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1.
Sci Total Environ ; 790: 148231, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380239

RESUMO

Studies have recently focused on microplastics (MPs) in tap and drinking water. Directly comparing the results of different studies is difficult owing to the use of various methodologies. In particular, a study of particles on a part of the filter to reduce the analysis time can lead to uncertainty regarding the number of MPs in tap water. In this study, the analysis of particles on the whole filtration area using a Fourier-transform infrared (FTIR) microscope was achieved in approximately 1 h using a filtration unit with a smaller filtration area (0.13 cm2) and a large-opening (26 µm) filter. Forty-two samples collected from five countries were analyzed using this method. The concentrations of the MPs at each site ranged from 1.9 to 225 particles L-1, with a mean concentration of all samples of 39 ± 44 particles L-1. The size ranged from 19.2 µm to 4.2 mm. Fragments were the predominant shape while fibers and spheres were also observed. Based on a combination of the shape, size, and chemical composition of the MPs, we discussed their sources. The MPs could have caused contamination after processing by a water treatment plant because we detected a significant number of polyester fibers > 100 µm, which were previously detected in the air, and PVC fragments > 50 µm, which are often used in water pipes. This study proposed technical improvements to the whole filtration area technique to detect MPs in tap water.


Assuntos
Água Potável , Poluentes Químicos da Água , Água Potável/análise , Monitoramento Ambiental , Microplásticos , Plásticos , Poluentes Químicos da Água/análise
2.
Andrology ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390622

RESUMO

BACKGROUND: Patients with cancer are treated with chemotherapeutics that cause adverse effects, including erectile dysfunction (ED). OBJECTIVES: We investigated erectile function in rats after the administration of anticancer agents based on data retrieved through mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database. MATERIALS AND METHODS: The statistical signal strength for the association between anticancer drugs and ED was calculated using the reporting odds ratio (ROR). A drug-event combination was detected when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1.00. Rats were administered anticancer agents detected in the FDA AERS analysis. Erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP) analysis after electrical stimulation of the cavernous nerve. Statistical significance was determined using Welch's t-test or two-way ANOVA. RESULTS: Melphalan (L-PAM; ROR = 4.72, 95% CI = 2.78-8.00), vincristine (VCR; ROR = 2.47, 95% CI = 1.54-3.97), docetaxel (DTX; ROR = 2.25, 95% CI = 1.28-3.95), methotrexate (MTX; ROR = 1.96, 95% CI = 1.39-2.75), and doxorubicin (DOX; ROR = 1.82, 95% CI = 1.07-3.19) enhanced ED risk. L-PAM and MTX decreased the ICP/MAP ratio 1 week after administration. VCR and DOX decreased erectile function 4 weeks after administration. DTX decreased erectile function at all assessed time points. DISCUSSION AND CONCLUSION: Certain anticancer agents should be considered risk factors for ED. Our results provide possible treatment strategies for maintaining erectile function in cancer survivors, including careful erectile function monitoring after treatment.

3.
J Sex Med ; 18(8): 1337-1345, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34281797

RESUMO

BACKGROUND: Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED). AIM: To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP). METHODS: Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9-10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation- and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22phox, interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student's t-test. OUTCOMES: The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P < .05). Compared to the Control group, the L-OHP group exhibited significantly lower responses to ACh and eNOS protein levels and significantly higher inflammatory biomarker levels. CLINICAL TRANSLATION: The results based on this animal model indicate that use of the anticancer agent L-OHP should be considered as a risk factor for ED occurring via reduction of NO bioavailability in humans; our results provide possible treatment strategies for maintaining the erectile function of cancer survivors. STRENGTHS AND LIMITATIONS: Our study showed that the anticancer agent L-OHP has the propensity to cause ED in rats. A major limitation of this study is the lack of an established cure for ED associated with L-OHP and the lack of clinical evidence. CONCLUSIONS: L-OHP causes ED in rats via reduction of NO bioavailability caused by endothelial dysfunction. Kataoka T, Mori T, Suzuki J, et al. Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction. J Sex Med 2021;18:1337-1345.


