Multidisciplinary models for pregnancy care in patients with rheumatic diseases: Clinical experiences and experts opinion.

OBJECTIVES: To describe different models of multidisciplinary pregnancy care for patients with inflammatory and autoimmune rheumatic diseases, and the steps to follow concerning their implementation. METHODS: A qualitative study was conducted including: (1) a comprehensive literature search in PUBMED focused on multidisciplinary care models; (2) structured interviews with seven rheumatologists from multidisciplinary pregnancy clinics for patients with inflammatory and autoimmune rheumatic diseases. Data were collected related to the hospitals, medical departments, populations cared for, and multidisciplinary care models (type, material, and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision-making, research and educational activities, multidisciplinary clinical sessions, initiation/start, planning, advantages/disadvantages, and barriers/facilitators for implementation); (3) a nominal meeting group in which the results of searches and interviews were analyzed and the recommendations for the implementation of the multidisciplinary care models defined. RESULTS: We analyzed seven models of multidisciplinary care in pregnancy, implemented 3-10 years ago, which can all be summarized by two different subtypes: parallel (patients are assessed the same day in the involved medical services) and preferential (patients are assessed on different days in the involved medical services) circuits. The implementation of a specific model results rather from an adaptation to the hospital's and professionals' circumstances. Correct planning and good harmony among professionals are key points to implementing a model. CONCLUSION: Different multidisciplinary care models have been implemented for patients with inflammatory and autoimmune rheumatic diseases during pregnancy. They pretend to improve care, system efficiency, and collaboration among specialists and should be carefully implemented.

Efficacy and safety of switching Jak inhibitors in rheumatoid arthritis: an observational study.

OBJECTIVES: Different Jak inhibitors (jakinibs) have shown efficacy in rheumatoid arthritis (RA), but in a significant proportion of patients, an insufficient response leads to therapy withdrawal. We describe the efficacy and safety of a second jakinib in patients stopping the first due to insufficient response or side effects. METHODS: This is an observational retrospective multicentric study of 31 patients with RA sequentially treated with baricitinib or tofacitinib in any order in clinical practice in ten medical centres in Spain. RESULTS: We identified 31 patients, sequentially treated with both jakinibs. An equal proportion had received tofacitinib or baricitinib first. Most patients (87%) had previously received one or several bDMARD, median 4 (2-5). Median survival for the first jakinib was 5 (3-8) months, and the reasons for withdrawal were inefficacy in 61% and adverse effects in 39%. Most patients (23/31, 74%) maintained the response to the second jakinib after a mean follow-up of 19.5 (12-24) months. In all 8 patients who discontinued the second jakinib, the reason was inefficacy. The treatment suspension rate was similar among patients that had discontinued the first jakinib for inefficacy (26%) or for adverse effects (25%). CONCLUSIONS: Therapy of RA with a second jakinib seems a safe and efficacious option after discontinuation of the first, either for inefficacy or for side effects.

Electrical synaptic transmission requires a postsynaptic scaffolding protein.

Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here, we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Using model electrical synapses in zebrafish Mauthner cells, we demonstrated that ZO1 is required for robust synaptic Connexin localization, but Connexins are dispensable for ZO1 localization. Disrupting this hierarchical ZO1/Connexin relationship abolishes electrical transmission and disrupts Mauthner cell-initiated escape responses. We found that ZO1 is asymmetrically localized exclusively postsynaptically at neuronal contacts where it functions to assemble intercellular channels. Thus, forming functional neuronal gap junctions requires a postsynaptic scaffolding protein. The critical function of a scaffolding molecule reveals an unanticipated complexity of molecular and functional organization at electrical synapses.

