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C Abad

Publications and source records attributed to C Abad.

At least 37 records · Page 2Linked to original sources

The lipid charge density at the bilayer surface modulates the effects of melittin on membranes.

The influence of melittin on two DMPA membrane systems at pH 4.2 and 8.2 has been investigated by solid-state 31P and 2H NMR, as a function of temperature and peptide concentration. Melittin promotes greater morphological changes for both systems in the fluid phase, the effect being larger at pH 4.2. Close inspection of fatty acyl chain dynamics suggests that some parallels can be drawn between the DMPA/melittin at pH 8.2 and PC/melittin systems. In addition, at pH 8.2 a direct neutralization at the interface of one of the lipid negative charges by a positive charge of the peptide occurs, as can be monitored by 31P NMR at the molecular level. For the system at pH 4.2 and at high temperature, a lipid-to-peptide molar ratio of 30 is sufficient to transform the whole system into an isotropic phase, proposed to be inverted micelles. When the system is cooled down towards the gel phase one observes an intermediate hexagonal phase in a narrow range of temperature.

Aniline Compounds↗

[The non Q wave myocardial infarction in conventional valvular surgery. Diagnosis with cardiac troponin I].

INTRODUCTION: Morbidity and mortality in elective valve surgery is still significant. The main cause of death in these patients is cardiogenic shock, of which the most frequent etiology is acute myocardial infarction (AMI) with Q wave in the ECG. However, there are patients with cardiogenic shock without Q wave in the ECG and with rises in CK-MB enzyme that makes us suspect non-Q wave AMI. OBJECTIVE: To analyze the use of the determination of cardiac troponin-I, a more specific marker of AMI than CK-MB after cardiac surgery, to detect perioperative non-Q wave AMI, and to establish its clinical significance. METHODS: A total of 147 patients without coronary artery disease scheduled for elective valve surgery were included. We used, based in anterior publications, ECG (presence or not of new Q wave) and cardiac troponin I to define perioperative AMI. Levels of cardiac troponin-I were analysed before surgery and 14 hours after. Non-Q wave AMI was diagnosed when troponin I was superior to 38.85 ng/ml and there was not a phatologic Q wave in ECG. RESULTS: One hundred twenty-three (83.67%) of patients did not have AMI, 9 (6.12%) suffered perioperative AMI with Q wave, and 15 (10.27%) carried out criteria of non-Q wave perioperative AMI. Morbidity and mortality in this last group was similar to that in the group with Q wave AMI. Morbidity and mortality were minimum in patients without AMI. CONCLUSIONS: This study suggest the possibility of in vivo identification of non-Q wave perioperative AMI, an entity with important morbidity and mortality in our series, with a simple determination of cardiac troponin I 14 hours after surgery.

Adult↗

Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease.

Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease of unknown etiology, characterized by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. We describe here a new strategy for the treatment of arthritis: administration of the neuropeptide vasoactive intestinal peptide (VIP). Treatment with VIP significantly reduced incidence and severity of arthritis in an experimental model, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of VIP was associated with downregulation of both inflammatory and autoimmune components of the disease. Our data indicate VIP as a viable candidate for the development of treatments for RA.

Animals↗

Immunology of VIP: a review and therapeutical perspectives.

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad distribution in the body that exerts very important pleiotropic functions in several systems. The present work reviews the immunology of VIP. Being daring, this neuropeptide could be included in the group of cytokines since it is produced and secreted by different immunocompetent cells in response to various immune signals, plays a broad spectrum of immunological functions, and exerts them, in a paracrine and/or autocrine way, through three different specific receptors. Although VIP has been classically considered as an immunodepressant agent, and its main described role has been as an anti-inflammatory factor, several evidences suggest that a better way to see this peptide is as a modulator of the homeostasis of the immune system. In the last decade, the pharmacology of VIP has spectacularly grown, and VIP itself, as well as more stable VIP-derived agents, have been used or proposed as efficient therapeutical treatments of several disorders, specially inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Crohn's disease and autoimmune diabetes. A broad field of perspectives is actually open, and further investigations will help us to definitively understand the immunology of this very important peptide.

Animals↗

Preparation of the internal mammary artery with the IMAG Fogarty balloon catheter.

