules, promoting alkylation. There are a high amount of studies regarding the medicinal chemistry of the STL, however there are few information about the metabolism of these compounds under physiological environments. On this way, the aims of this work are focused on the study of the metabolism as well as the fragmentation pathways of budlein A, which is a furanoheliangolide and belongs to the germacranolides class. On this work the following experiments were carried out: in vitro oxidative metabolism with metalloporphyrin and microsomes; intestinal metabolism by using the pig cecum model (microbiota). For microsomes and intestinal metabolism the compound 4,5- dihydro-2\',3\'-epoxy-15-deoxy-goyazensolide was also applied. Fragmentation studies compared the fragmentation patterns of budlein A and centratherin - which is a stereoisomer with -orientation for the side chain bonded at C-8 - by using different spectrometers being supported by computational methods for energies calculations (Gaussian 03 at level B3LYP/6-31G(d)). For the fragmentation studies it was observed the difference of signal intensities for fragment ions which are common for both STL (m/z 275, 257 e 83), moreover the ion m/z 293 was detected only for budlein A, allowing the differentiation between these isomers by electrospray ionization mass spectrometry instead nuclear magnetic resonance. The reactions with metalloporphyrin yielded two diastereoisomers of the STL with an epoxide at the side chain between C-2\'and C-3\'. On the microsome assay any product was detected for budlein A, while for the correlated compound the epoxide ring was opened and a hydroxyl was added at C-3\', forming a vicinal diol. On the pig cecum model it was observed the formation of adducts due to the reaction of the STL and the amino acid cysteine. These adducts were later degraded by the action of the microbiota yielding different metabolites composed by STL and residues of cysteine. Thus, this work may contribute to the improvement of the knowledge about the metabolism of STL furanoheliangolide type in different models as well as for the studies regarding the mass spectrometry of this type of compound. The development of a useful analytical tool for the differentiation of two isomers was also an important achievement

Comparação do processo de reparo ósseo em tíbias de ratas normais e osteopênicas Bone repair process in normal and osteopenic female rats' tibiae: a comparative study

O objetivo foi comparar a consolidação óssea em tíbias de ratas normais e osteopênicas. 49 ratas albinas fêmeas, linhagem Wistar, peso médio de 160 (&plusmn; 20g) e 100 dias foram distribuídas em 2 grupos: Ooforectomizado (OOF) e Pseudo-ooforectomizado (Grupo controle - SHAM). 30 dias após a ooforectomia e/ou cirurgia simulada, todas foram submetidas à produção de lesão óssea cortical. Foram sacrificadas na 2ª, 4ª, 6ª e 8ª semanas. Os osteoblastos foram contados. O peso aumentou progressivamente, porém as OOF apresentaram maior peso (p<0,05) quando comparadas as SHAM, à época da segunda cirurgia. 15 dias pós-lesão óssea, as OOF apresentaram maior número de osteoblastos (p<0,05) quando comparados as SHAM. 30 dias pós-lesão óssea houve diminuição no número de osteoblastos, porém os valores foram equivalentes entre os dois grupos OOF e SHAM. 45 dias pós-lesão, apesar da diminuição constante de osteoblastos, o grupo OOF permaneceu elevado quando comparado ao grupo controle (p<0,05). Aos 60 dias o grupo SHAM apresentou menos osteoblastos, sugerindo processo avançado de reparo ósseo. Os animais osteopênicos apresentaram resposta inicial acelerada à lesão óssea, possibilitando a equivalência entre os grupos 30 dias pós-lesão. Mas, após este período apresentaram retardo na mineralização do osteóide, sugerindo atraso tardio no processo de reparo ósseo.<br>The purpose was to compare tibial bone union in normal and osteopenic female rats. Forty-nine Wistar albino female rats weighing 160 g (&plusmn;20g) and 100 days were distributed into 2 groups: Oophorectomized (OOF) and Pseudo-oophorectomized (SHAM). Thirty days later, a cortical injury was produced in all the animals. They were sacrificed in the 2nd, 4th, 6th and 8th weeks. Osteoblasts count was performed. Progressive weight increase was observed, but the OOF group was shown to have gained more weight (p&pound;0.05) than the SHAM group, at the time of the second surgery. After 15 days post-injury, the animals in the OOF group presented a higher number of osteoblasts (p&pound;0.05) compared to the SHAM group. Thirty days after injury, the number of osteoblasts was reduced, but both groups showed similar amounts. Forty-five days after injury, despite a constant reduction, the number of osteoblasts in the OOF group remained high when compared to SHAM (p&pound;0.05) group. After 60 days, we found less osteoblasts in the SHAM group, suggesting an advanced bone repair process. The osteopenic animals showed an early accelerated response, which became equivalent between both groups 30 days after injury. However, after that period, they showed a delayed osteoid mineralization, suggesting delayed late bone repair process

The Current Approaches and Challenges of Biopreservation

WOS: 000460411800019