Assuntos
Antineoplásicos , Disfunção Erétil , Animais , Antineoplásicos/toxicidade , Modelos Animais de Doenças , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Óxido Nítrico Sintase Tipo III , Oxaliplatina/uso terapêutico , Ereção Peniana , Pênis , Ratos , Ratos Wistar
4.
Anticancer Drugs ; 32(10): 1076-1083, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232935

RESUMO

Acute kidney injury (AKI) associated with cancer chemotherapy can be life-threatening. Inhibitors of rapidly accelerated fibrosarcoma kinase B (BRAF)-mutants and mitogen-activated extracellular signal-regulated kinase (MEK) administered as combination therapy are effective against BRAF-mutant melanoma, but drug-associated AKI events were reported after marketing. Here, we examined the nephrotoxicity of two BRAF inhibitors, vemurafenib and dabrafenib, and two MEK inhibitors, cobimetinib and trametinib, in a real-world setting and human kidney cells. Target drug-associated AKI signals were detected by reporting odds ratio (ROR) derived from report data in the Food and Drug Administration Adverse Events Reporting System database. In-vitro cytotoxicity was evaluated in proximal renal tubular epithelial cells (RPTEC), glomerular endothelial cells (GEnC), and glomerular epithelial cells (GEpC). AKI RORs associated with vemurafenib [ROR, 3.28; confidence interval (CI), 2.91-3.69] and cobimetinib (ROR, 4.40; CI, 3.55-5.45) were higher than those associated with dabrafenib (ROR, 1.35; CI, 1.15-1.60) and trametinib (ROR, 1.32; CI, 1.11-1.56). Vemurafenib reduced cell viability and increased cell death in RPTEC and GEpC at 10 µM, which was below the mean maximum concentration in blood under steady-state condition [115.7 µM (56.7 µg/mL)]. No vemurafenib-associated cytotoxicity was detected in GEnC. Mean maximum concentrations of cobimetinib, dabrafenib and trametinib did not induce cell death. This work revealed that vemurafenib had stronger cytotoxic effects on tubular and glomerular epithelial cells than the other BRAF and MEK inhibitors. Hence, we recommend careful monitoring for clinical signs of kidney injury in patients treated with vemurafenib.

5.
Sex Med ; 9(4): 100348, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34186306

RESUMO

BACKGROUND: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. AIM: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum. METHODS: Rats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle. OUTCOMES: Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining. RESULTS: No increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 ± 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 ± 0.02, P < .05), drop rate, and smooth muscle/collagen ratio. CLINICAL TRANSLATION: The present study provides scientific evidence for the effect of late ART on erectile function. STRENGTHS AND LIMITATIONS: This study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results. CONCLUSIONS: Late ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results. Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX-XXX.

6.
J Pharmacol Sci ; 146(4): 226-232, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34116736

RESUMO

We aimed to control the relaxation of rat bladder neck specimens by using NORD-1, a red light-reactive nitric oxide (NO) releaser. Female and male 10-11-week-old Wistar/ST rats were divided into three groups: NORD-1, vehicle, and NORD-1+[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor). We infused 10-4 M NORD-1 into the bladders of NORD-1 and NORD-1+ODQ group rats and the vehicle into those of vehicle group rats. Isometric tension was analyzed using circular bladder neck specimens with 10-5 M NG-nitro-l-arginine methyl ester, an NO synthase inhibitor. Moreover, 10-5 M ODQ was added into the NORD-1+ODQ group bath. After precontraction with 10-5 M carbachol, the specimens were irradiated with red light and their relaxation responses were measured. We evaluated NORD-1 tissue permeability by observing the sliced bladder neck specimens. The NORD-1 group specimens relaxed during red light irradiation; the relaxation response increased with the increase in light intensity. The vehicle and NORD-1+ODQ group specimens did not respond to irradiation. Sex-related differences in responsiveness were not noted. NORD-1 permeated into the urothelium of NORD-1 group specimens. Rat bladder neck relaxation was controlled by NORD-1 and light irradiation in vitro. NORD-1 might be a novel therapeutic agent for voiding dysfunction.

