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Biomedical subjects

D Fernandes

Publications and source records attributed to D Fernandes.

At least 19 recordsLinked to original sources
PubMed2006

Kallikrein-kinin system activation by Lonomia obliqua caterpillar bristles: involvement in edema and hypotension responses to envenomation.

Lonomia obliqua envenomation induces an intense burning sensation at the site of contact and severe hemorrhage followed by edema and hypotension, and after few days death can occur usually due to acute renal failure. In order to understand more about the envenomation syndrome, the present study investigates the role played by kallikrein-kinin system (KKS) in edematogenic and hypotensive responses to the envenomation by L. obliqua. The incubation of L. obliqua caterpillar bristles extract (LOCBE) with plasma results in kallikrein activation, measured by cromogenic assay using the kallikrein synthetic substrate S-2302 (H-D-Pro-Phe-Arg-pNA). It was also showed that LOCBE was able to release kinins from low-molecular weight kininogen (LMWK). Moreover, it was demonstrated that previous administration of a kallikrein inhibitor (aprotinin) or bradykinin B2 receptor antagonist (HOE-140) significantly reduces the edema and hypotension in response to LOCBE, using mouse paw edema bioassay and mean arterial blood pressure analysis, respectively. The results demonstrate a direct involvement of the KKS in the edema formation and in the fall of arterial pressure that occur in the L. obliqua envenomation syndrome.

Analysis of Variance↗
PubMed2002

Nitric oxide-induced inhibition of mouse paw edema: involvement of soluble guanylate cyclase and potassium channels.

OBJECTIVE AND DESIGN: To investigate the effect of nitric oxide (NO) donors on inflammatory mouse paw edema (MPE). MATERIALS AND METHODS: Mice previously treated with sodium nitroprusside (SNP; 1.5, 5 and 10 micromol/kg) or S-nitroso-N-acetyl-DL-penicillamine (SNAP; 7, 14 and 28 micromol/kg) were injected with inflammatory mediators in the paw. Paw edema, myeloperoxidase activity and vascular dye leakage were measured. RESULTS: Pre-treatment with SNP and SNAP (4 h or 12 h) reduced (approximately 50%) MPE induced by carrageenan, dextran sulfate, bradykinin and histamine but not by serotonin. Pre-treatment with SNP also inhibited carrageenan-induced increases in myeloperoxidase activity and vascular dye leakage. Methylene blue blocked the SNP-induced reduction in MPE when injected 30 min before or 2 h after SNP, but not 4 or 6 h after the NO donor. Tetraethylammonium blocked the SNP-induced reduction in MPE if injected 30 min before or 2, 4 or 6 h after SNP. CONCLUSIONS: NO donors have a long-lasting anti-inflammatory effect in MPE, which involves guanylate cyclase and tetraethylammonium-sensitive potassium channels.

Animals↗
PubMed2001

Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes of cancer patients before and after radiation treatment.

The frequency of micronucleated binucleate lymphocyte (MNBNC) was determined in the peripheral blood lymphocytes of patients suffering from various types of cancer before the onset of radiation treatment, middle (mid-) of the treatment and after completion of the treatment (post-treatment). The frequency of micronuclei increased significantly in the pretreatment sample of cancer patients when compared with the normal untreated healthy volunteers. During the middle of the radiotherapy an approximate two or > two-fold increase was observed in the micronuclei frequency in most of the patients when compared with the concurrent pretreatment samples. Immediately after the completion of treatment, the frequency of micronuclei further increased, and this increase was significantly higher than that of pretreatment and mid-treatment samples. Out of 27 patients analyzed, only nine patients did not have any history of smoking, tobacco chewing or alcohol consumption, while the remaining 18 patients had a history of either smoking, tobacco chewing or alcohol consumption or combination of two or all habits at the time of blood collection.

Adult↗
PubMed2000

Thrombin-stimulated DNA synthesis in human cultured airway smooth muscle occurs independently of products of cyclo-oxygenase or 5-lipoxygenase.

Arachidonic acid (AA) liberation and metabolism via cyclo-oxygenase or lipoxygenases may be an important regulatory pathway for mitogenic signalling in human cultured airway smooth muscle (ASM) cells. In cytokine-treated cells, thrombin markedly enhances production of the anti-mitogenic arachidonic acid metabolite, PGE(2). In this study, in the absence of cytokines, we examined the role of endogenous AA metabolism in thrombin-stimulated ASM DNA synthesis. Selective inhibitors of cyclo-oxygenase of 5-lipoxygenase metabolism had no significant effect on 0.3 U/ml thrombin-stimulated DNA synthesis. However, the non-selective, redox-active lipoxygenase inhibitors NDGA and BWA4C inhibited thrombin-stimulated DNA synthesis. Under basal conditions, and following stimulation by thrombin, the levels of the AA metabolites PGE(2), TxA(2), and LTC(4), remained below assay detection limits. Exogenous addition of AA, LTD(4), or 5-, 12-, and 15-HETE and HpETE metabolites had no consistent or substantial stimulatory effect on either basal or thrombin-stimulated DNA synthesis. These data suggest that the non-selective lipoxygenase inhibitors influence DNA synthesis via effects unrelated to lipoxygenase inhibition. The lack of detection of AA metabolites, the lack of influence of selective antagonists/inhibitors of the AA pathway, and the failure of selected AA metabolites to either enhance or directly stimulate DNA synthesis suggest that in the absence of cytokines, cyclo-oxygenase and lipoxygenase metabolism has little role in signalling of human ASM DNA synthesis by thrombin.

Arachidonate 5-Lipoxygenase↗
PubMed2000

Percutaneous and limited open reduction of intra-articular distal radial fractures.

Fluoroscopy monitors intra-articular distal radial fracture reduction and stabilisation. The reduction is guided by traction, ligamentotaxis and manipulation, and when necessary, completed by minimally invasive percutaneous or limited open instrumentation. Kirschner wires effectively splint the reduction until fracture callus is visualised on X-ray. An occasional mini plate is required to buttress a displaced volar medial lunate facet (die punch) fragment into position. First, major metaphyseal articular fragments are approximated to restore the articular surface. Smaller fragments follow their larger counterparts into position or may be ignored (the "Rule of the Majority" or "Vassal Rule"). The repaired metaphysis is then aligned with and stabilised to the diaphysis. Cancellous bone may be inserted through small targeted incisions when defects and areas of comminution are present. The wrist is splinted in a functional (slightly extended) position for three to four weeks in uncomplicated cases. Digital elevation and rehabilitation are emphasised during the early stages of fracture healing. After callus appears on X-ray, progressive wrist rehabilitation is initiated and the patients are weaned from their splints. Minimally invasive surgical intervention, good pain control and early rehabilitation maximise functional recovery and minimise morbidity, medical costs and lost work time.

Bone Wires↗
PubMed1999

Tolfenamic acid decreases migraine recurrence when used with sumatriptan.

Although sumatriptan is an effective drug for the treatment of acute migraine attacks, recurrence has been cited as an important limitation for its use. Tolfenamic acid is also effective in the acute treatment of migraine attacks. We studied the recurrence rate of migraine attacks with the use of sumatriptan plus tolfenamic acid among patients who presented frequent recurrence with sumatriptan. Fifty migraineurs were retrospectively studied, all having treated at least 10 attacks with 100 mg P.O.; sumatriptan was effective in at least eight of them. The patients also presented recurrence in less than 24 h in at least five of the treated attacks. We then used sumatriptan 100 mg plus tolfenamic acid 200 mg P.O. during the first 60 min of the attack; 240 attacks were treated and there was recurrence in 57 (23.8%). With sumatriptan alone, 5 out of 8 attacks (62.5%) presented recurrence. We therefore conclude that the combination sumatritpan plus tolfenamic acid is effective in reducing the recurrence rate from 5 of 8 (62.5%) to 1.19 of 5 (23.8%). Further prospective studies with a double-blind design and a higher number of treated attacks are necessary to confirm these initial observations.

Adult↗
PubMed1999

Glucocorticoids inhibit proliferation, cyclin D1 expression, and retinoblastoma protein phosphorylation, but not activity of the extracellular-regulated kinases in human cultured airway smooth muscle.

We have previously shown that glucocorticoids inhibit mitogen-stimulated proliferation of human cultured airway smooth muscle (ASM) cells. The present study analyzed the effect of glucocorticoids on key regulatory pathways leading to passage of cells through the restriction point of the cell cycle, including those mediated by extracellular-regulated kinases (ERK) 1 and 2; the ERK upstream regulator MAPK kinase (MEK1); cyclin D1 levels; and levels and phosphorylation of retinoblastoma protein (pRb). Fluticasone propionate, a new inhaled glucocorticoid, was at least 10-fold more potent than dexamethasone in inhibiting thrombin-stimulated DNA synthesis and increases in cell number. Thrombin-stimulated increases in the levels and hyperphosphorylation of pRb were inhibited by glucocorticoids, which also reduced thrombin-stimulated cyclin D1 protein and messenger RNA (mRNA) levels. PD98059 (10 microM), an inhibitor of MEK1 activation, markedly attenuated thrombin stimulation of ERK activity and phosphorylation, DNA synthesis, and cyclin D1 levels. However, glucocorticoids had no effect on ERK activity or phosphorylation at 5 min, 2 h, or 12 h after addition of thrombin. In conclusion, glucocorticoid-induced reduction of cyclin D1 mRNA and protein levels, and of pRb phosphorylation, is sufficient to account for inhibition of ASM proliferation. Furthermore, these inhibitory effects of glucocorticoids on cyclin D1 and pRb occur on a component of the mitogen signaling cascade that is either downstream of or parallel to the ERK pathway.

Androstadienes↗
PubMed1998

Repair of unilateral cleft lip: a comparison of five techniques.

Repair of unilateral cleft lip is a challenging procedure with no single technique satisfactory for all types of unilateral cleft deformity. This study compares retrospectively five techniques of unilateral cleft lip repair in 72 children (45 boys, 27 girls). Twenty-two children had a Millard rotation-advancement repair, 5 children had a Davies Z-plasty, 22 had a modified Z-plasty, 10 had a Tennison-Randall triangular flap repair, and 13 had a Nakajima-Yoshimura straight-line repair. Assessment was performed clinically by a plastic surgeon not involved in the original surgery. Repairs were assessed objectively by measurement of the vertical length of both the repaired and normal sides of the lip with calipers. Subjective criteria used to evaluate the repair were the symmetry of Cupid's bow, the quality of scar, the alignment of white roll, the evenness of the vermilion, and the lip pout. The mean follow-up period was 5.4 years (range, 9 months-29 years). Sixty-five of the 72 repairs measured (90%) were within two standard deviations (SDs) of normal and thus were considered to be of "acceptable" length. Seven repairs were unacceptably short (>2 SDs) on measurement, six of which included a rotation-advancement repair for a complete cleft lip. Subjective results paralleled the objective results. The outcome following repair of unilateral cleft lip was similar for all five surgical methods assessed except for complete cleft lips repaired by the rotation-advancement technique, which tended to result in an unacceptably short lip as measured on the repaired side.

Adolescent↗
PubMed1998

Admissions, length of stay, and discharge barriers at the Hawaii State Hospital.

Based on data gathered from patients, psychiatrists, and social workers at the Hawaii State Hospital, it was determined that the majority of patients had been in the hospital for more than one year, were committed for forensic reasons, and did not need continued hospitalization. An inter-agency systems approach is needed to address the issue of length of patient stay.

Adult↗
PubMed1997

Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained.

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.

Amifostine↗
PubMed1997

Adult T-cell leukemia-lymphoma in a patient with HTLV-I/II associated myelopathy.

Chronic myelopathy associated with T-lymphotropic virus type I (HAM) has been described as an endemic disease in several areas of the world, meanwhile there are few papers describing the association between HAM and adult T cell leukemia-lymphoma. We report the case of a man that, after four years of progressive spastic paraparesis and neurogenic bladder, developed a clinical picture of a lymphoproliferative disorder characterized by dermal and systemic involvement, mimicking mycosis fungoides/Sézary syndrome.

Aged↗
PubMed1997

Minimally invasive iliac cancellous bone graft harvesting.

