Antiparasitic Effects of Asteraceae Species Extracts on Echinococcus granulosus s.s.

Cystic echinococcosis is a zoonotic disease caused by the parasite Echinococcus granulosus sensu lato (s.l.), which is worldwide distributed and causes long-lasting infections in animals and humans. The existing treatment is limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has unwanted side effects and its efficacy is about 50%. The Asteraceae family includes plants that have therapeutic applications (medicinal species) and has an important role in new drug development. The species belonging to a different genus of this family show a wide range of anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, and antiparasitic activities, among others. The aim of the present study was to evaluate the in vitro efficacy of extracts of four Asteraceae species against protoscoleces of E. granulosus sensu stricto (s.s.). On the other hand, the Stevia aristata extract was assessed on the murine cyst of E. granulosus (s.s.) and the efficacy of S. aristata extract was investigated in a murine model of CE. Stevia satureiifolia, S. aristata, Grindelia pulchella, and G. chiloensis extracts at 100 µg/mL caused a decrease in protoscoleces viability; however, S. aristata extract produced the greatest in vitro protoscolicidal effect. After 20 days of treatment with the highest concentration (100 µg/mL) of S. aristata extract, protoscoleces viability decreased to 0%. The tegumental changes observed by scanning electron microscopy were consistent with the reduction in vitality. The collapse of the germinal layer was registered in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated during 4 days with 50 and 100 µg/ml, respectively. The half maximal effective concentration (EC50) value of the S. aristata extract against E. granulosus (s.s.) cysts was 47.86 µg/mL (96 h). The dosage of infected animals with the 50 mg kg-1 dose of S. aristata extract resulted in a significant reduction in cyst weight in comparison with the control group. In conclusion, S. aristata extract was demonstrated to exert a marked effect, both in vitro and in the murine model.

Anthelmintic activity of Stevia multiaristata extract against Echinococcus granulosus sensu stricto.

Cystic echinococcosis is a zoonotic disease caused by the larval stage of the parasite Echinococcus granulosus sensu lato. The available anti-parasitic treatment is mostly limited to a continuous administration of albendazole. However, due to its numerous side-effects and efficacy of around 50%, there is a need to find new drugs to improve the treatment for this disease. In the current study, the in vitro and in vivo efficacy of a Stevia multiaristata extract against E. granulosus sensu stricto (s.s.) was demonstrated. Stevia multiaristata extract (100 and 50 µg mL−1) caused a quick viability decrease on protoscoleces which was consistent with the observed tegumental alterations. Loss of turgidity was detected in 95 ± 3.4% of cysts incubated with S. multiaristata extract during 2 days (100 µg mL−1) and the collapse of the germinal layer was observed in 60 ± 9.3% of cysts treated with 100 µg mL−1 of the S. multiaristata extract during 4 days. The half maximal effective concentration value was 69.6 µg mL−1 and the selectivity index for E. granulosus s.s. cysts was 1.9. In this clinical efficacy study, the treatment of infected mice with the S. multiaristata extract (50 mg kg−1) caused a significant decrease in the weight of the cysts compared with the control group. These results coincided with the tissue damage observed in the cysts at the ultrastructural level. In conclusion, we observed high protoscolicidal and cysticidal effects, and significant reduction in the weight of the cysts in experimentally infected mice following treatment with the S. multiaristata extract.

Could beta-myrcene be an alternative to albendazole for the treatment of experimental cystic echinococcosis?

