[SSRIs and depressive symptoms in schizophrenia: a systematic review]. / SSRI's en depressieve klachten bij schizofrenie: een systematische review.

BACKGROUND: Patients with schizophrenia frequently have depressive symptoms. Current guidelines do not provide specific recommendations regarding the treatment of these symptoms, nor do they mention the role that selective serotonin reuptake inhibitors (ssris) can play in the treatment.
AIM: To investigate whether ssris are more effective than placebo in treating depressive symptoms in patients with schizophrenia.
METHOD: We searched the literature systematically using PubMed, embase, Cochrane Library and Psycinfo. We selected articles on the basis of inclusion and exclusion criteria and the methodologies used and compared the severity of patients symptoms before and after treatment.
RESULTS: We found only four published studies of randomised, double blind, placebo-controlled trials. These showed that an ssri was significantly more effective than a placebo (the difference being 0.4 - 6.7 points on the Hamilton Depression Rating Scale and 0.2 - 2.6 on the Calgary Depression Scale for Schizophrenia).
CONCLUSION: There are indications that ssris are effective for the treatment of depressive symptoms in patients with schizophrenia. However, the total sample size was limited and individual studies had several methodological limitations.

Conflicts, security and marginalisation: institutional change of the pastoral commons in a 'glocal' world.

This paper argues that pastoral commons are under increasing pressure not just from overuse by pastoralists themselves, but from land management policies. Since colonial times, these have been based on a persistent misconception of the nature of pastoral economies and combined with increasing land alienation and fragmentation through government policies and covert privatisation of pastures. The paper focuses especially on pastoral populations in African drylands and is based on long-term research by independent researchers summarising some of their experiences in western, eastern and southern Africa. Most of them are organised in the African Drylands Dialogue, trying to shed some light on the developments in these areas. Before discussing the actual situation of African pastoralists, the authors focus on basic institutional features of the political and economic management of common grazing lands. This is followed by an overview of land alienation processes in colonial times, which serves as a basis for understanding the current land alienation constellations. The paper then moves on to explain how and why pastoralists are framed by the national discourses as the 'other' and the 'troublemaker', even being labelled as terrorists in nation state contexts. This goes hand in hand with a new wave of land alienation in the form of large-scale land acquisitions or 'land grabbing' (including water grabbing and 'green grabbing' processes). The paper then outlines different coping and adaptation strategies adopted by pastoral groups in a context in which a range of different global and local political, economic and ecological situations interrelate ('glocal'). Finally, the paper discusses the way in which pastoralism could be reframed in a participatory way in the future.

Les auteurs de cet article soutiennent que la pression foncière croissante exercée sur les terres collectives pastorales n'est pas seulement imputable à la surexploitation par les pasteurs eux-mêmes mais résulte surtout des politiques de gestion des terres. Depuis le temps des colonies, ces politiques ont reposé sur une perception erronée et tenace de la nature même des économies pastorales, à laquelle se sont greffées l'aliénation croissante des terres et leur fragmentation impulsée par les politiques gouvernementales et par la privatisation dissimulée des prairies. Les auteurs s'intéressent particulièrement aux populations pastorales des régions arides d'Afrique et exposent les conclusions d'une étude conduite sur une longue durée par une équipe indépendante de chercheurs, résumant l'essentiel de leurs observations en Afrique de l'Ouest, de l'Est et australe. La plupart d'entre eux oeuvrent sous les auspices d'African Drylands Dialogue et tentent de faire la lumière sur les évolutions constatées dans ces régions. Avant de se pencher sur la situation des pasteurs africains aujourd'hui, les auteurs décrivent les principales caractéristiques institutionnelles de la gestion politique et économique des terres collectives dédiées au pâturage. Ils retracent ensuite les processus d'aliénation des terres opérés durant l'époque coloniale, qui servent de grille de lecture pour mieux comprendre les constellations actuelles de terres aliénées. Puis les auteurs expliquent comment et pourquoi les discours nationaux désignent les pasteurs comme « l'autre ¼ et le « fauteur de troubles ¼, quand ils ne les dépeignent pas comme des terroristes dans les contextes d'étatsnations. Ces accusations sont indissociables d'une nouvelle vague d'aliénation des terres, qui prend la forme d'acquisitions à grande échelle ou de réquisitions (y compris les processus d'appropriation des cours d'eau ou d'écosystèmes [green grabbing]). Les auteurs détaillent les stratégies mises en oeuvre par les groupes pastoraux pour faire face à cette évolution et s'y adapter, dans un contexte de forte interaction entre de nombreuses situations politiques, économiques et écologiques de portée tant mondiale que locale (niveau dit « glocal ¼). Enfin, les auteurs examinent les perspectives d'avenir du pastoralisme à travers un nouveau cadre de type participatif.