Neurons 'talk' with each another at junctions called synapses, which can either be chemical or electrical. Communication across a chemical synapse involves a 'sending' neuron releasing chemicals that diffuse between the cells and subsequently bind to specialized receptors on the receiving neuron. These complex junctions involve a large number of well-studied molecular actors. Electrical synapses, on the other hand, are believed to be simpler. There, neurons are physically connected via channels formed of 'connexin' proteins, which allow electrically charged ions to flow between the cells. However, it is likely that other proteins help to create these structures. In particular, recent evidence shows that without a structurally supporting 'scaffolding' protein called ZO1, electrical synapses cannot form in the brain of a tiny freshwater fish known as zebrafish. As their name implies, scaffolding proteins help cells organize their internal structure, for example by anchoring other molecules to the cell membrane. By studying electrical synapses in zebrafish, Lasseigne, Echeverry, Ijaz, Michel et al. now show that these structures are more complex than previously assumed. In particular, the experiments reveal that ZO1 proteins are only present on one side of electrical synapses; despite their deceptively symmetrical anatomical organization, these junctions can be asymmetric, like their chemical cousins. The results also show that ZO1 must be present for connexins to gather at electrical synapses, whereas the converse is not true. This suggests that when a new electrical synapse forms, ZO1 moves into position first: it then recruits or stabilizes connexins to form the channels connecting the two cells. In many animals with a spine, electrical synapses account for about 20% of all neural junctions. Understanding how these structures form and work could help to find new treatments for disorders linked to impaired electrical synapses, such as epilepsy.

Recomendaciones sobre actuaciones a seguir durante la edad fértil, el embarazo, posparto y lactancia en pacientes con enfermedades reumáticas inflamatorias y autoinmunes / Recommendations for the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding

Objetivo. Desarrollar recomendaciones basadas en la mejor evidencia y experiencia sobre el manejo de pacientes con enfermedades reumáticas inflamatorias y autoinmunes durante la edad fértil, el embarazo, posparto y lactancia. Métodos. Se siguió la metodología de grupos nominales. Se seleccionó un grupo nominal de expertos (12 reumatólogos). Se realizó una actualización de una revisión sistemática de la literatura, una revisión literaria, así como una encuesta a nivel nacional sobre el manejo de estos pacientes. El grupo de expertos se encargó de definir el alcance, usuarios, apartados del manuscrito y posibles recomendaciones. El GA con las recomendaciones se votó siguiendo la metodología Delphi según una escala de 1 (total desacuerdo) a 10 (total acuerdo), definiéndose el acuerdo como una puntuación ≥ 7 por al menos el 70% de los participantes. El NE y GR se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford. El documento completo inicial fue revisado por los expertos y el proyecto estuvo coordinado, en todo momento, por un metodólogo experto. Resultados. Se generaron 14 recomendaciones sobre el periodo preconcepcional (anticoncepción, reproducción asistida), el embarazo (planificación, manejo farmacológico y seguimiento) y lactancia (manejo farmacológico y seguimiento). Incluye recomendaciones específicas sobre situaciones de especial riesgo como el lupus eritematoso sistémico y el síndrome antifosfolípido. Existió acuerdo > 90% con todas las recomendaciones menos en una de ellas. Conclusiones. En los pacientes con enfermedades inflamatorias y autoinmunes estas actuaciones pueden mejorar los resultados y el pronóstico de los mismos (AU)

Objective. To develop recommendations on the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, post-partum and breastfeeding based on the best evidence and experience. Methods. Recommendations were generated using nominal group and Delphi techniques. An expert panel of 12 rheumatologists was established. A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in its 1st meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinement. A national survey analyzing different aspects of this topic was undertaken separately, followed by a Delphi process (2 rounds). Agreement with each recommendation was ranked on a scale of 1 (total disagreement) to 10 (total agreement), and was considered to be achieved if at least 70% voted ≥ 7. The level of evidence and grade of recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Results. A total of 14 recommendations were generated for the preconception period (oral and hormonal contraception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High-risk situations such as lupus or antiphospholipid syndrome were included. A consensus > 90% was reached for all but one recommendation. Conclusions. These recommendations are intended to provide rheumatologists, patients, families and other stakeholders with a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding (AU)

Recommendations for the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding. / Recomendaciones sobre actuaciones a seguir durante la edad fértil, el embarazo, posparto y lactancia en pacientes con enfermedades reumáticas inflamatorias y autoinmunes.