Echinococcus granulosus causes hydatidosis or cystic echinococcosis in humans and livestock. In humans, this disease can be managed with surgery, percutaneous treatment, chemotherapy and/or observation. The chemotherapeutic agents used and approved for treatment of hydatidosis are benzimidazoles. Because of the difficulties in achieving successful treatment, considerable efforts have been made to find new natural compounds against hydatid disease. Beta-myrcene is a monoterpene presented in the essential oils of different plants. It is the principal component of essential oil of Rosmarinus officinalis (rosemary). The goal of the present study was to evaluate the in vitro effects of beta-myrcene against germinal cells, protoscoleces and murine cyst of E. granulosus, as well also, investigate its chemoprophylactic activity in a murine model of cystic echinococcosis. For the in vitro assays, the parasites were incubated with beta-myrcene at 10, 5 and 1 µg/mL. The treatments were dose and time-dependent, and consistent with the observed morphological alterations. In the chemoprophylactic efficacy study, the effect of beta-myrcene was similar to albendazole, the reference drug for human echinococcosis treatment.

In vitro effect of 5-fluorouracil and paclitaxel on Echinococcus granulosus larvae and cells.

Human cystic echinococcosis is a zoonosis caused by the metacestode stage of the tapeworm Echinococcus granulosus. Although benzimidazole compounds such as albendazole and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of 5-fluorouracil (5-FU) and paclitaxel (PTX) against E. granulosus germinal cells, protoscoleces and cysts. 5-FU or PTX inhibited the growth of E. granulosus cells in a time dependent manner. Although both treatments had a protoscolicidal effect, 5-FU had a considerably stronger effect than PTX. 5-FU produced a dose- and time-dependent effect, provoking the complete loss of viability after 24 days of incubation. Moreover, cysts did not develop following the inoculation of treated protoscoleces into mice. The loss of viability was slower in PTX treated protoscoleces, reaching to approximately 60% after 30 days. The results of the in vitro treatment with 5-FU and PTX were similar in secondary murine cysts. The employment of SEM and TEM allowed us to examine, at an ultrastructural level, the effects induced by 5-FU and PTX on E. granulosus germinal cells, protoscoleces and murine cysts. In conclusion, the data obtained clearly demonstrated that 5-FU and PTX at clinically achievable concentrations inhibit the survival of larval cells, protoscoleces and metacestodes. In vivo studies to test the antiparasitic activities of 5-FU and PTX are currently being undertaken on the murine model of cystic echinococcosis.

Quality of life in patients before and after haematopoietic stem cell transplantation measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30.

The EORTC Quality of Life Core Questionnaire QLQ-C30 is widely used, but no reference values are available for patients receiving HSCT. We retrieved data for 38 samples from 33 papers in English and German that provided evaluable information on QLQ-C30 scores (mean, s.d.) covering about 2800 patients. Results are presented as a table that provides reference data that allow QLQ-C30 scores at different points during the disease trajectory to be put in context. With respect to their central tendency and their variance, scores vary over time. Quality of life is lowest during inpatient time. About 1 year after HSCT, the pre-transplant level is reached. Physical functioning is the scale reaching the highest level of all scales. Fatigue, dyspnoea and insomnia are symptoms that remain at an elevated level and should thus be considered as persisting problems after HSCT. For the interpretation of differences between scores, a very conservative recommendation would be to set the s.d. at 30 points. Doing so, one could be quite sure of having found a clinically significant change if the difference of two scores exceeds 15 points. Differences below 5 points should be interpreted with caution.

[Psychiatric comorbidities in visceral surgery patients with cancer]. / Psychische Begleiterkrankungen bei Krebspatienten in der Viszeralchirurgie.

BACKGROUND: Cancer patients with mental disorders suffer from a decreased quality of life (QoL) and are in need of appropriate treatment. METHODS: A total of 99 cancer patients were interviewed during surgical inpatient treatment with a structured clinical interview for diagnosis of mental disorders (SCID). The QoL and distress were examined prospectively using the validated questionnaires EORTC QLQ-C30 and HADS. Patient psychological well-being and the need for psycho-oncological treatment were assessed by 31 doctors and 41 nurses. RESULTS: Of the patients 19% were diagnosed with having a mental disorder and in 10% immediate treatment was deemed necessary. This was identified by doctors and nurses in 38-60% and by HADS in 78% of the cases. The QoL of patients with psychiatric comorbidities was diminished 6 months after surgery, while patients without comorbidities recovered significantly better. CONCLUSION: Of the visceral surgery cancer patients studied 10% had a relevant mental disorder. To prevent symptoms becoming chronic they should be detected and treated early and efficiently.

