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C Abad

Publications and source records attributed to C Abad.

At least 19 recordsLinked to original sources
PubMed2006

VIP-PACAP system in immunity: new insights for multitarget therapy.

Our research about VIP/PACAP and the immune system goes back to 1990 when our group described the expression of VIP on lymphocytes for the first time. Since this year, using three models of disease, septic shock, rheumathoid arthritis, and Crohn's disease, we are trying to contribute with new pieces to the puzzle of immunity to approach the use of VIP/PACAP system as a therapeutic agent. In 1999 we established that the first step in the beneficial effect of the VIP/PACAP system exerts consists in its potent anti-inflammatory action. Thus, VIP and PACAP inhibit the expression and release of proinflammatory cytokines and chemokines, and enhance the production of the anti-inflammatory factors. These effects were reported both in vitro and in vivo, are mediated by the presence of PAC1, VPAC1, and VPAC2 receptors, in the three models of diseases used. The next step was that the system favors Th2 responses versus Th1 contributing to the remission of illness as rheumatoid arthritis or Crohn's disease by blocking the autoimmune component of these diseases. Because it appears that inflammatory processes requires more than blockade of a single mediator, new therapies blocking several components of both the infection- and the autoimmunity-induced inflammation cascades should be an interesting focus of attention. In this sense, at present we are trying to dissect new aspects of the potential therapeutic of the VIP/PACAP system in the control of CC and CXC chemokine and their receptors, coagulation factors, adhesion molecules, acute phase proteins, and osteoclastogenesis mediators as well as in the modulation of the expression of Toll-like receptors. Our more recent data open a hopeful door for the therapeutic use of VIP/PACAP in humans.

Animals↗
PubMed2006

VIP decreases TLR4 expression induced by LPS and TNF-alpha treatment in human synovial fibroblasts.

It has been demonstrated that VIP produces beneficial effects both in a murine model of rheumatoid arthritis and in human rheumatoid synovial fibroblasts through the modulation of proinflammatory mediators. Toll-like receptors (TLRs) play a key role in the immediate recognition of microbial surface components by immune cells prior to the development of adaptative microbe-specific immune responses. In this study, we demonstrate that VIP decreases lipopolysaccharide (LPS) and TNF-alpha-induced expression of TLR4 and its correlation with the production of CCL2 and CXCL8 chemokines in human synovial fibroblasts from patients with rheumatoid arthritis and osteoarthritis. Our results add a new step for the use of VIP, as a promising candidate, for the treatment of rheumatoid arthritis.

Cells, Cultured↗
PubMed2006

[Splenic artery aneurysm. Review of two surgically operated cases].

Among arterial aneurysms, splenic artery aneurysms are very uncommon in the current practice. The etiologic factors are in relation with: angiodysplasia, portal hypertension, pregnancy and atherosclerosis. The great majority are asymptomatic. Symptomatic cases are in relation with rupture in the peritoneum or in organs or structures of the vicinity. We present two cases of splenic artery aneurysm in a 57 year old man and in a 59 year old woman. In both cases the diagnosis was made by plain abdominal x-ray, abdominal scanner and abdominal aortography. Both cases were surgically treated by transverse laparotomy and total aneurysm resection. The pathology dictamen of the two cases was consistent with atherosclerosis. After 120 and 38 months of follow-up both patients are doing well and without evidence of splenic artery aneurysm. A review of this entity is exposed, with special reference in the etiology, symptomatology, diagnosis and treatment.

Anastomosis, Surgical↗
PubMed2005

Meiotic studies in two human reciprocal translocations and their association with spermatogenic failure.

BACKGROUND: Reciprocal translocations are often associated with infertility in male carriers. However, some carriers present normal semen profiles and are identified because of repetitive pregnancy failures. METHODS: Here, we report two different cases of reciprocal translocations. The first patient carried a t(10;14) and was normozoospermic. The second patient carried a t(13;20) and was azoospermic. Synaptonemal complexes from both carriers were analysed using immunocytogenetic techniques and multi-centromere fluorescent in situ hybridization (cenM-FISH). RESULTS: Associations between the quadrivalent and the sex body or other autosomes were seen only in the t(13;20) carrier. Heterosynapsis was observed only in the t(10;14) carrier. Synaptic pairing abnormalities were seen in 71% of the spreads in the t(13;20) carrier and 30% of the spreads in the t(10;14) carrier. Recombination frequency was decreased in the t(13;20) carrier, but not in the t(10;14) carrier. CONCLUSIONS: By comparing these two different translocation carriers with different fertility outcomes, we discuss the possible mechanisms by which translocations might cause the spermatogenesis process to fail.

Adult↗
PubMed2004

From spermatocytes to sperm: meiotic behaviour of human male reciprocal translocations.

BACKGROUND: Human male translocation carriers may present alterations in the meiotic process due to the presence of the translocated chromosomes. The aim of this work was to study the mechanisms that affect meiotic segregation in translocation carriers by analysing different stages of the meiotic process. METHODS: Meiotic studies using fluorescence in-situ hybridization on both spermatocytes and sperm nuclei were performed in two translocation carriers, t(11;17)(q13.1;p11.2) and t(10;14)(q24;q32). RESULTS: A ring configuration was the main type of quadrivalent found in metaphase I. Overall chiasma frequency was significantly decreased in the t(11;17) carrier. In the t(10;14) carrier, chiasma frequency within the interstitial region of chromosomes 10 and 14 was increased and the recombination pattern was modified. As expected from the frequencies of interstitial chiasmata found in metaphase I in the two subjects, the incidence of asymmetric dyads was sporadic in t(11;17) and very high in t(10;14). In both carriers, segregation frequencies observed at metaphase II were not different from the segregation data obtained in decondensed sperm nuclei. CONCLUSIONS: The concordance observed among results obtained in different spermatogenic stages indicates an absence of cellular selection based on chromosomal imbalances. Results obtained in the aneuploidy assay have not provided any evidence for an interchromosomal effect.

Adult↗
PubMed2004

Induction of neuropeptide gene expression and blockade of retrograde transport in facial motor neurons following local peripheral nerve inflammation in severe combined immunodeficiency and BALB/C mice.

Peripheral nerve inflammation is a common clinical problem that accompanies nerve injury and several diseases including Guillain-Barre syndrome and acute and chronic inflammatory demyelinating polyneuropathy. To determine if neuropeptides are induced in motor neurons after inflammation and to study the mechanisms involved, a nerve cuff soaked in complete Freund's adjuvant (CFA) was applied locally to the facial nerve of Balb/C mice. This procedure resulted in an influx of lymphocytes and macrophages to the affected area and a blockade of retrograde axonal transport distal, but not proximal, to the site of application. The same treatment resulted in a strong ipsilateral induction of pituitary adenylyl cyclase activating peptide (PACAP) gene expression in motor neurons in the facial motor nucleus. Because the changes could have occurred due to the loss of target-derived factors or to the production of new factors by immune cells, we studied the effect of the inflammatory stimulus on PACAP mRNA in mice with severe combined immunodeficiency (SCID). As expected, SCID mice showed a severely reduced influx of T-lymphocytes but not macrophages to the peripheral nerve. Moreover, although retrograde transport distal to the inflammation site was blocked similarly in control and SCID mice, the number of motor neurons expressing PACAP mRNA after CFA application was significantly reduced in SCID mice. The data indicate that the induction of PACAP mRNA during nerve inflammation requires the involvement of lymphocytes. However, because the induction of PACAP gene expression was only partially blocked in SCID mice, macrophages, loss of target-derived factors, or other mechanisms may also contribute to the upregulation of PACAP gene expression in motor neurons after nerve inflammation.

Animals↗
PubMed2003

Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in osteoarthritic and rheumatoid synovial cells.

OBJECTIVE: Vasoactive intestinal peptide (VIP) has demonstrated beneficial effects in several murine models of immune-mediated inflammation by inhibiting both the inflammatory and the autoimmune components of the disease. We investigate its potential to modulate the release of proinflammatory cytokines and chemokines by human synovial cells from patients with rheumatoid arthritis (RA). METHODS: Fresh suspensions of synovial tissue cells (STC) or cultured fibroblast-like synoviocytes (FLS) were obtained from patients with RA or osteoarthritis (OA). The effects of VIP on basal or tumour necrosis factor alpha (TNF-alpha)-stimulated production of CCL2 (MCP-1, monocyte chemotactic protein 1), CXCL8 [interleukin (IL)-8], IL-6 and TNF-alpha were studied by specific ELISAs (enzyme-linked immunosorbent assays). The mRNAs for CCL2, CXCL8 and IL-6 in FLS were analysed by real-time reverse transcription-polymerase chain reaction. RESULTS: VIP at 10 nm down-regulated chemokine production by STC and FLS from RA and OA patients. VIP also down-regulated the expression of mRNAs for CCL2, CXCL8 and IL-6. The effects of VIP were more clearly detected in RA samples and after stimulation with TNF-alpha. CONCLUSION: Our observations confirm that the proposed anti-inflammatory actions of VIP in murine models also apply to human synovial cells ex vivo. Further studies are encouraged to evaluate the use of VIP as a potential therapy for chronic inflammatory joint diseases.

Arthritis, Rheumatoid↗
PubMed2003

Binding of vinyl polymers to anionic model membranes.

The association of poly2-vinylpyridine (P2VPy) and poly4-vinylpyridine (P4VPy) to dimyristoylphosphatidic acid (DMPA) small unilamellar vesicles (SUVs) was studied as a function of pH, ionic strength (I), polymer concentration and temperature using spectrofluorimetry. Poly(vinylpyridine) (PVPy) data were transformed into association isotherms and analyzed in terms of binding and partition models. In the case of polyions, the inclusion of the activity coefficient in both models was essential. Moreover, a relating equation was proposed to compare parameters based on both theoretical approaches. On the basis of the results obtained, a model was developed to analyze polymer adsorption at the surface level, in which the length of the hydrophobic chain and the position of the N atom in the pyridinium ring play an important role. Transition temperature (Tc) for DMPA (ca. 55 degrees C) is decreased between 15 degrees C-19 degrees C in the presence of PVPy. Van't Hoff isochore showed that the binding constant (KA) accounted for average PVPy-DMPA two-dimensional solid and liquid interactions. KA decreased with I in the presence of both polymers, but was more sensitive to I in the case of P2VPy. Likewise, the number of phospholipid heads (N) involved in the binding process decreased with I in the presence of PVPy. The influence of I was more significant on N than on KA.

Aniline Compounds↗
PubMed2003

Endovascular repair of descending thoracic aortic aneurysm via midsternotomy and without extracorporeal circulation.

A 68-year-old man with peripheral vascular disease and associated risk factors, was diagnosed by CT-scan and aortography with an atherosclerotic descending thoracic aortic aneurysm. The patient was treated by successful endovascular grafting of the aneurysm using a midsternotomy incision and the insertion of a thoracic stent-graft through a T-Dacron tube sutured in the ascending aorta, without the aid of cardiopulmonary bypass.

Aged↗
PubMed2001

Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases.

Vasoactive intestinal peptide (VIP), a neuropeptide that is produced by lymphoid as well as neural cells, exerts a wide spectrum of immunological functions, controlling the homeostasis of the immune system through different receptors expressed in various immunocompetent cells. In the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, which acts by regulating the production of both anti- and pro-inflammatory mediators. In this sense, VIP has been described to prevent death by septic shock, an acute inflammatory disease with a high mortality. In addition, VIP regulates the expression of co-stimulatory molecules, this being an action that may be related to modulating the shift toward Th1 and Th2 differentiation. We have recently reported that VIP prevents the deleterious effects of an experimental model of rheumatoid arthritis, by downregulating both inflammatory and autoimmune components of the disease. Therefore, VIP has been proposed as a promising candidate alternative treatment for acute and chronic inflammatory and autoimmune diseases such as septic shock, arthritis, multiple sclerosis, Crohn disease, or autoimmune diabetes.

Animals↗
PubMed2001

Pituitary adenylate cyclase-activating polypeptide inhibits collagen-induced arthritis: an experimental immunomodulatory therapy.

Rheumatoid arthritis is a chronic, systemic, autoimmune, and inflammatory disorder that affects the synovial lining of the joints. We describe the beneficial effects of the pituitary adenylate cyclase-activating polypeptide (PACAP) in the collagen-induced arthritis experimental murine model being proposed as a novel therapeutic approach in the treatment of rheumatoid arthritis. PACAP greatly decreases arthritis frequency and severity in the studied mice by improving clinical symptoms, ameliorating joint damage, and blocking both the inflammatory and autoimmune mediators which are the main keys of the pathogenesis of this disease. With this study, PACAP emerges as a promising candidate for the treatment of a pathology with a high world incidence but currently no effective treatment.

Adjuvants, Immunologic↗
PubMed2001

Fatal pulmonary thromboembolism after laparoscopic cholecystectomy.

A 67-year-old woman presented with severe cardiopulmonary insufficiency 17 days after an uneventful laparoscopic cholecystectomy. Pulmonary thromboembolism was demonstrated by transthoracic echocardiogram and later confirmed at surgery. With the aid of a cardiopulmonary bypass, a thrombectomy of the right atrium and the pulmonary artery was accomplished. The patient could not be weaned off cardiopulmonary bypass and ultimately died. We therefore recommend antithromboembolism therapy with low-molecular-weight heparin in selected cases of laparoscopic cholecystectomy.

Aged↗
PubMed2001

The closed/open model for lipase activation. Addressing intermediate active forms of fungal enzymes by trapping of conformers in water-restricted environments.

The behavior of prototypic fungal lipases in a water-restricted environment has been investigated by exploiting the reported experimental strategy that allows the trapping (freeze-drying) of the enzyme in the conformation present in aqueous solution and to subsequently assay it in nonaqueous media [Mingarro, I., Abad, C., and Braco, L. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 3308-3312]. We now report, using simple esterification as well as acidolysis (triglycerides as substrates) as nonaqueous model reactions, that the presence of a detergent (n-octyl-beta-glucopyranoside) in the freeze-drying buffer, at concentrations below the critical micellar concentration, generates different catalytically active (kinetically trapped) conformational states of the enzyme. These activated forms exquisitely discriminate between short- and long-chain fatty acids, suggesting that they can be correlated with intermediate conformations of the protein sufficiently open to permit the access of relatively small but not large substrates. Additional data obtained from aqueous solution activity measurements in the presence of detergent revealed that the fungal lipase retains an active conformation induced by high detergent concentration (30 mM) for a long period of time, a 'memory effect', which is stabilized in the absence of a well-defined interface by few detergent molecules. Together these results provide support to a model of lipase action involving several equilibrium states (closed, intermediate, and open), which can be modulated by the composition of the microenvironment, i.e., by the detergent concentration.

Ascomycota↗