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1.
Parasit Vectors ; 17(1): 304, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003498

RESUMO

BACKGROUND: Malaria, a global health concern, is caused by parasites of the Plasmodium genus, which undergo gametogenesis in the midgut of mosquitoes after ingestion of an infected blood meal. The resulting male and female gametes fuse to form a zygote, which differentiates into a motile ookinete. After traversing the midgut epithelium, the ookinete differentiates into an oocyst on the basal side of the epithelium. METHODS: Membrane proteins with increased gene expression levels from the gamete to oocyst stages in P. berghei were investigated utilizing PlasmoDB, the functional genomic database for Plasmodium spp. Based on this analysis, we selected the 184-kDa membrane protein, Pb184, for further study. The expression of Pb184 was further confirmed through immunofluorescence staining, following which we examined whether Pb184 is involved in fertilization using antibodies targeting the C-terminal region of Pb184 and biotin-labeled C-terminal region peptides of Pb184. RESULTS: Pb184 is expressed on the surface of male and female gametes. The antibody inhibited zygote and ookinete formation in vitro. When mosquitoes were fed on parasite-infected blood containing the antibody, oocyst formation decreased on the second day after feeding. Synthesized biotin-labeled peptides matching the C-terminal region of Pb184 bound to the female gamete and the residual body of male gametes, and inhibited differentiation into ookinetes in the in vitro culture system. CONCLUSIONS: These results may be useful for the further studying the fertilization mechanism of Plasmodium protozoa. There is also the potential for their application as future tools to prevent malaria transmission.


Assuntos
Fertilização , Plasmodium berghei , Proteínas de Protozoários , Plasmodium berghei/genética , Plasmodium berghei/metabolismo , Animais , Feminino , Masculino , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Camundongos , Células Germinativas/metabolismo , Malária/parasitologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Zigoto/metabolismo , Anopheles/parasitologia , Anopheles/metabolismo , Oocistos/metabolismo , Gametogênese/genética
2.
J Vet Med Sci ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010217

RESUMO

The bear roundworm Baylisascaris transfuga has been identified in several host bears (Ursinae). However, limited genetic information is available on the bear roundworm in Japanese populations. This study evaluated the genetic composition of bear roundworms isolated from wild Japanese black bears indigenous to Lake Towada, Japan. First, we conducted genetic and/or molecular phylogenetic analyses based on cytochrome c oxidase subunit II and internal transcribed spacer 2 among Baylisascaris species. These analyses revealed that the identified roundworms were genetically B. transfuga. In addition, the average body size of the obtained roundworms in this study was almost the same as that previously reported for B. transfuga. This study represents an important step in genetic research on the roundworm B. transfuga in Ursinae bears not only from Japan but also from the rest of the world.

3.
JACC Asia ; 4(5): 403-417, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38765657

RESUMO

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).

4.
J Vet Med Sci ; 86(5): 485-492, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38569883

RESUMO

Plasmodium parasites within mosquitoes are exposed to various physiological processes, such as blood meal digestion activity, the gonotrophic cycle, and host responses preventing the entry of parasites into the midgut wall. However, when in vitro-cultured ookinetes are injected into the hemocoel of mosquitoes, Plasmodium parasites are not affected by the vertebrate host's blood contents and do not pass through the midgut epithelial cells. This infection method might aid in identifying mosquito-derived factors affecting Plasmodium development within mosquitoes. This study investigated novel mosquito-derived molecules related to parasite development in Anopheles mosquitoes. We injected in vitro-cultured Plasmodium berghei (ANKA strain) ookinetes into female and male Anopheles stephensi (STE2 strain) mosquitoes and found that the oocyst number was significantly higher in males than in females, suggesting that male mosquitoes better support the development of parasites. Next, RNA-seq analysis was performed on the injected female and male mosquitoes to identify genes exhibiting changes in expression. Five genes with different expression patterns between sexes and greatest expression changes were identified as being potentially associated with Plasmodium infection. Two of the five genes also showed expression changes with infection by blood-feeding, indicating that these genes could affect the development of Plasmodium parasites in mosquitoes.


Assuntos
Anopheles , Plasmodium berghei , Animais , Anopheles/parasitologia , Feminino , Masculino , Plasmodium berghei/fisiologia , Malária/parasitologia , Mosquitos Vetores/parasitologia , Camundongos , Interações Hospedeiro-Parasita
5.
World J Cardiol ; 15(11): 599-608, 2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38058398

RESUMO

BACKGROUND: Heart failure (HF) causes extracardiac organ congestion, including in the hepatic portal system. Reducing venous congestion is essential for HF treatment, but evaluating venous congestion is sometimes difficult in patients with chronic HF. The portal vein (PV) flow pattern can be influenced by right atrial pressure. Ultrasound images of the PV are quite easy to obtain and are reproducible among sonographers. However, the association between PV pulsatility and the condition of HF remains unclear. We hypothesize that PV pulsatility at discharge reflects the condition of HF. AIM: To evaluate the usefulness of PV pulsatility as a prognostic marker for hospitalized patients with acute HF. METHODS: This observational study was conducted from April 2016 to January 2017 and April 2018 to April 2019 at Shinko Hospital. We enrolled 56 patients with acute HF, and 17 patients without HF served as controls. PV flow velocity was measured by ultrasonography on admission and at discharge. We calculated the PV pulsatility ratio (PVPR) as the ratio of the difference between the peak and minimum velocity to the peak velocity. The primary endpoint was cardiac death and HF re-hospitalization. The observation period was 1 year from the first hospitalization. The Kaplan-Meier method was used to determine the stratified composite event-free rates, and the log-rank test was used for comparisons between groups. RESULTS: On admission, the PVPR was significantly higher in patients with acute HF than controls (HF: 0.29 ± 0.20 vs controls: 0.08 ± 0.07, P < 0.01). However, the PVPR was significantly decreased after the improvement in HF (admission: 0.29 ± 0.20 vs discharge: 0.18 ± 0.15, P < 0.01) due to the increase in minimum velocity (admission: 12.6 ± 4.5 vs discharge: 14.6 ± 4.6 cm/s, P = 0.03). To elucidate the association between the PVPR and cardiovascular outcomes, the patients were divided into three groups according to the PVPR tertile at discharge (PVPR-T1: 0 ≤ PVPR ≤ 0.08, PVPR-T2: 0.08 < PVPR ≤ 0.21, PVPR-T3: PVPR > 0.21). The Kaplan-Meier analysis showed that patients with a higher PVPR at discharge had the worst prognosis among the groups. CONCLUSION: PVPR at discharge reflects the condition of HF. It is also a novel prognostic marker for hospitalized patients with acute HF.

7.
Parasitol Int ; 97: 102793, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37562581

RESUMO

Philopinna higai is a species of Didymozoidae (Digenea: Hemiuroidea). The definitive hosts of this parasite only belong to the fish genus Sarcocheilichthys. Sarcocheilichthys fishes are endemic to Lake Biwa and southwestern Japan and were introduced into the northeastern (Tohoku) region. However, P. higai parasitism has not been investigated in the Tohoku region. In this study, we surveyed the distribution of P. higai in the Tohoku region and sequenced 28S rDNA (994 bp) and cytochrome oxidase subunit 1 (CO1) gene (721 bp) of P. higai. We also sequenced mitochondrial cytochrome b (581 bp) of Sarcocheilichthys fishes from the Tohoku region and Lake Biwa. Our findings confirmed the distribution of P. higai in all seven surveyed river systems in the four prefectures of the Tohoku region. The 28S rDNA sequence of P. higai did not differ among regions, whereas 10 haplotypes of CO1 were identified and clustered into two major clades. The haplotypes of Sarcocheilichthys fishes introduced in the Tohoku region were identical to the dominant haplotypes in Lake Biwa. Thus, P. higai from Lake Biwa and the Tohoku region were genetically the same species, although genetically differentiated populations formed in the Tohoku region.


Assuntos
Cipriniformes , Trematódeos , Animais , Japão/epidemiologia , Trematódeos/genética , Peixes/parasitologia , Rios , DNA Ribossômico/genética , Filogenia
8.
J Vet Med Sci ; 85(9): 921-928, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37407494

RESUMO

Malaria needs new strategies for its control. Plasmodium spp., the causative agent of malaria, is transmitted by mosquitoes. These parasites develop into oocysts and sporozoites in the body of the mosquitoes. A deeper understanding of oocysts that produce the infectious form of the parasite, sporozoites, can facilitate the development of novel countermeasures. However, the isolation of Plasmodium oocysts is challenging as these are formed between midgut epithelial cells and basal lamina after gametocytes enter the mosquito's body through blood feeding. Further research on oocysts has been impeded by issues related to oocyst isolation. Therefore, in this study, we injected Plasmodium into mosquitoes-an artificial and unique method-and aimed to clarify how oocysts were formed in mosquitoes after Plasmodium injection and whether free oocysts were formed from the mosquito tissue. Plasmodium berghei (ANKA strain) ookinetes cultured in vitro were injected into the thoracic body cavity (hemocoel) of female and male Anopheles stephensi mosquitoes. Oocysts were formed in the body of female and male mosquitoes at 14 days post injection. In addition, oocysts formed as a result of injection developed into sporozoites, which were infectious to mice. These findings suggest that P. berghei can complete its developmental stage in mosquitoes by injection. Some of the oocysts formed were free from mosquito tissue, and it was possible to collect oocysts with minimal contamination of mosquito tissue. These free oocysts can be used for investigating oocyst proteins and metabolism.


Assuntos
Anopheles , Malária , Masculino , Feminino , Animais , Camundongos , Oocistos , Anopheles/metabolismo , Anopheles/parasitologia , Malária/veterinária , Plasmodium berghei
9.
Int J Rheum Dis ; 26(3): 493-500, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36737419

RESUMO

OBJECTIVE: To determine whether complications of pulmonary hypertension (PH) can be predicted by noninvasive screening tests in systemic sclerosis (SSc). METHODS: Forty-seven of 113 SSc patients underwent right heart catheterization (RHC) during 2011-2014. Clinical data, hemodynamic features, echocardiography, and pulmonary function tests had been followed up from the first RHC until 5 years later. RESULTS: At the first RHC, out of 44 patients, 8 were diagnosed with pre-capillary PH (mean pulmonary arterial pressure [mPAP] > 20 mm Hg), and 36 patients were defined as no-PH (mPAP ≤ 20 mm Hg). Three patients with >15 mm Hg of pulmonary artery wedge pressure were excluded. Receiver operating characteristic analyses for pre-capillary PH using estimated systolic PAP (esPAP) revealed an area under the curve (AUC) of 0.736, with a sensitivity and specificity of 62.5% and 86.1%, respectively, at a cutoff level of 35.0 mm Hg. The predicted percentage diffusing lung capacity for carbon monoxide (DLCO%) revealed an AUC of 0.840, with a sensitivity and specificity of 85.7% and 80.0%, respectively, at a cutoff level of 70.0%. Six pre-capillary PH patients, including one who died from PH 14 months after the first RHC, indicated exacerbations of mPAP or esPAP within 5 years. When esPAP < 35.0 mm Hg and DLCO% > 70% were met as the cutoff, none had been newly diagnosed with PH over 5 years. CONCLUSIONS: The conventional screening tests may be useful for detecting pre-capillary PH with SSc, and both esPAP < 35.0 mm Hg and DLCO% > 70% indicated a lower risk of developing PH for at least 5 years.


Assuntos
Hipertensão Pulmonar , Escleroderma Sistêmico , Humanos , Hipertensão Pulmonar/diagnóstico , Ecocardiografia , Pulmão , Testes de Função Respiratória/efeitos adversos , Cateterismo Cardíaco/efeitos adversos , Escleroderma Sistêmico/complicações
10.
Parasitol Int ; 93: 102711, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36414198

RESUMO

Crithidia mellificae (C. mellificae) and Lotmaria passim (L. passim) are trypanosomatids that infect Apis mellifera. We analyzed the prevalence of C. mellificae and L. passim in six regions of Japan from 2018 to 2019. The detection rate of C. mellificae was 0.0% in all regions, whereas L. passim was detected in 16.7%-66.7% of the honeybees. L. passim was detected at a significantly lower rate in the Cyugoku-Shikoku region than in other regions. Furthermore, phylogenetic analysis of the internal transcribed spacer 1 (ITS1) locus of related species was performed. All the samples in this study could be assigned to the L. passim clade. This study reveals that L. passim infection is predominantly prevalent in Japan. Further epidemiological surveys are needed to clarify the prevalence of C. mellificae infection in honeybees in Japan.


Assuntos
Trypanosomatina , Abelhas , Animais , Japão/epidemiologia , Filogenia , Crithidia
11.
Parasit Vectors ; 15(1): 244, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804459

RESUMO

BACKGROUND: Malaria is a major global parasitic disease caused by species of the genus Plasmodium. Zygotes of Plasmodium spp. undergo meiosis and develop into tetraploid ookinetes, which differentiate into oocysts that undergo sporogony. Homologous recombination (HR) occurs during meiosis and introduces genetic variation. However, the mechanisms of HR in Plasmodium are unclear. In humans, the recombinases DNA repair protein Rad51 homolog 1 (Rad51) and DNA meiotic recombinase 1 (Dmc1) are required for HR and are regulated by breast cancer susceptibility protein 2 (BRCA2). Most eukaryotes harbor BRCA2 homologs. Nevertheless, these have not been reported for Plasmodium. METHODS: A Brca2 candidate was salvaged from a database to identify Brca2 homologs in Plasmodium. To confirm that the candidate protein was Brca2, interaction activity between Plasmodium berghei (Pb) Brca2 (PbBrca2) and Rad51 (PbRad51) was investigated using a mammalian two-hybrid assay. To elucidate the functions of PbBrca2, PbBrca2 was knocked out and parasite proliferation and differentiation were assessed in mice and mosquitoes. Transmission electron microscopy was used to identify sporogony. RESULTS: The candidate protein was conserved among Plasmodium species, and it was indicated that it harbors critical BRCA2 domains including BRC repeats, tower, and oligonucleotide/oligosaccharide-binding-fold domains. The P. berghei BRC repeats interacted with PbRad51. Hence, the candidate was considered a Brca2 homolog. PbBrca2 knockout parasites were associated with reduced parasitemia with increased ring stage and decreased trophozoite stage counts, gametocytemia, female gametocyte ratio, oocyst number, and ookinete development in both mice and mosquitoes. Nevertheless, the morphology of the blood stages in mice and the ookinete stage was comparable to those of the wild type parasites. Transmission electron microscopy results showed that sporogony never progressed in Brca2-knockout parasites. CONCLUSIONS: Brca2 is implicated in nearly all Plasmodium life cycle stages, and especially in sporogony. PbBrca2 contributes to HR during meiosis.


Assuntos
Culicidae , Malária , Parasitos , Animais , Culicidae/parasitologia , Feminino , Recombinação Homóloga , Estágios do Ciclo de Vida , Mamíferos , Camundongos , Oocistos/genética , Plasmodium berghei/genética
12.
J Vet Med Sci ; 84(7): 1015-1018, 2022 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-35644573

RESUMO

Trichodectes pinguis, referred to commonly as the bear-biting louse, has been reported in several bear species. However, graphical (blurred or coarse) and genetic information on the louse is limited. In this study, we identified T. pinguis collected from Japanese black bears in the Aomori Prefecture, Japan. We confirmed 12S rDNA sequences derived from the collected T. pinguis and performed molecular phylogenetic analysis based on 12S rDNA. The analysis revealed the parasitic louse to be T. pinguis. Interestingly, the body size of T. pinguis found in this study was smaller than the previous recorded body size of them in Japan and Turkey. To better understand the biting louse infesting bears, morphometric and genetic information from other bear hosts needs to be accumulated.


Assuntos
Ursidae , Animais , DNA Ribossômico , Japão , Filogenia , Turquia , Ursidae/genética , Ursidae/parasitologia
13.
Int J Cardiol Heart Vasc ; 40: 101031, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35495576

RESUMO

Background: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. Methods: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. Results: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005-1.048; p = 0.017). Conclusions: RC time was decreased after PEA, and might be a possible indicator for predicting PEA success.

14.
ERJ Open Res ; 7(3)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34409094

RESUMO

BACKGROUND: Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context. METHODS: 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation-perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation. RESULTS: Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA). CONCLUSIONS: The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.

15.
Parasit Vectors ; 14(1): 373, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289894

RESUMO

BACKGROUND: Plasmodium sp., which causes malaria, must first develop in mosquitoes before being transmitted. Upon ingesting infected blood, gametes form in the mosquito lumen, followed by fertilization and differentiation of the resulting zygotes into motile ookinetes. Within 24 h of blood ingestion, these ookinetes traverse mosquito epithelial cells and lodge below the midgut basal lamina, where they differentiate into sessile oocysts that are protected by a capsule. METHODS: We identified an ookinete surface and oocyst capsule protein (OSCP) that is involved in ookinete motility as well as oocyst capsule formation. RESULTS: We found that knockout of OSCP in parasite decreases ookinete gliding motility and gradually reduces the number of oocysts. On day 15 after blood ingestion, the oocyst wall was significantly thinner. Moreover, adding anti-OSCP antibodies decreased the gliding speed of wild-type ookinetes in vitro. Adding anti-OSCP antibodies to an infected blood meal also resulted in decreased oocyst formation. CONCLUSION: These findings may be useful for the development of a transmission-blocking tool for malaria.


Assuntos
Anticorpos Antiprotozoários/imunologia , Culicidae/parasitologia , Malária/parasitologia , Mosquitos Vetores/parasitologia , Plasmodium berghei/fisiologia , Proteínas de Protozoários/metabolismo , Animais , Feminino , Malária/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Oocistos , Plasmodium berghei/genética , Plasmodium berghei/imunologia , Plasmodium berghei/ultraestrutura , Proteínas de Protozoários/genética
16.
J Vet Med Sci ; 83(6): 927-930, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-33840724

RESUMO

The definitive hosts of Metagonimus hakubaensis are reported to be hamsters, rats, mice, dogs, cats, chickens, and quails in experimental infection and Japanese water shrews in natural infection. Here we report that raccoon dogs are new natural definitive hosts of M. hakubaensis, based on morphological and molecular analyses of Metagonimus flukes collected from the host species from Aomori Prefecture, Japan. Moreover, M. hakubaensis recovered from raccoon dogs showed higher fecundity than those recovered from Japanese water shrews. Therefore, raccoon dogs were considered as a more suitable natural definitive host of M. hakubaensis than Japanese water shrews.


Assuntos
Heterophyidae , Trematódeos , Animais , Gatos , Galinhas , Cricetinae , Japão , Camundongos , Cães Guaxinins , Ratos
17.
Pulm Circ ; 11(1): 2045894020983162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532057

RESUMO

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused (n = 49) or normally perfused group (n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score-0.793, R2 = 0.225, p < 0.01), but lung perfusion of blood volume score in poorly perfused group was not. Poorly perfused group had higher pulmonary vascular resistance (879 ± 409 dynes-s/cm5 vs. 574 ± 279 dynes-s/cm5, p < 0.01) and lower lung perfusion of blood volume score (22.1 ± 5.4 vs. 26.4 ± 6.6, p < 0.01) and % diffusing capacity for carbon monoxide divided by the alveolar volume (59.9 ± 15.4% vs. 78.8 ± 14.2%, p < 0.01). Perfusion of blood volume score in the normally perfused group showed an inverse correlation with pulmonary vascular resistance; however, that in poorly perfused group did not. Microvasculopathy might contribute to severe hemodynamics, apart from pulmonary vascular obstruction. In our experience, more than half of treatment-naïve chronic thromboembolic pulmonary hypertension patients have microvasculopathy.

18.
Circ J ; 85(4): 333-342, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33536399

RESUMO

BACKGROUND: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. CONCLUSIONS: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Transtornos Respiratórios , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Japão , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Estudos Prospectivos , Transtornos Respiratórios/complicações , Transtornos Respiratórios/tratamento farmacológico
19.
J Clin Rheumatol ; 27(8): e371-e377, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511146

RESUMO

BACKGROUND/OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance that can lead to right-sided heart failure. Connective tissue disease-associated PAH (CTD-PAH) often has poorer outcomes than idiopathic or hereditary PAH, suggesting the presence of non-PAH factors that could affect the prognoses. This cohort study aimed to identify prognostic factors for CTD-PAH management. METHODS: Medical records from April 1999 to November 2014 were reviewed to determine the time from treatment initiation to the occurrence of a clinically worsening event and the time elapsed until death. Data at baseline and the final assessment were used to identify prognostic factors associated with events using univariate and multivariate analyses by the stepwise Cox regression method. RESULTS: In 36 patients with CTD-PAH analyzed, the proportions with no clinically worsening events at 1, 2, and 3 years after treatment initiation were 62%, 52%, and 45%, respectively, with survival rates of 88%, 77%, and 77%, respectively. The regression model showed that reduced hemoglobin at baseline, reduced qR pattern in electrocardiogram lead V1, increased 60-minute erythrocyte sedimentation rate, and increased mean pulmonary arterial pressure at the final assessment were risk factors that were significantly associated with clinical worsening. For survival, no prognostic factor was identifiable. CONCLUSIONS: Hemodynamic and non-PAH factors, such as anemia, nutritional status, and inflammatory activity of the underlying CTD, which are not listed in the risk assessment table of PAH guidelines, should be strictly controlled to improve the prognosis of patients with CTD-PAH. A more multifactorial treatment strategy should be developed.


Assuntos
Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Estudos de Coortes , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/epidemiologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Prognóstico
20.
Can J Physiol Pharmacol ; 98(9): 625-628, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32433892

RESUMO

Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). It has been shown to improve symptoms of hypertension, exercise capacity, and hemodynamics and prolong time to clinical worsening. However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated aminotransferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single-nucleotide polymorphisms and two nongenetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model.


Assuntos
Bosentana/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Antagonistas dos Receptores de Endotelina/efeitos adversos , Modelos Estatísticos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Bosentana/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Creatinina/sangue , Antagonistas dos Receptores de Endotelina/farmacocinética , Feminino , Humanos , Japão/epidemiologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Mutação , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/genética , Medição de Risco/métodos , Sulfotransferases/genética , Sulfotransferases/metabolismo , Carboidrato Sulfotransferases
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