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1.
PLoS One ; 14(9): e0222613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31525238

RESUMO

Bovine milk extracellular vesicles (EVs) attract research interest as carriers of biologically active cargo including miRNA from donor to recipient cells to facilitate intercellular communication. Since toxicity of edible milk seems to be negligible, milk EVs are applicable to use for therapeutics in human medicine. Casein separation is an important step in obtaining pure EVs from milk, and recent studies reported that adding hydrochloric acid (HCl) and acetic acid (AA) to milk accelerates casein aggregation and precipitation to facilitate EV isolation and purification; however, the effects of acidification on EVs remain unclear. In this study, we evaluated the acidification effects on milk-derived EVs with that by standard ultracentrifugation (UC). We separated casein from milk by either UC method or treatment with HCl or AA, followed by evaluation of EVs in milk serum (whey) by transmission electron microcopy (TEM), spectrophotometry, and tunable resistive pulse sensing analysis to determine EVs morphology, protein concentration, and EVs size and concentration, respectively. Moreover, we used anti-CD9, -CD63, -CD81, -MFG-E8, -HSP70, and -Alix antibodies for the detection of EVs surface and internal marker proteins by western blot (WB). Morphological features of EVs were spherical shape and similar structure was observed in isolated EVs by TEM. However, some of the EVs isolated by HCl and AA had shown rough surface. Although protein concentration was higher in whey obtained by UC, EV concentration was significantly higher in whey following acid treatment. Moreover, although all of the targeted EVs-marker-proteins were detected by WB, HCl- or AA-treatments partially degraded CD9 and CD81. These findings indicated that acid treatment successfully separated casein from milk to allow efficient EV isolation and purification but resulted in partial degradation of EV-surface proteins. Our results suggest that following acid treatment, appropriate EV-surface-marker antibodies should be used for accurate assess the obtained EVs for downstream applications. This study describes the acidification effects on EVs isolated from bovine milk for the first time.

2.
Part Fibre Toxicol ; 16(1): 34, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477126

RESUMO

BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years. RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant. CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.

3.
Kidney Blood Press Res ; : 1-12, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509838

RESUMO

BACKGROUND: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models. METHODS: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles. RESULTS: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (-) group after 48 h was significantly lower than that in the nigericin (+) group. CONCLUSIONS: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.

4.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420441
5.
Retina ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31365520

RESUMO

PURPOSE: To determine the morphological and physiological outcomes and safety of vitrectomy with fovea-sparing internal limiting membrane peeling for myopic macular retinoschisis (MRS). METHODS: Highly myopic eyes (refractive error greater than -8.0 diopters or an axial length longer than 26.5 mm) with MRS that underwent vitrectomy with fovea-sparing internal limiting membrane peeling were analyzed retrospectively. The best-corrected visual acuity, retinal morphology, and the central and paracentral retinal sensitivities at 2°/6° by microperimetry were evaluated before and after the surgery. Postoperative microscotomas were also determined. RESULTS: Thirty-three eyes with MRS; 16 eyes with and 17 eyes without a foveal retinal detachment, were studied. All 33 eyes had an improvement of MRS and foveal retinal detachment partially or completely after surgery, and none developed a full thickness macular hole. The postoperative best-corrected visual acuity, the central retinal sensitivity, and the retinal sensitivity at 2° were significantly better than the preoperative values. Sixteen eyes developed postoperative microscotomas at paracentral 2° and/or 6°. CONCLUSION: The results showed that vitrectomy with fovea-sparing internal limiting membrane peeling is an effective and safe method to treat an MRS regardless of the presence of a foveal retinal detachment. However, careful follow-up should be performed to detect postoperative microscotomas.

6.
Cancer Sci ; 110(8): 2485-2492, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31265162

RESUMO

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 µg/mL MWCNT-7 or 0.250 µg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Pulmão/efeitos dos fármacos , Mesotelioma/induzido quimicamente , Nanotubos de Carbono/efeitos adversos , Neoplasias Pleurais/induzido quimicamente , Animais , Asbesto Crocidolita/efeitos adversos , Injeções Intraperitoneais/métodos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Ratos , Ratos Endogâmicos F344 , Traqueia/efeitos dos fármacos , Traqueia/patologia
7.
Biosci Trends ; 13(2): 145-151, 2019 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-30996209

RESUMO

Streptococcus pyogenes causes several infectious diseases such as tonsillitis, cellulitis, and streptococcal toxic shock syndrome. As antibiotics are used for the general treatment of S. pyogenes infection, cases of treatment failure due to drug-resistant bacteria have increased. Lonicera caerulea var. emphyllocalyx (LCE) has been used as a folk medicine in northern Japan (Hokkaido). In this study, we investigated the antibacterial effect of methanol extracts of the fruit, stem, and leaf of LCE (LCEEs) against S. pyogenes using disk diffusion assay. As LCEE (fruit) had the strongest antibacterial activity among the three LCEEs, we focused on functional analysis of antibacterial effects of LCEE (fruit). LCEE (fruit) suppressed the growth of S. pyogenes in a dose-dependent manner. Morphological analysis by transmission electron microscopy demonstrated that LCEE (fruit) damaged the shape of S. pyogenes. Microplate and confocal laser microscopy analysis showed that biofilm formation was also suppressed by LCEE (fruit) in a dose-dependent manner. To further evaluate the surface structure of these biofilms, we performed hydrophobic analysis, which demonstrated that LCEE (fruit) reduced the hydrophobicity of the bacterial surface structure. Our data demonstrated that LCEE (fruit) had anti-bacterial and anti-biofilm effects on S. pyogenes in vitro, suggesting that the direct anti-bacterial effects of the LCEE (fruit) may be useful for treatment of local S. pyogenes infection.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Frutas/química , Lonicera/química , Metanol/química , Extratos Vegetais/farmacologia , Streptococcus pyogenes/fisiologia , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Caules de Planta/química , Streptococcus pyogenes/citologia , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/crescimento & desenvolvimento
8.
BMC Ophthalmol ; 19(1): 83, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922271

RESUMO

BACKGROUND: To report 2 cases of bilateral granulomatous panuveitis accompanied by chronic active Epstein-Barr virus infection (CAEBV). CASE PRESENTATION: Case 1 was a 38-year-old man who had a history of bilateral mild panuveitis who was diagnosed with CAEBV. Fifteen months later, a severe bilateral granulomatous panuveitis developed. White infiltrates covered the optic disc and all the retinal vessels of the right eye, and white nodules were seen along the retinal veins and arteries of the left eye. Case 2 was a 34-year-old man with bilateral panuveitis showing mutton-fat keratic precipitates and diffuse vitreous opacity in both eyes. A snow ball-like vitreous opacity was present in the right eye. Systemic investigations revealed the presence of CAEBV. In both cases, a comprehensive polymerase chain reaction (PCR) analyses of the aqueous humor detected significant copy numbers of EBV-DNA. The intraocular inflammation did not respond to steroid, methotrexate, and other immunosuppressive therapies, but was ameliorated after hematopoietic stem cell transplantation with preceding chemotherapy and low-dose total body irradiation in both cases. CONCLUSION: Granulomatous panuveitis can develop in eyes with CAEBV as a primary symptom. Ophthalmologists should rule out CAEBV when EBV-DNA is positive in the intraocular fluids of steroid-resistant panuveitis.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Granuloma/virologia , Pan-Uveíte/virologia , Adulto , Doença Crônica , Humanos , Masculino
9.
Arch Toxicol ; 93(4): 909-920, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30759267

RESUMO

Potassium octatitanate (K2O·8TiO2, POT) fibers are used as an alternative to asbestos. Their shape and biopersistence suggest that they are possibly carcinogenic. However, inhalation studies have shown that respired POT fibers have little carcinogenic potential. We conducted a short-term study in which we administered POT fibers, and anatase and rutile titanium dioxide nanoparticles (a-nTiO2, r-nTiO2) to rats using intra-tracheal intra-pulmonary spraying (TIPS). We found that similarly to other materials, POT fibers were more toxic than non-fibrous nanoparticles of the same chemical composition, indicating that the titanium dioxide composition of POT fibers does not appear to account for their lack of carcinogenicity. The present report describes the results of the 3-week and 52-week interim killing of our current 2-year study of POT fibers, with MWCNT-7 as a positive control and r-nTiO2 as a non-fibrous titanium dioxide control. Male F344 rats were administered 0.5 ml vehicle, 62.5 µg/ml and 125 µg/ml r-nTiO2 and POT fibers, and 125 µg/ml MWCNT-7 by TIPS every other day for 2 weeks (eight doses: total doses of 0.25 and 0.50 mg/rat). At 1 year, POT and MWCNT-7 fibers induced significant increases in alveolar macrophage number, granulation tissue in the lung, bronchiolo-alveolar cell hyperplasia and thickening of the alveolar wall, and pulmonary 8-OHdG levels. The 0.5 mg POT- and the MWCNT-7-treated groups also had increased visceral and parietal pleura thickness, increased mesothelial cell PCNA labeling indices, and a few areas of visceral mesothelial cell hyperplasia. In contrast, in the r-nTiO2-treated groups, none of the measured parameters were different from the controls.

10.
Br J Ophthalmol ; 103(10): 1418-1422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30798264

RESUMO

AIMS: International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria. METHODS: A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%-75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement. RESULTS: The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations. CONCLUSIONS: Revised IWOS criteria were proposed by a consensus workshop.

11.
J Anesth ; 33(2): 238-249, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30617546

RESUMO

PURPOSE: Procedural sedation and analgesia (PSA) is widely performed outside of the operating theater, often in emergency departments (EDs). The practice and safety of PSA in the ED in an aging society such as in Japan have not been well described. We aimed to characterize the practice pattern of PSA including indications, pharmacology and incidence of adverse events (AEs) in Japan. METHODS: We formed the Japanese Procedural Sedation and Analgesia Registry, a multicenter prospective observation registry of ED patients undergoing PSA. We included all patients who received PSA in the ED. PSA was defined as any systemic pharmacological intervention intended to facilitate a painful or uncomfortable procedure. The main variables in this study were patients' demographics, American Society of Anesthesiologists (ASA) physical status, indication of PSA, medication choices, and AEs. The primary outcome measure was overall AEs from PSA. RESULTS: We enrolled 332 patients in four EDs during the 12-month period. The median age was 67 years (IQR, 46-78). In terms of ASA physical status, 79 (23.8%), 172 (51.8%), and 81 (24.4%) patients were class 1, 2, 3 or higher, respectively. The most common indication was cardioversion (44.0%). The most common sedative used was thiopental (38.9%), followed by midazolam (34.0%) and propofol (19.6%). Among all patients, 72 (21.7%, 95% confidence interval, 17-26) patients experienced one or more AEs. The most common AE was hypoxia (9.9%), followed by apnea (7.2%) and hypotension (3.5%). All of the AEs were transient and no patient had a serious AE. CONCLUSION: In a multicenter prospective registry in Japan, PSA in the ED appears safe particularly since the patients who underwent PSA were older and had a higher risk profile compared to patients in previous studies in different countries.

12.
Eur J Haematol ; 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30390359

RESUMO

OBJECTIVE: Primary vitreoretinal lymphoma (PVRL) is a rare type of lymphoma wherein the lesions are limited to the eyes. PVRL is difficult to diagnose because of the challenges related to obtaining sufficient samples for biopsy. Moreover, PVRL has poor outcomes and often leads to the development of central nervous system (CNS) lesions during its course. Two studies recently reported that approximately 70%-80% of patients with vitreoretinal lymphoma have MYD88L265P , which is frequently mutated in primary CNS lymphoma (PCNSL). PCNSL is closely associated with PVRL. The mutation of CD79BY196 has been also frequently detected in PCNSL. Thus, we examined the mutation in PVRL to clarify its diagnostic and prognostic potential. METHOD: By using direct sequencing and allele-specific polymerase chain reaction, we examined the mutation of CD79BY196 and MYD88L265P in the DNA extracted from the vitreous fluid of 17 patients with PVRL upon diagnosis. We also retrospectively analyzed their prognostic potential for PVRL. RESULTS: Among the included patients, six patients (35%) were found with CD79BY196 mutations. Twelve (71%) patients were positive for MYD88L265P , and six samples from patients with benign uveitis were negative for both mutations. Interestingly, six patients with CD79BY196 mutations developed CNS diseases significantly earlier (16.5 months) than 11 patients with CD79BWT (67 months; P = 0.0135). CONCLUSION: Detecting CD79BY196 in vitreous DNA may contribute to the confirmation of the diagnosis and may have a prognostic potential for patients with PVRL.

13.
Drug Dev Ind Pharm ; : 1-6, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30366501

RESUMO

OBJECTIVE: This study aimed to establish a rapid and simple method for isolating exosomes from raw bovine milk and to compare the quality of the isolated exosomes with those isolated by a standard method involving ultracentrifugation (UC). METHODS: To remove caseins, which are major milk proteins consisting more than 80% of milk protein (35% in human breast milk) and hamper isolation and purification of exosomes, hydrochloride (HCl) was added to milk for isoelectric precipitation (IP). The effects of acidification on morphological features, particle size distribution, surface charge, and exosome surface proteins were analyzed by electron microscopy, tunable resistive pulse sensing (TRPS), and Western blot (WB) analysis, respectively. RESULTS: Electron microscopy showed that some of the exosomes isolated using IP had rough surfaces; most exosomes were successfully isolated without breakage, and their morphological features were similar to those of exosomes isolated by UC. TRPS showed that their surface charge and peaks (mode) for particle size distribution did not significantly differ between both methods. WB analysis using antibodies against the exosome surface marker proteins - milk fat globule-epidermal growth factor 8 (MFG-E8) and CD63 - revealed that the structures of exosome surface proteins were not affected by adding HCl. CONCLUSIONS: IP can be used to remove caseins to reduce operation time. This method will be useful for efficient isolation and purification of bovine milk exosomes and contribute to progression of research on health management of dairy cattle and drug delivery systems in human medicine, which require large amounts of milk exosomes.

14.
Arch Toxicol ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341734

RESUMO

Very little is known about the in vivo toxicity of inhaled double-walled carbon nanotubes (DWCNTs). In the present study, we compared the pulmonary toxicity of DWCNT to MWCNT-7, a well-known multi-walled carbon nanotube. Rats were divided into six groups: untreated, vehicle, low-dose DWCNT, high-dose DWCNT, low-dose MWCNT-7, and high-dose MWCNT-7. The test materials were administered by intra-tracheal intra-pulmonary spraying (TIPS) every other day for 15 days: the low-dose and high-dose groups were administered final total doses of 0.25 and 0.50 mg/rat of the test material. The animals were sacrificed 1 and 6 weeks after the final TIPS administration. Six weeks after the final TIPS administration, rats administered MWCNT-7 had high levels of macrophage infiltration into the lung with dense alveolar wall fibrous thickening throughout the lung; significant elevation of lactate dehydrogenase activity, alkaline phosphatase activity, and total protein concentration in the bronchioalveolar lavage fluid; an increase in the pulmonary cell PCNA index; slightly elevated levels of 8-OHdG DNA adducts in lung tissue DNA; a small but significant increase in protein concentration in the pleural cavity lavage fluid and an increase in the visceral mesothelial cell PCNA index. None of these parameters was increased in rats administered DWCNT. The primary lesion in rats administered DWCNT was scattered formation of granulation tissue containing internalized DWCNT fibers. Our data indicate that DWCNT has lower pulmonary and pleural toxicity than MWCNT-7.

15.
Biochem Biophys Res Commun ; 505(1): 81-86, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241938

RESUMO

Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29853978

RESUMO

Streptococcus pyogenes (S. pyogenes) is a species of Gram-positive coccoid bacteria having many virulence factors. Its capsule and exotoxins can cause upper respiratory tract infections such as sinusitis. The general treatment for S. pyogenes-induced sinusitis is administration of antibiotics such as penicillin and macrolides; however, a serious problem associated with these antibiotics is their attenuated effect. Shin'iseihaito (Xinyiqingfeitang), a formula of Japanese traditional Kampo medicine and traditional Chinese medicine, has been used for the treatment of sinusitis. In general, formulas of Japanese traditional Kampo medicine are orally administered. This is in contrast to certain formulas of traditional Chinese medicine, which are being recently administered intramuscularly or intravenously. Regarding these traditional Chinese medicine formulas, the injection methodology is reported to be more effective than oral intake. In this study, we compared the efficacy between orally and intramuscularly administered Shin'iseihaito against S. pyogenes-induced sinusitis. We evaluated the antibacterial effect of Shin'iseihaito extract (SSHT) against S. pyogenes by K-B disk diffusion assay. Furthermore, we investigated the nasal colonization of S. pyogenes, determined cytokine (TNF-α, IL-1ß, and IL-6) levels, and conducted a splenocyte proliferative assay in a murine sinusitis model. SSHT displayed direct anti-S. pyogenes activity. Intramuscular administration of SSHT decreased the nasal colonization of S. pyogenes compared with oral administration. Thymidine uptake analysis revealed that the proliferation of splenocytes from S. pyogenes-infected mice under intramuscular SSHT treatment was upregulated compared to that of splenocytes from S. pyogenes-infected mice under oral SSHT treatment. We also found that TNF-α, IL-1ß, and IL-6 levels in the nasal discharge from intramuscularly treated S. pyogenes-infected mice were lower than those from orally treated mice. Our findings suggest that intramuscular administration of Shin'iseihaito may be useful for the treatment of murine S. pyogenes-induced sinusitis.

17.
Am J Ophthalmol Case Rep ; 10: 189-191, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29780935

RESUMO

Purpose: To report two cases of panuveitis in immunocompetent patients in which cytomegalovirus was involved. Observation: Case 1 was a 46-year-old man who had a history of recurrent anterior chamber inflammations in his left eye. After Nd:YAG laser posterior capsulotomy, he developed panuveitis with vitreous haze and periphlebitis. Polymerase chain reaction (PCR) examination revealed the presence of cytomegalovirus (CMV) DNA in the anterior chamber (AC). He responded well to a series of intravitreal injections of ganciclovir (GCV). Case 2 was a 63-year-old woman who had a history of recurrent anterior uveitis in her left eye. Two years after cataract surgery, AC inflammation, diffuse vitreous haze, and periphlebitis had developed. CMV DNA was detected in the AC. Intravitreal injections of GCV and oral valganciclovir were administered, and ocular inflammation finally improved. Conclusions: and importance: We experienced two cases of CMV panuveitis in immunocompetent adults, both of which responded well to anti-viral therapies.

18.
Int Ophthalmol ; 2018 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-29397539

RESUMO

PURPOSE: To analyze the change in refractive error and the axial length of chronic Vogt-Koyanagi-Harada (VKH) disease. METHODS: Medical records of 106 eyes of 54 adult VKH patients were analyzed. The refractive error and the axial length were compared between the baseline (defined as the time point at least 2 weeks after acute stage of VKH) and the final visit. The rate of the eyes with significant myopia progression [defined as refraction change toward myopia > 1 diopter (D)] was examined. The correlation of the degree of sunset glow fundus/choroidal thickness with the change in refractive error was also evaluated. RESULTS: At the final visit, the mean refractive error was more myopic and the axial length was longer than at baseline. Seventeen of the 106 eyes (16.0%) showed significant myopia progression. The mean change in refractive error during a follow-up in these 17 eyes was - 2.7 D (range - 7.5 to - 1.1 D). The axial length data both at baseline and at the final visit were obtained only in 8 eyes. The mean change in axial length during a follow-up in these 8 eyes was 1.3 mm (range 0-3.7 mm). In the cases with myopia progression, sunset glow fundus was more frequent and subfoveal choroid was thinner than those without myopia progression. CONCLUSIONS: Myopia progression as well as increase in axial length occurs in VKH disease. The link between choroidal thinning and axial length elongation in VKH patients gives some insights into axial length increase of pathologic myopia.

19.
Cell Transplant ; 26(9): 1542-1550, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-29113468

RESUMO

Despite having pathological changes in the brain associated with Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous reports have demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through ß2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-ß (Aß) oligomers. The cholinergic network from the medial septal nucleus (MSN) is also a main modulating system for hippocampal glutamatergic neural activation through nicotinergic and/or muscarinergic acetylcholine receptors. Previously, we reported the importance of a cholinergic regulator gene in the MSN, hippocampal cholinergic neurostimulating peptide (HCNP). By using hippocampal sections from mice, we here demonstrated that the cholinergic neural activation from the MSN enhanced the glutamatergic neuronal activity during unsaturated LTP but not during saturated LTP. Synthetic Aß oligomers suppressed the hippocampal glutamatergic activity in a concentration-dependent manner. Furthermore, HCNP, as well as a cholinergic agonist acting through the muscarinic M1 receptor, prevented the suppression of hippocampal glutamatergic neuronal activity induced by synthetic Aß oligomers. This result suggests that the persisting cholinergic activation might be a potential explanation for the individual differences in cognitive effects of AD pathological changes.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neuropeptídeos/uso terapêutico , Animais , Eletrofisiologia , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Artigo em Inglês | MEDLINE | ID: mdl-28808474

RESUMO

Streptococcus pneumoniae (S. pneumoniae) causes sinusitis. The general treatment of S. pneumonia sinusitis is by using antibiotics; however, one of their serious problems is the attenuation of their effect. Shin'iseihaito (Xinyiqingfeitang), a formula of Japanese traditional Kampo medicine, has been used for the treatment of sinusitis in Japan. In this study, we investigated the efficacy of Shin'iseihaito against S. pneumoniae-caused sinusitis in mice. Oral administration of Shin'iseihaito extract (SSHT) decreased the nasal colonization of S. pneumoniae in both prophylactic and therapeutic treatments, respectively, and the former was more effective than the latter. Histopathological analysis revealed that the epithelial tissue from S. pneumoniae-infected nose under SSHT treatment recovered the tissue destruction in comparison to infected nose. We also confirmed this result by scanning electron microscopic analysis. Murine peritoneal macrophages from SSHT-treated mice had significant phagocytic activity in comparison to those from untreated group. We also found that tumor necrosis factor-α, interleukin-1ß, interleukin-6, and monocyte chemotactic protein-1 levels and the migration of macrophages from S. pneumoniae-infected mice with the treatment with SSHT were increased compared to those from untreated group. Our data suggest that Shin'iseihaito may be useful for the treatment of S. pneumoniae-induced sinusitis.

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