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Describir los pacientes hospitalizados en medicina interna en términos de desnutrición y sarcopenia, en función de la presencia o no de diabetes mellitus tipo 2 (DM2), así como evaluar la mortalidad a corto y largo plazo relacionada con ambas.

Este trabajo tiene como objetivo describir la nutrición y la sarcopenia en pacientes hospitalizados con insuficiencia cardíaca (IC). También pretende evaluar los factores asociados con la mortalidad intrahospitalaria y, a corto plazo, relacionados con la nutrición y la sarcopenia.

There is a strong relationship between the kidney and the heart, where if one of these organs fails, so does the other, in the so-called cardiorenal syndrome (CRS). Besides, there are also interactions with the rest of the body leading to a metabolic state that establishes a feedback loop that is perpetuated. The CRS is characterized by hemodynamic changes, activation of neuro-humoral systems, natriuretic peptides, and changes in mineral metabolism. In this scenario, the kidney and heart, connected by a dysfunctional endothelium, inevitably fail. In obesity, this syndrome is exacerbated due to the complications of adipose tissue dysfunction, in the so-called cardiorenal metabolic syndrome (CRMetS). Obesity promotes adipose tissue dysfunction because it exceeds lipid storage capacity and leads to a lipotoxic state, characterized by inflammation, hypertension, insulin resistance and dyslipidemia, oxidative stress, and hyperuricemia, among others, that affect different organs other than the adipose tissue. In addition, the pro-inflammatory gut microbiota present in obese patients releases uremic toxins, contributing to oxidative stress and inflammation, perpetuating and accelerating the progression of this pathology. In this article, we describe the contribution of obesity, the factors and mechanisms implicated in the development of the CRMetS. Despite the great knowledge about the CRS, more research is needed to characterize the CRMetS given the global obesity epidemic.

•Proposal of new peak-shaving algorithm.•Application of a novel battery power estimation algorithm for the peak-shaving service.•Complete categorization of a microgrid power balance states.•Implementation on a real-time test-bench.

Presentamos un nuevo caso de una infrecuente lesión cutánea caracterizada por un quiste glandular apocrino rodeado por un estroma similar al dermatofibroma hemosiderótico. Revisamos la literatura, en particular con respecto a las características morfológicas, patogénicas y terminológicas de esta curiosa lesión.

En las últimas décadas han surgido diferentes métodos de tratamiento rehabilitador para pacientes con hemiparesia. Uno de ellos es la práctica mental (PM) del movimiento, consistente en la evocación de un movimiento o gesto por parte del sujeto con el fin de aprender o mejorar su ejecución. A pesar de que las técnicas de neuroimagen han demostrado que durante la PM se ejecutan patrones de activación neuronal similares a los que aparecen durante el movimiento, es necesario demostrar su efectividad clínica en la rehabilitación y recuperación funcional de pacientes.

AbstractZenker's diverticulum (ZD), also known as cricopharyngeal, pharyngoesophageal or hypopharyngeal diverticulum, is a rare condition characterized by an acquired outpouching of the mucosal and submucosal layers originating from the pharyngoesophageal junction. This false and pulsion diverticulum occurs dorsally at the pharyngoesophageal wall between the inferior pharyngeal constrictor and the cricopharyngeus muscle. The pathophysiology of ZD involves altered compliance of the cricopharyngeus muscle and raised intrabolus pressure. Decreased compliance of the upper esophageal sphincter and failure to open completely for effective bolus clearance both lead to an increase in the hypopharyngeal pressure gradient. Different open surgical techniques and transoral endoscopic approaches have been described for the management of ZD, although there is no consensus about the best option. We report the case of a 61-year-old patient with a 7-year history of dysphagia and odynophagia for solid food, which after 2 months progressed to dysphagia for liquids and after 4 months to regurgitation 2-6 h after meals. The patient experienced a 12-kg weight loss. Diagnosis was established by esophagogram, which showed a diverticulum through the posterior pharyngeal wall, suggestive of a ZD. Esophagogastroduodenoscopy showed a pouch with erythematous mucosa. Under general anesthesia, diverticulectomy and myotomy were performed. After an uneventful recovery and adequate oral intake, the patient remains free of symptoms at 4 months of follow-up.© 2014 S. Karger AG, Basel

