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BACKGROUND AND OBJECTIVES: The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown. METHODS: We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed. RESULTS: Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.
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Neoplasias Colorretais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Estadiamento de Neoplasias , Prognóstico , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Artificial intelligence (AI) using deep learning systems has recently been utilized in various medical fields. In the field of gastroenterology, AI is primarily implemented in image recognition and utilized in the realm of gastrointestinal (GI) endoscopy. In GI endoscopy, computer-aided detection/diagnosis (CAD) systems assist endoscopists in GI neoplasm detection or differentiation of cancerous or noncancerous lesions. Several AI systems for colorectal polyps have already been applied in colonoscopy clinical practices. In esophagogastroduodenoscopy, a few CAD systems for upper GI neoplasms have been launched in Asian countries. The usefulness of these CAD systems in GI endoscopy has been gradually elucidated. SUMMARY: In this review, we outline recent articles on several studies of endoscopic AI systems for GI neoplasms, focusing on esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cancer (GC), and colorectal polyps. In ESCC and EAC, computer-aided detection (CADe) systems were mainly developed, and a recent meta-analysis study showed sensitivities of 91.2% and 93.1% and specificities of 80% and 86.9%, respectively. In GC, a recent meta-analysis study on CADe systems demonstrated that their sensitivity and specificity were as high as 90%. A randomized controlled trial (RCT) also showed that the use of the CADe system reduced the miss rate. Regarding computer-aided diagnosis (CADx) systems for GC, although RCTs have not yet been conducted, most studies have demonstrated expert-level performance. In colorectal polyps, multiple RCTs have shown the usefulness of the CADe system for improving the polyp detection rate, and several CADx systems have been shown to have high accuracy in colorectal polyp differentiation. KEY MESSAGES: Most analyses of endoscopic AI systems suggested that their performance was better than that of nonexpert endoscopists and equivalent to that of expert endoscopists. Thus, endoscopic AI systems may be useful for reducing the risk of overlooking lesions and improving the diagnostic ability of endoscopists.
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BACKGROUND: Colorectal cancer (CRC) is a major global health concern, with a rising incidence in young individuals. Early-onset CRC displays unique clinicopathological and molecular characteristics, necessitating a closer examination of prognosis, particularly in the context of adjuvant chemotherapy. This study aimed to investigate the prognosis of early-onset CRC patients (< 50 years) diagnosed at stage II/III compared to older counterparts, utilizing propensity score matching to minimize heterogeneity. METHODS: A retrospective analysis of 3324 stage II/III CRC patients aged < 70 years was conducted, focusing on age-based subgroups (< 50 vs. ≥ 50 years). Propensity score matching balanced clinical characteristics. Relapse-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: In stage II CRC, age of onset did not impact prognosis after adjuvant chemotherapy, with no significant differences in RFS (5-year RFS rates: 80% in both groups, p = 0.98) and OS (5-year OS rates: 96% vs. 92%, p = 0.17). In stage III, a trend suggested slightly poorer OS in patients aged < 50 years than those ≥ 50 years (5-year OS rates: 85% vs. 88%, p = 0.077). However, in a propensity score-matched cohort, age-dependent differences were attenuated (5-year OS rates: 85% vs. 88%, p = 0.32). CONCLUSION: In the context of stage II/III CRC patients receiving adjuvant chemotherapy, age was not an independent predictor of prognosis. Age alone should not be the sole factor guiding treatment decisions.
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BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxicity that markedly limits the use of oxaliplatin and affects quality of life. Statins have been shown to exert neuroprotective effects in preclinical settings. The aim of the present study was to clarify whether statins prevented OIPN in patients with colorectal cancer (CRC) receiving adjuvant CAPOX therapy. METHODS: We examined 224 patients who received adjuvant CAPOX therapy for CRC between July 2010 and December 2021 at our hospital. Patients were divided into "Statin" and "Non-statin" groups based on statin use. Details on and the adverse events of adjuvant CAPOX therapy were examined in association with statin use. RESULTS: Thirty-one patients (14%) were treated with statins. There were no intergroup differences in the relative dose intensity or number of CAPOX cycles between the Statin and Non-statin groups. In total, 94% of patients in the Statin group and 95% of those in the Non-statin group developed OIPN (p=0.67). The severity of OIPN was similar between the two groups (p=0.89). The frequency of treatment delays in CAPOX did not significantly differ between the Statin and Non-statin groups (16% vs. 11%, p=0.45). CONCLUSIONS: The efficacy of statins to attenuate OIPN during adjuvant CAPOX therapy was not apparent in the current study. Further studies are needed to confirm the present results.
