Background: Dipyrone (metamizole) is one of the most widely used non-opioid analgesics for the treatment of cancer pain. Aim: Because evidence-based recommendations are not yet available, a systematic review was conducted for the German Guideline Program in Oncology to provide recommendations for the use of dipyrone in cancer pain. Design: First, a systematic review for clinical trials assessing dipyrone in adult patients with cancer pain was conducted. Endpoints were pain intensity, opioid-sparing effects, safety, and quality of life. Data sources: The search was performed in MedLine, Embase (via Ovid), and the Cochrane Library (1948–2013) and additional hand search was conducted. Finally, recommendations were developed and agreed in a formal structured consensus process by 53 representatives of scientific medical societies and 49 experts. Results: Of 177 retrieved studies, 4 could be included (3 randomized controlled trials and 1 cohort study, n = 252 patients): dipyrone significantly decreased pain intensity compared to placebo, even if low doses (1.5–2 g/day) were used. Higher doses (3 × 2 g/day) were more effective than low doses (3 × 1 g/day), but equally effective as 60 mg oral morphine/day. Pain reduction of dipyrone and non-steroidal anti-inflammatory drugs did not differ significantly. Compared to placebo, non-steroidal anti-inflammatory drugs, and morphine, the incidence of adverse effects was not increased. Conclusion: Dipyrone can be recommended for the treatment of cancer pain as an alternative to other non-opioids either alone or in combination with opioids. It can be preferred over non-steroidal anti-inflammatory drugs due to the presumably favorable side effect profile in long-term use, but comparative studies are not available for long-term use.

The anti-inflammatory properties of four medicinal plants were investigated. These plant extracts were subjected to screening for their possible effects as antioxidative, analgesic, and anti-inflammatory agents. In the antioxidant activity, the Plantago lancelota extracts resulted in an IC50 value of 0.4 mg/mL compared to the positive control quecertin with IC50 0.04 mg/mL Plantago lanceolata inhibited COX-2 activity with IC50 values of 0.41 mg/mL. However, the COX-1 inhibition indicated an IC50 of 68.99 mg/mL. The lipoxygenase assay indicated that Plantago lanceolata was the most active plant species with an IC50 value of 4.86 mg/mL compared to the positive control (quecertin) with an IC50<2mg/mL. The nitric oxide assay of the plant extracts indicates a dose-dependent activity of our plant extracts. Likewise the cell viability result indicated a good activity at dose 100 mg/mL. / Life and Consumer Sciences / M. Sc. (Life Sciences)

D. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences)|, Vaal University of Technology. / Medicinal plants provide valuable alternative sources of drugs and drug discovery because many have been used in traditional practices for centuries to manage or treat various forms of ailments. The aim of this study was to evaluate the biological activities of nine medicinal plants used by Zulus in Mabandla village, KwaZulu-Natal province, South Africa to treat inflammation and to isolate selected active compounds against studied pathogens from Alepidea amatymbica and Pomaria sandersonii. The plants were selected on the basis of an ethnobotanical survey based on questionnaire response and verbal interviews that were conducted in Mabandla village with the local traditional healers and herbalists. The isolation of compounds from Alepidea amatymbica and Pomaria sandersonii was based on the bioassay based study which was carried out in this study. Bioassay guided study involving in vitro anti-inflammatory measurement using soya bean derived 15 Lipoxygenase, free radical scavenging capacity against the ABTS●+ radical cation and DPPH● radicals; antimicrobial and bioautography assays against Staphylococcus aureus, ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Escherichia coli, ATCC25922, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus were carried out using the plants extracts, fractions and pure compounds. Isolation of compounds displaying biological activity was carried out by using open column chromatography and preparative thin layer chromatography (PTLC). The compounds were characterised by use of Nuclear Magnetic resonance, (NMR) and Mass Spectrometry (MS). The DPPH sprayed TLC showed that all the nine plants contained antioxidants. Most of which were contained in polar fractions of acetone and methanol. Results of the assays displayed a range of biological activities comparable to the positive controls used for each assay. DPPH● scavenging displayed EC50 values ranging between 1.008 and 467 Kg/ml. The highest activity was observed with the methanol fraction of Berkheya setifera with an EC50 value of 1.008 Kg/ml followed by the crude extract of Gunnera perpensa with EC50 value of 1.069 Kg/ml. Carissa bispinosa hexane fraction had the lowest activity of 467.7 Kg/ml. The Pomaria sandersonii DCM extract had the highest ABTS●+ radical scavenging activity by Pomaria sandersonii DCM extract, (1.273 Kg/ml) for the ethyl acetate, (5.973 Kg/ml) while the hexane fraction from Eucomis autumnalis had the lowest activity (929.4 Kg/ml). The activity of Pomaria sandersonii extracts and fractions demonstrated that the plant contains antioxidants that react with both DPPH and ABTS radicals although higher activities were shown by ABTS as displayed by the lower EC50 values. All the crude fractions and extracts had high to moderate antibacterial activities (20-625 Kg/ml) and anti-fungal activities (20-2500 Kg /ml). Pomaria sandersonii crude and fractions had the highest antimicrobial activity compared to other plants. Some MIC values for P. sandersonii dichloromethane and ethyl acetate fractions (80 Kg/ml in each case) compared well with gentamycin (4 Kg/ml) since they showed same values against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudonomus aeruginosa. The dichloromethane, acetone and methanol fractions were also active (20 Kg/ml) against both Candida albicans and Aspergillus fumigatus. Inhibition of pathogen growth demonstrated by the polar fractions of the studied plants suggested that some of the active compounds would be soluble in water. A total of seven compounds were isolated from Alepidea amatymbica and Pomaria sandersonii. We propose three were new compounds after considering literature search involving closely related research to this investigation. These were two diterpenes from Alepidea amatymbica, namely, 14-acetoxo-12-oxokaur-16-en-19-oic acid labelled as 0657 and 16-hydroxy-kaur-6-en-19-oic acid given the label 06-2 in this study. The third suspected new compound is the chalcone dimer, which is referred to as EM86 in this study from Pomaria sandersonii. EM80-2 was obtained as a mixture of the cis and trans of 2’, 4, 4,’-trihydroxychalcone or 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one, from Pomaria sandersonii. The three diterpenes, 14-acetoxokaur-16-en-19-oic acid (0652), 13-hydroxy-16-kauren-19-oic acid (06B) and 14-oxokaur-16-en-19-oic acid (06431) were isolated from Alepidea amatymbica for the first time. Isolated compounds were further tested as individual compounds and results showed that 16-hydroxy-kaur-6-en-19-oic acid (06-2) had weak activity against tested bacteria and fungi with the MIC: Staphylococcus aureus (320 Kg/ml) and Candida albicans, (320 Kg/ml). On the other hand 13-hydroxy-kaur-16-en-19-oic acid (06B) was more active against, Staphylococcus aureus (160 Kg/ml) and Aspergillus fumigatus (40 Kg/ml). The yellow compound that was isolated from Pomaria sandersonii, 1-(2, 4-ihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one was antimicrobial with the following MICs: Candida albicans: 80 Kg/ml; Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus: 160 Kg/ml and Aspergillus fumigatus: 625 Kg/ml. There were two mixtures referred to as EM 49 and EM 77 from Pomaria sandersonii which were difficult to purify but had anti-microbial inhibitory activities worth reporting. EM49 had MIC against Candida albicans of: 160μg/ml; Pseudomonas aeruginosa: 320 Kg/ml, Escherichia coli: 80μg/ml, Enterococcus faecalis 80μg/ml, and Staphylococcus aureus: 80μg/ml and Aspergillus fumigatus: 320μg/ml. EM 77 had MIC against Escherichia coli: 80 Kg/ml and Cryptococcus neoformans: 80μg/ml. Further work on their purification need to be done since in this research we are just reporting on their high MIC activities. The medicinal plants used to treat inflammation under different disease conditions in the Zulu community of Mabandla village, Kwa-Zulu Natal, South Africa have some relevant biological activities. The various antimicrobial, antioxidant and anti-inflammatory activities support the validity of their healing capacities that the traditional healers of the community claim to possess. Although there is evidence of good antimicrobial, antioxidant and anti-inflammatory activities by the crude extracts, the high levels of sucrose in P. prunelloides and glucose in G. perpensa should be borne in mind when using their decoctions in traditional medicine particularly by diabetic patients. In vitro results for the antioxidant, antinflammtory and antimicrobial activities carried out in this investigation illustrate that the plants can be a source of treatment and management for inflammation related conditions. These therefore justify their use in Zulu traditional medicine. However, in vivo assays should be carried out in order to completely validate claims by the traditional healers that they treat inflammation related conditions. / Vaal University of Technology

