Previously it was shown that early treatment with mycophenolate mofetil (MMF) attenuated renal inflammation, glomerulosclerosis (GS), and interstitial expansion in the 5/6 ablation (NX) model. Angiotensin II antagonists also mitigate renal injury in NX, presumably by lowering glomerular pressure (P(GC)). This study investigated: (1) whether combined MMF/angiotensin II antagonists treatment affords superior protection compared with the respective monotherapies; and (2) whether this association is effective even when instituted late in the course of the disease. Adult male Munich-Wistar rats underwent NX, remaining untreated for 30 d. BP, albuminuria, and the extent of GS, interstitial expansion, and macrophage infiltration were then determined in 17 rats. The remaining 118 rats received either inert vehicle or one of the following: MMF, 10 mg/kg by gavage once daily; losartan potassium (L), 20 mg/dl in drinking water; or combined MMF/L treatment. Sixty days after ablation, untreated NX rats exhibited marked glomerular hypertension, which was attenuated by MMF and, more effectively, by either L or combined MMF/L treatment. At 120 d, hypertension and albuminuria were worsened in untreated NX rats, which exhibited intense macrophage infiltration and severe glomerular and interstitial disease. L and, to a lesser extent, MMF monotherapies attenuated these abnormalities, without preventing their progression. In rats given combined MMF/L therapy, macrophage infiltration, GS, and interstitial expansion remained at pretreatment levels. By acting on two distinct pathogenic mechanisms, combined MMF/L treatment arrested established renal injury in the NX model. Further investigation is needed to determine whether this association can prevent renal scarring in other models and in human disease. 相似文献
Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition. 相似文献
OBJECTIVE: To evaluate our experience with thoracoscopy with small mediastinoscope in complicated parapneumonic effusion in children.METHODS: From July 1995 to June 1997, seven children with complicated parapneumonic pleural effusion underwent thoracoscopy with mediastinoscope at Hospital de Clínicas de Porto Alegre. The procedure was carried out with a small mediastinoscope built in our hospital.RESULTS: There were six girls and one boy. The procedure was preformed under general anesthesia, without selective intubation. Six patients had previous intercostal tube drainage; one underwent thoracoscopy as a primary procedure. No complication was observed after the procedure. During follow-up, two children underwent pleurotomy due to residual pleural effusion with persistent fever; two others presented asymptomatic small pleural effusion.CONCLUSION: Thoracoscopy with small mediastinoscope is safe, efficient and without severe complications. It is very useful to remove loculated complicated parapneumonic effusion at fibrinopurulent stage and to enable lung expansion. 相似文献
The antihypertensive effects of thiazide diuretics such as hydrochlorothiazide are commonly associated with erectile dysfunction. The association of hydrochlorothiazide/amiloride is not associated with erectile dysfunction. The hypothesis is that amiloride has beneficial effect in penile erection and, therefore, counterbalances the hydrochlorothiazide-induced disruptive effect.
Aim
To investigate the effects of amiloride and its analogues hexamethylamiloride and benzamil on rat isolated corpus cavernosa (CC) and intracavernous pressure (ICP) in anaesthetized rats.
Methods
Rat isolated CC were incubated with amiloride, hexamethylamiloride, and benzamil (10 and 100 μmol/L each), followed by phenylephrine, potassium chloride, and electrical field stimulation (EFS). Their effect on the relaxant responses to EFS and sodium nitroprusside were also determined. Oral (30 mg/kg) and intraperitoneal (3 mg/kg) treatments with amiloride were also investigated on nerve-evoked ICP.
Main Outcome Measures
In vitro functional studies and in vivo ICP measurement on rat CC were performed. Additionally, phosphodiesterase type V isoform A1 activity and the mRNA expressions of Na+/H+ pump, epithelial sodium channel exchangers (ENaC) channels (α-, β- and γ subunits) and Na+/Ca2+ exchangers were evaluated in CC tissues.
Results
Amiloride and its analogues significantly reduced the phenylephrine-, potassium chloride–, and EFS-induced CC contractions, which were not changed by nitro-L-arginine methyl ester (100 μmol/L) or indomethacin (6 μmol/L). In phenylephrine-precontracted CC tissues, amiloride itself caused concentration-dependent relaxation and significantly increased the EFS-induced relaxation. Oral and intraperitoneal treatment with amiloride significantly increased the ICP. Phosphodiesterase type V isoform A1 activity was not affected by amiloride. Na+/H+ pump, ENaC, and Na+/Ca2+ exchanger mRNA expressions were all detected in rat CC tissues.
Clinical Implication
Amiloride analogues may have therapeutic potential for erectile dysfunction.
Strength & Limitations
The interesting effect of amiloride in penile erection was observed in both in vitro and in vivo methods. The evidence at the moment is restricted to rat CC.
Conclusion
Amiloride reduces in vitro CC contractility and enhances erectile function after oral and intraperitoneal administration, possibly via inhibition of ENaC.Campos R, Claudino MA, de Oliveira MG, et al. Amiloride Relaxes Rat Corpus Cavernosum Relaxation In Vitro and Increases Intracavernous Pressure In Vivo. J Sex Med 2019;16:500–511.相似文献
Objective: The detection of the auditory steady-state responses is usually performed by an appropriate objective response detector applied to stimulus-related epochs of the raw electroencephalogram (EEG). In order to improve the detection time, sequential detection strategies are usually used. These multiple tests strategies increase the probability of mistakenly detecting a response. The aim of this study was to develop strategies to determine the critical values for the sequential detection strategies based on constant significance level tests.
Design: Extensive Monte Carlo simulations were used to test these strategies for the magnitude-squared coherence (MSC) detector. The performances of these strategies were compared with previous works found in the literature.
Study sample: All strategies were applied to synthetic and real EEG datasets.
Results: The strategies ensure the desired significance level at the end of the sequential detection strategy. The simulated results are in accordance with the real data results.
Conclusions: For the MSC detector, where the critical value depends on the number of epochs, the proposed sequential detection strategies obtain better performance regarding test time and detection rate, but worse overall detection rate compared to applying a test only once. 相似文献
The efficacy of ultrasound in removing cast metal posts was evaluated in this in vitro study using one or two ultrasound units and ultrasonic vibration for various lengths of time. The crowns of 30 healthy maxillary canines were removed, the roots were embedded in acrylic resin blocks, and the root canals were treated endodontically. The canals were prepared and their impressions were taken with self-curing acrylic resin. After casting with copper-aluminum alloy, the posts were blasted with aluminum oxide and cemented with Panavia F resin cement. The specimens were divided into five groups. In groups I and II, only one ultrasound unit was used for 30 and 60 s, respectively; in groups III and IV, two ultrasound units were used simultaneously for 30 and 60 s, respectively; in group V, ultrasound was not used (control). Ultrasonic vibrations were applied with an Enac OE-5 ultrasound unit and an ST-09 tip. All samples were subjected to traction on an Instron machine (model 4444) at a cross-head speed of 1 mm/min. Analysis of the results revealed a statistically significant difference between the groups (ANOVA, P < 0.01); however the difference between groups II and IV was not statistically significant. The efficacy of ultrasound in removing intraradicular posts was confirmed, and the most effective technique was the use of two ultrasound units, independent of the length of time ultrasound was applied. 相似文献