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Biomedical subjects

V Martinez

Publications and source records attributed to V Martinez.

At least 19 recordsLinked to original sources
PubMed2006

Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy.

Highly active antiretroviral therapy (HAART) reduces the incidence and improves the prognosis of Kaposi's sarcoma (KS). This study was designed to identify factors associated with KS clinical responses in HIV-infected patients during HAART. We reviewed the files of 138 HIV-1-infected patients with KS. Epidemiologic and HIV-related clinical and biological parameters were recorded at KS diagnosis (baseline) and every 6 months thereafter. In a subset of 73 antiretroviral-naive patients, we compared the clinical outcome of KS according to the use or nonuse of protease inhibitors (PI). After 6 months of follow-up, KS remission was more frequent in patients who were naive of HAART and who were at ACTG stage S0 at baseline (P = 0.03 and 0.02). Undetectable HIV viral load was strongly associated with KS remission (P< or = 0.004 at all time points), while CD4 cell count was not. Among the 73 antiretroviral-naive patients at baseline, and who were studied for 24 months, KS outcome did not differ between patients who were prescribed PI-containing and PI-sparing regimens. Intercurrent multicentric Castleman's disease was associated with poor outcome after 60 months of follow-up (P< or = 0.0001). Fourteen deaths occurred after a median follow-up of 37.5 months, eight of which were KS related. Suppression of HIV replication appears to be crucial to control KS. Non-PI-based regimens were equivalent to PI-based regimens as regards the clinical and virological outcome of antiretroviral-naive HIV-infected patients with KS.

Adult↗
PubMed2006

Role of brainstem TRH/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding.

Pavlov's pioneering work established that sham-feeding induced by sight or smell of food or feeding in dogs with permanent esophagostomy stimulates gastric acid secretion through vagal pathways. Brain circuitries and transmitters involved in the central vagal regulation of gastric function have recently been unraveled. Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions. TRH injected into the DMN or cisterna magna increases the firing of DMN neurons and gastric vagal efferent discharge, activates cholinergic neurons in gastric submucosal and myenteric plexuses, and induces a vagal-dependent, atropine-sensitive stimulation of gastric secretory (acid, pepsin) and motor functions. TRH antibody or TRH-R1 receptor oligodeoxynucleotide antisense pretreatment in the cisterna magna or DMN abolished vagal-dependent gastric secretory and motor responses to sham-feeding, 2-deoxy-D-glucose, cold exposure and chemical activation of cell bodies in medullary raphe nuclei. TRH excitatory action in the DMN is potentiated by co-released prepro-TRH-(160-169) flanking peptide, Ps4 and 5-HT, and inhibited by a number of peptides involved in the stress/immune response and inhibition of food-intake. These neuroanatomical, electrophysiological and neuropharmacological data are consistent with a physiological role of brainstem TRH in the central vagal stimulation of gastric myenteric cholinergic neurons in response to several vagal dependent stimuli including sham-feeding.

Acetylcholine↗
PubMed2006

Evaluation of eye and skin irritation of arginine-derivative surfactants using different in vitro endpoints as alternatives to the in vivo assays.

Arginine-derivative surfactants constitute a novel class of surfactants, which can be regarded as an alternative to conventional surfactants. Prior to human exposure, it is necessary to assess their irritation potential. The classical in vivo evaluation of the irritancy potential via the Draize test has been extensively criticized. In that regard, a great number of in vitro alternatives have been developed. Erythrocytes were chosen as the target cells for eye irritation assessment and hemolysis and hemoglobin denaturation were selected as appropriate endpoints. For skin irritancy assessment, the keratinocyte cell line NCTC 2544 was used and different in vitro endpoints were measured: two cytotoxicity assays (NRU and MTT) and the synthesis of the proinflammatory cytokine IL-1alpha. The eye and skin Draize tests were also performed for comparative purposes. The results point out that, according to in vivo and in vitro assays, the new arginine-derivative surfactants have lower eye and skin irritation potential than the synthetic surfactant SDS. Furthermore, in vitro methods were also able to detect differences in irritancy among the new surfactants not noticeable by the Draize tests, indicating that in vitro methods can be more sensitive than the in vivo test, offering the opportunity to detect subtle differences in irritancy.

