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1.
Behav Brain Res ; 416: 113536, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34416303

RESUMO

Increasing evidence has shown that adult hippocampal neurogenesis is closely related to the pathophysiological condition of depressive disorders. Recently, chronic social defeat stress paradigms have been regarded as important animal models of depression, accompanied with neural plastic changes in the hippocampus. However, little is known about influences of non-physical stress on neurogenesis. In the present study, we focused on the chronic vicarious social defeat stress paradigm and examined the effect of psychological stress on mouse hippocampal neurogenesis. Immediately after the chronic psychological stress, the cell survival rate in the dentate gyrus of the hippocampus was significantly diminished without modifying the cell proliferation rate. The decreased ratio in cell survival persisted for 4 weeks after the stress-loading period, while the differentiation and maturity of new-born neurons were identical to control groups. Furthermore, treatment with the chronic antidepressant fluoxetine reversed the social behavioral deficits and promoted new-born neurons survival. These results demonstrate that emotional stress in the vicarious social defeat stress paradigm influences neuronal cell survival in the hippocampus, which reinforces its validity as an animal model of depression.

2.
Acta Derm Venereol ; 101(8): adv00527, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34405247

RESUMO

Systemic inflammatory response markers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and monocyte-to-lymphocyte ratio, are useful prognostic factors for various malignant tumours. The aim of this study was to investigate the clinical relevance of these markers in primary cutaneous angiosarcoma. Twenty-six patients were retrospectively divided into 2 groups according to pretreatment peri-pheral blood cell counts or systemic inflammatory response marker levels; overall survival and progression-free survival were compared. Univariate analysis found that high neutrophil count (> 3.1×109/l), high neutrophil-to-lymphocyte ratio (> 2.4), high platelet-to-lymphocyte ratio (> 175) and low lymphocyte count (≤ 1.3×109/l) were related to shorter overall survival, while high neutrophil and low lymphocyte groups had shorter progression-free survival. In multivariate analysis, high neutrophil count and high neutrophil-to- lymphocyte ratio (hazard ratio 7.44 and 5.04, 95% confidence interval 1.48-37.2 and 1.26-20.1, respectiv-ely) were identified as independent prognostic factors for poor overall survival. These results indicate that systemic inflammatory response markers serve as prognostic predictors in primary cutaneous angiosarcoma, as well as in other types of soft-tissue sarcoma.


Assuntos
Hemangiossarcoma , Neutrófilos , Humanos , Linfócitos , Prognóstico , Estudos Retrospectivos
3.
Biofactors ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418170

RESUMO

This study aimed to reveal the possible mechanisms by which O-linked-N-acetylglucosaminylation (O-GlcNAcylation) regulates osteoblast differentiation using a series of bioinformatics-oriented experiments. To examine the influence of O-GlcNAcylation levels on osteoblast differentiation, osteoblastic MC3T3-E1 cells were treated with O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) inhibitors. Correlations between the levels of O-GlcNAcylation and the expression of osteogenic markers as well as OGT were evaluated by qPCR and western blotting. The O-GlcNAcylated proteins assumed to correlate with Runx2 expression were retrieved from several public databases and used for further bioinformatics analysis. Following the findings of the bioinformatics analysis, intracellular calcium ([Ca2+ ]i ) was monitored in the cells treated with OGT and OGA inhibitors using a confocal laser-scanning microscope (CLS). The interaction effect between O-GlcNAcylation and [Ca2+ ]i on osteogenic marker expression was determined using stable OGT knockdown MC3T3-E1 cells. O-GlcNAcylation was positively associated with osteoblast differentiation. The time-course profile of global O-GlcNAcylated proteins showed a distinctive pattern with different molecular weights during osteoblast differentiation. The expression pattern of several O-GlcNAcylated proteins was significantly similar to that of Runx2 expression. Bioinformatic analysis of the retrieved Runx2-related-O-GlcNAcylated-proteins revealed the importance of [Ca2+ ]i . CLS showed that alteration of O-GlcNAcylation rapidly changed [Ca2+ ]i in MC3T3-E1 cells. O-GlcNAcylation and [Ca2+ ]i showed an interaction effect on the expression of osteogenic markers. OGT knockdown disrupted the [Ca2+ ]i -induced expression changes of osteogenic markers. O-GlcNAcylation interacts with [Ca2+ ]i and elicits osteoblast differentiation by regulating the expression of osteogenic markers.

4.
Nat Biomed Eng ; 5(8): 926-940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34373601

RESUMO

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.


Assuntos
Proteínas de Homeodomínio/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Pluripotentes/citologia , Animais , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/transplante , Condrogênese , Doenças do Colágeno/terapia , Meios de Cultura/química , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Pluripotentes/metabolismo , Polímeros/química , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Antígenos Thy-1/metabolismo , Engenharia Tecidual
5.
Sci Rep ; 11(1): 16276, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381165

RESUMO

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. Traumatic stress during adolescence increases the risk of IBS in adults. The aim of this study was to characterize the juvenile social defeat stress (SDS)-associated IBS model in mice. Juvenile mice were exposed to an aggressor mouse for 10 min once daily for 10 consecutive days. Behavioral tests, visceral sensitivity, immune responses, and fecal bacteria in the colon were evaluated in 5 weeks after SDS exposure. Social avoidance, anxiety- and depression-like behavior, and visceral hypersensitivity were observed. Juvenile SDS exposure significantly increased the number of 5-HT-containing cells and calcitonin gene-related peptide-positive neurons in the colon. The gut microbiota was largely similar between the control and juvenile SDS groups. The alterations in fecal pellet output, bead expulsion time, plasma corticosterone concentration, and colonic 5-HT content in response to restraint stress were exacerbated in the juvenile SDS group compared with the control group. The combination of juvenile SDS and restraint stress increased the noradrenaline metabolite 3-Methoxy-4-hydroxyphenylglycol (MHPG) content and MHPG/noradrenaline ratio in the amygdala when compared with restraint stress in control mice. These results suggest that juvenile SDS exposure results in later onset of IBS-like symptoms.

6.
Int J Cancer ; 149(8): 1593-1604, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34152598

RESUMO

Lung adenocarcinoma (LUAD) is the most common types among lung cancers generally arising from terminal airway and understanding of multistep carcinogenesis is crucial to develop novel therapeutic strategy for LUAD. Here we used human induced pluripotent stem cells (hiPSCs) to establish iHER2-hiPSCs in which doxycycline induced the expression of the oncoprotein human epidermal growth factor receptor 2 (HER2)/ERBB2. Lung progenitors that differentiated from iHER2-hiPSCs, which expressed NKX2-1/TTF-1 known as a lung lineage maker, were cocultured with human fetal fibroblast and formed human lung organoids (HLOs) comprising alveolar type 2-like cells. HLOs that overexpressed HER2 transformed to tumor-like structures similar to atypical adenomatous hyperplasia, which is known for lung precancerous lesion and upregulated the activities of oncogenic signaling cascades such as RAS/RAF/MAPK and PI3K/AKT/mTOR. The degree of morphological irregularity and proliferation capacity were significantly higher in HLOs from iHER2-hiPSCs. Moreover, the transcriptome profile of the HLOs shifted from a normal lung tissue-like state to one characteristic of clinical LUAD with HER2 amplification. Our results suggest that hiPSC-derived HLOs may serve as a model to recapitulate the early tumorigenesis of LUAD and would provide new insights into the molecular basis of tumor initiation and progression.


Assuntos
Adenocarcinoma de Pulmão/patologia , Carcinogênese , Regulação Neoplásica da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/patologia , Neoplasias Pulmonares/patologia , Organoides/patologia , Receptor ErbB-2/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Receptor ErbB-2/genética , Transcriptoma , Células Tumorais Cultivadas
7.
Sci Rep ; 11(1): 11617, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078988

RESUMO

Immune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

8.
Biochem Biophys Res Commun ; 560: 192-198, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34000468

RESUMO

The medial prefrontal cortex (mPFC) plays a vital role in the processing of emotional events. It has been shown that activation of the glutamatergic transmission in prelimbic subregion of the mPFC (PL-PFC) evoked anxiety-like behavior in rodents. We previously reported that local perfusion of a selective agonist to delta-opioid receptor (DOP), KNT-127, attenuated the veratrine-induced elevation of extracellular glutamate in the PL-PFC and anxiety-like behavior in mice. These results suggested the possibility that KNT-127 suppresses glutamate release from the presynaptic site in the PL-PFC. To examine this possibility directly, we performed whole-cell patch-clamp recording from principal neurons in the PL-PFC and examined the spontaneous and electrically-evoked excitatory postsynaptic currents (EPSC)s. We found that bath application of KNT-127 significantly decreased the frequency of spontaneous and miniature EPSCs. Conversely, amplitude, rise time, and decay time of spontaneous and miniature EPSCs were not affected by bath application of KNT-127. Also, KNT-127 increased paired-pulse ratios of electrically-evoked EPSCs in the PL-PFC principal neurons tested. Further, we analyzed the firing properties of pyramidal neurons in the PL-PFC and found that KNT-127 treatment significantly reduced the number of action potentials and firing threshold. These results suggested that KNT-127 suppresses glutamatergic synaptic transmission by inhibiting glutamate release from the presynaptic site and reduces neuronal excitability in the mouse PL-PFC. We propose the possibility that these suppressing effects of KNT-127 on PL-PFC activity are part of the underlying mechanisms of its anxiolytic-like effects.


Assuntos
Morfinanos/farmacologia , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Receptores Opioides delta/agonistas , Transmissão Sináptica/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia
9.
BMC Urol ; 21(1): 75, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941161

RESUMO

BACKGROUND: There has been a limited number of reports on the significance and risk factors of urethrovesical anastomotic urinary leakage (AUL) following robot-assisted radical prostatectomy (RARP). We aimed to analyze the clinical significance of AUL and evaluated its risk factors. METHODS: We conducted a multi-institutional study to review patients with prostate cancer undergoing RARP in three centers (The University of Tokyo Hospital, Mitsui Memorial Hospital, and Chiba Tokushukai Hospital). "Positive AUL" was defined as urinary extravasation at the anastomosis detected by post-operative cystogram and was further categorized into minor or major AUL. Univariate and multivariate analyses were performed to identify predictors of AUL. Postoperative continence rates and time to achieve continence were also analyzed. RESULTS: A total of 942 patients underwent RARP for prostate cancer in 3 centers. Of these patients, a cystogram after the RARP procedure was not performed in 26 patients leaving 916 patients for the final analysis. AUL was observed in 56 patients (6.1%); 34 patients (3.7%) with minor AUL and 22 patients (2.4%) with major AUL. Patients with major AUL exhibited a significantly longer time to achieve continence than those without major AUL. Multivariate analysis demonstrated that longer console time (≥ 184 min) was significantly associated with overall AUL, and higher body mass index (≥ 25 g/kg2) was a significant predictor of both major and overall AUL. CONCLUSIONS: The presence of major AUL was associated with the achievement of urinary continence, suggesting clinical relevance of its diagnosis by postoperative cystogram. A selective cystogram has been proposed for high-risk cases. Furthermore, identification of the risk factors of AUL will lead to optimal application.


Assuntos
Fístula Anastomótica/epidemiologia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Uretra/cirurgia , Bexiga Urinária/cirurgia , Idoso , Anastomose Cirúrgica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
10.
BMC Cancer ; 21(1): 501, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947348

RESUMO

BACKGROUND: The objective of this study is to investigate the clinical significance and risk factors of upgrading in the International Society of Urological Pathology (ISUP) Grade Group System in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. METHODS: A total of 583 patients diagnosed with prostate cancer by systematic biopsy were treated with RARP without neoadjuvant therapy from November 2011 to December 2018. Clinicopathological data were obtained from our clinical records. ISUP grade upgrading (IGU) was defined as 'ISUP grade in prostatectomy specimen determined to be higher than that in the biopsy specimen'. Clinicopathological factors, including age, PSA, prostate volume at biopsy (PV), PSA density, clinical stage, body mass index (BMI), interval from biopsy to prostatectomy, maximum percentage of cancer involvement per core (%CI), total number of biopsy cores, percentage of cancer positive biopsy cores (%PC), and sampling density were analyzed to detect potential risk factors of IGU. Biochemical recurrence (BCR) rates were calculated to analyze the effect of IGU on cancer prognosis. RESULTS: In univariate analysis, BMI was a positive predictor of IGU, while %CI, %PC, and sampling density were negative predictors of IGU. BMI and %PC were statistically significant predictors of IGU in multivariate analysis. For cases diagnosed as ISUP grade group 2 or higher at biopsy, there was a significant difference in BCR rates between cases with and without IGU. CONCLUSIONS: The results from our cohort showed that elements of both high-grade cancer risk (such as BMI) and sampling efficiency (such as %PC) contribute to IGU. Excluding cases diagnosed as ISUP grade group 1 at biopsy, BCR-free rates were significantly worse in cases with IGU, highlighting the need for more accurate pathological diagnosis at biopsy.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Análise de Variância , Biópsia por Agulha , Índice de Massa Corporal , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Antígeno Prostático Específico/análise , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/química , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Sociedades Médicas , Urologia
11.
Sci Rep ; 11(1): 6547, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753829

RESUMO

For peritonitis, a serious complication of peritoneal dialysis (PD), we investigated the relation between duration from the sign (PD effluent abnormalities) to treatment with appropriate antibiotics (ST time) and catheter removal. For 62 PD hospital patients, data of PD-related peritonitis (n = 109) were collected retrospectively. We examined ST time and PD catheter removal times using univariate and multivariate analyses. The catheter removal rate in the delayed ST time group (≥ 24 h) was higher than that in early ST time group (< 24 h) (38 vs. 16%, p = 0.02). Concomitant tunnel infection and delayed ST time were associated with catheter removal (OR [95% CI] 32.3 [3.15-329] and 3.52 [1.11-11.1]). Rates of catheter removal and re-development of peritonitis within 1 month after starting treatment were higher in the delayed ST time group (p = 0.02). PD duration at peritonitis and the first peritonitis episode were associated with delayed ST time (1.02 [1.00-1.04] and 3.42 [1.09-10.7]). Significant association was found between PD catheter removal and the start of treatment more than 24 h after appearance of abnormal effluent. Education for patients about prompt visitation at the onset of peritonitis with long PD duration might improve outcomes.

12.
J Med Case Rep ; 15(1): 136, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33773597

RESUMO

BACKGROUND: Vulvar Paget's disease (VPD) is a rare malignant disorder originating in the external genitalia. It occasionally invades into urethral or vaginal mucosa of female, making surgical treatment more complicating. In case of urethral invasion of Paget's cells, systematic mapping biopsy of urethral mucosa is the standard of care to determine the range of surgical resection. Resection of urethral mucosa and simple skin grafting often result in urethral stricture after surgery, which severely deteriorates patient's quality of life. CASE PRESENTATION: We applied a new technique of advancement urethral meatoplasty using buccal mucosa, in two Japanese cases of VPD with urethral invasion. After broad resection of vulvar skin together with the urethral mucosa, buccal mucosa was implanted between advanced urethral mucosa and skin graft. In both cases, we could prevent urethral stricture one year and two years after surgery, respectively. CONCLUSION: This technique prevented urethral stricture after surgery and could be a useful technique as part of urethroplasty for VPD.


Assuntos
Mucosa Bucal , Estreitamento Uretral , Feminino , Humanos , Masculino , Mucosa Bucal/cirurgia , Qualidade de Vida , Transplante de Pele , Uretra/cirurgia , Estreitamento Uretral/cirurgia
14.
Sci Rep ; 11(1): 105, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420263

RESUMO

Electrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of < 400 mL at the first session was a significant risk factor for MBC loss with further sessions. No other clinical parameters were associated with MBC over time. This study demonstrates a significant relationship between the frequency of electrocautery of Hunner lesions and MBC changes in HIC patients. Low MBC at the first session is a poor prognostic marker for MBC loss over multiple sessions.


Assuntos
Cistite Intersticial/cirurgia , Eletrocoagulação , Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Cistite Intersticial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Bexiga Urinária/fisiopatologia , Micção
15.
BMC Urol ; 21(1): 8, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413292

RESUMO

BACKGROUND: Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. CASE PRESENTATION: A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. CONCLUSIONS: We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.


Assuntos
Adenocarcinoma/complicações , Dermatomiosite/complicações , Neoplasias da Próstata/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Dermatomiosite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
16.
Brain Res ; 1757: 147297, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33516811

RESUMO

Although delta opioid receptors (DOP) are now known to play a major role in modulating chronic pain and controlling emotional processes, unfortunately, some DOP agonists, such as SNC80, reportedly produced convulsive-like behaviors manifesting as tremor-like behaviors in a preclinical study. Therefore, these induced convulsions limit the progress of the clinical development of DOP agonists. However, mechanisms underlying DOP-induced convulsant activity remain unclarified. Thus, the study aimed to elucidate mechanisms that could cause tremor-like behaviors of SNC80. These drugs were microinjected into the ventral hippocampus CA3 (vCA3), amygdala (AMY), and insular cortex (IC) of mice. In addition, we examined the extracellular glutamate levels after DOP agonist local treatment. Microinjection of SNC80 into the vCA3 increased the number of tremor-like behaviors and extracellular glutamate levels but did not cause tremor-like behaviors in mice when microinjected into IC and AMY. Pretreatment with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainite receptor antagonist CNQX into vCA3 totally inhibited the SNC80-induced increases in tremor-like behaviors. In contrast, another DOP agonist, KNT-127, did not cause tremor-like behaviors in any of the tested brain areas. Further, the extracellular glutamate levels in the hippocampus were significantly lower in the KNT-127-treated mice than in the SNC80-treated mice. Our results showed that the administration of SNC80, but not KNT-127, into vCA3 induced tremor-like behaviors by activating glutamatergic neurons in mice. We propose that KNT-127 should be further studied clinically as a DOP agonist that is expected to have a low risk for convulsions than those resulting in antinociceptive and antidepressant effects.

17.
J Invest Dermatol ; 141(7): 1780-1791, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33485880

RESUMO

We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.

18.
Urol Int ; 105(7-8): 619-623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33508829

RESUMO

INTRODUCTION: Management of patients with atypical urinary cytology (class III) of the upper urinary tract is often complicated because some patients develop upper urinary tract urothelial carcinoma (UTUC). Here, we aimed to help define the optimal management of these patients. METHODS: We investigated 31 patients who underwent retrograde ureteropyelography (RP) and were diagnosed with atypical findings of upper urinary tract cytology. RESULTS: UTUC was revealed in 17 of 31 patients during the follow-up period of 1 year or longer. Tumor-like lesions and wall thickening in the upper urinary tract on initial computed tomography (CT) were significant predictors of UTUC (p = 0.0002 and p = 0.012, respectively). All 11 patients with tumor-like lesions and 3 of 8 patients with wall thickening on initial CT underwent nephroureterectomy, and UTUC was confirmed histologically. Moreover, 3 of 12 patients with hydronephrosis only or with normal findings later went on to develop UTUC. Repeated RP performed within 6 months from the initial RP was able to distinguish patients with UTUC from those without, even in individuals with normal CT findings. DISCUSSION/CONCLUSION: Repeated RP based on initial CT findings is recommended in patients with atypical urinary cytology of the upper urinary tract. Nephroureterectomy without repeated RP may be warranted in patients with tumor-like lesions on initial CT findings.

19.
Photodiagnosis Photodyn Ther ; 33: 102179, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33429097

RESUMO

BACKGROUND: Severe hypotension is a notable adverse event caused by administration of 5-aminolevulinic acid (5-ALA) during photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT). Hypotension can be prolonged following induction of anesthesia and may require continuous administration of a vasopressor. Here, we investigated the risk factors for severe hypotension caused by oral administration of 5-ALA. METHODS: A total of 128 patients with bladder tumors who underwent PDD-TURBT using 5-ALA were included in this study. Clinicopathological data were collected retrospectively and the correlations between the incidence of severe hypotension and clinicopathological factors were analyzed. RESULTS: Severe hypotension developed in 8 cases (6.3 %). Age ≥ 80 years, body mass index (BMI) ≥ 25 (kg/m2), and estimated glomerular filtration rate (eGFR) < 45 (mL/min/1.73 m2) were significantly correlated with severe hypotension (P = 0.003, 0.017, and 0.027, respectively). Severe hypotension developed in 1 of 89 cases (1.1 %) which have 0 or 1 risk factor, and in 3 of 31 cases (9.7 %) which have 2 risk factors, whereas it developed in 4 of 8 cases (50 %) which have all risk factors. Patients with all risk factors developed severe hypotension significantly more frequently compared with patients with 1 or fewer risk factors (P < 0.001). CONCLUSION: Age ≥ 80 years, BMI ≥ 25, and eGFR < 45 are risk factors for severe hypotension in PDD-TURBT using 5-ALA. The risk of developing severe hypotension is extremely high in patients who have all factors. Adjustment of the 5-ALA dose may be desirable in those patients.


Assuntos
Hipotensão , Fotoquimioterapia , Neoplasias da Bexiga Urinária , Administração Oral , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/efeitos adversos , Índice de Massa Corporal , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Hipotensão/epidemiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia
20.
Jpn J Clin Oncol ; 51(1): 156-159, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32875336

RESUMO

Prostate cancer is one of the most common malignancies, but a substantial portion remains latent throughout the patients' lifetime. Analysis of temporal change in the latent prostate cancer pool would be beneficial for clinical decision-making, but longitudinal autopsy studies are rare. We conducted a hand-search of the Annual of Pathological Autopsy Cases in Japan from 1980 to 2016 for cases of latent prostate cancer. Of 570 997 males aged 30 or older, latent prostate cancer was detected in 12 562 patients (2.2%). Proportion of detected cases correlated strongly with 'aging rate', the percentage of population aged 65 or older (squared Pearson's correlation coefficient r2 = 0.972, P value <0.0001). Temporal increase in proportion was also seen in each age group as well. This continuous growth reinforces evidence from past Japanese reports on latent prostate cancer. The rapidly rising ageing rate of Japan may forecast further increase in the latent prostate cancer pool moving forward.


Assuntos
Bibliometria , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Autopsia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia
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