Granulocitos de baja densidad: Un nuevo marcador de deterioro óseo en pacientes en diálisis peritoneal / Low-density granulocytes: A new marker of bone deterioration in peritoneal dialysis patients

Objetivo: En enfermos renales, la enfermedad ósea-metabólica, la inflamación sistémica y la malnutrición exacerban el riesgo de calcificación vascular (CV) y la morbimortalidad. Dada la fuerte asociación entre CV y fracturas por fragilidad, el objetivo de este estudio es evaluar la contribución de los mayores determinantes de CV al deterioro óseo en pacientes en diálisis peritoneal (DP).Métodos: En 31 pacientes no diabéticos en DP (>6 meses), se estudiaron marcadores de alteraciones del metabolismo óseo, daño vascular, inflamación y desnutrición, y, su impacto en el deterioro óseo (osteopenia radiológica y/o antecedentes de fractura por fragilidad).Resultados: En estos pacientes, (20 varones y 11 mujeres; edad=54±15 y 60±11 años respectivamente (p=0,24)), la prevalencia de fracturas por fragilidad fue de 5% en hombres y del 27% en mujeres. El deterioro óseo fue mayor en personas de edad avanzada, sexo femenino, índices de Charlson y Kauppila elevados, menor masa muscular y con expansión de una subpoblación altamente inflamatoria de granulocitos inmaduros de baja densidad (LDGi). Un análisis de regresión logística demostró que el riesgo de deterioro óseo está más influenciado por el sexo femenino que por la edad y que, de los múltiples factores asociados a mayor deterioro óseo estudiados, sólo la expansión de LDGi estima el riesgo de alteraciones óseas en estos pacientes independientemente de su edad y sexo.Conclusión: La expansión de LDGi provee de un biomarcador certero para el diagnóstico de deterioro óseo y para monitorizar estrategias que atenúen su progresión en pacientes en DP de cualquier edad y sexo. (AU)

Asociación de parámetros bioquímicos del metabolismo óseo con progresión y/o desarrollo de nuevas calcificaciones aórticas / Association of biochemical parameters of bone metabolism with progression and/or development of new aortic calcifications

Objetivo: Los parámetros bioquímicos siguen siendo la opción más utilizada para el seguimiento de pacientes con alteraciones metabólicas óseas. El objetivo del estudio fue valorar la asociación de algunos marcadores bioquímicos del metabolismo óseo con aparición y progresión de calcificaciones aórticas. Material y métodos: Se seleccionaron aleatoriamente 624 hombres y mujeres mayores de 50 años que cumplimentaron un cuestionario y a los que se realizaron dos radiografías laterales dorso?lumbares y densitometría ósea. Cuatro años más tarde, en 402 sujetos se repitieron los mismos estudios junto con un estudio bioquímico. Resultados: La edad y la proporción hombres fue superior en los que tuvieron “progresión global” de calcificación aórtica (progresión de las ya existentes más las nuevas). Los niveles séricos de calcio y calcitriol fueron significativamente superiores y los de osteocalcina significativamente inferiores en los que se observó “progresión global” de calcificación aórtica. El análisis multivariante mostró que únicamente la osteocalcina se asoció de forma independiente con “progresión global” de calcificación aórtica, con una disminución del 18% por cada incremento de 1 ng/mL en los niveles de osteocalcina (odds ratio (OR)=0,82; intervalo de confianza del 95% (IC 95%): 0,71-0,92). La categorización de la osteocalcina en terciles mostró que los sujetos del primer tercil (<4,84 ng/mL) se asociaron con mayor proporción de nuevas calcificaciones aórticas: (OR=2,45; IC 95%: 1,03-3,56) respecto al tercer tercil (>6,40 ng/mL). Conclusión: Los niveles séricos de osteocalcina podrían ser un marcador bioquímico para evaluar la aparición y/o a evolución de la calcificación aórtica. No obstante, se necesita determinar con mayor precisión como podría ejercer este efecto protector en el proceso de calcificación vascular (AU)

