Mapa de evidências sobre a efetividade clínica da medicina antroposófica: informe executivo / Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos da Medicina Antroposófica, referida na PNPIC como Antroposofia Aplicada à Saúde, em função de sua natureza multiprofissional. A partir de uma ampla busca bibliográfica foram incluídos no mapa 33 estudos de revisão que analisaram o efeito de intervenções com medicamentos antroposóficos, terapias antroposóficas e terapias multimodais para desfechos clínicos. No mapa estão representadas 63 associações entre 5 tipos de intervenções e 19 desfechos clínicos, com indicação do efeito reportado e nível de confiança da evidência reportada nos estudos. Principais Achados: • As intervenções foram organizadas em três grupos: Medicamentos Antroposóficos (Viscum album ­ 22 revisões e Outros medicamentos ­ 4 revisões), Terapias Antroposóficas (Euritmia ­ 2 revisões e Outras terapias ­ 1 revisão) e Terapias Multimodais (Em Geral ­ 4 revisões). • As intervenções foram associadas a 19 desfechos ordenados em cinco grupos: Bem-estar e Qualidade de Vida, Câncer, Atenção à Saúde, Indicadores Fisiológicos e Metabólicos e Outras Condições Patológicas. • A maioria das associações foi para o grupo de desfecho Câncer, seguido pelo grupo Bem-estar e Qualidade de Vida. Dentre os desfechos, destaque para: Qualidade de Vida (12 revisões), Sobrevida (9 revisões), Segurança do Paciente (8 revisões) e Sintomas de Quimioterapia e Radioterapia (7 revisões). • Dentre as intervenções, a maioria das associações foi para Viscum album (48 associações). • As intervenções multimodais, outros medicamentos, Euritmia e outras terapias foram associadas aos desfechos: Resultado do tratamento (5 associações), Satisfação e Segurança do paciente (2 associações cada), Infecções respiratórias (3 associações), Coordenação cardiorrespiratória, Transtornos gastrointestinais e Edema (1 associação cada). Implicações para a prática e pesquisa: • Considerando os efeitos positivos reportados (em 27 associações), destaque para o uso de medicamento antroposófico Viscum album (19 associações) para os desfechos Qualidade de Vida, Segurança do Paciente e Sintomas de Quimioterapia e Radioterapia. • Quanto aos efeitos potencialmente positivos (em 21 associações), a maioria foi associado ao Viscum album (18 associações) para os desfechos: Sobrevida ao câncer, Sintomas de Quimioterapia e Radioterapia e Qualidade de Vida. • Identificaram-se efeitos inconclusivos em 15 associações para 11 diferentes desfechos, o que sugere uma necessidade de novos estudos primários sobre intervenções com medicamentos e terapias antroposóficas. • Não foram identificados estudos com ausência de efeito ou efeitos negativos.

Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

The map provides an overview of the evidence on the effects of Anthroposophic Medicine, referred to in the National Policy on Integrative and Complementary Practices (PNPIC) as applied Anthroposophy in Health, due to its multiprofessional nature. Based on an extensive literature search, the map includes 33 review studies that analyzed the effects of interventions with anthroposophic medicines, anthroposophic therapies, and multimodal therapies on clinical outcomes. The map represents 63 associations between 5 types of interventions and 19 clinical outcomes, indicating the reported effect and level of confidence in the evidence reported in the studies. Key Findings: • The interventions were organized into three groups: Anthroposophic Medicines (Viscum album - 22 reviews and Other medicines - 4 reviews), Anthroposophic Therapies (Eurythmy - 2 reviews and Other therapies - 1 review), and Multimodal Therapies (Overall - 4 reviews). • The interventions were associated with 19 outcomes grouped into five categories: Well-being and Quality of Life, Cancer, Healthcare, Physiological and Metabolic Indicators, and other Pathological Conditions. • The majority of associations were found in the Cancer outcome group, followed by the Well-being and Quality of Life group. Notable outcomes included Quality of Life (12 reviews), Survival (9 reviews), Patient Safety (8 reviews), and Chemotherapy and Radiotherapy Symptoms (7 reviews). • Among the interventions, the majority of associations were related to Viscum album (48 associations). • Multimodal interventions, other medicines, eurythmy, and other therapies were associated with outcomes such as Treatment Outcome (5 associations), Patient Satisfaction and Safety (2 associations each), Respiratory Infections (3 associations), Cardiorespiratory Coordination, Gastrointestinal Disorders, and Edema (1 association each). Implications for Practice and Research: • Considering the reported positive effects (in 27 associations), the use of anthroposophic medicines Viscum album (19 associations) stands out for Quality of Life, Patient Safety, and Chemotherapy and Radiotherapy Symptoms outcomes. • Regarding potentially positive effects (in 21 associations), the majority were associated with Viscum album (18 associations) for Cancer Survival, Chemotherapy and Radiotherapy Symptoms, and Quality of Life outcomes. • Inconclusive effects were identified in 15 associations for 11 different outcomes, suggesting a need for further primary studies on interventions with anthroposophic medicines and therapies. • No studies were identified with no effect or negative effects.

