Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death.

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from different plant species), but there are no prior reports regarding the mechanism for this bioactivity. Here, we have evaluated the effects of plagiochiline A on cell cycle progression in DU145 prostate cancer cells. A cell cycle analysis indicated that plagiochiline A caused a significant increase in the percentage of cells in the G2/M phase when compared with control cells. When cells were stained and observed by fluorescence microscopy to examine progress through the mitotic phase, we found a significant increase in the proportion of cells with features of late cytokinesis (cells connected by intercellular bridges) in the plagiochiline A-treated samples. These results suggest that plagiochiline A inhibits cell division by preventing completion of cytokinesis, particularly at the final abscission stage. We also determined that plagiochiline A reduces DU145 cell survival in clonogenic assays and that it induces substantial cell death in these cells.

G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.

BACKGROUND: AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. SCOPE OF REVIEW: Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. MAJOR CONCLUSIONS: Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. SIGNIFICANCE: Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways.

[Glaucoma: trends in the study of its etiology]. / Glaucoma: corrientes en estudio sobre su etiología.

BACKGROUND: There are different etiologies related to glaucoma, with the involvement of different systems in the origin and development of the disease. METHODS: We performed a literature review. RESULTS: The data is divided, with an emphasis on five main topics: systemic disease, neurodegenerative disease, genetic disease, immunological disease, and aging of the trabecular meshwork. Older and recent important findings of each subject are reported to establish a relationship with glaucoma, and mention is made of some of the current research lines. CONCLUSION: Glaucoma is a multifactorial disease with complex interaction of events at various levels of the organism. Study of the etiology should guide the search for new therapies.

Tenon Cyst Patch Graft for Ahmed Glaucoma Valve Tube Exposure: Case Series Report.

PURPOSE: To report our experience using a Tenon cyst autograft in the management of tube exposure post Ahmed glaucoma valve (AGV) implantation. METHODS: This is a retrospective case series. RESULTS: Four patients who underwent tube exposure repair using Tenon cyst autograft were identified in our tertiary care center. The duration between initial AGV implantation and tube exposure ranged between 3 and 36 months with a mean of 16 months (±14.35 mo). All patients were followed postoperatively for a range of 4 to 24 months with a mean of 11.75 months (±9.03 o) and all remain exposure free at last follow-up. CONCLUSION: The use of a Tenon cyst autograft for the surgical repair of a tube exposure is valuable, as it involves using autologous scar tissue that is available in eyes that have undergone AGV implantation. The patch autograft is technically easy to harvest, and represents a significantly lower cost when compared with other available options.

The Nucleolin Antagonist N6L Inhibits LINE1 Retrotransposon Activity in Non-Small Cell Lung Carcinoma Cells.

Lung cancer is the most common cause of cancer death in the United States. The genome of non-small cell lung cancer (NSCLC), the most frequent lung cancer type, is strongly affected by Long Interspersed Nuclear Element (LINE1) insertions. Active LINE1s are repetitive DNA sequences that can amplify themselves in the genome utilizing a retrotransposition mechanism whereby LINE1 is copied via reverse transcription and inserted at target sites. ORF1p and ORF2p are LINE1 encoded proteins essential for LINE1 retrotransposition. LINE1s are silenced epigenetically in somatic tissues, and their reactivation has been associated with cancer pathogenesis. Here, we present evidence that nucleolin (NCL) regulates expression of LINE1-ORF1p (L1-ORF1p) in NSCLC cells. Genetic knockdown of NCL significantly inhibited expression of L1-ORF1p in various NSCLC cell lines. Treatment with the investigational NCL antagonist N6L ablated L1-ORF1p expression in all cell lines constitutively expressing L1-ORFp. N6L displayed a stronger antiproliferative activity in NSCLC tumor cell lines expressing the highest L1-ORF1p protein levels. Moreover, N6L treatment of nude mice bearing NSCLC tumor xenografts blocked L1-ORF1p expression and effectively inhibited tumor growth. These data indicate that L1-ORF1p expression is regulated by NCL and identify NCL as a novel promising target for pharmacological inhibition of LINE1.

