PubMed Health⌕ Search

Biomedical subjects

F Martín

Publications and source records attributed to F Martín.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effects of calcium buffering on glucose-induced insulin release in mouse pancreatic islets: an approximation to the calcium sensor.

1. The properties of the calcium sensor for glucose-induced insulin secretion have been studied using cell-permeant Ca2+ buffers with distinct kinetics and affinities. In addition, submembrane cytosolic Ca2+ distribution has been modelled after trains of glucose-induced action potential-like depolarizations. 2. Slow Ca2+ buffers (around 1 mmol l-1 intracellular concentration) with different affinities (EGTA and Calcium Orange-5N) did not significantly affect glucose-induced insulin release. Modelling showed no effect on cytosolic Ca2+ concentrations at the outermost shell (0.05 microm), their effects being observed in the innermost shells dependent on Ca2+ affinity. 3. In contrast, fast Ca2+ buffers (around 1 mmol l-1 intracellular concentration) with different affinities (BAPTA and Calcium Green-5N) caused a 50 % inhibition of early insulin response and completely blocked the late phase of glucose-induced insulin response, their simulations showing a decrease of [Ca2+]i at both the inner and outermost shells. 4. These data are consistent with the existence in pancreatic beta-cells of a higher affinity Ca2+ sensor than that proposed for neurons. Moreover, these data are consistent with the proposed existence of two distinct pools of granules: (i) 'primed' vesicles, colocalized with Ca2+ channels and responsible of the first phase of insulin release; and (ii) 'reserved pool' vesicles, not colocalized and responsible for the second phase.

Animals↗
PubMed1999

Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer.

Raised serum levels of interleukin 6 (IL-6) have been described in cancer patients. This cytokine mediates the acute phase response and has been also involved in the pathogenesis of cancer cachexia. The objectives of the present study were: (1) to determine the relationships of IL-6 and other cytokines with neoplasia extension, acute phase response and nutritional status, in lung cancer patients; and (2) to establish the prognostic value of serum cytokine levels. A prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly diagnosed lung cancer patients. Nutritional status was assessed objectively. Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were determined. Increased IL-6 levels were related to extensive disease, impaired performance status, enhanced acute phase response and malnutrition. Raised serum IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase response and low IFN-gamma were all related to a shorter survival. When assessed by a multivariate analysis, IL-6 kept its independent prognostic value together with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is increased in lung cancer patients, enhances the acute phase response in them, and is correlated with poor nutritional status, impaired performance status and shorter survival.

Acute-Phase Reaction↗
PubMed1999

Impact of the American Diabetes Association diagnosis criteria on high-risk Spanish population. IGT Research Group. Impaired glucose tolerance.

To research into the impact of the new American Diabetes Association (ADA) diagnostic criteria on high risk Spanish population, two cross-sectional studies involving seven primary health care centers in Catalonia (Spain) were revised. Individuals aged > 40 years with any major risk factor for diabetes were screened according to the World Health Organization (WHO) rules using a 75 g oral glucose tolerance test to measure fasting plasma glucose (FPG) and 2 h plasma glucose. The changes on diabetes prevalence and on epidemiological characteristics were evaluated applying the ADA criteria on the basis of FPG alone. A total of 970 individuals, 453 males (46.7%), mean age 59 years and mean body mass index (BMI) 30.6 kg/m2 were screened. Among the 459 diabetic subjects according to either the WHO or the ADA criteria, 314 (68.4%) were classified as having diabetes with respect to both sets of criteria (WHO and ADA). The overlap between impaired glucose tolerance (WHO) and impaired fasting glucose (ADA) diagnoses was 20.7%. Using the ADA criteria results in a decrease of the prevalence of diabetes by 1.5% (95% confidence interval (CI) = -2.2 to -0.8%). No changes in the diabetic phenotype (age, sex and BMI) were found. Impaired fasting glucose prevalence was 18.4% (95% CI = 16-21%). Overall concordance in terms of crude and weighted kappa-value was only acceptable (kappa = 0.51 and kappa = 0.61, respectively). To apply the new ADA diagnostic criteria on high risk Spanish population evidenced a decrease on diabetes prevalence. Nevertheless, the change of criteria undervalued the risk of postprandial hyperglycaemia related to impaired glucose tolerance.

Adult↗
PubMed1999

Mechanisms of glucose hypersensitivity in beta-cells from normoglycemic, partially pancreatectomized mice.

Increased beta-cell sensitivity to glucose precedes the loss of glucose-induced insulin secretion in diabetic animals. Changes at the level of beta-cell glucose sensor have been described in these situations, but it is not clear whether they fully account for the increased insulin secretion. Using a euglycemic-normolipidemic 60% pancreatectomized (60%-Px) mouse model, we have studied the ionic mechanisms responsible for increased beta-cell glucose sensitivity. Two weeks after Px (Px14 group), Px mice maintained normoglycemia with a reduced beta-cell mass (0.88 +/- 0.18 mg) compared with control mice (1.41 +/- 0.21 mg). At this stage, the dose-response curve for glucose-induced insulin release showed a significant displacement to the left (P < 0.001). Islets from the Px14 group showed oscillatory electrical activity and cytosolic Ca2+ ([Ca2+]i) oscillations in response to glucose concentrations of 5.6 mmol/l compared with islets from the control group at 11.1 mmol/l. All the above changes were fully reversible both in vitro (after 48-h culture of islets from the Px14 group) and in vivo (after regeneration of beta-cell mass in islets studied 60 days after Px). No significant differences in the input resistance and ATP inhibition of ATP-sensitive K+ (K(ATP)) channels were found between beta-cells from the Px14 and control groups. The dose-response curve for glucose-induced MTT (C,N-diphenyl-N''-4,5-dimethyl thiazol 2 yl tetrazolium bromide) reduction showed a significant displacement to the left in islets from the Px14 group (P < 0.001). These results indicate that increased glucose sensitivity in terms of insulin secretion and Ca2+ signaling was not due to intrinsic modifications of K(ATP) channel properties, and suggest that the changes are most likely to be found in the glucose metabolism.

Adenosine Triphosphate↗
PubMed1999

[Atrial standstill and rheumatic mitral valvulopathy].

Atrial standstill is a very rare form of bradyarrhythmia and consists of a transitory or permanent loss of the electrical and mechanical activity of the atria. We report a series of 8 patients, all of them with rheumatic valve disease (5 of them with a prosthetic valve) with symptomatic bradyarrhythmia secondary to atrial standstill, requiring an implantable pacemaker.

Aged↗
PubMed1998

[The selective detection of glucose intolerance and diabetes in primary care. The ITG-Reus (Tarragona) Study. The Glucose Intolerance Research Group].

OBJECTIVE: To investigate the number of people with intolerance to glucose (ITG) and undiagnosed diabetes (DM) among primary care users at risk. DESIGN: Prospective, selective urban polling of a representative sample of those attended in the city of Reus (88,000 inhabitants). SETTING: Two base health areas (10 Primary Care teams) with an approximate overall reference population of 45,000 inhabitants. PATIENTS AND OTHER PARTICIPANTS: Clinical and examination data were recorded with a pre-designed questionnaire. Diagnoses were established by means of base glycaemia (mmol.l-1 or a 75 g glucose oral overload (0 and 120 minutes) for users over 40 with some Diabetes risk factor. Further tests were HbA1C (%), base peptide-C (nmol.l-1, total cholesterol, HDL cholesterol, triglycerides (mmol.l-1 and 24-hour microalbuminuria (mg). MEASUREMENTS AND MAIN RESULTS: After a year included in the survey, the data of 345 people were evaluated: 151 men, 58 years old (95% CI, 57-60) and BMI of 30.8 (30.3-31.4), with 197 diagnoses (57.1%) of normal tolerance to glucose (52-62%). 82 (23.8%) of ITG (20-28%) and 66 (19.1%) of undiagnosed DM (15-23%). Significant differences between the three were detected in age (56/61.5/61.7 years, p < 0.001), proportion of men (38/50/53%, p < 0.05), diagnosis of hypertension (40.6/59.8/53%, p < 0.01), previous anomaly in tolerance 28.4/45.1/51.5%; p < 0.001), HbA1C (4.6/4.9/5.4; p < 0.001), systolic pressure (140.5/143.6/151 mmHg, p < 0.007). Triglycerides (1.4/1.6/2.1, p < 0.001) and microalbuminuria (16/29/51, p < 0.001). Base peptide-C (3.5/3.8/3.8) showed no statistical differences. CONCLUSIONS: Selective detection in primary care amply exceeds opportunist detection in identifying patients with ITG who might be susceptible to preventive measures. In function of the intolerance level, from normality through to DM, statistical differences were found in HbA1C, systolic pressure, Triglyceridaemia and urinary excretion of albumin. These were not extendable to the rest of the lipid profile or to endogenous insulinaemia.