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OBJECTIVE: To analyze the clinical characteristics of patients from a Department of Autoimmune Diseases presenting chronic hepatitis C virus (HCV) infection, systemic autoimmune disease, and B cell lymphoma. METHODS: We analyzed the records of 100 consecutive patients with systemic autoimmune diseases and associated HCV infection seen in our department between 1994 and 2000. We retrospectively investigated the development of B cell malignancies after the diagnosis of HCV related autoimmune disease. RESULTS: Six patients with HCV related systemic autoimmune disease presented B cell non-Hodgkin's lymphoma (NHL). These patients fulfilled the diagnostic criteria for Sjögren's syndrome (n = 4) and polyarteritis nodosa (PAN; n = 2). Four patients were female and 2 male, with a mean age at lymphoma diagnosis of 62 years (range 45–78). The main immunologic markers were hypocomplementemia in all patients and cryoglobulinemia in 5 (83%). Primary extranodal localization of lymphoma was observed in 3 (50%) patients: prostate (n = 1), liver and ovary (n = 1), and ocular annexa (n = 1). Clinically, NHL was classified as indolent lymphoma in 3 patients and aggressive lymphoma in 3. NHL histologic types were diffuse large cell lymphoma (n = 4), extranodal marginal zone B cell lymphoma (n = 1), MALT lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1). CONCLUSION: We describe 6 patients with a triple association of HCV infection, systemic autoimmune disease, and NHL. Characteristics of these patients included a high prevalence of cryoglobulinemia (that clearly contributes to fulfilment of diagnostic criteria for PAN) and an elevated frequency of primary extranodal involvement. We recommend careful evaluation of patients with B cell NHL to detect silent autoimmune or chronic viral diseases. This triple association reinforces the suspected links between autoimmunity, infection, and cancer.

To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr).

We present 5 new cases of coexisting sarcoidosis and Sjögren syndrome (SS) and review the literature for additional cases in order to analyze the clinical, immunologic, and histologic characteristics that may help physicians differentiate the mimicry of SS by sarcoidosis from a true coexistence of both autoimmune diseases. We considered the coexistence of sarcoidosis with SS to be when patients presented specific histologic patterns of both diseases, simultaneously or at different times.

OBJECTIVE: To study the clinical course, response to therapy, and longterm outcome of pure sensory neuropathy (PSN) in a series of patients with primary Sjögren's syndrome (SS) followed prospectively in our referral centers. METHODS: We studied 15 patients (13 women, 2 men) with primary SS and PSN. All patients fulfilled 4 or more of the European diagnostic criteria. RESULTS: At diagnosis of PSN, clinical manifestations included numbness and paresthesias (11 patients), trigeminal neuropathy (6 patients), and Adie's pupil syndrome (4 patients). In 7 patients, PSN was diagnosed prior to SS, in 5 the diagnoses were made simultaneously, and in the remaining 3 patients PSN was diagnosed after the appearance of SS symptomatology. The mean duration of the prospective PSN followup was 10 years (range 1–20). The progression of PSN was acute in 1 patient (producing severe dysfunction in less than 1 month), subacute in 3 patients, and in the remaining 11, the symptoms progressed slowly over the ensuing years to other extremities. Patients were treated with corticosteroids (n = 13), cyclophosphamide (n = 4), and intravenous immunoglobulins (n = 1), and 2 patients received no treatment. In spite of treatment, most patients showed an indolent and insidious longterm PSN course. CONCLUSION: We found 3 differentiated clinical courses of the PSN in patients with primary SS: subacute progression in less than 1 month (7%), late acceleration of PSN 2–4 years after an initial indolent onset (20%), and a very longterm insidious, chronic evolution (73%). Prospective analysis of the longterm course of PSN shows a chronic and insidious evolution in most patients with PSN and SS, with a poor response to treatment, although stabilization of symptomatology for long periods is often observed.