OBJECTIVE: To develop recommendations on the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, post-partum and breastfeeding based on the best evidence and experience. METHODS: Recommendations were generated using nominal group and Delphi techniques. An expert panel of 12 rheumatologists was established. A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in its 1st meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinement. A national survey analyzing different aspects of this topic was undertaken separately, followed by a Delphi process (2 rounds). Agreement with each recommendation was ranked on a scale of 1 (total disagreement) to 10 (total agreement), and was considered to be achieved if at least 70% voted≥7. The level of evidence and grade of recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. RESULTS: A total of 14 recommendations were generated for the preconception period (oral and hormonal contraception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High-risk situations such as lupus or antiphospholipid syndrome were included. A consensus>90% was reached for all but one recommendation. CONCLUSIONS: These recommendations are intended to provide rheumatologists, patients, families and other stakeholders with a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding.

Ajuste en la práctica clínica de las directrices treat-to-target para la artritis reumatoide: resultados del estudio ToARCan / Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid arthritis: results of the ToARCan study

Objetivo. Analizar el cumplimiento de las directrices t2t en la práctica clínica. Métodos. Estudio observacional transversal en pacientes consecutivos con artritis reumatoide (AR) de 5 hospitales canarios. Los pacientes cumplimentaron escalas de actividad, el HAQ y respondieron si el médico les había explicado el objetivo del tratamiento. El médico recogió además: visitas en el último año, empleo de índices y HAQ, DAS28 de la visita actual y fecha de la siguiente consulta. Se analizó el porcentaje de cumplimiento de las recomendaciones t2t (R) 1, 3, 5-7 y 10. Resultados. Se reclutó a 343 pacientes, 77% mujeres, con edad promedio de 57 años y duración de la AR de 10 años. La mediana de visitas en el último año fue de 3 y el promedio de meses entre la visita anterior y la actual de 5,6. El 93% estaba en tratamiento con FAME y el 44% en remisión por DAS (R1). Se había realizado recuento articular en la visita previa al 85%, HAQ al 19%, EVA actividad del paciente al 41% y DAS28 al 35% (R6). La siguiente visita se programó en un promedio entre uno y 3 meses (R5) al 64% de los pacientes con DAS28>3,2. El 96% de los pacientes dijo haber sido informado del objetivo del tratamiento (R10). La variabilidad entre centros era moderada, pero existía. El único factor que determinaba la realización de un DAS28 en la última consulta era el centro de procedencia del paciente. Conclusiones. Los centros canarios estudiados logran altas cotas de remisión y baja actividad en sus pacientes; la realización de índices compuestos y la frecuencia de seguimiento recomendado por el t2t se cumplen, aunque hay oportunidad de mejora (AU)

Objective. To analyze compliance with t2t clinical practice guidelines. Methods. Cross-sectional observational study in consecutive patients with rheumatoid arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity scales, HAQ and answered the question of whether the doctor had explained the treatment target. The rheumatologist also collected: visits in the past year, use of activity indices and HAQ, DAS28 of current visit and date of the next visit. The percentage of compliance to indicators based on the t2t recommendations (R) 1, 3, 5-7 and 10 was analyzed. Results. A total of 343 patients were recruited, 77% female, mean age 57, RA duration of 10 years. Median visits in the last year were 3 and mean time between last and current visit was 5.6 months. A total of 93% of the patients were treated with DMARDs and 44% were in remission by DAS (R1). In the previous visit, documented joint count was present in 85%, a HAQ in 19%, patient VAS in 41%, and a DAS28 in 35% of the patients (R6). The next visit was scheduled at an average of 4.3 months (R5). In 64% of patients with DAS28> 3.2 a visit between one and 3 months was scheduled (R5). A total of 96% of patients said they had been informed of the treatment target (R10). Variability between centers existed but was moderate. The only factor determining the performance of a DAS28 in the last visit was the patient's center of origin. Conclusions. The Canary Island centers studied achieved high levels of remission and low activity in their patients. The performance of composite indices and follow-up frequency recommended by the t2t are met, although there is room for improvement (AU)

Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid arthritis: Results of the ToARCan study.

