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Biomedical subjects

L Fernandes

Publications and source records attributed to L Fernandes.

At least 19 recordsLinked to original sources

Macrophage formation of angiostatin during inflammation. A byproduct of the activation of plasminogen.

Angiostatin is a potent inhibitor of tumor angiogenesis and the growth of metastatic foci. Recent studies have indicated that neoplastic cells can generate angiostatin directly or in cooperation with tumor-associated macrophages. In studies reported here, we determined whether angiostatin is generated in mice under non-neoplastic settings. Utilizing murine RAW264.7 macrophages and thioglycollate-elicited peritoneal macrophages, we demonstrate that angiostatin-like fragments are generated as a byproduct of the proteolytic regulation of membrane-bound plasmin. Plasmin proteolysis and subsequent loss in membrane-bound plasmin activity requires active plasmin but was unaffected by inhibitors of metalloproteinases. Lysine binding fragments of plasmin, isolated from macrophage-conditioned media utilizing affinity chromatography, appeared as a major (48 kDa) and two minor bands (42 and 50 kDa) in SDS-polyacrylamide gel electrophoresis and were immunoreactive with anti-kringle 1-3 IgG. Each peptide begins with Lys77 and contains the entire sequence of angiostatin. The affinity isolated plasmin fragments inhibited bFGF-induced endothelial cell proliferation. Lavage fluid recovered from the peritoneal cavities of mice previously injected with thioglycollate contained angiostatin-like plasmin fragments similar to those generated in vitro. This is the first demonstration that angiostatin-like plasmin fragments are generated in a non-neoplastic inflammatory setting. Thus, in addition to regulating pericellular plasmin activity, proteolysis of plasmin generates inactive kringle-containing fragments expressing angiostatic properties.

Angiostatins↗

An initially double-blind controlled 96 week trial of depot methylprednisolone against oral prednisolone in the treatment of polymyalgia rheumatica.

The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is considerably smaller than that with conventional OP, and may therefore be associated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was multicentre hospital out-patient based and included 60 patients with untreated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gradual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation rate, pain and morning stiffness, and percentage of adverse reactions and serious complications such as fractures, were the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and similar disease control in the succeeding open phase. With steroid tapering, the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose in subjects treated with i.m. MP was equivalent to 56% that of subjects treated with OP. There were eight fractures with OP compared to one on i.m. MP. Mean weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P < 0.005). Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m. MP. Only patients on OP reported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long-term disease control in PMR with i.m. MP compared to OP. I.m. MP was associated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and non-rheumatic diseases.

Administration, Oral↗

Public awareness and attitudes toward epilepsy in different social segments in Brazil.

PURPOSE: To assess public awareness and attitudes toward epilepsy in Brazilians of different cultural and socioeconomic backgrounds. BACKGROUND: Several studies have examined public awareness and attitudes toward epilepsy in various countries but there are no equivalent data for Brazil or South America. MATERIAL AND METHODS: We have applied the survey proposed by Caveness and Gallup, with some modifications and adaptations to four groups (I-IV) of subjects: I--105 individuals accompanying patients to the Ophthalmologic outpatient clinic of the Hospital das Clínicas of the State University of Campinas (UNICAMP); II--93 students recently admitted to medical and nursing school; III--101 senior non-medical students; and IV--69 senior medical students. Group II, III, and IV were students at UNICAMP. RESULTS: Individuals with a low socioeconomic standing had a poor profile of familiarity, knowledge and attitudes toward epilepsy. The pre-university and university students had a relatively good profile when compared to the published international polls. Senior medical students had an excellent level of familiarity and knowledge, but showed no change in their objection to having a son or a daughter marry an epileptic person. CONCLUSIONS: Our data suggest that there is a clear-cut relationship between the level of education and the individual's familiarity and attitudes toward epilepsy. Effective elimination of the prejudice toward epilepsy requires specific training and not just general, superficial information about the condition.

Adolescent↗

The role of electronic merges in an integrated delivery system.

The electronic-only merge method poses a serious challenge to HIM management for ensuring that all clinical documentation for patient care is provided in a timely manner. The organization must be aware of all of the issues affecting the departments so that informed decisions can be made before, during, and after the project. This approach can be successful with comprehensive planning, meticulous procedures for record retrieval and chart folder updating, and extensive staff training. The proactive, traditional merge approach remains the community standard. However, the reactive, electronic-only merge approach has found a niche and can be a viable, cost-effective option when faced with time and budgetary constraints. However, a combination of these approaches may provide the best solution, depending upon an organization's resources, time requirements, and strategic goals.

Computer Systems↗

Glucose respiration and fermentation in Zygosaccharomyces bailii and Saccharomyces cerevisiae express different sensitivity patterns to ethanol and acetic acid.

In the yeast Zygosaccharomyces bailii ISA 1307, respiration and fermentation of glucose were exponentially inhibited by ethanol, both processes displaying similar sensitivity to the alcohol. Moreover, the degree of inhibition on fermentation was of the same magnitude as that reported for Saccharomyces cerevisiae. Acetic acid also inhibited these two metabolic processes in Z. bailii, with the kinetics of inhibition again being exponential. However, inhibition of fermentation was much less pronounced than in S. cerevisiae. The values estimated with Z. bailii for the minimum inhibitory concentration of acetic acid ranged from 100 to 240 mmol 1(-1) total acetic acid compared with values of near zero reported for S. cerevisiae. The inhibitory effects of acetic acid on Z. bailii were not significantly potentiated by ethanol.

Acetic Acid↗

Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions.

Saccharomyces cerevisiae contains eight members of a novel and fungus-specific family of bZIP proteins that is defined by four atypical residues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistance. Although initially described as AP-1 factors, at least four Yap proteins bind most efficiently to TTACTAA, a sequence that differs at position +/-2 from the optimal AP-1 site (TGACTCA); further, a Yap-like derivative of the AP-1 factor Gcn4 (A239Q S242F) binds efficiently to the Yap recognition sequence. Molecular modeling suggests that the Yap-specific residues make novel contacts and cause physical constraints at the +/-2 position that may account for the distinct DNA-binding specificities of Yap and AP-1 proteins. To various extents, Yap1, Yap2, Yap3, and Yap5 activate transcription from a promoter containing a Yap recognition site. Yap-dependent transcription is abolished in strains containing high levels of protein kinase A; in contrast, Gcn4 transcriptional activity is stimulated by protein kinase A. Interestingly, Yap1 transcriptional activity is stimulated by hydrogen peroxide, whereas Yap2 activity is stimulated by aminotriazole and cadmium. In addition, unlike other yap mutations tested, yap4 (cin5) mutations affect chromosome stability, and they suppress the cold-sensitive phenotype of yap1 mutant strains. Thus, members of the Yap family carry out overlapping but distinct biological functions.

Amino Acid Sequence↗

[Importance of nutritional aspects in attention deficit hyperactivity disorders].

The attention deficit hyperactivity disorder is a common childhood syndrome that is recognized as an important medical-social problem, being the object of an exhaustive investigation related to its etiology, diagnostic approach and prevention, and treatment forms. Among the factors that can alter the cerebral function, is the malnutrition. The authors discuss the association of the syndrome with the nutritional condition of students from elementary schools.

Analysis of Variance↗

[Use of manual vacuum aspiration in reducing cost and duration of hospitalization due to incomplete abortion in an urban area of northeastern Brazil].

INTRODUCTION: In most developed countries vacuum aspiration has been shown to be safer and less costly than sharp curettage (SC) for uterine evacuation. In many of the developing countries, including Brazil, sharp curettage (SC) is the most commonly used technique for treating cases of incomplete abortion admitted to hospital. The procedure often involves light to heavy sedation for pain control and an overnight hospital stay for patient recuperation and monitoring. Two hypotheses are examined: the first, that the use of manual vacuum aspiration (MVA)--a variation of the vacuum aspiration, would be less costly than SC for the treatment of cases of incomplete abortion admitted to hospital; and the second, that the treatment of incomplete abortion with MVA would substantially reduce the length of hospital stay. METHODOLOGY: Thirty women with diagnosis of first trimester incomplete abortion were randomly allocated to the SC or MVA group. Rapid-assessment data collection techniques were used to identify factors that contributed to cost reduction and hospital stay. RESULTS AND CONCLUSION: The results of the study show that, overall, patients treated for incomplete abortion with MVA spent 77% less time in the hospital and consumed 41% fewer resources than similarly diagnosed patients treated with SC. Recommendations are made as to the need of certain changes in patient management. Particularly necessary is information regarding cultural perception and concepts of abortion treatment.

Abortion, Incomplete↗

Degrees of poverty.

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Costs and Cost Analysis↗

Continuous measurement of porcine renal cortex microcirculation with enhanced thermal diffusion technology.