Viscumalbum L. homeopathic mother tinctures: metabolome and antitumor activity

Viscum album L. is a semi-parasitic plant with antitumor activity attributed to theaqueous extracts. However, European V. album ethanolic extracts (VAE) have also demonstrated invitro activity in tumor models. Aims: Evaluate the metabolic profiles of fifty VAE harvested duringsummer and winter seasons and their antitumor activity through 2D and 3D models. Methodology:VAEwerepreparedbymacerationfrom:V.albumsubsp.albumgrowingonMalus domestica,Quercus sp.and Ulmus sp.; V. album subsp. austriacum from Pinus sylvestris; V. album subsp. abietis from Abies alba.Chemical analyses were performed through liquid chromatography coupled with high resolutionmass spectrometry and Partial Least Squares Discriminant Analysis (PLS-DA) was performed in theMetaboanalyst 4.0. The antitumor potential of the selected VAE was evaluated in 2D and 3D models(MDA-MB-231 cancer cells) by MTT, crystal violet and glycolytic pathway analysis. Results anddiscussion:Thefirst3principalcomponentsinPLS-DAexplained60%and40%ofdatavariationin positive andnegativemodesrespectively.Threegroupswereformedandshowedchemicalsimilarityamong V. album subspecies. The compounds responsible for group separation were tentativelyidentifiedas:pinobankasinornaringenin hexoside;isorhamnetin-3-hexoside,meglutolanddifferent aminoacids.ThesummerVAEat0.5%v/vinducedhighercytotoxicdamagethanthewinterpreparations, and Abies alba and Quercus sp. VAE promoted 49% and 42% reduction of tumorviability in 3D model (72h incubation), respectively. MDA-MB-231 glycolytic pathway in 2D modelshowed a decrease in the glucose consumption and extracellular lactate production. Also, PFK (6-phosphofructo-1-kinase)andPK(Pyruvatekinase)activitieswereinhibitedbyAbiesalbaandQuercus sp. VAE at 48h of incubation. Conclusion: VAE extracts showed different metabolomes andthe glycolytic pathway should be an important target involved in the inhibition of tumor growth bytheseextracts

In vitro evaluation of the effects of Viscum album homeopathic preparations on murine melanoma cells