BACKGROUND: Demonstrate the augmentation of flow of the internal mammary artery (IMA) after inflation of the graft with an atraumatic balloon catheter (Fogarty IMAG balloon catheter) before performing the anastomosis IMA-coronary artery, in coronary artery bypass operated patients. METHODS: In 1992 and 1993 a group of 87 coronary artery bypass patients underwent dilatation of the IMA with the Fogarty balloon catheter. The flow of the IMA was measured during 1 minute before and after balloon dilatation, prior to go on cardiopulmonary bypass. RESULTS: In all patients but one the flow increased after balloon dilatation. The mean free flow before dilatation was 52.8 ml/min (range 16-120 ml/min) and after balloon dilatation 122.6 ml/min (range 36-380 ml/min). The flow increased more than two folds which was of statistical significance (p<0.001). The hospital mortality was 6.8% (6 patients) not related with the mechanical manipulation of the arterial graft. CONCLUSIONS: Balloon dilatation of IMA is an alternative in cases in which the IMA graft presented with: 1) low free flow, 2) small size and 3) arterial spasm. The IMAG balloon catheter has to be properly adjusted and the shear force regulated at 30 grams.

Adult↗

Binding of a fluorescent dansylcadaverine-substance P analogue to negatively charged phospholipid membranes.

We have investigated the binding of a new dansylcadaverine derivative of substance P (DNC-SP) with negatively charged small unilamellar vesicles composed of a mixture of phosphatidylcholine (PC) and either phosphatidylglycerol (PG) or phosphatidylserine (PS) using fluorescence spectroscopic techniques. The changes in fluorescence properties were used to obtain association isotherms at variable membrane negative charges and at different ionic strengths. The experimental association isotherms were analyzed using two binding approaches: (i) the Langmuir adsorption isotherm and the partition equilibrium model, that neglect the activity coefficients; and (ii) the partition equilibrium model combined with the Gouy-Chapman formalism that considers electrostatic effects. A consistent quantitative analysis of each DNC-SP binding curve at different lipid composition was achieved by means of the Gouy-Chapman approach using a peptide effective interfacial charge (v) value of (0.95 +/- 0.02), which is lower than the physical charge of the peptide. For PC/PG membranes, the partition equilibrium constant were 7.8 x 10(3) M(-1) (9/1, mol/mol) and 6.9 x 10(3) M(-1) (7/3, mol/mol), whereas for PC/PS membranes an average value of 6.8 x 10(3) M(-1) was estimated. These partition equilibrium constants were similar to those obtained for the interaction of DNC-SP with neutral PC membranes (4.9 x 10(3) M(-1)), as theoretically expected. We demonstrate that the v parameter is a determinant factor to obtain a unique value of the binding constant independently of the surface charge density of the vesicles. Also, the potential of fluorescent dansylated SP analogue in studies involving interactions with cell membranes is discussed.

Cadaverine↗

Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock.

Vasoactive intestinal peptide (VIP) is a neuropeptide that can modulate several immune aspects. Previous reports showed that VIP attenuates the deleterious consequences of septic shock by inhibiting the production of pro-inflammatory agents and stimulating the production of anti-inflammatory cytokines in activated macrophages. In this study, by using selective VIP agonists, we investigated the differential involvement of the VIP receptors in the anti-inflammatory role of VIP. Both the type 1 VIP receptor (VPAC1) agonist, [K(15), R(16), L(27)] VIP 1-7-GRF 8-27, and the type 2 VIP receptor (VPAC2) agonist, Ro25-1553, protected mice from lethal endotoxemia by inhibiting the macrophage-derived pro-inflammatory mediators IL-6, TNF-alpha, IL-12 and NO, and by stimulating the production of the anti-inflammatory cytokine IL-10. In addition, both VIP and VPAC1 agonist, but not the VPAC2 agonist, reduced in vitro and in vivo the expression of the co-stimulatory B7. 1/B7.2 molecules, and the subsequent stimulatory activity for T helper cells in stimulated macrophages. The higher effectiveness of the VPAC1 agonist compared with the VPAC2 agonist suggests that VPAC1 is the major mediator of the anti-inflammatory action of VIP. Since VIP and the two agonists appear to affect multiple cytokines and inflammatory factors, they might provide a more efficient therapeutical alternative to the use of specific cytokine antibodies or antagonists.

Animals↗

Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP.