Fatigue assessment questionnaire: standardization of a cancer-specific instrument based on the general population.

OBJECTIVES: Fatigue has become a major issue of concern in the care of cancer patients, as it has been shown to compromise their quality of life in a significant and lasting way. However, there is a lack of economic and specific measures. The Fatigue Assessment Questionnaire (FAQ) has been developed based on thorough interviews and tested on a large mixed sample of cancer patients. The purposes of this paper are to test the psychometric properties of the FAQ and to provide norms for the German population. METHODS: The FAQ was administered to a representative sample of the German population (1,340 female and 1,101 male participants) along with standardized scales of depression, mood and life satisfaction. RESULTS: We could confirm that fatigue is multidimensional and can be measured by the scales of physical, affective and cognitive fatigue with good reliability and validity. The dependency of fatigue on sex and age makes it useful to have standard fatigue scores for oncological research as provided in this paper. CONCLUSION: The FAQ is a promising, differentiated, yet economic instrument for further use in oncological research.

[Subjective health of older people in view of the SF-36: Values from a large community-based sample]. / Die subjektive Gesundheit älterer Menschen im Spiegel des SF-36: Normwerte aus einer bevölkerungsrepräsentativen Erhebung.

This paper presents data regarding the German version of the SF-36 (Short Form 36 Questionnaire; Bullinger and Kirchberger, 1998) that were obtained from a large community based sample of the German population. Results are reported for the elderly at the age of 60 and older from the German general population (N = 690; 57% female). Presented are the internal consistencies of the scales (Cronbach's Alpha), the intercorrelations of the scales, mean values of the scales separated by sex, age group (60-64 years, 65-69 years, 70-74 years, 75-79 years, 80 years and older) and residence (Eastern and Western Germany) as well as percentile ranks for the whole sample.

[The emotional sensitivity of elderly people--validation of the Profile of Mood States for people over 60 years]. / Die emotionale Befindlichkeit älterer Menschen -- Normierung des Profile of Mood States für über 60-Jährige.

The German short version of the "Profile of Mood States (POMS)" with 35 items (seven-point response scale; rating related to the past 24 hours) was psychometrically tested in a sample of elderly people of 60 years of age and older (n=690; 57% female). The internal structure of the POMS with four factors (dejection, fatigue, displeasure, vigour) could largely be replicated, even though the first three factors are intercorrelated. Reliability of the scales appears to be very good. The convergent validity of the POMS scales could be proved by correlations with the Beck Depression Inventory and the SF-36. Specific norms are presented for four age groups, men and women and elderly living in Eastern and Western Germany. So it seems appropriate to use the German short version of the POMS as a valid and economic instrument for gerontological studies.

[Mental disorders in the peripartum period--early detection and multi-professional cooperation]. / Peripartale psychische Störungen - Früherkennung und multiprofessionelle Kooperation.

Given the great prevalence of mood disorders in early motherhood, the danger of chronic, particularly depressive mood disorders and the negative long-term effects on the socio-emotional development of the child requires specific and individual treatment. Midwives could serve as mediators between women patients and health care professionals. Therefore the project "Early detection and care of peripartum mood disorders, increasing options for reaching affected women" was initiated by the "German chapter of the International Marce Society" in cooperation with midwives. This paper presents results of the preliminary investigation. 111 midwives were interviewed in 12 centres in Germany, Switzerland and Austria regarding their experience and knowledge of psychic disturbances in early motherhood. Psychic disturbances are seen as an essential issue by the participating midwives. In their estimation 39 % of the pregnant women they cared for are exceptionally psychically burdened. In approximately 43 % of the cases they believe that the physical complaints of pregnant women have a psychic background. In addition to "classic" mood complaints, midwives often perceive dysfunctions in the relationship between the mother and her child and that with her partner in the context of psychic disturbances during the peripartum period. In the diagnosis of psychic disturbances in early motherhood, attention should be paid to possible dysfunctional interactions between the mother and her child and that with her partner. Successful treatment of women with psychic disturbances in early motherhood requires cooperation between midwives, obstetricians and other health professionals.