Viscum album extract (VA) is a complementary treatment in cancer, with in vitro and in vivo cytotoxic effects on several tumor types when applied in phytochemical doses. However, highly diluted ethanolic homeopathic preparations' effects and mechanisms need further study. Aims:To assess the in vitro effects of highly diluted VA from the subspecies V. album abietis and V. album album at different potency levels in different dilution ratios on murine melanoma cells. Methodology:The VA mother tinctures (MT)from Abies alba (MTA) and Quercus robur (MTQ) were prepared with summer and winter samples, harvested in Switzerland. They were submitted to homeopathic ethanolic maceration and a subsequent dynamization process. MTA, MTQ and the following respective potencies were tested in B16F10 murine cells: 3x, 12x, 30x, 6cH, 12cH, 200cH, 2LM, 3LM, and 5LM. Dynamized water, dynamized and non-dynamized ethanol, and carboplatin were used as control groups. The mitochondrial activity and cell viability analysis were performed at 1, 24, 48, and 72 hours by in vitro incubation. MTA and MTQ harvested in summer, as well as 12x, 200cH and 5LM potencies were also tested to cell apoptosis and necrosis markers, reactive oxygens species (ROS) production, inflammatory cytokines profile, cell morphology, and migratory capacity. Results and discussion: MTA and MTQ induced a decrease in cell metabolism and higher cytotoxicity within 1 hour, with significant morphological changes and increased production of ROS and inflammatory cytokines. Both homeopathic dilutions 12x and 5LM showed an influence on cell metabolism, cell replication, and oxidative stress modulation with inflammatory cytokines, mitosis, and migration pattern changes. On the other hand, Quercus robur and Abies alba 200cH showed increased on cytotoxicity and ROS levels, respectively. Conclusion:The in vitro effects of Viscum album homeopathic solutions in melanoma cells highlight the promising antitumoral potential and reinforce the need for further research to better understanding their mechanisms of action.

Homoeopathic Viscum album (10-3) is More Cytotoxic to in vitro Culture of Human Breast Cancer Cell Line than to Human Mesenchymal Stem Cells

BackgroundBreast cancer has been considered a public health problem and homeopathic treatments are becoming increasingly recommended due to its ways of action and absence of adverse effects. MCF-7 is an adenocarcinoma of human breast cell line useful as preclinicalmodel to screen therapeutic agents such as ultra-diluted Viscum album, an European plant which extract is commonly used in cancer therapy. AIMS MCF-7 and mesenchymal stem cells (MSC) were used to evaluate the in vitrocytotoxicity of homoeopathic Viscum album 1x10-3(VA3X). Methodscells were cultured for 24 hours in controlled environment (37.5oC and 5% CO2) in 96-well plates. After this time, VA3X was added to the culture medium in concentrations varying from 10 to 100 L/mL.A control group was maintained with culture medium only. Cells were cultivated for 48 hours in these conditions for evaluation of cell viability by MTT assay. ResultsHigher cytotoxicity was observed in MCF-7 when compared to MSC, as the lower concentration of VA3X was capable of inducing tumor cell death and not healthy cell death. The MTT assay results were that 42 L/mL of VA3X reduced MCF-7 cells viability to 50% and 62 L/mL reduced MSC cells to the same percentage, what means that tumor cells are more sensible to VA3X than heathy cells. ConclusionViscum albumpresented higher cytotoxic action on human breast cancer cell line culture than on mesenchymal stem cells. This medicine is extensively used against cancer, and the use of the homoeopathic form of it brings new possibilities as no or fewer adverse effects would be present.(AU)

Two symmetrical unsaturated acids isolated from Viscum album / 中国天然药物

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.

Chemical Pleurodesis Using Doxycycline and Viscum album Extract

BACKGROUND: In chemical pleurodesis for managing pulmonary air leak, tetracycline derivatives are commonly used, and their effectiveness has been established in many studies. Recently, a Viscum album extract was used in chemical pleurodesis. We compared the effects of V. album with those of a tetracycline derivative (doxycycline) to demonstrate the therapeutic effectiveness of the V. album extract in chemical pleurodesis for managing pulmonary air leak. METHODS: Between October 2010 and October 2016, chemical pleurodesis was performed using doxycycline in 40 patients and the V. album extract in 37 patients. Thirty-three patients were in the postoperative state after pulmonary resection, and 44 patients suffered from spontaneous pneumothorax. RESULTS: No statistically significant difference in the success rate was observed between the 2 groups (V. album extract and doxycycline). In both groups, chest pain was the most common complication. More patients in the doxycycline group complained of severe chest pain (42.1% vs. 13.5%, p=0.006). In the V. album extract group, 24.3% of the patients required a chest tube to drain the pleural effusion after cessation of the air leak (doxycycline group: 5%, p=0.022). Further, the amount of pleural effusion drained on the day after the last chemical pleurodesis in the V. album extract group was greater than that in the doxycycline group (162.2±170.2 mL vs. 97.0±77.2 mL, p=0.032). All patients were discharged from the hospital without complications after pleural effusion drainage. CONCLUSION: Considering that treatment using the V. album extract was less painful, V. album might be a feasible option for chemical pleurodesis. However, pleural effusion should be monitored carefully when using V. album extract for treating patients suffering from air leak.