Animal Testing Alternatives↗
PubMed2006

Deficit irrigation and rootstock: their effects on water relations, vegetative development, yield, fruit quality and mineral nutrition of Clemenules mandarin.

Differences between rootstocks, 'Cleopatra' mandarin and 'Carrizo' citrange, in soil-plant water relations and the influence of these factors on vigor, crop yield, fruit quality and mineral nutrition were evaluated in field-grown Clemenules mandarin trees irrigated at 100% of potential seasonal evaporation (ET(c)) (control treatment), or irrigated at 100% ET(c), except during Phases I and III of fruit growth and post-harvest when no irrigation was applied (deficit irrigation (DI) treatment), for 3 years. Differences between rootstocks in plant-soil water relations were the primary cause of differences among trees in vegetative development and fruit yield. After 3 years of DI treatment, trees on 'Cleopatra' showed more efficient soil water extraction than trees on 'Carrizo', and maintained a higher plant water status, a higher gas exchange rate during periods of water stress and achieved faster recovery in gas exchange following irrigation after water stress. The DI treatment reduced vegetative development more in trees on 'Carrizo' than in trees on 'Cleopatra'. Cumulative fruit yield decreased more in DI trees on 'Carrizo' (40%) than on 'Cleopatra' (27%). The yield component most affected by DI in 'Cleopatra' was the number of fruit, whereas in 'Carrizo' it depended on the severity of water stress reached in each phase (severe water stress in Phase I affected mainly the number of fruit, whereas it affected fruit size the most in Phase III). In the third year of DI treatment, water-use efficiency decreased sharply in trees on 'Carrizo' (70%) compared to trees on 'Cleopatra' (30%). Thus, trees on 'Cleopatra' were able to tolerate moderate water stress, whereas trees on 'Carrizo' were more sensitive to changes in soil water content.

Agriculture↗
PubMed2006

CRF1 receptors as a therapeutic target for irritable bowel syndrome.

The characterization of the corticotropin-releasing factor (CRF) family of neuroendocrine regulatory peptides, the cloning and pharmacological characterization of two CRF receptor subtypes (CRF(1) and CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress and the potential involvement of the CRF system in different pathophysiological conditions, including functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and psychopathologies such as anxiety/depression. Compelling pre-clinical data showed that brain CRF administration mimics acute stress-induced colonic responses and enhances colorectal distension-induced visceral pain in rats through CRF(1) receptors. Similarly, peripheral CRF reduced the pain threshold to colonic distension and increased colonic motility in humans and rodents. These observations mimic the manifestations of IBS, characterized by abdominal bloating/discomfort and altered bowel habits. Moreover, CRF-CRF(1) pathways have been implicated in the development of anxiety/depression. These psychopathologies, together with stressful life events, have high comorbidity with IBS, and are considered significant components of the disease. From these observations, CRF(1) receptors have been suggested as a target to treat IBS. Peripherally acting CRF(1) antagonists might directly improve IBS symptoms, as related to motility, secretion and immune response. On the other hand, central actions will be beneficial as to prevent the psychopathologies that co-exist with IBS and as a way to modulate the central processing of stress- and visceral pain-related signals. Here, we review the pre-clinical and clinical data supporting these assumptions, and address the efforts done at a pharmaceutical level to develop effective therapies targeting CRF(1) receptors for functional gastrointestinal disorders.

Animals↗
PubMed2006

[Incontinentia pigmenti: clinical and neuroimaging findings in a series of 12 patients].

