Alice Maria Costa Martins

Universidade Federal do Ceará, Ceará, Ceará, Brazil

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Publications (33)79.08 Total impact

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    ABSTRACT: As the dopamine D3R receptor is a promising target for schizophrenia treatment, an improved understanding of the binding of existing antipsychotics to this receptor is crucial for the development of new potent and more selective therapeutic agents. In this work, we have used X-ray co-crystallization data of the antagonist eticlopride bound to D3R as a template to predict, through docking essays, the placement of the typical antipsychotic drug haloperidol at the D3R receptor binding site. Afterwards, classical and quantum mechanics/molecular mechanics (QM/MM) computations were employed to improve the quality of the docking calculations, the QM part of the simulations being accomplished by using the density functional theory (DFT) formalism. After docking, the calculated QM improved total interaction energy EQMDI = -170.1 kcal/mol was larger (in absolute value) than that obtained with classical molecular mechanics improved (ECLDI = -156.3 kcal/mol) and crude docking (ECRDI = -137.6 kcal/mol) procedures. The QM/MM computations reveal the pivotal role of the Asp110 amino acid residue in the D3R haloperidol binding, followed by Tyr365, Phe345, Ile183, Phe346, Tyr373 and Cys114. Besides, it highlights the relevance of the haloperidol hydroxyl group axial orientation, which interacts with the Tyr365 and Thr369 residues enhancing its binding to dopamine receptors. Finally, our computations indicate that functional substitutions in the 4-clorophenyl and in the 4-hydroxypiperidin-1-yl fragments (such as C3H and C12H hydrogen replacement by OH or COOH) can lead to haloperidol derivatives with distinct dopamine antagonism profiles. The results of our work are a first step using in silico quantum biochemical design as means to impact the discovery of new medicines to treat schizophrenia.
    ACS Chemical Neuroscience 09/2014; · 3.87 Impact Factor
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    ABSTRACT: We aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease.
    BMC Infectious Diseases 08/2014; 14(1):451. · 3.03 Impact Factor
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    ABSTRACT: AimsDinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus.Methods and ResultsDqV was tested against a standard strain of Methicillin-Sensitive Staphylococcus aureus (MSSA), S. aureus ATCC 6538P and 2 standard strains of Methicillin-Resistant Staphylococcus aureus (MRSA), S. aureus ATCC 33591 and S. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested in order to check its action on S. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6.25 μg ml−1 and 12.5 μg ml−1 for S. aureus ATCC 6538P, 12.5 μg ml−1 and 50 μg ml−1 for S. aureus CCBH 5330 and 100 μg ml−1 and 100 μg ml−1 for S. aureus ATCC 33591, respectively. Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy.Conclusion The results suggest antibacterial activity of DqV against S. aureus and that the venom acts in the cell membrane.Significance and Impact of the StudyAlteration in membrane permeability may be associated with the antimicrobial activity of Hymenopteran venoms.This article is protected by copyright. All rights reserved.
    Journal of Applied Microbiology 05/2014; · 2.20 Impact Factor
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    ABSTRACT: The aim of the present work was to evaluate antileishmanial activity of Astronium fraxinifolium and Plectranthus amboinicus. For the in vitro tests, essential oil of P. amboinicus (OEPA) and ethanolic extracts from A. fraxinifolium (EEAF) were incubated with 10(6) promastigotes of L. (Viannia) braziliensis. The OEPA was able to reduce the parasite growth after 48 h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c mice were infected subcutaneously (s.c.) with 10(7) L. braziliensis promastigotes. Treatment was done by administering OEPA intralesionally (i.l.) for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 10(6) L. braziliensis promastigotes. The first protocol of treatment consisted of ethanolic leaf extract from A. fraxinifolium (ELEAF) administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract from A. fraxinifolium.
    BioMed research international. 01/2014; 2014:848293.
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    ABSTRACT: Apis mellifera stings are a problem for public health worldwide, particularly in Latin America due to the aggressiveness of its Africanized honeybees. Massive poisoning by A. mellifera venom (AmV) affects mainly the cardiovascular system, and several works have described its actions on heart muscle. Nevertheless, no work on the pharmacological action mechanisms of the AmV in isolated aorta has been reported. Thus, the present work aimed to investigate the actions of AmV and its main fractions, phospholipase A2 (PLA2) and melittin, on isolated aorta rings and a probable action mechanism. AmV and the complex PLA2 + melittin (0.1-50 mug/mL) caused contraction in endothelium-containing aorta rings, but neither isolated PLA2 nor melittin were able to reproduce the effect. Endothelium removal did not change the maximum vasoconstrictor effect elicited by AmV. Ca2+-free medium, as well as treatment with phentolamine (5 muM), verapamil (10 muM), losartan (100 muM), and U-73122 (10 muM, a phospholipase C inhibitor), eliminated the AmV-induced contractile effects. In conclusion, AmV caused contractile effect in aorta rings probably through the involvement of voltage-operated calcium channels, AT1 and alpha-adrenergic receptors via the downstream activation of phospholipase C. The protein complex, PLA2 + melittin, was also able to induce vasoconstriction, whereas the isolated proteins were not.
    Journal of Venomous Animals and Toxins including Tropical Diseases 09/2013; 19(1):24. · 0.55 Impact Factor
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    ABSTRACT: Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5 mg/kg) increased the time until the first seizure and the percentage of survival (155.4±27.7 seconds / 12.5%, p<0.05) compared to the control group (79.75±3.97 seconds / 0%), whereas endovenous treatment (0.1 and 0.5 mg/kg) decreased the time until the first seizure (0.1 mg/kg: 77.83±5.3 seconds versus 101.0±3.3 seconds in the control group; 0.5 mg/kg: 74.43±3.9 seconds versus 101.0±3.3 seconds for the control group, p<0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0 mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5 mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5 mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the Dinoponera quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.
    Neurochemistry International 06/2013; · 2.66 Impact Factor
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    ABSTRACT: The present work aimed to evaluate the effectiveness of Plectranthus amboinicus (Lour.) Spreng against MRSA clinical isolates. The in vitro antimicrobial activity of the hydroalcoholic extract (HE), the ethyl acetate (EA) fraction and its subfractions were determined by broth microdilution and bioautography against MRSA clinical isolates. The microdilution checkerboard method was used to assess in vitro drug combination studies. To induce abscess formation, bacterial suspensions were added to Citodex and inoculated subcutaneously into male Swiss mice. The treatment protocol consisted of 2 doses of HE, the EA fraction or vancomycin introduced intraperitoneally into mice 3 and 12 h after infection. The EA fraction and its subfractions presented the lowest minimal inhibitory concentrations (MIC, 0.25 to 0.5 mg/mL). The plant samples were bacteriostatic at 2x and 4x MIC and bactericidal at 100 mg/mL. The EA fraction presented synergism with vancomycin and an additive effect with ciprofloxacin. A significant reduction of abscess volume, bacterial cell counts in abscess slurries, and inflammatory scores was observed in the HE and EA fraction-treated groups. The samples were effective in treating the animals in a dose-dependent fashion. The present study proved the effectiveness of P. amboinicus fractions against MRSA using in vitro and in vivo assays.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:291592. · 1.72 Impact Factor
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    ABSTRACT: The aim of this study is to investigate renal markers and the biomarker MCP-1 in patients with schistosomiasis mansoni. This is a cross-sectional study with 85 patients aged 5 to 48 years, with a confirmed diagnosis of schistosomiasis mansoni through the Kato-Katz method. The patients were divided in three groups: control (G-I); infected by S. mansoni before treatment (G-II) and infected by S. mansoni after treatment (G-III). Renal function was evaluated by tubular and glomerular biomarkers and through urinary MCP-1. Patients' mean age was 23.2±13 years. There was no statistically significant difference between the groups regarding tubular and glomerular function evaluated through the traditional biomarkers. MCP-1 was higher in G-II and G-III, when compared to G-I; p=0.009 and p=0.007, respectively. There was no difference when comparing groups G-II and G-III (p=0.892). Although it was not different among the groups, there was a significant correlation between albuminuria and MCP-1. There was a significant increase in urinary MCP-1 levels in patients with schistosomiasis mansoni, which was associated with albuminuria. This protein has a role in the recruitment of monocytes to injury and inflammation sites . The increase of MCP-1 in the urine evidences that there is silent renal inflammation in these patients and the inflammatory status is not interrupted by specific treatment of the offending agent. Our findings suggest that urinary MCP-1 can be a sensitive marker of renal injury in patients with schistosomiasis mansoni.
    PLoS ONE 01/2013; 8(11):e80421. · 3.73 Impact Factor
  • British Journal of Haematology 11/2012; · 4.94 Impact Factor
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    ABSTRACT: Bites from snake (Bothrops genus) cause local tissue damage and systemic complications, which include alterations such as hemostatic system and acute renal failure (ARF). Recent studies suggest that of ARF pathogenesis in snakebite envenomation is multifactorial and involves hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. The aim of the work was to investigate the effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV (10 μg/mL) reduced the perfusion pressure at 90 and 120 min. The renal vascular resistance decreased at 120 min of perfusion. The effect on urinary flow (UF) and glomerular filtration rate (GFR) started 30 min after BlV infusion, was transient and returned to normal at 120 min of perfusion. It was also observed a decrease on percentual tubular transport of sodium (%TNa(+)) at 120 min and of chloride (%TCl(-)) at 60 and 90 min. The treatment with BlV caused decrease in cell viability to the lowest concentration tested with an IC(50) of 1.25 μg/mL. Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by necrosis. However, a cell death process may involve apoptosis in lower concentrations. BlV treatment (1.25 μg/mL) led to significant depolarization of the mitochondrial membrane potential and, indeed, we found an increase in the expression of cell death genes in the lower concentrations tested. The venom also evoked an increase in the cytosolic Ca(2+) in a concentration dependent manner, indicating that Ca(2+) may participate in the venom of B. leucurus effect. The characterization of the effects in the isolated kidney and renal tubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism.
    Toxicon 11/2012; · 2.92 Impact Factor
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    ABSTRACT: The effect was investigated of the K+ channel blocker, glibenclamide, on the ability of Crotalus durissus cumanensis venom (CDCM) to promote peripheral antinociception. This was measured by formalin-induced nociception in male Swiss mice. CDCM (200 and 300 microg/kg) produced an antinociceptive effect during phase 2 in the formalin test. The effect of CDCM (200 microg/kg) was unaffected by the ATP-sensitive K+ channel blocker glibenclamide (2 mg/kg). These results suggest that CDCM is effective against acute pain. However, the ATP-sensitive K+ channels pathway is not contributable to the antinociceptive mechanism of CDCM.
    Natural product communications 07/2010; 5(7):1103-6. · 0.96 Impact Factor
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    ABSTRACT: Bothrops marajoensis is found in the savannah of Marajó Island in the State of Pará and regions of Amapá State, Brazil. The aim of the work was to study the renal and cardiovascular effects of the B. marajoensis venom and phospholipase A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino acid sequencing of sPLA(2) showed amino acid identity with other lysine K49 sPLA(2)s of snake venom. B. marajoensis venom (30 microg/mL) decreased the perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and sodium tubular transport. PLA(2) did not change the renal parameters. The perfusion pressure of the mesenteric bed did not change after infusion of venom. In isolated heart, the venom decreased the force of contraction and increased PP but did not change coronary flow. In the arterial pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac frequency. The presence of atrial flutter and late hyperpolarisation reversed, indicating QRS complex arrhythmia and dysfunction in atrial conduction. In conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia while simultaneously blocking electrical conduction in the heart. Moreover, the decrease in glomerular filtration rate, urinary flow and electrolyte transport demonstrates physiological changes to the renal system.
    Toxicon 06/2010; 55(6):1061-70. · 2.92 Impact Factor
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    ABSTRACT: In the present study we show that phospholipases A2 isolated from porcine pancreas (PP-PLA2) and Crotalus durissus terrificus snake venom (SV-PLA2) induced dose-dependent increases of LDH release from rabbit proximal tubules in suspension. Both porcine and crotalic PLA(2)s induced increases in non-esterified fatty acid (NEFA) levels (microg of NEFA/mg of tubule protein). It was observed that the NEFA levels in the pellets were higher than in the supernatant for both PLA2, and were dose-dependent for the crotalic PLA2 group. Furthermore, snake venom PLA2 induced a decrease in mitochondrial membrane potential (DeltaPsi(m)) assessed by both JC-1 uptake and safranin O uptake. Porcine PLA2 produced no effects on JC-1 uptake with the highest concentrations and an unexpected increase in the group treated with the lowest concentration. In contrast, the safranin O method revealed decreases of energization with both phospholipases, so it had higher sensitivity to the presence of the increased NEFA levels. Addition of delipidated bovine serum albumin (dBSA) completely reversed the effects induced by phospholipases on DeltaPsi(m) measured with safranin O. Incubation with pancreatic and crotalic phospholipases A2 produced no changes on cell ATP levels. We conclude that the treatment of proximal tubule suspensions with porcine or crotalic phospholipases disturbed membrane integrity as well as mitochondrial function. Specific early NEFA-mediated mitochondrial effects of the phospholipases used in the present study are indicated by the benefit provided by dBSA.
    Toxicon 10/2008; 52(8):852-7. · 2.92 Impact Factor
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    ABSTRACT: Alginates isolated from Sargassum vulgare, present a strong antitumor activity, associated with kidney reversible damage, as analysed by histopathology of treated animals. In the present study, the renal alteration mechanisms of S. vulgare alginates were investigated using the isolated perfused rat kidney and the isolated perfused rat mesenteric blood vessel methods. The results showed that the effects of Sargassum vulgare low viscosity (SVLV) alginate were more potent than those of Sargassum vulgare high viscosity (SVHV) alginate in the isolated rat kidney. The SVLV alginate caused considerable changes in renal physiology, as shown by an increase in parameters such as perfusion pressure, renal vascular resistance, glomerular filtration rate, urinary flow and sodium, potassium and chloride excretion and by reduction of chloride tubular transport. The effects of SVHV were weaker than those of SVLV. The effects of SVLV on kidney could be related to direct vascular action as demonstrated with SVLV alginate on mesenteric blood vessels. In conclusion, the Sargassum vulgare alginate altered the renal function parameters evaluated. S. vulgare low viscosity alginate renal effects were more potent than S. vulgare high viscosity alginate. It is suggested that physicochemical differences between SVHV and SVLV could explain the differences found in the results.
    Journal of Applied Toxicology 05/2008; 28(3):364-9. · 2.60 Impact Factor
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    ABSTRACT: Bothrops insularis venom contains a variety of substances presumably responsible for several pharmacological effects. We investigated the biochemical and biological effects of phospholipase A(2) protein isolated from B. insularis venom and the chromatographic profile showed 7 main fractions and the main phospholipase A(2) (PLA(2)) enzymatic activity was detected in fractions IV and V. Fraction IV was submitted to a new chromatographic procedure on ion exchange chromatography, which allowed the elution of 5 main fractions designated as IV-1 to IV-5, from which IV-4 constituted the main fraction. The molecular homogeneity of this fraction was characterized by high-performance liquid chromatography (HPLC) and demonstrated by mass spectrometry (MS), which showed a molecular mass of 13984.20 Da; its N-terminal sequence presented a high amino acid identity (up to 95%) with the PLA(2) of Bothrops jararaca and Bothrops asper. Phospholipase A(2) isolated from B. insularis (Bi PLA(2) ) venom (10 microg/mL) was also studied as to its effect on the renal function of isolated perfused kidneys of Wistar rats (n=6). Bi PLA(2) increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa(+)) and chloride tubular reabsorption (%TCl(-)) decreased at 120 min, without alteration in potassium transport. In conclusion, PLA(2) isolated from B. insularis venom promoted renal alterations in the isolated perfused rat kidney.
    Toxicon 03/2008; 51(2):181-90. · 2.92 Impact Factor
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    ABSTRACT: Bothrops insularis is a snake from Ilha da Queimada Grande, an island located about 20 miles away from the Southeastern coast of Brazil. Compared with other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood, and so far, no fraction from this venom with amino acid oxidase activity had been isolated or its biological activity tested. We investigated the biochemical and biological effects of one l-amino acid oxidase enzyme isolated from B. insularis snake venom (BiLAO), which was purified using HPLC and sequence grade. We also evaluated the renal effects induced by BiLAO. Chromatographic profile of B. insularis whole venom disclosed seven main fractions (I, II, III, IV, V, VI and VII) and the main LAO enzymatic activity was detected in fraction II. The group treated with BiLAO showed a decrease in perfusion pressure (C(120)=110.28+/-3.69; BiLAO(120)=82.2+/-5.6 mmHg*); renal vascular resistance (C(120)=5.48+/-0.53; BiLAO(120)=4.12+/-0.42 mmHg/mL/g/min*), urinary flow (C(120)=0.160+/-0.020; BiLAO(120)=0.064+/-0.012 mL/g/min*), glomerular filtration rate (C(120)=0.697+/-0.084; BiLAO(120)=0.176+/-0.017 mL/g/min*), sodium (C(120)=79.76+/-0.56; BiLAO(120)=65.39+/-6.19%*), potassium (C(120)=69.94+/-6.86; BiLAO(120)=60.26+/-2.24%*) and chloride tubular reabsortion (C(120)=78.53+/-2.33; BiLAO(120)=64.58+/-6.68%*). Acute tubular necrosis foci were observed in the group treated with the LAO fraction of the B. insularis snake venom. Some findings have the same morphological aspect of apoptosis, more evident cortically; otherwise, reversible degenerative phenomena represented by hydropic ballooning with extensive cytoplasmic vacuolization and discontinuity of the cell brush borders in the proximal tubular epithelium were observed; furthermore, necrotic detachment of these cells into the tubular lumina, and increased amount of protein deposits in the distal and proximal tubules were observed. In conclusion, the slowness of blood flow and of glomerular filtration resulted in more time for filtration and tubular reabsorption, with elevation of the total percentage of sodium and chlorine reabsorption. The maintenance of the decrease in glomerular filtration rate would determine the subsequent decreases, which were noticed in these parameters. The necrosis observed was the result of damage cell induced by l-amino acid oxidase isolated from B. insularis venom.
    Toxicon 03/2008; 51(2):199-207. · 2.92 Impact Factor
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    ABSTRACT: Renal abnormalities in leprosy have been largely described in medical literature, but there are few studies evaluating renal function in these patients. This is a cross-sectional study in 59 consecutive paucibacillary (PB) and multibacillary (MB) leprosy patients. Glomerular filtration rate (GFR) was estimated by simplified-MDRD formula. Microalbuminuria was determined by 24 h urine collection. Urinary acidification capacity was measured after water deprivation and acid-loading with CaCl(2). Urinary concentration capacity was evaluated after desmopressin acetate administration, using the urinary to plasma osmolality (U/P(osm)) ratio. All parameters except microalbuminuria were measured in a control group of 18 healthy volunteers. Age and gender were similar between leprosy (MB or PB) and control groups. GFR <or= 80 ml/min/1.73 m(2) was observed in 50% of the leprosy patients. GFR and U/P(osm) in leprosy patients were significantly lower than in controls (P<0.001). Urinary acidification defect was found in 32% of PB and in 29% of MB patients and urinary concentrating ability was abnormal in 83% of PB and 85% of MB patients. Microalbuminuria was found in 4 patients (8.5%), leukocyturia was found in 13 (22%) and haematuria was present in 16 patients (27%). Plasma creatinine (P(cr)) >1.2 mg/dl was observed in 17.9% of MB patients and in none of the controls (P=0.020). A negative correlation was observed between GFR and time of treatment (r= -0.339; P=0.002). Age and time of treatment were independent risk factors for GFR <or= 80 ml/min/1.73 m(2) in multivariate analysis. Asymptomatic GFR changes and renal tubular dysfunction, including urine concentration defect and impaired acidifying mechanisms, can be caused by leprosy on specific treatment and without any reaction episodes.
    Nephrology Dialysis Transplantation 02/2008; 23(1):256-62. · 3.37 Impact Factor
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    ABSTRACT: Medication noncompliance has a harmful impact on reaching therapeutic goals of delaying the progression of chronic kidney disease (CKD). The aim of the present study is to calculate the prevalence of medication noncompliance and to identify medication noncompliance-associated factors in CKD. A cross-sectional study was performed with 130 CKD patients from a university nephrology outpatient clinic, mean age 48.8 +/- 15.8 years, who were continuously self-administering an antihypertensive or immunosuppressive drug, and who were neither on dialysis nor had received a kidney transplant. Noncompliance was measured through self-report (during an interview) and physician assessment. Patients were considered noncompliers if noncompliance had been detected by any of these methods. Sociodemographic, clinical and laboratory and medication characteristics were surveyed, as well as patients' knowledge regarding prescribed medicines and opinions of the quality of the health care service provided. Prevalence of medication noncompliance was 36.9% (95% confidence interval [95% CI], 28.6%-45.8%). Lack of access to medicines was the most commonly reported problem with medication use (62.5%). Multiple logistic regression analysis showed that patients' insufficient knowledge regarding prescribed medicines (p=0.040) and bad opinions of the quality of the provided health care service (p=0.027) were independently associated with noncompliance. Medication noncompliance prevalence was high among the patients studied. Lack of access to medicines remains an important public health problem. The noncompliance-associated factors identified in CKD were the patients' poor knowledge regarding the pharmacotherapy and dissatisfaction with the health care service provided.
    Journal of nephrology 01/2008; 21(3):354-62. · 2.02 Impact Factor
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    Revista Brasileira De Ciencias Farmaceuticas - RBCF. 01/2008; 44(2).
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    ABSTRACT: The venom of Bothrops insularis snake, known in Brazil as jararaca ilhoa, contains a variety of proteolytic enzymes such as a thrombin-like substance that is responsible for various pharmacological effects. B. insularis venom chromatography profile showed an elution of seven main fractions. The thrombin-like activity was detected in fractions I and III, the latter being subjected to two other chromatographic procedures, so to say DEAE and Hi Trap Benzamidine. The purity degree of this fraction was confirmed by analytical reverse phase HPLC, which displayed only one main fraction confirmed by SDS-PAGE constituting fraction III. About 5 microg of fraction III protein potentiated the secretion of insulin induced by 2.8 mM of glucose in rats isolated pancreatic beta-cells treated; the increase being around 3-fold higher than its respective control. B. insularis lectin (BiLec; 10 microg/mL) was also studied as to its effect on the renal function of isolated perfused rat kidneys with the use of six Wistar rats. BiLec increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa+) and chloride tubular reabsorption (%TCl-) decreased at 120 min, without alteration in potassium transport. In conclusion, the thrombin-like substance isolated from B. insularis venom induced an increase in insulin secretion, in vitro, and transiently altered vascular, glomerular and tubular parameters in the isolated rat kidney.
    Toxicon 04/2007; 49(3):329-38. · 2.92 Impact Factor