Acute Respiratory Distress Syndrome after Viscum album Pleurodesis for Primary Spontaneous Pneumothorax

A 52-year-old male patient who underwent multiple wedge resections experienced postoperative acute respiratory distress syndrome in both lungs after Viscum album pleurodesis. Despite initial rapid deterioration in clinical condition and rapid progression of bilateral lung infiltration, he exhibited a relatively smooth clinical recovery with marked response to glucocorticoid treatment. Our case report suggests that care must be taken to guard against the development of acute respiratory complications in the use of Viscum album for pleurodesis. However, in view of the clinically benign course, initial aggressive management of complications can prevent suffering and sequelae.

Korean Mistletoe (Viscum album var. coloratum) Inhibits Amyloid beta Protein (25-35)-induced Cultured Neuronal Cell Damage and Memory Impairment

The present study aims to investigate the effect of methanol extract of Korean mistletoe (KM; Viscum album var. coloratum), on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons and memory impairment in mice. Exposure of cultured neurons to 10 microM Abeta (25-35) for 24 h induced a neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM (10, 30 and 50 microg/ml) significantly inhibited the Abeta (25-35)-induced apoptotic neuronal death. KM (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of intracellular calcium concentration ([Ca2+]i), which was measured by a fluorescent dye, Fluo-4 AM. Glutamate release into medium and generation of reactive oxygen species (ROS) induced by 10 microM Abeta (25-35) were also inhibited by KM (10, 30 and 50 microg/ml). These results suggest that KM may mitigate the Abeta (25-35)-induced neurotoxicity by interfering with the increase of [Ca2+]i and then inhibiting glutamate release and generation of ROS in cultured neurons. In addition, orally administered KM (25 and 50 mg/kg, 7 days) significantly prevented memory impairment induced by intracerebroventricular injection of Abeta (25-35) (8 nmol). Taken together, it is suggested that anti-dementia effect of KM is due to its neuroprotective effect against Abeta (25-35)-induced neurotoxicity and that KM may have therapeutic role in prevention of the progression of Alzheimer's disease.

A medicina dos druidas e o Viscum album / The medicine of the druids and the Viscum album

Os autores apresentam uma revisão histórica sobre o Viscum album, planta utilizada na Farmacopeia homeopática e sua relação com a cultura Druida.

Methanolic extract of African mistletoe (Viscum album) improves carbohydrate metabolism and hyperlipidemia in streptozotocin-induced diabetic rats

OBJECTIVE@#To justify the use of African mistletoe (AM) Viscum album (V. album) in folkoric medicine to treat diabetes.@*METHODS@#In one experiment, the fasting blood glucose (FBG) levels of diabetic rats were monitored for 4 h. Diabetic rats were treated with AM at doses of 50 mg/kg (AM1) and 100 mg/kg (AM2), glibenclamide (GB) (positive control) and saline solution (SS). In another experiment, diabetic rats were treated with AM2, GB and SS daily for 3 weeks.@*RESULTS@#AM1 and AM2 elicited significant (P<0.05) hypoglycaemic effects within 4 h of extract administration. AM1 and AM2 decreased the FBG by 41% and 49%, respectively, at 2 h. AM2 was found to lower FBG by 51%, relative to baseline, which was comparable to GB at 3 h. In the second experiment, AM2 and GB significantly (P<0.05) decreased the FBG by 34% and 51%, respectively. This was followed by marked decrease in levels of HbA1C in AM2- and GB- treated diabetic rats. AM2 significantly (P<0.05) decreased the STZ-induced increase in levels of serum triglyceride, urea, lactate dehydrogenase, α-amylase and low-density lipoprotein-cholesterol. Furthermore, diabetic rats treated with AM2 had significantly (P<0.05) elevated high-density lipoprotein-cholesterol. In contrast, STZ administration produced insignificant (P<0.05) effect on the levels of serum creatinine and total bilirubin.@*CONCLUSIONS@#Extract of African mistletoe has anti-diabetic and anti-hyperlipidemic effects in STZ-diabetic rats. AM may find clinical application in the amelioration of diabetes-induced lipid disorders.

