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Biomedical subjects

J M Carrascosa

Publications and source records attributed to J M Carrascosa.

At least 19 recordsLinked to original sources
PubMed2006

A prospective evaluation of the cost of psoriasis in Spain (EPIDERMA project: phase II).

OBJECTIVE: To estimate the direct and indirect costs related to psoriasis in Spain. METHODS: We performed a 12-month, multicentre, prospective longitudinal and observational study. Overall expense of care was assessed as the sum of direct and indirect costs. RESULTS: A total of 797 patients with varying demographics and different degrees of severity of psoriasis were included in the study. The mean total cost of psoriasis, including direct and indirect items, was 1,079 euro per patient and year. The major sources of expenditure were prescription drugs (46.6%), followed by medical activities (34.5%). Mean costs in patients with moderate and severe psoriasis were approximately 1.5 and 2.5 times higher than in those with mild psoriasis, respectively. CONCLUSIONS: In Spain, psoriasis is associated with substantial costs both to the National Health System and to the patients.

Adolescent↗
PubMed2005

Differential gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat adipose tissue.

The insulin receptor (IR) occurs as two alternatively spliced isoforms, IR-A (exon 11-) and IR-B (exon 11+), which exhibit functional differences and are expressed in a tissue-specific manner. The IR substrate (IRS) proteins 1, 2 and 3 also differ in function and tissue distribution. Here we show the differential gene expression of IRs and IRSs in several rat target tissues of insulin action. IR-B is significantly higher than IR-A in epididymal white adipose tissue and adipogenesis induces a shift in the alternatively spliced species of IR from the A to the B isoform. Moreover, since aging in the rat is associated with the development of insulin resistance we looked for alterations of expression of these proteins in adipocytes from old rats. Our results reveal that there is a specific decrease in the expression of the IR-B isoform, as well as both mRNA and protein levels of IR, IRS-1 and IRS-3 being significantly decreased, in epididymal adipose tissue from old compared with adult rats. It is concluded that the down-regulation of early components of the insulin transduction pathway in a primary insulin target tissue could be related to the insulin resistance of aging.

Adipose Tissue↗
PubMed2003

Alternative splicing generates a novel non-secretable resistin isoform in Wistar rats.

Resistin is a secreted adipose tissue hormone that belongs to the resistin-like molecule family. We report here a new alternatively spliced isoform of the rat resistin gene, named S-resistin (short resistin), detected in adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). A comparison of this cDNA variant and genomic sequences indicates the lack of the second exon containing the secretory consensus signal. Both cDNAs, resistin and S-resistin, were carboxy-tagged with FLAG epitope and transiently expressed in cultured cell lines. While the resistin-FLAG construct gives the expected pattern for a secretion protein, the S-resistin-FLAG construct yielded a predominant nuclear staining. These results indicate that this splicing event regulates the fate and probably the function of the mature protein.

3T3-L1 Cells↗
PubMed2002

Ageing increases SOCS-3 expression in rat hypothalamus: effects of food restriction.

Aged Wistar rats are characterized by leptin and insulin resistance. The expression of SOCS-3 in hypothalamus increases with ageing. Food restriction during 3 months decreases obesity Lee index in aged rats with respect to their ad libitum aged-mates and brings serum leptin concentrations to values close to those of young rats. Food restriction partially reverts the increases in SOCS-3 mRNA levels associated with ageing. These results suggest that SOCS-3 may be a mediator of hypothalamic leptin resistance in the aged Wistar rat and that the hyperleptinemia associated with ageing is, at least in part, responsible for the increase of SOCS-3 expression in hypothalamus.

Aging↗
PubMed2002

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats.

AIMS/HYPOTHESIS: Ageing is associated with insulin and leptin resistance in mammals. These alterations might be caused by the increased adiposity associated with ageing, by ageing alone or both. We studied whether leptin resistance occurs at the central level in the Wistar rat and we aimed to discriminate between the effects of ageing from those of the increased adiposity associated with ageing. METHODS: Leptin was infused intracerebroventricularly at a constant rate in young adult, old and old Wistar rats fasted for 3 months, using osmotic pumps. The effects on body weight, daily food intake, Lee index, adiposity and serum leptin values were analysed. The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied. RESULTS: Leptin decreased daily food intake and body weight in young and old Wistar rats. With a dose of 10 microg/day similar responses were obtained in young and old rats but with a dose of 0.2 microg/day, only young rats showed decreases in these parameters. Food-restriction in old rats lowered adiposity and serum leptin to values close to those of young rats, recovered responsiveness to i.c.v. administration of leptin at the dose of 0.2 microg/day and increased leptin receptor expression in the hypothalamus. CONCLUSION/INTERPRETATION: Our data show that old Wistar rats have a decreased response to leptin at the central level. Food-restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing.