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Neoplasias Colorretais , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças do Sistema Nervoso Periférico , Humanos , Oxaliplatina , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fluoruracila/efeitos adversos , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Organoplatínicos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , CapecitabinaRESUMO
Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.
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Dermatite Atópica , Eczema , Humanos , Criança , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Qualidade do Sono , Índice de Gravidade de Doença , Prurido/diagnóstico , Prurido/etiologia , SonoRESUMO
INTRODUCTION: Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. However, the safety and efficacy of oxaliplatin-based chemotherapeutic regimens for elderly patients remains to be elucidated. The aim of the present study was to examine the tolerability and efficacy of adjuvant CAPOX (capecitabine and oxaliplatin) therapy for elderly patients in comparison with young patients. METHODS: We examined 138 Japanese patients who received adjuvant CAPOX therapy for high-risk stage II or III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. Treatment details of CAPOX therapy were analyzed in association with age. Moreover, prognosis of stage III CRC was compared between the patient groups. RESULTS: Twenty-three patients (17%) were ≥70 years old. Male patients were predominant in the ≥70 years group (p = 0.006). Patients ≥70 years old had more comorbidities (diabetes, p = 0.014; cardiovascular disease, p < 0.001; renal disease, p = 0.042) than patients <70 years old. There were no age-dependent differences in dose intensity, the number of cycles, or DLTs of CAPOX therapy. CSS and RFS were also similar between the ≥70 and <70 years old patients with stage III CRC. CONCLUSIONS: Adjuvant CAPOX therapy was tolerable in elderly Japanese patients. The prognosis of elderly patients with stage III CRC was similar to that of their younger counterparts. Advanced age itself may not be a contraindication for adjuvant chemotherapy in CRC. Future studies with a larger patient cohort are required to confirm the present results.
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Neoplasias Colorretais , Compostos Organoplatínicos , Humanos , Masculino , Idoso , Capecitabina , Oxaliplatina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/patologia , Fluoruracila , Estadiamento de NeoplasiasRESUMO
PURPOSE: Temporary ileostomy is sometimes created after colorectal surgery and may cause renal impairment. However, the impact of ileostomy on renal function during adjuvant chemotherapy for colorectal cancer (CRC) remains unknown. The aim of the present study was to examine the effects of ileostomy on renal function during adjuvant chemotherapy. METHODS: We examined 184 patients who received adjuvant CAPOX therapy (capecitabine and oxaliplatin) for CRC with or without ileostomy between January 2011 and December 2020 at the University of Tokyo Hospital. Clinicopathological factors, including renal function, were retrospectively reviewed in association with temporary ileostomy. Factors associated with reductions in the estimated glomerular filtration rate (eGFR) during CAPOX therapy were analyzed. RESULTS: Eighteen patients (10%) underwent temporary ileostomy. The maximum decrease in eGFR during CAPOX therapy was significantly higher in patients with than in those without ileostomy (- 16.1 vs. - 5.6 mL/min/1.73m2, p = 0.003). A multivariate analysis identified ileostomy as one of factors independently associated with reductions in eGFR during CAPOX therapy (p = 0.003). The cumulative number of readmission due to dehydration was also higher in patients with ileostomy (33% vs. 1%, p < 0.001). CONCLUSIONS: Ileostomy significantly reduced eGFR during adjuvant CAPOX therapy. Therefore, renal function needs to be monitored during CAPOX therapy, particularly in patients with ileostomy.
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Ileostomia , Compostos Organoplatínicos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Fluoruracila , Humanos , Ileostomia/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown. METHODS: We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data. RESULTS: Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040). CONCLUSIONS: Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.
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Dermatite Atópica , Dispositivos Eletrônicos Vestíveis , Adulto , Humanos , Prurido , Mãos , Extremidade SuperiorRESUMO
Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 µg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 µg/mL) ranged from 0.03 to 0.06 µg/mL and from 0.25 to 0.5 µg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 µg/mL and from 0.5 to 4 µg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes.