[Effects of Viscum album and Nigella sativa extracts on survival rate, growth factors and resistance to Aeromonas hydrophila infection in gold fish [Carassius auratus]]

Recently several types of herbal immune and growth stimulants have been used in aquaculture troughout the world. This study was performed to evaluate the effects of oral administration of Viscum album and Nigella sativa extracts, on survival rate, growth factors and resistance against Aeromonas hydrophila infection in gold fish. 270 gold fishes were divided into 2 immune and non-immune groups and each group into 3 treatments; V.album, N.sativa and control [each with 3 repeats]. Each treatment groups fed for 7 weeks with food supplemented with 0.5% of V.album, N.sativa or water. At the end of treatment, survival rate, growth factors and resistance to A.hydrophila infection were compared among the groups. Percentage of mortality in different groups were 9.33 to 12% and prescription of either extracts has no significant effect on survival of groups [p>0.05]. Food conversion rate and percentage of weight gain were 2.56 +/- 0.31 and 131.6+/-25.05% in V.album treatment and 3.12 +/- 0.37 and 73.2 +/- 4.53% in control treatment, respectively which showed a significant increase [p<0.05], growth factors didn't show any significant difference between N.sativa and control treatments [p=0.15]. Mortality rate after bacterial infection showed a significant decrease in V.album treatment [p<0.05] in a way that mortality in V.album treatments of immune and nonimmune groups were 40 and 80% and in control treatment were 63.3 and 100%, respectively. N.sativa had no significant effect on mortality after challenge [p=0.45]. Oral administration of V.album in gold fish has similar effects on immune and growth stimulation as those reported in other warm-blooded animals but N. sativa didn't show such effects

Estudos de casos clínicos oncológicos em caninos e felinos tratados com homeopatia injetável (2005-2007) / Clinical case studies cancer in dogs and cats treated with homeopathy injectable (2005-2007)

Este experimento clínico relata o resultado do tratamento de oito animais com tipos variados de neoplasias que foram tratados com uma combinação de medicamentos homeopáticos injetáveis, Arnica montana, Lachesis muta, thuya occidentalis, Echinacea e o Viscum album - um antineoplásico que estimula o sistema imune - e possuem efeitos citotóxicos, sendo uma alternativa ao tratamento convencional empregado nos animais domestícos. O resultado obtido no decorrer de 12 meses de acompanhamento indica que a medicação estuda auxilia na qualidade de vida demostrando ser uma possibilidade terapêutica auxiliando no controle da evolução da doença neoplásica em cães e gatos.

Ação do Viscum album em cultivo celular de carcinoma epidermoide de cabeça e pescoço / Viscum album effect in head and neck squamous cell carcinoma cell culture

O carcinoma epidermoide de cabeça e pescoço, hoje considerada mundialmente uma das neoplasias mais frequentes desta região, tornou-se um problema de saúde pública, necessitando urgente de medidas a serem tomadas, a fim de melhorar a qualidade de vida dos pacientes acometidos, consequentemente aumentando a sobrevida, avaliada em cinco anos. O carcinoma epidermoide de cabeça e pescoço é uma doença complexa, e inclui vários fatores etiológicos, além de alterações moleculares, capazes de desencadear e dar continuidade a alguns eventos. No geral os carcinomas orais são tratados primeiramente com cirurgia excisional ou radioterapia individualmente, ou em combinação para os estágios mais avançados. As preparações dos extratos fermentados de Viscum album (VA), uma planta semiparasita da família das Lorantáceas, vêm sendo utilizada, principalmente em países da Europa, com resultados promissores no âmbito das terapias coadjuvantes, especialmente a medicina antroposófica. Em conjunto com as terapias convencionais, tem demonstrado uma melhora na qualidade de vida dos pacientes portadores de neoplasias malígnas. Estudos in vitro, realizados em células cancerígenas, têm demonstrado que vários tipos de VA podem apresentar citotoxicidade em células de carcinoma, sendo capazes de ativar a cascata apoptótica ou levando as células à necrose. Este estudo teve por objetivo verificar a ação de três tipos de extratos de VA (Iscador Qu Spezial, Iscador P e Iscador M), em linhagens celulares de carcinoma epidermoide de língua (SCC9 e SCC25). Para isso foi verificada a ação citotóxica do fármaco Iscador Qu Spezial, por meio do teste de viabilidade celular, para a obtenção da IC50...

