RESUMO
Soft tunic syndrome is an infectious disease caused by the flagellate Azumiobodo hoyamushi, which severely damages the aquaculture of the edible ascidian Halocynthia roretzi. Tunic is a cellulosic extracellular matrix entirely covering the body in ascidians and other tunicates, and its dense cuticle layer covers the tunic surface as a physical barrier against microorganisms. When the tunic of intact H. roretzi individuals was cut into strips, electron-dense fibers (DFs) appeared on the cut surface of the tunic matrix and aggregated to regenerate a new cuticular layer in seawater within a few days. DF formation was partially or completely inhibited in individuals with soft tunic syndrome, and DF formation was also inhibited by the presence of some proteases, indicating the involvement of proteolysis in the process of tunic softening as well as cuticle regeneration. Using pure cultures of the causative flagellate A. hoyamushi, the expression of protease genes and secretion of some proteases were confirmed by RNA-seq analysis and a 4-methylcoumaryl-7-amide substrate assay. Some of these proteases may degrade proteins in the tunic matrix. These findings suggest that the proteases of A. hoyamushi is the key to understanding the mechanisms of cuticular regeneration inhibition and tunic softening.
Assuntos
Urocordados , Animais , Regeneração , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genéticaRESUMO
Medaka Oryzias latipes is a small freshwater fish widely distributed in Japan. It is a popular ornamental fish and now has been recognized as an important model organism in many areas of biological research. Here we report microsporidian infections for the first time in medaka, from 2 research facilities and a wild population. Infected medaka exhibited abnormal appearance with whitish trunk muscle, and microsporidian spores were detected from the affected tissue. The size of spores was similar in all the three cases: 7.0 µm in length and 3.7-4.2 µm in width. In the histological observation, numerous sporophorous vesicles containing spores or other developmental stages were observed within the myocytes of the trunk muscle. Nucleotide sequence of the ribosomal RNA gene was determined and it was identical among all three cases. A BLAST search revealed it shared 99.5-99.6% identity with Pleistophora hyphessobryconis, a microsporidian known to infect >20 freshwater fish species. Light microscopic observation of spores and histological features also indicated the microsporidian infection in medaka is caused by P. hyphessobryconis. This is the first record of the microsporidian species from medaka and from Japan.
Assuntos
Microsporídios , Microsporidiose , Oryzias , Pleistophora , Animais , Japão/epidemiologia , Pleistophora/genética , Pleistophora/ultraestrutura , Microsporidiose/epidemiologiaRESUMO
A new microsporidian disease of cultured rainbow trout Oncorhynchus mykiss has recently been confirmed in Japan, and the causative species was tentatively designated as Microsporidium sp. RBT-2021. Involvement of common prawn Palaemon paucidens in its transmission was suggested based on the previous feeding trials, although the microsporidian infection in P. paucidens was not confirmed. In this study, P. paucidens in Lake Biwa, Japan was investigated for microsporidian infection and 4 types of spores (types 1-4) were newly found. The nucleotide sequence of the small subunit ribosomal RNA gene was identical between type 1 and Microsporidium sp. RBT-2021, indicating they are conspecific. However, intriguingly, the spore morphology and the mode of development in fish and prawn were strikingly different. Morphological observations revealed type 1 in the prawn possesses characteristics of the genus Inodosporus Overstreet and Weidner, 1974, while Microsporidium sp. RBT-2021 in the trout exhibited the characteristics of the genus Kabatana Lom, Dyková and Tonguthai, 2000. In the phylogeny, type 1 was placed within a clade comprising Kabatana spp. and Inodosporus octosporus. Based on the morphological and molecular analyses, we describe Microsporidium sp. RBT-2021 as Inodosporus fujiokai n. sp. Together with the success of the previous prawn-feeding trials, this study strongly suggests I. fujiokai n. sp. has a multi-host life cycle utilizing fish and crustacean hosts and different modes of development in each host. Such polymorphic life cycle has barely been known among fish microsporidians. This study also suggests that the genus Kabatana is a junior synonym of the genus Inodosporus.