[Religiosity and spirituality in the elderly]. / Religiosität und Spiritualität im Alter.

The present paper presents results regarding religious attitudes and behaviors as well as the perceived social support by religious communities in n = 593 elderly over 60 years (31.2% female, mean age 69.5 years) from the German general population. The results are based on the German 15-item version SBI-15R-D of the "Systems of Belief Inventory" (Holland et al., 1998). Furthermore, religiosity was analyzed as a potential protective factor regarding body complaints in the elderly. Higher scores on religiosity could be found in women compared to men and in elderly from Western Germany compared to those from Eastern Germany. There were no significant correlations between religiosity and body complaints. It is discussed whether the self-ratings of religiosity reflect conventional ideas of a religious orientated person rather than a genuine spiritual attitude.

[Central relationship patterns in comparison with different objects]. / Zentrale Beziehungsmuster im Vergleich verschiedener Objekte.

In the present study the Relationship Episode Paradigm Interviews of 70 female patients with different psychoneurotic diseases were analysed with respect to object-specific patterns with the CCRT method. The most frequent categories are the same in all relationship episodes and in subsamples of relationship episodes with mother and father. These categories are also predominant in episodes with women and men. Relationship episodes with mother do not differ from episodes with father, and relationship episodes with women are not different from episodes with men. But there are substantial differences in relationship episodes with the mother and women and between episodes with the father and men. Patients recount much more positive relationship patterns with women and men than with their parents. This could be understood as a hint of interpersonal resources.

[Method of plan formulation: first German language rehabilitation study of the Joseph Weiss "control mastery theory"]. / Die Methode der Plan-Formulierung: Erste deutschsprachige Reliabilitätsstudie zur "Control Mastery Theory" von Joseph Weiss.

The paper gives a survey of the "Control Mastery Theory" (CMT) of Joseph Weiss. CMT is a cognitive-affective, psychoanalytic theory of the psychotherapeutic process. The San Francisco Psychotherapy Research Group empirically investigated und confirmed several concepts of the CMT. Some research results are summarized and the "Plan Formulation Method" is described in detail. The results of the first German reliability study applying the plan formulation method on the case "Amalie" show that the method can be used reliably for research purposes outside the USA.

[Critical review of the categorical structures of the core Conflictual Relationship Theme Method (CCRT)]. / Kritik der kategorialen Strukturen der Methode des Zentralen Beziehungs-Konflikt-Themas (ZBKT).

The CCRT-method developed by Lester Luborsky is the most widespread and best established method to assess relationship structures in the field of psychodynamic psychotherapy research. Although its categorical structures are criticised in many different ways there have not been any attempts to modify them. This article points out the inconsistency of the current categorical system and demonstrates first approaches to alternative solutions. For this purpose genetic algorithms are used. Their application in psychotherapy research is demonstrated here for the first time.

Stereotypical relationship patterns and psychopathology.

BACKGROUND: We explored the relationship between the consistency of relationship patterns and the severity of psychopathology. METHOD: Relationship patterns were assessed by means of Relationship Anecdote Paradigm interviews rated according to the Core Conflictual Relationship Theme (CCRT) method. The repetition of the same type of CCRT components across relationship narratives indicated stereotypical patterns. RESULTS: Subjects treated in an inpatient setting (n = 25) told narratives with more consistent patterns than subjects in an outpatient setting (n = 32). Relationship episodes of normal adults (n = 23) were more flexible compared with the two clinical groups. Especially repetitions of the wish component were closely associated with the severity of psychopathology assessed by SCL-90R. CONCLUSIONS: The consistency of relationship patterns seems to be connected with the severity of psychopathology.

