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Heart failure is one of the main cardiovascular system diseases at present, and it is a clinical syndrome caused by changes in cardiac structure and function, resulting in impaired ejection function or ventricular filling. Therefore, heart failure has become the most important cardiovascular disease in the 21st century. In recent years, the incidence of heart failure is increasing, and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine, more and more attention has been paid to the research, development, and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus, a traditional Chinese medicine, is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics, protecting myocardial muscle, and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure, yielding remarkable results. In recent years, it has been found that astragaloside, Astragalus polysaccharide, quercetin, calyx isoflavones, and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response, myocardial apoptosis, and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature, with a view to providing a reference for its further research, development, and application in the prevention and treatment of heart failure.
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Objective:With network pharmacology, this paper aims to explore the potential active constituents, related targets and signal pathways to elucidate the mechanism of Calyx seu Fructus Physalis in the treatment of lung cancer. Methods:By searching for Pharmacology Database of Traditional Chinese Medicine Systems and Analysis Platform (TCMSP) to obtain the active constituents of Calyx seu Fructus Physalis, and predict the target genes of active constituents by using SWISS and SEA. By collecting the corresponding targets approved by FDA and search for different database, including Therapeutic Target Database (TTD), Database of Gene-disease Associations (DisGeNET) and Online Mendelian Inheritance in OMIM to build a database of lung cancer related target genes; To get the target genes of herb-disease proteins by the intersection of the two databases and display the results through the network software of Cytoscape 3.7.2. Then to use the Database of Annotation, Visualization and Integrated Discovery (DAVID) to conduct key enrichment analysis of Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis. Combining related literature to analize the active ingredients and mechanism of Calyx seu Fructus Physalis in the prevention and treatment of lung cancer. Results:It was found that 11 active constituents of Calyx seu Fructus Physalis could play the role of anti-lung cancer by regulating 19 lung cancer related targets such as EGFR, ESR1, MDM2, MMP2 and MET. There were 15 signal pathways involved Proteoglycans in cancer, MicroRNAs in cancer, Pathways in cancer, Transcriptional misregulation in cancer, PI3K-Akt signaling pathway and other key signal pathways. Conclusion:The results show that the active constituents of anti-lung cancer effect of Calyx seu Fructus Physalis may be Oleic acid, Cycloartenol, Obturator, Graminesterol, β-sitosterol, etc. The mechanism of action may be related to multiple cancer-related signaling pathways such as Proteoglycans pathway, Transcriptional misregulation pathway, and PI3K-Akt signaling pathway.
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Roselle (Hibiscus sabdariffaL.) is natural source of valuable components such as phenolics, flavonoids and anthocyanins. Anthocyaninis normally used in the food technology to replace synthetic pigments as well as medicinal properties due to antioxidants. Microwave irradiation is a feasible green solvent extraction method receiving great attention as it utilizes solvent at elevated temperature and controlled pressure conditions. Microwave extraction emerges as a promising inexpensive, simple and efficient technique. In our research, various variable like microwave power (20, 40, 60, 80, 100 W), microwave frequency (10, 20, 30, 40, 50 GHz), the micrwave irradiation duration (5, 10, 15, 20, 25 min), liquid to solid ratio (water: material, 2:1, 3:1, 4:1, 5:1, 6:1), extraction temperature (50, 55, 60, 65, 70C), number of extraction cycles (1, 2, 3, 4, 5) influencing to the microwave-assisted extraction of phytochemicals in roselle (Hibiscus sabdariffa L.)calyx were thoroughly examined. Total total phenolic (mg GAE/ 100g), total flavonoid (mg GE/ 100g), anthocyanin (mg/100g) were key indicators to define the optimal variable. Our resultsrevealed that microwave power at 80 W, frequency 40 GHz, duration 15 min, liquid to solid ratio 4:1, temperature 55C, 4 cycles of extraction were appropriate for extraction of phytochemical components inside roselle (Hibiscus sabdariffa L.)calyx