O tratamento mais comumente utilizado na inflamação é o uso de agentes antiinflamatórios não-esteróides (AINE). Estes fármacos, por sua vez, inibem as cicloxigenases, enzima responsável pela transformação do ácido araquidônico em prostaglandinas flogísticas, pela ação da fosfolipase A2. A síntese de compostos antiinflamatórios contendo núcleo pirrólico em suas estruturas vêm sendo um tópico muito atrativo e bastante estudado. O conhecimento do sítio de interação do fármaco ao receptor possibilita o planejamento de estruturas de novas substâncias candidatas a protótipos de novos fármacos. Portanto, esse trabalho consiste na síntese de derivados, contendo núcleo pirrólico, com potencial atividade antiinflamatória, com base na indometacina, protótipo da classe dos derivados arilalcanóicos. Os compostos foram obtidos, inicialmente via ciclização de &#946;-enaminoésteres, entretanto devido à complexidade da rota sintética e alto custo de determinados reagentes, propôs-se a metodologia de Hantzsch, descrita por Roomi e McDonald (1970). Esta metodologia consiste na formação de derivados pirrólicos à partir da condensação de &#945-halocetonas e compostos 1,3-dicarbonílicos na presença de amônia. Com base nesta metodologia, foram sintetizados compostos contendo núcleo pirrólico em suas estruturas, partindo de &#946;-enaminoésteres já sintetizados em nosso laboratório, como apresentado de maneira resumida no esquema 1 abaixo. (Veja arquivo em PDF). / Non-steroidal anti-inflammatory drugs (NSAIDs) have successfully been employed in the treatment of inflammation. These drugs are potent and highly selective as cyclo-oxigenase (COX-2) inhibitors. Recently, several pyrroles have been synthesized and evaluated for selective COX-1 / COX-2 enzyme inhibition. This is an extremely attractive topic. Thus, these recent findings have led us to design new pyrroles from &#946-enaminoesters and &#945;-halo ketonas (scheme 1). (See PDF file)

O tratamento mais comumente utilizado na inflamação é o uso de agentes antiinflamatórios não-esteróides (AINE). Estes fármacos, por sua vez, inibem as cicloxigenases, enzima responsável pela transformação do ácido araquidônico em prostaglandinas flogísticas, pela ação da fosfolipase A2. A síntese de compostos antiinflamatórios contendo núcleo pirrólico em suas estruturas vêm sendo um tópico muito atrativo e bastante estudado. O conhecimento do sítio de interação do fármaco ao receptor possibilita o planejamento de estruturas de novas substâncias candidatas a protótipos de novos fármacos. Portanto, esse trabalho consiste na síntese de derivados, contendo núcleo pirrólico, com potencial atividade antiinflamatória, com base na indometacina, protótipo da classe dos derivados arilalcanóicos. Os compostos foram obtidos, inicialmente via ciclização de &#946;-enaminoésteres, entretanto devido à complexidade da rota sintética e alto custo de determinados reagentes, propôs-se a metodologia de Hantzsch, descrita por Roomi e McDonald (1970). Esta metodologia consiste na formação de derivados pirrólicos à partir da condensação de &#945-halocetonas e compostos 1,3-dicarbonílicos na presença de amônia. Com base nesta metodologia, foram sintetizados compostos contendo núcleo pirrólico em suas estruturas, partindo de &#946;-enaminoésteres já sintetizados em nosso laboratório, como apresentado de maneira resumida no esquema 1 abaixo. (Veja arquivo em PDF). / Non-steroidal anti-inflammatory drugs (NSAIDs) have successfully been employed in the treatment of inflammation. These drugs are potent and highly selective as cyclo-oxigenase (COX-2) inhibitors. Recently, several pyrroles have been synthesized and evaluated for selective COX-1 / COX-2 enzyme inhibition. This is an extremely attractive topic. Thus, these recent findings have led us to design new pyrroles from &#946-enaminoesters and &#945;-halo ketonas (scheme 1). (See PDF file)