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Aminopiridinas/farmacologia , Antibacterianos/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Quinolonas/farmacologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Levofloxacino/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against each 50 isolates of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were recovered from cutaneous specimens of Japanese adult and pediatric patients who visited hospitals in 2014. The MIC90s of ozenoxacin against MSSA, MRSA and S. pyogenes isolates from adult patients were ≤0.06, 4 and ≤0.06 µg/mL, respectively. The MIC90s of ozenoxacin against MSSA and S. pyogenes isolates from pediatric patients were equal to those against the adult isolates. On the other hand, the MIC90s of ozenoxacin against the pediatric MRSA isolates was 0.12 µg/mL, and was 32 times lower than that against the adult isolates. The antimicrobial activity of ozenoxacin against MSSA, MRSA and S. pyogenes was equal to or greater than those of 7 reference antimicrobial agents had been used for the treatment of skin infections. The MICs of ozenoxacin was highly correlated with those of nadifloxacin and levofloxacin in the 50 MRSA isolates (r(2) = 0.906 and 0.833, respectively). However, ozenoxacin kept the potent antimicrobial activity with the MIC ranging from 1 to 4 µg/mL even against MRSA low susceptible (MIC: >64 µg/mL) to nadifloxacin or levofloxacin. Ozenoxacin could represent the first-in-class non-fluorinated quinolone for the topical treatment of various superficial skin infections caused by MSSA, MRSA and S. pyogenes.
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Aminopiridinas/farmacologia , Antibacterianos/farmacologia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Quinolonas/farmacologia , Dermatopatias Bacterianas/tratamento farmacológico , Streptococcus pyogenes/efeitos dos fármacos , Administração Cutânea , Adolescente , Adulto , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Japão , Levofloxacino/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Quinolizinas/administração & dosagem , Quinolizinas/farmacologia , Quinolizinas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/uso terapêutico , Creme para a Pele/administração & dosagem , Creme para a Pele/uso terapêutico , Dermatopatias Bacterianas/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
Benzoyl peroxide (BPO), a therapeutic agent for acne vulgaris, was assessed for in vitro antimicrobial activity against Propionibacterium acnes using a novel broth microdilution testing that improved BPO solubility. We searched for a suitable culture medium to measure the minimum inhibitory concentration (MIC) of BPO against P. acnes and finally found the Gifu anaerobic medium (GAM) broth supplemented with 0.1(v/v)% glycerol and 2(v/v)% Tween 80, in which BPO dissolved up to 1250 µg/mL and P. acnes grew well. The MICs and minimum bactericidal concentrations (MBCs) of BPO against 44 clinical isolates of P. acnes collected from Japanese patients with acne vulgaris were determined by our testing method using the supplemented GAM broth. The MICs of BPO were 128 or 256 µg/mL against all isolates of P. acnes regardless of susceptibility to nadifloxacin or clindamycin. The MBCs of BPO were also 128 or 256 µg/mL against the same isolates. Moreover, BPO at the MIC showed a rapid bactericidal activity against P. acnes ATCC11827 in time-kill assay. In conclusion, we could develop a novel assay for the MIC and MBC determinations of BPO against P. acnes, which is reliable and reproducible as a broth microdilution testing and the present results suggest that BPO has a potent bactericidal activity against P. acnes.
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Antibacterianos/farmacologia , Peróxido de Benzoíla/farmacologia , Testes de Sensibilidade Microbiana/métodos , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/microbiologia , Meios de Cultura , Humanos , Propionibacterium acnes/isolamento & purificação , Reprodutibilidade dos TestesRESUMO
PURPOSE: Banoxantrone is a topoisomerase II inhibitor that is selectively activated in hypoxia. Although it has exhibited anti-tumor activity against several types of cancers in preclinical models, its efficacy against colorectal cancer (CRC) remains unclear. METHODS: We examined the antitumor effects of 1,4-bis[2-(dimethylamino)ethylamino]-5,8-dihydroxyanthracene-9,10-dione (AQ4), an activated metabolite of banoxantrone, in CRC cell lines (HT-29, CaR-1) using in vitro experiments under normoxic and hypoxic conditions. The inhibition of cell growth was assessed using a proliferation assay. The induction of apoptosis and changes in the cell cycle were measured using flow cytometry. Signaling pathways involved in apoptosis and hypoxia were analyzed. The anti-tumor activity of temsirolimus, an inhibitor of mammalian target of rapamycin, and the combined effects of temsirolimus and AQ4 were also evaluated. RESULTS: Regardless of the oxygen condition, a single drug treatment with AQ4 or temsirolimus inhibited proliferation and induced apoptosis in both cell lines, accompanied by a reduction in the phosphorylation of S6. AQ4 induced G2/M cell cycle arrest, whereas temsirolimus induced G0/G1 arrest. Moreover, the combined treatment markedly reduced the proportion of cells in the S phase and enhanced apoptosis, as evidenced by an increased Bax/Bcl-2 ratio. The hypoxia-induced activation of the HIF-1α pathway was suppressed by AQ4 and temsirolimus. CONCLUSION: Based on the cooperative anti-tumor activity of AQ4 and temsirolimus in vitro, the combination of banoxantrone plus temsirolimus has potential as a treatment option for CRC in preclinical and clinical settings.
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Neoplasias Colorretais , Hipóxia , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , ApoptoseRESUMO
Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. The aim of the present study is to review appropriate chemotherapeutic regimens for elderly patients. We examined 1138 Japanese patients who were operated for high-risk stage II or stage III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. The efficacy of adjuvant therapy was analyzed in association with age and adjuvant chemotherapeutic regimens. A total of 507 patients (45%) were ≥70 years old. They were less likely to receive adjuvant chemotherapy (p < 0.001) or palliative chemotherapy after recurrence (p < 0.001) than patients aged <70 years. Cancer-specific survival (CSS) in stage III CRC patients was longer in the <70 years group than in the ≥70 years group (p = 0.006); however, CSS by regimens did not significantly differ between these groups. Adjuvant chemotherapy was associated with the longer relapse-free survival of stage III CRC patients in the <70 years group (p = 0.005). Although adjuvant chemotherapy was associated with a favourable CSS regardless of age, the implementation rate of adjuvant chemotherapy for elderly CRC patients was low, which may explain shorter CSS in stage III CRC patients the ≥70 years group than in the <70 years group.
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Microinjection of the α(2)-adrenoceptor agonist clonidine into the hypothalamic periventricular nuclei (PVN) induces the pressor response associated with bradycardia in freely-moving conscious rats. This study investigated the involvement of γ-aminobutyric acid nerves (GABAergic nerves) and glutamatergic nerves in the cardiovascular response to microinjection of clonidine in the PVN. Male Wistar rats were chronically implanted with a microinjection cannula into the PVN and an arterial catheter into the abdominal aorta through the femoral artery. Blood pressure and heart rate were measured under a conscious unrestrained state. PVN injection of clonidine induced a dose-dependent pressor response concomitant with bradycardia. PVN pretreatment with GABA, muscimol (GABA(A)-receptor agonist), or bicuculline (GABA(A)-receptor antagonist) significantly inhibited the pressor response to PVN-injected clonidine without affecting bradycardia. PVN pretreatment with baclofen (GABA(B)-receptor agonist), 2-hydroxysaclofen (GABA(B)-receptor antagonist), or kynurenic acid (non-selective NMDA-type glutamate-receptor and ionotropic glutamate-receptor antagonist) did not affect the pressor response to PVN-injected clonidine. These results suggest that clonidine induces a pressor response by stimulating the presynaptic α(2)-adrenoceptor of GABAergic nerves in the PVN, thereby inhibiting GABAergic nerve activity.
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Anti-Hipertensivos/farmacologia , Clonidina/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Baclofeno/análogos & derivados , Baclofeno/farmacologia , Bicuculina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , GABAérgicos/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Agonistas dos Receptores de GABA-B/farmacologia , Antagonistas de Receptores de GABA-B/farmacologia , Neurônios GABAérgicos/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo , Ácido Cinurênico/farmacologia , Masculino , Muscimol/farmacologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Wistar , Receptores de Glutamato/fisiologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
BACKGROUND: Persistent descending mesocolon (PDM) is a fetal abnormality in which the left-sided colon is not fused to the retroperitoneum, and it is often accompanied by the adhesion between the mesocolon and small bowel mesentery. Due to its rarity, whether PDM exhibits anatomical characteristics of the inferior mesenteric artery (IMA) and left colic artery (LCA), and how the anomaly affects laparoscopic surgery are largely unknown. We investigated the branches of these arteries and outcomes of patients who underwent laparoscopic surgery. METHODS: Based on computed tomography (CT) and three-dimensional CT angiography, branching patterns of the IMA, LCA and branches originating from the LCA were analysed in 954 patients with left-sided colon or rectal cancer. PDM was diagnosed by preoperative CT colonography, and confirmed at time of surgery. The anatomical features of the vessels and short-term outcomes of laparoscopic surgery were compared between patient groups stratified by PDM. RESULTS: Twelve patients (1.3%) were diagnosed with PDM. No branching pattern of the IMA specific to PDM was noted. On the other hand, patients with PDM had fewer branches (mean: 1.0) from the LCA than those without PDM (mean: 1.8, p = 0.009). In patients undergoing laparoscopic surgery, outcomes such as operative time, intraoperative blood loss, and number of harvested nodes were comparable between the two patient groups. CONCLUSION: Few branches of the LCA characterize PDM. PDM does not complicate laparoscopic surgery of the left-sided colon and rectum. However, the above anatomical feature increases the risk of poor colonic perfusion when dividing the LCA.
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Cólica , Laparoscopia , Mesocolo , Neoplasias Retais , Cólica/etiologia , Humanos , Laparoscopia/métodos , Artéria Mesentérica Inferior/diagnóstico por imagem , Artéria Mesentérica Inferior/cirurgia , Mesocolo/cirurgia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgiaRESUMO
The in vitro microbicidal activity of benzoyl peroxide against Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia furfur, Malassezia restricta, and Malassezia globosa was investigated. These strains were incubated for 1 h in the presence of 0.25, 0.5, 1, or 2 mmol/L benzoyl peroxide in phosphate buffered saline supplemented with 0.1% glycerol and 2% Tween 80. After exposure to benzoyl peroxide, counts of viable Gram-positive bacteria and fungi were markedly decreased, whereas counts of Gram-negative bacteria were unchanged. Transmission electron microscopy images showed a decrease in electron density and the destruction of C. acnes and M. restricta cell walls after exposure to 2 mmol/L benzoyl peroxide. In conclusion, this study showed that benzoyl peroxide has a potent and rapid microbicidal activity against Gram-positive bacteria and fungi that are associated with various cutaneous diseases. This suggests that the direct destruction of bacterial cell walls by benzoyl peroxide is an essential mechanism of its rapid and potent microbicidal activity against microorganisms.
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Peróxido de Benzoíla , Propionibacterium acnes , Malassezia , Testes de Sensibilidade MicrobianaRESUMO
The Deloyers procedure is performed after extended left colectomy, enabling the reach of the proximal colon to the rectum for anastomosis while preserving sufficient blood supply. We report a case of the Deloyers procedure performed safely under indocyanine green (ICG) fluorescence guidance. A 50-year-old man with obesity (body mass index, 35.7 kg/m2) and a history of diabetes underwent an extended left hemicolectomy and ultralow anterior resection of the rectum as radical resection for transverse and sigmoid colon cancers and a lower rectal neuroendocrine tumor. Reconstruction was performed by the Deloyers procedure. A necessary length of the transverse colon with reduced blood flow was additionally resected under ICG fluorescence guidance, and a transanal hand-sewn coloanal anastomosis was performed. This is the first report in which the Deloyers procedure was performed successfully with the ICG fluorescence method. ICG fluorescence may be useful when combined with the Deloyers procedure.
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Propolis is known to have abundant bioactive constituents and a variety of biological activities. To investigate the effect of Brazilian propolis on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent type 2 diabetic model, were treated for 4 weeks with propolis (100 and 300 mg/kg, p.o.) or vehicle (control). Propolis treatment significantly decreased the plasma levels of insulin and insulin resistance index (Homeostasis Model Assessment-Insulin Resistance; HOM-IR), without affecting blood glucose levels and tended to lower systolic blood pressure compared with the control. In isolated and perfused mesenteric vascular beds of OLETF rats, propolis treatment resulted in significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS compared with in vehicle-treated OLETF rats. However, propolis treatment did not significantly affect the vasoconstrictor and vasodilator response to noradrenaline, CGRP, acetylcholine, and sodium nitroprusside. These results suggest that propolis could be an effective and functional food to prevent development of insulin resistance.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina , Própole/administração & dosagem , Própole/farmacologia , Administração Oral , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas In Vitro , Insulina/sangue , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/inervação , Ratos , Ratos Endogâmicos OLETF , Sistema Nervoso Simpático/fisiologia , Sístole/efeitos dos fármacos , Fatores de Tempo , Vasoconstrição/efeitos dos fármacosRESUMO
Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. The production of IL-1ß by THP-1 was also inhibited by ozenoxacin at the concentration of 30 µg ml-1. Phosphorylation of the mitogen-activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes. Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes. These findings suggest that ozenoxacin possesses an anti-inflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.