OBJECTIVE: To describe the clinical, neuroimaging 51 with magnetic resonance imaging (MRI) and evolutive findings in 12 patients with incontinentia pigmenti (IP). Five patients show cutaneous and neurological lesions and seven only show cutaneous lesions without neurologic or/ and ophthalmologic abnormalities. MATERIAL AND METHODS: Five mothers and seven daughters from four families were studied and followed between 1965 and 2004. The studies consisted of detailed clinical history since birth, physical examination, family history, EEG recordings and MRI studies. In some patients, at least three MRI studies were performed during our follow-up. All patients were followed-up since their first visit until 2004. Including four patients since birth or early infancy. Skin biopsies were obtained from two infants for histological study. RESULTS: MRI studies revealed brain abnormalities in five girls who had neurologic signs associated with the cutaneous lesions of IP. Brain lesions were bilateral in four and unilateral in one. Cerebellar changes were observed only in one case who also showed severe cerebral lesions. The lesions involved cortex, subcortical and deep white matter, ependymal and subependymal zones of one or both cerebral hemispheres. Lesions usually were localized and extended radially to involve all the cerebral parenchyma between ependyma and cortex. Affected areas did not correspond to territories vascularized by any determined artery. The corpus callosum showed generalized or localized atrophy in the five patients who had cerebral hemispheric lesions. Although parenchymal changes were seen in both the T1 and T2 weighted images, these were most evident in the latter. Parenchymal abnormalities were most severe in patients with neonatal severe cutaneous lesions, especially if these were located in the scalp. Cerebral lesions were present from birth or the first months of life and changed little thereafter. The acute appearance and distribution of cerebral lesions always during the neonatal period, associated with scalp lesions in stage 1, suggest an acute inflammatory origin of unknown etiology and of nonprogressive course. Ocular lesions were directly related with cerebral abnormalities. Patients who only had cutaneous lesions without neurologic symptoms showed no MRI abnormalities. CONCLUSIONS: Neuroimaging studies reveals brain lesions only in patients with neurologic disease in this serie. The brain lesions may involve one or both cerebral hemispheres, corpus callosum, and cerebellum. The brain lesions correlate with the neonatal scalp lesions in stage 1, suggests an inflammatory process of unknown etiology and non-progressive course. The appearance and distribution of the cerebral lesions do not follow the territories vascularized by specific arteries. Ocular lesions are observed only in patients with severe cerebral changes. Early onset of cerebral lesions may be the most reasonable explanation for the progressive microcephaly within the first year of life in IP.

Abnormalities, Multiple↗
PubMed2005

Peripheral adrenomedullin inhibits gastric emptying through CGRP8-37 -sensitive receptors and prostaglandins pathways in rats.

The effects of intravenous (iv) adrenomedullin (AM) on gastric emptying were investigated in conscious rats. AM induced a maximal 50% inhibition of gastric emptying at a dose of 1.2 nmol/kg. AM was about two-fold less potent than alpha-calcitonin gene-related peptide (alpha-CGRP), which induced a similar 50% maximal inhibition of gastric emptying at 0.6 nmol/kg. Delayed gastric emptying induced by i.v. AM and alpha-CGRP was prevented by peripheral injection of the selective CGRP1 antagonist, CGRP8-37, and by pretreatment with indomethacin, while not altered by blockade of the sympathetic nervous system with propranolol. These data indicate that peripheral AM inhibits gastric emptying through the interaction with CGRP8-37 -sensitive receptors, likely CGRP1 receptors, and the recruitment of prostaglandin-dependent mechanisms.

Adrenomedullin↗
PubMed2005

[Risk of smallpox, vaccination, bioterrorism].

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

Bioterrorism↗
PubMed2005

[Laboratory diagnosis of mycobacterial infections].