7.
J Pharmacol Sci ; 146(2): 116-119, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33941322

RESUMO

We aimed to investigate detrusor function in a previously developed rat neurogenic voiding dysfunction model that we have developed previously. We performed sham or bilateral accessory nerve injury (BACNI) surgeries on ten-week-old male Wistar/ST rats. One week after surgery, we evaluated detrusor contractility in the bladder using isometric tension and mRNA expression assays. Cholinergic contraction was attenuated in the injury model, whereas carbachol-evoked contraction was enhanced, and mRNA expression of the cholinergic receptor increased. These findings suggest that there was a reduction in neurotransmitter release causing detrusor underactivity.


Assuntos
Traumatismos do Nervo Acessório/complicações , Bexiga Inativa/complicações , Animais , Carbacol/farmacologia , Modelos Animais de Doenças , Expressão Gênica , Contração Isométrica/efeitos dos fármacos , Contração Isométrica/genética , Masculino , Neurotransmissores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Receptores Colinérgicos/metabolismo , Bexiga Urinária/fisiopatologia , Bexiga Urinaria Neurogênica , Bexiga Inativa/fisiopatologia
8.
Mar Pollut Bull ; 169: 112542, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34052588

RESUMO

Unmanned aerial systems (UAS, aka drones) are being used to map macro-litter on the environment. Sixteen qualified researchers (operators), with different expertise and nationalities, were invited to identify, mark and categorize the litter items (manual image screening, MS) on three UAS images collected at two beaches. The coefficient of concordance (W) among operators varied between 0.5 and 0.7, depending on the litter parameter (type, material and colour) considered. Highest agreement was obtained for the type of items marked on the highest resolution image, among experts in litter surveys (W = 0.86), and within territorial subgroups (W = 0.85). Therefore, for a detailed categorization of litter on the environment, the MS should be performed by experienced and local operators, familiar with the most common type of litter present in the target area. This work provides insights for future operational improvements and optimizations of UAS-based images analysis to survey environmental pollution.


Assuntos
Praias , Resíduos , Monitoramento Ambiental , Poluição Ambiental/análise , Processamento de Imagem Assistida por Computador , Plásticos , Resíduos/análise
9.
Cancer Res ; 81(7): 1654-1666, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648930

RESUMO

Overcoming drug resistance is one of the biggest challenges in cancer chemotherapy. In this study, we examine whether targeting the long noncoding RNA taurine upregulated gene 1 (TUG1) could be an effective therapeutic approach to overcome drug resistance in pancreatic ductal adenocarcinoma (PDAC). TUG1 was expressed at significantly higher levels across 197 PDAC tissues compared with normal pancreatic tissues. Overall survival of patients with PDAC who had undergone 5-FU-based chemotherapy was shorter in high TUG1 group than in low TUG1 group. Mechanistically, TUG1 antagonized miR-376b-3p and upregulated dihydropyrimidine dehydrogenase (DPD). TUG1 depletion induced susceptibility to 5-FU in BxPC-3 and PK-9 pancreatic cell lines. Consistently, the cellular concentration of 5-FU was significantly higher under TUG1-depleted conditions. In PDAC xenograft models, intravenous treatment with a cancer-specific drug delivery system (TUG1-DDS) and 5-FU significantly suppressed PDAC tumor growth compared with 5-FU treatment alone. This novel approach using TUG1-DDS in combination with 5-FU may serve as an effective therapeutic option to attenuate DPD activity and meet appropriate 5-FU dosage requirements in targeted PDAC cells, which can reduce the systemic adverse effects of chemotherapy. SIGNIFICANCE: Targeting TUG1 coupled with a cancer-specific drug delivery system effectively modulates 5-FU catabolism in TUG1-overexpressing PDAC cells, thus contributing to a new combinatorial strategy for cancer treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/7/1654/F1.large.jpg.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Oligonucleotídeos Antissenso/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , RNA Longo não Codificante/antagonistas & inibidores , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Estudos de Coortes , Sistemas de Liberação de Medicamentos/métodos , Sinergismo Farmacológico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inativação Metabólica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Terapia de Alvo Molecular/métodos , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , RNA Longo não Codificante/efeitos dos fármacos , RNA Longo não Codificante/genética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Nutrients ; 13(2)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562242