Adult↗
PubMed1998

Alveolar-interstitial pneumopathy after gold-salts compounds administration, requiring mechanical ventilation.

The pulmonary toxicity of gold salts is an uncommon cause of life-threatening respiratory failure. Currently, patients who suffer from this do not need mechanical ventilation, and the toxicity can be difficult to diagnose when it occurs in patient with an illness producing pulmonary manifestations. We report a case of severe respiratory failure due to gold salt toxicity in a patient suffering from rheumatoid arthritis requiring mechanical ventilation. At such a time, the poor respiratory function makes some diagnostic procedures harmful. The diagnosis can be made after the exclusion of other causes of rheumatoid lung when the patient's poor respiratory status precludes invasive exploration. The clinical findings, radiological features, and results of pulmonary function tests may be enough to diagnose gold-related pneumopathy. This avoids the need for bronchoscopic examination or transfer of the patient for computed tomography. Attention must be paid to this complication because the outcome and functional prognosis are better when pulmonary involvement is gold related: in our case steroid therapy was life-saving and induced complete recovery of the lung damage.

Aged↗
PubMed1998

Intracellular diadenosine polyphosphates: a novel second messenger in stimulus-secretion coupling.

In pancreatic beta-cells, stimulatory glucose concentrations increase cytosolic diadenosine polyphosphates ([ApnA]i) to concentrations sufficient to block ATP-sensitive K+ (KATP) channels. High-performance liquid chromatography and patch clamp techniques were used to study the metabolic pathways by which pancreatic beta-cells synthesize ApnA and the mechanism through which ApnA inhibit KATP channels. ApnA show a glucose- and time-dependent cytosolic concentration increase parallel, though 30- to 50-fold higher, to changes observed in adenine nucleotides. Other fuel secretagogues, leucine and 2-ketoisocaproate, raise [ApnA]i as efficiently as 22 mM glucose. Blockade of glycolysis or Krebs cycle decreases glucose-induced [ApnA]i. No significant increase in cytosolic ApnA concentrations is induced by nonnutrient secretagogues or nonmetabolizable nutrient secretagogues. Inorganic pyrophosphatase inhibition with sodium fluoride blocks 22 mM glucose-induced [ApnA]i increase. ApnA inhibition of KATP channel resembles that of ATP in efficacy, but shows clear functional differences. Unlike ATP, Ap4A does not restore channel activity after rundown. Furthermore, these compounds do not compete with each other for the same site. These features suggest a prominent role for Ap4A in beta-cell function, comparable to ATP. We conclude that nutrient metabolism through pyrophosphatase activation is necessary to induce ApnA synthesis, which in turn constitutes a new, ATP-independent, metabolic regulator of KATP channel activity.

Adenosine↗
PubMed1998

[Outbreak of nosocomial diarrhea by Clostridium difficile in a department of internal medicine].

BACKGROUND: Clostridium difficile (DCD) is the main etiologic agent of nosocomial diarrhea of infectious origin. Most of the cases of DCD have been detected in a hospital environment. PATIENTS, MATERIAL AND METHODS: From October to November 1996 five cases of nosocomial diarrhea were detected with the presence of the toxin A of Clostridium difficile being observed in the stools. These patients were compared with a group of 19 patients without diarrhea (controls) who were admitted to the same ward during the same period as the patients with DCD. RESULTS: The hospital stay of the cases was greater (25 +/- 8 days) than that of the controls (14 +/- 10 days; p < 0.05). One hundred percent of the cases received antibiotics during admission (2 +/- 1.2 antibiotics per patient), versus 68% of the controls (1.1 +/- 0.9 antibiotics per patient, p > 0.05). The length of antibiotic treatment prior to the onset of the symptoms was 8 +/- 3 days (range 7-11 days). The type of antibiotic administered was similar in both groups. More of the cases with DCD (60%) had vesicle catheterization than the controls (11%, p < 0.05). All the patients with DCD presented abdominal pain and several liquid stools per day without blood or pus (3.2 +/- 0.45 stools per patient) and 2 (40%) fever. The mean length of diarrhea was 5.6 +/- 3.6 days. The serum albumin concentration on the first day of admission was significantly lower in the cases of DCD (2.9 +/- 0.4 mg/dl) than in the controls (3.3 +/- 3.4 mg/dl, p < 0.05). All the cases received antibiotic treatment for Clostridium difficile (oral metronidazol or vancomycin) with good clinical evolution. CONCLUSIONS: The patients with DCD had more often had vesicle catherization and presented a lower serum albumin concentration than the controls.

Adult↗
PubMed1997

Cytosolic Ca2+ gradients in pancreatic islet-cells stimulated by glucose and carbachol.

Digital image analysis was employed to resolve the spatial differences in distribution of cytosolic free Ca2+ concentrations ([Ca2+]i) in mouse pancreatic islet-cells stimulated with glucose and carbachol. Using Indo-1 loaded mouse islet-cells, we have demonstrated that glucose induces steep spatial gradients of [Ca2+]i in isolated mouse islet-cells. Furthermore, the largest [Ca2+]i increase was always spatially restricted to a region just beneath the plasma membrane. Low concentrations of carbachol (0.6 microM) induced steep spatial gradients of [Ca2+]i which originated from the center of the cells. However, 10 microM carbachol increased [Ca2+]i to high levels collapsing the [Ca2+]i gradients in the center of the cells. Different patterns of [Ca2+]i oscillations were observed between dissociated pancreatic islet-cells and mouse pancreatic islets when challenged with 11 mM glucose. Under these conditions we could identify cells within the islet which oscillate with the same pattern as the whole islet. We postulate that "initiators" of insulin release, as glucose, induce greater [Ca2+]i increases at exocytotic sites than those induced by "potentiators", as carbachol.

Animals↗
PubMed1997

Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia.

The immunophenotypic characteristics of both bone marrow (BM) and peripheral blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic mast cell disease (SMCD), were sequentially analyzed by flow cytometry using direct immunofluorescence. Analysis was carried out at diagnosis, during clinical response induced by interferon alfa-2h/prednisone therapy, and later at relapse. Our results show that together with the CD117 and IgE characteristic markers, at diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45, CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54 although at a lower level. PB MC displayed similar immunophenotypic characteristics although they had a lower expression of CD11c, CD25, CD33, CD63, CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were weakly positive for CD41a and CD61. Sequential studies showed decreased numbers of both BM and PB MC during clinical response associated with a higher expression of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had become negative at the last follow-up study. In addition, an increased proportion of S-phase MC was observed at relapse. These findings suggest that the assessment of the quantitative expression of cell-adhesion molecules and growth-factor receptors together with cell cycle studies of mast cells could be of value for monitoring therapy and predicting clinical outcome in aggressive SMCD.

Aged↗
PubMed1997

Regulation of pancreatic beta-cell electrical activity and insulin release by physiological amino acid concentrations.