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 6 uppsatser.

Dissertation (Ph.D.)--University of South Florida, 2007. / Includes vita. Includes bibliographical references. Also available online.

The anti-inflammatory properties of four medicinal plants were investigated. These plant extracts were subjected to screening for their possible effects as antioxidative, analgesic, and anti-inflammatory agents. In the antioxidant activity, the Plantago lancelota extracts resulted in an IC50 value of 0.4 mg/mL compared to the positive control quecertin with IC50 0.04 mg/mL Plantago lanceolata inhibited COX-2 activity with IC50 values of 0.41 mg/mL. However, the COX-1 inhibition indicated an IC50 of 68.99 mg/mL. The lipoxygenase assay indicated that Plantago lanceolata was the most active plant species with an IC50 value of 4.86 mg/mL compared to the positive control (quecertin) with an IC50<2mg/mL. The nitric oxide assay of the plant extracts indicates a dose-dependent activity of our plant extracts. Likewise the cell viability result indicated a good activity at dose 100 mg/mL. / Life and Consumer Sciences / M. Sc. (Life Sciences)

The snakebite is a public health problem worldwide, especially in tropical countries. The objective of this study was to investigate the mechanisms involved in the effect of hydroethanolic extract of the stem bark Abarema cochliacarpos (EAc) in muscle injury induced by Bothrops leucurus. Male swiss mice were used (28-32g ; n= 6 groups), where they received perimuscular injection Bothrops leucurus venom (BlV 1 mg/Kg/paw Volume 50 ìl) the right hind limb, treated orally (po), with vehicle (saline) or EAc (100, 200 or 400 mg / kg). In the mechanical hypernociception animals were evaluated in time 2, 4 and 6 hours using digital analgesymeter (von Frey). Edema activity in the animals were evaluated at 15, 30, 60 and 90 minutes, using a digital caliper. Have motor activity was assessed by the rota -rod test and the animals were evaluated at 1, 3 and 7 days. Histological evaluation extensor digitorum longus muscle (EDL) was isolated, removed, fixed, paraffin emblocado (Optical Microscopy) and resin (Electron Microscopy) and cut. Tissues were stained with hematoxylin and eosin and observed under optical and electron microscopy and subsequently photographed. The experimental protocols were approved by the ethical committee for animal research at UFS (CEPA: 61/12). The results were analyzed using followed by Student.s t-test. The treatment orally with EAc (400 mg / kg ) inhibited mechanical hypernociception (2h 5.1 ± 0.76, 5.70 ± 0.65 4h, 6h 5.93 ± 0.49, (p < 0, 05) compared with the BlV venom group (2h 2.08 ± 0.33; 4h 2.28 ± 0.18; 6h 2.52 ± 0.24). The inhibition of edema was also seen in activity with EAc (400 mg / kg) (15 min 15.35 ± 0.27; 30 min 12.63 ± 0.69; 60 min 9.38 ± 0,29 and 90 min 6.83 ± 0.66, p < 0.05) compared with the BlV venom group (15 min 29.7 ± 0.17; 30 min 25.8 ± 0.26; 60 min 20.15 ± 0.24 and 90 min 14.76 ± 0.21). Regarding motor activity, the EAc (400 mg / kg) preserved motor ability (1day 83.22 ± 0.46; 3 days 98.02 ± 0.20 and 7 days 119.24 ± 0.48, p < 0.05) compared to the BlV venom group (1 day 20.03 ± 0.26, 3 days 35.22 ± 0.36 and 7 days 111.21 ± 0.18). Histological analysis showed an protection of muscle injury after administration