Erratum: Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex.

[This corrects the article DOI: 10.18632/oncotarget.27589.].

Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex.

The androgen receptor (AR) is a major driver of prostate cancer development and progression. Men who develop advanced prostate cancer often have long-term cancer control when treated with androgen-deprivation therapies (ADT). Still, their disease inevitably becomes resistant to ADT and progresses to castration-resistant prostate cancer (CRPC). ADT involves potent competitive AR antagonists and androgen synthesis inhibitors. Resistance to these types of treatments emerges, primarily through the maintenance of AR signaling by ligand-independent activation mechanisms. There is a need to find better ways to block AR to overcome CRPC. In the findings reported here, we demonstrate that the nuclear scaffold protein, nucleolin (NCL), suppresses the expression of AR. NCL binds to a G-rich region in the AR promoter that forms a G-quadruplex (G4) structure. Binding of NCL to this G4-element is required for NCL to suppress AR expression, specifically in AR-expressing tumor cells. Compounds that stabilize G4 structures require NCL to associate with the G4-element of the AR promoter in order to decrease AR expression. A newly discovered G4 compound that suppresses AR expression demonstrates selective killing of AR-expressing tumor cells, including CRPC lines. Our findings raise the significant possibility that G4-stabilizing drugs can be used to increase NCL transcriptional repressor activity to block AR expression in prostate cancer. Our studies contribute to a clearer understanding of the mechanisms that control AR expression, which could be exploited to overcome CRPC.

Environmental toxicity, oxidative stress and apoptosis: ménage à trois.

Apoptosis is an evolutionary conserved homeostatic process involved in distinct physiological processes including organ and tissue morphogenesis, development and senescence. Its deregulation is also known to participate in the etiology of several human diseases including cancer, neurodegenerative and autoimmune disorders. Environmental stressors (cytotoxic agents, pollutants or toxicants) are well known to induce apoptotic cell death and to contribute to a variety of pathological conditions. Oxidative stress seems to be the central element in the regulation of the apoptotic pathways triggered by environmental stressors. In this work, we review the established mechanisms by which oxidative stress and environmental stressors regulate the apoptotic machinery with the aim to underscore the relevance of apoptosis as a component in environmental toxicity and human disease progression.

Characterizing Oligonucleotide Uptake in Cultured Cells: A Case Study Using AS1411 Aptamer.

Oligonucleotides can be designed or evolved to bind to specific DNA, RNA, protein, or small molecule targets and thereby alter the biological function of the target. The therapeutic potential of oligonucleotides targeted to intracellular molecules will depend largely on their ability to be taken up by the cells of interest, as well as their subsequent subcellular distribution. Here we describe methods to characterize the extent and mechanism of cellular uptake of AS1411, an aptamer oligonucleotide that has progressed to human clinical trials and which is also widely used by researchers as a cancer-targeting ligand.

mTOR/AMPK signaling in the brain: Cell metabolism, proteostasis and survival.

The mechanistic (or mammalian) target of rapamycin (mTOR) and the adenosine monophosphate-activated protein kinase (AMPK) regulate cell survival and metabolism in response to diverse stimuli such as variations in amino acid content, changes in cellular bioenergetics, oxygen levels, neurotrophic factors and xenobiotics. This Opinion paper aims to discuss the current state of knowledge regarding how mTOR and AMPK regulate the metabolism and survival of brain cells and the close interrelationship between both signaling cascades. It is now clear that both mTOR and AMPK pathways regulate cellular homeostasis at multiple levels. Studies so far demonstrate that dysregulation in these two pathways is associated with neuronal injury, degeneration and neurotoxicity, but the mechanisms involved remain unclear. Most of the work so far has been focused on their antagonistic regulation of autophagy, but recent findings highlight that changes in protein synthesis, metabolism and mitochondrial function are likely to play a role in the regulatory effects of both mTOR and AMPK on neuronal health. Understanding the role and relationship between these two master regulators of cell metabolism is crucial for future therapeutic approaches to counteract alterations in cell metabolism and survival in brain injury and disease.