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Background: This work was intended to distinguish the results of Percutaneous Nephrolithotomy (PCNL) related to stone-free rates (SFR) by the varying body mass index (BMI) of the patients who subjected for lower calyx stone treatment (with a stone range of ≥2 cm). Materials and methods:Atotal of 287 patients who went through the PCNLfor kidney stones were selected for the study. Only patients treated at Shahid-Ghazi Hariri Surgical Specialties Hospital (Medical City) and Al-Qima Private Hospital (Baghdad) within the time frame of January 2015 to April 2018 selected for the study. Information on patients' BMI and SFR was collected and analyzed to compare and contrast the differences in obese patients. Results: The average age and BMI of the patients are 41 years old and 34kg/m2 respectively. For total mean stone size 2.2 cm. Besides that, the average value for height was 173cm and weight 101kg. The overall stone-free rate was 82% and the mean hospital stay was 115±51.21 min, Major complications were seen in 65 patients (22.6%). No statistically significant differences were found in SFR, age and stone side among the four groups. The stone-free rates (SFRs) of a single procedure for the groups were 85%, 79.3%, 79%, and 84%, respectively. Major complications were not observed either during or after the operations. Conclusion: The effectiveness of PCNLtreatment for removal of lower calyceal stone is influenced by the varying patients' BMI value and results in high SFR value
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Introduction: Decision making regarding the surgicalapproach for ACOM artery is based on A1 dominancy,projection and how is the plane of the both A2 vessels. Thepresent study was conducted with the aim to analyze theprognosis of superiorly projecting anterior communicatingartery aneurysm with respect to position of A2 anteriorcerebral artery.Material and methods: The present retrospective analysisconsisted of 543 cases of all cerebral aneurysms operatedfrom Jan 2012 to December 2015 at Sree Chitra TirunalInstitute for Medical Sciences and Technology (SCTIMST),Trivandrum. The open A2 plane was defined as when the A2of the pterional approach side was present more posteriorlythan the contralateral A2. All patients were evaluated throughGlasgow outcome scale at the time of discharge. All the dataobtained was arranged in a tabulated form and analyzed usingSPSS software.Results: The mean age of the subjects was 54.2 years.There were 63 males and 32 females. Among 95 patients,A1dominant was present in 83 patients and co-dominance waspresent in 12 cases. Out of 54 superiorly projecting aneurysms.Intraoperative rupture was present in the 18 patients (33.3%),Gyrus rectus aspiration was done in the 35 patients (64.9%), 1patient had the perforator injury.Conclusion: Surgical approach from the A2 posteriordisplacement side (the open A2 plane) in patients with superiorprojecting aneurysms allows neurosurgeon to secure aneurysmnecks safely and prevent postoperative complications.
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Objective To demonstrate a simple and cost-effective method to develop a telescopic renal sheath for treatment of complex kidney stones in percutaneous nephrolithotomy. Methods From October 2013 to October 2017, the clinical data of 94 patients with complex kidney stones and renal calyx diverticulum calculi who had underwent percutaneous nephrolithotomy were collected and were divided into two groups according with operation methods. In group A (45 patients), the 16F Peel-away sheath was inserted into the 20F outside sheath as the inner sheath. The stones were fragmented and removed through the telescopic renal sheath. In group B (49 patients), the stones were fragmented and removed through the 20F Peel-away sheath. The blood lose (hemoglobin decrease), operation time, rate of stone clear and perioperative complication between two groups were compared. Results All patients completed operation. The operation time in group A was significantly shorter than that in group B:(75.9 ± 15.8) min vs. (87.1 ± 21.6) min, P=0.005. The decreased level of hemoglobin was less than that in group B: (0.72 ± 0.57) g/L vs. (1.22 ± 1.13) g/L, P=0.009. The rate of stone clear in group A was higher than that in group B: 93.33%(42/45) vs. 77.55%(38/49), P=0.032. All patients in group A had mild hematuria, which resolved within 2 d, and none received blood transfusion.Two patients in group B received blood transfusion. A small proportion in group A (1/45) and group B(4/49) received perioperative anti-infection therapy and fever rates were similar in the two groups. There were no serious complications such as pneumothorax and intestinal injury. Conclusions Telescopic renal sheath in mini-percutaneous nephrolithotomy is an effective method to treat complex kidney stones and renal calyx diverticulum.
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Persistent hiccups impair the quality of life of patients, and are sometimes difficult to treat. In our hospital, we usually use a shiteito decoction to treat hiccups, however, there are no published data about the effect of shiteito on hiccups. We retrospectively investigated patients with hiccups treated with a shiteito decoction as a first-line drug from February 1, 2014 to February 28, 2016. Twenty-seven patients were included (three women), and their ages ranged from 24 to 89 years (mean age : 65.4 ± 15.1 years). The shiteito decoction was completely or partially effective in 66.7% of all patients, and 59.3% of all patients completely recovered. In most cases, the hiccups disappeared within two days, and 88.9% of the patients with complete or partial recovery found the decoction to be effective within four days. Shiteito was an effective hiccup treatment, and since it could be easily administered at bedside, it would be useful regardless of patient pattern.
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Objective To explore the feasibility and safety of visualization puncture combined with flexible ureteroscopy in the treatment of lower calyx stones.Method Visualization puncture combined with flexible ureteroscopy to treat the lower calyx stones was done in our center from January to August 2016 in our hospital.32 cases of patients were enrolled to have a retrospective analysis.There were 18 males and 14 females,aged from 25 to 65 years,with an average age of 43 years.The diameter of stone was 1.0-2.0 cm,with an average of (1.4 ± 0.6) cm.We used general anesthesia and then adjusted the surgery bed to operation side lateral elevation was 30 °-35.Flexible ureteroscopy with 200μm holmium laser was used firstly to break calculi as much as possible.Ultrasound-guided F4.8 visualization puncture system was used to establish F4.8 channel.The power option was 2001μm hohnium laser to crush calculus of the renal calculi to treat the calculus of the distal end of soft lens which still can not be touched by ureteroscopy.Routine nephrostomy tube was not placed.The soft ureter sheath F5 double-J tube,and indwelling balloon catheter were routinely placed.We removed the catheter after 1-2 days and the double J tube after 4 to 6 weeks.Results The flexible ureteroscopy lithotripsy operation time was 8-25 mins in all of the 32 patients.Visualization puncture channels were successfully established in 3-7 mins,and the visualized puncture stone search rate of 100% (32/32).The success rate of first stage lithotripsy was 93.8% (30/32).Two cases of lower calyx stones diverticulum diverted to PNCL due to poor visibility by bleeding.The operation time was 30-60 mins and the average of 45 mins.KUB review at day one after the surgery showed that there were residual stones in 5 cases.The stone free rate at one month after the surgery is 100.0%.The average postoperative hospital stay was (2.0 ± 1.5) days.There were uo bleeding,ureteral avulsion and perforation,septic shock,pleural effusion and intestinal injury and other serious complications.Conclusions Navigation ultrasound-guided visualization puncture combined with flexible ureteroscopy is safe and effective to treat lower calyx stones.
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Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.
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Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.
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Objective To evaluate if the flexible ureteroscopy could treat stones located in lower calyx with the infundibulopelvic angle (IPA) less than 30°.Methods Thirty-six patients with inferior caliceal calculi on whom flexible ureteroscopic procedures were performed between November 2009 and June 2015 were reviewed.The mean age of the patients was 52.1 years (34-71),with the mean stone diameter of (1.5 ± 0.8) cm (1.2-2.6 cm).IPA was smaller than 30° in all 36 cases,which confirmed by CTU examination.IPA was less than 10° in 15 patients,between 11 ° and 20° in 13 patients and between 21 ° and 30° in 8 patients.Results The success rate was 63.9% (23/36 patients) in patients with IPA smaller than 30° after first session of procedure,and the stone free rate reached 100% after the second session of procedure.The mean operation duration was (95.5 ± 31.4) min(51-127 min).The mean hospital stay after operation was(4.1 ± 1.2)days (3-5 days).No major complications were recorded and no patients needed to convert to open surgery.Double J tube was removed after 4 weeks postoperatively.Patients were followed up for 4-12 months,during which ultrasound and CT scan were used for stone detection.Conclusions The small IPA (<30°) negatively affected the SFR in the first session operation.However,its negative effect was solvable by using modern endoscopes.A complete stone clearance was achievable even in case of unfavorable anatomic conditions in experienced hand.
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OBJECTIVE@#To investigate the effect of the roselle calyx extract (RCE) (Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria.@*METHODS@#RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the pH was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration was determined using the microdilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells.@*RESULTS@#The RCE had antibacterial activity against oral bacteria used in this study. In particular, most significant antibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/mL-28.8 mg/mL and 14.4 to >57.6 mg/mL. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells.@*CONCLUSIONS@#Thus, our results indicate that the RCE may be used for preventing oral diseases.
