We have studied in a model of premature ageing in mice based on their impaired behavioural respon... more We have studied in a model of premature ageing in mice based on their impaired behavioural response in a simple T-maze test the effect of the ingestion of thioproline (TP) plus N-acetylcysteine (NAC) (0.1% w/w of each antioxidant) by female and male mice of Swiss and BALB/c strains on performance in two behaviour tests. The antioxidant treatment (4 weeks in two different periods of life, i.e., adult and old age) protected all animals against early-age-associated behavioural impairment, but this improvement was more evident in the prematurely ageing mice (PAM) in comparison to the control group or non-prematurely ageing mice (NPAM). An improvement of the exploratory activity and neuromuscular coordination after the thiolic antioxidant treatment was found in the PAM, bringing the behavioural parameters to the NPAM levels. These effects could be due to the glutathione precursor role of NAC and TP that replenish the intracellular reduced glutathione (GSH) levels despite advancing age. In conclusion, diet supplementation with thiolic compounds appears to be an effective therapy for protection against early behavioural decline in prematurely ageing mice.
Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lym... more Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lymphocytes from axillary nodes, spleen and thymus of young (15 +/- 2 weeks) and old (60 +/- 5 weeks) BALB/c mice. Ascorbic acid content in lymphocytes from spleen and thymus was found to be significantly higher and the lymphoproliferative response in the three immunocompetent organs significantly lower in old mice as compared to young mice. Moreover, young and old BALB/c mice were required to maintain a swimming activity until exhaustion (exhaustive exercise) or 90 min of swimming each day for a total of 20 days (continuous exercise). In both young and old mice the stress produced by exhaustive exercise and confirmed by the existence in serum of significantly increased levels of corticosterone compared to controls, caused a significant decrease in ascorbic acid content as well as in lymphoproliferative response. Continuous exercise, characterized by the presence in serum of significantly decreased levels of corticosterone compared to controls, produced the most significant decrease in ascorbic acid content from young and old murine lymphocytes. Moreover, this exercise resulted in a significant increase in lymphoproliferative response. Our results suggest that aging results in an increase in the ascorbic acid content of lymphocytes accompanied by a decline in the lymphoproliferative response in old BALB/c mice.
Annals of the New York Academy of Sciences, Apr 1, 1992
Occurrence of Vasoactive Intestinal Peptide (VIP) in Lymphoid Organs from Rat and Mouse0ROSA P. G... more Occurrence of Vasoactive Intestinal Peptide (VIP) in Lymphoid Organs from Rat and Mouse0ROSA P. GOMARIZ,* MONICA DE LA FUENTE,c ANGEL HERNANZ/ AND JAVIER LECETA* bDepartamento de Biologia Celular ^Departamento de Fisiologia Animal Facultad de ...
Several investigations have suggested that the interactions between the nervous and immune system... more Several investigations have suggested that the interactions between the nervous and immune systems are modified with age. The aim of the present work was to study the effect of three neuropeptides: gastrin-releasing peptide (GRP), neuropeptide Y (NPY) and sulfated cholecystokinin octapeptide (CCK-8 s) on natural killer (NK) activity of spleen, thymus and axillary node leukocytes from BALB/c male, young (8 ± 1 weeks), adult (24 ± 2 weeks) and old (72 ± 2 weeks) mice. We used cells from murine lymphoma YAC-1 as targets for the cytotoxic assay and three physiological concentrations of the neuropeptides (10−8, 10−10 and 10−12 M). In control samples, in the absence of neuropeptide, we observed a decreased NK activity in young and old mice with respect to the adults in the three organs studied. Regarding the effect of the neuropeptides, GRP stimulates the cytotoxic activity of leukocytes from all locations, in adult animals. At the same age, NPY also stimulates the NK activity of leukocytes from axillary nodes and thymus, whereas it decreases the NK activity of spleen leukocytes from young mice. CCK-8 s has an inhibitory effect on the axillary node leukocytes from young mice and spleen leukocytes from old animals. However, CCK-8 s increased the NK activity of thymus leukocytes from young and adult mice. The results indicate that the highest values of NK activity are found in adult mice, and that the stimulating effect of the three neuropeptides studied on NK activity of leukocytes from adult mice are reduced or disappeared, in general, in old as well as in young animals. Furthermore, the changes observed with ageing in the modulation of NK activity by the neuropeptides studied suggest an altered integration of the nervous and immune systems.
