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Biomedical subjects

F Vargas

Publications and source records attributed to F Vargas.

At least 19 recordsLinked to original sources

Effect of statin treatment on oxidative stress and renal function in renal transplantation.

The beneficial action of statins on the lipid profile, cardiovascular disease, and death is well known. Besides their lipid-lowering role, these drugs have pleiotropic action that derive from their prevention of the synthesis of isoprenoids, mediators in cell signaling. Thus, due to their antioxidant capacity, statins can decrease the production of reactive oxygen species by inhibiting NAD(P)H oxidase activity. Previous studies by our group have described increased oxidative stress status in renal transplantation that might benefit from HMG CoA reductase inhibitor therapy. The aim of this study was to assess the influence of statins on stress parameters and their relevance to renal function in kidney transplantation. In 58 transplanted patients a first blood sample was obtained, without statins followed by 21 patients treated with statins (group 1) and 37 patients without drug (group 0) for a 6-month study period. We collected clinical data as well biochemical results on lipid profile, creatinine and oxidative stress. Lipid profile reduction was significant among group 1 compared with group 0. An increased glutathione peroxidase (GPx) among observed in all patients was greater in the statin-treated group (P = .006). No differences in creatinine or Cockroft-Gault values were observed between before versus after drug administration. In conclusion, statin treatment in renal transplantation improves the lipid profile and may increase GPx-measured antioxidant capacity but appears to have no short-term effect on renal function.

Humans↗

Influence of thyroid disorders on kidney angiotensinase activity.

Thyroid disorders affect renal function, which involves changes in local renin angiotensin system (RAS). Angiotensin peptide levels in the tissue are regulated by the activity of several aminopeptidases (AP) known as angiotensinases. The nature and consequences of the thyroid-induced RAS changes are not completely understood. We investigated the relationship between thyroid status (hyper- and hypothyroidism) and several kidney AP actions involved in RAS control. We have determined fluorometrically soluble (SOL) and membrane-bound (M-B) alanylaminopeptidase (AlaAP), glutamylaminopeptidase (GluAP) and aspartylaminopeptidase (AspAP) activity using naphthylamide derivatives as substrates. Sprague-Dawley rats were divided into three groups--control, hyperthyroid, and hypothyroid. Hyperthyroidism was induced by daily subcutaneous injection of L-thyroxin (300 microg/kg/day). Hypothyroidism was induced by continuous administration of methimazole (0.03%) in drinking water. Hypothyroid animals demonstrated a significant increase in SOL and M-B GluAP activity in renal cortex and a decrease in M-B AlaAP compared to euthyroid rats. This result may suggest higher Ang III availability. In hyperthyroid animals, M-B AlaAP and M-B AspAP activity increased significantly, which may suggest increased Ang III to Ang IV metabolism and greater formation of Ang 2-10, respectively. In contrast, no differences were observed between euthyroid and hypothyroid animals for SOL and M-B AP activity in renal medulla. However, hyperthyroid animals demonstrated a significant decrease in SOL and M-B GluAP activity compared to euthyroid rats, which may suggest a greater availability of Ang II in renal medulla. Alterations in angiotensin metabolism may, in part, account for some changes in renal function during thyroid disorders.

Angiotensin II↗

[Salivary cortisol determination in the diagnosis of pediatric Cushing's disease].

Endogenous Cushing's syndrome in children is a very rare entity. Diagnosis is complex due to the wide variety of tests available. Recently, the utility of salivary cortisol has been proposed for the diagnosis of this entity, although greater evidence is required, especially in pediatric patients. We report a 14-year-old girl with Cushing's disease due to a pituitary microadenoma in whom salivary cortisol determination was very useful for the diagnosis.

Adenoma↗

Approaches to Scrapie diagnosis by applying immunohistochemistry and rapid tests on central nervous and lymphoreticular systems.

Comparative studies evaluating the performance of Transmissible Spongiform Encephalopathies (TSE) rapid tests (validated for Bovine Spongiform Encephalopathy samples) on Scrapie samples have not been reported widely, particularly those dealing with lymphoreticular system tissues to a much lesser extent. The main objective of this study was to compare the ability of two current rapid tests (Western blot and Luminiscence Immunoassay Prionics-Check; WB and LIA, respectively) to detect PrPsc using central nervous system as well as lymphoreticular system samples corresponding to naturally infected animals. Thirty-four Scrapie-affected sheep, 26 with clinical signs of the disease, were included in the study. Tonsil, retropharyngeal lymph node and medulla oblongata were assessed by three tests: immunohistochemistry (confirmatory test), WB and LIA (rapid tests). The conclusion which can be drawn from this study is the fact that all animals involved in the study, including those at a preclinical stage, could be diagnosed regardless of the test used (with immunohistochemistry consistently showing higher sensitivity) only when the analyses of both the central nervous system and the lymphoreticular system were considered. The choice of these tissues for routine diagnosis is, therefore, proposed as a valuable tool to highly reduce the number of undetected positive cases.

Animals↗

Modulation factors of oxidative status in stable renal transplantation.

Reactive oxygen species (ROS) trigger a biomolecular alteration that causes functional and structural changes. In renal transplantation, there is an increase in oxidative phenomena related to endothelial dysfunction, inflammation, and atherosclerosis, the main cause of cardiovascular complications and chronic allograft failure. The present study was designed to assess the oxidative state of transplant patients with stable renal function, in order to establish differences in oxidative, biochemical, and clinical parameters between patients treated with tacrolimus versus cyclosporine. We studied 67 stable kidney transplant patients treated with calcineurin inhibitors who were not receiving cholesterol-lowering therapy, and 14 healthy subjects. Data were collected on biochemical parameters: lipid profile (apoA, apoB, total cholesterol and fractions, and triglycerides); urea; and creatinine; oxidative parameters: malondialdehyde (MDA) as a lipid peroxidation marker, glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD), glutathione reductase (GR), and antibodies against oxidized LDL; and clinical variables. Transplanted patients showed a higher oxidative status (MDA increase and GPx decrease) than healthy subjects. The oxidative status did not differ between the cyclosporine and tacrolimus cohorts. Some factors during the posttransplant period, such as delayed graft function, cytomegalovirus infection, and microalbuminuria, which may damage renal function, produce a decreased antioxidant capacity (lower GPx).

Cholesterol↗

Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus.

BACKGROUND: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. OBJECTIVE: To identify the best drug, dose, and treatment. PATIENTS AND METHODS: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. RESULTS: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). CONCLUSIONS: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.

Acute Disease↗

Clozapine prevents apoptosis and enhances receptor-dependent respiratory burst in human neutrophils.

The present study was undertaken to determine if the antipsychotic drug clozapine (CLZ) in the concentration range 2-50 microM can rescue polymorphonuclear cells (PMNs) from undergoing apoptosis. Our results indicate that 20 microM CLZ can rescue PMNs both from UVB-accelerated (28.0% vs. 45.9% for control without CLZ; P < 0.05) and from spontaneous (35.8% vs. 57.6%; P < 0.05) apoptosis whereas 50 microM CLZ could rescue PMNs from spontaneous (34.3% vs. 57.6%; P < 0.05) apoptosis only. Furthermore, since apoptosis has been reported to involve the impairment of PMN function, we evaluated the effects of CLZ on respiratory burst in UVB-irradiated and in unirradiated PMNs. When 20 or 50 microM CLZ-pretreated PMNs were aged in a culture during 4 h, the luminol-dependent chemiluminescence (CL) response was 3-fold (P < 0.01) and 2.5-fold (P < 0.05) increased, respectively, by subsequent exposure to serum opsonized zymosan (OZ). When 50 microM-pretreated PMNs were either UVB-irradiated or unirradiated, the CL response was 2.6-fold (P < 0.05) and 3.3-fold (P < 0.05) increased, respectively, after subsequent exposure to formyl-methionyl-leucyl-phenylalanine (fMLP). In contrast, the degree of enhancement was negligible upon subsequent exposure to ionomycin or phorbol myristate acetate (PMA). When incubation times were extended up to 22 h, the CL response induced by OZ in 20 microM CLZ-treated PMNs had a 4.9-fold increase (P < 0.001). This priming effect could be reverted when 20 microM CLZ-treated PMNs (aged 4 h in culture) were coincubated for 5 min with the protein tyrosine kinase inhibitor genistein as well as with the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin. These findings suggest that CLZ primes respiratory burst and prevents PMN apoptosis as a consequence of tyrosine phosphorylation- and PI3-K activation-dependent signal transduction pathways.