Objetive: Biochemical parameters continue to be the most widely used option for the follow-up of patients with bone metabolic disorders. The objective of our study was to assess the association of some biochemical markers of bone metabolism with the appearance and progression of aortic calcifications. Material and methods: In this study, 624 men and women older than 50 years were selected at random. The participants completed a questionnaire and underwent two lateral dorsal-lumbar x-rays and bone densitometry. Four years later, the same studies were repeated in 402 subjects along with a biochemical study. Results: Age and the proportion of men were higher in those who had “global progression” of aortic calcification (progression of the existing ones plus new ones). The serum levels of calcium and calcitriol were significantly higher and those of osteocalcin significantly lower in which “global progression” of aortic calcification was observed. Multivariate analysis showed that only osteocalcin was independently associated with “global progression” of aortic calcification, with an 18% decrease for each 1 ng/mL increase in osteocalcin levels (odds ratio (OR)=0, 82; 95% confidence interval (95% CI): 0.71-0.92). The categorization of osteocalcin into tertiles showed that the subjects of the first tertile (<4.84 ng/mL) were associated with a higher proportion of new aortic calcifications: (OR=2.45; 95% CI: 1.03-3, 56) with respect to the third tertile (>6.40 ng/mL). Conclusion: Serum levels of osteocalcin could be a biochemical marker to evaluate the appearance and/or evolution of aortic calcification. However, it is necessary to determine with greater precision how it could exert this protective effect in the process of vascular calcification. (AU)

Efecto de la fragilidad y la sarcopenia sobre el riesgo de caídas y de fracturas osteoporóticas en población no seleccionada / Effect of frailty and sarcopenia on the risk of falls and osteoporotic fractures in an unselected population

OBJETIVOS: Valorar si la fuerza de agarre y la dificultad para realizar actividades cotidianas podrían ser predictores de caídas y fracturas osteoporóticas. MATERIAL Y MÉTODOS: Se seleccionaron aleatoriamente 624 hombres y mujeres mayores de 50 años, que fueron seguidos durante 8 años para conocer la incidencia de caídas y fracturas osteoporóticas no vertebrales. Al inicio se midió la fuerza de agarre en manos y se cumplimentó un cuestionario con variables clínicas, factores de riesgo relacionados con la osteoporosis y cuestiones relativas a la dificultad o incapacidad para realizar actividades cotidianas. RESULTADOS: La fuerza de agarre en manos no se asoció con la incidencia de caídas y fracturas. Sin embargo, la imposibilidad o dificultad de "estar sentado más de 1 hora en silla dura", "quitarse los calcetines o las medias" e "inclinarse desde una silla para coger un objeto del suelo" se asoció con caídas: 1,83 (1,16-2,89); 1,85 (1,14-3,00) y 1,68 (1,04-2,70), respectivamente. Del mismo modo, la imposibilidad o dificultad de "llevar durante 10 metros un objeto de 10 kilos" y "levantar una caja con 6 botellas y ponerlas sobre una mesa" se asoció con fractura: 2,82 (1,21-6,59) y 2,54 (1,12-5,81) respectivamente. CONCLUSIONES: No se encontró asociación entre la fuerza de agarre e incidencia de caídas y fracturas osteporóticas, pero sí con dificultad o incapacidad para realizar actividades cotidianas. Las relacionadas con mayor fuerza se asociaron con fractura, mientras que las relacionadas con capacidad funcional se asociaron con caídas. Realizar cuestionarios sencillos podría ayudar a predecir eventos antes de que ocurran