Adipose Tissue↗
PubMed2002

Activation of MAP kinase by insulin and vanadate in adipocytes from young and old rats.

Vanadate has insulin-like effects in adipocytes without stimulating insulin receptor kinase activity. However, it activates IRS-1 associated PI 3-kinase, suggesting that it mimics insulin effects by stimulating signaling elements downstream of PI 3-kinase. Here we analysed the stimulation of MAPK by insulin and vanadate and observed that both elicit a rapid 3.5-4 fold activation which is abolished by wortmannin and PD98059. Simultaneous addition of insulin and vanadate does not result in an additive effect neither on MAPK nor in MEK. Whereas insulin action is transient, vanadate stimulation lasts up to 20 min. In insulin-resistant adipocytes from old rats, insulin stimulates poorly MAPK, whereas a normal activation is achieved with vanadate. We conclude that: (a) insulin and vanadate use a common signaling pathway from PI 3-kinase to MEK and MAPK; (b) vanadate but not insulin, elicits a sustained activation of both enzymes; (c) this pathway is functional in old rat adipocytes.

Adipocytes↗
PubMed2001

Effects of chronic treatment with acarbose on glucose and lipid metabolism in obese diabetic Wistar rats.

AIMS: The effect of chronic treatment with acarbose on fasting plasma glucose, insulin, triglyceride, cholesterol and free fatty acid (FFA) concentrations, as well as on the glucose and insulin excursions during oral glucose tolerance test (OGTT), in obese diabetic Wistar (WDF) rats was investigated. METHODS: Forty-five mature male WDF rats were randomly distributed to one of the three treatment groups (no acarbose, 20 mg and 40 mg of acarbose/100 g of chow, respectively). After 3.5, 7.5 and 11.5 months, animals were tested for glucose tolerance by means of an OGTT, and their respective metabolic profiles were determined. Control determinations were done in obese and age-matched lean animals before the start of the trial. RESULTS: The WDF rats exhibit higher body weight and fasting blood glucose, insulin, triglyceride and cholesterol concentrations compared to lean animals. Moreover, they show marked glucose intolerance as indicated by the glucose and insulin excursions during OGTT. Interestingly, in both treated and untreated animals, a reversion of the hyperglycaemic state as well as an improvement of the glucose tolerance is observed. However, whereas in the group receiving no acarbose this is accounted for by dramatic increases in fasting plasma insulin concentrations and insulin secretion during OGTT (as indicated by the DeltaInsulin area), in rats treated with acarbose the reversion of the diabetic state takes place without increments in hormone concentration. In addition, rats treated with acarbose for 3.5 and 7.5 months show lower plasma triglyceride and FFA concentrations, and the same was observed for cholesterol at the highest dosage of the drug. CONCLUSIONS: Chronic treatment with acarbose of WDF rats improves the glycaemic and lipidic control as well as the glucose tolerance, with a lower demand of pancreatic insulin than in untreated rats. This data suggests that the long-term modulation of glucose and insulin excursions after meals improves the insulin sensitivity in this rat strain.

Acarbose↗
PubMed2001

Decreased leptin uptake in hypothalamic nuclei with ageing in Wistar rats.

Leptin interacts with specific receptors in hypothalamic nuclei and modulates energy balance. Growing evidence has shown the association of obesity and hyperleptinaemia with non-insulin-dependent diabetes mellitus and insulin resistance. The aged Wistar rat shows peripheral insulin resistance in the absence of obesity and alterations of glucose homeostasis. However, it is not known whether, in these animals, the leptin action is altered. Here we studied the effect of ageing on plasma leptin concentration and the ability of hypothalamic nuclei to capture i.c.v.-injected digoxigenin-labelled leptin. Our data indicate that 24-month-old animals are hyperleptinaemic. However, daily food intake was greater in old animals, suggesting that they are leptin resistant. Leptin uptake in the hypothalamus was reduced in old rats. This uptake was a receptor-mediated process as demonstrated by displacement. Leptin accumulation in hypothalamic nuclei was partially colocalized with neuropeptide Y fibres. Immunohistochemical and western blot analyses showed a lower amount of the long form of leptin receptors in the hypothalamus of aged rats. Analysis by RT-PCR also demonstrated a decreased expression of leptin receptor mRNA in old animals. We conclude that the lower leptin uptake may be explained, at least in part, by a decreased amount of receptors in hypothalamic neurones of the aged rats.

