Identification of regulatory T cell molecules associated with severity of multiple sclerosis.

BACKGROUND: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-ß is a key regulator of Treg development and function. OBJECTIVE: The objective of this study is to determine whether the expression of functionally relevant TGF-ß-regulated molecules is altered in Tregs from patients with MS. METHODS: Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4+ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought. RESULTS: Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-ß signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity. CONCLUSION: We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.

Efficient generation of 1.9 W yellow light by cascaded frequency doubling of a distributed Bragg reflector tapered diode.

Watt-level yellow emitting lasers are interesting for medical applications, due to their high hemoglobin absorption, and for efficient detection of certain fluorophores. In this paper, we demonstrate a compact and robust diode-based laser system in the yellow spectral range. The system generates 1.9 W of single-frequency light at 562.4 nm by cascaded single-pass frequency doubling of the 1124.8 nm emission from a distributed Bragg reflector (DBR) tapered laser diode. The absence of a free-space cavity makes the system stable over a base-plate temperature range of 30 K. At the same time, the use of a laser diode enables the modulation of the pump wavelength by controlling the drive current. This is utilized to achieve a power modulation depth above 90% for the second harmonic light, with a rise time below 40 µs.

TIMP4 Modulates ER-α Signalling in MCF7 Breast Cancer Cells.

Tissue inhibitor of metalloprotease 4 (TIMP4) contributes to poor prognosis in breast and other tumours. However, the mechanisms of how TIMP4 influences breast cancer cell behaviour are unknown. Our aim was to explore the signalling pathways modulated by TIMP4 in breast cancer cells. Human recombinant TIMP4 was added to MCF7 breast cancer cells and RNASeq was performed. TIMP4 RNASeq results were validated by RT-PCR. Network analyses of TIMP4-exposed cells showed that ER-α, HIF1A and TGF-ß signalling were activated, whereas FOXO3 signalling was downregulated. ER-α protein levels were increased and concordantly, promoters of TIMP4-upregulated genes were significantly enriched in oestrogen-binding sites. We concluded that TIMP4 modulates multiple signalling pathways relevant in cancer in MCF7 cells, including the ER-α cascade.

Hernia de Amyand, reporte de un caso / Amyand's hernia, a case report

Introducción: La hernia de Amyand es la presencia del apéndice cecal en el interior de una hernia inguinal, observándose en el 0,5-1% del total de hernioplastías en los adultos. Presentación del caso: Mujer de 81 años ingresó al servicio de urgencias por dolor en fosa iliaca derecha de una semana de evolución, de intensidad progresiva, asociado a aumento de volumen inguinal derecho, redondo de 10 centímetros de diámetro, sensible a la palpación, no reductible y sin signos de irritación peritoneal. Se decidió realizar intervención quirúrgica por sospecha de hernia inguinal derecha complicada, evidenciándose contenido purulento entre asas intestinales, el cual se drenó, descubriéndose el apéndice cecal en el interior del saco herniario, de aspecto necrótico y perforado, procediéndose a realizar apendicectomía más hernioplastia. La paciente evoluciona en el postoperatorio con cuadro bronquial obstructivo, el cual se trató con antibioticoterapia, respondiendo favorablemente, otorgándose el alta 13 días después de la cirugía. Discusión: El 6,7% de las causas de abdomen agudo en adultos mayores se deben a cuadros apendiculares, mientras que un 13,3% se deben a hernias complicadas. Sin embargo es extremadamente infrecuente encontrar el apéndice cecal inflamado intraherniano, lo que ocurre aproximadamente en el 0,1% de todas las apendicectomías. El cuadro clínico consiste en síntomas inespecíficos con confirmación usualmente intraoperatoria. Se ha descrito el diagnóstico pre-quirúrgico imagenologico con tomografía computarizada (TC). El tratamiento consiste en dos procedimientos: apendicectomía con aseo de la cavidad y la reparación del defecto herniario.