OBJECTIVE: Assess whether grip strength and difficulty in carrying out daily activities could be predictors of falls and osteoporotic fractures. MATERIAL AND METHODS: 624 men and women over 50 years of age were randomly selected and followed for 8 years to determine the incidence of falls and non-vertebral osteoporotic fractures. At the beginning, the grip strength in the hands was measured and a questionnaire was filled out with clinical variables, risk factors related to osteoporosis, and questions related to difficulty or inability to perform daily activities. RESULTS: Grip strength in the hands was not associated with the incidence of falls and fractures. However, the impossibility or difficulty of "sitting for more than 1 hour in a hard chair", "taking off socks or stockings" and "leaning from a chair to pick up an object from the floor" were associated with falls: 1.83 (1.16-2.89); 1.85 (1.14-3.00) and 1.68 (1.04-2.70), respectively. Similarly, the impossibility or difficulty of "carrying a 10-kilogram object for 10 meters" and "lifting a box with 6 bottles and putting them on a table" was associated with fracture: 2.82 (1.21-6.59) and 2.54 (1.12-5.81) respectively. CONCLUSIONS: No association was found between grip strength and incidence of falls and osteoporotic fractures, but it was found with difficulty or inability to perform daily activities. Those related to greater strength were associated with fracture, while those related to functional capacity were associated with falls. Taking simple questionnaires could help predict events before they happen

Epidemiology, molecular characterisation and antimicrobial susceptibility of Neisseria gonorrhoeae isolates in Madrid, Spain, in 2016.

With the aim to elucidate gonococcal antimicrobial resistance (AMR)-risk factors, we undertook a retrospective analysis of the molecular epidemiology and AMR of 104 Neisseria gonorrhoeae isolates from clinical samples (urethra, rectum, pharynx and cervix) of 94 individuals attending a sexually transmitted infection clinic in Madrid (Spain) from July to October 2016, and explored potential links with socio-demographic, behavioural and clinical factors of patients. Antimicrobial susceptibility was determined by E-tests, and isolates were characterised by N. gonorrhoeae multi-antigen sequence typing. Penicillin resistance was recorded for 15.4% of isolates, and most were susceptible to tetracycline, cefixime and azithromycin; a high incidence of ciprofloxacin resistance (~40%) was found. Isolates were grouped into 51 different sequence types (STs) and 10 genogroups (G), with G2400, ST5441, ST2318, ST12547 and G2992 being the most prevalent. A significant association (P = 0.015) was evident between HIV-positive MSM individuals and having a ciprofloxacin-resistant strain. Likewise, a strong association (P = 0.047) was found between patient age of MSM and carriage of isolates expressing decreased susceptibility to azithromycin. A decrease in the incidence of AMR gonococcal strains and a change in the strain populations previously reported from other parts of Spain were observed. Of note, the prevalent multi-drug resistant genogroup G1407 was represented by only three strains in our study, while the pan-susceptible clones such as ST5441, and ST2318, associated with extragenital body sites were the most prevalent.

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density.

BACKGROUND AND AIMS: Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors. METHODS AND RESULTS: In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders. CONCLUSION: SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.

Anti-ribosomal P antibodies are associated with elevated circulating IFNα and IL-10 levels in systemic lupus erythematosus patients.

OBJECTIVE: The objective of this paper is to analyze the relationship of anti-protein ribosomal P (RibP) antibodies with circulating levels of IFNα, TNFα, IFNγ, IL-17 and IL-10 in SLE. Disease activity and other systemic lupus erythematosus (SLE) features were also analyzed. METHODS: Anti-RibP and other SLE-related antinuclear antibodies (ANA) were determined by fluoro-enzyme immunoassay in the sera of 107 SLE patients. Circulating cytokines were quantified by flow cytometry (IFNα, IL-10 and IL-17) or ELISA (TNFα and IFNγ). RESULTS: Anti-RibP-positive patients (14.9%) displayed significantly higher serum levels of IFNα (p = 0.023) and IL-10 (p = 0.016) than their negative counterparts. This cytokine upregulation was independent of the presence of other ANA even though, in our patient cohort, anti-dsDNA was found to be associated with anti-RibP (OR, CI 95%: 6.03, 1.32-27.93, p = 0.021) and to correlate with IL-10 levels (r = 0.204, p = 0.036). In fact, patients positive for anti-RibP but negative for anti-dsDNA exhibited the highest amounts of both IL-10 and IFN-α that were not related to disease activity since these patients showed lower SLEDAI than patients also positive for anti-dsDNA (p = 0.018). Anti-RibP positivity was also associated with early diagnosis, hypocomplementemia and leukopenia. CONCLUSIONS: Presence of anti-RibP was found to be related to increased serum IFNα and IL-10 levels independently of both antibody status and disease activity.