Every 10 seconds, one person in the world dies of tuberculosis (TB). It is estimated that one third of the world's population is latently infected with Mycobacterium tuberculosis. The proportion of multidrug-resistant strains of M. tuberculosis is increasing at an alarming rate in some parts of the world linked in part with the human immunodeficiency virus epidemic. For these reasons, TB remains a major public health problem, both in less-developed countries and in many industrialized countries, with 8-10 million new cases and 2 million deaths yearly in the world. Clinical, radiological and histological signs are not specific for tuberculosis or for other mycobacterial infections and allow only a presumptive diagnosis. In the same way, the tuberculin skin test is useful if the reaction is strong or phlyctenular because this test depends on various factors as previous BCG vaccination, contact or primary infection and host immune responses. The diagnosis of mycobacterial infection is proved only when bacilli are present in biological samples. Nevertheless, only 50% of cases in adults and 30% in infants have a positive bacteriological result. It seems necessary to develop new methods for a rapid and efficient diagnosis to optimize the therapy and the control of the epidemic. Laboratory testing in the mycobacterium field is experiencing more changes today than ever before. Determining what assays will be most useful to the clinician is a challenge, and acceptance of the new technology is under discussion. Progress in future will be linked probably to the progress of the genomic area. However the incidence rate is higher in less-developed countries, it is also important to develop now techniques possible to use in these countries. This review focuses on the current state-of-the-art resources useful for accurate and rapid laboratory diagnosis of mycobacterial infections.

Bacteriological Techniques↗
PubMed2004

CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome.

1. The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF(1)) and 2 (CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF(1) receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2. Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3. Nonselective CRF(1)/CRF(2) antagonists and selective CRF(1) antagonists inhibit exogenous (central or peripheral) CRF- and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF(2) antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4. These findings implicate CRF(1) receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF(1)-dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders.

Animals↗
PubMed2003

[Extracranial and intracranial vascular abnormalities and nevus of Ota in the same family].

We present a 17 year old patient suffering from hemangioma on the left side of his face and neck. The evolution of his disease has been followed-up since he was 8 1/2 months old. His mother has nevus of Ota in the sclera and adjacent zones in both sides. At the age of 8 1/2 months, the patient had an ischemic stroke in the territory of the left middle cerebral artery during the surgical correction of the aortic arch coarctation. The conventional arteriogram performed at 10 months of life showed several malformations of the intracranial and extracranial arteries. At the age of 16 years the cutaneous hemangioma was atrophic and a new angiographic study by magnetic resonance arteriography (MRA) showed all the vascular anomalies with higher objectivity than the conventional arteriography, especially the absence of some arteries and the abnormal position of some others. Moreover it could detect the decrease of the caliber of the intracranial arteries and the disappearance of hemangiomatous malformations even though the patient had not received any treatment for the cutaneous hemangioma. We think that this syndrome, which still has no definite name, has a parallel spontaneous biological process with progressing vascular size during the first months or years of life and, later, the vessels regress slowly but progressively, leading to a small caliber or even the occlusion of the vessels of the cutaneous hemangioma and of the abnormal extracranial and intracranial arteries. At the same time, there is a slow but progressive presence of transdural collateral vascularization of the brain. We do not find any relationship between the hemangiomatous syndrome of the patient and the nevus of Ota of his mother.

Adolescent↗
PubMed2003

[Pain in kidney disease].

There are little data concerning the prevalence of pain and its intensity in the population suffering from kidney diseases. However, according to number of pathologies with a kidney impact, the sequellae of the kidney disease itself and the technology in this area, there is a risk for a high prevalence rate of either acute and/or chronic pain. This can be responsible for some degree of psychologic disturbances as a major impact on the quality of life. Pain management must be a challenge in this field as it may interfere with the kidney disease.

Analgesics, Non-Narcotic↗
PubMed2002

Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in the CRF(2)-mediated animal model whereby the inhibition of gastric emptying of a solid meal in mice by urocortin administered intraperitoneally at time zero is antagonized by the administration of astressin(2)-B but not by antisauvagine-30 at times -3 and -6 h while both peptides are effective when given 10 min before urocortin.

Animals↗
PubMed2002

A role for CCN3 (NOV) in calcium signalling.