Introduction: Amyand's hernia is the presence of cecal appendix within an inguinal hernia, observed in 0.5-1% of total hernioplasties in adults. Case Report: 81 year old woman admitted to the emergency room for pain in the right iliac fossa, one week of evolution, progressive in intensity associated with an increase in right round inguinal volume, 10 centimeters (cm) in diameter, sensitive to palpation, non reducible without signs Peritoneal irritation. It was decided to undergo surgery for suspicion of complicated right inguinal hernia, showing purulent contents between the intestinal loops, which managed to drain, discovering the cecal appendix in the sack of necrotic and perforated inguinal hernia, proceeding to the subsequent appendectomy of hernioplasty. Postoperatively, the patient developed bronchial obstruction, which was treated with antibiotics, responding favorably, granting discharge 13 days after surgery. Discussion: 6.7% of the causes of acute abdominal pain in older adults are due to appendiceal pictures, while 13.3% are due to complicated hernias. However it is extremely rare to find the intraherniano inflamed cecal appendix, which occurs in approximately 0.1% of all appendectomies. The clinical picture is nonspecific symptoms usually intraoperative confirmation. It described the pre-surgical diagnosis imaging with computed tomography (CT). Treatment consists of two procedures: appendectomy with toilet cavity and repair of the hernia defect

NF-κB signaling in cancer stem cells: a promising therapeutic target?

BACKGROUND: Cancer stem cells (CSCs) are regulated by several signaling pathways that ultimately control their maintenance and expansion. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) forms a protein complex that controls DNA transcription and, as such, plays an important role in proliferation, inflammation, angiogenesis, invasion and metastasis. The NF-κB signaling pathway, which has been found to be constitutively activated in CSCs from a variety of cancers, participates in the maintenance, expansion, proliferation and survival of CSCs. Targeted disruption of this pathway may profoundly impair the adverse phenotype of CSCs and may provide a therapeutic opportunity to remove the CSC fraction. In particular, it may be attractive to use specific NF-κB inhibitors in chronic therapeutic schemes to reduce disease progression. Exceptional low toxicity profiles of these inhibitors are a prerequisite for use in combined treatment regimens and to avoid resistance. CONCLUSION: Although still preliminary, recent evidence shows that such targeted strategies may be useful in adjuvant chemo-preventive settings.

Effect of adenosine on injury caused by ischemia and reperfusion in rats: functional and morphologic study.

To study whether treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ADO (15 mg/kg or saline solution (SS) intravenously before 60 minutes occlusion of the superior mesenteric artery (I) and/or 120 minutes after its release (R). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCI with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were reduced in I+SS and IR+SS but similar after treatment with ADO (I+ADO and IR+ADO groups). We concluded that rat jejunal enteric nerves were damaged in I+SS and IR+SS but not in the I+ADO and IR+ADO groups. These results suggested that ADO attenuated intestinal dysfunction due to I and R.

Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis.

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis. In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-ß1 and α-1-type I collagen was analysed. Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-ß1 (mean ± sd 1.8 × 10(3) ± 0.2 × 10(3) versus 1.2 × 10(3)± 0.3 × 10(3) mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93 × 10(2)± 0.66 × 10(2) versus 3.28 × 10(2) ± 0.5 × 10(2); p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-ß1 activation (163 ± 34 versus 110 ± 15 pg active TGF-ß1 per mg total protein). These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.

Gene regulation by BCL3 in a cervical cancer cell line.

BCL3 is a putative proto-oncogene deregulated in haematopoieitic and solid tumours. It has been suggested that its oncogenic effects could be mediated, at least in part, by inducing proliferation and inhibiting cell death. To provide more insight into the mediators of these effects, we used an unbiased approach to analyse the mRNA expression changes after knocking-down BCL3 using specific shRNAs. One hundred eighty genes were up-regulated and sixtynine genes were down-regulated after knocking down BCL3. Function analyses showed enrichment in genes associated with cellular growth and proliferation, cell death and gene expression. We found that STAT3, an important oncogene in human cancer, was the central node of one of the most significant networks. We validated STAT3 as a bona fide target of BCL3 by additional interference RNA and in silico analyses of previously reported lymphoma patients.