Androstadienes↗

Vaginal misoprostol 800 microg every 12 h for second-trimester abortion.

The objective of the study was to evaluate the efficacy and safety of 800 microg misoprostol every 12 h, up to three doses, for pharmacological second-trimester abortion. The misoprostol doses were always administered by doctors into the vagina. Two-hundred and sixty-nine women with gestations within 12 and 20 weeks were recruited into the study. The main outcomes measured were successful abortion (passage of fetus and placenta without surgery), side effects and mean drop in hemoglobin, vaginal bleeding and mean time of return of menstruation. Complete abortion occurred in 245/269 (91.1%, 95% confidence interval 87-94%) patients. Vaginal bleeding lasted 15.7 +/- 4.1 days. The mean drop in hemoglobin, calculated 24 h after abortion, were statistically significant (p = 0.0001), as also was the mean hemoglobin measured 14 days after abortion, but without clinical relevance. According to the results obtained, 800 microg of misoprostol administered every 12 h, up to a maximum of three doses, could be a valid method for abortion within 12 and 20 weeks of gestation.

Abortion, Induced↗

Role of neuronal nitric oxide synthase in response to hypertonic saline loading in rats.

AIMS: This study analyses the influence of neuronal nitric oxide synthase (nNOS) blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). METHODS: The following groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg(-1), and rats treated with L-NAME at 0.5 or 5 mg kg(-1). A further five groups received an isotonic saline load (ISL). RESULTS: Mean arterial pressure (MAP) was significantly increased in control rats after HSL. MAP was further increased in both 7NI-treated groups, and the L-NAME groups showed marked dose-related pressor responses. During ISL, MAP was only significantly increased in the group treated with 5 mg kg(-1) of L-NAME. The pressure-natriuresis relationship during the experimental period after the HSL was reduced in the 7NI group treated with 5 mg kg(-1) and severely attenuated in both L-NAME groups. The increase in plasma sodium was significantly greater after the HSL in both 7NI groups and both L-NAME groups compared with controls. CONCLUSIONS: The present results suggest that nNOS and other NOS isozymes play a counter-regulatory role in the pressor response to HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a blunted pressure-natriuresis relationship in response to the HSL. Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis.

Animals↗

Effects of deoxycorticosterone on renal vascular reactivity and flow-pressure curve in spontaneously hypertensive rats.

The role of mineralocorticoids as sodium retaining hormones has been recently enlarged to include their function as modulators of cardiovascular function and injury. This study evaluated the contribution of possible functional changes in resistance vessels to the additional BP increase produced by the chronic administration of DOCA to SHR. The flow-pressure curve and renal responses to vasoconstrictors (phenylephrine [Phe] and angiotensin II [AII]) and vasodilators (acetylcholine [ACh] and nitroprusside [NP]) were characterized in isolated kidneys from Wistar Kyoto (WKY) and SHR treated or untreated with DOCA for nine weeks. DOCA increased BP in SHR but did not modify BP in WKY rats. Kidneys from SHR showed enhanced reactivity to Phe and AII that was not increased by DOCA. DOCA reduced sensitivity to AII in SHR. Responsiveness to ACh was increased in SHR and was not attenuated by DOCA in WKY or SHR. Vasodilator response to NP was not significantly affected by DOCA in WKY or SHR. The flow-pressure curve was markedly up-shifted in SHR when compared with kidneys from WKY rats. DOCA administration did not modify the flow-pressure curve in WKY but produced attenuation at low flow levels in SHR. Our results demonstrate that DOCA increases BP in SHR but does not increase the flow-pressure curve or renal vascular reactivity to vasoconstrictors, and does not reduce responsiveness to endothelium-dependent and independent vasodilators in SHR or WKY rats. Therefore, our data suggest that the BP increase produced by DOCA in SHR is not related to abnormalities in vascular function in resistance vessels.

Acetylcholine↗

Human mixed infections of Leishmania spp. and Leishmania-Trypanosoma cruzi in a sub Andean Bolivian area: identification by polymerase chain reaction/hybridization and isoenzyme.