OBJECTIVE: To analyze compliance with t2t clinical practice guidelines. METHODS: Cross-sectional observational study in consecutive patients with rheumatoid arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity scales, HAQ and answered the question of whether the doctor had explained the treatment target. The rheumatologist also collected: visits in the past year, use of activity indices and HAQ, DAS28 of current visit and date of the next visit. The percentage of compliance to indicators based on the t2t recommendations (R) 1, 3, 5-7 and 10 was analyzed. RESULTS: A total of 343 patients were recruited, 77% female, mean age 57, RA duration of 10 years. Median visits in the last year were 3 and mean time between last and current visit was 5.6 months. A total of 93% of the patients were treated with DMARDs and 44% were in remission by DAS (R1). In the previous visit, documented joint count was present in 85%, a HAQ in 19%, patient VAS in 41%, and a DAS28 in 35% of the patients (R6). The next visit was scheduled at an average of 4.3 months (R5). In 64% of patients with DAS28> 3.2 a visit between one and 3 months was scheduled (R5). A total of 96% of patients said they had been informed of the treatment target (R10). Variability between centers existed but was moderate. The only factor determining the performance of a DAS28 in the last visit was the patient's center of origin. CONCLUSIONS: The Canary Island centers studied achieved high levels of remission and low activity in their patients. The performance of composite indices and follow-up frequency recommended by the t2t are met, although there is room for improvement.

Factors associated with the intensification of treatment in rheumatoid arthritis in clinical practice.

The aim of the present study was to analyse the patterns of treatment adjustment in rheumatoid arthritis (RA) patients with active disease in routine clinical care. This was a cross-sectional study of consecutive patients with RA conducted in five hospitals. Activity scales (DAS28-ESR) and function (HAQ) were measured, as well as whether ultrasound was performed as part of the assessment. Treatment decision (no changes/reduction/intensification) and time to the next scheduled visit were the outcomes variables. Associated factors were analysed by multilevel regression models. A total of 343 patients were included (77 % women, mean age 57 years, mean RA duration 10 years), of whom 44 % were in remission by DAS28. Treatment was continued in 202 (59 %) patients, reduced in 57 (16 %), and intensified in 83 (24 %). In the 117 patients with active RA (DAS28 ≥ 3.2), treatment was intensified in 61 (52 %). Factors associated with treatment intensification were physician and patient VAS, and DAS28, but not the centre. In the multilevel regression analysis with intensification of treatment as dependent variable, the following factors were significantly associated: DAS28 [OR 3.67 (95 % CI 2.43-5.52)], patient VAS [OR 1.04 (95 % CI 1.01-1.08)], and have performed an ultrasound [OR 3.36 (95 % CI 1.47-7.68)]. Factors associated with time to the next scheduled visit (an average of 4.3 months) were patient and physician VAS, DAS28, and centre. In clinical practice, half of the patients with active RA maintain or reduce the treatment. The decision to intensify treatment in active RA as recommended by a treat-to-target strategy is complex in practice.

Na(+), K(+)-ATPase subunit composition in a human chondrocyte cell line; evidence for the presence of α1, α3, ß1, ß2 and ß3 isoforms.

Membrane transport systems participate in fundamental activities such as cell cycle control, proliferation, survival, volume regulation, pH maintenance and regulation of extracellular matrix synthesis. Multiple isoforms of Na(+), K(+)-ATPase are expressed in primary chondrocytes. Some of these isoforms have previously been reported to be expressed exclusively in electrically excitable cells (i.e., cardiomyocytes and neurons). Studying the distribution of Na(+), K(+)-ATPase isoforms in chondrocytes makes it possible to document the diversity of isozyme pairing and to clarify issues concerning Na(+), K(+)-ATPase isoform abundance and the physiological relevance of their expression. In this study, we investigated the expression of Na(+), K(+)-ATPase in a human chondrocyte cell line (C-20/A4) using a combination of immunological and biochemical techniques. A panel of well-characterized antibodies revealed abundant expression of the α1, ß1 and ß2 isoforms. Western blot analysis of plasma membranes confirmed the above findings. Na(+), K(+)-ATPase consists of multiple isozyme variants that endow chondrocytes with additional homeostatic control capabilities. In terms of Na(+), K(+)-ATPase expression, the C-20/A4 cell line is phenotypically similar to primary and in situ chondrocytes. However, unlike freshly isolated chondrocytes, C-20/A4 cells are an easily accessible and convenient in vitro model for the study of Na(+), K(+)-ATPase expression and regulation in chondrocytes.