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Objective: To investigate the effect of the roselle calyx extract (RCE) (Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods: RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the pH was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration was determined using the microdilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells. Results: The RCE had antibacterial activity against oral bacteria used in this study. In particular, most significant antibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/mL-28.8 mg/mL and 14.4 to >57.6 mg/mL. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells. Conclusions: Thus, our results indicate that the RCE may be used for preventing oral diseases.
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To establish the identification method for Physalis angulatae fructus Seu calyx and Physalis calyx Seu fruc-tus. Methods:Four methods including macroscopy,microscopy,TLC and HPLC were used. Results: There were some differences in macroscopic and microscopic characteristics and physicochemical identification between Physalis angulatae Fructus Seu Calyx and Phys-alis Calyx Seu Fructus. Conclusion:The established method is simple and easy,which can objectively and accurately distinguish Phys-alis angulatae Fructus Seu Calyx from Physalis Calyx Seu Fructus.
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We aimed, in this study, to determine the distribution of α-1 AR subtypes in rat and human pelvis and calyces, and to evaluate, by comparing these two species, the possibility of rats to be used as models for humans. Twenty patients with renal carcinoma were included into the study. The patients underwent radical nephrectomy for renal cell carcinoma (RCC). After nephrectomy, specimens were evaluated and excisional biopsies from healthy pelvis and calyces tissues were performed. When pathology confirmed the non-invasion of RCC, specimen was included into the study. A total of 7 adult Wistar Albino (250-300 g) female rats were used in this study. Specimens included renal pelvis and calyces. All specimens were evaluated under light microscope histopathologically. The concentrations of the receptor densities did not differ between the two groups. With the demonstration of the α receptors in rat kidneys and calyces, many receptor-based studies concerning both humans and rats can take place. Novel medication targeting these subtypes -in this matter α1A and α1D for renal pelvis and calyces- may be helpful for expulsive therapy and/or pain relief. With the demonstration of similar receptor densities between human and rat tissues, rat model may be useful for α-receptor trials for renal pelvis and calyces.
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Animais , Feminino , Humanos , Cálices Renais/química , Pelve Renal/química , Modelos Animais , Receptores Adrenérgicos alfa/análise , Biópsia , Carcinoma de Células Renais/química , Imuno-Histoquímica , Neoplasias Renais/química , Nefrectomia , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
s: Objective To investigate the efficacy and safety of ultrasound-guided upper-pole access percutaneous nephrolithotomy (PCNL) for the treatment of renal staghorn calculi. Methods From October 2008 to July 2012,193 cases of renal staghorn calculi treated with ultrasound-guided upper-pole access PCNL were reviewed. Among the 193 cases,74 cases were complete staghorn calculi while the other 119 cases were partial staghorn calculi, and the calculi diameter was 2. 5 to 9. 0 cm. All the 193 cases were treated through upper-pole ac-cess successfully,70 accesses were accomplished below the 12th rib,while the other 123 accesses were accomplished between the 11th adn 12th rib. Disintegration of the stone was accomplished using Holmium laser. Results The mean operative time was 70 min (45~150 min), single tract was used in 186 cases, and double tracts were used in the other 7 cases. The stone clearance rate for one session was 72. 0%(139/193),and the total stone clearance rate was 88. 1%(170/193). Transfusion was required in 6 patients, while 2 patients with signifi-cant bleeding were treated with selective renal arterial embolization. Hydrothorax occured in 4 patients, and closed thoracic drainage was re-quired in 2 of them. 20 patients had fever, and they recovered after effective antibiotic treatment. No patients had injury to the lung or other viscera. Conclusion Upper-pole access offers optimal visibility and convenience for rigid ureteroscope to achieve a high rate of stone-free status and operating time reduce. Ultrasound guided upper-pole access PCNL should be attempted in selected cases of renal staghorn stone.