RESUMO

High salt intake has been reported as a risk factor for urinary storage symptoms. However, the association between high salt intake and detrusor muscle contraction is not clear. Therefore, we investigated the effects of high salt intake on the components of detrusor muscle contraction in rats. Six-week-old male Dahl salt-resistant (DR; n = 5) and Dahl salt-sensitive (DS; n = 5) rats were fed a high salt (8% NaCl) diet for one week. The contractile responses of the detrusor muscle to the cumulative administration of carbachol and electrical field stimulation (EFS) with and without suramin and atropine were evaluated via isometric tension study. The concentration-response curves of carbachol were shifted more to the left in the DS group than those in the DR group. Contractile responses to EFS were more enhanced in the DS group than those in the DR group (p < 0.05). Cholinergic component-induced responses were more enhanced in the DS group than those in the DR group (p < 0.05). High salt intake might cause urinary storage symptoms via abnormalities in detrusor muscle contraction and the enhancement of cholinergic signals. Excessive salt intake should be avoided to preserve bladder function.


Assuntos
Contração Isométrica/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio na Dieta/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Masculino , Ratos Endogâmicos Dahl , Suramina/farmacologia
11.
Biol Reprod ; 104(4): 875-886, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33511393

RESUMO

Male penis is required to become erect during copulation. In the upper (dorsal) part of penis, the erectile tissue termed corpus cavernosum (CC) plays fundamental roles for erection by regulating the inner blood flow. When blood flows into the CC, the microvascular complex termed sinusoidal space is reported to expand during erection. A novel in vitro explant system to analyze the dynamic erectile responses during contraction/relaxation is established. The current data show regulatory contraction/relaxation processes induced by phenylephrine (PE) and nitric oxide (NO) donor mimicking dynamic erectile responses by in vitro CC explants. Two-photon excitation microscopy (TPEM) observation shows the synchronous movement of sinusoidal space and the entire CC. By taking advantages of the CC explant system, tadalafil (Cialis) was shown to increase sinusoidal relaxation. Histopathological changes have been generally reported associating with erection in several pathological conditions. Various stressed statuses have been suggested to occur in the erectile responses by previous studies. The current CC explant model enables to analyze such conditions through directly manipulating CC in the repeated contraction/relaxation processes. Expression of oxidative stress marker and contraction-related genes, Hypoxia-inducible factor 1-alpha (Hif1a), glutathione peroxidase 1 (Gpx1), Ras homolog family member A (RhoA), and Rho-associated protein kinase (Rock), was significantly increased in such repeated contraction/relaxation. Altogether, it is suggested that the system is valuable for analyzing structural changes and physiological responses to several regulators in the field of penile medicine.

12.
Neurourol Urodyn ; 40(2): 624-631, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33492702

RESUMO

AIMS: To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). METHODS: Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. RESULTS: All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p < .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups. CONCLUSION: The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.


Assuntos
Nervo Acessório/fisiopatologia , Plexo Hipogástrico/fisiopatologia , Incontinência Urinária de Urgência/fisiopatologia , Animais , Masculino , Ratos , Ratos Wistar
13.
Cancer Treat Res Commun ; 25: 100245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33291048

RESUMO

BACKGROUND: It is difficult to objectively evaluate chemotherapy-related adverse events early in elderly patients with urothelial carcinoma. A delayed response causes a reduction in quality of life (QoL). Wearable activity systems that objectively record life logs have recently been used. OBJECTIVES: This study was undertaken to verify the reliability and effectiveness of a wearable activity system (Fitbit) to monitor subjective symptoms in an objective manner during chemotherapy for elderly patients with urothelial cancer (UC). MATERIALS AND METHODS: This was a cohort prospective study. Elderly patients with UC were enrolled who received short hydration gemcitabine and cisplatin (shGC) combination therapy at Nagoya City University Hospital from January 2018 to March 2020. A Fitbit was used to monitor heart rate, distance moved, and cardio zone time. Heart rate was also monitored by an oscillometric method. The relationship between Fitbit recordings and perceived adverse events, such as fatigue, constipation and nausea, observed during chemotherapy was investigated using a general linear mixed effects model. RESULTS: Twenty-one of 28 inpatients were enrolled and observed for a total of 824 days. A significant, moderately strong correlation was found between two measurements of heart rate (Pearson's r = 0.65, p < 0.05). The measurement of fatigue using Fitbit was effective (p = 0.03). CONCLUSION: Fitbit monitoring can measure the QoL of a patient and was useful for monitoring elderly patients with UC undergoing shGC therapy in an outpatient setting. Fitbit may be useful for monitoring outpatients and their QoL during chemotherapy.

