The Experts below are selected from a list of 858 Experts worldwide ranked by ideXlab platform
Rüdiger Kries - One of the best experts on this subject based on the ideXlab platform.
-
Oral Versus Intramuscular Phytomenadione
Drug Safety, 1999Co-Authors: Rüdiger KriesAbstract:Oral and intramuscular Phytomenadione (vitamin K1) prophylaxis became an issue following the report of a potential carcinogenic effect of intramuscular but not oral Phytomenadione prophylaxis. There is increasing evidence, however, that oral Phytomenadione prophylaxis is less effective for the prevention of late vitamin K deficiency bleeding (VKDB) than intramuscular prophylaxis. Following a report of an increased cancer risk after intramuscular Phytomenadione, a series of papers on this issue appeared. Although an increased risk for solid tumours could almost certainly be excluded, a potential risk for acute lymphatic leukaemia in childhood could not be ruled out definitively. Almost all cases of late VKDB are preventable with intramuscular Phytomenadione prophylaxis administered once at birth, whereas a single oral dose given at birth is much less effective. Repeated oral Phytomenadione doses given to breast-fed infants either weekly (1mg) or daily (25μg) seem to be as effective as intramuscular Phytomenadione prophylaxis. The efficacy of 3 oral 2mg doses with the new mixed micellar preparation (‘Konakion MM’) remains to be established. Although a number of studies have failed to confirm a cancer risk with Phytomenadione, these studies have been unable to rule out a risk definitely because absence of evidence is not evidence of absence. A meta-analysis of the available studies might provide 95% confidence intervals narrow enough to exclude even a small cancer risk with some certainty. Oral prophylaxis will probably be as safe as the intramuscular prophylaxis if given daily (25μg) or weekly (1mg).
M. Pettit - One of the best experts on this subject based on the ideXlab platform.
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio (prothrombin time)
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio prothrombin time
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re-admission for bleeding during a 4-week follow-up period after cholangeopancreatography. Conclusion: Oral menadiol appears to be an effective alternative to intravenous Phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out-patients.
Murilo Fagundes De Castro - One of the best experts on this subject based on the ideXlab platform.
-
Avaliação da atividade anti-trypanosoma cruzi in vitro e in vivo de derivados de vitamina K
2012Co-Authors: Murilo Fagundes De CastroAbstract:Chagas disease (AD) is considered a neglected disease. Currently, it is estimated 10 million people infected with Trypanosoma cruzi, worldwide, mostly in Latin America. It is known that some derivatives of naphthoquinones can act on the trypanothione reductase (TR), specific enzyme of trypanosomatids responsible for controlling oxidative stress. Inhibition of TR favors an oxidative process and death of the parasite. This work aimed to investigate the potential anti-T. cruzi of Phytomenadione, (K1) and menadione (K3), both vitamin K derived from naphthoquinones. For this purpose, the trypanocidal effect of K1 and K3 was evaluated by in vitro assays with epimastigotes and trypomastigotes of T. cruzi in strains Colombian and Y using the inhibition tests, cytotoxicity of compounds of infection in macrophages test, evaluation of ultrastructural alterations as well as in vivo test to evaluate the reduction of the parasitemia. The best IC50 values to trypomastigote forms of T. cruzi were 27.55 μM to K1 and 2.19 μM to K3, compared to 12.46 μM of benznidazole, the standard drug. However, the treatment with vitamin K1 did not reduce parasitemia in vivo, which remains high similar to the vehicletreated control group. Vitamin K3 was able to inhibit both strains and different forms of the parasite in in vitro assays. In macrophage infection assay, vitamin K3 at a concentration of 21.4 μM significantly inhibited T. cruzi infection of cells when compared to the standard drug (benznidazole) in a concentration of 38.4 μM. Although this compound had a high cytotoxicity, vitamin K3 showed greater selectivity than the parasite mammalian cells, and in a low dose caused a reduction in parasitemia in vivo. The ultrastructural evaluation by transmission electron microscopy revealed cellular alterations induced by these compounds, especially the swelling of the kinetoplast and the presence of vacuoles. The ultrastructural quantification in the evaluation by scanning electron microscopy showed changes in about 80% of parasites observed when treated with 5 μM K3. Our results demonstrate the anti-T. cruzi molecules tested, suggesting that they may serve as a basis for designing new drug candidate compounds for the treatment of Chagas disease.
