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M Mata

Publications and source records attributed to M Mata.

At least 19 recordsLinked to original sources
PubMed2006

Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARalpha-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARalpha to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.

Adipogenesis↗
PubMed2006

In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis.

1 Bleomycin-induced lung injury is widely used as an experimental model to investigate the pathophysiology of pulmonary fibrosis but the alterations in the pharmacological responsiveness of airways isolated from bleomycin-exposed animals has been scarcely investigated. The aim of this study was to examine the in vitro tracheal responses to muscarinic receptor stimulation with carbachol in a rat bleomycin model. 2 Concentration-response curves to carbachol (10 nm to 0.1 mm) were obtained in tracheal rings isolated from Sprague-Dawley rats 14 days after endotracheal bleomycin or saline. The intracellular calcium signal in response to carbachol (10 microm) was measured by epifluorescence microscopy using fura-2 in primary cultures of tracheal smooth muscle cells from bleomycin- and saline-exposed rats. Circulating plasma tumour necrosis factor (TNF)-alpha/interleukin (IL)-1beta levels were measured by enzyme-linked immunosorbent assay. 3 Maximal contraction in response to carbachol was significantly greater in tracheal rings from bleomycin-exposed rats compared with controls (15.8 +/- 1.3 mN vs. 11.8 +/- 1.4 mN; n = 19, P < 0.05). 4 Carbachol (10 microm) elicited a transient increase of intracellular calcium with greater increment in tracheal smooth muscle cells from bleomycin-exposed rats compared with controls (372 +/- 42 nmvs. 176 +/- 20 nm; n = 7, P < 0.01). 5 Circulating plasma levels of TNF-alpha/IL-1beta were augmented in bleomycin-exposed rats compared with controls. Tissue incubation with TNF-alpha (100 ng ml(-1))/IL-1beta (10 ng ml(-1)) increased in vitro tracheal responsiveness to carbachol. 6 In conclusion, tracheal contraction in response to muscarinic receptor stimulation with carbachol was increased in bleomycin-exposed rats. This in vitro cholinergic hyperresponsiveness may be related to the augmented levels of inflammatory cytokines in bleomycin-exposed rats.

Animals↗
PubMed2005

HSV-mediated gene transfer of vascular endothelial growth factor to dorsal root ganglia prevents diabetic neuropathy.

We examined the utility of herpes simplex virus (HSV) vector-mediated gene transfer of vascular endothelial growth factor (VEGF) in a mouse model of diabetic neuropathy. A replication-incompetent HSV vector with VEGF under the control of the HSV ICP0 promoter (vector T0VEGF) was constructed. T0VEGF expressed and released VEGF from primary dorsal root ganglion (DRG) neurons in vitro, and following subcutaneous inoculation in the foot, expressed VEGF in DRG and nerve in vivo. At 2 weeks after induction of diabetes, subcutaneous inoculation of T0VEGF prevented the reduction in sensory nerve amplitude characteristic of diabetic neuropathy measured 4 weeks later, preserved autonomic function measured by pilocarpine-induced sweating, and prevented the loss of nerve fibers in the skin and reduction of neuropeptide calcitonin gene-related peptide and substance P in DRG neurons of the diabetic mice. HSV-mediated transfer of VEGF to DRG may prove useful in treatment of diabetic neuropathy.

Animals↗
PubMed2005

Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland.

GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.

Animals↗
PubMed2005

Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells.

BACKGROUND: A common pathological feature of chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic and COPD patients. Recent clinical trials indicate that phosphodiesterase type 4 (PDE4) inhibitors may have therapeutic value for COPD and asthma. However, their direct effects on mucin expression have been scarcely investigated. METHODS: MUC5AC mRNA and protein expression were examined in cultured human airway epithelial cells (A549) and in human isolated bronchial tissue stimulated with epidermal growth factor (EGF; 25 ng/ml). MUC5AC mRNA was measured by real time RT-PCR and MUC5AC protein by ELISA (cell lysates and tissue homogenates), Western blotting (tissue homogenates) and immunohistochemistry. RESULTS: EGF increased MUC5AC mRNA and protein expression in A549 cells. PDE4 inhibitors produced a concentration dependent inhibition of the EGF induced MUC5AC mRNA and protein expression with potency values (-log IC(50)): roflumilast (approximately 7.5) > rolipram (approximately 6.5) > cilomilast (approximately 5.5). Roflumilast also inhibited the EGF induced expression of phosphotyrosine proteins, EGF receptor, and phospho-p38- and p44/42-MAPK measured by Western blot analysis in A549 cells. In human isolated bronchus, EGF induced MUC5AC mRNA and protein expression was inhibited by roflumilast (1 microM) as well as the MUC5AC positive staining shown by immunohistochemistry. CONCLUSION: Selective PDE4 inhibition is effective in decreasing EGF induced MUC5AC expression in human airway epithelial cells. This effect may contribute to the clinical efficacy of this new drug category in mucus hypersecretory diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Hypogalactosylation of serum IgG in patients with coeliac disease.