Los autores postulan que el patrimonio pastoral común se encuentra sometido a presiones crecientes, no solo a resultas de su explotación excesiva por parte de los propios pastores, sino también a consecuencia de las políticas de ordenación del territorio. Desde los tiempos coloniales, estas se basan en un equívoco pertinaz acerca del carácter de las economías pastorales, a lo que se suma un nivel creciente de enajenación y fragmentación de las tierras a resultas de las políticas públicas y la privatización encubierta de los pastos. Los autores prestan especial atención a las poblaciones pastorales de las tierras áridas africanas, basándose en investigaciones de larga duración realizadas por investigadores independientes y resumiendo parte de su experiencia en el África occidental, oriental y meridional. La mayoría de ellos están adscritos al African Drylands Dialogue [diálogo sobre las tierras áridas africanas] y tratan por esta vía de arrojar luz sobre la evolución de esas zonas. Antes de presentar la situación real de las sociedades de pastores africanas, los autores se detienen en una serie de rasgos institucionales básicos de la gestión política y económica de los pastizales de propiedad común. A continuación exponen a grandes líneas los procesos de enajenación de las tierras en la época colonial, que encierran elementos básicos para comprender la actual constelación de tierras enajenadas. Después pasan a explicar cómo y por qué en el discurso de ciertos países las sociedades de pastores han acabado representando la alteridad, percibida además como «agitadora¼, hasta llegar a ser etiquetadas de «terroristas¼ en algunos estados-nación, paralelamente a una nueva oleada de enajenación de tierras en forma de adquisiciones a gran escala o «acaparamiento de tierras¼ (lo que incluye procesos de acaparamiento del agua y «acaparamiento ecológico¼). Tras exponer diferentes estrategias de respuesta y adaptación adoptadas por los grupos pastorales en un contexto marcado por la imbricación entre diversas realidades políticas, económicas y ecológicas («glocal¼), los autores concluyen reflexionando sobre el modo en que en el futuro sería posible reestructurar el pastoreo pasando por métodos participativos.

Evidence of genetic change in the flowering phenology of sea beets along a latitudinal cline within two decades.

Sea beets grown from seeds collected in 1989 and 2009 along the coasts of France and adjacent regions were compared for flowering date under controlled conditions. Seeds from both collection years were sown simultaneously and cultivated under the same glasshouse conditions. Date of flowering onset and year of first flowering were recorded. There was an overall northward shift in flowering time of about 0.35° latitude (i.e. 39 km) over the 20-year period. The southern portion of the latitudinal gradient--that is, from 44.7°N to 47.28°N--flowered significantly later by a mean of 1.78 days, equivalent to a 43.2-km northward shift of phenotypes. In the northern latitudes between 48.6°N and 52°N, flowering date was significantly earlier by a mean of 4.04 days, corresponding to a mean northward shift of 104.9 km, and this shift was apparently due to a diminished requirement of exposure to cold temperatures (i.e. vernalization), for which we found direct and indirect evidence. As all plants were grown from seed under identical conditions, we conclude that genetic changes occurred in the sensitivity to environmental cues that mediate the onset of flowering in both the northern and the southern latitudes of the gradient. Microevolution and gene flow may have contributed to this change. There was no significant change in the frequency of plants that flowered without vernalization. The lack of vernalization requirement may be associated with environmental instability rather than with climate conditions.