Diurnal Variations of Peripapillary and Macular Vessel Density in Glaucomatous Eyes Using Optical Coherence Tomography Angiography.

PURPOSE: The purpose of this study was to investigate the diurnal variation in peripapillary and macular vessel density (VD) measurements using optical coherence tomographic angiography (OCT-A) and its correlation to intraocular pressure (IOP) changes in glaucoma patients. METHODS: Prospective, observational cross-sectional study including 37 patients (74 eyes; age, 63.8±12.9 y) with open-angle glaucoma. OCT-A imaging and IOP measurements were performed at 08:00, 11:00, 14:00, and 16:00 timepoints on a single day. At each timepoint, 2 scan protocols were used to generate 3-dimensional en face OCT angiograms: 4.5×4.5-mm scan centered on the optic nerve head and 6×6-mm scan centered on the fovea. For each scan mode, the "radial peripapillary capillary" segment, composed of the vasculature of the retinal nerve fiber layer and ganglion cell layer, was calculated. Two trained readers reviewed OCT-A image quality. Only scans with signal strength intensity (SSI) higher than 46 and without image artifacts interfering with measurements were included. Variation in VD measurements assessed using analysis of variance (ANOVA) and the association between VD and IOP changes assessed using linear mixed modeling methods. RESULTS: The optic nerve head and peripapillary VD measurements at 14:00 and 16:00 timepoints were greater than the measurements at 08:00 and 11:00 timepoints. The 14:00 and 16:00 VD measurements were statistically significantly greater (P<0.05) than the 08:00 measurements for the whole en face (50.1% and 50.1% vs. 49.4%), inside disc (50.6% and 50.5% vs. 49.6%), and average peripapillary (58.2% and 58.5% vs. 57.5%) VDs. The macular VD measurements at the 14:00 timepoint were greater than the measurements at 08:00 and 11:00 timepoints. Changes in VD were significantly associated with changes in SSI but not IOP. CONCLUSIONS: Diurnal changes in OCT-A-measured VD in glaucoma patients were small and clinically insignificant. These changes were not associated with IOP changes.

Optic Nerve Head Drusen: Imaging Using Optical Coherence Tomography Angiography.

PURPOSE: To describe findings and utility of optical coherence tomography angiography (OCTA) in optic nerve head drusen (ONHD). OBSERVATIONS: A 57-year-old white man presented with a decrease in contrast sensitivity of the inferior visual field in both eyes. Clinical examination, visual fields, optical coherence tomography, fundus autofluorescence and OCTA revealed ONHD bilaterally. A focal decrease in vessel density within the localization of ONHD in both eyes was demonstrated suggesting a connection between those findings. CONCLUSIONS AND IMPORTANCE: This is the first report in which peripapillary vessel density is analyzed using OCTA technology for this entity. OCTA could confirm the diagnosis and has the potential to assist with the diagnosis and evaluation of progression of ONHD.

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells.

Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-ß1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-ß1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-ß1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFß1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

The aryl hydrocarbon receptor agonist benzo(a)pyrene reactivates LINE-1 in HepG2 cells through canonical TGF-ß1 signaling: implications in hepatocellular carcinogenesis.