14.
Physiol Rep ; 8(17): e14556, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889777

RESUMO

Phosphodiesterase 5 inhibitors are widely used to treat erectile dysfunction and lower urinary tract symptoms with benign prostatic hyperplasia. Recent studies have indicated the renoprotective effects of this class of compounds. Whether renoprotection depends on blood pressure reduction remains controversial. In this study, we investigated the renoprotective effects of the phosphodiesterase 5 inhibitor, tadalafil, in a rat model of high-salt induced kidney injury with hypertension. Dahl salt-sensitive rats were fed a normal diet, high-salt (8% sodium chloride) diet, or high-salt diet with oral administration of either low- or high-dose tadalafil (1 and 10 mg kg-1  day-1 , respectively). Serum creatinine, urinary protein, and blood pressure were measured at baseline and after 8 weeks, at which point the rats were examined for glomerular injury and fibrosis. PAI1 mRNA levels were also evaluated. After 8 weeks, blood pressure, serum creatinine, and urinary protein levels were significantly higher in the high-salt group than those in the normal-salt group. Serum creatinine and urinary protein were significantly lower in both tadalafil groups than those in the high-salt group, while only high-dose tadalafil affected blood pressure. In addition, glomerulosclerosis and α-smooth muscle actin expression significantly decreased in both tadalafil treatment groups. PAI1 mRNA increased significantly in the high-salt group but decreased in both tadalafil-treated groups. Our results indicated that both low- and high-dose tadalafil prevented fibrosis and glomerular injury in a chronic kidney disease rat model. Mechanistically, these effects may be associated with PAI1 expression and glomerular structure protection.


Assuntos
Inibidores da Fosfodiesterase 5/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Tadalafila/uso terapêutico , Animais , Pressão Sanguínea , Creatinina/sangue , Masculino , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteinúria/tratamento farmacológico , Ratos , Ratos Endogâmicos Dahl , Tadalafila/administração & dosagem
15.
Mar Pollut Bull ; 160: 111548, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32805535

RESUMO

A model is proposed for the beach process of buoyant marine plastics, specifically its beaching and backwashing, by introducing beaching and backwashing diffusion coefficients and the onshore-offshore advection-diffusion equations of plastics for the upper layers in the beach and adjacent coastal sea. The backwashing diffusion coefficient was estimated from the average residence time of the beached plastics and the beach width, and then the beaching diffusion coefficient was estimated from the flux-balance assumption between the beaching and backwashing fluxes. Finite difference calculations in the staggered-grid system demonstrated that the amount of beached plastics responds as predicted by the linear system analysis when the beach had an exponential decay type of unit impulse response regardless of the ratio between the residence time and the period of beaching flux fluctuation from the nearshore. The condition in which the flux balance assumption holds was also discussed.


Assuntos
Monitoramento Ambiental , Plásticos , Análise de Sistemas , Resíduos/análise
16.
J Sex Med ; 17(7): 1280-1287, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32624131

RESUMO

BACKGROUND: High salt intake is a risk factor for hypertension, which can potentially lead to erectile dysfunction (ED); however, the underlying pathological mechanisms remain unclear. AIM: To investigate whether erectile function is directly impaired by high salt intake and whether selective inhibition of mineralocorticoid receptor (MR) could provide protection from ED. METHODS: 6-week-old male Dahl salt-sensitive rats were randomly divided into 3 groups: normal diet (0.3% NaCl; control, n = 8), high-salt diet (8% NaCl; HS, n = 8), and high-salt diet plus eplerenone (HS + EPL, n = 11). HS + EPL rats were orally administered daily doses of EPL (75 mg/kg) for 6 weeks; control and HS rats received purified water on the same schedule. OUTCOMES: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure and mean arterial pressure after cavernous nerve stimulation. Serum levels of asymmetric dimethylarginine and L-arginine were determined using ultraperformance liquid chromatography-tandem mass spectrometry. Quantitative PCR was used to assess the expression of MR, inflammation, and oxidative stress markers (nicotinamide adenine dinucleotide phosphate oxidase-1/4, p22phox, interleukin-6, and superoxide dismutase-1), and protein arginine N-methyltransferase-1. RESULTS: The intracavernosal pressure/mean arterial pressure ratio was significantly lower, whereas systolic blood pressure, MR expression, serum asymmetric dimethylarginine levels, oxidative stress, and levels of inflammatory biomarkers were significantly higher in HS rats than in control rats (P < .05). EPL administration significantly improved each of these parameters except systolic blood pressure and MR expression. No significant intergroup differences were observed for L-arginine and superoxide dismutase-1 levels. CLINICAL TRANSLATION: Our results provide a rationale for the need of salt restriction and the use of selective MR inhibitors in prophylaxis or treatment of ED in men consuming a high-salt diet. STRENGTHS & LIMITATIONS: We are the first to report that the adverse impact of high salt intake on erectile function is mediated via MR activation, independent of its effect on blood pressure. A major limitation of this study is that responses of salt-resistant rats were not studied. CONCLUSIONS: High salt intake directly impaired erectile function in Dahl salt-sensitive rats, whereas selective MR inhibition ameliorated this effect. Kishimoto T, Kataoka T, Yamamoto Y, et al. High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure. J Sex Med 2020;17:1280-1287.


Assuntos
Disfunção Erétil , Hipertensão , Animais , Pressão Sanguínea , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Masculino , Ratos , Ratos Endogâmicos Dahl , Receptores de Mineralocorticoides , Cloreto de Sódio , Cloreto de Sódio na Dieta/efeitos adversos
17.
Neurourol Urodyn ; 39(7): 1922-1929, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32725853

RESUMO

AIMS: To investigate the effect of anagliptin (Ana), a dipeptidyl peptidase-4 (DPP-4) inhibitor, on acute ischemia-induced bladder dysfunction in rats. METHODS: Eight-week-old female Wistar-ST rats were randomly assigned into four groups: (a) sham; (b) ligation (Lig); (c) Lig + Ana; and (d) Lig + Liraglutide (a glucagon-like peptide-1 [GLP-1] receptor agonist; Lira). Rats in the Lig, Lig + Ana, and Lig + Lira groups underwent ligature of the bilateral internal iliac arteries. Ana was orally administered mixed with the CE-2 diet. Lira was subcutaneously administered once a day. Blood glucose levels, plasma dipeptidyl peptidase 4 (DPP-4) activity, GLP-1 levels, and bladder function were measured in all groups. Bladder blood flow was measured in the sham, Lig, and Lig + Ana groups, 4 weeks postsurgery. RESULTS: No differences in blood glucose levels among the groups were observed. DPP-4 activity decreased in the Lig + Ana group (P < .01). GLP-1 levels in the Lig + Ana and Lig + Lira groups were higher than those in the sham and Lig groups (P < .01). Intercontraction intervals (ICIs) were longer in the Lig and Lig + Lira groups than in the sham group (P < .05), but similar to those observed in the Lig + Ana and sham groups. The Lig group exhibited reduced bladder blood flow relative to the sham group (P < .01); however, this measure improved in the Lig + Ana group (P < .01). CONCLUSIONS: Ana administration improved ICIs and bladder blood flow after acute bladder ischemia through a GLP-1 receptor-independent signaling pathway, without altering the blood glucose levels. Therefore, Ana dosing might be useful to prevent ischemia-induced bladder dysfunctions.