[The importance of neighborhood social cohesion and social capital for the well being of older adults in the community]. / Het belang van sociale cohesie en sociaal kapitaal in de buurt voor het welzijn van ouderen.

PURPOSE OF THE STUDY: We aimed to investigate whether social capital (obtaining support through indirect ties such as from neighbors) and social cohesion (interdependencies among neighbors) within neighborhoods positively affect the well-being of older adults. DESIGN AND METHODS: This cross-sectional study included 945/1440 (66 % response rate) independently living older adults (aged >70 years) in Rotterdam. We fitted a hierarchical random-effects model to account for the hierarchical structure of the study design: 945 older adults (level 1) nested in 72 neighborhoods (level 2). RESULTS: Univariate analyses showed that being born in the Netherlands, house ownership, education, income, social capital of individuals, neighborhood security, neighborhood services, neighborhood social capital, and neighborhood social cohesion were significantly related to the well-being of older adults. Multilevel analyses showed that social capital of individuals, neighborhood services, neighborhood social capital, and neighborhood social cohesion predicted the well-being of older adults. Single and poor older adults reported lower well-being than did better-off and married older adults. However, the effects of marital status and income were mediated by neighborhood services, social capital, and social cohesion. Neighborhood services, social capital and social cohesion may act as buffer against the adverse effects of being single and poor on the well-being of older adults. IMPLICATIONS: The results of this study support the importance of social capital of individuals, as well as social capital within the neighborhood and social cohesion within the neighborhood for well-being of older adults. The well-being of older adults may also be enhanced through the improvement of quality of neighborhood services.

A systematic review of the methodology of telemedicine evaluation in patients with postural and movement disorders.

We reviewed the methodology used in telemedicine research concerning patients with postural and movement disorders. Literature searches were performed using various computerized databases through to October 2005. Twenty-two studies met the criteria for review. Two broad models of telemedicine delivery were represented in the literature: (1) telemedicine between health-care professionals at each telemedicine site (n=16) and (2) telemedicine between health-care professionals and a patient at a remote site (n=6). Disparate research methodologies were used to investigate these two models. Most studies were limited to investigating the technical feasibility and acceptability of a telemedicine service rather than focusing on the overall effect of introducing the telemedicine service into routine health care. Nonetheless, it is possible to conclude that telemedicine is acceptable for both patients and professionals when used in rehabilitation. Since the two models of telemedicine evaluation tend to explore different outcomes (diagnostic accuracy versus health status), it is recommended that separate methodologies should be used. In contrast to evaluations of telemedicine model 2, randomized controlled trials appear to be less valuable for telemedicine model 1.

Increasing self-directed training in neurorehabilitation patients through competition.

This proof-of-concept study aimed to test whether competition could be a useful tool to increase intensity and amount of self-directed training in neurorehabilitation. Stroke patients undergoing inpatient neurorehabilitation (n=93) conducted self-directed endurance training on a (wheelchair-compatible) bicycle trainer under three experimental conditions: a "Competition" condition and two noncompetition control conditions (repeated randomized within-subject design). Training performance and perceived exertion were recorded and statistically analyzed. Three motivational effects of competition were found. First, competition led to an increase in self-directed training. Patients exercised significantly more intensively under competition than in the two noncompetition control conditions. Second, (winning a) competition had a positive influence on performance in the subsequent training session. Third, training performance was particularly high during rematch competitions; that is to say, during second encounter competitions against an opponent that the patient had just beaten. No systematic effect of competition upon perceived exertion (controlled for training performance) was found. Together, our results demonstrate that competition is a potent motivational tool to increase self-directed training in neurorehabilitation.

Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia.

Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.

Gender differences in postprandial ketone bodies in normolipidemic subjects and in untreated patients with familial combined hyperlipidemia.

