Osteopetrosis: presentación de caso clínico

La osteopetrosis, en particular la variante autosómica recesiva, es una patología con alta mortalidad de muy baja incidencia, lo cual conlleva al retraso de su diagnóstico perdiendo la posibilidad de un tratamiento oportuno para mejorar su pronóstico. Esta enfermedad se produce por una falla en la función o diferenciación osteoclástica con reabsorción ósea defectuosa. Presentamos un caso clínico motivados por la necesidad de agudizar su sospecha ante la presencia de los siguientes signos clínicos (hipocalcemia, alteraciones hematológicas, disfunción de pares craneales) y radiológicos característicos (engrosamiento cortical con colapso medular, esclerosis difusa afectando cráneo, huesos largos y columna, esclerosis focal, líneas escleróticas y radiolucidas que se alternan). Es necesario estar alertas a esta entidad para dar la posibilidad de un pronto estudio genético para arribar más rápido al transplante de medula ósea mejorando la sobrevida de estos pacientes.The osteopetrosis, including autosomal recessive variant is a disease with high mortality of very low incidence which leads to delay in diagnosis losing the possibility of early treatment to improve their prognosis. This disease is caused by a failure to function or osteoclastic differentiation with defective bone resorption We report a case motivated by the need to sharpen their suspicion in the presence of the following clinical signs (hypocalcemia, blood disorders, cranial nerve dysfunction) and radiological characteristic (core collapse cortical thickening, diffuse sclerosis affecting skull, long bones and spine, focal sclerosis, sclerotic and radiolucent lines alternating). You need to be alert to this organization to give the possibility of a genetic study soon to arrive faster by improving bone marrow transplant survival in these patients

Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice

Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and arterial stiffness. We hypothesized that the absence of CT-1 influences arterial fibrosis and stiffness, senescence, and life span. In senescent 29-month- old mice, vascular function was analyzed by echotracking device. Arterial histomorphology, senescence, metabolic, inflammatory, and oxidative stress parameters were measured by immunohistochemistry, reverse transcription polymerase chain reaction, Western blot, and ELISA. Survival rate of wild-type and CT-1–null mice was studied. Vascular smooth muscle cells were treated with CT-1 (10 −9 mol/L) for 15 days to analyze senescence. The wall stress-incremental elastic modulus curve of old CT-1–null mice was shifted rightward as compared with wild-type mice, indicating decreased arterial stiffness. Media thickness and wall fibrosis were lower in CT-1–null mice. CT-1–null mice showed decreased levels of inflammatory, apoptotic, and senescence pathways, whereas telomere-linked proteins, DNA repair proteins, and antioxidant enzyme activities were increased. CT-1–null mice displayed a 5-month increased median longevity compared with wild-type mice. In vascular smooth muscle cells, chronic CT-1 stimulation upregulated apoptotic and senescence markers and downregulated telomere-linked proteins. The absence of CT-1 is associated with decreased arterial fibrosis, stiffness, and senescence and increased longevity in mice likely through downregulating apoptotic, senescence, and inflammatory pathways. CT-1 may be a major regulator of arterial stiffness with a major impact on the aging proces

Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction

Cardiotrophin 1 (CT-1), a cytokine belonging to the interleukin 6 family, is increased in hypertension and in heart failure. We aimed to study the precise role of CT-1 on cardiac, vascular, and renal function; morphology; and remodeling in early stages without hypertension. CT-1 (20 g/kg per day) or vehicle was administrated to Wistar rats for 6 weeks. Cardiac and vascular functions were analyzed in vivo using M-mode echocardiography, Doppler, and echo tracking device and ex vivo using a scanning acoustic microscopy method. Cardiovascular and renal histomorphology were measured by immunohistochemistry, RT-PCR, and Western blot. Kidney functional properties were assessed by serum creatinine and neutrophile gelatinase-associated lipocalin and microalbuminuria/creatininuria ratio. Without alterations in blood pressure levels, CT-1 treatment increased left ventricular volumes, reduced fractional shortening and ejection fraction, and induced myocardial dilatation and myocardial fibrosis. In the carotid artery of CT-1–treated rats, the circumferential wall stress-incremental elastic modulus curve was shifted leftward, and the acoustic speed of sound in the aorta was augmented, indicating increased arterial stiffness. Vascular media thickness, collagen, and fibronectin content were increased by CT-1 treatment. CT-1–treated rats presented unaltered serum creatinine concentrations but increased urinary and serum neutrophile gelatinase-associated lipocalin and microalbuminuria/creatininuria ratio. This paralleled a glomerular and tubulointerstitial fibrosis accompanied by renal epithelial-mesenchymal transition. CT-1 is a new potent fibrotic agent in heart, vessels, and kidney able to induce cardiovascular-renal dysfunction independent from blood pressure. Thus, CT-1 could be a new target simultaneously integrating alterations of heart, vessels, and kidney in early stages of heart failure

Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region

Comparing continuous and batch operation for high-rate treatment of urban wastewater