Transanal rectocele repair using linear stapler and bioabsorbable staple line reinforcement material: short-term results of a prospective study.

PURPOSE: This study was designed to determine the short-term results of transanal rectocele repair with use of a linear stapler and Bioabsorbable Seamguard. METHODS: Ten women (median age, 56.1 y) with obstructed defecation syndrome were enrolled in the study. The preoperative study consisted of a medical history, physical examination, anoscopy, endoanal ultrasound, and defecography. All patients completed a severity score and a visual analog scale for global quality of life, and provided the postoperative dates of complications. RESULTS: Overall, the treatment significantly improved the obstructed defecation: the severity score improved from a median of 19.8 +/- 4.2 at baseline to 6.10 +/- 8.2 at one month (P < .005), 5.9 +/- 8.3 at 6 months (P < .005), and 6 +/- 8.3 at one year after the operation (P < .005). A significant improvement was observed in the visual analog scale, which improved from a median of 1.8 +/- 1.4 at baseline to 6 +/- 1.6 at one month (P < .005), 6.6 +/- 2.1 at 6 months (P < .004), and 7 +/- 2.5 at one year (P < .004). A significant improvement was also observed in various symptoms. Only 2 patients manifested urgent defecation. CONCLUSIONS: The present study demonstrates that rectocele repair using a linear stapler and Seamguard is a safe, easy procedure, with a very low rate of complications and good immediate outcome.

Chronic inflammatory demyelinating polyradiculoneuropathy in a boy with systemic lupus erythematosus.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy. Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease that can affect the central nervous system in about 40% of patients, with prevalence and incidence unknown in the pediatric population due to lack of multicenter studies. We report the case of a 13-year-old Mexican boy, diagnosed with CIDP at the onset of SLE, beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. The patient had positive ANA, antiDNAdc, antiBeta2glycoprotein, anti-cardiolipin, ANCA-C and X. He received intravenous immunoglobulin, cyclophosphamide, steroids, and azathioprine and showed clinical improvement. It is important to take into account the presence of peripheral neurological disorders in patients with pediatric SLE, considering CIDP as an uncommon presentation, making the diagnosis important for better treatment and evolution.

Hemicorea-hemibalismo asociado a hiperglucemia no cetósica con hiperintensidad estriatal / Hemichorea-hemiballism associated to non-ketonic hyperglycemia with striatal hyperintensity

No disponible

No disponible

Evaluation by three-dimensional anal endosonography of injectable silicone biomaterial (PTQ) implants to treat fecal incontinence: long-term localization and relation with the deterioration of the continence.

BACKGROUND: The purposes of the study were the long-term evaluation of silicone implants with three-dimensional (3D) anal endosonography and its correlation with anal incontinence. METHODS: Fifteen patients were injected with silicone because of anal incontinence and co-existing internal anal sphincter disruption (n = 8) or thinning (n = 7). The evaluation was performed with the Wexner score and 3D anal endosonographies. RESULTS: Forty-four implants were performed. The endosonography at 3 months detected that all the implants were properly located. At 24 months, it detected 37/44 implants of initially injected and 33/37 were properly located. Four of 37 implants had moved and 7/44 were neither in the anus nor in the rectum. A total of 8/15 patients had their implants correctly placed. Globally, silicone implants significantly improved fecal continence. CONCLUSIONS: The silicone implants might have moved or even be lost. The continence deterioration suffered by most patients after the first year of the injection has no relation with the localization and number of implants that the patients have.

NF-kappa B is required for the development of tumor spheroids.