Coeliac disease (CD) is described as an autoimmune enteropathy associated with the presence of IgG and IgA antigliadin and antitransglutaminase autoantibodies. While of diagnostic significance, the role of these autoantibodies in the immunopathogenesis of CD is elucidated. An inappropriate T cell immune response to gluten is also involved in the pathogenesis of CD, as evidenced by autoantibody switching. The N-glycans released from serum IgG of CD patients and three groups of healthy controls, of differing age ranges, were analysed by NH2-high performance liquid chromatography (HPLC). The fucosylated biantennary N- glycans were the most abundant neutral oligosaccharides; in particular, the agalacto form (G0F) showed a mean value of 42% (s.d. +/- 7.4), 30% (s.d. +/- 5.9), 26% (s.d. +/- 4.2) and 35% (s.d. +/- 6.8) for CD patients, healthy children, healthy adults under 40 and healthy adults over 40 years old, respectively. The ratio of asialo agalacto fucosylated biantenna to asialo monogalacto fucosylated biantenna (G0F)/(G1F) for CD patients showed a significant increase compared to healthy children (P < 0.0002), healthy adults under 40 (P < 0.0002) and healthy adults over 40 years old (P < 0.01). Hypogalactosylation was more pronounced for CD patients than for the patients with other autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis.

Adult↗
PubMed2003

Factitial oral lesions in an autistic paediatric patient.

Self Injurious Behaviour (SIB) is a deliberate harm to the body that may lead to factitial injuries. Its origin may be functional or biological and it has a higher prevalence in females and in psychologically impaired individuals. Seventy per cent of autistic patients have SIB. Seventy-five per cent of factitial injuries are located in the head and neck region. A paediatric case report concerning a 4-year-old autistic female is presented. Detailed medical history, physical examination, clinical intraoral and radiographic examination, incisional biopsy, neuropaediatrical, psychological and speech evaluation were undertaken. Diagnosis included hypochromic macrocytic anaemia, caries, coronal fracture, factitial ulcer, factitial periodontitis, self-extraction of primary teeth and permanent teeth buds, non-specific oral ulcer with inflammatory reaction, mild mental retardation, speech impairment, autistic syndrome and self injurious behaviour consisting of putting fingers and foreign objects in the gingiva, fingernail biting and hair pulling. Differential diagnosis included hystiocitosis X, prepuberal periodontitis and leukocyte adhesion deficiency. Dental preventive and restorative treatment was performed. Non-contingent reinforcement therapy was successfully used to diminish SIB. Treatment of factitial oral injuries must be interdisciplinary and requires cooperation of the patient, the parents, health care providers, and medical team.

Autistic Disorder↗
PubMed2003

Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.

Acetylcysteine↗
PubMed2003

Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen.

Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects of N-acetylcysteine on sensitised brown Norway rats were examined. N-Acetylcysteine (3 mmol kg body weight(-1) administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied. Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor-KB-binding activity was increased 2 h after challenge, and BALF tumour necrosis factor-alpha and inducible nitric oxide synthase expression in lungs peaked 4 h after challenge. Expression of intercellular adhesion molecule-1 and mucin MUC5AC was also increased 4 h after challenge. These changes in oxidant status, transcription factor activation, and inflammatory cytokine and gene expression were reduced by N-acetylcysteine. This thiol did not affect the immediate bronchospasm reaction to antigen in anaesthetised rats but inhibited airways hyperresponsiveness to 5-hydroxytryptamine and the augmented eosinophil numbers in BALF, which appear 24 h after exposure of conscious rats to antigen aerosol, and abolished antigen-induced extravasation of Evans blue into BALF. These results indicate that oral N-acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.

Acetylcysteine↗
PubMed2002

Evaluation of risk factors for development of complications in Type II diabetes in Europe.

AIMS/HYPOTHESIS: The Cost of Diabetes in Europe - Type II study is the first large coordinated attempt to measure the current standard of care and determine the costs of managing patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: The study evaluated glycaemic control, blood lipid levels and blood pressure, all of which are risk factors for complications. Records of these clinical characteristics were collected from over 7000 patients during the 6-month study period. RESULTS: The mean HbA(1c) value for the entire study population was 7.5%, ranging from 7.0% in Sweden to 7.8% in the United Kingdom. Only 31% of individuals achieved good glycaemic control (HbA(1c)< or = 6.5%) according to current European guidelines. Only 64% of the total study population were tested for HbA(1c) values at least once within the 6-month study period (ranging from 49% in Spain to 71% in the UK), although HbA(1c) testing every 3 months is recommended for all patients, by European Diabetes Policy Group guidelines. The majority of patients had borderline total cholesterol values, with a mean value of 5.7 mmol/l. Overall, 21% of patients were classified as having low risk cholesterol levels (<4.8 mmol/l). Good triglyceride levels (<1.7 mmol/l) were achieved by 47% of the total study population. During the study period, 81% of patients had their blood pressure measured, with 35% and 53.3% of the patients reaching the recommended targets for systolic and diastolic blood pressure, respectively. CONCLUSION/INTERPRETATION: This study showed that a high proportion of patients with risk factors for diabetes-related complications are not adequately controlled. Improvements in disease management and monitoring are therefore required to ensure that guideline targets are met, thus reducing the long-term complications of Type II diabetes.

Blood Glucose↗
PubMed2002

Effectiveness of oral N -acetylcysteine in a rat experimental model of asthma.

Oxidative stress appears to be relevant to asthma pathogenesis. Therefore, the effectiveness of the antioxidant N -acetylcysteine was examined on antigen-induced pulmonary responses in sensitized Brown-Norway rats. N -acetylcysteine (oral, 1 mmol kg(-1)per day for 7 days before challenge) did not reduce the immediate bronchospasm that followed aerosol antigen exposure but prevented airway hyperreactivity to 5-hydroxytryptamine at 24 h after antigen challenge, and reduced the eosinophils (from 0.178 +/- 0.038 in the absence to 0.064 +/- 0.020 x10(6)cells ml(-1)in the presence of N -acetylcysteine;P< 0.05), and Evans blue dye extravasation in bronchoalveolar lavage fluid. Taurine levels in bronchoalveolar lavage fluid from antigen-challenged rats were higher than control values but treatment with N -acetylcysteine failed to further increase these augmented levels. In conclusion, oral N -acetylcysteine showed beneficial effects in an in vivo model of experimental asthma, which confirm and extend the previous positive findings obtained in other models of lung injury.

Acetylcysteine↗
PubMed2001

Effects of taurine on pulmonary responses to antigen in sensitized Brown-Norway rats.

Oxidative stress appears relevant to asthma. Therefore, the effects of the antioxidant taurine (oral, 1 and 3 mmol x kg(-1) x day(-1) for 7 days before challenge) were examined on antigen-induced responses in sensitized Brown-Norway rats. Taurine did not reduce the bronchospasm produced by aerosol antigen but prevented airway hyperreactivity to 5-hydroxytryptamine (5-HT) at 24 h after antigen exposure, and reduced the eosinophils (from 0.178+/-0.038x10(6) to 0.044+/-0.014x10(6)* and 0.048+/-0.013x10(6)* cells ml(-1) in antigen and antigen+taurine 1 or 3 mmol x kg(-1), respectively; *P<0.05 vs. antigen), lipid hydroperoxides, and Evans blue dye extravasation in bronchoalveolar lavage fluid. Taurine levels in bronchoalveolar lavage fluid from antigen-challenged rats were higher than control values but treatment with taurine failed to further increase these levels. In conclusion, oral taurine showed beneficial effects in an in vivo model of experimental asthma, which confirm and extend the previous positive findings obtained in other models of lung injury.

Airway Resistance↗
PubMed2001

Evaluation of a recombinant Listeria monocytogenes expressing an HIV protein that protects mice against viral challenge.

Vaccine strategies that utilize cell mediated immunity to control infection will be a necessary component of human immunodeficiency virus (HIV) vaccines. In previous studies we have shown that a Listeria monocytogenes recombinant expressing HIV-Gag elicits strong CD8+ and CD4+ T cell responses against HIV Gag in addition to its own secreted proteins. Here, we show that Lm-Gag can protect mice against a viral challenge with a recombinant vaccinia virus expressing Gag, in an antigen specific manner, and that this protection is T cell mediated. These results further support the use of L. monocytogenes as a vaccine approach for HIV through the induction of T cell immunity.