¿Qué opinan los residentes de reumatología sobre su formación? Una encuesta de la Comisión Nacional de Reumatología / What do rheumatology residents think of their training? A survey of the National Rheumatology Commission

La Comisión Nacional de Reumatología ha elaborado una encuesta sobre la satisfacción de los residentes respecto a su periodo formativo. Contestaron un 37% de los 176 invitados a participar. Un 71% manifestó que estaba satisfecho o muy satisfecho de la influencia de la actividad asistencial en su formación. El 38% estaba insatisfecho o muy insatisfecho de la supervisión por parte de la plantilla. El 39% estaba insatisfecho o muy insatisfecho del adiestramiento en microscopía de luz polarizada. El 52% contestó que no existían reuniones periódicas estructuradas de monitorización de su formación. El 66% declaró que no había existido ningún tipo de evaluación efectiva de su formación. El 39% se mostró insatisfecho o muy insatisfecho respecto a las facilidades para publicar que le brindó su unidad docente. La satisfacción global sobre la formación asistencial de los residentes de reumatología es elevada. Existen oportunidades de mejora referentes al entrenamiento en determinadas técnicas, la monitorización y evaluación del periodo formativo y la formación en habilidades de investigación (AU)

The National Commission of Rheumatology has developed a satisfaction survey for residents concerning their training period. 37% of the 176 invited to participate answered the survey. 71% said they were satisfied or very satisfied with the influence of the assistance activities during their training. 38% were dissatisfied or very dissatisfied with supervision by staff. 39% were dissatisfied or very dissatisfied with their training in polarized light microscopy. 52% said no regular meetings were structured to monitor their training. 66% said that there had been no effective evaluation of their training. 39% were dissatisfied or very dissatisfied on the tools they were given to publish at their teaching unit. Overall satisfaction on classroom training for residents of Rheumatology is high. There are opportunities for improvement relating to training in certain techniques, monitoring and evaluation of the training period and training in research skills (AU)

[What do rheumatology residents think of their training? A survey of the National Rheumatology Commission]. / ¿Qué opinan los residentes de reumatología sobre su formación? Una encuesta de la Comisión Nacional de Reumatología.

The National Commission of Rheumatology has developed a satisfaction survey for residents concerning their training period. 37% of the 176 invited to participate answered the survey. 71% said they were satisfied or very satisfied with the influence of the assistance activities during their training. 38% were dissatisfied or very dissatisfied with supervision by staff. 39% were dissatisfied or very dissatisfied with their training in polarized light microscopy. 52% said no regular meetings were structured to monitor their training. 66% said that there had been no effective evaluation of their training. 39% were dissatisfied or very dissatisfied on the tools they were given to publish at their teaching unit. Overall satisfaction on classroom training for residents of Rheumatology is high. There are opportunities for improvement relating to training in certain techniques, monitoring and evaluation of the training period and training in research skills.

Criterios de acreditación para la formación de especialistas de reumatología / Formation of specialists in rheumatology: accreditation criteria

La Comisión Nacional de Reumatología es el garante de la formación postgrado en reumatología. Se presentan a continuación los criterios de acreditación de unidades docentes. Estos criterios tienen en cuenta 4 dominios, a saber: la estructura, la asistencia, la docencia y la investigación. Cada dominio se subdivide en subdominios e ítems. Algunos de ellos son de obligado cumplimiento. Este documento es el marco de referencia para las evaluaciones de las solicitudes de acreditación. Es un documento que puede ser revisado en un futuro (AU)

The National Rheumatology Board is responsible for postgraduate formation in rheumatology. Herein we present the new criteria for accreditation of teaching units. These criterion contemplate four domains, namely: structure, clinical work, teaching and research. Each domain is divided in subdomains and items. Some of them are of an obligatory nature. This document serves as reference for future applications. The document may be reviewed in the future (AU)

[Formation of specialists in rheumatology: Accreditation criteria]. / Criterios de acreditación para la formación de especialistas de reumatología.