Continuous monitoring of renal cortical blood flow (RCBF) in the perioperative setting of aortic or renal vascular surgery could facilitate the early detection of vascular complications, possibly resulting in a reduction of postoperative renal failure. A new prototype system for measurement of parenchymous organ perfusion based on the principle of thermal diffusion ("TD"-Thermal Diffusion Electrode, Thermal Technologies Inc., Cambridge, MA, USA) was used for RCBF measurements in the outer cortex of the porcine kidney. We validated the sensitivity of the device to detect renal blood flow impairment, comparing TD flow data with renal artery blood flow values (RABF), measured by ultrasonic flow probes. The hypothesis was tested that acute disturbances of RCBF, induced by a variable degree of renal artery stenosis, can be immediately detected and continuously monitored by TD measurements in the porcine renal cortex. Mean baseline RCBF measured by TD electrodes was 68.1 +/- 25.0 ml/100 g/min. Mean baseline RABF was 102.1 +/- 26.6 ml/min. Controlled induction of a variable degree of renal arterial occlusion by implanted vascular balloon occluders was always followed by an immediate and proportional decline of RCBF, as measured by TD. Flow data obtained with both methods were significantly correlated by linear regression (r=.82, r2=.68; P < 0.0001). Dynamic changes of RABF in the time course of renal artery partial/total occlusion and arterial flow release could be continuously followed by detection of corresponding flow changes of RCBF. We conclude that the TD system investigated in the current study allows a continuous and sensitive determination of porcine renal cortex perfusion. A clinical evaluation of the method, e.g., in the perioperative setting of aortic or renal transplantation surgery, now appears to be justified.

Animals↗

Anacardium occidentale (cashew) pollen allergy in patients with allergic bronchial asthma.

BACKGROUND: The cashew tree grows in abundance in the hills and plains of Goa, India. Because of the financial yield, more and more trees are being planted each year. The cashew tree flowers once a year between January and March, but pollination is mostly entomophilous. OBJECTIVE: For the first time, a study was conducted to establish the possible role of the cashew pollen in triggering allergic asthma. METHODS: A stock solution of pollen extract was prepared with the standard weight/volume method for intradermal skin tests and a bronchial provocation tests (BPTs). The protein content of the antigen, estimated with the use of Folin phenol reagent and a spectrophotometer, was 28.72 mg/ml. Ten healthy volunteers and 65 subjects with allergic asthma, as documented by previous positive skin test reactions to various pollens, were studied. RESULTS: Of the 65 patients, 26 (40%) had positive skin test reactions in various grades. BPTs were performed in 22 of the 26 patients after their baseline peak expiratory flow volume was assessed. Twenty (90.9%) patients had a positive BPT result, and the majority of patients had grade III and grade IV reactions. None of the control subjects (n = 10) had positive responses to either intradermal tests or the BPT. Serum IgE levels, estimated by ELISA, were high in patients with positive skin test responses and showed a linear correlation with cutaneous sensitivity. Control subjects showed normal levels of IgE (39.0 +/- 7.87 IU/ml). CONCLUSIONS: This study provided us with knowledge of an additional pollen, Anacardium occidentale, which could trigger an asthmatic response in allergic individuals.

Adolescent↗

[Induction of impaired hepatic microcirculation by in situ hilus preparation in liver explantation].

AIM: Usually, in-situ preparation of the hepatic hilar structures is performed prior to the perfusion with preservation solution. Aim of this study was to investigate mechanical effects of liver preparation on the hepatic microcirculation. METHODS: 16 pigs (German landrace) were randomized in two groups. In both groups, laparotomy was performed after intratracheal intubation. Subsequently, a thermal diffusion probe was implanted into the medial left liver lobe for quantification of microperfusion. In group A (n = 8), bile duct, hepatic artery, and portal vein were exposed and the lesser omentum transsected thereafter. Ultrasound-volume-probes were placed around the hepatic artery and portal vein. Simultaneous measurement of hepatic microperfusion and total liver blood flow was performed five minutes after the end of liver preparation. In group B (n = 8) hepatic microperfusion was quantified 45 minutes after laparotomy without further manipulations. RESULTS: By the preparation, liver perfusion was significantly reduced in group A from 78 +/- 13 ml/100g/min to 61 +/- 16 ml/100g/min. After preparation a total liver blood flow of 137 +/- 46 ml/100g/min was recorded indicating a shunt fraction of 51 +/- 21%. In contrast, hepatic microperfusion in group B remained at baseline during the whole observation period (79 +/- 3 ml/100g/min vs. 78 +/- 5 ml/100g/min). CONCLUSION: In-situ liver preparation induces a relevant disturbance of hepatic microcirculation. Preservation perfusion shortly after surgical manipulation could become ineffective because of an increase in shunt flow. If the regeneration period is too short, e.g. lack of heart explantation, the quality of the liver graft could be limited.

Animals↗

Complete DNA sequence of yeast chromosome XI.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.

Base Sequence↗