Aging↗
PubMed2000

An immunohistopathologic study in cutaneous necrotizing vasculitis.

In order to investigate the importance of timing in the immunophenotypical characteristics of the inflammatory infiltrate and in the adhesion molecules expression in cutaneous necrotizing vasculitis (CNV) we carried on an immunohistopathologic study. An avidin-biotin-streptavidin peroxidase technique was performed on 21 lesional skin biopsy specimens obtained sequentially at 0 to 24, 72 and 120 hours from seven patients with a CNV presenting as palpable purpura. A panel of monoclonal antibodies specific for inflammatory cells (T lymphocytes, polymorphonuclear leukocytes, macrophages, dendritic cells) and different adhesion molecules (E-selectin, ICAM-1, VCAM-1, LFA-1, VLA-4) was used. Moreover, HECA-450 monoclonal antibody was used to identify cutaneous lymphocyte antigen (CLA) in the inflammatory infiltrate. In all cases, polymorphonuclear leukocytes predominated in the early phase of CNV and their number decreased significantly with time (p = 0.0001). The T lymphocytes were present from the beginning and their number remained stable or increased slightly in time (p = 0.1), thus becoming predominant in the perivascular infiltrate in older lesions. Macrophages were scattered on interstitium since the early phase and they showed a time-dependent increase (p = 0.0003). E-selectin (ELAM-1) expression was detected at the first biopsy and it decreased depending on the age of the evolving vasculitis (p = 0.0033). The expression of CLA decreased also with time in 5 of the 7 cases (p = 0.0001). Our study supports the existence of an unique histopathologic pattern in CNV, in which the inflammatory infiltrate varies with time at the expense of the number of polymorphonuclear cells and macrophages.

Antibodies, Monoclonal↗
PubMed1998

Vanadate fully stimulates insulin receptor substrate-1 associated phosphatidyl inositol 3-kinase activity in adipocytes from young and old rats.

Vanadate stimulates adipocyte 2-deoxyglucose transport and GLUT-4 translocation to the membrane through an insulin receptor-independent but wortmannin-inhibitable pathway. Vanadate stimulates PI 3-kinase in anti-IRS-1 immunoprecipitates and the binding between IRS-1 and the p85alpha subunit of PI 3-kinase. In insulin-resistant adipocytes from old rats vanadate fully stimulates IRS-1-associated PI 3-kinase, but partially activates glucose uptake. We conclude that: (a) vanadate stimulates 2-deoxyglucose uptake using a pathway that converges with that of insulin at the level of PI 3-kinase; and (b) adipocytes from old rats are defective in the insulin pathway at steps located both upstream and downstream of PI 3-kinase.

Adipocytes↗
PubMed1998

Changes in the kinase activity of the insulin receptor account for an increased insulin sensitivity of mammary gland in late pregnancy.

Mammary gland is an organ that undergoes cycles of growth, differentiation, and function during pregnancy and lactation. Although it is known that the gland enhances its sensitivity to insulin during lactation, it remains to be investigated whether this increased sensitivity develops during pregnancy and which are the molecular mechanisms underlying such a change. To address this issue, virgin and late-pregnant rats were subjected to a continuous infusion with 50% glucose for 72 h to produce a prolonged hyperinsulinemic-euglycemic condition. Insulin sensitivity in mammary gland was determined as the glucose utilization index by using 2-[3H]-deoxyglucose. Furthermore, binding characteristics and kinase activity were studied by means of both [125I]insulin binding and in vitro phosphorylation studies with insulin receptors partially purified from mammary gland. Whereas the glucose utilization index in mammary gland from nonpregnant rats remained unaffected by hyperinsulinemia, glands from pregnant rats displayed a high insulin-dependent glucose uptake. This effect was not paralleled by changes in the binding characteristics of insulin to the high-affinity receptor, suggesting that the high insulin sensitivity of mammary gland in pregnancy is not accounted for by changes at the level of hormone-receptor interaction. Autophosphorylation studies showed that insulin-stimulated kinase activity of insulin receptors from mammary gland was 6- and 20-fold higher in pregnant than in virgin animals under normo- and hyperinsulinemic conditions, respectively. Moreover, insulin dose-response curves revealed that the efficacy of insulin to stimulate kinase activity of the insulin receptor was markedly higher in pregnant than in virgin rats, whereas its potency (ED50 approximately 15 nM) was not changed. These data, therefore, show that mammary glands develop increased insulin sensitivity during late pregnancy, caused by an augmented kinase activity of the insulin receptor.

Animals↗
PubMed1998

Papular acrodermatitis of childhood related to poxvirus and parvovirus B19 infection.