American Journal of Respiratory and Critical Care Medicine, 2016
Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemi... more Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in diabetic patients. To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels ≥ 6.5% were randomized to CPAP (n=26) or no CPAP (control; n=24), while their usual medication for diabetes remained unchanged. HbA1c levels, scores of the Homeostasis Model Assessment (HOMA) and Qualitative Insulin Sensitivity Check Index (QUICKI), systemic biomarkers and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6 and adiponectin also improved in the CPAP group compared with the control group after 6 months. In the patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related with 6-month change in HbA1c levels (r2=0.510, P=0.002). Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months, when compared to a control group, resulted in improved glycemic control and insulin resistance. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01801150.
We studied interleukin-1/3 (IL-1/3), /32-microglobulin (/3z-m) , /3-endorphin, substance P, neuro... more We studied interleukin-1/3 (IL-1/3), /32-microglobulin (/3z-m) , /3-endorphin, substance P, neuropeptide Y and somatostatin concentrations in the cerebrospinal fluid of 13 patients with dementia of the Alzheimer type (DAT), 13 patients with multi-infarct dementia (MID) and 15 age-matched control subjects. Substance P was significantly lower in DAT than in controls (P < 0.05), as well as somatostatin in DAT as compared to both controls (P < 0.01) and MID (P < 0.05), whereas /32-m was higher in DAT than in controls (P < 0.01). Neuropeptide Y, /3-endorphin and IL-1/3 showed similar concentrations in the three groups studied. A significantly positive correlation was observed between IL-1/3 and substance P (r = 0.79, P < 0.01) and somatostatin (r = 0.75, P < 0.05) in DAT, which was not observed in MID. In addition, /32-m showed a negative correlation with IL-1/3 (r = -0.73, P < 0.05) in DAT, and age correlated negatively with IL-1/3 in controls and MID, but positively in DAT. Therefore, these results support the idea that an altered relationship may exist in Alzheimer's disease between the nervous and immune system.
There are a variable number of obese subjects with self-reported diagnosis of asthma but without ... more There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg-oxygen uptake (V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;O2) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1β levels, whereas peak respiratory frequency, ventilatory equivalent for CO2, and IL-6 and IL-1β levels were independent predictors of the Borg-V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;O2 slope during exercise (r(2) = 0.853, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.
Pancreatic beta-cell and gut regulatory peptide responses were investigated in 13 healthy elderly... more Pancreatic beta-cell and gut regulatory peptide responses were investigated in 13 healthy elderly and 12 young subjects (control group) after a standard meal test. In addition to hyperinsulinemia and hypergastrinemia, we found lower basal and postprandial total integrated responses (TIR) for gastric inhibitory polypeptide and bombesin in the elderly group. The mean postprandial TIR for neurotensin (NT) was significantly higher in the aged subjects, but the somatostatin response was suppressed in this group.
A statistical study was carried out to determine if fasting serum bile acid levels are clinically... more A statistical study was carried out to determine if fasting serum bile acid levels are clinically useful in differentiating children with chronic persistent hepatitis from children with chronic aggressive hepatitis. Serum bile acid levels were determined in 27 patients with chronic aggressive hepatitis, 41 with chronic persistent hepatitis and 55 control children. Several other biochemical tests of liver function were also determined in these children. There were significant differences in the mean fasting serum bile acid levels between chronic hepatitis patients and control children (p less than 0.001). These levels were significantly higher for the chronic aggressive group than the chronic persistent hepatitis group (p less than 0.001). Other biochemical &#39;hepatic function&#39; tests did not show statistically different values between these two groups. Using stepwise discriminant analysis for the biochemical &#39;liver function&#39; tests studied, only serum bile acid levels are able to distinguish statistically between chronic aggressive hepatitis and chronic persistent hepatitis children. These data suggest that fasting serum bile acid levels may have clinical utility in identifying children with asymptomatic chronic hepatitis and differentiating between chronic aggressive hepatitis and chronic persistent hepatitis children.
Plasma vitamin E levels were measured by high performance liquid chromatography in 42 children wi... more Plasma vitamin E levels were measured by high performance liquid chromatography in 42 children with cystic fibrosis and were correlated with the following parameters: sex, age, time of follow-up, clinical evolution (Schwachman score), vitamin E/cholesterol and faecal fat excretion. All children in this study received oral alfa-tocoferol (50-100 mg daily) from the diagnosis. According to the vitamin E level patients were distributed in two groups. Group I: 27 patients (64.3%) with normal concentrations. Group II: 15 patients (35.7%) with decreases plasma levels but without clinical manifestations. Steatorrhea was present in all children except 4 patients from group I and one patient from group II. On the other hand, vitamin E/cholesterol was normal in 80% of patients with vitamin E deficiency (group II). We did not find any correlation between plasma vitamin E levels and the different clinical and biological parameters studied. Further studies should be carried out to throw more light on the mechanism underlying the pathogenesis of vitamin E deficiency in patients with cystic fibrosis.
Serum levels of immunoreactive trypsin (TIRS) were determined in 61 children having either alpha ... more Serum levels of immunoreactive trypsin (TIRS) were determined in 61 children having either alpha 1 antitrypsin deficit, chronic hepatitis, syndromic or non-syndromic ductular hypoplasia, or extrahepatic biliary atresia. Fasting TIRS values in both patients with chronic hepatitis (213 M 81 ng/ml) and with extrahepatic biliary atresia (159 +/- 88 ng/ml) didn&#39;t show statistically significant differences in relation to control values (172 +/- 44 ng/ml). However, in children with alpha 1-antitrypsin deficit (518 +/- 275 ng/ml; p less than 0.02) or syndromic (594 +/- 331 ng/ml; p less than 0.01) and non-syndromic ductular hypoplasia (558 +/- 183 ng/ml; p less than 0.02) TIRS levels were significantly above control values. Even more, in these last three groups of patients, their TIRS values were clearly greater than in extrahepatic biliary atresia patients. According to the above findings, we suggest that TIRS values may be a valuable marker for the differential diagnosis between intra and extrahepatic cholestasis.
Methods and Findings in Experimental and Clinical Pharmacology
Semicarbazide was injected intraperitoneally to pregnant rats in single doses of 50, 75, 100 or 1... more Semicarbazide was injected intraperitoneally to pregnant rats in single doses of 50, 75, 100 or 150 mg/kg. Treatment was administered on days 7, 10 or 13 of pregnancy. Semicarbazide produced abnormalities in 21 day old fetuses, found mainly in liver and kidney and in the skull and sternum, as well as resorptions and fetal deaths throughout gestation. This substance also caused a high postnatal mortality rate during the first month of life, especially with the 100 mg/kg dose. This dose reduced the nucleic acid and protein content in the lung and liver of the rats whether they were adult, pregnant, fetus or newborn. Statistically significant decrease of the nucleic acid level in adult rats appeared 48 hours after treatment. This decrease varied in the two organs studied. The lungs of pregnant rats which received semi-carbazide on day 10 of gestation showed a statistically significant decrease of the nucleic acid and protein levels on day 18 of gestation; there was also a significant decrease of RNA in the liver on this day, while a decrease in the proteins did not appear until day 21. The fetuses of treated mothers showed a significant decrease of DNA and RNA in the lung when they were 21 days old and a continuous decrease of the protein levels lasting up to the end of the first week of life. DNA and RNA in the liver of these offspring decreased when they were 30 days old. As for the protein content, it decreased throughout fetal life and continued to do so during the first month of fetal life.
A bile acid analysis by a fluorometric-enzymic method was carried out in serum from infants with ... more A bile acid analysis by a fluorometric-enzymic method was carried out in serum from infants with neonatal hepatitis and biliary atresia. Serum bile acids were determined in 51 infants: 34 with extrahepatic biliary atresia and 17 with neonatal hepatitis syndrome. The following results were obtained: 1) There were no significant differences between neonatal hepatitis and biliary atresia concerning total serum bile acids. 2) The ratio of trihydroxylated to dihydroxylated bile acids in serum was less than one in 30 patients with biliary atresia and greater than one in 15 patients with neonatal hepatitis. 3) Conventional hepatic tests did not show any statistically significant difference between these types of patients. These results suggest that trihydroxy/dihydroxy bile acid ratio may be of clinical interest to differentiate biliary atresia from neonatal hepatitis in infants.
Journal of clinical chemistry and clinical biochemistry. Zeitschrift für klinische Chemie und klinische Biochemie
Plasma samples (100 μl) were treated with 150 μl of acetonitrile and centrifuged at 5800g for 10 ... more Plasma samples (100 μl) were treated with 150 μl of acetonitrile and centrifuged at 5800g for 10 min and 50 μl of 10 mM borate buffer (pH 9.2) were added to the supernatant solution. This was followed by the addition of a 50 μl aliquot of 5 mM fluorescamine in acetonitrile and immediate vortex mixing. A 20 μl sample was
International archives of allergy and applied immunology
Immediate hypersensitivity responses, as acute urticaria, produce a release of neuropeptides by n... more Immediate hypersensitivity responses, as acute urticaria, produce a release of neuropeptides by nerve endings, which present specificity of recognition by mast cells, basophils and other target cells. We have measured vasoactive intestinal peptide (VIP), somatostatin, bombesin, neurotensin and beta-endorphin by radioimmunoassay in plasma extracts of 20 patients with acute idiopathic urticaria and of 20 healthy subjects. VIP- and beta-endorphin-like immunoreactivities were found to be significantly decreased with respect to controls (p less than 0.001 and p less than 0.01, respectively). On the contrary, somatostatin- and bombesin-like immunoreactivities were significantly increased (p less than 0.001 and p less than 0.05, respectively). These findings could be a reflection in blood of a raised release of somatostatin and bombesin by nerve endings in the urticaria process. Moreover, the decreased plasma levels of VIP- and beta-endorphin-like immunoreactivities could be explained by a raised specific metabolism of these peptides in the urticaria process.
We have studied in a model of premature ageing in mice based on their impaired behavioural respon... more We have studied in a model of premature ageing in mice based on their impaired behavioural response in a simple T-maze test the effect of the ingestion of thioproline (TP) plus N-acetylcysteine (NAC) (0.1% w/w of each antioxidant) by female and male mice of Swiss and BALB/c strains on performance in two behaviour tests. The antioxidant treatment (4 weeks in two different periods of life, i.e., adult and old age) protected all animals against early-age-associated behavioural impairment, but this improvement was more evident in the prematurely ageing mice (PAM) in comparison to the control group or non-prematurely ageing mice (NPAM). An improvement of the exploratory activity and neuromuscular coordination after the thiolic antioxidant treatment was found in the PAM, bringing the behavioural parameters to the NPAM levels. These effects could be due to the glutathione precursor role of NAC and TP that replenish the intracellular reduced glutathione (GSH) levels despite advancing age. In conclusion, diet supplementation with thiolic compounds appears to be an effective therapy for protection against early behavioural decline in prematurely ageing mice.
Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lym... more Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lymphocytes from axillary nodes, spleen and thymus of young (15 +/- 2 weeks) and old (60 +/- 5 weeks) BALB/c mice. Ascorbic acid content in lymphocytes from spleen and thymus was found to be significantly higher and the lymphoproliferative response in the three immunocompetent organs significantly lower in old mice as compared to young mice. Moreover, young and old BALB/c mice were required to maintain a swimming activity until exhaustion (exhaustive exercise) or 90 min of swimming each day for a total of 20 days (continuous exercise). In both young and old mice the stress produced by exhaustive exercise and confirmed by the existence in serum of significantly increased levels of corticosterone compared to controls, caused a significant decrease in ascorbic acid content as well as in lymphoproliferative response. Continuous exercise, characterized by the presence in serum of significantly decreased levels of corticosterone compared to controls, produced the most significant decrease in ascorbic acid content from young and old murine lymphocytes. Moreover, this exercise resulted in a significant increase in lymphoproliferative response. Our results suggest that aging results in an increase in the ascorbic acid content of lymphocytes accompanied by a decline in the lymphoproliferative response in old BALB/c mice.
Annals of the New York Academy of Sciences, Apr 1, 1992
Occurrence of Vasoactive Intestinal Peptide (VIP) in Lymphoid Organs from Rat and Mouse0ROSA P. G... more Occurrence of Vasoactive Intestinal Peptide (VIP) in Lymphoid Organs from Rat and Mouse0ROSA P. GOMARIZ,* MONICA DE LA FUENTE,c ANGEL HERNANZ/ AND JAVIER LECETA* bDepartamento de Biologia Celular ^Departamento de Fisiologia Animal Facultad de ...
Several investigations have suggested that the interactions between the nervous and immune system... more Several investigations have suggested that the interactions between the nervous and immune systems are modified with age. The aim of the present work was to study the effect of three neuropeptides: gastrin-releasing peptide (GRP), neuropeptide Y (NPY) and sulfated cholecystokinin octapeptide (CCK-8 s) on natural killer (NK) activity of spleen, thymus and axillary node leukocytes from BALB/c male, young (8 ± 1 weeks), adult (24 ± 2 weeks) and old (72 ± 2 weeks) mice. We used cells from murine lymphoma YAC-1 as targets for the cytotoxic assay and three physiological concentrations of the neuropeptides (10−8, 10−10 and 10−12 M). In control samples, in the absence of neuropeptide, we observed a decreased NK activity in young and old mice with respect to the adults in the three organs studied. Regarding the effect of the neuropeptides, GRP stimulates the cytotoxic activity of leukocytes from all locations, in adult animals. At the same age, NPY also stimulates the NK activity of leukocytes from axillary nodes and thymus, whereas it decreases the NK activity of spleen leukocytes from young mice. CCK-8 s has an inhibitory effect on the axillary node leukocytes from young mice and spleen leukocytes from old animals. However, CCK-8 s increased the NK activity of thymus leukocytes from young and adult mice. The results indicate that the highest values of NK activity are found in adult mice, and that the stimulating effect of the three neuropeptides studied on NK activity of leukocytes from adult mice are reduced or disappeared, in general, in old as well as in young animals. Furthermore, the changes observed with ageing in the modulation of NK activity by the neuropeptides studied suggest an altered integration of the nervous and immune systems.
American Journal of Respiratory and Critical Care Medicine, 2016
Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemi... more Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in diabetic patients. To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels ≥ 6.5% were randomized to CPAP (n=26) or no CPAP (control; n=24), while their usual medication for diabetes remained unchanged. HbA1c levels, scores of the Homeostasis Model Assessment (HOMA) and Qualitative Insulin Sensitivity Check Index (QUICKI), systemic biomarkers and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6 and adiponectin also improved in the CPAP group compared with the control group after 6 months. In the patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related with 6-month change in HbA1c levels (r2=0.510, P=0.002). Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months, when compared to a control group, resulted in improved glycemic control and insulin resistance. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01801150.
We studied interleukin-1/3 (IL-1/3), /32-microglobulin (/3z-m) , /3-endorphin, substance P, neuro... more We studied interleukin-1/3 (IL-1/3), /32-microglobulin (/3z-m) , /3-endorphin, substance P, neuropeptide Y and somatostatin concentrations in the cerebrospinal fluid of 13 patients with dementia of the Alzheimer type (DAT), 13 patients with multi-infarct dementia (MID) and 15 age-matched control subjects. Substance P was significantly lower in DAT than in controls (P < 0.05), as well as somatostatin in DAT as compared to both controls (P < 0.01) and MID (P < 0.05), whereas /32-m was higher in DAT than in controls (P < 0.01). Neuropeptide Y, /3-endorphin and IL-1/3 showed similar concentrations in the three groups studied. A significantly positive correlation was observed between IL-1/3 and substance P (r = 0.79, P < 0.01) and somatostatin (r = 0.75, P < 0.05) in DAT, which was not observed in MID. In addition, /32-m showed a negative correlation with IL-1/3 (r = -0.73, P < 0.05) in DAT, and age correlated negatively with IL-1/3 in controls and MID, but positively in DAT. Therefore, these results support the idea that an altered relationship may exist in Alzheimer's disease between the nervous and immune system.
There are a variable number of obese subjects with self-reported diagnosis of asthma but without ... more There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg-oxygen uptake (V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;O2) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1β levels, whereas peak respiratory frequency, ventilatory equivalent for CO2, and IL-6 and IL-1β levels were independent predictors of the Borg-V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;O2 slope during exercise (r(2) = 0.853, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.
Pancreatic beta-cell and gut regulatory peptide responses were investigated in 13 healthy elderly... more Pancreatic beta-cell and gut regulatory peptide responses were investigated in 13 healthy elderly and 12 young subjects (control group) after a standard meal test. In addition to hyperinsulinemia and hypergastrinemia, we found lower basal and postprandial total integrated responses (TIR) for gastric inhibitory polypeptide and bombesin in the elderly group. The mean postprandial TIR for neurotensin (NT) was significantly higher in the aged subjects, but the somatostatin response was suppressed in this group.
A statistical study was carried out to determine if fasting serum bile acid levels are clinically... more A statistical study was carried out to determine if fasting serum bile acid levels are clinically useful in differentiating children with chronic persistent hepatitis from children with chronic aggressive hepatitis. Serum bile acid levels were determined in 27 patients with chronic aggressive hepatitis, 41 with chronic persistent hepatitis and 55 control children. Several other biochemical tests of liver function were also determined in these children. There were significant differences in the mean fasting serum bile acid levels between chronic hepatitis patients and control children (p less than 0.001). These levels were significantly higher for the chronic aggressive group than the chronic persistent hepatitis group (p less than 0.001). Other biochemical &#39;hepatic function&#39; tests did not show statistically different values between these two groups. Using stepwise discriminant analysis for the biochemical &#39;liver function&#39; tests studied, only serum bile acid levels are able to distinguish statistically between chronic aggressive hepatitis and chronic persistent hepatitis children. These data suggest that fasting serum bile acid levels may have clinical utility in identifying children with asymptomatic chronic hepatitis and differentiating between chronic aggressive hepatitis and chronic persistent hepatitis children.
Plasma vitamin E levels were measured by high performance liquid chromatography in 42 children wi... more Plasma vitamin E levels were measured by high performance liquid chromatography in 42 children with cystic fibrosis and were correlated with the following parameters: sex, age, time of follow-up, clinical evolution (Schwachman score), vitamin E/cholesterol and faecal fat excretion. All children in this study received oral alfa-tocoferol (50-100 mg daily) from the diagnosis. According to the vitamin E level patients were distributed in two groups. Group I: 27 patients (64.3%) with normal concentrations. Group II: 15 patients (35.7%) with decreases plasma levels but without clinical manifestations. Steatorrhea was present in all children except 4 patients from group I and one patient from group II. On the other hand, vitamin E/cholesterol was normal in 80% of patients with vitamin E deficiency (group II). We did not find any correlation between plasma vitamin E levels and the different clinical and biological parameters studied. Further studies should be carried out to throw more light on the mechanism underlying the pathogenesis of vitamin E deficiency in patients with cystic fibrosis.
Serum levels of immunoreactive trypsin (TIRS) were determined in 61 children having either alpha ... more Serum levels of immunoreactive trypsin (TIRS) were determined in 61 children having either alpha 1 antitrypsin deficit, chronic hepatitis, syndromic or non-syndromic ductular hypoplasia, or extrahepatic biliary atresia. Fasting TIRS values in both patients with chronic hepatitis (213 M 81 ng/ml) and with extrahepatic biliary atresia (159 +/- 88 ng/ml) didn&#39;t show statistically significant differences in relation to control values (172 +/- 44 ng/ml). However, in children with alpha 1-antitrypsin deficit (518 +/- 275 ng/ml; p less than 0.02) or syndromic (594 +/- 331 ng/ml; p less than 0.01) and non-syndromic ductular hypoplasia (558 +/- 183 ng/ml; p less than 0.02) TIRS levels were significantly above control values. Even more, in these last three groups of patients, their TIRS values were clearly greater than in extrahepatic biliary atresia patients. According to the above findings, we suggest that TIRS values may be a valuable marker for the differential diagnosis between intra and extrahepatic cholestasis.
Methods and Findings in Experimental and Clinical Pharmacology
Semicarbazide was injected intraperitoneally to pregnant rats in single doses of 50, 75, 100 or 1... more Semicarbazide was injected intraperitoneally to pregnant rats in single doses of 50, 75, 100 or 150 mg/kg. Treatment was administered on days 7, 10 or 13 of pregnancy. Semicarbazide produced abnormalities in 21 day old fetuses, found mainly in liver and kidney and in the skull and sternum, as well as resorptions and fetal deaths throughout gestation. This substance also caused a high postnatal mortality rate during the first month of life, especially with the 100 mg/kg dose. This dose reduced the nucleic acid and protein content in the lung and liver of the rats whether they were adult, pregnant, fetus or newborn. Statistically significant decrease of the nucleic acid level in adult rats appeared 48 hours after treatment. This decrease varied in the two organs studied. The lungs of pregnant rats which received semi-carbazide on day 10 of gestation showed a statistically significant decrease of the nucleic acid and protein levels on day 18 of gestation; there was also a significant decrease of RNA in the liver on this day, while a decrease in the proteins did not appear until day 21. The fetuses of treated mothers showed a significant decrease of DNA and RNA in the lung when they were 21 days old and a continuous decrease of the protein levels lasting up to the end of the first week of life. DNA and RNA in the liver of these offspring decreased when they were 30 days old. As for the protein content, it decreased throughout fetal life and continued to do so during the first month of fetal life.
A bile acid analysis by a fluorometric-enzymic method was carried out in serum from infants with ... more A bile acid analysis by a fluorometric-enzymic method was carried out in serum from infants with neonatal hepatitis and biliary atresia. Serum bile acids were determined in 51 infants: 34 with extrahepatic biliary atresia and 17 with neonatal hepatitis syndrome. The following results were obtained: 1) There were no significant differences between neonatal hepatitis and biliary atresia concerning total serum bile acids. 2) The ratio of trihydroxylated to dihydroxylated bile acids in serum was less than one in 30 patients with biliary atresia and greater than one in 15 patients with neonatal hepatitis. 3) Conventional hepatic tests did not show any statistically significant difference between these types of patients. These results suggest that trihydroxy/dihydroxy bile acid ratio may be of clinical interest to differentiate biliary atresia from neonatal hepatitis in infants.
Journal of clinical chemistry and clinical biochemistry. Zeitschrift für klinische Chemie und klinische Biochemie
Plasma samples (100 μl) were treated with 150 μl of acetonitrile and centrifuged at 5800g for 10 ... more Plasma samples (100 μl) were treated with 150 μl of acetonitrile and centrifuged at 5800g for 10 min and 50 μl of 10 mM borate buffer (pH 9.2) were added to the supernatant solution. This was followed by the addition of a 50 μl aliquot of 5 mM fluorescamine in acetonitrile and immediate vortex mixing. A 20 μl sample was
International archives of allergy and applied immunology
Immediate hypersensitivity responses, as acute urticaria, produce a release of neuropeptides by n... more Immediate hypersensitivity responses, as acute urticaria, produce a release of neuropeptides by nerve endings, which present specificity of recognition by mast cells, basophils and other target cells. We have measured vasoactive intestinal peptide (VIP), somatostatin, bombesin, neurotensin and beta-endorphin by radioimmunoassay in plasma extracts of 20 patients with acute idiopathic urticaria and of 20 healthy subjects. VIP- and beta-endorphin-like immunoreactivities were found to be significantly decreased with respect to controls (p less than 0.001 and p less than 0.01, respectively). On the contrary, somatostatin- and bombesin-like immunoreactivities were significantly increased (p less than 0.001 and p less than 0.05, respectively). These findings could be a reflection in blood of a raised release of somatostatin and bombesin by nerve endings in the urticaria process. Moreover, the decreased plasma levels of VIP- and beta-endorphin-like immunoreactivities could be explained by a raised specific metabolism of these peptides in the urticaria process.
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Papers by Angel Hernanz