-
Avalia????o da atividade anti-trypanosoma cruzi in vitro e in vivo de derivados de vitamina K
Centro de Pesquisas Gon??alo Moniz, 2012Co-Authors: Murilo Fagundes De CastroAbstract:A doen??a de Chagas (DC) ?? considerada um agravo ainda negligenciado. Atualmente, estima-se cerca de 10 milh??es de pessoas infectadas pelo Trypanosoma cruzi, em todo o mundo, principalmente na Am??rica Latina. Sabe-se que alguns derivados de naftoquinonas podem agir sobre a tripanotiona redutase (TR), enzima espec??fica dos tripanossomat??deos respons??vel pelo controle oxidativo celular. A inibi????o da TR favorece um processo oxidativo e morte do protozo??rio. Este trabalho teve como objetivo investigar o potencial anti-T.cruzi da fitomenadiona, (K1) e menadiona (K3), ambas vitaminas K derivadas de naftoquinonas. Com este prop??sito, o efeito tripanocida de K1 e K3 foi avaliado atrav??s de ensaios in vitro com as formas tripomastigotas e epimastigotas do T. cruzi nas cepas Colombiana e Y utilizando os testes de inibi????o, citotoxicidade dos compostos, ensaio de infec????o em macr??fagos, avalia????o de altera????es ultraestruturais, bem como ensaio em in vivo para avalia????o na redu????o da parasitemia. Os valores de IC50 mais significativos para formas tripomastigotas do T. cruzi foram 27,55 ??M para K1, 2,19 ??M para K3 e 12,46 ??M para o benzonidazol, a droga padr??o. Contudo, o tratamento com a vitamina K1 n??o reduziu a parasitemia in vivo, que permaneceu alta assim como a do controle tratado com ve??culo. A vitamina K3 foi capaz de inibir ambas as cepas e diferentes formas do parasito em ensaios in vitro. No ensaio de infec????o de macr??fagos, a vitamina K3 em concentra????o de 21,4 ??M inibiu de forma mais significativa a infec????o de c??lulas em rela????o ?? droga padr??o, em concentra????o de 38,4 ??M. Apesar da citotoxicidade mais elevada, esta droga apresentou uma seletividade maior ao parasito do que a c??lulas de mam??feros e, em baixas doses, causou a redu????o na parasitemia in vivo. As avalia????es ultraestruturais por microscopia eletr??nica de transmiss??o evidenciaram altera????es celulares induzidas por estes compostos, destacando-se a tumefa????o do cinetoplasto e a presen??a de vac??olos. A quantifica????o ultraestrutural na avalia????o por microscopia eletr??nica de varredura demonstrou altera????es em cerca de 80% dos parasitos observados quando tratados com K3 a 5 ??M. Nossos resultados demonstram o efeito anti-T. cruzi das mol??culas testadas e sugerem que estas possam servir de base para o desenho de novos compostos candidatos a f??rmacos para o tratamento da doen??a de Chagas.Chagas disease (AD) is considered a neglected disease. Currently, it is estimated 10 million people infected with Trypanosoma cruzi, worldwide, mostly in Latin America. It is known that some derivatives of naphthoquinones can act on the trypanothione reductase (TR), specific enzyme of trypanosomatids responsible for controlling oxidative stress. Inhibition of TR favors an oxidative process and death of the parasite. This work aimed to investigate the potential anti-T. cruzi of Phytomenadione, (K1) and menadione (K3), both vitamin K derived from naphthoquinones. For this purpose, the trypanocidal effect of K1 and K3 was evaluated by in vitro assays with epimastigotes and trypomastigotes of T. cruzi in strains Colombian and Y using the inhibition tests, cytotoxicity of compounds of infection in macrophages test, evaluation of ultrastructural alterations as well as in vivo test to evaluate the reduction of the parasitemia. The best IC50 values to trypomastigote forms of T. cruzi were 27.55 ??M to K1 and 2.19 ??M to K3, compared to 12.46 ??M of benznidazole, the standard drug. However, the treatment with vitamin K1 did not reduce parasitemia in vivo, which remains high similar to the vehicletreated control group. Vitamin K3 was able to inhibit both strains and different forms of the parasite in in vitro assays. In macrophage infection assay, vitamin K3 at a concentration of 21.4 ??M significantly inhibited T. cruzi infection of cells when compared to the standard drug (benznidazole) in a concentration of 38.4 ??M. Although this compound had a high cytotoxicity, vitamin K3 showed greater selectivity than the parasite mammalian cells, and in a low dose caused a reduction in parasitemia in vivo. The ultrastructural evaluation by transmission electron microscopy revealed cellular alterations induced by these compounds, especially the swelling of the kinetoplast and the presence of vacuoles. The ultrastructural quantification in the evaluation by scanning electron microscopy showed changes in about 80% of parasites observed when treated with 5 ??M K3. Our results demonstrate the anti-T. cruzi molecules tested, suggesting that they may serve as a basis for designing new drug candidate compounds for the treatment of Chagas disease
S. Cairns - One of the best experts on this subject based on the ideXlab platform.
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio (prothrombin time)
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio prothrombin time
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re-admission for bleeding during a 4-week follow-up period after cholangeopancreatography. Conclusion: Oral menadiol appears to be an effective alternative to intravenous Phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out-patients.
R. Harvey - One of the best experts on this subject based on the ideXlab platform.
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio (prothrombin time)
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P
-
Phytomenadione or menadiol in the management of an elevated international normalized ratio prothrombin time
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Bruce Green, S. Cairns, R. Harvey, M. PettitAbstract:Aim: To evaluate the efficacy of oral menadiol compared to intravenous Phytomenadione when correcting coagulopathies associated with cholestasis. Methods: A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous Phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days. Results: Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous Phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re-admission for bleeding during a 4-week follow-up period after cholangeopancreatography. Conclusion: Oral menadiol appears to be an effective alternative to intravenous Phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out-patients.