Tumor cells cultured in three-dimensional models provide a more realistic and biologically meaningful analysis of the initial phases of cancer development and drug resistance. Several studies have demonstrated that culture of cancer cells in three dimensions induces cellular resistance to a variety of anti-neoplastic drugs by poorly understood mechanisms. The role of the transcription factor NF-kappaB and inhibitors of apoptosis proteins (IAPs) in the onset and development of drug resistance during tumor spheroid growth has not been established. In this work, we found a significant increase in the activity and expression of NF-kappaB and its downstream target XIAP (X-linked IAP) in cancer cells grown as multi-cellular tumor spheroids. Blocking XIAP expression with RNA interference markedly increased the sensitivity of cancer tumor spheroid cells toward anti-neoplastic drugs, indicating a role for IAPs in establishing drug resistance. In turn, inhibition of NF-kappaB by negative dominants suppressed spheroid formation, whereas overexpression of the upstream kinase IkappaBKbeta increased their growth and resistance. The present data suggested that NF-kappaB and its downstream target XIAP were essential for the growth and drug resistance of small avascular tumor.

Participation of Omi Htra2 serine-protease activity in the apoptosis induced by cisplatin on SW480 colon cancer cells.

Apoptosis is triggered by two interconnected pathways, extrinsic and intrinsic. The intrinsic pathway is activated by genomic stress promoting mitochondrial release of apoptotic proteins. One of these proteins is Omi/Htra2, a serine protease which inactivates Inhibitor of Apoptosis Proteins (IAPs). In the present work, we assessed the participation of Omi/Htra2 in the cell death induced by the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP) in SW480 colon cancer cells. CDDP and 5-FU induced apoptosis mediated by the intrinsic pathway in colon cancer cells, as demonstrated by morphological analyses, mitochondrial cytochrome c release and cleavage of caspase 3. Omi/Htra2 was also released from mitochondria of cells exposed to these drugs, as demonstrated by immunofluorescence and western blot assays of subcellular fractions. Exposure of cells to the Omi/Htra2 serine protease inhibitor UCF-101 prevented death p<0.0001 and partially suppressed reproductive cell death of cells exposed to cisplatin p<0.05, but not to 5-FU p=0.49. From these experiments we show that Omi/Htra2 serine protease activity participates in the cell death induced by CDDP but not of 5-FU in colon cancer cells.

Evaluation of the use of PTQ implants for the treatment of incontinent patients due to internal anal sphincter dysfunction.

OBJECTIVE: This study reports the results of injectable silicone PTQ implants for faecal incontinence due to internal anal sphincter (IAS) dysfunction. METHOD: Twenty patients (12 women) with partial faecal incontinence aged from 55 to 65 years were treated by a PTQ implant. All patients completed the Cleveland Clinic Continence and Quality of Life questionnaire. Endoluminal ultrasound and anorectal physiological testing were performed in each patient. All implants were inserted into the submucosal plane without ultrasound guidance. RESULTS: Faecal continence was significantly improved up to 1 year. The Wexner continence score fell from a median of 13.05 (range, 5-20) before treatment to 4.5 (range 2-7.7) at 1 month after (P < 0.005). This rose gradually to 6.2 (range, 0-16) at one year (P = 0.02) and 9.4 (range, 1-20) at 2 years (P = 0.127). There were no differences in resting or squeeze pressure before and at 3 months after treatment (P = 0.86 and P = 0.93). Fourteen (70%) patients experienced pruritus ani during the first few weeks after the procedure and one developed infection at the implant site. CONCLUSION: Silicone implantation is minimally invasive and technically simple. It is effective over 1 year in the treatment of faecal incontinence due to IAS dysfunction.

Heavy metal content in soils under different wastewater irrigation patterns in Chihuahua, Mexico.