Monoterapia biológica en pacientes con artritis reumatoidea en Argentina / Biological monotherapy in patients with rheumatoid arthritis in Argentina

Introducción: La utilización de agentes biológicos para el tratamiento de la Artritis Reumatoidea (AR) es habitualmente usada en aquellos pacientes con enfermedad activa que no hayan respondido al tratamiento con drogas modificadoras de la Artritis Reumatoidea convencionales (DMARD, por sus siglas en inglés) o que hayan presentado intolerancia a las mismas. Al estado actual de la evidencia, la terapia combinada de agentes biológicos más un DMARD convencional (principalmente metotrexato) constituye el estándar de tratamiento. Sin embargo existen algunos escenarios como la intolerancia, la falta de adherencia y la aparición de eventos adversos a las DMARDs convencionales donde la monoterapia biológica emerge como una opción terapéutica válida. Según los distintos registros a nivel internacional, la frecuencia de utilización de agentes biológicos en monoterapia oscila entre 12 a 39%. Debido a la ausencia de estos datos a nivel local decidimos realizar este estudio para conocer el porcentaje de pacientes que se encuentran en monoterapia biológica y analizar las causas que llevaron a este tipo de tratamiento. Materiales y métodos: Estudio de tipo corte transversal donde se invitó a participar a diferentes centros reumatológicos distribuidos a lo largo de Argentina. Cada centro revisó las historias clínicas de los últimos 30 a 50 pacientes consecutivos vistos con AR, mayores de 18 años, que habían presentado inadecuada respuesta al tratamiento con DMARDs y que estaban bajo tratamiento biológico. Se completaba una ficha por cada paciente incluido, registrando datos demográficos, de la enfermedad y tratamientos previos. Resultados: Se incluyeron 32 centros y se evaluaron 1148 historias clínicas de pacientes con AR durante el mes de octubre y noviembre del 2012. Un 21,4% (246) de los pacientes al momento del estudio se encontraba bajo tratamiento biológico en monoterapia...

Introduction: The use of biological agents for the treatment of rheumatoid arthritis (RA) is commonly used in patients with active disease who have not responded to treatment with conventional rheumatoid arthritis-modifying drugs (DMARDs) or Who have presented intolerance to them. At the present state of evidence, combined therapy of biological agents plus conventional DMARD (mainly methotrexate) is the standard of treatment. However, there are some scenarios such as intolerance, lack of adherence and the appearance of adverse events to conventional DMARDs where biological monotherapy emerges as a valid therapeutic option. According to different international registries, the frequency of use of biological agents in monotherapy ranges from 12 to 39%. Due to the absence of these data at the local level we decided to carry out this study to know the percentage of patients who are in biological monotherapy and to analyze the causes that led to this type of treatment. Materials and methods: A cross-sectional study where different rheumatologic centers throughout Argentina were invited to participate. Each center reviewed the medical records of the last 30 to 50 consecutive patients seen with RA, older than 18 years, who had inadequate response to treatment with DMARDs and who were under biological treatment. One card was completed for each patient included, recording demographic, disease and previous treatment data. Results: Thirty-two centers were included and 1148 clinical records of patients with RA were evaluated during October and November 2012. A total of 244 patients (246) at the time of the study were under monotherapy...

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum.

The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres prepared. All the antimony IC50 values from encapsulated meglumine antimoniate (3.80 +/- 0.34 to 9.53 +/- 0.70 microg SbV/ml for promastigotes assay) are considerably lower compared to the mean value of IC50 in Glucantime solution (112 +/- 12.74 microg SbV/ml). Interesting IC50 values for the excipient chitosan (112.64 +/- 0.53 mg/ml for promastigotes and 100.81 +/- 26.45 mg/ml for amastigotes) were obtained (without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects because of meglumine antimoniate.