Introduction:Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective:To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-α, TNF-α), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods:p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-α were studied by enzyme-linked immunonosorbent assay. Results:SLE patients had higher levels of p53 protein (0.16 ± 0.33 ng/dl) than controls (0.014 ± 0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31 ± 0.48 ng/dl) than those with inactive disease (0.08 ± 0.17 ng/dl; p = 0.003) who in turn had higher levels than controls (0.01 ± 0.02 ng/dl; p = 0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10 levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-α levels. Conclusions:The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.

AbstractIntroduction: Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective: To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-α, TNF-α), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods: p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-α were studied by enzyme-linked immunonosorbent assay. Results: SLE patients had higher levels of p53 protein (0.16 ± 0.33 ng/dl) than controls (0.014 ± 0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31 ± 0.48 ng/dl) than those with inactive disease (0.08 ± 0.17 ng/dl; p = 0.003) who in turn had higher levels than controls (0.01 ± 0.02 ng/dl; p = 0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10 levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-α levels. Conclusions: The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.Copyright © 2003 S. Karger AG, Basel

To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon α therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 × 109/L, and severe thrombocytopenia as a platelet count <30 × 109/L.

OBJECTIVE: To determine the prevalence of Raynaud's phenomenon (RP) in a large series of patients with primary Sjögren's syndrome (SS) and to identify the clinical and immunological features related to its presence. METHODS: In a cross sectional study, we investigated 320 consecutive patients with primary SS (294 women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Diagnosis of RP in patients with SS was defined as intermittent attacks of digital pallor and/or cyanosis in the absence of any other associated disease or anatomical abnormalities. RESULTS: RP was present in 40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering factor was exposure to cold, which induced RP in all patients, while emotional stress was a factor in 12 patients, as was job related predisposition in 2. Fifteen (38%) patients required pharmacological treatment with calcium channel blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients) during colder months, and one patient required treatment with intravenous prostacyclin for ischemic complications. Compared with SS patients without RP, those with RP showed a higher prevalence of articular involvement (50 vs 31%; p = 0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95 vs 65%; p < 0.001), anti-Ro/SSA (59 vs 31%; p < 0.001) and anti-La/SSB antibodies (44 vs 20%, p = 0.003). CONCLUSION: We found RP in 13% of patients with primary SS, in almost half of whom RP was the first autoimmune symptomatology. These patients constituted a subset of SS with a higher frequency of some extraglandular features and positive immunological markers. The clinical course of RP seems to be milder in patients with primary SS than in those with other systemic autoimmune diseases such as systemic sclerosis, with no vascular complications and pharmacological treatment needed in only 40% of patients.

Objective. To determine the existence of circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome (SS), and to analyse the correlation with clinical and immunological features of SS.
Methods. Ninety consecutive patients with primary SS were studied. All patients fulfilled four or more of the European diagnostic criteria for SS. sCD5 and sCD6 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA) developed in our laboratory.
Results. Detectable levels of sCD5 were found in 39 (43%) SS patients. The mean±standard error values of sCD5 were 3.5±0.5 ng/ml for patients with SS and 1.9±0.1 ng/ml for healthy blood donors (P&lt;0.001). We found higher levels of sCD5 in patients with hypocomplementaemia (6.5 vs 3.5 ng/ml, P=0.03) and cryoglobulinaemia (6.9 vs 2.6 ng/ml, P=0.001). On the other hand, detectable levels of sCD6 were found in 60 (67%) SS patients. The mean±standard error values of sCD6 were 25.5±7.8 ng/ml in SS patients and 5.27±1.40 ng/ml in healthy blood donors (P=0.01). When the sCD6 levels were compared according to the presence or absence of immunological features, patients with cryoglobulinaemia showed higher levels of circulating sCD6 (77.3 vs 17 ng/ml, P=0.01) than those without cryoglobulinaemia.
Conclusion. Patients with primary SS showed higher levels of circulating sCD5 and sCD6 when compared with controls. Moreover, the existence of some immunological features (hypocomplementaemia and cryoglobulinaemia) was associated with high levels of both soluble scavenger receptors. These facts may reflect an enhanced lymphocytic activation in patients with primary SS.