An area near the city of Chihuahua has been traditionally irrigated with wastewater to grow forage crops. It has been hypothesized that metal levels could be found in these soils high enough to cause potential health problems to the population. The objective of this study was to determine heavy metal concentrations in different soils due to irrigation practices. Four soil types were evaluated; a soil with a past and present history of wastewater irrigation (S1), a soil with a history of wastewater irrigation until 2003 (S2), a soil with no irrigation history (S3), and a soil similar to S1 and adjacent to the river where the wastewater is transported (S11). Three soil depths were evaluated; 0-15, 15-30 and 30-50 cm. Consequently, a total of 150 soil samples were analyzed evaluating pH, EC, OM and the following elements; Na, K, Cd, Pb, Ni, Cr, Cu and Fe. The pH (P=0.000) and EC (P=0.000) were different for each soil type but no differences were noted for soil depth and the interaction. Maximum pH levels were noted in S3 with a value of 8.74 while maximum EC was observed in S1 with a value of 0.850 dSm-1. The OM level was different for soil type (P=0.000), soil depth (P=0.005) and the interaction (P=0.014). S1 and S11 obtained maximum levels of OM while minimum levels were noted in S3. Maximum OM levels were observed at the 0-15 cm depth followed by the 15-30 cm depth and finally at the 30-50 cm depth. The highest concentration of metals was as follows: K in S1 (359.3 mg kg-1); Cd in S1 (4.48 mg kg-1); Pb in S11 (155.83 mg kg-1); Ni in S1 (10.74 mg kg-1); Cu in S1 (51.36 mg kg-1); B in S3 (41.5 mg kg-1); Fe in S3 (20,313.0 mg kg-1), Cr in S3 (44.26 mg kg-1) and Na in S3 (203.0 mg kg-1). The conclusion is that some metals are present in the soils due to anthropogenic activities but others are present in natural forms.

Regulation of mitochondrial Smac/DIABLO-selective release by survivin.

The intrinsic apoptotic pathway is characterized by the release of several mitochondrial intermembrane proteins into the cytosol of dying cells. It is unclear whether the release of these proteins follows a common or specific pathway. In the present report we show that survivin and, to a lesser extent, the survivin splice variant survivin DeltaEx3 regulate the specific liberation of second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (Smac/DIABLO), an inhibitor of apoptosis proteins binding protein, during apoptosis induced by etoposide, a DNA damaging agent. This antineoplastic drug induced posttranscriptional upregulation of survivin and survivin DeltaEx3. In turn, mitochondrial survivin associated with Smac/DIABLO, delaying its release. In addition, cytosolic survivin also stabilized the cytosolic levels of released Smac/DIABLO. These results provide an explanation for the observed differences in the release of mitochondrial intermembrane proteins in various apoptotic models and present a new mechanism for the anti-apoptotic effects of survivin in cancer cells.

Tumor HGF lacks prognostic significance in Mexican breast cancer patients.

Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic protein implicated in tumor formation and metastasis. Since increased levels of HGF-SF were first identified in breast cancer tissue or patient serum, some evidence has suggested that tumor or serum HGF-SF concentration could be one of the most accurate prognostic factors for this disease. However, other recent investigations have not been able to corroborate this finding. The study aims to establish the prognostic significance of HGF-SF in Mexican breast cancer women. Surgical specimens were obtained from 67 incident breast cancer patients at the Mexican National Cancer Institute between 1994 and 1995. Primary breast cancer tissue HGF-SF was measured by quantitative sandwich enzyme immunoassay. Relapse-free and overall survival curves were generated using Kaplan-Meier method. Significance of survival differences was calculated by log-rank test. chi2 was used for the association analysis between prognostic variables. Disease-free survival and overall survival were similar between the high tumor HGF group of patients and the low HGF patients (p = 0.7 and p = 0.36 respectively). No association was found between HGF and other clinicopathological variables (age, menopause status, clinical tumor size, clinical node involvement, metastasis, tumor grade, Estrogen Receptor and Progesterone Receptor). We found no prognostic significance for HGF, nor did we find a clear association between HGF and other known prognostic factors. A firm conclusion cannot be established regarding the role of HGF as a prognostic tool in breast cancer patients.