RESUMO
Bats (order, Chiroptera) account for more than one-fifth of all mammalian species in the world and are infected by various intra-erythrocytic parasites of the family Plasmodiidae (Apicomplexa: Haemosporida), including Polychromophilus Dionisi, 1899. Recent advance in the molecular characterization of haemosporidian isolates has enabled their accurate identification, particularly in the last decade. Studies are actively conducted in tropical regions, Europe, and Australia; however, data on haemosporidian infection in bats in Asian temperate areas, including Japan, remain limited. In this study, 75 bats of 4 species (Miniopterus fuliginosus, Myotis macrodactylus, Rhinolophus nippon, and Rhinolophus cornutus) were captured at three sites in western Japan (Yamaguchi Prefecture), and haemosporidian parasites were screened microscopically and molecularly via nested polymerase chain reaction (PCR) targeting the cytochrome b (cytb), cytochrome c oxidase subunit I (cox-1), apicoplast caseinolytic protease C (clpc), and nuclear elongation factor 2 (EF2) genes. The survey detected Polychromophilus melanipherus in 15 (40.5%) miniopterid bats (M. fuliginosus) and Polychromophilus murinus in 6 (46.2%) vespertilionid bats (M. macrodactylus), whereas none of the 25 rhinolophid bats (R. nippon and R. cornutus) was infected, indicating the robust host specificity for miniopterid (P. melanipherus) and vespertilionid (P. murinus) bats regardless of orthotopic nesting. The 15 Polychromophilus cytb sequences obtained from 11 miniopterid and 4 vespertilionid bats were classified into six cytb haplotypes (three for each species), showing no region-specific variation in a phylogenetic tree of Polychromophilus isolates in the Old World. Similarly, multiple haplotypes (seven for cox-1 and nine for clpc) and genotypes (three for EF2) were characterized for the Japanese isolates of Polychromophilus, and the results were consistent with those based on a haemosporidian cytb analysis. Bat flies (Nycteribia allotopa and another undetermined Nycteribia sp.) collected from the body surface of bats harbored Polychromophilus oocysts on the external surface of the midgut. This is the first study to report the isolation and molecular characterization of Polychromophilus spp. in miniopterid and vespertilionid bats in the temperate area of Asia (western Japan). Future studies should evaluate the global prevalence of haemosporidian infections in bats.
Assuntos
Quirópteros/parasitologia , Haemosporida/genética , Haemosporida/isolamento & purificação , Infecções Protozoárias em Animais/parasitologia , Animais , Citocromos b/genética , Haemosporida/classificação , Japão/epidemiologia , Filogenia , Prevalência , Infecções Protozoárias em Animais/epidemiologiaRESUMO
The infection of the kinetoplastid flagellate Azumiobodo hoyamushi causes soft tunic syndrome that often results in mass mortality in the aquaculture of the edible ascidian Halocynthia roretzi. In the diseased ascidian individuals, the flagellates are exclusively found in the tunic matrix that entirely cover the epidermis, and never invade into internal tissues, such as a mantle. The present study for the first time demonstrated that the ascidian blood plasma and hemolymph have an activity to agglutinate and disintegrate the flagellates, suggesting the innate immunity protects the internal tissue from the invasion of A. hoyamushi. This activity is indifferent between the healthy and the diseased individuals. Allo-specific recognition and cytotoxic reaction among ascidian hemocytes, so-called contact reaction, occur among the individuals of healthy-healthy, healthy-diseased, and diseased-diseased combination, and therefore, the hemocytes from diseased individuals still retain the allo-reactivity. Moreover, the allo-reactive combinations are not changed under the presence of the flagellates, indicating the flagellates neither suppress nor induce the effector system of the contact reaction. These results suggest that the infection of A. hoyamushi does not impair the innate immunity in the ascidian hemolymph.
Assuntos
Hemócitos , Hemolinfa , Imunidade Inata , Urocordados , Animais , Hemócitos/imunologia , Hemolinfa/imunologia , Urocordados/imunologiaRESUMO
Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3â Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.