We have described a technique for harvesting cancellous bone from the ilium that is minimally invasive and safe. This technique results in minimal donor-site morbidity, is quick and easy to perform without the need for special equipment or instruments, and allows a two-team operative approach. Sufficient bone graft material can be obtained for wide or bilateral clefts. We now use this technique routinely to harvest cancellous bone for secondary alveolar bone grafting in children with clefts. The procedure could be used in adults, it could also be used to obtain bone graft for treating other conditions, and other donor sites could be approached with the same technique.

Bone Transplantation↗
PubMed1996

The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels.

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.

Adolescent↗
PubMed1995

The effect of glucocorticoids on proliferation of human cultured airway smooth muscle.

1. Airway smooth muscle proliferation is a significant component of the airway wall remodelling that occurs in asthma. In this study, the effects of glucocorticoids on mitogenic responses of human airway smooth muscle have been examined. 2. Pretreatment of smooth muscle cells with dexamethasone (100 nM, 60 min) inhibited thrombin-induced increases in [3H]-thymidine incorporation (DNA synthesis) and cell number. 3. Inhibition of thrombin-induced [3H]-thymidine incorporation was also observed with hydrocortisone (0.01-1 microM) and methylprednisolone (0.001-0.1 microM) pretreatment. In contrast, pretreatment with either testosterone (0.001-1 microM) progesterone (0.001-1 microM), 17 beta-oestradiol (0.001-1 microM), or aldosterone (0.001-1 microM) had no effect on the response to thrombin. 4. Responses to a range of mitogens including thrombin (0.01-. 10 u ml-1), epidermal growth factor (EGF, 3-3000 pM), basic fibroblast growth factor (bFGF, 0.3-300 pM) and foetal calf serum (FCS, 0.1-10% v/v) were inhibited by dexamethasone (100 nM) pretreatment. However, the magnitude of the inhibitory effect was dependent on the mitogen, with EGF being the least, and thrombin being the most sensitive to the inhibitory effect. 5. The potency of hydrocortisone as an inhibitor of [3H]-thymidine incorporation was reduced when FCS (10% v/v, which caused a 40 fold increase in [3H]-thymidine incorporation) was used as the mitogen in place of thrombin (0.3 u ml-1, which caused a 10 fold increase in [3H]-thymidine incorporation). 6. The effect of post-treatment with dexamethasone (100 nM) indicated that addition of the glucocorticoid up to 17-19 h after thrombin (0.3 u ml-1) produced similar degrees of inhibition to those obtained when it was added as a pretreatment. Dexamethasone no longer produced an inhibitory effect if added 21 h or more after the addition of thrombin. 7. These results suggest that glucocorticoids regulate airway smooth muscle proliferation initiated by a range of stimuli. This effect may be of importance in the therapeutic actions of these compounds in asthma, particularly when they are used for prolonged periods of time.

Anti-Inflammatory Agents↗
PubMed1995

[A peripheral neuroectodermal tumor of the vulva].

A case of malignant peripheral neuroectodermal tumor occurring in the vulva of a 29-year-old woman is reported. It is a rare malignant tumor with aggressive biological behavior belonging to a wide group, the so-called small round-cell tumors. The patient is well and free of disease 8 months after surgery, chemotherapy and radiation therapy.

Adult↗
PubMed1994

Simultaneous determination of lidocaine, prilocaine and the prilocaine metabolite o-toluidine in plasma by high-performance liquid chromatography.

An HPLC assay is described for the measurement of prilocaine and lidocaine (components of the local anesthetic cream EMLA) as well as the prilocaine metabolite, o-toluidine, in plasma. The method uses UV detection, is simple, sensitive and most important, only a single 200-microliters plasma sample is needed for simultaneous analysis of prilocaine, lidocaine and o-toluidine with a detection limit of 4 ng/ml. The plasma, together with the internal standard (bupivacaine) is extracted with diethyl ether under alkaline conditions, followed by the extraction of the analytes from the organic phase into dilute sulphuric acid. An aliquot of the acid extract is injected onto the HPLC system and the effluent is monitored by a UV detector.

Animals↗