The mutual enhancement of insulin release by glucose and amino acids is not clearly understood. In this study, the effects on electrical activity and insulin release of a mixture of amino acids and glucose at concentrations found in fed (aaFD) and fasted (aaFT) animals were determined using freshly isolated mouse islets. Islets perifused with aaFD mixture showed an oscillatory pattern of electrical activity at lower glucose concentrations (5 mmol/l) than in islets perifused with the aaFT mixture and with glucose (G) alone (10 mmol/l). The concentration/response curve for the fraction of time spent by the membrane potential in the active phase in aaFD-stimulated islets was found to be significantly shifted to the left and had a smaller slope than that for glucose-stimulated islets. Insulin release followed the same pattern. This resulted in a concentration/response curve for glucose that was closer to that recorded "in vivo". We have also found that four amino acids (leucine, isoleucine, alanine and arginine) are largely responsible for the observed effects and that there is a non-linear enhancement of insulin release as a consequence of the combined effect of amino acids and glucose. This effect was more pronounced in the second phase of insulin release and was dependent on intracellular Ca2+. These findings indicate that amino acids account for most of the left-ward shift in the concentration/response curve for glucose and that a reduction in the threshold for the glucose-induced oscillatory electrical activity response and in the generation of Ca2+ spikes accounts for the triggering of insulin release at lower glucose concentrations. Nevertheless, the effects on insulin release at high glucose concentrations cannot be explained solely by the increase in glucose-induced electrical activity.

Amino Acids↗
PubMed1997

Identification of a Trypanosoma cruzi antigenic epitope implicated in the infectivity of fibroblast LLC-MK2 cells.

In the present paper we describe the identification of an antigenic epitope that appears to be associated with the surface membrane of the Trypanosoma cruzi parasite, probably implicated in infectivity. Anti-TcMe antibodies inhibited the infectivity of fibroblast LLC-MK2 cells by 34% relative to a preimmune serum. The epitope was specifically recognized by 55% of the sera from 80 chagasic patients. The anti-TcMe antibody immunoprecipitated proteins of about 60 and 40 kDa from epimastigote and cell-culture trypomastigote forms, respectively. It is likely that the 60- and 40-kDa proteins are processed from higher-molecular-weight precursors, since the antibody immunoprecipitated protein fractions in the range of 115-150 kDa from in vitro translation products of poly A+ RNA.

Amino Acid Sequence↗
PubMed1997

Reverse transcriptase-like activity in Trypanosoma cruzi.

The use of specific synthetic RNA homopolymers as templates and short oligonucleotides as primers has allowed evidence of the existence of a reverse transcriptase-like activity in Trypanosoma cruzi, to be revealed. The RNA:DNA products derived from this reaction are of approximately 110 nucleotides in length. The enzyme has greater affinity for poly(rA)/ oligo(dT) templates than for poly(rC)/oligo(dG) having a 20 mM Mg+2 ion requirement. The detected reverse transcriptase-like activity is not affected by aphidicolin and ddTTP but is inhibited by actinomycin D. novobiocin, rifamycin SV and AZT.

Animals↗
PubMed1997

Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study.

AIMS: To evaluate the efficacy and safety of a single loading oral dose of propafenone in the interruption of recent-onset atrial fibrillation. METHODS: After a complete medical history, physical examination, 12-lead ECG, chest X-ray, and routine biochemical laboratory testing, 55 consecutive patients with recent-onset atrial fibrillation were randomized double-blind in the emergency department for the administration of either a single oral dose (450 to 750 mg) of propafenone (29 cases) or a placebo (26 cases). After the 24-h observation period, comprehensive echocardiographic examination was performed. RESULTS: The groups were homogeneous as regards biological, clinical and echocardiographic characteristics. Two hours after treatment, 12 patients (41%) on propafenone but only two (8%) on placebo had converted to sinus rhythm (P = 0.005). This striking difference was maintained 6 h after treatment (65 vs 31%; P = 0.015) but lessened at 12 h (69% vs 42%; P = 0.060) and was insignificant at the end of the 24-h treatment period (79%, vs 73%; P = 0.752). Apart from hypotension, transient in three cases and sustained in one whose later echocardiographic examination demonstrated left systolic ventricular dysfunction, propafenone was well tolerated. CONCLUSION: Although there is no significant difference in the rates of conversion 24 h after treatment, propafenone works faster than placebo in achieving sinus rhythm. This rapid action of oral propafenone can be useful to solve quickly the clinical problems of a high proportion of patients arriving at the emergency department with acute atrial fibrillation.

Acute Disease↗