OBJECTIVE: An increased hepatic flow of free fatty acids (FFAs) is associated with impaired peripheral FFA trapping by malfunctioning of the complement component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have not been determined yet. Gender differences in postprandial ketone bodies and C3 changes were investigated in normolipidemic patients and patients with untreated FCHL. METHODS AND RESULTS: Thirty-two normolipidemic patients (16 female and 16 male) and 19 patients with untreated normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total and incremental areas under the curves (AUC and dAUC, respectively) after the oral fat load were calculated. Triglyceride AUC was similar between genders in each group. Normolipidemic female subjects showed a higher levels of dAUC-hydroxybutyric acid than male subjects (1.37+/-0.49 and 0.98+/-0.43 mmol x h/L). In FCHL, a similar trend was observed in female (1.92+/-0.38) compared with male (1.55+/-0.87) subjects. In contrast to normolipidemia, FCHL did not show a postprandial increase in C3, although C3 was higher in FCHL. CONCLUSIONS: Women have higher postprandial ketone bodies than men, probably reflecting enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher fasting and postprandial C3 levels in FCHL may reflect resistance of the C3/acylation-stimulating protein system to promote peripheral fatty acid trapping.

Postprandial increase of complement component 3 in normolipidemic patients with coronary artery disease: effects of expanded-dose simvastatin.

Plasma concentrations of the third complement component (C3) predict the risk of myocardial infarction. Because chylomicrons stimulate C3 production by adipocytes in vitro, we investigated plasma C3 changes in vivo after an oral fat load. Thirty-seven subjects (20 normolipidemic patients with coronary artery disease [CAD] and 17 healthy control subjects) underwent an oral fat load (50 g/m(2)). C3 was measured at baseline and at 2-hour intervals after fat intake for 10 hours. The effects of lipid lowering by simvastatin were evaluated in 16 patients. Fasting plasma C3 was 1.06+/-0.26 and 0.90+/-0.12 g/L in CAD patients and control subjects, respectively. Fasting C3 was correlated with several parameters associated with insulin resistance. The best determinant of fasting C3 was waist circumference (adjusted R(2)=0.48, beta=0.71, P<0.001); the addition of postprandial triglyceridemia to the model improved it (adjusted R(2)=0.63). Plasma C3 levels at 2, 4, and 6 hours after fat ingestion were significantly higher than fasting levels in patients and control subjects. C3 increased maximally to 1.39+/-0.33 g/L in patients and to 1.11+/-0.18 g/L in control subjects (P<0.01 for patients versus control subjects). Total postprandial triglyceridemia was the best determinant of maximal C3 increase (adjusted R(2)=0.47, beta=0.70; P<0.001). Treatment with simvastatin decreased fasting and postprandial C3 by 6% and 39%, respectively (P<0.05 for both versus no treatment). Postprandial plasma C3 concentrations increase in CAD patients and control subjects. Fasting C3 is associated with waist circumference, but postprandial C3 increment is associated with postprandial lipemia. Fasting and postprandial C3 concentrations decrease after treatment with simvastatin.

C1-inhibitor prevents PEG fractionation-induced, EDTA-resistant activation of mouse complement.

Fractionation of mouse serum by precipitation with a critical amount of polyethylene glycol 6000 (PEG; 11% w/v) results in a classical and alternative pathway-independent activation of the terminal complement route. The activation can take place after the separation of an activating principle together with the terminal route components from a natural regulator. The isolation and identification of the regulatory component preventing this activation in serum, is subject of this paper. The regulator was purified by fractionated PEG-precipitation (15-25%), followed by heparin-Sepharose affinity, Mono Q anion-exchange, and Superose 12 gel filtration chromatography. The regulator appeared to be a single-chain protein with a Mr of 96 k. A protein with similar activity purified from human serum had a Mr of 104 k and was functionally and antigenically indistinguishable from C1-INH. The mouse 96 k protein inhibited C1-esterase activity indicating that this protein is indeed C1-INH. Mouse C1-INH regulates the PEG fractionation-induced bypass activation of complement, but does not interfere with the assembly or the lytic activity of membrane attack complexes. alpha 2-Macroglobulin appeared also to be capable of inhibiting the PEG-precipitation-induced activation process, but with lower efficiency.

Direct and indirect estimates of the selfing rate in small and large individuals of the bumblebee pollinated Cynoglossum officinale L (Boraginaceae).