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Objective To review the safety and efficacy of upper-pole access percutaneous nephrolithotomy (PCNL). Methods From May 2008 to May 2010,237 cases ( 135 males and 102 females with mean age of 42 yrs) of renal or proximal ureteral calculi treated with upper-pole access PCNL were reviewed.The indications included calculus larger than 1.5 cm or impacted proximal ureteral calculi in 94 cases,calculus≥2 cm or impacted renal pelvic calculi in 26 cases,staghorn or multiple calculi in 68 cases,complex lower calyx calculi in 13 cases,upper calyx calculi not amenable to ESWL or URS in 12 cases,calculi within upper calyx diverticulum in 3 cases,combined UPJ obstruction or upper ureteral stenosis in 8 cases,morbidly obese patients in 3 cases,calculi within horseshoe kidneys in 6 cases,calculi within transplanted kidneys or ureters in 4 cases.Of the 237 cases,175 tracts (73.8%) were above the 12th rib,46were above the 11th rib,12 were below the 12th rib,4 were in the lower abdomen for renal transplant patients. Results The overall stone clearance rate with upper-pole access PCNL monotherapy was 74.3%.Additional punctures were required in 55 cases and combined ESWL in 6 cases.Total stone clearance rate at 3 months after operation was 88.2%.16 patients (6.8%) had a pleural injury.Thoracentesis was required in 8 patients,closed thoracic drainage in 5 patients,conservative treatment in 3 patients.After nephrostomy tube removed,pleural irritation symptom appeared in 12 cases (5.1%) who required symptomatic treatment.No patient had injury to the lung or other viscera.Significant bleeding requiring blood transfusion was olserved in 5 patients,while selective renal arterial embolization was required in 2 cases. Conclusions Upper-pole access offers optimal visibility,convenience for the movement of rigid nephroscope and high stone-free rate.It should be attempted in selected cages of upper ureteral calculi and complex renal calculi.
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A literatura relata somente alguns casos de recém-nascidos com ascite urinária, geralmente secundária a ruptura de bexiga urinária e não de um cálice renal. Este relato de caso descreve um caso raro de ascite urinária em recém-nascido com válvula de uretra posterior que teve ruptura de um cálice renal, neste caso diagnosticada, até onde sabemos, pela primeira vez por ultrassonografia.
The literature reports only rare cases of urinary ascites, usually secondary to rupture of the bladder and not to renal calyx rupture. The present report describes an uncommon case of posterior urethral valve in a newborn with ascites caused by the rupture of a renal calyx that, to our knowledge, was diagnosed for the first time by ultrasonography.
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Humanos , Masculino , Recém-Nascido , Ascite/diagnóstico , Cálices Renais/lesões , Ureterostomia , Doenças Uretrais , Cistoscopia , Doenças da Bexiga Urinária , RupturaRESUMO
The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.
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Animais , Ratos , Tronco Encefálico/crescimento & desenvolvimento , Sinalização do Cálcio/fisiologia , Cálcio/fisiologia , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/fisiologia , Animais Recém-Nascidos , Soluções Tampão , Tronco Encefálico/fisiologia , Cóclea/inervação , Exocitose/fisiologia , Ratos Sprague-DawleyRESUMO
A variety of G protein coupled receptors (GPCRs) are expressed in the presynaptic terminals of central and peripheral synapses and play regulatory roles in transmitter release. The patch-clamp whole-cell recording technique, applied to the calyx of Held presynaptic terminal in brainstem slices of rodents, has made it possible to directly examine intracellular mechanisms underlying the GPCR-mediated presynaptic inhibition. At the calyx of Held, bath-application of agonists for GPCRs such as GABAB receptors, group III metabotropic glutamate receptors (mGluRs), adenosine A1 receptors, or adrenaline alpha2 receptors, attenuate evoked transmitter release via inhibiting voltage-activated Ca2+ currents without affecting voltage-activated K+ currents or inwardly rectifying K+ currents. Furthermore, inhibition of voltage-activated Ca2+ currents fully explains the magnitude of GPCR-mediated presynaptic inhibition, indicating no essential involvement of exocytotic mechanisms in the downstream of Ca2+ influx. Direct loadings of G protein beta gamma subunit (G beta gamma) into the calyceal terminal mimic and occlude the inhibitory effect of a GPCR agonist on presynaptic Ca2+ currents (IpCa), suggesting that G beta gammamediates presynaptic inhibition by GPCRs. Among presynaptic GPCRs glutamate and adenosine autoreceptors play regulatory roles in transmitter release during early postnatal period when the release probability (p) is high, but these functions are lost concomitantly with a decrease in p during postnatal development.