Long interspersed nuclear element-1 (L1) is a genetic element that mobilizes throughout the mammalian genome via retrotransposition and damages host DNA via mutational insertions, chromosomal rearrangements, and reprogramming of gene expression. The cellular mechanisms responsible for aberrant L1 expression during cancer pathogenesis are unclear. Previously, we have shown that L1 reactivation in several human cell lines is dependent upon the activation of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor member of the PAS superfamily of proteins. We also showed that ectopic expression of L1 reprograms the HepG2 genome leading to epithelial-to-mesenchymal transition (EMT). Here we present evidence that reactivation of L1 and modulation of EMT in HepG2 cells by the AhR ligand benzo(a)pyrene (BaP) is effected through the canonical TGF-ß1 signaling pathway. BaP increased TGF-ß1 mRNA, SMAD2 phosphorylation and decreased expression of E-Cadherin. The functional relevance of these interactions and the involvement of TGFBR1/ALK5 and SMAD2/3 were confirmed by siRNA interference. Furthermore, expression of L1-encoded ORF1p was positively correlated with the activation of TGF-ß1 signaling in human hepatocarcinoma samples at various stages of malignant progression. These results indicate that ligand-mediated AhR activation regulates L1 via canonical TGF-ß1 signaling and raise important questions about the molecular etiology of human hepatocarcinomas.

AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.

AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2.

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.

Epidemiology of spondyloarthritis in Colombia.

There are no formal statistics about the incidence, prevalence or demographics of patients with spondyloarthropathies (SpAs) in Colombia. However, information from a few studies provides a preliminary snapshot of SpAs in the country. In this article, the authors review what has been published; document what their group is doing and outline what they still need to do in the future. The analysis suggests that although information on SpA in Colombia is limited, it is known that the diagnostic entities of SpA are different than those reported at other latitudes. Thus, it is important to improve and expand the current database of SpA, particularly undifferentiated SpA, not only in Colombia but in all of Latin America.

Autotransplante exitoso de Células Madres Hematopoyéticas en una mujer con Esclerosis Sistémica Severa Refractaria al manejo inmunosupresor / Successful autologous Stem Cell transplantation in a woman with Severe Systemic Sclerosis, refractory to immunosuppressive therapy

Describimos el caso de una paciente femenina de 49 años con esclerosis sistémica difusa con compromiso cutáneo y pulmonar severo, rápidamente progresivo, sin respuesta al manejo inmunosupresor convencional; quien fue sometida a transplante de células madres hematopoyéticas (TCMH) con mejoría sostenida del compromiso cutáneo y pulmonar a los 6 meses post-TCMH.

The following case presents a 49 year-old patient with diffuse SSc and poor evolution given by rapidly progressive of severe skin and lung involvement, who had undergone autologous stem cell transplantation in December 2008. Sustained improvement of skin thickening and of major organ involvement was achieved at six months.

Caracterización de pacientes con compromiso pulmonar intersticial asociado a esclerosis sistémica atendidos en el Hospital Militar Central desde enero de 1998 a mayo de 2008 / No presenta