Parasites belonging to Leishmania braziliensis, Leishmania donovani, Leishmania mexicana complexes and Trypanosoma cruzi (clones 20 and 39) were searched in blood, lesions and strains collected from 28 patients with active cutaneous leishmaniasis and one patient with visceral leishmaniasis. PCR-hybridization with specific probes of Leishmania complexes (L. braziliensis, L. donovani and L. mexicana) and T. cruzi clones was applied to the different DNA samples. Over 29 patients, 8 (27.6%) presented a mixed infection Leishmania complex species, 17 (58.6%) a mixed infection Leishmania-T. cruzi, and 4 (13.8%) a multi Leishmania-T. cruzi infection. Several patients were infected by the two Bolivian major clones 20 and 39 of T. cruzi (44.8%). The L. braziliensis complex was more frequently detected in lesions than in blood and a reverse result was observed for L. mexicana complex. The polymerase chain reaction-hybridization design offers new arguments supporting the idea of an underestimated rate of visceral leishmanisis in Bolivia. Parasites were isolated by culture from the blood of two patients and lesions of 10 patients. The UPGMA (unweighted pair-group method with arithmetic averages) dendrogram computed from Jaccard's distances obtained from 11 isoenzyme loci data confirmed the presence of the three Leishmania complexes and undoubtedly identified human infections by L. (V.) braziliensis, L. (L.) chagasi and L. (L.) mexicana species. Additional evidence of parasite mixtures was visualized through mixed isoenzyme profiles, L. (V.) braziliensis-L. (L.) mexicana and Leishmania spp.-T. cruzi. The epidemiological profile in the studied area appeared more complex than currently known. This is the first report of parasitological evidence of Bolivian patients with trypanosomatidae multi infections and consequences on the diseases' control and patient treatments are discussed.

Animals↗

Evidence of expression of endotoxin receptors CD14, toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells.

CD14, a GPI-linked membrane protein, is a component of the lipopolysaccharide (LPS) receptor complex, one of the pattern-recognizing receptors (PRR) expressed by myeloid lineage cells. Here we report that CD14, the functionally linked toll-like receptor molecules, TLR2 and TLR4, and the associated molecule MD-2 are expressed in endocrine cells of the human pancreatic islets. CD14 expression in human pancreatic islets was determined by immunofluorescence staining of tissue sections and primary cultures, and confirmed by flow cytometry of dispersed normal islets and SV40-transformed islet cells (HP62). The latter cells synthesized and secreted CD14 in response to lipopolysaccharide (LPS) in a time- and dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR)-Southern was positive for CD14, TLR2, TLR4 and MD-2 in human pancreas, purified islets and HP62 cells. In vitro experiments using rat islets (also positive for CD14 by RT-PCR) and HP62 cells showed that LPS regulates glucose-dependent insulin secretion and induces inflammatory cytokines [interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)-alpha]. The functional expression of CD14 and associated molecules in islet beta cells adds a new pathway that islet cells may follow to adjust their function to endotoxaemia situations and become vulnerable to the inflammatory events that occur during diabetogenic insulitis.

Adolescent↗

Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.

A local renin-angiotensin system (RAS) that may be involved in their regulatory functions has been identified in hypothalamus and pituitary. Altered thyroid status induces modifications in the secretory function of hypothalamus and pituitary. However, few studies have analyzed the role of the RAS in hypothalamus and, to our knowledge, there is no data on the pituitary RAS during thyroid dysfunction. In the present study, angiotensinase activities (glutamyl, aspartyl and alanyl aminopeptidase: GluAP, AspAP and AlaAP, respectively) were studied in hypothalamus and in the anterior and posterior lobes of pituitary of euthyroid, hypothyroid and hyperthyroid adult male rats. In the anterior pituitary, compared with euthyroid and hyperthyroid rats, hypothyroid animals showed a highly significant increase of GluAP and AspAP activities; the percentage increase in GluAP was markedly higher than the percentage increase in AspAP. This suggests an increased metabolism of angiotensin (Ang) I and Ang II to des-Asp 1-Ang I and Ang III, respectively. We also observed an increase of Ang III-degrading activity (AlaAP) in the hypothalamus of hyperthyroid rats in soluble fraction. Increased Ang I and Ang II metabolism in the anterior pituitary of hypothyroid rats and increased metabolism of Ang III in the hypothalamus of hyperthyroid animals may be related to alterations in the secretory function of hypothalamus and pituitary in these thyroid dysfunctions.