Efficacy of liposomal amphotericin B for secondary prophylaxis of visceral leishmaniasis in HIV-infected patients.

BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL) is characterized by frequent relapses in HIV-infected patients, even in those who receive secondary prophylaxis. The aim of our study was to evaluate the efficacy of liposomal amphotericin B (L-AMB) for secondary prophylaxis of VL in HIV-infected patients. METHODS: From January 2001 to December 2005, 17 HIV patients, with at least one previous episode of VL who received L-AMB as secondary prophylaxis for VL, were included in the study. Efficacy was measured as the proportion of patients remaining free (non-relapse) of VL at different time points. Relapses were analysed as time-to-relapse distribution and were evaluated by survival analysis using the Kaplan-Meier method. RESULTS: Twenty-one episodes of VL were diagnosed and nine relapsed. The median follow-up time was 14 (5-44) months. The probability of remaining free of relapse at 6 months was 89.7% (95% CI, 76.2-100); at 12 months, the probability was 79.1% (95% CI, 61-97.2) and at 24 and 36 months, the probability was 55.9% (95% CI, 30.5-81.3). In the non-relapsing group, patients had a significant increase in CD4 cell levels of 102 (10-174) and 126 (4-159) cells/mm(3) at 12 and 24 months, respectively (P = 0.037), whereas in the relapsing group, no significant increase was observed. Prophylaxis with L-AMB was well tolerated and only three patients had a mild impairment of renal function without requiring any change in treatment. CONCLUSIONS: L-AMB is well tolerated and useful for secondary prophylaxis of VL.

Evaluation of a latex agglutination test (KAtex) for detection of Leishmania antigen in urine of patients with HIV-Leishmania coinfection: value in diagnosis and post-treatment follow-up.

The usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with Leishmania-HIV coinfection was evaluated with a latex agglutination test (KAtex; Kalon Biological, UK). Forty-nine HIV-infected patients with visceral leishmaniasis were included in the study. Antigen detection in urine (ADU) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. After treatment, a follow-up study in 23 patients was performed by simultaneous ADU and culture of peripheral blood mononuclear cells in 148 determinations. The two methods gave concordant results in 94 cases, 38 of which were positive and 56 negative. In five cases, ADU was negative and culture of peripheral blood mononuclear cells was positive: two of these cases corresponded to clinical relapses. In 49 cases, culture of peripheral blood mononuclear cells was negative and ADU was positive. In the absence of clinical symptoms, the detection of parasite antigens in 71 of 130 (54.6%) urine samples was not associated with clinical disease. The Kaplan-Meier estimates of the probability of relapse at 6, 12, 18, and 24 months were 16% (95%CI, 15-17%), 20% (95%CI, 18-22%), 31% (95%CI, 27-35%), and 71% (95%CI, 52-89%), respectively, in patients with a positive ADU result. In contrast, when ADU was negative, the probability of relapse was 5% at 6 months (95%CI, 2-8%) (only 2 of 11 patients who relapsed had a negative test). ADU by KAtex is appropriate for primary diagnosis of visceral leishmaniasis, for monitoring the efficacy of treatment, and for detection of subclinical infection.

[Bladder carcinoma with osteoclast-type giant cells. A case with a rare presentation. Review of the literature]. / Carcinoma con células gigantes tipo osteoclasto de vejiga. Un caso de rara presentación. Revisión de la literatura.

We report a case of neoplasm of the urinary bladder with pseudosarcomatous stromal differentiation. Heterologous carcinosarcomas are extremely rare malignant neoplasms (seventy-eight cases have been previously described). This is a case of carcinoma containing numerous osteoclast type giant cells that stained for vinmentin and acid phosphatase and were negative for cytokeratin and lysozyme.