Assuntos
Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Artéria Ilíaca , Pirimidinas/uso terapêutico , Doenças da Bexiga Urinária/tratamento farmacológico , Animais , Glicemia/metabolismo , Dieta , Dipeptidil Peptidase 4/sangue , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Isquemia , Ligadura , Liraglutida/uso terapêutico , Ratos , Ratos Wistar , Doenças da Bexiga Urinária/fisiopatologia
18.
Mar Pollut Bull ; 152: 110910, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32479285

RESUMO

A model of the beach process of marine plastics was proposed based on the assumption of the beaching and backwashing flux balance, and its applicability was examined by means of time-invariant linear system analysis and particle tracking experiments with respect to the ratio between the residence time of plastics on a beach (τr) and the period of nearshore current variability (T0). Based on the theory, the balance was expected to hold when τr/T0 was much smaller than 1; however, good agreement was obtained between the theory and the particle tracking method for much larger values of τr/T0. The parameters, which are diagnostically given in the model, will be prognostically decided by the coastal dynamics in the future to develop robust beach process models. Nevertheless, we believe that a diagnostic approach would be another pillar in the strategy for estimating the amounts and distributions of marine plastics in the coming years.


Assuntos
Monitoramento Ambiental , Plásticos , Praias , Análise de Sistemas , Resíduos/análise
19.
Sci Rep ; 10(1): 2198, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042032

RESUMO

A new algorithm has been developed to quantify floating macro-debris transport on river surfaces that consists of three fundamental techniques: (1) generating a difference image of the colour difference between the debris and surrounding water in the CIELuv colour space, (2) detecting the debris pixels from the difference image, and (3) calculating the debris area flux via the template matching method. Debris pixels were accurately detected from the images taken of the laboratory channel and river water surfaces and were consistent with those detected by visual observation. The area fluxes were statistically significantly correlated with the mass fluxes measured through debris collection. The mass fluxes calculated by multiplying the area fluxes with the debris mass per unit area (M/A) were significantly related to the flood rising stage flow rates and agreed with the mass fluxes measured through debris collection. In our algorithm, plastic mass fluxes can be estimated via calibration using the mass percentage of plastics to the total debris in target rivers. Quantifying riverine macro-plastic transport is essential to formulating countermeasures, mitigating adverse plastic pollution impacts and understanding global-scale riverine macro-plastic transport.

20.
Sex Med Rev ; 8(2): 297-302, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31351914

RESUMO

INTRODUCTION: Nitric oxide (NO) is known as the key factor involved in initiating and maintaining an erection. Therefore, NO supplementation may be a target for erectile dysfunction. However, the use of NO donors carries the risk of systemic side effects. Recently, novel NO donors, such as a light-controllable NO donor or NO donor in nanoparticles, have been developed. In this review, we introduce such novel compounds and methods. AIM: To review light-controllable and nanotechnological NO donors for the treatment of erectile dysfunction. METHODS: We conducted a review of relevant articles via PubMed in December 2018. MAIN OUTCOME MEASURES: In this study, we reviewed novel NO donors, such as light-controllable NO donors and nanotechnological NO donors. RESULTS: Some light-controllable NO donors have been already reported. A light-controllable NO donor without metal has also been recently developed. Light-controllable NO donors and light irradiation can control the release of NO spatiotemporally. In an isometric tension study, a relaxing response of the aortic tissue and penile corpus cavernosum was observed under light irradiation with a light-controllable NO donor. In addition, the effects of nanoparticles and nanoemulsions containing sodium nitrate on erectile function have been reported. The nanoformulation containing an NO donor can likely be absorbed percutaneously and, thus, enhance erectile function. CONCLUSIONS: A light-controllable NO donor might be useful for treating erectile dysfunction because light irradiation is a convenient method to be applied for patients. However, light permeability might be an issue that needs to be solved. Nanoformulation is also likely to be a useful, non-invasive approach. The application of these procedures and compounds may help in the development of future treatments for erectile dysfunction. Hotta Y, Kataoka T, Taiki Mori T, et al. Review of a Potential Novel Approach for Erectile Dysfunction: Light-Controllable Nitric Oxide Donors and Nanoformulations. Sex Med Rev 2020;8:297-302.

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