Analysis of double-joint movements in controls and in parkinsonian patients.

The motor performance of seven patients with Parkinson's disease and seven control subjects was tested in a choice reaction aiming task. The subjects were instructed to aim as fast and as accurately as possible to a light stimulus, which defined one of eight possible target positions. In order to reach the targets, elbow flexions had to be combined with forearm supinations or with forearm pronations. For single-joint movements, forearm supinations or pronations were executed faster than the long elbow flexions in both groups. In the double-joint movements of the control group, the flexion movement times (flex.MTs) and the supination movement times (sup.MTs) or pronation movement times (pron.MTs) were similar to the MTs of the corresponding single-joint movements. MTs of parkinsonian patients were significantly longer than those of control subjects. MTs were most increased in the forearm supination and forearm pronation of double-joint movements. In contrast to the controls, sup.MT and pron.MT were significantly increased in double-joint movements as compared to single-joint movements. The variations in the flex.MT and sup.MT of the double-joint movements neither correlated for a control subject nor for a parkinsonian patient. For controls, the independent MTs in double-joint movements cannot be explained by minimal principles (minimum energy, minimal torque change), but suggest that two separate motor programs are superimposed. In Parkinson's disease, there seems to be a deficit in superimposing two separate motor programs.

A model of human aiming movements applied to Parkinson's disease.

Healthy control subjects and Parkinsonian patients with and without l-DOPA medication were tested in a motor paradigm. The subjects were instructed to aim with the forearm as fast and as accurately as possible to the illuminated target. A quantitative dynamic model for planning and execution of voluntary aiming movements is developed. The proposed 'motor model' reproduces Parkinsonian symptoms and the therapeutic effects of the drug. The proposed model implies that the basal ganglia store movement and limb specific parameters which are necessary for the control of voluntary aiming movements. The model is contrasted against analytic concepts of motor control. Analytic concepts assume that movements are planned in space coordinates and then transformed to neural activities corresponding to the muscle force. In contrast, the neuronal activities simulated in the proposed 'motor model' can not be described by the terms 'planned trajectory', 'muscle force' or similar terms but suggest a more abstract dynamic concept.

A dynamic model of motor basal ganglia functions.

Fast aiming movements were measured in a choice reaction paradigm in a healthy control group and in Parkinsonian patients. The patients were tested without ('off') and with 3,4-dihydroxyphenylalanine ('on') (L-dopa) medication. The movement trajectories were used to estimate the parameters of a dynamic linear model. The model is based on the functional structure of the basal ganglia-thalamocortical circuit with direct and indirect pathways linking the putamen to the basal ganglia output nuclei (Albin et al. 1989). The output of the circuit is connected to a model for the motor neuron-musculo-skeletal system. The gain kd for the direct pathway and the gain ki for the indirect pathway were estimated. They were found to be significantly decreased for Parkinsonian patients in 'off' compared with the control group. L-dopa therapy in Parkinsonian patients increased the gains of the direct and the indirect pathway almost to normal values which implies that the long-term dopamine level in the striatum was excitatory for the direct and for the indirect pathway. This result is restricted to movements of correct size. For movements of diminished size, which are typical for Parkinsonian patients, the model predicts that the dopamine level in the striatum is excitatory for the direct pathway but inhibitory for the indirect pathway. The simulated values for neuronal activities are in agreement with expected values according to the experimental data. The proposed model of the 'motor' basal ganglia thalamocortical circuit implies that information about biomechanical properties of the musculo-skeletal system is stored in the 'motor' basal ganglia-thalamocortical circuit, and that the basal ganglia are involved in computation of the desired movement amplitude.