The National Rheumatology Board is responsible for postgraduate formation in rheumatology. Herein we present the new criteria for accreditation of teaching units. These criterion contemplate four domains, namely: structure, clinical work, teaching and research. Each domain is divided in subdomains and items. Some of them are of an obligatory nature. This document serves as reference for future applications. The document may be reviewed in the future.

Aquaporin water channels AQP1 and AQP3, are expressed in equine articular chondrocytes.

Chondrocytes exist in an unusual and highly variable ionic and osmotic environment in the extracellular matrix of articular cartilage. Alterations to the ionic and osmotic environment of chondrocytes influence the volume and ionic content of the cells, which, in turn, modifies the rate at which extracellular matrix macromolecules are synthesized and degraded. Thus, regulation of the water and solute content of chondrocytes will profoundly affect their anabolic and catabolic functions. The water content of cells is effectively influenced by the abundance of aquaporin (AQP) water channels. Recent studies have shown that several AQP water channel isoforms are expressed in chondrocytes from Meckel's cartilage, developing teeth and other orofacial tissues. The aim of the present investigation was to determine if chondrocytes from equine articular cartilage express AQP water channels. Polyclonal antibodies to AQP1, AQP2 and AQP3 were used in conjunction with immunohistochemistry, immunoblotting and quantitative flow cytometry to determine if AQP1, AQP2 and AQP3 are expressed in equine articular chondrocytes. Our studies show that AQP1 and AQP3 are expressed by chondrocytes in articular cartilage in situ and in isolated chondrocytes. We found no evidence for expression of AQP2, the vasopressin-regulated water channel in chondrocytes. AQP1 and AQP3 may be involved in the transport of water and small solutes and osmotically active metabolites across the chondrocyte plasma membrane during volume regulatory behaviour. AQP1 may be involved in transporting metabolic water. AQP3 may participate in the transport of glycerol and structurally related molecules.

hIscA: a protein implicated in the biogenesis of iron-sulfur clusters.

This article describes the gene called hIscA, its transcription product and protein (hIscA) and its putative function. We screened a human brain cDNA expression library with serum from a patient suffering from the autoimmune Sjögren's syndrome (S5:823/94). One cDNA of 1.6-kbp clone was isolated. This clone contains the entire coding sequence for a protein unknown in human. IscA is ubiquitously expressed and expression levels vary among tissues. The 15.5-kDa predicted protein contains a structural domain named HESB, is located in the mitochondria and is implicated in the biogenesis of iron-sulfur clusters. Since this unknown protein is related to IscA-like protein, we suggest as name for this protein hIscA. The recombinant protein is recognized by a rabbit polyclonal antiserum generated against the carboxyl extreme of the Saccharomyces cerevisiae orthologue Isa1. In this article, we demonstrate the functional homology between hIscA and Isa1 proteins using Isa1 null mutant S. cerevisiae transformed with hIscA in a yeast functional complementation test. We also describe the rat homologue to this gene.

ATPase pumps in osteoclasts and osteoblasts.

Osteoblasts, osteocytes and osteoclasts are specialised cells of bone that play crucial roles in the formation, maintenance and resorption of bone matrix. Bone formation and resorption critically depend on optimal intracellular calcium and phosphate homeostasis and on the expression and activity of plasma membrane transport systems in all three cell types. Osteotropic agents, mechanical stimulation and intracellular pH are important parameters that determine the fate of bone matrix and influence the activity, expression, regulation and cell surface abundance of plasma membrane transport systems. In this paper the role of ATPase pumps is reviewed in the context of their expression in bone cells, their contribution to ion homeostasis and their relation to other transport systems regulating bone turnover.