Two polymeric compounds built from mononuclear and tetrameric squarate-copper(II) complexes by deprotonation of 3,3-bis(2-imidazolyl)propionic acid (HBIP). Synthesis, crystal structure, and magnetic characterization of [Cu(HBIP)(BIP)](C(4)O(4))(1/2).2H(2)O and [[Cu(BIP)(OH(2))](4)(mu-C(4)O(4))](ClO(4))(2).4H(2)O.

Two polynuclear copper(II)-squarate compounds of formulas [Cu(HBIP)(BIP)](C(4)O(4))(1/2).2H(2)O (1) and [[Cu(BIP)(OH(2))](4)(mu-C(4)O(4))](ClO(4))(2).4H(2)O (2) (HBIP = 3,3-bis(2-imidazolyl)propionic acid) have been synthesized and characterized by single-crystal X-ray diffraction. Both compounds crystallize in the triclinic system, space group P1, with a =7.947(1) A, b =12.327(4) A, c = 13.150(3) A, alpha = 113.91(2) degrees, beta = 99.85(2) degrees, gamma = 90.02(2) degrees for compound 1 and a = 8.010(1) A, b = 13.073(1) A, c = 14.561(1) A, alpha = 72.13(1) degrees, beta = 80.14(1) degrees, gamma = 84.02(1) degrees for compound 2. The structure of compound 1 can be viewed as made up of [Cu(HBIP)(BIP)] units linked together by the BIP carboxylate groups to form a one-dimensional chain structure along the a axis in the crystal. The copper ion is five-coordinated (CuN(4)O chromophore) with BIP and HBIP acting as tridentate and bidentate ligands, respectively. The coordination geometry is intermediate between SP and TBP. The structure of compound 2 is made of infinite chains built from cationic tetranuclear [[Cu(BIP)(OH(2))](4)(mu-C(4)O(4))](2+) complex units, two uncoordinated perchlorate anions, and four water molecules of crystallization. The squarato group bridges the copper(II) ions, while BIP acts as a tridentate ligand, connecting through its carboxylate group the tetrameric units along the a axis. The two crystallographically independent copper(II) ions are pentacoordinated within a distorted square-based pyramid. Electronic and EPR spectra are consistent with the crystallographic data. Both compounds follow a Curie-Weiss law with very low values of theta (-0.13 and +0.12 K). In compound 2, the weak ferromagnetism interaction is discussed on the basis of the structural features and correlated with published magnetostructural data on similar squarato-bridged copper(II) compounds.

Leishmania infantum: stage-specific activity of pentavalent antimony related with the assay conditions.

The determination of the intrinsic sensitivity of Leishmania strains to pentavalent antimonials in clinical trials, before treatment is begun, is essential in order to avoid failures and to allow alternative drugs to be chosen. A comparative study of SbV activity on promastigotes, axenic amastigote-like cells, and intracellular amastigotes of Leishmania infantum, when administered in the form of meglumine antimoniate and free, in hydrochloric solution, was performed. Results indicate that the conditions under which the promastigotes were cultured affect the IC(50) obtained, although results were homogeneous when the products were assayed on axenic-like and intracellular amastigotes. The IC(50) obtained for SbV in the form of meglumine antimoniate or in hydrochloric solution on promastigotes cultured in Schneider's medium depends on the growth rate of the culture and therefore could be regulated by modifying the fetal calf serum concentration in the medium. The pH of the culture medium strongly affected the activity of meglumine antimoniate but not that of the SbV hydrochloric solution on promastigotes cultured in Schneider's medium. This influence of pH was observed to a much lesser extent when promastigotes were cultured on M199 or RPMI media. In homogeneous culture conditions, which included the regulation of the promastigote growth rate through the heat-inactivated fetal calf serum concentration in the medium and the dilution of the meglumine antimoniate with Schneider's medium at pH 6.5, the activity of SbV, free or in the form of meglumine antimoniate, was the same in promastigotes, intracellular amastigotes, and axenic amastigote-like cells.