Papular acrodermatitis of childhood (Gianotti-Crosti syndrome) is considered an unspecific cutaneous pattern related to an increasing number of infectious diseases. We report two cases of Gianotti-Crosti syndrome, one of which occurred in the setting of parvovirus B19 primary infection and the other followed poxvirus infection. Parvovirus B19 and poxvirus may represent new causative agents of Gianotti-Crosti syndrome.

Acrodermatitis↗
PubMed1997

Sequential combined therapy with thalidomide and narrow-band (TL01) UVB in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic disease of which treatment choices are limited. Among them, thalidomide and phototherapy have been used with satisfactory results. Unfortunately, the possibility of side effects limits their use. OBJECTIVE: To evaluate the efficacy of a sequential combined treatment with thalidomide and ultraviolet B (UVB) therapy in order to minimize side effects and, thus, making possible a long-term treatment. METHODS: A prospective open trial combining thalidomide as initial therapy followed by narrow-band UVB (TL01) irradiation until complete or almost complete remission of the disease was achieved. RESULTS: An excellent response was obtained after an average of 12 weeks of thalidomide therapy and 32 UVB courses. CONCLUSIONS: Sequential combined therapy with thalidomide and narrow-band UVB therapy could improve the management of prurigo nodularis with minimal side effects, although it should probably be reserved to men and women over 50 years of age.

Administration, Oral↗
PubMed1997

In vivo insulin-dependent glucose uptake of specific tissues is decreased during aging of mature Wistar rats.

Aging has been associated with peripheral insulin resistance in both humans and rats. However, the specific tissues that become insensitive to insulin before glucose homeostasis is altered remain to be elucidated. In the present work we studied the glucose metabolic index of a number of tissues known to be insulin sensitive in 3- and 24-month-old Wistar rats by measuring 2-deoxy-D-[1-3H]glucose uptake both under euglycemic-hyperinsulinemic conditions and in the basal state. Analysis of the glucose infusion rate to maintain normoglycemia during the clamp confirmed that the old rats show overall insulin resistance at both saturating and subsaturating insulin concentrations. The maximal response of glucose uptake to insulin as well as insulin sensitivity in red and white quadriceps were unaltered in old rats. In contrast, glucose uptake by soleus and diaphragm was poorly stimulated in old animals, and a marked decrease in insulin sensitivity was observed in both tissues. In heart, only the sensitivity to the hormone, not the maximal response, was impaired in old rats. In white adipose tissue, no significant stimulation was detected. We conclude that during aging in Wistar rats and before fasting plasma insulin and glucose levels become altered, specific tissues develop insulin resistance, whereas other remain insulin sensitive. We postulate that fat tissue plays a qualitative important role in eliciting the insulin resistance in old animals. Due to the metabolic characteristics of the aged Wistar rat, the changes reported might reflect what occurs in nonobese elderly humans, nongenetically committed to develop type 2 diabetes.

Adipose Tissue↗
PubMed1995

Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

Partially purified liver insulin receptors from full-term pregnant rats show decreased autophosphorylation rates if compared with receptors from virgins. We studied the molecular mechanism of this phenomenon, looking at possible structural and functional changes of several domains. The ATP-binding domain seems to be unaltered in receptors from pregnant rats since Km for ATP was similar to that observed in virgins. In contrast, the Vmax. is decreased some 45%, suggesting changes in the kinase domain. Truncation of a fragment of 10 kDa from the C-terminal tail does not normalize the kinase activity in receptors from pregnant rats, suggesting that this domain is not involved in the inhibitory regulation. Treatment with alkaline phosphatase increases the [32P]Pi incorporation into receptors from pregnant rats; however, the autophosphorylation remains lower than that observed in virgin rats. Tryptic phosphopeptide maps of phosphorylated receptors show that the same phosphopeptides are present in receptors from virgin and pregnant rats. However, the progression through the autoactivation cascade in the kinase domain is impaired in receptors from pregnant rats. Differences in the cleavage by trypsin at the two alternative sites in the kinase domain were observed, indicating possible structural changes in receptors from pregnant rats that could be related to the impairment of the autoactivation cascade. Integrity of the alpha- and beta-subunits, as well as differential expression of the two receptor isotypes, were shown to be unaltered. We conclude that (1) the decreased autophosphorylation rate of the liver insulin receptor from pregnant rats is associated with the impairment of its autoactivation cascade, probably as a consequence of the basal Ser/Thr phosphorylation; and (2) the inhibition of the autoactivation cascade does not account for the overall inhibition of autophosphorylation observed in receptors from pregnant rats.

Adenosine Triphosphate↗