AIMS: In animals and humans increased expression of CCN3 (NOV) is detected in tissues where calcium is a key regulator, such as the adrenal gland, central nervous system, bone and cartilage, heart muscle, and kidney. Because the multimodular structure of the CCN proteins strongly suggests that these cell growth regulators are metalloproteins, this study investigated the possible role of CCN3 in ion flux and transport during development, control of cell proliferation, differentiation, and pathobiology. METHODS: The isolation of CCN3 partners was performed by means of the two hybrid system. Yeasts were cotransfected with an HL60 cDNA library fused to the transactivation domain of the GAL4 transcription factor, and with a plasmid expressing CCN3 fused to the DNA binding domain of GAL4. Screening of the recombinant clones selected on the basis of leucine, histidine, and tryptophan prototrophy was performed with a beta-galactosidase assay. After the interaction between CCN3 and its putative partners was checked with a GST (glutathione S-transferase) pull down assay, the positive clones were identified by cloning. To establish whether the CCN3 protein affected calcium ion flux, a dynamic imaging microscopy system was used, which allowed the fluorometric measurement of the intracellular calcium concentration. The proteins used in the assays were GST fused with either CCN3 or CCN2 (CTGF) and GST alone as a control. RESULTS: The two hybrid system identified the S100A4 (mts1) calcium binding protein as a partner of CCN3 and the use of the GST fusion proteins showed that the addition of CCN3 and CCN2 to G59 glioblastoma and SK-N-SH neuroblastoma cells caused a pronounced but transient increase of intracellular calcium, originating from both the entry of extracellular calcium and the mobilisation of intracellular stores. CONCLUSIONS: The interaction of CCN3 with S100A4 may account, in part, for the association of CCN3 with carcinogenesis and its pattern of expression in normal conditions. The increased intracellular calcium concentrations induced by CCN3 and CCN2 both involve different processes, among which voltage independent calcium channels might be of considerable importance in regulating the calcium flux associated with cell growth control, motility, and spreading. These observations assign for the first time a biological function to the CCN3 protein and point out a broader role for the CCN proteins in calcium ion signalling.

Amino Acid Sequence↗
PubMed2002

Andes virus associated with hantavirus pulmonary syndrome in northern Argentina and determination of the precise site of infection.

Hantavirus pulmonary syndrome (HPS) has been documented in the Salta and Jujuy provinces of northern Argentina since 1991 and 1997, respectively, accounting for almost 50% of the cases of HPS reported in this country. Andes (AND) virus, specifically the AND virus Nort lineage, was previously associated with human disease in this region. Genetic analysis of viral medium RNA segments obtained from 18 HPS cases showed the existence of three AND virus Nort sublineages co-circulating in these two provinces. They showed a nucleotide sequence diversity of up to 11.1% between the sublineages. The putative site of infection of one of these cases (Sal3/97) was determined. A 100% nucleotide sequence identity was observed between the viral sequence found in patient Sal3/97 and in two virus-positive Oligoryzomys chacoensis captured in the same place where the case lived and worked. These results indicated the putative site of infection and identified this rodent species as the source of infection.

Argentina↗
PubMed2001

Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity.

Lipoprotein lipase (LPL) in the arterial wall has been proposed to enhance the retention of apoB-containing lipoproteins, an early event in atherosclerosis. As the neointima is considered the primary site of lipid accumulation in atherogenesis, the arterial expression and location of LPL was investigated in distinct experimental models of neointimal formation in normolipidemic rabbits and rats. Neointima elicited by balloon aortic denudation or raised beneath an anatomically intact endothelial layer by placing a silastic collar around the common carotid artery, both showed a striking LPL immunostaining that mostly co-localized with neointimal smooth muscle cells. Besides, increased LPL protein and mRNA in deendothelialized aortas was demonstrated by Western and Northern blot analysis, respectively, suggesting an enhanced expression of LPL in injured arteries. It was concluded that LPL is increased in neointima developed in either denuded vessels or arteries with a preserved endothelium, a finding which suggests that LPL abundance may be an attribute of the neointima, whatever the stimulus that promotes its formation. On the basis of former evidence concerning the role of LPL in lipid retention, this study provides a possible explanation for the injury-induced vessel susceptibility to atherosclerosis, and the particular proneness of the neointimal layer to lipid accretion.

Animals↗