Head and neck squamous cell carcinoma, one of the most common malignancies worldwide in this area, became a public health problem that requires urgent attitudes to be taken in order to improve the quality of life of the affected patients, increasing survival that today valued at five years. Head and neck squamous cell carcinoma is a complex disease which includes several etiologic factors and different molecular changes that may trigger and get on with some events. In general, oral carcinomas are treated primarily with surgical excision or radiotherapy alone or in combination for cases in more advanced stages. Preparations of fermented extracts from fermented Viscum album (VA), a plant from the Loranthaceae family have been used, mainly in European countries, with promising results as adjuvant therapies, especially in the Anthroposophy Medicine. In combination with conventional therapies, VA has lead to improvement in quality of life of patients with cancer. in vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells being able to activate the apoptotic cascade or leading cells to necrosis. The present study aimed to verify the effect of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue (SCC9 and SCC25). The cytotoxic action of Iscador Qu Spezial was verified by cell viability test obtaining the IC50. The three drugs were tested as follow: Tunnel to evaluate apoptosis, Annexin V and FITC/propidium iodide were evaluated by flow cytometry to quantify the apoptosis rate induced by the drugs...

Dissertation abstract: Viscum album citotoxicity in Caco-2 cells (in vitro) analyzed by Dispersive Raman Spectroscopy

In the last decades, it has been observed a gradual increase in the diagnosis of neoplasm in both human beings and animals. This can be attributed to the advances in research and technology, which facilitated detection, promoting, thus, survival. On the other hand, the current incidence of cancer may also be attributed to an excess of chemicals in food products, radiation arising from antennae, environmental pollutants, indiscriminate use of hormone therapies, besides genetic alterations. Conventional oncologic treatments traditionally employ chemotherapic drugs. Later on, vegetal immunomodulators were also introduced, such as Viscum album. In the present study, the effectiveness of injectable extract Viscum album was tested in vitro in Caco-2 cells, in dilutions D3 (0.1ìg/ml ), D6 (0.1 ng/ml), D9 (0.1x10-³ ng/ml), D12 (0.1x10-6 ng/ml) and D30 (0.1x10-6 ng/ml). The optical method used was the Dispersive Raman Spectroscopy at 830nm by comparison to MTT Assay. The results showed that Viscum album has an action on mitochondrial activity, reducing cellular viability in Caco-2 cells in dilutions D3, D6 and D9. Correlation of Raman spectrum to the values obtained in the MTT test was statistically analyzed by PLS, revealing a sensitive tool for the detection of changes in the mitochondrial activity of Caco-2 cells. Raman spectroscopy is a non invasive diagnostic procedure, allowing for real-time diagnosis and reduction of costs, besides indicating the best therapy for each type of tumor as well as modifications in the therapeutic strategy.

Viscum album is another therapeutic option for HCC in patients with cirrhosis, value of GP 73 Golgi protein as a marker

Hepatocellular carcinoma [HCC] is one of the most common cancers worldwide. Efficacy of available treatments remains disappointing. Mistletoe extract [Viscum album], a cytotoxic, immune stimulating and immune modulating agent has been tried by subcutaneous or intralesional route in the management of this disease. Is to evaluate the effect of viscum fraxini 2 in the management of advanced HCC in patients with liver cirrhosis not amenable for other therapeutic intervention and evaluate the value of the recently investigated GP 73 Golgi protein as a marker of such disease. 26 patients with advanced cirrhosis and HCC were subjected to investigation and treatment in this study. All patients provided a complete history and physical examination, including performance status, concurrent non-malignant diseases and therapy. Laboratory studies included a complete blood cell counts, differential count, biochemical liver and renal function tests, electrolyte, chest x-rays, a-fetoprotein, triphasic liver computed scan [CT] and Child class evaluation were performed before treatment. Immunoblot Analysis for GP73 was performed in all patients before and at end of follow up. 2 ampoules of viscum fraxini-2 were administered subcutaneously once weekly. Each ampoule is 15 mg extract of 20 mg mistletoe herb from ash tree, diluted in dinatrium-mono-hydrogen phosphate, ascorbic acid and water] which is equivalent to 10000 ng/ml injection ampoules. The study included 26 patients. They were 19 males and 7 females, aged 37-62 years with a mean of 50.58 +/- 7.51 years. Modified Child-Pugh stage A was found in 2 patients [7.7%], stage B in 14 patients [53.8%] and stage C in 10 patients [38.5%]. The diagnosis of HCC was based on marked elevation of alpha-fetoprotein level and imaging studies indicating advanced HCC in 19 patients [73.1%] and on fine-needle aspiration cytology of liver tumors in 7 patients [16.9%]. The median duration of treatment on viscum fraxini-2 is 16 months [range 4-24 months]. The mean GP protein signal intensities by Westernblot in all patients before and at end of follow up were 30.38 +/- 9.43 and 25.15 +/- 12.15 respectively with P < 0.001 [highly significant]. In those showing reduction of tumor size, it was 27.46 +/- 11.04 and 17.31 +/- 8.12 respectively with P < 0.001 [highly significant]. In those showing increase in the size of tumor it was 33.31 +/- 6.69 and 30.00 +/- 10.40 respectively with P< 0.01 [also highly significant]. According to conventional radiological response criteria, only 2 patients [7.7%] achieved complete response. Three patients [11.6%] achieved partial response. Sub-optimal response was detected in 8 [30.8%] patients. The remaining 13 cases [50%] showed progressive disease or early death. Eight patients [30.8%] died early before 12 months of follow up. At the time of analysis after 24 months, 9 [34.6%] patients remained alive including two patients with CR, the three patients with partial response, two patients with sub-optimal response and 2 patients with slowly progressive disease. The median survival time for patients who died during the two years of follow up [17 patients, 65.4%] was 11.88 +/- 4.7 months. The overall follow up period including those who were alive at the end of the second year was 16.5 +/- 7.16 month. There were no drug related discontinuation or toxic deaths. Viscum fraxini 2 produced complete response in 7.7% and partial response in 11.6% while suboptimal response in 30.8% of patients. Thus, some beneficial effect can be achieved in half of patients. From these results, we can conclude that the drug can be added at the moment to the drug list for the treatment of HCC. Being safe, simply administered by weekly injections, cheep and nearly of similar efficacy to other drugs; it can be used either alone or in combinations for long periods in the treatment of HCC. This study also added another evidence for the value of the recently investigated, GP73 Golgi protein, in the diagnosis and follow up of patients with liver cirrhosis who develop HCC during treatment

Effect Crude Extract of Viscum album (mistletoe) on Plasma Lipids : an insight into its possible Antihyperglycaemic and Antihypertensive Properties

Background: Reports on the hypoglycaemic property of mistletoe leaf is abundant in the literature. In this study; we have investigated this property in relation to the lipid profile in Wistar rats.Methods: Six groups of five rats per group were used for the study. Diabetes was induced with alloxan (60mg/kg. ip) and hypertension by high salt- loading. The treated groups received the crude extract (150mg/kg. oral) for 5 weeks in addition to normal rat feed; water ad libitum. Plasma glucose; total cholesterol; triglyceride and LDL-cholesterol levels were determined using standard procedures.Results: The diabetic and the hypertensive rats had about 30.8and 9.1increase in blood sugar levels respectively compared to the control. The extract (150 mg/kg. oral) produced about 84.2and 33.2(P0.05) decrease in blood sugar levels in the diabetics and hypertensives respectively. Also the total cholesterol; triglyceride; and LDL-cholesterol levels were increased in both diabetics and hypertensives (P 0.05). The LDL levels were lowered by the extract by about 21.4and 24.3(P0.05) in the diabetics and hypertensives respectively. Finally the extract also produced about 34.5and 8.3depression of blood pressure of the hypertensives and normotensives respectively.Conclusion: We suggest the reduction of plasma lipid fractions by the extract as being responsible for the antihyperglycaemic and antihypertensive activities of the mistletoe extract

El extracto acuoso de viscum album induce la expresión de las sintasas de oxido nítrico inducible y endotelial en corazón aislado y perfundido de cobayo. Evidencia del mecanismo de vasodilatación coronaria / Viscum album aqueous extract induces inducible and endothelial nitric oxide synthases expression in isolated and perfused guinea pig heart. Evidence of the coronary vasodilation mechanism

The pharmacological effect of a Viscum album aqueous extract was evaluated on the Langendorff isolated and perfused heart model in normotense male guinea pig hearts. Coronary vascular resistance, left intraventricular pressure, nitric oxide release in the perfusion liquid, cyclic guanosine monophosphate production, and analysis of inducible and endothelial nitric oxide synthases expression by Western Blot in ventricular tissue were recorded in absence and presence of blockers and inhibitors, such as 3 microM gadolinium chloride, 100 microM N(omega)-nitro-L-arginine methyl ester and 10 microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. V. album aqueous extract exerts a significant decrease in the coronary vascular resistance, which courses with significant increases in nitric oxide and cyclic guanosine monophosphate production. Analysis of the expression of both nitric oxide synthases revealed that this extract significantly induces the expression of both isoforms in guinea pig hearts. These effects were inhibited by the presence of blockers and inhibitors. The coronary vasodilation induced by the extract is mediated by the nitric oxide/soluble guanylyl cyclase pathway. In addition, this extract shows a positive inotropic effect which that is tyramine-mediated by means of beta1-adrenergic stimulation.

Haematopoietic Agent(s) in the Crude Extract from the Leaves of Viscum album (Mistletoe)

Preliminary studies showed that the crude extract from viscum album leaves had an LD50 value of 420.70mg/kg mice. Thirty-six male albino Wistar rats were randomly divided into six groups of 6 rats per group. The groups were: Group 1; the normal rats (controls) were fed with normal rat chow and given water ad libitum. Group 2; consisted of normal rats administered with the extract. Group 3; the salt-induced hypertensive group consisted of hypertensive rats that did not receive extract treatment. Group 4; the salt-induced hypertensives that received extract treatment. Group 5; the alloxan-induced diabetics that were not treated with the extract; and group 6; the alloxan-induced diabetics that received extract treatment. Treatments were by daily administration of the extract (150mg/kg; oral); for six weeks after which the animals in each group were sacrificed and blood samples collected in heparinized tubes for counting using an electronic cell counter (ADVIA TM 60 Haematology system by Bayer). Results showed significant increase in the RBC counts; PCV

Viscum Album Therapy in Malignant Pleural Effusion / 대한흉부외과학회지

BACKGROUND: Malignant pleural effusion is a common clinical problem in neoplastic patients. With the diagnosis of a malignant pleural effusion, palliative therapy was done. One of the treatments was a chemical pleurodesis. Talc was the most commonly used a sclerosing agent, but the quality of patient's life was not improved. We was evaluated by other agents such as Viscum album for relief of malignant pleural effusion. MATERIAL AND METHOD: From November 2001 to October 2003, 17 patients who underwent to chemical pleurodesis for the malignant pleural effusion. We compared the talc (group I: 10 patients) and Viscum album (group II: 7 patients). We analysed them retrospectively in term of various factors and results. RESULT: There were no significant differences between group I and group II in the sex ratio, mean age, origin of primary cancer and site, but, group I had higher successful rate (80%:71%) than group II. Group II had better length of chest tube stay after procedure, Karnofsky performance and recurrence than group I. The failed treatement group was related to the pleural fluid pH and interval of initial chemical pleurodesis after thoracostomy. CONCLUSION: Although the chemical pleurodesis with Viscum album was slightly lower than talc in the successful rate, there was an alternative method instead of the chemical pleurodesis with talc to improve the patient's quality of life in malignant pleural effusion.