Animals↗

[Non-invasive ventilation in immunosuppressed patients].

INTRODUCTION: In immunosuppressed patients with acute respiratory insufficiency (ARI) mechanical ventilation is associated with a high mortality. Therefore, in this situation, avoidance of intubation could be an important objective. However, experience of non-invasive ventilation (NIV) in the immunosuppressed remains limited. STATE OF ART: The first descriptive studies have shown that NIV could be an alternative to intubation, particularly in patients with malignant haematological disorders. In a prospective randomised controlled study Antonelli et al. showed that the use of NIV significantly improved the prognosis of patients with ARI following organ transplantation. We have carried out a prospective randomised controlled trial in 52 immunosuppressed patients to determine whether NIV improved the prognosis in patients admitted to intensive care with pulmonary infiltrates, fever and ARI. The use of NIV was associated with significant reductions in the intubation rate, serious complications and ICU and hospital mortality. PERSPECTIVES: Further studies are needed in order to better define the patients susceptible to benefit from NIV, and to establish variables predictive of the success or the failure of the method. CONCLUSIONS: NIV leads to an improvement in the prognosis of some immunosuppressed patients admitted to intensive care.

Acquired Immunodeficiency Syndrome↗

Photochemistry and in vitro phototoxicity studies of levomepromazine (methotrimeprazine), a phototoxic neuroleptic drug.

The neuroleptic drug levomepromazine (1, previously known as methotrimeprazine) is photolabile under UV-A and UV-B light in aerobic conditions. Irradiation of a methanol solution of this drug produces one photoproduct, resulting from the oxidation of 1 to its sulfoxide parent. It is demonstrated that photodegradation occurs via type II mechanism involving irreversible trapping of self-photogenerated singlet molecular oxygen. 1 shows a photohemolytic effect on human erythrocytes and photoinducers lipid peroxidation.

Antipsychotic Agents↗

Antioxidant properties of dipyridamole as assessed by chemiluminescence.

The ability of dipyridamole (DIP) to scavenge oxygen metabolites generated by either activated human neutrophils (PMNs) or cell-free systems using luminol(s)- and lucigenin-enhanced chemiluminescence was investigated. In the presence of DIP (15-50 microM) a dose-dependent inhibition period was seen in phorbol myristate acetate (PMA)-stimulated PMNs as assayed by isoluminol-enhanced chemiluminescence (ILCL) with horseradish peroxidase (HRP). Although such a lag period was not observed in the absence of HRP, 50 microM DIP inhibited extracellular ILCL by more than 50%. Intracellular luminol-enhanced chemiluminescence (LCL) as assayed in either PMA- or in ionomycin-activated PMNs was not affected by dipyridamole (15-50 microM). In cell-free systems, DIP produced concentration-dependent inhibition in H2O2-(45% at 50 microM), OH- (40%, at 0.1 microM) and HOCl-(20% at 10 microM). Both absorbance and fluorescence scans revealed that DIP is able to react with equimolar quantities of either H202 or HOCl. These results suggest that DIP scavenges reactive oxygen species (ROS) presumably secreted by activated human PMNs in the following decreasing order: *OH > HOCl > H2O2 >> O2-.

Acridines↗

[Association of type 1 neurofibromatosis and primary hyperparathyroidism].

INTRODUCTION: The combination of neurofibromatosis type I with hyperparathyroidism is classical but rare. OBSERVATION: Our report is on the original observation of a patient affected with Von Recklinghausen's disease complicated by chronic restrictive breathing deficiency. After an intense breathing decompensation and a spreading convulsive attack, hyperparathyroidism was diagnosed. DISCUSSION: The similarity of the bone lesions seen in type I neurofibromatosis and in hyperparathyroidism strongly suggests a genetic link between these two pathologies. Hence, hyperparathyroidism should be searched for in all patients affected with Von Recklinghausen's disease, since the adjustment of hypercalcemia can lead to partial reversibility of the bone abnormalities.

Acute Disease↗