Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report. / Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Histoplasmosis diseminada en una paciente pediátrica inmunocompetente / Disseminated histoplasmosis in an immunocompetent pediatric patient

La histoplasmosis es una micosis endémica producida por el hongo Histoplasma capsulatum. La forma diseminada en pediatría conlleva alta morbimortalidad. Reportamos el caso de una niña inmunocompetente con diagnóstico de histoplasmosis diseminada. Paciente de 3 años de edad con cuadro clínico de síndrome febril prolongado acompañado de hepatoesplenomegalia confirmada por ecografía. Laboratorio con anemia normocítica, normocrómica y leucopenia. Se arribó al diagnóstico por biopsia de ganglio periportal y periesplénico. El cultivo fue positivo para Histoplasma capsulatum y en estudios histopatológicos se observó linfadenitis granulomatosa con elementos levaduriformes intracelulares. Realizó tratamiento con anfotericina B 1 mg/kg/día durante 6 semanas con favorable resolución clínica. Se debe considerar histoplasmosis diseminada en aquellos pacientes provenientes de zonas endémicas que presentan la tríada de fiebre, hepatoesplenomegalia y citopenias, para poder brindar un tratamiento oportuno, mejorar el pronóstico y disminuir la mortalidad de la enfermedad.

Histoplasmosis is an endemic fungal infection caused by the fungus Histoplasma capsulatum. The disseminated form is associated with a high morbidity and mortality in pediatrics. Here we report the case of an immunocompetent female patient diagnosed with disseminated histoplasmosis. She was 3 years old and presented with protracted febrile syndrome and hepatosplenomegaly confirmed by ultrasound. Lab tests showed normocytic anemia and leukopenia. Diagnosis was made by periportal and perisplenic lymph node biopsy. The culture was positive for Histoplasma capsulatum and histopathological studies showed granulomatous lymphadenitis with intracellular yeast-like elements. Amphotericin B was administered at 1 mg/kg/day for 6 weeks, with a favorable clinical course. Disseminated histoplasmosis should be considered in patients from endemic areas who present the triad of fever, hepatosplenomegaly, and cytopenias so as to provide a timely treatment, improve prognosis, and reduce the mortality from this disease.

Disseminated histoplasmosis in an immunocompetent pediatric patient. / Histoplasmosis diseminada en una paciente pediátrica inmunocompetente.

Histoplasmosis is an endemic fungal infection caused by the fungus Histoplasma capsulatum. The disseminated form is associated with a high morbidity and mortality in pediatrics. Here we report the case of an immunocompetent female patient diagnosed with disseminated histoplasmosis. She was 3 years old and presented with protracted febrile syndrome and hepatosplenomegaly confirmed by ultrasound. Lab tests showed normocytic anemia and leukopenia. Diagnosis was made by periportal and perisplenic lymph node biopsy. The culture was positive for Histoplasma capsulatum and histopathological studies showed granulomatous lymphadenitis with intracellular yeast-like elements. Amphotericin B was administered at 1 mg/kg/day for 6 weeks, with a favorable clinical course. Disseminated histoplasmosis should be considered in patients from endemic areas who present the triad of fever, hepatosplenomegaly, and cytopenias so as to provide a timely treatment, improve prognosis, and reduce the mortality from this disease.

La histoplasmosis es una micosis endémica producida por el hongo Histoplasma capsulatum. La forma diseminada en pediatría conlleva alta morbimortalidad. Reportamos el caso de una niña inmunocompetente con diagnóstico de histoplasmosis diseminada. Paciente de 3 años de edad con cuadro clínico de síndrome febril prolongado acompañado de hepatoesplenomegalia confirmada por ecografía. Laboratorio con anemia normocítica, normocrómica y leucopenia. Se arribó al diagnóstico por biopsia de ganglio periportal y periesplénico. El cultivo fue positivo para Histoplasma capsulatum y en estudios histopatológicos se observó linfadenitis granulomatosa con elementos levaduriformes intracelulares. Realizó tratamiento con anfotericina B 1 mg/kg/día durante 6 semanas con favorable resolución clínica. Se debe considerar histoplasmosis diseminada en aquellos pacientes provenientes de zonas endémicas que presentan la tríada de fiebre, hepatoesplenomegalia y citopenias, para poder brindar un tratamiento oportuno, mejorar el pronóstico y disminuir la mortalidad de la enfermedad.

Effect of process parameters and surfactant additives on the obtained activity of recombinant tryptophan hydroxylase (TPH1) for enzymatic synthesis of 5-hydroxytryptophan (5-HTP).

5-hydroxytryptophan (5-HTP) is an intermediate molecule in the biosynthesis of serotonin, an important neurotransmitter, regulating a series of metabolic and psychological functions in humans. In this work, we studied the heterologous production of Human tryptophan hydroxylase (TPH1) in Escherichia coli, for the synthesis of 5-hydroxytryptophan (5-HTP) from Tryptophan (Trp). To quantify TPH1 activity, a simple fluorescence-based microtiter plate assay was established, based on the changes in fluorescence emission at 340 nm between substrate and product when excited at 310 nm, allowing quick and reliable quantification of released 5-HTP. To increase enzyme production, heterologous TPH1 production was studied in stirred tank bioreactor scale. The effect of rate of aeration (0.25, 0.50 and 0.75 vvm) and agitation (150, 250 and 500 rpm) was evaluated for biomass production, pH, volumetric oxygen transfer coefficient (kLa) and volumetric TPH1 activity. We determined that high agitation and low aeration allowed reaching the maximum measured enzyme activity. Under such conditions, we observed a 90% substrate conversion, obtaining 90 µM (~0.02 g/L) 5-HTP from a 100 µM Tryptophan substrate solution. Finally, we observed that the addition of Tween 20 (0.1%) in the culture broth under production conditions expanded the pH operation range of TPH1. Our results establish a base for a biocatalytic approach as a potential alternative process for the synthesis of 5-HTP using recombinant TPH1.

Sketching neoteric solvents for boosting drugs bioavailability.

Emerging neoteric solvents are being the subject of growing attention due to their lower cost and environmental impact, so they are being applied in a broad spectrum of industries. Among them, the pharmaceutical sector is demanding new environmentally friendly and non-toxic solvents able to enhance drugs solubility and stability. The introduction of ionic liquids turned out to be a breakthrough in the field of Green Chemistry opening up new separation and catalysis opportunities. In this sense, the options represented by Deep Eutectic Solvents make up an attractive alternative due to the low cost of their raw material, simple synthesis, and eco-friendly character. In line with these findings, Therapeutic Deep Eutectic Solvents and Natural Deep Eutectic Solvents are new and promising alternatives to improve the bioavailability of drugs in pharmaceutical formulations. This leading article is focused on providing a general picture of the advantages and drawbacks of these new solvents as well as the main research lines and perspectives to achieve efficient drugs delivery systems.

Utilidad de los registros sanitarios locales para vincular la tasa de incidencia de diarreas con la calidad del agua de consumo / Usefulness of local health reports to link the incidence rate of diarrhea with the quality of drinking water

En este trabajo se realizó un relevamiento de los informes del centro de salud ubicado en Vaqueros (Salta, Argentina) durante un período de 8 meses. Al mismo tiempo se determinó la concentración de Escherichia coli y de quistes de Giardia spp. en muestras procedentes de cuatro fuentes de agua diferentes. No se encontró una relación estadísticamente significativa entre la calidad del agua y los casos de diarrea. Sin embargo, mediante un cálculo de odds ratios, se pudo determinar que uno de los sistemas de potabilización estudiados actúa como factor de protección contra diarreas. El presente trabajo brinda información útil para la planificación de medidas preventivas por parte del sistema de salud local.

In this study, we analyzed the reports of the health care center located in Vaqueros (Salta, Argentina) over an 8-month period. Moreover, we determined the concentration of Escherichia coli and Giardia spp. cysts in samples from four different drinking water sources. A statistical relationship between water quality and cases of diarrhea could not be found. However, using an odds ratio calculation, it was possible to determine that one of the studied drinking water systems acts as a protection factor in cases of diarrhea. The present work provides useful information for planning preventive measures by the local health system.

[Usefulness of local health reports to link the incidence rate of diarrhea with the quality of drinking water]. / Utilidad de los registros sanitarios locales para vincular la tasa de incidencia de diarreas con la calidad del agua de consumo.