AIDS Vaccines↗
PubMed2001

Herpes simplex virus vector-mediated expression of Bcl-2 protects spinal motor neurons from degeneration following root avulsion.

Proximal axotomy in adult animals results in delayed death of motor neurons. Features characteristic of both necrosis and apoptosis have been described in motor neurons of the spinal cord following proximal avulsion of the ventral roots. We have previously demonstrated that a genomic herpes simplex virus (HSV)-based vector expressing the anti-apoptotic peptide Bcl-2 protects dopaminergic neurons of the substantia nigra from neurotoxin-induced apoptotic cell death and preserves the neurotransmitter phenotype of those cells. In this study we examined whether the same vector could protect adult rat lumbar motor neurons from cell death following proximal ventral root avulsion. Injection of the Bcl-2-expressing vector 1 week prior to root avulsion increased the survival of lesioned motor neurons, determined by retrograde Fluorogold labeling, by 50%. The Bcl-2-expressing vector did not preserve choline acetyltransferase neurotransmitter phenotype of the lesioned cells. These results shed light on the mechanism of cell death following axonal injury, and have implications for developing an effective treatment for the clinical problem of proximal root avulsion.

Animals↗
PubMed2001

Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration.

Previous studies have demonstrated that either the neurotrophin glial-derived neurotrophic factor (GDNF) or the antiapoptotic peptide Bcl-2 delivered into striatum by a viral vector protects dopaminergic neurons of the substantia nigra in vivo from degeneration induced by the administration of the neurotoxin 6-hydroxydopamine (6-OHDA). In this study we used recombinant, replication-incompetent, genomic herpes simplex virus-based vectors to deliver the genes coding for Bcl-2 and GDNF into rat substantia nigra (SN) 1 week prior to 6-OHDA injection into the striatum. Vector-mediated expression of either Bcl-2 or GDNF alone each resulted in a doubling in cell survival as measured by retrograde labeling with fluorogold (FG) and a 50% increase in tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the lesioned SN compared to the unlesioned side. Gene transfer of Bcl-2 and GDNF were equivalent in this effect. Coadministration of the Bcl-2-expressing vector with the GDNF-expressing vector improved the survival of lesioned SN neurons as measured by FG labeling by 33% and by the expression of TH-IR by 15%. These results suggest that the two factors delivered together act in an additive fashion to improve DA cell survival in the face of 6-OHDA toxicity.

Animals↗
PubMed2001

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion.

Endogenous opiate peptides acting pre- and post-synaptically in the dorsal horn of spinal cord inhibit transmission of nociceptive stimuli. We transfected neurons of the dorsal root ganglion in vivo by footpad inoculation with 30 microl (3 x 10(7) p.f.u.) of a replication-incompetent (ICP4-deleted) herpes simplex virus (HSV) vector with a cassette containing a portion of the human proenkephalin gene coding for 5 met- and 1 leu-enkephalin molecules under the control of the human cytomegalovirus immediate-early promoter (HCMV IEp) inserted in the HSV thymidine kinase (tk) locus. Vector-directed expression of enkephalin produced a significant antinociceptive effect measured by the formalin footpad test, that was most prominent in the delayed ("tonic") phase 20-70 min after the administration of formalin. The magnitude of the antinociceptive effect diminished over 4 weeks after transduction, but reinoculation of the vector reestablished the analgesic effect, without evidence for the development of tolerance. The antinociceptive effect was blocked completely by intrathecal naltrexone. These results suggest that gene therapy with an enkephalin-producing herpes-based vector may prove useful in the treatment of pain.

Analgesia↗
PubMed2001

HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons, of the rat peripheral nervous system.

The entry of herpes simplex virus (HSV)-1 into cells is a complex process mediated in part by the binding of the HSV glycoprotein D (gD) to a specific cellular receptor identified as HveC, or nectin-1. We examined the distribution of HveC in sensory and motor neurons of the peripheral nervous system (PNS) by immunocytochemistry. HveC is expressed at high levels in sensory neurons of dorsal root ganglion and their peripheral axons, at lower levels in motor neurons of spinal cord, and without detectable expression in motor nerve terminals at the neuromuscular junction. These results have implications regarding the tropism of HSV to specific neuronal populations, and for the construction of HSV-based vectors for the peripheral nervous system.

Animals↗