We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age‐ and sex‐matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11–67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow‐up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p[lt ]0.001), hypertension (44% vs. 9%, p[lt ]0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end‐stage renal failure. Hyperlipidaemia (78% vs. 27%, p[lt ]0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.

To determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in patients with systemic lupus erythematosus (SLE). We investigated 134 consecutive SLE patients (121 women and 13 men; mean age 35 years) who fulfilled the 1982 revised criteria for SLE of the American College of Rheumatology. Two hundred consecutive volunteer blood donors were also studied. Serum from all patients and controls was tested for antibodies to HCV (by third generation enzyme-linked immunosorbent assay and confirmed by third generation recombinant immunoblot assay [RIBA-3]). Antibodies to HCV were present in 18 patients with SLE (13%) and in 2 (1%) of the blood donors studied. Among the anti-HCV–positive group, HCV infection was confirmed (by RIBA-3 and polymerase chain reaction) in 15 SLE patients (11%) and in the 2 blood donors (1%) (P &lt; 0.001). We observed a lower frequency of cutaneous SLE features (40% versus 76%; P = 0.01) and positivity for anti–double-stranded DNA (anti-dsDNA) (33% versus 81%; P &lt; 0.001), and a higher frequency of hepatic involvement (93% versus 2%; P &lt; 0.001), low C4 levels (73% versus 39%; P = 0.002), low CH50 levels (73% versus 44%; P = 0.03), and cryoglobulins (60% versus 22%; P = 0.02) in SLE patients with HCV infection compared with SLE patients without infection. The prevalence of HCV infection in SLE patients was higher than in blood donors from the same geographic area. SLE HCV-positive patients showed a lower frequency of cutaneous SLE features and anti-dsDNA antibodies, and a higher prevalence of liver involvement, hypocomplementemia, and cryoglobulinemia. HCV testing should be considered in the diagnosis of SLE, especially in patients who lack the typical cutaneous features of SLE or who have low titers of autoantibodies, cryoglobulinemia, or liver involvement.

Abstract:: Sjögren’s Syndrome (SS) is an autoimmune disease that mainly affects exocrine glands and usually presents as a persistent dryness of the mouth and eyes. The spectrum of the disease extends from an organ-specific autoimmune disease to a systemic process. Viral infection has long been suspected as a potential cause of SS because several viruses have been incriminated in the aetiology of this disease, and a possible relationship between SS and hepatitits C virus (HCV) was postulated in 1992. In this paper, we review the literature concerning SS and HCV infection and summarise the current knowledge regarding their association and their pathogenic, clinical and immunological significances. The main conclusions of this review are that the prevalence of antibodies to HCV in patients with primary SS ranges between 14 and 19% using third-generation ELISA, chronic HCV infection may mimic the main clinical, histological and immunologic features of ‘primary’ SS and, finally, testing for HCV infection must be performed in patients with SS, especially in those patients with evidence of liver involvement or associated cryoglobulinaemia. HCV seems to be a rare cause of ‘primary’ SS in the absence of recognised liver disease or cryoglobulinaemia.

Resumen: Este trabajo contiene la definición, justificación intuitiva, caracterización y principales propiedades y casos particulares de las denominadas functiones de evaluación modales. Se considera un problema de decisión con espacio paramétrico finito y conjunto de acciones igual al conjunto de posibles distribuciones de probabilidad sobre él; se trata de estudiar las funciones de utilidad que, en este caso y mediante el criterio Bayes, conducen a tomar como acción óptima la distribución degenerada en la moda. Los resultados fundamentales son la caracterización mediante la función de incertidumbre correspondiente al máximo y la obtención de las diversas clases modales.

This paper is devoted to the Fisher’s quantity of information study, it is focused in the same way than that ysed in the Shannon’s information and planned under the conditions of regularity that Fourgeaud (5) considered. From this baseline, the corresponding criterion for comparing experiments is defined and studied.