We measured the relationship between selfing rates and flower number in an experimental population of bumblebee pollinated Cynoglossum officinale, with plants differing in flower number. Results were compared with the prediction of a model based on pollen dynamics and pollinator behaviour. The selfing rate, as measured by multilocus oligonucleotide DNA fingerprinting, increased with flower number and ranged from 0% to 70%. Flowers on large plants received an equal number of visits from bumblebees as flowers on small plants. On large plants more flowers in a row were visited, inducing geitonogamy. The overall relationship between selfing rate and number of flowers can be explained by pollen dynamics and pollinator behaviour without invoking postpollination processes such as differential pollen tube growth and abortion.

Metabolic activation of natural phenols into selective oxidative burst agonists by activated human neutrophils.

Phenols isolated from the traditional medicinal plant Picrorhiza kurroa inhibit the release of superoxide anion (O2-) by activated human neutrophils, but leave the phagocytotic capacity intact. Resting neutrophils and resting or activated human lymphocytes are insensitive to these agents. The underlying mechanism of this highly selective activity is investigated. A critical event is the reaction of the phenols with secretory products from the activated neutrophils. The reaction products interfere with the assembly of a functional NADPH-oxidase in the membrane. Analysis of the mode of activation of the phenols reveals two possible pathways. Catechols react directly with reactive oxygen species (ROS) from the oxidative burst. For the activation of the orthomethoxy-substituted catechols the combined activity of ROS and myeloperoxidase (MPO) is obligatory. Catechols with a dimethoxy substitution cannot be activated metabolically by neutrophil-derived ROS.

Reaction products of 1-naphthol with reactive oxygen species prevent NADPH oxidase activation in activated human neutrophils, but leave phagocytosis intact.

Activation of human neutrophils with opsonized particles in the presence of a nontoxic dose of 1-naphthol resulted in inhibition of superoxide anion production but not of the phagocytotic activity of the cells. In this study we have investigated the mechanism of action of 1-naphthol. The inhibition is not at the level of cellular activation since the FMLP-induced rise of intracellular free calcium was unaffected. Our results show that the (metabolic) activation of 1-naphthol to 1,4-naphthoquinone by reaction with H2O2 from the oxidative burst is a necessary event for the inhibition to occur. The study provides evidence that by its reactivity with essential thiol groups 1,4-naphthoquinone (1,4-NQ) prevents the assembly of a functional NADPH-oxidase in the neutrophil membrane.

Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins.

OBJECTIVE: After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination. BACKGROUND: ADEM is a demyelinating disorder of the CNS sharing many similarities with MS. Demyelination in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens. METHODS: Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; and TCR repertorium analysis by PCR-ELISA and cytokine production. RESULTS: 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S. pyogenes exotoxins. 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation. MBP-reactive T cells showed crossreactivity to S. pyogenes supernatant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile. CONCLUSION: In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.

Quantification of in vitro antibody secretion by immune spleen cells.

A simple method to study 19S anti-SRBC antibody production is described. This technique, performed by incubation of immune spleen cells, SRBC and C in the fluid phase, utilises photomeric estimation of antibody mediated haemoglobin release. The test is quicker and more accurate than the two-step haemolytic plaque assay (Jerne technique). In combination with the Jerne technique this method gives information about haemolysin production per PFC. This was maximal on day 2 and on day 6 after immunisation, and least on day 4. The steady state value was reached again at day 9. In principle this method is suitable for the estimation of IgG production.

Rapid, activity-guided isolation of sex-limited protein (Slp) from mouse serum by fractionated precipitation and high-performance liquid chromatography.

We have recently demonstrated that sex-limited protein (Slp) plays a key role in an EDTA-resistant mouse complement activation pathway. A rapid procedure, utilizing classical chromatography methods on an FPLC system, was developed for the isolation of functionally active Slp. The method is based on the fractionated precipitation of serum by polyethylene glycol 6000, followed by heparin Sepharose Cl-6B affinity chromatography, Mono Q anion exchange and Superose 12 gel filtration. The isolation of Slp was monitored by a hemolytic assay. The procedure resulted in the purification of Slp, which by SDS-PAGE gave a single band of M(r) 2000,000 under non-reducing conditions, and under reducing conditions three bands corresponding to M(rs) of 105,000, 76,000 and 37,000.