of EAc (400 mg / kg), maintaining muscle fibers. Our results demonstrated that EAc inhibited the harmful effects of the venom, suggesting that this compound has biotechnological potential in adjuvant treatment of snakebite. / O ofidismo e um problema de saude publica em todo o mundo, especialmente nos paises tropicais. O objetivo deste trabalho foi de investigar os mecanismos envolvidos no efeito do extrato hidroetanolico da entrecasca da Abarema cochliacarpos (EAc) (popularmente conhecida como gbarbatimao h) na lesao muscular induzida pelo veneno de Bothrops leucurus (BlV). Foram utilizados camundongos Swiss machos (28-32 g; n=6 por grupo), que receberam injecao perimuscular do veneno Bothrops leucurus (BlV . 1 mg/Kg/pata . Volume 50 Êl) no membro posterior direito, tratados por via oral (v.o.), com veiculo (solucao salina) ou EAc (100, 200 ou 400 mg/kg). Na hipernocicepcao mecanica os animais foram avaliados nos tempos 2, 4 e 6 horas, utilizando o analgesimetro digital (Von Frey). Na atividade edematogenica os animais foram avaliados nos tempos 15, 30, 60 e 90 minutos, utilizando o paquimetro digital. Ja atividade motora foi avaliada pelo teste de rota-rod e os animais foram avaliados em 1, 3 e 7 dias. Na avaliacao histologica o musculo Extensor digitorum longus (EDL) foi isolado, retirado, fixado, emblocado com parafina (Microscopia optica) e resina (Microscopia eletronica) e cortados. Os tecidos foram corados com hematoxilina- eosina e observados ao microscopio optico e eletronico e posteriormente fotografados. Os protocolos experimentais foram aprovados pelo comite de etica em pesquisa com animais da UFS (CEPA: 61/12). Os resultados foram analisados utilizando o teste Student.S t-test. O tratamento, por v.o, com EAc (400 mg/Kg) inibiu a hipernocicepcao mecanica, (2h 5,1 }0,76; 4h 5,70 }0,65; 6h 5,93 }0,49; p<0,05) quando comparados aos animais do grupo BlV (veneno) (2h 2,08 }0,33; 4h 2,28 }0,18; 6h 2,52 }0,24). A inibicao tambem foi verificada na atividade edematogenica, com EAc (400 mg/kg), (15 min. 15,35 }0,27; 30 min. 12,63 }0,69; 60 min. 9,38 }0,29 e 90 min. 6,83 }0,66; p<0,05), quando comparados aos animais do grupo BlV (veneno) (15 min. 29,7 }0,17; 30 min. 25,8 }0,26; 60 min. 20,15 }0,24 e 90 min. 14,76 }0,21). Quanto a atividade motora, o EAc (400 mg/Kg) preservou a capacidade motora (1 dia 83,22 }0,46; 3 dias 98,02 }0,20 e 7 dias 119,24 }0,48; p<0,05), comparados ao grupo BlV (veneno) (1 dia 20,03 }0,26; 3 dias 35,22 }0,36 e 7 dias 111,21 }0,18). Na analise histologica verificou-se uma protecao da lesao muscular apos administracao do EAc (400 mg/Kg), preservando as fibras musculares. Nossos resultados demonstraram que o EAc inibiu os efeitos nocivos do veneno, sugerindo que este composto apresenta potencial biotecnologico no tratamento coadjuvante do ofidismo.

The deleterious effects of MPO make it a new target for medicinal research. The aim of our study is to find promising inhibitors of MPO for using them as starting point of new anti-inflammatory drugs. Depending on previous researches on MPO inhibitors, we selected 5-fluorotryptamine as starting compounds. Using docking experiments, we designed a series of compounds derived from 5-fluorotryptamine. Two modifications were proposed: <p>& / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished