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1.
Pathol Res Pract ; 253: 154965, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38039740

ABSTRACT

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.


Subject(s)
Esophageal Neoplasms , Polymorphism, Single Nucleotide , Humans , Immunohistochemistry , Superoxide Dismutase/genetics , Genotype , Prognosis , Esophageal Neoplasms/genetics
2.
Sci Rep ; 13(1): 11236, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37433851

ABSTRACT

Here we analyze the trends of rainfall and the frequency of rainy days over the Brazilian Cerrado between 1960 and 2021 in four distinct periods according to the seasonal patterns over the region. We also evaluated trends in evapotranspiration, atmospheric pressure, winds, and atmospheric humidity over the Cerrado to elucidate the possible reasons for the detected trends. We recorded a significant reduction in rainfall and frequency of rainy days in the northern and central Cerrado regions for all periods except at the beginning of the dry season. The most pronounced negative trends were recorded during the dry season and the beginning of the wet season, where we recorded reductions of up to 50% in total rainfall and the number of rainy days. These findings are associated with the intensification of the South Atlantic Subtropical Anticyclone, which has been shifting atmospheric circulation and raising regional subsidence. Moreover, during the dry season and the beginning of the wet season, there was a reduction in regional evapotranspiration, which also potentially contributed to the rainfall reduction. Our results suggest an expansion and intensification of the dry season in the region, potentially bringing broad environmental and social impacts that transcend the Cerrado boundaries.

3.
Article in English, Spanish | MEDLINE | ID: mdl-30679039

ABSTRACT

OBJECTIVE: Breast cancer is a health problem worldwide with high incidence and mortality rates. It is well known that the development of more sensitive and specific diagnostic methods is of great importance since an early diagnosis is essential to successfully treat tumors. Lapachol is a natural compound, belonging to the naphthoquinone group that has been widely used in traditional medicine to treat various illnesses, including cancer. The aim of this study was to evaluate technetium-99m (99mTc) labeled lapachol as an imaging probe for breast cancer identification. METHODS: To achieve this purpose, lapachol was labeled with 99mTc, radiochemical purity and in vitro stability were determined. Blood clearance, in healthy mice, and biodistribution, in 4T1 tumor-bearing mice, were also evaluated. RESULTS: Lapachol was successfully labeled with 99mTc, with high values of radiochemical yield (95.9±3.4%). In vitro stability showed that the radiolabeled complex remained stable for up to 24h, with values above 90% for both saline and plasma (95.6±3.6% and 96.4±1.7%, respectively). The radiolabeled complex decays in a biphasic manner, with a half-life of distribution and elimination equal to 3.3 and 50.0min, respectively. Biodistribution and scintigraphic images showed high uptake in organs of excretion (kidneys, liver, and intestine). It could be also noted that tumor uptake was higher than the muscle at all time points. Tumor-to-muscle ratio reaches ∼4.5 at 24h after administration. CONCLUSION: These findings suggest that 99mTc-lapachol can be a potential diagnostic agent for breast tumors.


Subject(s)
Breast Neoplasms/diagnostic imaging , Naphthoquinones , Technetium , Animals , Breast Neoplasms/metabolism , Female , Mice , Mice, Inbred BALB C , Naphthoquinones/pharmacokinetics , Technetium/pharmacokinetics , Tissue Distribution
4.
Parasitol Res ; 117(5): 1333-1340, 2018 May.
Article in English | MEDLINE | ID: mdl-29502297

ABSTRACT

Trichomoniasis is the most common non-viral, sexually transmitted infection affecting humans worldwide. The main treatment for trichomoniasis is metronidazole (MTZ). However, adverse effects and reports of resistance have stimulated the development of therapeutic alternatives. The ease of manipulation of the side chains of MTZ coupled with its safety makes this molecule attractive for the development of new drugs. In this context, we evaluated the activity of the chlorinated MTZ derivative, MTZ-Cl, on sensitive and resistant strains of Trichomonas vaginalis. MTZ-Cl presented a remarkable activity against both sensitive and resistant strains. In vitro and in vivo toxicity assays indicated that the new molecule is safe for future clinical trials. Furthermore, we noticed different rates of free radical production between the sensitive and resistant strains. MTZ-Cl induced a higher release of nitric oxide (NO, ~ 9000 a.u.) by both sensitive and resistant strains. However, the sensitive strain produced a greater amount of H2O2 (~ 1,800,000 a.u.) and superoxide radicals (~ 350,000 a.u.) in the presence of MTZ. In the resistant strain, production of these radicals was more prominent when MTZ-Cl was used. Collectively, these results suggest that NO is an important molecule in the trichomonacidal activity against resistant and sensitive strains, suggesting an alternative pathway for MTZ-Cl activation. We highlight the high trichomonacidal potential of MTZ-Cl, improving the effectiveness of treatment and reducing side effects. In addition, MTZ-Cl is derived from a well-established drug on the world market that presents low toxicity to human cells, suggesting its safety to proceed with future clinical trials.


Subject(s)
Antiprotozoal Agents/pharmacology , Metronidazole/analogs & derivatives , Metronidazole/pharmacology , Sexually Transmitted Diseases/drug therapy , Trichomonas Infections/drug therapy , Trichomonas vaginalis/drug effects , Animals , Cell Line , Halogenation , Humans , Hydrogen Peroxide/metabolism , Nitric Oxide/metabolism , Rats , Sexually Transmitted Diseases/parasitology
5.
Microb Cell Fact ; 16(1): 155, 2017 Sep 19.
Article in English | MEDLINE | ID: mdl-28927409

ABSTRACT

BACKGROUND: Lactobacillus species produce biosurfactants that can contribute to the bacteria's ability to prevent microbial infections associated with urogenital and gastrointestinal tracts and the skin. Here, we described the biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P6A and Lactobacillus gasseri P65. RESULTS: The biosurfactants produced by L. jensenii P6A and L. gasseri P65 reduced the water surface tension from 72 to 43.2 mN m-1 and 42.5 mN m-1 as their concentration increased up to the critical micelle concentration (CMC) values of 7.1 and 8.58 mg mL-1, respectively. Maximum emulsifying activity was obtained at concentrations of 1 and 5 mg mL-1 for the P6A and P65 strains, respectively. The Fourier transform infrared spectroscopy data revealed that the biomolecules consist of a mixture of carbohydrates, lipids and proteins. The gas chromatography-mass spectrum analysis of L. jensenii P6A biosurfactant showed a major peak for 14-methypentadecanoic acid, which was the main fatty acid present in the biomolecule; conversely, eicosanoic acid dominated the biosurfactant produced by L. gasseri P65. Although both biosurfactants contain different percentages of the sugars galactose, glucose and ribose; rhamnose was only detected in the biomolecule produced by L. jensenii P6A. Emulsifying activities were stable after a 60-min incubation at 100 °C, at pH 2-10, and after the addition of potassium chloride and sodium bicarbonate, but not in the presence of sodium chloride. The biomolecules showed antimicrobial activity against clinical isolates of Escherichia coli and Candida albicans, with MIC values of 16 µg mL-1, and against Staphylococcus saprophyticus, Enterobacter aerogenes and Klebsiella pneumoniae at 128 µg mL-1. The biosurfactants also disrupted preformed biofilms of microorganisms at varying concentrations, being more efficient against E. aerogenes (64%) (P6A biosurfactant), and E. coli (46.4%) and S. saprophyticus (39%) (P65 biosurfactant). Both strains of lactobacilli could also co-aggregate pathogens. CONCLUSIONS: This report presents the first characterization of biosurfactants produced by L. jensenii P6A and L. gasseri P65. The antimicrobial properties and stability of these biomolecules indicate their potential use as alternative antimicrobial agents in the medical field for applications against pathogens that are responsible for infections in the gastrointestinal and urogenital tracts and the skin.


Subject(s)
Lactobacillus gasseri/metabolism , Surface-Active Agents/chemistry , Surface-Active Agents/metabolism , Anti-Infective Agents/chemistry , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Bacterial Adhesion/drug effects , Bacterial Infections/microbiology , Biofilms/drug effects , Candida albicans/drug effects , Escherichia coli/drug effects , Humans , Lactobacillus/metabolism , Spectroscopy, Fourier Transform Infrared , Surface-Active Agents/pharmacology
6.
Braz J Biol ; 74(2): 355-62, 2014 May.
Article in English | MEDLINE | ID: mdl-25166320

ABSTRACT

Currently campo rupestre (CR) is a name accepted and used internationally by botanists, zoologists, and other naturalists, usually applied to a very specific ecosystem, despite the lack of a consensual published circumscription. We present a tentative geographic circumscription of the term, combining data on climate, geology, geomorphology, soil, flora, fauna and vegetation. The circumscription of campo rupestre proposed herein is based on the following premises: (1) the classification of vegetation is not an exact science, and it is difficult to attain a high degree of consensus to the circumscription of vegetation names; (2) despite this, vegetation classification is useful for conservation and management. It is thus desirable to circumscribe vegetation types with the greatest attainable precision; (3) there is a need to preserve all montane and rocky vegetation types, regardless of classification, biome, etc; (4) the CRs are formed by a complex mosaic of vegetation types including rock-dwelling, psammophilous, aquatic, epiphytic, and penumbral plant communities. Campos rupestres stricto sensu are a Neotropical, azonal vegetation complex endemic to Brazil, forming a mosaic of rocky mountaintop "archipelagos" inserted within a matrix of zonal vegetation, mainly in the Cerrado and Caatinga provinces of the Brazilian Shield (southeastern, northeastern and central-western regions), occurring mainly above 900 m asl. up to altitudes exceeding 2000 m, having measured annual precipitation between 800 and 1500 mm, and an arid season of two to five months.


Subject(s)
Biodiversity , Trees/classification , Brazil
8.
Biomed Pharmacother ; 64(9): 624-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20888176

ABSTRACT

Trypanocidal activity of a number of lipophilic diamines and amino alcohols was evaluated in vitro against Trypanosoma cruzi blood stream forms. Several of the studied compounds showed inhibition of T. cruzi growth. The most active ones were compounds 3, 4 and 5 with a IC50 of 31.2 µg/mL, activity similar to the reference drug crystal violet.


Subject(s)
Amino Alcohols/pharmacology , Diamines/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Amino Alcohols/chemistry , Animals , Diamines/chemistry , Dose-Response Relationship, Drug , Gentian Violet/pharmacology , Molecular Structure , Solubility , Trypanocidal Agents/chemistry , Trypanosoma cruzi/growth & development
9.
Bioelectrochemistry ; 63(1-2): 353-7, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15110302

ABSTRACT

Because redox properties are central to bioreductive drug activity and selectivity, six 2-methyl-5-nitroimidazole, substituted at the N1-ethyl side chain with I, Br, Cl, OAc, OMs and NH(3)(+) were synthesized and submitted to cyclic voltammetry and electrolyses, in order to define their electrodic reduction mechanism, in aprotic [dimethylsulphoxide (DMSO)+0.1 mol l(-1) tetrabuthylammonium perchlorate (TBAP)] and phosphate-buffered media, on glassy carbon electrode, in comparison with metronidazole. Three of these compounds, namely, the iodo, bromo and ammonium salt derivatives showed significant anti-Helicobacter pylori (strain resistant to metronidazole) activity. All the cyclic voltammograms (CV), in aprotic medium, are similar to the one for metronidazole, except for -I, -Br and -NH(3)(+) derivatives. The CV of the N1-ethylhalide (-I, -Br) 5-nitroimidazole showed more intense and irreversible first waves, even at faster sweep rates (nu<2 V s(-1)). The absence of the first wave anodic counterpart, along with analysis of the dependence of E(p), I(p) and other parameters with nu, and results from electrolysis (consumption of two electrons) showed the process to be an ECE system, with halide release, after uptake of two electrons. This behaviour represents a case of dissociative electron transfer (ET). For the ammonium salt, self-protonation mechanism was evident. The facility of reduction represented by the first wave potential and concerning the substituents is NH(3)(+)>Br>I>Cl>OMs>OH>OAc. In aqueous phosphate-buffered medium, the electrochemical behaviour of all the compounds is similar to the one of metronidazole, represented by a unique and irreversible 4e(-)/4H(+) wave. The order of reduction ease is NH(3)(+)>Br approximately OMs>I>OH>OAc. Aprotic medium allows a better discrimination between the substituents. Concerning biological activity, despite the impossibility of establishing a correlation, it has been observed that the more electrophilic compounds showed better anti-H. pylori activity.


Subject(s)
Anti-Bacterial Agents/chemistry , Electrochemistry/methods , Helicobacter pylori/drug effects , Metronidazole/analysis , Metronidazole/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Dimethyl Sulfoxide/chemistry , Drug Evaluation, Preclinical/methods , Electrodes , Hydrogen-Ion Concentration , Metronidazole/analogs & derivatives , Oxidation-Reduction , Quaternary Ammonium Compounds/chemistry , Structure-Activity Relationship
10.
Antimicrob Agents Chemother ; 40(3): 613-5, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8851580

ABSTRACT

Since transmission of Chagas' disease by the insect vector is under control in Brazil, transmission by blood transfusion is acquiring special relevance in areas where the disease is endemic and also in countries whose populations are free of infection but that are receiving immigrants from areas where the disease is endemic. Gentian violet, a phenylmethane dye, was the first agent used for the chemical prophylaxis of blood destined for transfusion. A concentration of 0.6 mmol of this dye per liter is effective at eliminating trypomastigotes from blood after 24 h of incubation at 4 degrees C. It is the only effective trypanosomicidal agent available. In the search of alternate compounds, we examined a number of synthetic compounds. They were screened for their activities against blood trypomastigotes of the Y, CL, and B229 strains of Trypanosoma cruzi by using two or more dilutions of each compound. We found that compound Q45, a 6-methoxy-8(diethylaminohexylamino)lepidine dihydrochloride, was highly effective at clearing parasites from infected blood. Doses of 65 and 130 micrograms of this compound eliminated trypomastigotes from blood experimentally contaminated with T. cruzi parasites. These results indicate that Q45 is remarkably active against circulating trypomastigotes. Further studies evaluating Q45 as a prophylactic agent for preventing the transmission of T. cruzi by blood transfusion are of interest.


Subject(s)
Aminoquinolines/pharmacology , Antiprotozoal Agents/pharmacology , Chagas Disease/prevention & control , Chagas Disease/transmission , Transfusion Reaction , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Aminoquinolines/therapeutic use , Animals , Antiprotozoal Agents/therapeutic use , Chagas Disease/parasitology , Drug Evaluation, Preclinical , Male , Mice , Trypanocidal Agents/therapeutic use
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