Rapid isolation and characterization of native mouse complement components C3 and C5.

A rapid, 1 day procedure for the purification of mouse complement factors C3 and C5 is described. The method is based on fractionated precipitation by polyethylene glycol 6000, followed by Mono Q anion exchange chromatography on a system for fast protein liquid chromatography (FPLC). For C3 isolation, an additional FPLC separation step using Superose 12 (gel filtration) was used. C3 was purified 71-fold with a yield of 32% as measured by biological activity; the preparation contained no detectable contaminants as judged by SDS-PAGE. A comparable procedure for the isolation of C5 resulted in a preparation with a considerable contamination which could be easily removed by affinity chromatography using antibodies directed against these contaminants. With this combined procedure C5 was purified 536-fold with a yield of 28% based on biological activity. SDS-polyacrylamide gel electrophoresis revealed that mouse C3 and C5 had apparent Mrs of 170,000 and 190,000, respectively. Under reducing conditions the alpha and beta chains showed Mrs of 107,000 and 62,000 for C3, and 104,000 and 85,000 for C5.

Functional assay of C5-activating and nonactivating cobra venom factor preparations in the mouse system.

This paper deals with a new, functional assay of cobra venom factor (CVF) preparations with or without C5-activating property. Existing methods lack sensitivity and use diluted human complement as target of inactivation. An adapted assay using diluted mouse serum as complement source was hampered by underestimation of C3 depletion by bystander lysis and an overvaluation of C5 consumption resulting from C3 inactivation in the reagent used. These disadvantages prompted us to develop the new assay which is based on the incubation of CVF preparations with undiluted mouse serum. After incubation, residual total C activity, as well as functional C3 and C5 are estimated by titration. The procedure permits the assessment of CVF activities with minimal interference from undesired processes. The conditions in the new assay approach the in vivo situation in mice by the use of undiluted serum from the same animal species.

Determination of alternative pathway of complement activity in mouse serum using rabbit erythrocytes.

Rabbit, mouse and sheep erythrocytes expressing different concentrations of membrane sialic acid were used to study possible modes of activation of the alternative complement (C) pathway in mouse, human and guinea pig serum. Mouse erythrocytes activated only human serum, whereas rabbit erythrocytes activated the sera of all three species. Based on the observation that rabbit erythrocytes activate the murine alternative C pathway a method for estimation of alternative C pathway activity (AP50 value) in mouse serum was devised analogous to that used for human AP50 determination. The method is not very sensitive to ageing or to batch variation of the indicator cells. The AP50 value of mouse serum measured by this method is of the same order as for human and guinea pig serum. Mouse serum AP50 activity is partly determined by natural anti-rabbit erythrocyte antibodies and is sensitive to heating (15' at 48 degrees C and 4' at 56 degrees C), and to the actions of cobra venom factor, zymosan and cysteine. Strain and sex differences with respect to AP50 activities of mouse sera were observed.

In vivo anti-complementary activities of the cobra venom factors from Naja naja and Naja haje.

The kinetics of complement (C) depletion and recovery of C levels upon injection of BALB/c mice with cobra venom factors (CVF), from N. naja (C3- and C5-depleting) and N. haje (selectively C3-depleting) were studied. The animals received i.p. or i.v. injections of either of the two preparations. CH50 and hemolytic C3 and C5 levels were followed as parameters of residual complement activity. N. naja CVF turned out to be as efficient in depleting total complement activity as N. haje CVF. Decreased CH50 values could largely be ascribed to C3 depletion. Complement consumption after N. naja CVF, however, lasted longer than after N. haje CVF administration. Estimated functional half-lives of N. naja and N. haje CVF were 11.5 and 4.5 h, respectively. Inhibition ELISAs showed that, after in vivo administration of either of the two CVF preparations, antigenic C3 and C5 kept circulating for days.