RESUMO
Sharks of the genus Sphyrna are under intense exploitation globally. In Brazil's northern coast, this genus represents a high proportion of fisheries landings and comprises four species. However, due to difficulty of specific identification when specimens are landed, most of the records are limited to the genus level. Here we analyzed the effectiveness of ITS2 (Internal Transcribed Spacer 2 of rDNA) fragment length protocol (Abercrombie et al., 2005) for identifying hammerhead shark species, comparing with the analysis of COI (Cytochrome oxidase subunit I) and ITS2 sequences. We evaluated samples of muscle tissue acquired in the main fishing ports of Maranhão: Carutapera, Raposa e Tutóia. Sampling was conducted between March 2017 to March 2018 and complemented with material deposited in collection (2015). COI results indicated the occurrence of endangered species which are prohibited to be landed. These include Sphyrna mokarran (67%), S. lewini (15%), S. tudes (3%), and S. tiburo (15%). For the ITS2 marker, we investigated the optimization of the protocol developed by Abercrombie (2005) for to improve the use in this geographical area througout design of a new primers.
Assuntos
Tubarões , Animais , Tubarões/genética , Brasil , Espécies em Perigo de Extinção , Pesqueiros , Alimentos MarinhosAssuntos
Alopecia/patologia , Dermatoses Faciais/patologia , Hiperpigmentação/patologia , Líquen Plano/patologia , Adulto , Idoso , Alopecia/diagnóstico por imagem , Dermoscopia/métodos , Diagnóstico Diferencial , Feminino , Humanos , Líquen Plano/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
Chagas' disease is one of the most impactful and prevalent neglected tropical diseases in the Americas, specially affecting the poor and underdeveloped areas in Latin America. Aggravating this scenario, the medicines used in the current chemotherapy are old, toxic and present a low efficacy to treat the chronic stage of this disease. In addition, resistant strains of Trypanosoma cruzi, the etiological agent, are frequently reported. So, there is an imperative requirement for novel chemotherapeutic options to treat this debilitating disease. In this context, peptidases have emerged as potential targets and, consequently, proteolytic inhibitors have confirmed to be valuable drugs against several human pathologies. In this line of thinking, T. cruzi produces a major multifunctional cysteine peptidase, named cruzipain, which directly and/or indirectly orchestrates several physiological and pathological processes, which culminate in a successful parasitic infection. Taken together, these findings point out that cruzipain is one of the most important targets for driving a chemotherapy approach against the human pathogen T. cruzi. The present review summarizes some of the recent advances and failures in this area, with particular emphasis on recently published studies.
Assuntos
Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Cisteína Endopeptidases/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Antineoplásicos/química , Antiprotozoários/química , Cisteína Endopeptidases/química , Conformação Molecular , Testes de Sensibilidade Parasitária , Proteínas de ProtozoáriosAssuntos
Alopecia/patologia , Dermatoses Faciais/patologia , Líquen Plano/patologia , Idoso , Feminino , Testa , Humanos , Pessoa de Meia-IdadeRESUMO
Aspartic peptidases are proteolytic enzymes present in many organisms like vertebrates, plants, fungi, protozoa and in some retroviruses such as human immunodeficiency virus (HIV). These enzymes are involved in important metabolic processes in microorganisms/virus and play major roles in infectious diseases. Although few studies have been performed in order to identify and characterize aspartic peptidase in trypanosomatids, which include the etiologic agents of leishmaniasis, Chagas' disease and sleeping sickness, some beneficial properties of aspartic peptidase inhibitors have been described on fundamental biological events of these pathogenic agents. In this context, aspartic peptidase inhibitors (PIs) used in the current chemotherapy against HIV (e.g., amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) were able to inhibit the aspartic peptidase activity produced by different species of Leishmania. Moreover, the treatment of Leishmania promastigotes with HIV PIs induced several perturbations on the parasite homeostasis, including loss of the motility and arrest of proliferation/growth. The HIV PIs also induced an increase in the level of reactive oxygen species and the appearance of irreversible morphological alterations, triggering parasite death pathways such as programed cell death (apoptosis) and uncontrolled autophagy. The blockage of physiological parasite events as well as the induction of death pathways culminated in its incapacity to adhere, survive and escape of phagocytic cells. Collectively, these results support the data showing that parasites treated with HIV PIs have a significant reduction in the ability to cause in vivo infection. Similarly, the treatment of Trypanosoma cruzi cells with pepstatin A showed a significant inhibition on both aspartic peptidase activity and growth as well as promoted several and irreversible morphological changes. These studies indicate that aspartic peptidases can be promising targets in trypanosomatid cells and aspartic proteolytic inhibitors can be benefic chemotherapeutic agents against these human pathogenic microorganisms.
Assuntos
Ácido Aspártico Proteases/antagonistas & inibidores , Proteínas de Protozoários/antagonistas & inibidores , Trypanosoma/enzimologia , Ácido Aspártico Proteases/classificação , Ácido Aspártico Proteases/metabolismo , Inibidores da Protease de HIV/farmacologia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Nelfinavir/farmacologia , Proteínas de Protozoários/metabolismo , Saquinavir/farmacologia , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Trypanosoma/efeitos dos fármacos , Trypanosoma/patogenicidade , Tripanossomíase/tratamento farmacológico , Tripanossomíase/parasitologiaRESUMO
Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.
Assuntos
Anti-Infecciosos/farmacologia , Antiprotozoários/farmacologia , Quelantes/farmacologia , Fungos/efeitos dos fármacos , Animais , Fungos/crescimento & desenvolvimento , Fungos/patogenicidade , Humanos , Plasmodium/efeitos dos fármacos , Plasmodium/crescimento & desenvolvimento , Plasmodium/patogenicidade , Trypanosoma/efeitos dos fármacos , Trypanosoma/crescimento & desenvolvimento , Trypanosoma/patogenicidadeRESUMO
Ring chromosomes are often associated with abnormal phenotypes due to loss of genomic material and also because of ring instability at mitosis after sister chromatid exchange events. We investigated ring chromosome instability in six patients with ring chromosomes 4, 14, 15, and 18 by examining 48- and 72-h lymphocyte cultures at the first, second and subsequent cell divisions after bromodeoxyuridine incorporation. Although most cells from all patients showed only one monocentric ring chromosome, ring chromosome loss and secondary aberrations were observed both in 48- and 72-h lymphocyte cultures and in metaphase cells of the different cell generations. We found no clear-cut correlation between ring size and ring instability; we also did not find differences between apparently complete rings and rings with genetic material loss. The cytogenetic findings revealed secondary aberrations in all ring chromosome patients. We concluded that cells with ring chromosome instability can multiply and survive in vivo, and that they can influence the patient's phenotype.
Assuntos
Instabilidade Cromossômica/genética , Cromossomos em Anel , Contagem de Células , Criança , Pré-Escolar , Replicação do DNA , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metáfase , GravidezRESUMO
Trypanosomatids of the genus Herpetomonas comprises monoxenic parasites of insects that present pro- and opisthomastigotes forms in their life cycles. In this study, we investigated the Ca(2+) transport and the mitochondrial bioenergetic of digitonin-permeabilized Herpetomonas sp. promastigotes. The response of promastigotes mitochondrial membrane potential to ADP, oligomycin, Ca(2+), and antimycin A indicates that these mitochondria behave similarly to vertebrate and Trypanosoma cruzi mitochondria regarding the properties of their electrochemical proton gradient. Ca(2+) transport by permeabilized cells appears to be performed mainly by the mitochondria. Unlike T. cruzi, it was not possible to observe Ca(2+) release from Herpetomonas sp. mitochondria, probably due to the simultaneous Ca(2+) uptake by the endoplasmic reticulum. In addition, a vanadate-sensitive Ca(2+) transport system, attributed to the endoplasmic reticulum, was also detected. Nigericin (1 microM), FCCP (1 microM), or bafilomycin A(1) (5 microM) had no effect on the vanadate-sensitive Ca(2+) transport. These data suggest the absence of a Ca(2+) transport mediated by a Ca(2+)/H(+) antiport. No evidence of a third Ca(2+) compartment with the characteristics of the acidocalcisomes described by A. E. Vercesi et al. (1994, Biochem. J. 304, 227-233) was observed. Thapsigargin and IP(3) were not able to affect the vanadate-sensitive Ca(2+) transport. Ruthenium red was able to inhibit the Ca(2+) uniport of mitochondria, inducing a slow mitochondrial Ca(2+) efflux, compatible with the presence of a Ca(2+)/H(+) antiport. Moreover, this efflux was not stimulated by the addition of NaCl, which suggests the absence of a Ca(2+)/Na(+) antiport in mitochondria.
Assuntos
Cálcio/química , Cálcio/metabolismo , Macrolídeos , Trypanosomatina/química , Difosfato de Adenosina/metabolismo , Animais , Antibacterianos/farmacologia , Antimicina A/farmacologia , Transporte Biológico/efeitos dos fármacos , Calcimicina/farmacologia , Carbonil Cianeto p-Trifluormetoxifenil Hidrazona/farmacologia , Digitonina/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Guanosina Trifosfato/metabolismo , Indicadores e Reagentes/farmacologia , Inositol 1,4,5-Trifosfato/farmacologia , Membranas Intracelulares/metabolismo , Ionóforos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/metabolismo , Oligomicinas/farmacologia , Rutênio Vermelho/farmacologia , Trocador de Sódio e Cálcio/fisiologia , Tapsigargina/farmacologia , Fatores de Tempo , Trypanosomatina/fisiologia , Desacopladores/farmacologia , Vanadatos/farmacologiaRESUMO
Enzymes entrapped in reverse micelles can be studied in low-water environments that have the potential of restricting conformational mobility in specific steps of the reaction cycle. Sarcoplasmic reticulum Ca2+-ATPase was incorporated into a reverse-micelle system (TPT) composed of toluene, phospholipids, Triton X-100 and varying amounts of water (0.5-7%, v/v). Phosphorylation of the Ca2+-ATPase by ATP required the presence of both water and Ca2+ in the micelles. No phosphoenzyme (EP) was detected in the presence of EGTA. Phosphorylation by Pi (inorganic phosphate) in the absence of Ca2+ was observed at water content below that necessary for phosphorylation by ATP. In contrast to what is observed in a totally aqueous medium, EP formed by Pi was partially resistant to dephosphorylation by Ca2+. However, the addition of non-radioactive Pi to the EP already formed caused a rapid decrease in radiolabelled enzymes, as expected for the isotopic dilution, indicating the existence of an equilibrium (E+Pi<-->EP). Phosphorylation by Pi also occurred in TPT containing millimolar Ca2+ concentrations in a range of water concentrations (2-5% v/v). The substrates p-nitrophenyl phosphate, acetyl phosphate, ATP and GTP increased the EP level under these conditions. These results suggest that: (1) the rate of conversion of the ATPase conformer E2 into E1 is greatly reduced at low water content, so that E2-->E1 becomes the rate-limiting step of the catalytic cycle; and (2) in media of low water content, Pi can phosphorylate both E1Ca and E2. Thus, the effect of enzyme hydration is complex and involves changes in the phosphorylation reaction at the catalytic site, in the equilibrium between E2 and E1 conformers, and in their specificity for substrates.
Assuntos
ATPases Transportadoras de Cálcio/química , Cálcio/farmacologia , Retículo Sarcoplasmático/enzimologia , Água/farmacologia , Trifosfato de Adenosina , Animais , Guanosina Trifosfato , Micelas , Nitrofenóis , Organofosfatos , Compostos Organofosforados , Fosfatos/química , Fosforilação , CoelhosRESUMO
A urticária Ú uma enfermidade comum e multifatorial. Estima-se que 10 por cento a 20 por cento da populaçäo apresente um episódio de urticária em alguma fase de sua vida. As neoplasias estÒo entre as causas mais raras. Apresentamos um caso de urticária crônica cujo diagnóstico final foi de mieloma múltiplo (MM), alertando para a necessidade de uma investigaçäo sistemática e criteriosa destes pacientes.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Neoplasias Cutâneas/complicações , Urticária/etiologia , Mieloma Múltiplo/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
Five patients living in Rio de Janeiro, Brazil, were found to have Lyme disease. These are among the first known cases in South America.
Assuntos
Eritema Migrans Crônico/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Doença de Lyme/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Os autores fazem um estudo aberto sobre o uso de fluorandrenolida sob oclusao, apresentada numa concentracao de 4 mcg/cm2 de fita cirurgica, adesiva, plastica e transparente. Avaliam 32 pacientes portadores de diversas dermatoses principalmente neurodermatite circunscrita a psoriase, concluindo pela eficacia, seguranca e comodidade de uso desta nova forma medicamentos