A novel heterocyclic sulfonamide: N-benzyl-5-[N-benzyl-N-(tert-butyloxycarbonyl)amino]-N-(tert-butyloxycarbonyl)-1,3,4-thiadiazole-2-sulfonamide.

The title compound, C(26)H(32)N(4)O(6)S(2), is a heterocyclic sulfonamide which is a 1,3,4-thiadiazole derivative. Structural data for this compound are compared with those of related compounds.

Serological and parasitological follow-up in dogs experimentally infected with Leishmania infantum and treated with meglumine antimoniate.

Six healthy beagle dogs were infected with Leishmania infantum (MCAN/ES/92/BCN-83/MON-1) by intravenous inoculation of 5 x 10(7) promastigotes and two others were used as controls. When animals showed clinical signs of disease at 29, 37, 41 and 45 weeks post-infection (p.i.), they were treated with meglumine antimoniate (20.4 mg Sb/kg/12 h) subcutaneously for two periods of 10 days each. Sera were tested periodically for Leishmania antibodies by Dot-ELISA, ELISA and Western blot (WB). Aspirates of popliteal lymph node (PLN), peripheral blood sample (PB) and healthy skin were cultured in NNN and Schneider's medium. PLNs were positive between 8 and 20 weeks p.i. and in one animal PB was positive 6 weeks p.i. Samples of healthy skin, obtained before treatment, were also positive. Dot-ELISA and ELISA detected specific antibodies at an early stage between 4 and 12 weeks p.i and surpassed the cut-off between 16-24 weeks p.i., while the WB was positive between 10-19 weeks p.i. The pattern of bands revealed during the first stages of infection was variable and only in two cases did the positivity start with bands of low molecular weight (12-14 kD); the number of bands increased until 15-24 weeks p.i., after which sera revealed a complete pattern of bands, from 12 to 85 kD, in the antigen of Leishmania. After treatment the clinical improvement of the animals was accompanied by a decrease in antibody titers (Dot-ELISA and ELISA) although the parasites remained in the PLN. This was reflected in the WB by a decrease in the intensity of bands, especially those in the region of 12-30 kD. A new increase in the antibody levels between 3 and 5 months after terminating the therapy was detected in the WB by a restoration of the initial complete pattern of bands.

Epidemiology of canine leishmaniosis in Catalonia (Spain) the example of the Priorat focus.

An epidemiological survey of canine leishmaniosis was conducted in the Priorat, a rural region in the Northeast of Spain, for 10 years (1985-1994). Seroprevalence throughout the region, determined by dot-ELISA and IFI, was 10.2% (8-12%). Forty percent of the dogs studied had a low level of anti-Leishmania antibodies, whereas only 50% were seronegative. Only one-third of the seropositive dogs had evident symptoms of the disease. Annual incidence of the disease was 5.7% and the level of endemicity was stable during the study. Four Leishmania zymodemes (MON-1, MON-29, MON-77, MON-105) were present in the focus, and their distribution in the different hosts is discussed. Apart from dogs and foxes, no other reservoir host has been found in the region.

Synthesis, Crystal Structure, and Magnetic Properties of Oxalato-Copper(II) Complexes with 3,3-Bis(2-imidazolyl)propionic Acid, an Imidazole-Carboxylate Polyfunctional Ligand: From Mononuclear Entities to Ladder-Like Chains.