VIP and PACAP modulate the function of inflammatory cells through specific receptors. VIP/PACAP inhibit the production of TNF alpha, IL-6, IL-12, and nitric oxide (NO), and stimulate IL-10 in peritoneal macrophages and Raw 264.7 cells. Here we report on the specific VIP/PACAP receptors, transduction pathways, and transcriptional factors involved in the regulation of these macrophage factors by VIP and PACAP. Both neuropeptides inhibit IL-6 production mainly through PAC1 binding, PKC activation, and the subsequent shedding of the LPS receptor CD14 in macrophages. However, the effects on TNF alpha, IL-10, IL-12, and NO are mostly mediated through the constitutively expressed VPAC1 receptor, although the inducible expressed VPAC2 may also participate. VIP/PACAP binding to VPAC1 induces both a cAMP-dependent and a cAMP-independent pathways that regulate cytokine and NO production at the transcriptional level. VIP/PACAP inhibit TNF alpha through reduction in NFkB binding and changes in the composition of CRE-binding complexes; they inhibit IL-12 through reduction in NFkB binding and changes in the composition of the ets-2 complexes. VIP/PACAP inhibit iNOS expression through reduction in NFkB and IRF-1 binding, and augment IL-10 by increasing CREB-binding. Whereas the inhibition of IRF-1 and CRE-binding complexes seems to be mediated through the cAMP-dependent pathway, VIP/PACAP inhibition of NFkB nuclear translocation is mediated through a reduction in IkB alpha degradation mediated by the cAMP-independent pathway. This study provides new evidence for the understanding of the molecular mechanism by means of which VIP and PACAP attenuate the inflammatory response.

Animals↗

Implantation of a composite bifurcated cryopreserved aorto-iliac-femoral homograft in a patient with Candida albicans endocarditis.

A 35 year old woman, cocaine addict, suffered Candida albicans aortic valve endocarditis complicated with embolisation of infected vegetations in the distal abdominal aorta. She underwent successful staged aortic valve replacement followed by transaortic and transfemoral thrombectomy. One month later an arteriogram disclosed partial occlusion of the left iliac artery, bilateral aneurysmal degeneration of both iliac arteries and right iliac artery-right iliac vein fistula. She was operated again, performing re-laparotomy and re-exploration. A composite bifurcated cryopreserved homograft was implanted end-to-side between the infrarenal abdominal aorta, right external iliac artery and left common femoral artery. The right iliac artery-iliac vein fistula was obliterated with suture. The patient had an uneventful recovery but a relapsing arterio-venous fistula was diagnosed by arteriography. Three months later she underwent percutaneous transluminal closure of the reopened fistula. At present, 17 months after the implantation of the homograft, the patient is symptom-free, on antifungal agents and with arteriographic and clinical evidence of a well-functioning arterial homograft.

Adult↗

Cardiac surgery in patients infected with human immunodeficiency virus.

From January 1991 through December 1999, 5 consecutive patients who were infected with human immunodeficiency virus presented in need of cardiac surgery. All were men; the median age was 44 years. Two of them presented with mitral and aortic infectious valve endocarditis, 1 with tricuspid endocarditis, 1 with prosthetic valve endocarditis, and 1 with pericarditis and pericardial tamponade. Under cardiopulmonary bypass, the 4 patients with endocarditis underwent these procedures: mitral and aortic valve replacement (2), tricuspid valve replacement (1), and aortic valve replacement (reoperation) and concomitant repair of a mycotic ascending aortic aneurysm (1). In the patient who had pericardial effusion, subxifoid pericardiostomy and drainage were performed, and a pericardial window was created. There was no intraoperative mortality. The patient with pericardial effusion died 8 days after surgery; he was in septic shock and had multiple organ failure. Two deaths occurred at 2 and 63 months, due to hemoptysis and sudden death, respectively. The 2 patients who underwent double valve replacement are alive and in good condition after a median follow-up of 71 months. Cardiac surgery is indicated in selected patients infected by the human immunodeficiency virus. These patients are frequently drug abusers or homosexual. Valvular endocarditis is the most common finding. Hospital morbidity and mortality rates are higher than usual in this group of patients.

AIDS-Related Opportunistic Infections↗

Endovascular repair of abdominal aortic aneurysm in a renal transplant patient.

A 65-year-old man presented with an asymptomatic infrarenal abdominal aortic aneurysm of 6 cm in transverse diameter. Five years before he received a cadaveric renal transplant. The patient also had the following risk factors and associated diseases: arterial hypertension, coronary artery disease, previous myocardial infarction, coronary angioplasty and stent, ileal resection secondary to Chron disease, hepatopathy, hyperlipidemia and hepato-renal cystic disease. The ASA classification was III, IV. Considering previous abdominal operations and risk factors, we decided to repair the aneurysm with a minimal aggression. The aneurysm was successfully approached by an endovascular route implanting a 22x10 bifurcated aorto-iliac endovascular prosthesis. The patient died 13 months later after being diagnosed of enterocolitis by cytomegalovirus complicated with sepsis and lung infection. We consider this less invasive modality of treatment a valid and useful alternative in this high-risk group of patients.