Resumen: La información cuadrática es una buena alternativa a la información de Shannon para todos aquellos problemas que, por su naturaleza, interesa tratarlos con una utilidad no local. El objetivo de este trabajo es dar, para estas situaciones, un método secuencial de construción de diseños para discriminación entre modelos, basado en la maximización de la información cuadrática. Después de una introducción, donde se resumen los conceptos y resultados principales sobre información cuadrática, se plantea el problema, reduciéndolo a un caso particular de comparación de experimentos, con un espacio paramétrico de tipo mixto, y donde la cantidad de interés es alternativamente un subconjunto de sus componentes o todo él. Se dan los diseños óptimos en ambos casos, su relación y posibles alternativas y aplicaciones.

En este trabajo se estudia el criterio de comparación de experimentos basado en una medida de información generalizada definida por De Groot (1962). Se define el criterio, se estudian sus propiedades y se obtienen diversas relaciones con los criterios de suficiencia. Al estar el estudio restringido a espacios paramétricos finitos, los resultados de mayor interés corresponden a las diversas relaciones obtenidas con el criterio de Blackwell. Debido al gran número de casos particulares que la medida de información generaliza incluye, los corolarios e implicaciones de las diversas propiedades y teoremas son de gran riqueza y variedad.

Se estudia el problema de la asignación de tratamiento desde el punto de vista de la decisión predictiva. Se supone definida la utilidad de obtener unas características finalesyal aplicar un tratamientoaa un individuo de características inicialesx. El problema se reduce a hallar la utilidad deadadox; se hace mediante distribuciones prognósticas y diagnósticas.

The aim of the current study was to analyze the frequency and characteristics ofsymptomatic myopathies occurring in rheumatoid arthritis (RA) patients, to correlate these findings with clinical data, and to evaluate their therapeutic implications. All RA patients from a cohort of 350 RA patients from a single institution who developed muscular symptomatology during an 8-year period were included in the study (n = 21). Clinical and laboratory data and electromyographic results were recorded in all cases, and an open muscle biopsy was performed. Weakness and muscle atrophy were the most common symptoms. Serum creatine kinase was increased in 8 cases (38%). Histopathologic study showed type 2 atrophy in 12 cases. In 13 cases, a treatable disease was diagnosed: dermatomyositis (n = 2), d-penicillamine-related dermatomyositis (n = 2), polymyositis (n = 1), muscular mononuclear cell infiltration (n = 3), polyarteritis nodosa (n = 1), glucocorticoid myopathy (n = 3), and toxic chloroquine myopathy (n = 1). In all but 1 patient, muscular clinical response to new therapy and/or drug withdrawal was satisfactory. Although symptomatic muscular involvement in RA is low (6% in the current series), we have found that nearly two thirds of cases were caused by potentially treatable conditions, mainly myositis or toxic myopathies.

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/−) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/− mice exhibited incipient renal fibrosis with epithelial–mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/− mice. Kidneys of Tgfb3+/− mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1. This article has an associated First Person interview with the first author of the paper.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6–12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies.