The synthesis of five new Cu(II) compounds of formula [Cu(HBIP)(C(2)O(4))].H(2)O (1), [Cu(HBIP)(C(2)O(4))(OH(2))].2H(2)O (2), [{Cu(HBIP)Cl}(2)(&mgr;-C(2)O(4))].2H(2)O (3), [{Cu(BIP)}(2)(&mgr;-C(2)O(4))].2H(2)O (4) and [{Cu(BIP)}(2)(&mgr;-C(2)O(4))].6H(2)O (5), together with their spectral and magnetic characterization, is reported. Crystal structures of compounds 2, 3 and 5 have been solved. All these compounds crystallize in the triclinic system, space group P&onemacr;, with a = 7.3322(3) Å, b = 10.014(1) Å, c = 11.541(1) Å, alpha = 113.22(1) degrees, beta = 91.37(1) degrees, gamma = 94.51(1) degrees, Z = 2 for compound 2; a = 7.444(2) Å, b = 8.518(2) Å, c = 11.231(2) Å, alpha = 97.45(2) degrees, beta = 98.99(2) degrees, gamma = 97.95(2) degrees, Z = 1 for compound 3; and a = 7.977(1) Å, b = 8.656(1) Å, c = 11.807(1) Å, alpha = 69.06(1) degrees, beta = 86.07(1) degrees, gamma = 67.36(1) degrees, Z = 1 for compound 5. In compound 2 the asymmetric unit consists of one isolated neutral [Cu(HBIP)(C(2)O(4))(OH(2))] molecule and two noncoordinated water molecules. The Cu(II) ion is five-coordinated (4+1 coordination mode) with HBIP and oxalato entities acting as bidentate ligands and the water molecule as the fifth ligand. The structure of compound 3 is made up of centrosymmetric binuclear [{Cu(HBIP)(Cl)}(2)(&mgr;-C(2)O(4))] units and noncoordinated water molecules. The two copper atoms are linked through a bis-bidentate oxalato group leading to a metal-metal separation of 5.28(3) Å. The coordination stereochemistry of the CuN(2)O(2)Cl chromophore is approximately SP. Compound 5 exhibits a structure built of ladder-like chains. In these chains the rungs are constituted by the neutral dinuclear centrosymmetric [(BIP)Cu(C(2)O(4))Cu(BIP)] entities. The oxalato group bridges two copper atoms in a bis-bidentate fashion, whereas the BIP acts as a tridentate ligand, connecting through their carboxylate groups these dimeric units along the a axis. The copper atom is involved in a five-coordinated CuN(2)O(2)O' chromophore, with a coordination geometry intermediate between SP and TBP. The magnetic properties of all complexes have been investigated. Compound 1 and 2 follow a Curie-Weiss law with very low values of theta. The other three compounds exhibit an antiferromagnetic coupling, with 2J = -265 cm(-)(1) for 3, 2J = -108 cm(-)(1) for 4, and 2J = -5.7 cm(-)(1) for 5. The strength of the exchange interaction is discussed on the basis of the structural features and correlated with published magneto-structural data on similar oxalato-bridged copper(II) compounds.

Cinoxacin complexes with divalent metal ions. Spectroscopic characterization. Crystal structure of a new dinuclear Cd(II) complex having two chelate-bridging carboxylate groups. Antibacterial studies.

Several cinoxacin (HCx) complexes with divalent metal ions have been prepared and characterized by spectroscopic techniques. The crystal structure of [Cd2(Cx)4(H2O)2].10H2O has been determined by X-ray diffraction. The complex is triclinic, space group P1 with unit-cell dimensions: a = 10.412(2), b = 11.119(2), c = 13.143(6)A, chi== 76.78(4) degrees, beta = 74.59(3) degrees, gamma = 77.12(3) degrees, V = 1406.0(8) A3. In this complex each cadmium atom is heptacoordinated: the metal environment is formed by two Oketo and two Ocarbox atoms from two different cinoxacinate monoanions, two carboxylate oxygen atoms from a third cinoxacinate ligand and by one water oxygen atom on the seventh position. Two of the cinoxacinate ions act as tridentate chelate and bridging ligands and the other one as a bidentate chelate ligand. In the bridging monoanions the carboxylate group is behaving as a chelate ligand. All the complexes were screened for their activity against several bacteria, showing activity similar to that of cinoxacin. Additionally, the number of bacteria killed after 3 h of incubation with cinoxacin, [Cu(Cx)2].2H2O and [Co(Cx)3]Na.10H2O complexes was determined against E. coli ATCC 25922; the copper compound presents paradoxical effect which has been described and related to the mechanism of action of quinolones.