Assuntos
Transferência Genética Horizontal , Parasitos , Animais , Bovinos , Geografia , Parasitos/genética , Filogenia , Comportamento Predatório , Retroelementos , Vertebrados/genéticaRESUMO
Taeniasis remains a prevalent public health problem in Thailand. National helminthiasis surveys report only the incidence of Taenia spp. eggs. The ability to differentiate Taenia species using morphological and molecular techniques is vital for epidemiological surveys. This study detected taeniasis carriers and other helminthic infections by Kato's thick smear technique and identified the Taenia species by multiplex PCR. The study subjects were the ethnic Karen people in Tha Song Yang District, Tak Province, Thailand, bordering Myanmar. In total, 983 faecal samples from villagers were examined for helminthiases. Interview-based questionnaires were used to gather information on possible risk factors for infection. The prevalence of helminth infections was 42.7% (420/983), including single (37.3%, 367/983) and mixed infections (5.4%, 53/983). The most common infection (19.23%, 189/983) was Ascaris lumbricoides, whereas taeniasis carriers comprised 2.8% (28/983). Multiplex PCR of Cox1 was used for species identification of Taenia tapeworms, eggs, or both in 22 taeniasis carriers. Most of the parasites (20 cases) were Taenia solium, with two cases of Taenia saginata. Taenia saginata asiatica was not found in the villagers examined. The analysis of 314 completed questionnaires showed that a statistically significant (p < 0.05) risk of taeniasis was correlated with being male, a history of being allowed to forage during childhood, a history of seeing tapeworm proglottids, and a history of raw or undercooked pork consumption. Health education programmes must seek to reduce and prevent reinfection in these communities.
TITLE: Facteurs de risque et prévalence de la téniase chez les Karens du district de Tha Song Yang, province de Tak, Thaïlande. ABSTRACT: La téniase reste un problème de santé publique répandu en Thaïlande. Les enquêtes nationales sur les helminthiases ne rapportent que l'incidence des Åufs de Taenia spp. La capacité de différencier les espèces de Taenia à l'aide de techniques morphologiques et moléculaires est vitale pour les enquêtes épidémiologiques. Cette étude a détecté des porteurs de téniase et d'autres infections helminthiques par la technique de frottis épais de Kato et a identifié les espèces de Taenia par PCR multiplex. Les sujets de l'étude étaient les Karens du district de Tha Song Yang, province de Tak, Thaïlande, à la frontière du Myanmar. Au total, 983 échantillons de matières fécales provenant de villageois ont été examinés pour les helminthiases. Des questionnaires basés sur des entretiens ont été utilisés pour recueillir des informations sur les facteurs de risque possibles d'infection. La prévalence des helminthes était de 42,7 % (420/983), dont des infections uniques (37,3 %, 367/983) et mixtes (5,4 %, 53/983). L'infection la plus courante (19,23 %, 189/983) était Ascaris lumbricoides, tandis que les porteurs de téniase représentaient 2,8 % (28/983). La PCR multiplexe de Cox1 a été utilisée pour l'identification des adultes ou des oeufs de Taenia, ou des deux, chez 22 porteurs de téniase. La plupart des parasites (20 cas) étaient Taenia solium, avec deux cas de Taenia saginata. Taenia saginata asiatica n'a pas été trouvé chez les villageois examinés. L'analyse de 314 questionnaires a montré qu'un risque statistiquement significatif (p < 0,05) de téniase était en corrélation avec le fait d'être un homme, et des antécédents d'avoir été autorisé à ramasser sa nourriture pendant l'enfance, d'avoir vu des proglottis de ténia et de consommation de porc cru ou insuffisamment cuit. Les programmes d'éducation sanitaire doivent chercher à réduire et à prévenir la réinfection dans ces communautés.
Assuntos
Taenia , Teníase , Animais , Humanos , Masculino , Mianmar , Prevalência , Fatores de Risco , Teníase/epidemiologia , Tailândia/epidemiologiaRESUMO
Global distributions of zoonotic pathogens have been strongly affected by the history of human dispersal and domestication of livestock. The pork tapeworm Taenia solium is distributed worldwide as the cause of neurocysticercosis, one of the most serious neglected tropical diseases. T. solium has been reported in Indonesia but only endemic to restricted areas such as Bali and Papua. Previous studies indicated the distinctiveness of a mitochondrial haplotype confirmed in Papua, but only one isolate has been examined to date. In this study, genetic characterization of T. solium and pigs in Bali and Papua was conducted to clarify the distributional history of the parasite. Mitochondrial haplotype network analysis clearly showed that Indonesian T. solium comprises a unique haplogroup which was the first to diverge among Asian genotypes, indicating its single origin and the fact that it was not introduced in the recent past from other area in Asia in which it is endemic. Although phylogenetic analysis based on the mitochondrial D-loop revealed multiple origins of pigs in Bali and Papua, the majority of pigs belonged to the Pacific Clade, which is widely dispersed throughout the Island Southeast Asia (ISEA) and Oceania due to Neolithic human dispersal. Given the results of our network analysis, it is likely that the Pacific Clade pigs played a key role in the dispersal of T. solium. The data suggest that T. solium was introduced from mainland Asia into Western Indonesia, including Bali, by modern humans in the late Pleistocene, or in the early to middle Holocene along with the Pacific Clade pigs. Introduction into New Guinea most likely occurred in the late Holocene through the spread of Pacific Clade pigs. Over time, T. solium has been eradicated from most of Indonesia through the middle to modern ages owing to religious and cultural practices.
Assuntos
Distribuição Animal , Sus scrofa/genética , Doenças dos Suínos/parasitologia , Taenia solium/genética , Teníase/veterinária , Animais , Indonésia , Ilhas , Filogenia , Sus scrofa/classificação , Suínos , Taenia solium/classificação , Teníase/parasitologiaRESUMO
Gastrointestinal myxosporean parasites from the genus Enteromyxum are known to cause severe disease, resulting in high mortalities in numerous species of cultured marine fishes globally. Originally described as Myxidium spp., they were transferred to a new genus, Enteromyxum, to emphasize their novel characteristics. Their retention in the family Myxidiidae at the time was warranted, but more comprehensive phylogenetic analyses have since demonstrated the need for a new family for these parasites. We discovered a novel Enteromyxum in wild fish from Malaysia and herein describe the fourth species in the genus and erect a new family, the Enteromyxidae n. fam., to accommodate them. Enteromyxum caesio n. sp. is described infecting the tissues of the stomach in the redbelly yellowtail fusilier, Caesio cuning, from Malaysia. The new species is distinct from all others in the genus, as the myxospores although morphologically similar, are significantly smaller in size. Furthermore, small subunit ribosomal DNA sequence data reveal that E. caesio is <84% similar to others in the genus, but collectively they form a robust and discrete clade, the Enteromyxidae n. fam., which is placed as a sister taxon to other histozoic marine myxosporeans. In addition, we describe, using transmission electron microscopy, the epicellular stages of Enteromyxum fugu and show a scanning electron micrograph of a mature myxospore of E. caesio detailing the otherwise indistinct sutural line, features of the polar capsules and spore valve ridges. The Enteromyxidae n. fam. is a commercially important group of parasites infecting the gastrointestinal tract of marine fishes and the histozoic species can cause the disease enteromyxosis in intensive finfish aquaculture facilities. Epicellular and sloughed histozoic stages are responsible for fish-to-fish transmission in net pen aquaculture systems but actinospores from an annelid host are thought to be necessary for transmission to fish in the wild.
RESUMO
Avitellina tapeworms are common intestinal parasites of ruminants with a worldwide distribution. In Senegal, only Avitellina centripunctata tapeworm has been reported to date, and genetic diversity was previously confirmed by enzymatic analysis. This study aims to clarify the diversity of Avitellina tapeworms isolated from sheep and cattle in Senegal. In total, 613 adult Avitellina tapeworms were collected from sheep and cattle. Morphological analysis by the light microscopy and scanning electron microscopy identified three Avitellina "morphospecies": A. centripunctata and Avitellina sp.2 were detected in sheep while Avitellina sp.3 was identified in cattle. Molecular phylogenetic analysis based on the complete mitochondrial cytochrome c oxidase subunit 1 gene (cox1) sequences revealed that 101 Avitellina tapeworms were divided into 54 haplotypes grouped into three clades, of which two were specific to sheep and one specific to cattle. Three morphospecies corresponded to each of three clades and the maximum pairwise divergence among the clades ranged from 9.7 to 18.5% in cox1. The present study demonstrates the unexpected diversity of Avitellina tapeworms in domestic ruminants, and emphasize the necessity of re-evaluation of the taxonomy of the genus.
Assuntos
Doenças dos Bovinos/epidemiologia , Cestoides/genética , Infecções por Cestoides/veterinária , Doenças das Cabras/epidemiologia , Doenças dos Ovinos/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Cestoides/anatomia & histologia , Cestoides/classificação , Cestoides/ultraestrutura , Infecções por Cestoides/epidemiologia , Infecções por Cestoides/parasitologia , DNA Mitocondrial/análise , Doenças das Cabras/parasitologia , Cabras , Proteínas de Helminto/análise , Microscopia/veterinária , Microscopia Eletrônica de Varredura/veterinária , Prevalência , Senegal/epidemiologia , Ovinos , Doenças dos Ovinos/parasitologiaRESUMO
Taeniasis is an important parasitic condition in Asia, especially since all three human-infecting Taenia spp., Taenia solium, Taenia saginata, and Taenia asiatica are found in this region. These three species are believed to be sympatrically distributed, with the largest disease burden found in remote and rural areas where people raise pigs and cattle in a traditional manner. Recent studies revealed that T. asiatica and T. saginata are genetically-related sister species that are not completely reproductively isolated from each other. Current evidence indicates that most T. asiatica adult worms are hybrid-derived descendants. Moving forward, nuclear DNA analysis will be critical in further assessing the species circulating locally. Lifestyle choices, such as the consumption of undercooked meat, are important in maintaining the life cycles of these parasites. In addition, poor hygiene and sanitation, in highly endemic areas, make disease control difficult, resulting in the need for sustainable education programs. An overview of the present situation of taeniasis and cysticercosis in Asia is provided, followed by a discussion of molecular approaches to species assessment and the impact of human lifestyles on parasite transmission.
Assuntos
Taenia/classificação , Teníase/epidemiologia , Teníase/parasitologia , Animais , Ásia/epidemiologia , Humanos , Fatores de Risco , Taenia/genéticaRESUMO
Taeniasis and cysticercosis are known to be endemic in several Indonesian islands, although relatively little recent epidemiological data are available. As most Indonesian people are Muslims, taeniasis/cysticercosis caused by the pork tapeworm, Taenia solium, has a restricted presence in non-Muslim societies and is endemic only among some Hindu communities on the island of Bali. Bali has long been known to be endemic for taeniasis/cysticercosis; almost a century ago levels of cysticercosis of 20-30% were described in cattle and 2-3% in pigs. Few studies of taeniasis/cysticercosis were undertaken in Bali prior to a series of research programs commenced since the 1990s. Both Taenia saginata and T. solium continue to be endemic in Bali. Molecular studies have revealed that all T. saginata-like tapeworms detected in Bali are T. saginata. No evidence has been found for the presence of Taenia asiatica in Bali. Economic, sanitary and education improvements across much of the island over the past decades have been associated with a decline in the amount of transmission of T. solium such that the parasite now seems to be restricted to the eastern part of the island, a small area on the northeastern slope of Mt. Agung, the highest mountain in Bali. The living environment including sanitation and hygiene condition in this endemic area remains relatively poor especially during the half-year dry season, and pigs continue to roam freely. In this review, historical records and ongoing projects towards elimination of taeniasis/cysticercosis in Bali are reviewed to provide a better understanding of the present situation of taeniasis/cysticercosis in Bali towards a future, cysticercosis-free tropical resort island.
Assuntos
Cisticercose/epidemiologia , Teníase/epidemiologia , Animais , Bovinos/parasitologia , Cisticercose/prevenção & controle , Humanos , Indonésia/epidemiologia , Ilhas , Suínos/parasitologia , Teníase/prevenção & controleRESUMO
In North Sumatra, Indonesia, taeniasis has previously been reported solely from Samosir Island located in Lake Toba. In 2014, however, three individuals were identified with taeniasis after voluntarily reporting for treatment, stimulating a subsequent investigation conducted in 2017. This investigation indicated that a previously unidentified endemic area exists in Simalungun District. Molecular analysis showed the worms to be hybrid-derived descendants of Taenia asiatica and Taenia saginata, which is consistent with specimens identified previously from Samosir Island.
Assuntos
Doenças Endêmicas , Teníase/epidemiologia , Animais , Portador Sadio , Humanos , Indonésia/epidemiologia , TaeniaRESUMO
The infection caused by a kinetoplastid flagellate, Azumiobodo hoyamushi, in an ascidian, Halocynthia roretzi, results in softening of the tunic, and finally death. This disease is usually recognized using palpation of the softening tunic, and A. hoyamushi infection is detectable using microscopy or PCR amplification of specific gene fragments. The present study is the first quantitative evaluation of the symptoms of soft tunic syndrome by measuring the amount of bending (bending) and the peak force required to pierce the tunic (force). There was a strong correlation between bending and force. Correlation analyses among other parameters (ascidian total weight, tunic thickness, and tunic water content) indicated that larger ascidians had harder and thicker tunics with a higher water content. As compared to the tunic of healthy individuals, softened tunic was thinner and had lower water content. Infected tunics thus possibly lose water and become softer and thinner. Mechanisms for maintaining the appropriate water level content may be crucial for preventing tunic softening.
Assuntos
Estruturas Animais/fisiologia , Kinetoplastida/fisiologia , Urocordados/microbiologia , Urocordados/fisiologia , Animais , Fenômenos Biomecânicos , Interações Hospedeiro-PatógenoRESUMO
The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6. We tried to improve these issues of cinacalcet for a new pharmaceutical agent as a preferable CaSR agonist. Optimization from cinacalcet resulted in the identification of pyrrolidine compounds and successfully led to the discovery of evocalcet as an oral allosteric CaSR agonist. Evocalcet, which exhibited highly favorable profiles such as CaSR agonistic activity and good DMPK profiles, will provide a novel therapeutic option for secondary hyperparathyroidism.
Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Descoberta de Drogas , Hiperparatireoidismo/tratamento farmacológico , Pirrolidinas/farmacologia , Receptores de Detecção de Cálcio/agonistas , Animais , Inibidores das Enzimas do Citocromo P-450/síntese química , Inibidores das Enzimas do Citocromo P-450/química , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Pirrolidinas/síntese química , Pirrolidinas/química , Ratos , Relação Estrutura-AtividadeRESUMO
Recent molecular re-evaluation of Echinococcus granulosus, which causes cystic echinococcosis (CE), has revealed that it is not a single species, but instead consists of 5 cryptic species. Among them, E. granulosus (dog-sheep strain) is predominant (75%) followed by Echinococcus canadensis (22%). The major affected organs, in humans, are the liver (88%) and lungs (11%). Primary cerebral CE comprises less than 1% of all cases. As cerebral CE cases are rare, there are few reports with molecular confirmation of the causative species. This study reports mitochondrial gene analysis from 4 Mongolian pediatric cerebral CE cases. Molecular confirmation was obtained for 3 of the 4 cases, with all 3 cases determined to be due to E. canadensis (G6/G7) infection. None of the cases had other organ involvement. This is only the third report on the molecular identification of the Echinococcus species responsible for cerebral CE, and only the second report of E. canadensis (G6/G7) being the causative agent of cerebral CE.
Assuntos
Infecções Parasitárias do Sistema Nervoso Central/diagnóstico , Infecções Parasitárias do Sistema Nervoso Central/etiologia , Cérebro/parasitologia , Equinococose/complicações , Echinococcus/genética , Adolescente , Animais , Cérebro/diagnóstico por imagem , Criança , Pré-Escolar , Echinococcus/isolamento & purificação , Echinococcus granulosus/genética , Feminino , Genes Mitocondriais/genética , Genótipo , Humanos , Masculino , Técnicas de Diagnóstico Molecular , MongóliaRESUMO
Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580). In a rat model of CKD induced by 5/6 nephrectomy, oral administration of evocalcet efficiently suppressed the secretion of parathyroid hormone (PTH). With regard to the gastro-intestinal effects, cinacalcet induced a significant delay in gastric emptying in rats, while evocalcet did no marked effects on it. Evocalcet also demonstrated the less induction of emesis compared to cinacalcet in common marmosets. The pharmacological effects of evocalcet were observed at lower doses because of its higher bioavailability than cinacalcet, which may have contributed to the reduced GI tract symptoms. In addition, evocalcet showed no substantial direct inhibition of any CYP isozymes in in vitro liver microsome assay, suggesting a better profile in drug interactions than cinacalcet that inhibits cytochrome P450 (CYP) 2D6. These findings suggest that evocalcet can be a better alternative to cinacalcet, an oral calcimimetic agent, with a wider safety margin.
Assuntos
Calcimiméticos/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Glândulas Paratireoides/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Animais , Calcimiméticos/química , Calcimiméticos/farmacocinética , Callithrix , Cinacalcete/farmacologia , Inibidores das Enzimas do Citocromo P-450/química , Inibidores das Enzimas do Citocromo P-450/farmacocinética , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Trato Gastrointestinal/fisiopatologia , Células HEK293 , Humanos , Isoenzimas/metabolismo , Masculino , Estrutura Molecular , Glândulas Paratireoides/enzimologia , Hormônio Paratireóideo/metabolismo , Ratos Wistar , Receptores de Detecção de Cálcio/antagonistas & inibidores , Receptores de Detecção de Cálcio/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Vômito/induzido quimicamenteRESUMO
Most part of Southeast Asia is considered endemic for human-infecting Taenia tapeworms; Taenia solium, T. saginata, and T. asiatica. However, until now there was no report of the occurrence of human cases of T. asiatica in Lao PDR. This study, conducted in Savannakhet Province, Lao PDR, microscopically examined a total of 470 fecal samples by Kato Katz method and found 86% of people harboring at least one helminth. Hookworms were detected in 56% of the samples besides Opisthorchis like eggs (42%), Trichuris trichiura (27%), Ascaris spp. (14%), and Taenia spp. (4%) eggs. Serology for cysticercosis showed 6.8% positives with results varying from 3% to 14.3% in Ethnic School students and Kalouk Kao village respectively. Species-specific PCR targeting mitochondrial DNA (mtDNA) of 28 tapeworms, recovered from 16 patients, revealed T. solium (n = 2), T. saginata (n = 21), and T. asiatica (n = 5). Two patients were confirmed to be coinfected with T. saginata and T. asiatica, indicating the endemicity of the 3 human Taenia in Lao PDR. However, nucleotide sequencing of a nuclear DNA gene, DNA polymerase delta (pold) revealed that all the tapeworms identified as T. asiatica using mtDNA had T. saginata type allele at pold locus, demonstrating that they are not "pure T. asiatica" but the hybrid descendants between the two species, confirming the wide distribution of hybrids of T. saginata/ T. asiatica in Southeast Asia. The high prevalence of several helminthic NTDs in east Savannakhet area even with conventional control measures indicates the importance to establish wide and multifaceted health programs to sustainably improve the quality of life of the populations living in these communities.
Assuntos
Cisticercose/epidemiologia , Doenças Endêmicas , Doenças Negligenciadas/epidemiologia , Taenia/isolamento & purificação , Teníase/epidemiologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Criança , Cisticercose/sangue , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , DNA de Helmintos/genética , DNA Mitocondrial/genética , Fezes/parasitologia , Feminino , Humanos , Laos , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/parasitologia , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , Especificidade da Espécie , Taenia/classificação , Taenia/genética , Taenia/imunologia , Taenia saginata/genética , Taenia saginata/imunologia , Taenia saginata/isolamento & purificação , Taenia solium/genética , Taenia solium/imunologia , Taenia solium/isolamento & purificação , Teníase/parasitologia , Adulto JovemRESUMO
Genetic and morphological diversity of Thysaniezia tapeworms from cattle and sheep in Senegal was investigated using light and scanning microscopic observations and molecular analysis based on mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear small subunit ribosomal RNA gene (SSU rDNA). A total of 52 adult tapeworms were collected from sheep and cattle. Although the tapeworms of the two hosts were morphologically very close, phylogenetic analysis based on cox1 and SSU rDNA gene sequences showed that they were divided into two clades corresponding each to a host. The maximum pairwise divergence between the clades were 12.1% in cox1 and 2.9% in SSU rDNA, indicating they are distinct species. The tapeworms collected from sheep were morphologically identified as Thysaniezia ovilla, a cosmopolitan species in domestic ruminants. Detailed morphological observations revealed a consistent difference between the tapeworms obtained from sheep and those from cattle. The latter were identified as Thysaniezia connochaeti. The present study highlights presence of two species of Thysaniezia among domestic ruminants in Senegal: T. ovilla specific to sheep and T. connochaeti specific to cattle. Our work is the first report of T. connochaeti from domestic animals.