Artemisia kruhsiana leaf extract induces autophagic cell death in human prostate cancer cells / 中国天然药物

Some species of Artemisia have been reported to induce apoptosis and autophagy, but little is known of the apoptotic and autophagic effects of the stems and leaves of Artemisia kruhsiana Bess. (AkB). This study was conducted to investigate the antioxidant and anti-autophagic effects of the methanol extracts of the stems (EAkBs) and leaves (EAkBl) of AkB on human prostate cancer PC-3 cells. The antioxidant effects of EAkBs and EAkBl were measured using in vitro total flavonoid and total phenolic assays and a free radical scavenging assay. The effects of EAkBl on cell viability, apoptosis, autophagy, intracellular reactive oxygen species (ROS) generation and protein expression levels were also investigated. EAkBl was found to induce apoptosis, autophagy, and intracellular ROS generation in PC-3 cells. In terms of protein levels, EAkBl reduced phospho (p)-protein kinase B (AKT)/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratios, and the activations of beclin 1/β-actin and microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3 I ratios in PC-3 cells. The results of this study indicate EAkBl has antioxidant and anticancer effects on prostate cancer cells, and that these effects are associated with suppressions of p-AKT, p-mTOR, Bcl-2, and Bax, and the activations of beclin 1 and LC3. Our results indicate EAkBl has potential as a treatment for prostate cancer.

Dracocephalum palmatum Stephan extract induces apoptosis in human prostate cancer cells via the caspase-8-mediated extrinsic pathway / 中国天然药物

Dracocephalum palmatum Stephan is a medicinal plant traditionally used by nomadic people in Eastern Russia; however, research on this plant is currently limited. Recently, although studies have been conducted on the constituents of this plant and their antioxidant effects, data on its various pharmacological activities are still lacking. Thus, this study examined the anticancer potential of the dried leaves of D. palmatum S. (DpL) using human prostate cancer PC-3 cells. The antioxidant potential of DpL was evaluated by estimating the total flavonoid and total phenolic content (TFC and TPC, respectively). Additionally, we investigated the effects of the DpL ethyl acetate fraction (DpLE) on cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis, and cell cycle arrest in this cell line. The expression levels of superoxide dismutase (SOD)-1, SOD-2, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) ratio, phospho-protein kinase B (p-AKT), cleaved caspase-8, poly adenosine diphosphate (ADP) ribose polymerase (PARP), and cleaved-PARP were evaluated by western blotting. The results indicated that DpLE causes apoptosis and exerts intracellular ROS-independent anticancer effects on prostate cancer cells, associated with increased SOD-2, cleaved caspase-8, and cleaved-PARP expression and inhibited p-AKT signaling. Thus, DpLE may be a potential resource for the development of promising chemotherapeutic agents for prostate cancer.

Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats

This study investigated effect of extract containing quercetin-3-O-beta-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

Intravenous fluid prescription practices among pediatric residents in Korea / 소아과

PURPOSE: Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children, and have contended that hypotonic fluids be removed from routine practice. To assess current intravenous fluid prescription practices among Korean pediatric residents and to call for updated clinical practice education. METHODS: A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question supposed a unique scenario in which the respondents were to prescribe either a hypotonic or an isotonic fluid for the patient. RESULTS: Ninety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy. CONCLUSION: In the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required.

Renal transplantation in a patient with Bartter syndrome and glomerulosclerosis / 소아과

Bartter syndrome (BS) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism. There have been several case reports of BS complicated by focal segmental glomerulosclerosis (FSGS). Here, we have reported the case of a BS patient who developed FSGS and subsequent end-stage renal disease (ESRD) and provided a brief literature review. The patient presented with classic BS at 3 months of age and developed proteinuria at 7 years. Renal biopsy performed at 11 years of age revealed a FSGS perihilar variant. Hemodialysis was initiated at 11 years of age, and kidney transplantation was performed at 16 years of age. The post-transplantation course has been uneventful for more than 3 years with complete disappearance of BS without the recurrence of FSGS. Genetic study revealed a homozygous p.Trp(TGG)610Stop(TGA) mutation in the CLCNKB gene. In summary, BS may be complicated by secondary FSGS due to the adaptive response to chronic salt-losing nephropathy, and FSGS may progress to ESRD in some patients. Renal transplantation in patients with BS and ESRD results in complete remission of BS.

A case of pseudohypoaldosteronism type 1 with a mutation in the mineralocorticoid receptor gene / 소아과

Pseudohypoaldosteronism type 1 (PHA1) is a rare form of mineralocorticoid resistance characterized in newborns by salt wasting with dehydration, hyperkalemia and failure to thrive. This disease is heterogeneous in etiology and includes autosomal dominant PHA1 owing to mutations of the NR3C2 gene encoding the mineralocorticoid receptor, autosomal recessive PHA1 due to mutations of the epithelial sodium channel (ENaC) gene, and secondary PHA1 associated with urinary tract diseases. Amongst these diseases, autosomal dominant PHA1 shows has manifestations restricted to renal tubules including a mild salt loss during infancy and that shows a gradual improvement with advancing age. Here, we report a neonatal case of PHA1 with a NR3C2 gene mutation (a heterozygous c.2146_2147insG in exon 5), in which the patient showed failure to thrive, hyponatremia, hyperkalemia, and elevated plasma renin and aldosterone levels. This is the first case of pseudohypoaldosteronism type 1 confirmed by genetic analysis in Korea.