Altres ajuts: Acord transformatiu CRUE-CSICThe water-energy nexus has changed the concept of wastewater treatment plants (WWTPs), which should move from energy consumers into energy neutral or even energy positive facilities. The A/B process aims at achieving self-sufficient energy WWTPs: organic matter is removed in the first step (A-stage) and derived to biogas production whereas autotrophic nitrogen removal is implemented in a second step (B-stage). This work compares two high-rate systems that can be used as A-stage in view of organic matter removal: a continuous high rate activated sludge (HRAS) reactor and a high-rate sequencing batch reactor (HRSBR). Both systems were operated with real urban wastewater at a short hydraulic retention time (2.5 h) and at short sludge retention time (SRT) of 1-2 d to minimize COD mineralization and to maximize organic matter diversion to methane production and, hence, energy recovery. The HRAS showed higher COD removal efficiencies and better energy recovery. On the other hand, the HRSBR was better to avoid undesired nitrification and provided lower COD mineralization for all the SRTs tested (ranging 20-48% for the HRSBR, and 41-58% for the HRAS). Then, the energy as methane recovered per unit of COD degraded was higher in the HRSBR. The HRSBR seems to be a good option, because the solids content in the effluent was similar for both systems and its COD removal efficiency can be further improved by optimizing the SBR cycle configuration

Assessment of the significance of heavy metals, pesticides and other contaminants in recovered products from water resource recovery facilities

Acord transformatiu CRUE-CSICThe recovery of valuable materials from municipal water resource recovery facilities (WRRF) is a promising option to implement circular economy in wastewater treatment. Different technologies are being evaluated at different WRRF to recover products such as struvite, bioplastics and cellulose. However, the quality of these recovered products remains to be assessed in terms of their possible contamination with various hazardous compounds that may compromise their application in agriculture or construction. The aim of this article is therefore to assess the quality of products recovered from various recovery techniques implemented at demonstration sites. The results obtained for heavy metals, pesticides, chloroalkanes and PAHs from the analysis of 15 recovered products are reported and compared to the closest regulation framework possible. In general, the results showed that the products met current regulations and only some of them slightly exceeded the limits for very specific pollutants and only for a specific use, such as the food industry. These results are promising to accelerate the market penetration of these recovered products. However, this work highlights the need for a novel regulatory framework for these products that fits with its current uses

Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice

Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and arterial stiffness. We hypothesized that the absence of CT-1 influences arterial fibrosis and stiffness, senescence, and life span. In senescent 29-month- old mice, vascular function was analyzed by echotracking device. Arterial histomorphology, senescence, metabolic, inflammatory, and oxidative stress parameters were measured by immunohistochemistry, reverse transcription polymerase chain reaction, Western blot, and ELISA. Survival rate of wild-type and CT-1–null mice was studied. Vascular smooth muscle cells were treated with CT-1 (10 −9 mol/L) for 15 days to analyze senescence. The wall stress-incremental elastic modulus curve of old CT-1–null mice was shifted rightward as compared with wild-type mice, indicating decreased arterial stiffness. Media thickness and wall fibrosis were lower in CT-1–null mice. CT-1–null mice showed decreased levels of inflammatory, apoptotic, and senescence pathways, whereas telomere-linked proteins, DNA repair proteins, and antioxidant enzyme activities were increased. CT-1–null mice displayed a 5-month increased median longevity compared with wild-type mice. In vascular smooth muscle cells, chronic CT-1 stimulation upregulated apoptotic and senescence markers and downregulated telomere-linked proteins. The absence of CT-1 is associated with decreased arterial fibrosis, stiffness, and senescence and increased longevity in mice likely through downregulating apoptotic, senescence, and inflammatory pathways. CT-1 may be a major regulator of arterial stiffness with a major impact on the aging proces

Endothelial function in small mesenteric arteries.

<p>A: Flow-induced dilatation in small mesenteric arteries from control, aldosterone-salt (Aldo-salt), aldosterone-salt spironolactone (Aldo-salt Spiro) and aldosterone-salt Provinols™ (Aldo-salt Prov) calculated as Δdiameter. Absolute values for baseline diameters were 133±9, 136±7, 142±5 and 153±6 µm, respectively. *<i>P</i><0.05 Aldo-salt <i>vs</i> control. B: NO-dependent dilatation calculated as the difference between the dilatation in basal conditions and the dilatation in the presence of nitro-L-arginine (L-NA, 100 µM). Absolute values for baseline diameters ere 133±4, 135±4, 143±6 and 154±4 µm, respectively. n = 5 for each group. Values are means ± SEM. <i>*P<0.05</i> Aldo-salt <i>vs</i> control vessels.</p

Effects of treatment by spironolactone (Spiro) or Provinols™ (Prov) on blood pressure, carotid diameter and organ weights in aldosterone-salt (Aldo-salt) treated rats.

<p>DAP: diastolic arterial pressure; SAP: systolic arterial pressure; MAP: mean arterial blood pressure; PP: pulse pressure.</p><p>Values are means ± SEM.</p>*<p><i>P</i><0.05 <i>vs</i> Control.</p>#<p><i>P</i><0.05 <i>vs</i> Aldo-salt.</p