Aged↗

Shedding of membrane-bound CD14 from lipopolysaccharide-stimulated macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide.

Macrophage activation and deactivation play essential roles in the initiation and maintenance of a successful immune response. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), two structurally related neuropeptides, act as macrophage deactivating factors. We reported previously that VIP and PACAP inhibit IL-6, IL-12, TNF alpha and NO production, and enhance IL-10 production, from lipopolysaccharide (LPS)-stimulated macrophages. In this study, we demonstrate that VIP and PACAP down-regulate the expression of CD14, the membrane-bound LPS receptor, by inducing its rapid shedding. The soluble CD14 released by VIP and PACAP corresponds in size to the soluble CD14 released by PMA. Neither VIP/PACAP nor PMA, affect the steady-state levels of CD14 mRNA. The CD14 shedding induced by VIP/PACAP is mediated through the PAC1 specific receptors and the major transduction pathway involves the protein kinase C (PKC). The VIP/PACAP inhibition of TNF alpha and NO occurs through both CD14-dependent and -independent mechanisms, whereas the inhibition of IL-6 production appears to be strictly CD14-dependent. The shedding of CD14 by VIP and PACAP represents an important mechanism by which these neuropeptides limit the macrophage inflammatory response.

Animals↗

Addressing substrate glutamine requirements for tissue transglutaminase using substance P analogues.

We have investigated the effect on the substrate requirements for guinea pig liver (tissue) transglutaminase of a set of 11 synthetic glutamine substitution analogues making up the full sequence of the naturally occurring tissue transglutaminase substrate substance P. While a number of peptide sequences derived from proteins that are well-recognized as tissue transglutaminase substrates have been studied, the enzyme activity using substitution analogues of full-length natural substrates has not been investigated as thoroughly. Thus, our set of substance P analogues only differs from one to other by one amino acid mutation while the length (of the peptide) is maintained as in the natural parent peptide. Our results indicate that a glutamine residue is not recognized as substrate by the enzyme whether it is placed at the N- or C-terminal or between two positively charged residues or between two proline residues. To further address the effect on enzyme activity of charged amino acids in the vicinity of the reactive glutamine residue, a new set of synthetic charge replacement analogues of substance P has been also studied. Together, the results have identified new minimal requirements for modification of a particular glutamine residue in a polypeptide chain. It would be of interest to set up a full set of such requirements in order to highlight potential glutamine residues as enzyme targets in the growing list of proteins that are being described as transglutaminase substrates.

Amino Acid Sequence↗

Regulation of VIP production and secretion by murine lymphocytes.

Vasoactive intestinal peptide (VIP) is a neuropeptide present in the lymphoid microenvironment with a multiplicity of actions. Two sources for VIP have been described in the immune system, the terminals present in central and peripheral lymphoid organs and the immune cells. Although VIP is synthesized by lymphocytes, there is no evidence demonstrating that VIP is released, and which stimuli are able to induce VIP production and secretion. In this study, we demonstrated for the first time, that agents that mediate important immune functions, such as proliferation and antigenic stimulation (Con A, LPS, and anti-TCR antibody), inflammation (LPS, TNFalpha, IL-6 and IL-1beta) or apoptosis (dexamethasone) induce the production and release of VIP to the lymphoid microenvironment. We conclude that VIP is produced and secreted by lymphocytes and propose that during an immune response, the timely release of VIP within the lymphoid organs and peritoneum should influence the differentiation and/or downregulation of the ongoing response.

Animals↗

[Fortuitous diagnosis of an undifferentiated large cell carcinoma during cardiac surgery].

A 57 years old man was operated for aortic valve replacement. During the operation a mediastinal lymph node was biopsed with the result of undifferenciated large cell carcinoma with neuroendocrine features. Three months after surgery the patient died of non-cardiac related reasons, postmorten examination was not performed. Although the primary tumor could not be assessed, probably the lung was the original location. The histological classification of lung cancer is exposed, with special reference in the undifferenciated large cell type with neuroendocrine features.

Carcinoma, Large Cell↗