In this study, we analyzed the reports of the health care center located in Vaqueros (Salta, Argentina) over an 8-month period. Moreover, we determined the concentration of Escherichia coli and Giardia spp. cysts in samples from four different drinking water sources. A statistical relationship between water quality and cases of diarrhea could not be found. However, using an odds ratio calculation, it was possible to determine that one of the studied drinking water systems acts as a protection factor in cases of diarrhea. The present work provides useful information for planning preventive measures by the local health system.

Caracterización espacial y estacional del agua de consumo proveniente de diversas fuentes en una localidad periurbana de Salta / Spatial and seasonal characterization of the drinking water from various sources in a peri-urban town of Salta

El control del agua de consumo es importante, ya sea que esta provenga de sistemas de potabilización o que carezca de tratamiento previo. El acceso creciente a agua potabilizada ha sido monitorizado a lo largo de los últimos anos a fin de alcanzar los denominados «Objetivos de desarrollo del milenio¼, cuyo plazo se cumplió en 2015. De cara al futuro, los llamados «Objetivos de desarrollo sostenible¼, que se han propuesto para el año 2030, buscan garantizar el acceso a agua segura de toda la población mundial. En el marco de estas metas mundiales, es importante la monitorización de los sistemas locales. En este trabajo se estudió una población que cuenta con diferentes sistemas de provisión de agua de consumo, que incluyen o no el tratamiento de aquella. Se realizó la monitorización de todos los indicadores microbiológicos regidos por el Código Alimentario Argentino y de diversas variables fisicoquímicas, a fin de diferenciar los sitios de muestreo de acuerdo con la influencia de la estacionalidad, el tipo de fuente de provisión de agua y la correlación entre las variables microbiológicas y las fisicoquímicas. Se observó que el agua proveniente de fuentes con tratamiento presentó desviaciones en algunas de sus variables en época de lluvias, mientras que las fuentes sin tratamiento no cumplieron con los requerimientos bacteriológicos en forma permanente. Este estudio pone de manifiesto la importancia de reevaluar los sistemas de potabilización, que deberían garantizar su eficacia de manera constante, así como la inmediata necesidad de desarrollar nuevos sistemas de tratamiento para dar solución a la población que aún no cuenta con agua de consumo segura.

Drinking water monitoring plans are important to characterize both treated and untreated water used for drinking purposes. Access to drinking water increased in recent years as a response to the Millennium Development Goals set for 2015. The new Sustainable Development Goals aim to ensure universal access to safe drinking water by 2030. Within the framework of these global goals, it is crucial to monitor local drinking water systems. In this paper, treated and untreated water from different sources currently consumed in a specific town in Salta, northern Argentina, was thoroughly assessed. Monitoring extended along several seasons and included the physical, chemical and microbiological variables recommended by the Argentine Food Code. On the one hand, treated water mostly complies with these standards, with some non-compliances detected during the rainy season. Untreated water, on the other hand, never meets microbiological standards and is unfit for human consumption. Monitoring seems essential to detect anomalies and help guarantee a constant provision of safe drinking water. New treatment plants are urgently needed to expand the water grid to the entire population.

[Spatial and seasonal characterization of the drinking water from various sources in a peri-urban town of Salta]. / Caracterización espacial y estacional del agua de consumo proveniente de diversas fuentes en una localidad periurbana de Salta.

Drinking water monitoring plans are important to characterize both treated and untreated water used for drinking purposes. Access to drinking water increased in recent years as a response to the Millennium Development Goals set for 2015. The new Sustainable Development Goals aim to ensure universal access to safe drinking water by 2030. Within the framework of these global goals, it is crucial to monitor local drinking water systems. In this paper, treated and untreated water from different sources currently consumed in a specific town in Salta, northern Argentina, was thoroughly assessed. Monitoring extended along several seasons and included the physical, chemical and microbiological variables recommended by the Argentine Food Code. On the one hand, treated water mostly complies with these standards, with some non-compliances detected during the rainy season. Untreated water, on the other hand, never meets microbiological standards and is unfit for human consumption. Monitoring seems essential to detect anomalies and help guarantee a constant provision of safe drinking water. New treatment plants are urgently needed to expand the water grid to the entire population.

Scaling-up and ionic liquid-based extraction of pectinases from Aspergillus flavipes cultures.

The viability of the scaling-up of pectinases production by Aspergillus flavipes at 5L-bioreactor scale has been demonstrated by keeping constant the power input, and a drastic increase in the endo- and exopectinolytic enzyme production was recorded (7- and 40-fold, respectively). The main process variables were modelled by means of logistic and Gompertz equations. In order to overcome the limitations of the conventional downstream strategies, a novel extraction strategy was proposed on the basis of the adequate salting-out potential of two biocompatible cholinium-based ionic liquids (N1112OHCl and N1112OHH2PO4) in aqueous solutions of Tergitol, reaching more than 90% of extraction.

Simultaneous biotreatment of Polycyclic Aromatic Hydrocarbons and dyes in a one-step bioreaction by an acclimated Pseudomonas strain.

A Pseudomonas stutzeri strain acclimated to the presence of neoteric contaminants has been proposed for simultaneously remediating an effluent polluted with Polycyclic Aromatic Hydrocarbons and a diazo dye. The pollutants chemical nature imposed a strict control of both the medium composition and the operating conditions. pH, temperature and agitation rates of 7.0, 37.5 and 146 rpm, respectively, led to optimum levels of contaminant removal (higher than 60%) after RSM optimization. The validity of these conditions was checked at flask and bioreactor scale and the kinetics of the biotreatment was elucidated. The simulation of this one-step process applied at larger scale for the remediation of a 200,000 m(3)/year-effluent from a leather factory was compared with a conventional two-steps option. Great reductions in treatment times and in investment and manufacturing costs were concluded, proving the promising potential of the proposed process.

North Western Spain hot springs are a source of lipolytic enzyme-producing thermophilic microorganisms.

Several hot springs in Galicia (North Western Spain) have been investigated as potential sources of lipolytic enzyme-producing thermophilic microorganisms. After isolating 12 esterase producing strains, 9 of them were assured to be true lipase producers, and consequently grown in submerged cultures, obtaining high extracellular activities by two of them. Furthermore, a preliminary partial characterization of the crude lipase, obtained by ultrafiltration of the cell-free culture supernatant, was carried out at several pH and temperature values. It is outstanding that several enzymes turned out to be multiextremozymes, since they had their optimum temperature and pH at typical values from thermoalkalophiles. The thermal stability in aqueous solution of the crude enzymes was also assayed, and the influence of some potential enzyme stabilizing compounds was tested. Finally, the viability of the selected microorganisms has been demonstrated at bioreactor scale.

A process for extracellular thermostable lipase production by a novel Bacillus thermoamylovorans strain.

A lipolytic enzyme-producing thermophilic microorganism, recently isolated from a hot spring in Galicia (North Western Spain), has been investigated. First, the strain was genetically identified and tentatively named Bacillus thermoamylovorans CH6B. It produced significant levels (around 450 U/L) of extracellular lipolytic activity in shake flask cultures, and the most suitable conditions for this biological process were found at temperatures between 50 and 55 °C, and an initial pH value around 7.0. Next, a preliminary scaling up of the process was carried out in a 5-L stirred tank bioreactor, and it was concluded that operation at agitation and aeration rates of 300 rpm and 0.33 vvm, respectively, were advisable. In both type of cultures, the results were successfully fitted to logistic equations, and the relationship between lipase production and cell growth was investigated. Furthermore, some relevant properties of the crude lipolytic enzyme extracts were assessed. The crude biocatalyst preferentially hydrolysed p-nitrophenyl esters of medium and long-chain fatty acids. Thermal stability in aqueous solution of the produced enzyme was also promising, and the deactivation profiles were fitted to a series-type deactivation model.

[Heart failure and depression. A psychosocial perspective]. / Insuficiencia cardíaca y depresión desde una perspectiva biopsicosocial.

Heart failure is the final stage of many heart diseases and the main cause of mortality. It affects the patient, the family and the health system. Depression affects between the 13.9% and 75% of inpatients, and between 11% and 42% of outpatients. It also affects social life and quality of life, causes hospitalization and rehospitalization, and it activates biological mechanisms that worsen the evolution of heart diseases. From a bibliographic review we discuss psychosocial and biological aspects that relate both diseases.