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1.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753513

RESUMO

Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. In this study, we successfully in vitro cultured H. suis directly from human stomachs. Unlike Helicobacter pylori, the viability of H. suis decreases significantly on neutral pH; therefore, we achieved this using a low-pH medium for transport of gastric biopsies. Ultimately, we isolated H. suis from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings. Oral infection of mice with H. suis clinical isolates elicited gastric and systemic inflammatory responses; in addition, progression of gastric mucosal metaplasia was observed 4 mo postinfection. Because H. suis could be isolated from the stomachs of infected mice, our findings satisfied Koch's postulates. Although further prospective clinical studies are needed, H. suis, like H. pylori, is likely a gastric pathogen in humans. Furthermore, comparative genomic analysis of H. suis using complete genomes of clinical isolates revealed that the genome of each H. suis isolate contained highly plastic genomic regions encoding putative strain-specific virulence factors, including type IV secretion system-associated genes, and that H. suis isolates from humans and pigs were genetically very similar, suggesting possible pig-to-human transmission.


Assuntos
Infecções por Helicobacter/genética , Helicobacter heilmannii/genética , Helicobacter heilmannii/patogenicidade , Gastropatias/microbiologia , Estômago/microbiologia , Fatores de Virulência/genética , Adulto , Animais , Modelos Animais de Doenças , Feminino , Genoma Bacteriano , Helicobacter heilmannii/isolamento & purificação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Suínos , Sistemas de Secreção Tipo IV/genética , Virulência/genética
2.
Infection ; 51(2): 355-364, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35902511

RESUMO

PURPOSE: We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan. METHODS: Data for 200 adult IHD patients in 2014-2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR. RESULTS: The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15-64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15-64-year group (7.5%) (p = 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15-64-year group (p < 0.001). The percentage of cases with bacteremia was significantly higher in the 15-64-year group than in the ≥ 65-year group (p = 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone. CONCLUSION: The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine.


Assuntos
Bacteriemia , Infecções por Haemophilus , Meningite , Humanos , Lactente , Idoso , Japão/epidemiologia , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae , Meningite/complicações , Bacteriemia/epidemiologia , Bacteriemia/complicações
3.
Helicobacter ; 25(5): e12700, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32790220

RESUMO

BACKGROUND: The clinical significance of non-Helicobacter pylori Helicobacter (NHPH) is still unknown. There are many reports of NHPH-infected patients suffering from gastric diseases. Here, we investigated the polymerase chain reaction (PCR) positivity of NHPH infection in gastric disease patients who were negative for H. pylori (Hp) by the rapid urease test and by pathological observation. MATERIALS AND METHODS: We collected the 296 endoscopically obtained gastric mucosal samples of Hp-negative gastric disease patients diagnosed based on a rapid urease test and pathology from 17 hospitals in Japan from September 2013 to June 2019, and we analyzed the existence of Hp and NHPH by PCR. The samples were also treated by indirect immunohistochemistry using an anti-Helicobacter suis VacA paralog antibody and were observed by confocal laser microscopy. RESULTS: Among the 236 non-Hp-eradicated cases, 49 cases (20.8%) were positive for NHPH. Among them, 20 cases were positive for Helicobacter suis, 7 cases were positive for Helicobacter heilmannii sensu stricto/ Helicobacter ailurogastricus (Hhss/Ha), and the other 22 cases could not be identified. The regional differences in the infection rates were significant. Forty percent of the nodular gastritis cases, 24% of the MALT lymphoma, 17% of the chronic gastritis cases, and 33% of the gastroduodenal ulcer cases were NHPH positive. Forty-five patients had been treated with one of the four types of combinations of a proton pump inhibitor and two antibiotics, and in all of these cases, the NHPH diagnosed by PCR was successfully eradicated. Immunohistochemistry using the Helicobacter suis-specific HsvA antibody coincided well with the PCR results. Among the 29 post-Hp eradication cases, three were NHPH positive, including one Hhss/Ha-positive case. Thus, approx. 20% of the Hp-negative non-Hp-eradicated gastric disease patients treated at 17 hospitals in Japan were infected with NHPH.


Assuntos
Antibacterianos , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter , Inibidores da Bomba de Prótons , Gastropatias , Adulto , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Helicobacter/classificação , Helicobacter/efeitos dos fármacos , Helicobacter/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/terapia , Humanos , Imuno-Histoquímica , Japão , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Gastropatias/diagnóstico , Gastropatias/epidemiologia , Gastropatias/terapia
4.
Microbiol Immunol ; 64(2): 113-122, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31750556

RESUMO

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive streptococcal infections, especially in elderly people. Between 2013 and 2018, 88 streptococci were isolated from clinical blood culture in a hospital in Toyama prefecture, Japan. The collection included six Group A SDSE (ASD) strains, which are rarely isolated. Multilocus sequence typing categorized five of the six strains into ST128 and the remaining strain into a new type. Maximum-likelihood phylogenetic analysis revealed that the six ASD strains had highly similar genome sequences. Bayesian analysis indicated that the most recent common ancestor of the strains appeared 39 years ago. The ASD strains possessed carbohydrate synthase genes that are conserved in Streptococcus pyogenes strains, whereas one strain featured a different arrangement of the gene cluster. The carbohydrate synthase genes varied by Lancefield type (A, C, and G).


Assuntos
Infecções Estreptocócicas , Streptococcus/genética , Idoso , Teorema de Bayes , Sangue/microbiologia , Metabolismo dos Carboidratos/genética , DNA Bacteriano , Resistência Microbiana a Medicamentos/genética , Genoma Bacteriano , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Filogenia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus/classificação , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação , Fatores de Virulência/genética , Sequenciamento Completo do Genoma
5.
J Infect Chemother ; 26(1): 119-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300378

RESUMO

Slackia exigua is an obligate anaerobic coccobacillus associated with dental infection, but rarely causes extraoral infection. We report two cases of monomicrobial bacteremia caused by S. exigua isolated from two institutions. The first case involved community-acquired bacteremia associated with pleural empyema in a 69-year-old man. The second case involved hospital-acquired bacteremia secondary to postoperative intra-abdominal abscess in a 73-year-old man with primary intestinal diffuse large B-cell lymphoma. S. exigua was finally identified by 16S ribosomal RNA gene sequencing analyses in both cases. In the first case, our attempts to identify the organism using commercial identification kits for anaerobes resulted in inaccurate identification as Gemella morbillorum. However, S. exigua was promptly identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in the second case. The epidemiology and clinical characteristics of S. exigua extraoral infection remain unclear because of the limitations in accurate identification and because only 19 cases of extraoral S. exigua infection have been reported previously, including four cases of bacteremia. Physicians should focus on this species, which can cause community-acquired infections and spread via various routes even in patients with no comorbidities. Further studies are needed to clarify the clinical characteristics of extraoral S. exigua infections.


Assuntos
Actinobacteria , Bacteriemia , Infecções por Bactérias Gram-Positivas , Abscesso Abdominal , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Idoso , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Tipagem Molecular , Derrame Pleural , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
6.
Zoolog Sci ; 36(2): 154-158, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120651

RESUMO

Sperm competition can theoretically affect sperm morphology; however, it remains unclear whether and how sperm morphology tracks the intensity of sperm competition in each population. The barn swallow Hirundo rustica is a model species used in the study of sexual selection, and exhibits considerable variation in extra-pair paternity (percentage extra-pair young, ca. 3-30%) among populations. In the Joetsu population of the barn swallow, extra-pair paternity is virtually absent (< 3%), providing a rare opportunity to study sperm morphology under limited sperm competition, and to compare it with those reported in populations with frequent extra-pair paternity (>15%). We found that head, midpiece, and total sperm length were significantly shorter in the Joetsu population than in populations with frequent extra-pair paternity. Moreover, the variability in total sperm length, measured as the coefficient of variation in the Joetsu population, was twice as high as that of populations with frequent extra-pair paternity. These results are consistent with a positive, directional, and stabilizing effect of sperm competition on sperm morphology. Together with previous studies in populations with frequent extra-pair paternity, the current study provides one of few sets of evidence to show a link between the intensity of sperm competition and the mean and variance of sperm morphology within a wild bird species.


Assuntos
Espermatozoides/citologia , Andorinhas , Animais , Japão , Masculino , Espermatozoides/fisiologia
7.
Am J Emerg Med ; 36(3): 528.e3-528.e5, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29248270

RESUMO

Coronary artery spasm (CAS) rarely worsens from single-vessel to simultaneous multivessel CAS naturally, and simultaneous multivessel CAS leads to serious conditions such as cardiopulmonary arrest (CPA). A 77-year-old Japanese man who took medications for CAS was transferred to our hospital due to persistent chest pain. On arrival, his vital signs were stable, but his electrocardiogram (ECG) showed ST-segment elevation in leads II, III and aVF. Ventricular fibrillation developed suddenly. Although routine cardiopulmonary resuscitation (CPR) including intravenous administration of epinephrine was performed immediately, he could not be resuscitated. After initiation of percutaneous cardiopulmonary support (PCPS), there was a return of spontaneous circulation. His ECG showed exacerbation of myocardial ischemia with ST-segment elevation in leads I, II, III, aVL, aVF and V3-V6. Emergency coronary angiography revealed severe CAS of the right and left coronary arteries, which was relieved completely by intracoronary administration of nitrates. He was diagnosed with acute myocardial infarction due to simultaneous 3-vessel CAS that progressed over time. About 6h after arrival, he developed hemodynamic instability and died. CAS worsened from single-vessel to simultaneous 3-vessel spasm, and intracoronary administration of nitrates was effective in relieving CAS, which was documented by the ECG and coronary angiogram. Since CAS can progress over time, nitrates must be administered immediately. When CAS leads to CPA, epinephrine may be ineffective in CPR because of its vasoconstrictive effect on coronary arteries; therefore, PCPS should be initiated, and intracoronary nitrates should be administered.


Assuntos
Vasoespasmo Coronário/complicações , Infarto do Miocárdio/etiologia , Idoso , Dor no Peito/etiologia , Angiografia Coronária , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/diagnóstico por imagem , Progressão da Doença , Eletrocardiografia , Humanos , Masculino , Infarto do Miocárdio/diagnóstico
8.
Am J Forensic Med Pathol ; 39(2): 164-168, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29401110

RESUMO

A crossbow is a bow that shoots an arrow when a gun-like trigger is pulled. Deaths caused by accidental crossbow shootings are extremely rare. Here we describe an autopsy case of a penetrating wound to the left cerebral hemisphere caused by an accidental shooting with a crossbow. A man in his early 60s who lived with his wife and had used crossbows for 20 years as his hobby was found one early morning in the shed of his house, collapsed and bleeding from the head and neck. He was taken to a hospital and died after approximately 3 days of conservative treatment. At autopsy, a penetrating wound between the upper part of the left anterior neck and the left frontoparietal region was evident. Traumatic intracerebral hematoma was observed in the left frontal lobe, and severe traumatic subarachnoid hemorrhage was present throughout the brain. Cerebral contusion and hematoma without any organization were noted around the penetration. The cause of death was determined to be cerebral contusion and intracerebral hematoma due to the penetrating wound by the crossbow arrow. He was probably trying to load an arrow into the crossbow by placing it on the floor, pointing upward, and made a mistake in its operation that resulted in the shooting of the arrow. This case is unique because it was a rare accidental death caused by a crossbow arrow, and a detailed histopathological examination was performed.


Assuntos
Acidentes , Cérebro/lesões , Traumatismos Cranianos Penetrantes/etiologia , Armas , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/patologia , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/patologia , Cérebro/diagnóstico por imagem , Cérebro/patologia , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Traumatismos Cranianos Penetrantes/patologia , Hematoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/lesões , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/patologia
9.
Helicobacter ; 22(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28834011

RESUMO

BACKGROUND: We have previously revealed that omega-3 polyunsaturated fatty acids can prevent Helicobacter pylori infection by blocking the futalosine pathway, an alternative route for menaquinone (MK) biosynthesis. MATERIALS AND METHODS: 1, Different H. pylori strains were grown in liquid media supplemented with linoleic acid, an omega-6 fatty acid, or its 10-hydroxy derivative, 10-hydroxy-cis-12-octadecenoic acid (HYA), in the presence or absence of MK. The bacterial numbers in the media were estimated by plating; 2, C57BL/6NCrl mice received drinking water supplemented with different fatty acids starting from 1 week before infection with H. pylori or Helicobacter suis until the end of the experiment. The gastric colonization levels of H. pylori or H. suis were determined 2 weeks after infection by plating or quantitative PCR, respectively; 3, Mice were given HYA, starting 1 week before infection with H. suis and continuing until 6 months after infection, for analysis of the gastric conditions. RESULTS: 1, A low concentration (20 µmol/L) of HYA in culture broth suppressed the growth of H. pylori, and this inhibition was reduced by MK supplementation; 2, HYA treatment protected mice against H. pylori or H. suis infection; 3, HYA treatment suppressed the formation of lymphoid follicles in the gastric mucus layer after H. suis infection. CONCLUSIONS: HYA prevents gastric Helicobacter infections by blocking their futalosine pathways. Daily HYA supplementation is effective for the prevention of gastric mucosa-associated lymphoid tissue lymphoma induced by persistent infection with H. suis.


Assuntos
Ácidos Graxos Ômega-6/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Ácidos Esteáricos/administração & dosagem , Animais , Carga Bacteriana , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Feminino , Helicobacter heilmannii/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento , Vitamina K 2/administração & dosagem
10.
Digestion ; 95(1): 61-66, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28052279

RESUMO

BACKGROUND: Non-Helicobacter pylori-helicobacters (NHPH) compose a group of gram negative zoonotic bacteria that may induce in humans gastric diseases including gastritis, gastroduodenal ulcer and MALT lymphoma. Their prevalence in the general population has previously been reported to 0.1-6.2%, although such reports still remain less in number. AIMS: This study aimed at estimating the prevalence of gastric NHPH in Japanese people, and further aimed at linking this to different gastric diseases and co-infection with H. pylori. METHODS: Endoscopically obtained biopsy samples from 280 Japanese patients with various gastric diseases were collected. Samples were analyzed by immunohistochemistry and by species-specific PCR for detection of gastric helicobacters. RESULTS: The total prevalence of gastric NHPH among 280 Japanese patients was 6.1%, and the prevalence of H. pylori was 65.7%. There was no significant difference in prevalence of either NHPH or H. pylori when infected with H. pylori or NHPH, respectively. NHPH infection was found to be the highest in patients with gastric MALT lymphoma and duodenal ulcer, the former being independent of co-infection with H. pylori and the latter being dependent. CONCLUSIONS: This study reports a total prevalence of 6.1% of gastric NHPH in Japanese patients, and further highlights gastric MALT lymphoma and duodenal ulcer (when co-infected with H. pylori) as important related diseases.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter , Gastropatias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Gastropatias/epidemiologia , Gastropatias/patologia , Adulto Jovem
11.
Cytokine ; 84: 1-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27203664

RESUMO

The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9mg/kg DNR (i.v). Followed by curcumin (100mg/kg) administration orally every day for 6weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)κB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats.


Assuntos
Curcumina/farmacologia , Daunorrubicina/farmacologia , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Regulação para Baixo/efeitos dos fármacos , Inflamação/metabolismo , Interleucina-10/metabolismo , Rim/metabolismo , Testes de Função Renal/métodos , Macrófagos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Insuficiência Renal/sangue , Insuficiência Renal/metabolismo , Tetraspanina 30/metabolismo
12.
Digestion ; 93(4): 260-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27160882

RESUMO

Non-Helicobacter pylori-Helicobacters including H. suis, H. heilmanniisensu stricto and H. felis comprise a group of bacteria that may inhabit the stomach of humans and animals. Human gastric infection has been associated with gastritis, ulcer, MALT lymphoma and cancer. Although the fastidious nature of these organisms has hampered their research, recent advancements in in vitro cultivation and recent reports on in vivo models and prevalence studies in humans suggest this group of bacteria to be of more clinical significance than earlier believed. The present review discusses their history, microbiology and relevance to human health.


Assuntos
Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter , Linfoma não Hodgkin/microbiologia , Neoplasias Gástricas/microbiologia , Estômago/microbiologia , Animais , Mucosa Gástrica/patologia , Helicobacter/classificação , Helicobacter/genética , Helicobacter/isolamento & purificação , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Humanos , Filogenia
13.
J Infect Chemother ; 22(4): 229-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26908231

RESUMO

The Streptococcus dysgalactiae subspecies equisimilis (SDSE) possesses clinical similarities to group A streptococcus (GAS) and has recently been recognized as a causative pathogen of life-threatening streptococcal infections. Human membrane cofactor protein (CD46), a complement regulatory protein ubiquitously expressed on every cell type except for erythrocytes, has been implicated as a receptor for human-specific pathogens including GAS. In the present report, SDSE strain GGS_124 was isolated from a patient suffering from streptococcal toxic shock syndrome. When CD46-expressing transgenic (Tg) and non-Tg mice were infected subcutaneously into a hind footpad with 1 × 10(7) colony-forming units of GGS_124, both CD46 Tg and non-Tg mice showed similar levels of colonization in the popliteal lymph nodes at day 3 after infection. However, the following differences were found between CD46 Tg and non-Tg mice after infection. First, there was a statistically significant difference in mortality rates between CD46 Tg (33%) and non-Tg (0%) mice within 35 days after infection. Second, all surviving CD46 Tg mice developed ankle arthritis at day 35 after infection, whereas non-Tg mice did not develop ankle arthritis on the infected hind paws. Finally, CD46 Tg mice developed a pus-filled abscess accompanied by renal failure at day 6 or later after infection. These observations suggest that CD46, the host cell-surface pathogen receptor, functioned to attract GGS_124 into deep tissues, so that the subcutaneous infection with GGS_124 induced invasive streptococcal diseases in CD46 Tg mice.


Assuntos
Artrite Infecciosa/microbiologia , Proteína Cofatora de Membrana/genética , Choque Séptico/microbiologia , Infecções Estreptocócicas/microbiologia , Animais , Artrite Infecciosa/imunologia , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Humanos , Injeções Subcutâneas , Masculino , Proteína Cofatora de Membrana/administração & dosagem , Proteína Cofatora de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Choque Séptico/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus
14.
J Infect Chemother ; 22(9): 587-92, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27346378

RESUMO

We aimed to identify narrow-spectrum natural compounds that specifically inhibit an alternative menaquinone (MK; vitamin K2) biosynthetic pathway (the futalosine pathway) of Helicobacter pylori. Culture broth samples of 6183 microbes were examined using the paper disc method with different combinations of 2 of the following 3 indicator microorganisms: Bacillus halodurans C-125 and Kitasatospora setae KM-6054(T), which have only the futalosine pathway of MK biosynthesis, and Bacillus subtilis H17, which has only the canonical MK biosynthetic pathway. Most of the active compounds isolated from culture broth samples were from the families of polyunsaturated fatty acids (PUFAs). Only one compound isolated from the culture broth of Streptomyces sp. K12-1112, siamycin I (a 21-residue lasso peptide antibiotic), targeted the futalosine pathway. The inhibitory activities of representative PUFAs and siamycin I against the growth of B. halodurans or K. setae were abrogated by supplementation with MK. Thereafter, the growth of H. pylori strains SS1 and TN2GF4 in broth cultures was dose-dependently suppressed by eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or siamycin I, and these inhibitory effects were reduced by supplementation with MK. Daily administration of EPA (100 µM), DHA (100 µM), or siamycin I (2.5 µM) in drinking water reduced the H. pylori SS1 colonization in the gastric mucosa of C57BL/6 mice by 96%, 78%, and 68%, respectively. These data suggest that EPA, DHA, and siamycin I prevented H. pylori infection by inhibiting the futalosine pathway of MK biosynthesis.


Assuntos
Vias Biossintéticas/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Nucleosídeos/biossíntese , Vitamina K 2/farmacologia , Animais , Ácidos Docosa-Hexaenoicos/antagonistas & inibidores , Ácidos Docosa-Hexaenoicos/farmacologia , Quimioterapia Combinada , Ácido Eicosapentaenoico/antagonistas & inibidores , Ácido Eicosapentaenoico/farmacologia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/antagonistas & inibidores , Peptídeos/farmacologia
15.
Cytokine ; 74(2): 305-12, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25873126

RESUMO

The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1ß, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.


Assuntos
Benzimidazóis/farmacologia , Benzoatos/farmacologia , Colite , Citocinas/imunologia , Sulfato de Dextrana/toxicidade , Doença Aguda , Animais , Caspase 3/imunologia , Caspase 7/imunologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/imunologia , Modelos Animais de Doenças , Feminino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Telmisartan
16.
Cytokine ; 76(2): 206-213, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26049169

RESUMO

Polyphenolic compound tannic acid, which is mainly found in grapes and green tea, is a potent antioxidant with anticarcinogenic activities. In this present study, we hypothesized that tannic acid could inhibit nuclear factor (NF)κB signaling and inflammation in atopic dermatitis (AD) NC/Nga mice. We have analyzed the effects of tannic acid on dermatitis severity, histopathology and expression of inflammatory signaling proteins in house dust mite extract induced AD mouse skin. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) were measured by enzyme-linked immunosorbent assay. Treatment with tannic acid ameliorated the development of AD-like clinical symptoms and effectively inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells in the AD mouse skin. Serum levels of IFNγ and IL-4 were significantly down-regulated by tannic acid. Furthermore, tannic acid treatment inhibited DfE induced tumor necrosis factor (TNF)α, high mobility group protein (HMG)B1, receptor for advanced glycation end products (RAGE), extracellular signal-regulated kinase (ERK)1/2, NFκB, cyclooxygenase (COX)2, IL-1ß and increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ. Taken together, our results demonstrate that, DfE induced skin inflammation might be mediated through NFκB signaling and tannic acid may be a potential therapeutic agent for AD, which may possibly act via induction of PPARγ protein.


Assuntos
Dermatite Atópica/tratamento farmacológico , NF-kappa B/metabolismo , PPAR gama/genética , Transdução de Sinais/efeitos dos fármacos , Taninos/uso terapêutico , Animais , Antígenos de Dermatophagoides/imunologia , Citocinas/sangue , Dermatite Atópica/imunologia , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína HMGB1/genética , Interferon gama/sangue , Interleucina-4/sangue , Mastócitos/efeitos dos fármacos , Camundongos , PPAR gama/metabolismo , Pele/imunologia , Pele/patologia , Taninos/administração & dosagem , Fator de Necrose Tumoral alfa/sangue
17.
Exp Dermatol ; 24(6): 418-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25739980

RESUMO

Quercetin, glycosylated form of flavonoid compound, has potent antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of quercetin on skin lesion, high-mobility group box (HMGB)1 cascade signalling and inflammation in atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga transgenic mouse. After AD induction, quercetin (50 mg/kg, p.o) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)4, nuclear factor (NF)κB, nuclear factor erythroid-2-related factor (Nrf)2, kelch-like ECH-associated protein (Keap)1, extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, interleukin (IL)-1ß, IL-2Rα and other inflammatory markers in the skin of AD mice. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, IL-4) were measured by enzyme-linked immunosorbent assay. Quercetin treatment attenuated the development of AD-like skin lesions. Histological analysis showed that quercetin inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells. Furthermore, quercetin treatment downregulated cytoplasmic HMGB1, RAGE, nuclear p-NFκB, p-ERK1/2, COX2, TNFα, IL-1ß, IL-2Rα, IFNγ and IL-4 and upregulated nuclear Nrf2. Our data demonstrated that the HMGB1/RAGE/NFκB signalling might play an important role in skin inflammation, and quercetin treatment could be a promising agent for AD by modulating the HMGB1/RAGE/NFκB signalling and induction of Nrf2 protein.


Assuntos
Dermatite Atópica/tratamento farmacológico , Proteína HMGB1/genética , NF-kappa B/fisiologia , Quercetina/farmacologia , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Transdução de Sinais/efeitos dos fármacos , Translocação Genética/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Dermatite Atópica/etiologia , Dermatite Atópica/fisiopatologia , Dermatophagoides farinae/patogenicidade , Modelos Animais de Doenças , Feminino , Proteína HMGB1/efeitos dos fármacos , Proteína HMGB1/fisiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/fisiologia , NF-kappa B/efeitos dos fármacos , NF-kappa B/genética , Quercetina/uso terapêutico , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Índice de Gravidade de Doença , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Pele/efeitos dos fármacos , Pele/patologia , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/fisiologia , Translocação Genética/genética , Translocação Genética/fisiologia
18.
Helicobacter ; 20(4): 291-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25627811

RESUMO

BACKGROUND: Helicobacter suis strain TKY infection has been strongly associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in a C57BL/6J mouse model. MATERIALS AND METHODS: 1. C57BL/6J mice were intragastrically administered Lactobacillus strains once daily with 10(8)-10(9) colony-forming units (CFU), starting 2 days before intragastric infection with H. suis TKY (approximately 1 × 10(4) copies of 16S rRNA genes) or H. pylori Sydney strain 1 (SS1; 3 × 10(8) CFU) and continuing for 14 days after infection. 2. C57BL/6J mice were given powdered feed mixed with lyophilized L. gasseri SBT2055 (LG2055) cells (5 × 10(8) CFU/g), starting 2 weeks before intragastric infection with H. suis TKY and continuing 12 months after infection. RESULTS: 1. Among the 5 Lactobacillus strains that we examined, only LG2055 exhibited significantly preventive efficacy against both H. suis TKY and H. pylori SS1 at day 15 after infection. 2. Dietary supplementation with LG2055 protected mice from the formation of round protrusive lesions in the gastric fundus 12 months after infection with H. suis TKY, whereas such lesions had developed in the gastric fundus of nonsupplemented mice 12 months after infection. In addition, the formation of lymphoid follicles in gastric mucus layers was suppressed by dietary LG2055 at 3 months after infection. CONCLUSIONS: LG2055 administration is effective for suppressing the progression of gastric MALT lymphoma by reducing H. suis colonization.


Assuntos
Infecções por Helicobacter/prevenção & controle , Helicobacter heilmannii/patogenicidade , Lactobacillus/metabolismo , Linfoma de Zona Marginal Tipo Células B/prevenção & controle , Probióticos/uso terapêutico , Animais , Suplementos Nutricionais/microbiologia , Modelos Animais de Doenças , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Camundongos , Camundongos Endogâmicos C57BL
19.
Exp Mol Pathol ; 98(3): 558-62, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25872160

RESUMO

We have previously reported the mechanism behind the myocardial injury and the activation of autonomic nervous system during the ischemia-reperfusion (IR) of the rat brain. This study was planned to investigate the effect of carvedilol, a ß-blocker, in improving the myocardial injury caused by IR of the rat brain. We have used a whole cerebral IR model in rats by clamping both the right and left common carotid arteries. Rats were divided into five groups; Sham surgery group (Group-Sham), carvedilol treatment before ischemia group (Group-Is+C), vehicle control group (Group-Is+V), carvedilol treatment before reperfusion group (Group-Re+C) and the vehicle control group (Group-Re+V). We have measured the blood pressure and heart rate via a catheter, myocardial tissue ß1-adrenaline receptor (ß1-AR) levels, phosphor-p38 mitogen-activated protein kinase (p-p38 MAPK) signaling factor, malondialdehyde (MDA), and apoptosis (TUNEL assay and expression of caspase-7 protein). The results indicated that the increased expressions of ß1-AR, p-p38 MAPK, caspase-7, apoptotic cells and MDA level in the myocardial tissue due to brain ischemia-reperfusion were significantly reduced by carvedilol treatment. From these observations we can suggest that, with the advantage of its antioxidant and ß blocking action, carvedilol had played the improvement of myocardial injury in ischemia-reperfusion of the brain.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Encéfalo/irrigação sanguínea , Carbazóis/uso terapêutico , Coração/efeitos dos fármacos , Propanolaminas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose , Pressão Sanguínea , Carvedilol , Coração/fisiopatologia , Frequência Cardíaca , Masculino , Malondialdeído/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
J Infect Chemother ; 21(6): 410-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25817352

RESUMO

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be ß-lactamase-non-producing ABPC-resistant and 11.0% to be ß-lactamase-producing ABPC-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.


Assuntos
Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/microbiologia , Humanos , Japão , Testes de Sensibilidade Microbiana
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