La esclerosis sistémica es una enfermedad clínicamente heterogénea, caracterizada por sobreproducción y depósito de tejido colágeno en piel, órganos internos y pared de vasos sanguíneos. El pronóstico depende en gran parte del compromiso de órganos internos, particularmente el pulmón, siendo éste el segundo órgano más afectado, sólo superado por el esófago. Las dos principales presentaciones clínicas de compromiso pulmonar son la enfermedad pulmonar intersticial y la hipertensión arterial pulmonar, siendo la principal causa de mortalidad en estos pacientes. El objetivo del presente estudio consiste en describir las características clínicas, epidemiológicas, de función pulmonar e imagenológicas del compromiso pulmonar intersticial en pacientes con esclerosis sistémica. Materiales y métodos: revisión de historias clínicas de 112 pacientes con esclerosis sistémica atendidos en el Hospital Militar Central entre enero de 1998 y mayo de 2008. Signos clínicos de compromiso pulmonar, test de función pulmonar, TACAR y BAL fueron utilizados para detectar enfermedad pulmonar intersticial. Resultados: 41 pacientes con esclerosis sistémica presentaron enfermedad pulmonar intersticial por hallazgos tomográficos y por disminución en la capacidad de difusión de monóxido de carbono. El promedio de edad fue de 46 años al inicio de los síntomas de ES. La relación mujer: hombre fue de 9:1. El compromiso pulmonar intersticial fue más frecuente en pacientes con esclerosis sistémica difusa (70%). El síntoma más común fue la disnea (80%). Los ANAS estuvieron presentes en el 100% de los pacientes. La presencia de anti-SLC-70 se asoció con mayor severidad y mayor probabilidad de daño pulmonar. A diferencia de la difusión de monóxido de carbono la espirometría fue normal en un gran porcentaje, teniendo poca utilidad en el diagnóstico inicial. Conclusión: el compromiso pulmonar intersticial asociado a la esclerosis sistémica no es infrecuente en nuestra población, especialmente en pacientes con esclerosis sistémica difusa, sexo femenino y positividad para anti-SCL-70. El diagnóstico temprano de alveolitis es fundamental para prevenir el deterioro en la función pulmonar y reducir la morbimortalidad asociada al compromiso pulmonar. Las herramientas diagnósticas utilizadas para detectar enfermedad pulmonar intersticial son la DLCO, TACAR y BAL. La DLCO es el parámetro de función pulmonar que mejor refleja la presencia de alveolitis. La positividad para el anticuerpo anti-SLC-70 podría estar asociada a mayor severidad y mayor probabilidad de daño pulmonar. La radiografía de tórax tiene menor utilidad que el TACAR en la evaluación de la presencia y extensión de compromiso pulmonar intersticial en ES. Además del TACAR, el BAL con recuento celular diferencial debe ser realizado para diagnosticar alveolitis.

Systemic sclerosis (SSc) is a clinically heterogeneous, systemic disorder which affects the connective tissue of skin, internal organs and the walls of blood vessels. Prognosis of SSc largely depends on involvement of internal organs, particulary the lungs. The frecuency of lung involvement in SSc ranks second to gastrointestinal manifestation. Two major clinical features of lung involvement are interstitial lung disease (ILD) and pulmonary arterial hipertension. Pulmonary complications are the most common causes of death in SSc. The aims of the study was to describe the clinical characteristics, epidemiological, of pulmonary function test and radiological signs of interstitial lung fibrosis in ours patients with SSc. Methods: we reviewed the records of 112 patients with SSc who were seen between 1998 to 2008 at the Hospital Militar Central, Bogota D.C. Clinical signs of pulmonary involvement, Lung Function Tets, High Resolution CT (HRCT) and Bronchoalveolar lavage (BAL) with differential cell counting were used to detect ILD. Results: 41 subjects had SSc asociate to interstitial lung disease as indicated by radiological signs of lung fibrosis by HRCT and decreased carbon monoxide diffusing capacity (DLCO). Women were affected nine times as often as men (9:1). The mean (SD) age of the 46 years (20-79 years). Interstitial lung fibrosis were noticed often in patients with diffuse cutaneous SSc (70%) but less frecuently in patients with limited cutaneous SSc (30%). The most common symptom was dyspnea (80%). Antinuclear antibodies were present in 100% of patients. Antitopoisomerasa I (Scl-70) were found in 57% of patients and in 95% of those with diffuse cutaneous SSc. Unlike the carbon monoxide diffusing, the spirometry was normal in a great percentage, having usefulness small in the early diagnosis. Conclusion: the interstitial lung disease in patients with SSc, is not infrequent in our population, with discharge prevalencia in patients with diffuse cutaneous SSc with Antitopoisomerase I and feminine sex (9:1) in productive ages of the life. Early diagnosis of alveolitis is essential to prevent the deterioration of pulmonary function, improving outcome in SSc patients. Diagnostic procedures used to detect ILD are DLCO, HRCT and BAL. DLCO is the lung function parameter that best reflects the alveolitis in SSc. Chest radiography is less informative than HRCT of the lungs in the evaluation of the presence and extent of ILD in SSc. Antitopoisomerasa I (Scl-70) are associated with interstitial pulmonary disease. In addition to HRCT, BAL with differential cell counting should be performed for diagnosing SSc alveolitis.