&lt;it>Objective&lt;/it>. To analyse the role of polymorphisms of the interleukin&hyphen;10 promoter region in the epidemiologic, clinical and immunologic characteristics of patients with primary Sjögren's syndrome &lpar;SS&rpar;. &lt;it>Methods&lt;/it>. Sixty&hyphen;three consecutive patients &lpar;59 women and four men; mean age 57 yr; range 20–83 yr&rpar; were studied in our Unit. All patients fulfilled four or more of the modified diagnostic criteria for SS proposed by the European Community Study Group in 1996. As controls, 150 healthy volunteers were recruited from the medical and laboratory staff working in our hospital. All the samples from patients and controls were analysed by PCR amplification and direct sequencing. &lt;it>Results&lt;/it>. The frequency of the interleukin&hyphen;10 &lpar;IL&hyphen;10&rpar; GCC haplotype was higher &lpar;0.48 &lt;it>vs&lt;/it> 0.34, &lt;it>P&lt;/it>&equals;0.006&rpar; and the frequency of the IL&hyphen;10 ACC haplotype lower &lpar;0.25 &lt;it>vs&lt;/it> 0.39, &lt;it>P&lt;/it>&equals;0.005&rpar; in patients with primary SS compared with healthy controls. In the genotype analysis, the frequency of the GCC&sol;ATA genotype was higher &lpar;29 &lt;it>vs&lt;/it> 11&percnt;, &lt;it>P&lt;/it>&equals;0.001&rpar; and that of the ACC&sol;ACC genotype lower &lpar;3 &lt;it>vs&lt;/it> 12&percnt;, &lt;it>P&lt;/it>&equals;0.044&rpar; in patients with primary SS compared with healthy controls. GCC&hyphen;carriers showed an earlier onset of the disease &lpar;48.06±14.98 yr &lt;it>vs&lt;/it> 57.53±14.20 yr, &lt;it>P&lt;/it>&equals;0.034&rpar;. The existence of systemic involvement &lpar;defined by cutaneous vasculitis, peripheral neuropathy, renal and&sol;or pulmonary involvement&rpar; was more frequent in carriers of the GCC haplotype, although the difference did not reach statistical significance &lpar;40 &lt;it>vs&lt;/it> 27&percnt;, &lt;it>P&lt;/it>&equals;0.278&rpar;. No significant differences in the haematologic &lpar;hypergammaglobulinaemia, elevated ESR&rpar; and immunologic &lpar;ANA, RF, anti&hyphen;Ro&sol;SS&hyphen;A and anti&hyphen;La&sol;SS&hyphen;B antibodies&rpar; parameters were observed in carriers of the GCC haplotype. &lt;it>Conclusion&lt;/it>. We describe an abnormal distribution of IL&hyphen;10 promoter haplotypes in patients with primary SS compared with healthy controls. This consists of a predominance of the GCC haplotype, mainly related to a higher frequency of the heterozygote haplotype GCC&sol;ATA. The presence of the GCC haplotype does not originate a different immunologic pattern but leads to an earlier onset of primary SS.

&lt;it>Objectives&lt;/it>. To examine salivary function in patients with primary Sjögren's syndrome &lpar;SS&rpar; by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5&percnt; solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. &lt;it>Methods&lt;/it>. We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated &lpar;basal&rpar; salivary flow &lpar;BSF&rpar; in all patients. In patients with BSF ≤1.5 ml, stimulated salivary flows &lpar;SSF&rpar; were also measured after stimulation with an ophthalmic 5&percnt; pilocarpine solution &lpar;0.1 ml&equals;5 mg, administered sublingually&rpar;. SSF was also measured after oral administration of 50 mg anetholetrithione &lpar;ANTT&rpar; in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. &lt;it>Results&lt;/it>. Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr &lpar;range 18–82 yr&rpar;. The mean BSF for SS patients was 1.40±0.17 ml. Fifty &lpar;83&percnt;&rpar; patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group &lpar;&lt;it>P&lt;/it>&lt;0.001&rpar;; after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group &lpar;&lt;it>P&lt;/it>&equals;0.02&rpar; and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group &lpar;&lt;it>P&lt;/it>&equals;0.046&rpar;. No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently &lpar;42 &lt;it>vs&lt;/it> 0&percnt;, &lt;it>P&lt;/it>&equals;0.01&rpar;. SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS &lpar;73.3 &lt;it>vs&lt;/it> 31.3 months, &lt;it>P&lt;/it>&equals;0.03&rpar; and a higher prevalence of positive anti&hyphen;Ro&sol;SS&hyphen;A &lpar;70 &lt;it>vs&lt;/it> 36&percnt;, &lt;it>P&lt;/it>&equals;0.038&rpar;, anti&hyphen;La&sol;SS&hyphen;B &lpar;65 &lt;it>vs&lt;/it> 32&percnt;, &lt;it>P&lt;/it>&equals;0.038&rpar;, parotid scintigraphy class III–IV &lpar;79 &lt;it>vs&lt;/it> 9&percnt;, &lt;it>P&lt;/it>&lt;0.001&rpar; and positive salivary gland biopsy &lpar;90 &lt;it>vs&lt;/it> 43&percnt;, &lt;it>P&lt;/it>&lt;0.001&rpar;. &lt;it>Conclusion&lt;/it>. The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5&percnt; pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty&hyphen;two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These ‘responder’ patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the ‘non&hyphen;responder’ patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands.