Biomedical subjects
Publications and source records attributed to F Delgado.
Mass spectrometric detection and identification of ortho- and para-benzyltoluenes and oligotoluenes, C(21)-C(49), in several reaction mixtures was performed. Thus, the corresponding electron impact spectra were acquired and analyzed, this in addition to constant B/E linked scans and high-resolution data. Copyright 2000 John Wiley & Sons, Ltd.
A mass spectrometric study of several tricarbonyl (eta(6)-phenyl methanols) of chromium(0) was performed. Electron ionization (EI), chemical ionization (CI) and fast atom bombardment (FAB) mass spectra were acquired for each molecule, and compared in order to establish a general fragmentation pattern. The suggested pathways were investigated and confirmed by means of constant b/e linked scans and high resolution data. In addition a Hammett-McLafferty correlation for some peaks derived from the molecular ions was accomplished.
The production of free radicals seems to be involved in the mechanisms of ototoxicity. Aminoglycosides produce ototoxicity, which can be determined through distortion product otoacoustic emissions (OAEs) that measure the activity of the outer hair cells of the organ of Corti. An ototoxic chart was obtained in rats using gentamicin or tobramycin. Together with this treatment, the animals ingested melatonin in the drinking water, or melatonin was injected subcutaneously or intramuscularly. The distortion product OAEs were determined over a prolonged period of time for each of the groups. The effect of melatonin on the antibiotic capacity of the aminoglycosides used was also studied. Antibiograms inoculated with Escherichia coli or Pseudomonas aeruginosa and treated with gentamicin or tobramycin in the presence or absence of melatonin at quantities from pharmacological to physiological doses were performed. The ototoxicity produced by gentamicin and tobramycin was maximal from days 3 to 5 post-treatment, returning to normal values in 2 wk. When melatonin was present, the recovery was at day 5 post-treatment, independently of the means of administration of the pineal product. The antibiograms showed that melatonin had no effect on the antibiotic capacity. It is concluded that the ototoxicity caused by gentamicin and tobramycin is ameliorated by melatonin and that the pineal hormone does not interfere with the antibiotic capacity of these antibiotics.
The mechanism of the ototoxicity caused by cisplatin is based in the generation of reactive oxygen species, which interferes with the antioxidant protection of the organ of Corti. Conversely, the protection of the cochlea with antioxidants ameliorates the ototoxicity by cisplatin. The ototoxicity produced by cisplatin can be reversible or persistent, depending on the age of the patient, cumulative doses, number of chemotherapy cycles, history of noise exposure, and deteriorating renal function. We have obtained in rats an ototoxic chart utilizing cisplatin (10 mg/kg body weight injected intraperitoneally, once only). Together with this treatment, the animals were treated with melatonin in the drinking water (10 mg/L) or injected subcutaneously (250 microg), and with an antioxidant mixture, injected subcutaneously, composed of 0.25 mg alpha-tocopherol acid succinate, 3 mg ascorbic acid, 1 mg glutathione, and 60 mg N-acetylcysteine. The distortion product otoacoustic emissions were determined for a prolonged period of time for each animal. The ototoxicity produced by cisplatin was maximal from days 7 to 10 post-treatment, returning to normal values in a month. When melatonin and the antioxidant mixture were present, the recovery was between days 10 and 15 post-treatment, independent of the means of administration of the pineal product. We conclude that the ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants.
Raised levels of microalbuminuria pointing out glomerular abnormality and indicate renal damage. Glomerulonephritis is caused by immune reaction leading to the formation of circulating immune complexes that are deposited on the basal membrane of the glomerulus. The time course and the appearance of antibodies against infectious agents both play very important roles in its clinical presentation. Antibodies against streptococci have not a protective role, but offers a useful marker of the presence or absence of recent infection. This work studies the presence of microalbuminuria and circulating anti-streptococcal antibodies, namely, anti-streptolysin O and anti-deoxyribonuclease B antibodies in ninety children which underwent tonsillectomy due to infectious and obstructive tonsillar pathology. These children were divided in recurrent acute tonsillitis (n= 34), recurrent tonsillitis with tonsillar hypertrophy (n = 26), and tonsillar hypertrophy (n = 30). It was found in recurrent acute tonsillitis a moderate correlation between microalbuminuria and anti-streptolysin O, and a weak correlation between microalbuminuria and anti-deoxyribonuclease B antibodies. It was also found significant differences of the levels of anti-streptococcal antibodies between the three groups of pathologies. It is proposed the determination of microalbuminuria, an inexpensive and harmless test, as an indicator of possible renal damage in recurrent acute tonsillitis.
UNLABELLED: The pathogenic mechanism of tonsillar hypertrophy is unknown and lacks a proper infectious or immunological explanation. Epidemiological studies point to polluted environments as the main cause of tonsillar hypertrophy in the adaptation of the juvenile organism. Tonsils and adenoids of 67 children aged 2-16 years (mean 5.9 years) were divided into three groups: recurrent tonsillitis (n = 21), recurrent tonsillitis with tonsillar hypertrophy (n = 21) and tonsillar hypertrophy without history of tonsillitis (n = 25). The following biological markers were studied: anti-streptolysin O antibody and anti-deoxy ribonuclease B antibody serology, microbiology and cell count of granulocytes in tonsils and adenoids as well as lymphocyte subsets and "ex vivo" endonuclease activity in tonsils. Anti-streptolysin O antibody and anti-deoxyribonuclease B antibody titres were significantly raised in recurrent tonsillitis. Positive bacterial cultures for Streptococcus pyogenes were rare in cases of tonsillar hypertrophy. T-lymphocytes counts were lower and the proportion of basophils was higher in hypertrophic tonsils than in recurrent tonsillitis. Two parameters of apoptosis were studied; the activation of endonuclease, inducing breakdown of DNA resulting in cell death, and the sensitivity to thapsigargin, known to trigger the cleavage of DNA by apoptotic endonuclease. In children with tonsillar hypertrophy both parameters were decreased contrasting with those with recurrent tonsillitis where apoptosis is increased. It may be speculated that the increase of basophils in children with tonsillar hypertrophy results in increased release of interleukin-4, which could prevent lymphoid apoptosis and lead to cell proliferation in tonsillar tissue. CONCLUSION: Whereas recurrent tonsillitis is characterised by apoptotic death of lymphoid tissue, tonsillar hypertrophy is caused by environmental pollution agents that trigger the chronic inflammatory process without apoptotic cell death.
The ototoxicity of antibiotics, particularly of aminoglycosides, is a well-known undesirable side effect which may be based on a free radical mechanism. We studied the effect of different antibiotics in the production of reactive oxygen species in freshly isolated cochleas of mature and 2-10 weeks old developing rats. Phorbol myristate acetate induced the release of reactive oxygen species after a lag time close to 30 s and declined back to basal values in 10-20 min. The rate of reactive oxygen species production correlated inversely to the age in 2-10 weeks old rats. The study of a set of antibiotics showed that a very low concentration of gentamicin and streptomycin (10-100 ng/ml) enhanced the effect of phorbol myristate acetate. At the above-indicated concentrations, ciprofloxacin did not modify phorbol myristate acetate-induced activation. These results show the enhancement by aminoglycosides of reactive oxygen species production in cochlear tissues, particularly in developing rats.
The pathogenic role of anti-type II collagen was analysed in a variety of hearing losses, in age-matched controls and in different autoimmune diseases. The immune reactivity of peripheral blood lymphocytes to type II collagen was studied by the degree of proliferation measured as the incorporation of bromodeoxyuridine in cultured lymphocytes. The anti-type II collagen antibodies showed a very low incidence in the hearing loss group. Lymphocytes of otosclerosis, Meniere's disease and other sensorineural deafness patients proliferated in response to concanavalin A and to type II collagen to a lower extent than peripheral blood lymphocytes from healthy controls. Nonetheless, these differences were not statistically significant. The immune hyperreactivity to type II collagen cannot explain the autoimmune mechanism of hearing losses. Humoral and cellular hyperreactivities to inner ear proteins different from type II collagen, could explain the autoimmune mechanism of deafness.
The outer hair cells of the organ of Corti transform sound into electrical signals, beginning the nervous auditive process. These cells produce acoustic emissions when working routinely, known as otoacoustic emissions. Otoacoustic emissions (OAEs) are recorded from the hearing duct through a probe which incorporates a sound source and a sensitive microphone. On the other hand, the cochlea produces oxygen-derived free radicals and nitric oxide, in addition, melatonin is present in the cochlea. The authors have studied the influence of melatonin or an antioxidant mixture (alpha-tocopherol acid succinate, ascorbic acid, glutathione, and N-acetylcysteine) on the postmortem activity of the outer hair cells of the organ of Corti of the rat, measuring distortion product otoacoustic emissions. Control rats showed postmortem distortion product otoacoustic emissions for about 2 min when sacrificed by decapitation, and for about 3 min when sacrificed by chloroform inhalation. Melatonin prolonged the postmortem activity 3.5 times when the animals were sacrificed by decapitation, and 7 times when animals were sacrificed by chloroform inhalation. Similar results were obtained with the antioxidant mixture. Results show that melatonin and other antioxidants have, in general, a protective role on the postmortem activity of the outer hair cells of the organ of Corti.
Tonsils and adenoids are secondary lymphoid organs exposed to the environment. The most important classifications of AIDS include the lymphocyte subsets of peripheral blood. We have studied the lymphocyte subsets in peripheral blood and secondary lymphoid organs in a control group of children suffering adenotonsillar pathology and in five children with AIDS and the same adenotonsillar pathology. The antigen surface markers were determined by flow cytometry in lymphocytes isolated from peripheral blood, and from tonsils and adenoids after tonsillectomy and adenoidectomy, in the control group and in children diagnosed with AIDS. The most important findings in tonsils and adenoids were a decrease of the total T lymphocytes, helper T lymphocytes and CD4/CD8 ratio; an increase of cytotoxic T lymphocytes and B lymphocytes, as well as a 200% increase in monocytes of AIDS-affected children. These observations show the value of analyzing the lymphocyte subsets of the tonsils and adenoids of AIDS-affected children, and establishing an earlier relation to clinical symptoms.
Tonsils have a privileged situation in the immune system in that they are in touch with the environment. Melatonin is a hormone that is influenced by the circadian environmental variations of dark-light and is a modulator of the immune system. We have studied a group of thirty five children with recurrent acute tonsillitis that were submitted for tonsillectomy. Tonsillar lymphocyte subsets were determined before and after culture through flow cytometry in a tonsillar mononuclear suspension. After the culture, the lymphocyte subsets of type B suffered a decrease that was restored in the presence of melatonin or phytohemaglutinin, and even increased above the values of the control when the culture was accomplished in the presence of both substances. This process was specific for B cells, no occurrence for T lymphocytes or natural killer cells. Melatonin is found in the crossroads of the interaction of the microorganisms, pollens or inert substances with the tonsillar lymphocytes in the production of the immune defences. Further study is required on tonsillar pathology to explain its physiopathology and its possible therapeutic role.
OBJECTIVE: To investigate the efficacy of respiratory rehabilitation in preventing postoperative pulmonary complications (PPC) and to define which patients can benefit. DESIGN: A randomized clinical trial. SETTING: A public hospital. PATIENTS: Eighty-one patients who had upper abdominal surgery were distributed into two homogeneous groups: control (n = 41) and rehabilitation (n = 40). INTERVENTION: Breathing exercises in the rehabilitation group. MAIN OUTCOME MEASURES: Preoperative and postoperative clinical evaluation, spirometry, arterial gasometry, and simple chest X-rays. RESULTS: The incidence of PPC was 7.5% in the rehabilitation group and 19.5% in the control group; the control group also had more radiologic alterations (p = .01). Stratified PPC analysis did not reveal significant differences between groups. However, high- and moderate-risk patients in the rehabilitation group had fewer PPC. Multivariate analysis showed a greater PPC risk associated with pulmonary history (p = .02) and duration of surgery longer than 120 min (p = .03), while rehabilitation exerted a protective effect (p = .06). Significant postoperative decreases in pulmonary volumes and arterial gas values were recorded in both groups, without significant differences. CONCLUSIONS: Respiratory rehabilitation protects against PPC and is more effective in moderate- and high-risk patients, but does not affect surgery-induced functional alterations.
Recurrent acute tonsillitis is usually produced directly by micro-organisms, mainly beta-hemolytic streptococcus. Idiopathic tonsillar hypertrophy is presented without infection history and usually leads to obstructive sleep apnea. We have measured lymphocyte subsets in tonsillar cellular suspensions of infectious and obstructive tonsillar pathology by flow cytometry. Comparing with peripheral blood, the CD4+/CD8+ ratio for tonsillar pathology varies from 4.0 to 5.0 while in peripheral blood the ratio was 1.3. In tonsils the ratio of B lymphocytes/T lymphocytes is 1.6, being 0.3 in peripheral blood, cytotoxic T lymphocytes represent 8% in tonsils and 29% in peripheral blood, virgin or nonstimulated T lymphocytes (CD4+ CD62L+) consist of 3% in tonsils and 16% in peripheral blood. The immature B lymphocytes (CD20+ CD5+) represent 23% in tonsils and 12% in peripheral blood. In regards to NK cells (CD3- CD16+), 1% was found in tonsils and 11% in peripheral blood. In tonsils B lymphocytes and a low proportion of cytotoxic T lymphocytes predominate, in comparison to peripheral blood, with a CD4+/CD8+ ratio four times greater than tonsils. We have found in tonsils a significant increase of T cells (CD3+ and TCR alpha+ beta+) in infectious processes in comparison to obstructive pathology.
Rat cochleas were analysed for free oxygen radicals (FOR) and nitric oxide (NO) production by the chemiluminescent oxidation of luminol. 4Beta-phorbol-12beta-myristate-13alpha-acetate (PMA), a well-known agonist of protein kinase C, induced the release of FOR after a time lag close to 30 s and reverted to basal values in approximately 10 min. Sphingosine inhibited by nearly 50% the response to PMA, whereas staurosporine caused an inhibition of 100%. The incubation of rat cochleas with 0.5 mM arginine potentiated the chemiluminescent reaction induced by PMA causing an additional oxidation of luminol that was inhibited by the NO synthase inhibitor N-methyl-arginine (NMA). Our results show for the first time the presence in the cochlea of cell populations producing FOR and NO and the real time production following cell activation. This procedure may help to explain the mechanisms involved in ototoxicity, as in the case of streptomycin and gentamicin that enhanced PMA-dependent production of FOR and NO.
OBJECTIVE: To investigate the impairment of pulmonary function and complications after laparoscopic compared with open cholecystectomy through an upper midline incision. DESIGN: Prospective randomised trial. SETTING: Teaching hospital, Spain. SUBJECTS: 40 patients, 20 in each group. INTERVENTIONS: Clinical examination, spirometry, arterial blood gas analysis, and chest radiographs before and after operation. RESULTS: 48 hours postoperatively FVC and FEV1 had decreased to 56.7% and 53%, respectively, in the patients who had had open cholecystectomy, compared with 85.3% and 84.8% in the laparoscopic group (p < 0.0001). The mean (SD) postoperative percentage reductions in both PaO2 (86.1 (11.1) compared with 98.3 (11.3)) and SatO2 (98.6 (1.3) compared with 100 (1.5)) were also greater in the open group (p < 0.005 in both cases). CONCLUSIONS: Laparoscopic cholecystectomy causes less impairment of lung function than cholecystectomy through an upper midline incision.
We have studied the behavior of peripheral blood lymphocytes in healthy controls and in patients with various hearing losses. These hearing losses were of an autoimmune origin in which type II collagen and melatonin were either present or absent, activated or not with concanavalin A (Con A). In patients with autoimmune hearing losses, the results showed lymphocytes that displayed hyporeactivity to type II collagen in terms of their proliferative activity in the presence of Con A. The hyporeactivity is specially relevant in those cells which are melatonin incubated. When different nosologic entities were studied, we observed similar lymphocyte hyporeactivity to type II collagen in bilateral sensorineural hearing loss, Ménière's disease and otosclerosis. We conclude that in the lymphocytes of patients with autoimmune hearing losses, there is hyporeactivity to type II collagen when compared to the hyporeactivity of lymphocytes in control groups. This hyporeactivity is revealed when the lymphocytes are activated in the presence of melatonin.
Within the normal inner ear, there are elements that belong to the immune system. Different inner ear disorders can be explained by autoimmune mechanisms, affecting both humoral and cellular immunity. Melatonin, the principal hormone of the pineal gland, modulates the immune system and extensively participates in the autoimmune processes related to type II collagen. Therefore, we have studied the presence of melatonin in rat cochlea, proving that its concentrations change depending on lighting conditions. Rats show high levels when confined to darkness and low levels when subject to continuous light exposure. The results correlate with the concentration of melatonin in peripheral circulation. Further experimental and clinical studies are necessary to clarify the role and the possible therapeutic applications of melatonin.
OBJECTIVE: To determine whether increased calcium intake (2 g/day) in pregnancy is effective in reducing the risk of preeclampsia in pregnant teenagers. METHODS: The present study was a prospective, randomized, double-blind, controlled clinical trial. Two hundred sixty teenaged pregnant girls attending the Hospital Gíneco-Obstétrico Isidro Ayora in Quito, Ecuador, were included. Selection criteria were age less than 17.5 years, nulliparity, first prenatal visit before 20 weeks' gestation, and residency in Quito (2800-m altitude). We used a table of random numbers to assign 125 girls to receive 2000 mg of elemental calcium daily, beginning at 20 weeks of gestation and continuing until delivery; 135 women in the control group received a placebo. Blood pressure (BP) was measured twice every 4 weeks until delivery and at 48 hours after delivery. The diagnosis of preeclampsia was defined as BP greater than 140/90 mmHg on at least two occasions more than 6 hours apart and proteinuria greater than 30 mg/dL (over one cross by dipstick on two occasions 4-24 hours apart). RESULTS: The average daily calcium intake in this population was approximately 51% of the Recommended Dietary Allowance. Calcium supplementation was associated with a significantly decreased risk of preeclampsia (risk reduction 12.35%; P < .001), with 3.2% (n = 4) developing preeclampsia in the treatment group versus 15.5% (n = 21) in the placebo group. Moreover, calcium supplementation led to a reduction in systolic BP of 9.1 mmHg and in diastolic BP of 6.0 mmHg. CONCLUSION: These results suggest that calcium supplementation during pregnancy in populations with low calcium intake is a safe, effective, and inexpensive preventive measure that significantly reduces the risk of preeclampsia.