Clinical Characteristics and Associated Anomalies in Children with Solitary Kidney

PURPOSE: The clinical characteristics and associated anomalies in children with solitary kidney (SK) were analyzed retrospectively. METHODS: Total 38 children diagnosed to have SK at our hospital between December 1989 and December 2009 were recruited, and the clinical records including imaging studies were retrospectively reviewed. SK was defined as unilateral renal agenesis by imaging studies only, and patients with regression of unilateral dysplastic kidney were excluded. RESULTS: Among total 38 patients, 12 were male. The median age at the diagnosis of SK was 6.5 months (at birth-13 years). SK was detected by prenatal ultrasonography in 14 patients and during work-up for renal or urinary tract diseases in 13 (including urinary tract infection in 7). In 10 patients, SK was detected incidentally. Anomalies in the SK were noted in 17 patients including vesicoureteral reflux in 11. Other anomalies in the genitourinary tract were present in 16 patients, and multi-organ-involving syndromes or chromosomal anomalies were detected in 9. The mean duration of follow-up was 9 years (9 months-20 years). Two patients developed chronic renal failure during follow-up, and the median serum creatinine concentration of the remaining 36 at their last follow-up was 0.6 mg/dL. CONCLUSION: SK may be isolated and clinically asymptomatic; it is frequently accompanied by other anomalies in genitourinary tract and other organs, some of which can induce progressive renal dysfunction. Early recognition of associated anomalies with SK and regular follow-up is recommended to reduce long-term risk.

Peritonitis in Children Undergoing Peritoneal Dialysis: 10 Years' Experience in a Single Center

PURPOSE: The organisms causing peritonitis and their antibiotic sensitivities vary in different regions and centers, and these data are necessary to establish regional treatment guidelines. The aim of this study was to investigate the changes in incidence and characteristics of the organisms that cause peritonitis in children undergoing peritoneal dialysis (PD) during recent 10 years. METHODS: We retrospectively collected and analyzed the data from medical records of 110 children on PD during the period from 2000 to 2010. RESULTS: One hundred and forty episodes of peritonitis have occurred in 57 patients. The overall incidence of peritonitis was 0.43 episodes/patient.year, and similar incidence have been maintained since 2003. Sixty percent of the patients experienced peritonitis within 1 year of PD, and all patients commencing PD in infancy experienced peritonitis. Gram positive (G (+)), gram negative (G (-)) organisms and fungi were cultured in 58%, 38%, and 4.1% respectively and cultures were negative in 13.6%. Staphylococcus was the most common G (+) organism, and Pseudomonas and Acinetobacter were 2 most frequent G (-) organisms isolated. Fifty-six percent of the G (+) organisms were sensitive to first generation cephalosporin and 91% of G (-) pathogens were sensitive to ceftazidime. Methicillin-resistance rate was not higher in children less than 2 years of age than in those more than 2 years. CONCLUSION: An additional breakthrough has to be made to further reduce the incidence of peritonitis. Treatment guideline customized for peritonitis in Korean children on PD need to be established through a nationwide co-work.

The Inhibitory Effect of Quercetin-3-O-beta-D-Glucuronopyranoside on Gastritis and Reflux Esophagitis in Rats

It was evaluated the inhibitory action of quercetin-3-O-beta-D-glucuronopyranoside (QGC) on reflux esophagitis and gastritis in rats. QGC was isolated from the herba of Rumex Aquaticus. Reflux esophagitis or gastritis was induced surgically or by administering indomethacin, respectively. Oral QGC decreased ulcer index, injury area, gastric volume, and acid output and increased gastric pH as compared with quercetin. Furthermore, QGC significantly decreased gastric lesion sizes induced by exposing the gastric mucosa to indomethacin. Malondialdehyde levels were found to increase significantly after inducing reflux esophagitis, and were reduced by QGC, but not by quercetin or omeprazole. These results show that QGC can inhibit reflux esophagitis and gastritis in rats.

Peritoneal Protein Loss in Nephrotic Syndrome on Peritoneal Dialysis

PURPOSE: The pathophysiologic mechanism of nephrotic syndrome is not yet known clearly. At least in some cases, certain 'circulating factors' are thought to increase the glomerular protein permeability. Considering the systemic effect of the circulating factor on peritoneal membrane, we evaluated the loss of protein through peritoneal membrane in patients on peritoneal dialysis due to the end stage renal disease (ESRD) caused by steroid resistant nephrotic syndrome (SRNS). METHODS: We retrospectively reviewed the medical records of 26 pediatric patients on peritoneal dialysis ensued during the period from 2001 to 2007 at our clinic. Twelve patients had SRNS, while 14 patients had ESRD caused by the congenital anomalies of urinary system. RESULTS: While the other parameters including nPNA indicating the adequacy of protein intake were similar between the two groups, serum albumin was lower in SRNS patients than the non- SRNS patients (3.7+/-0.3 g/dL vs. 4.0+/-0.4 g/dL, P=0.021). Peritoneal protein loss was higher in SRNS patients than in non-SRNS patients (3,044.4+/-837.6 mg/m2/day vs. 1,791.6+/-1,244.0 mg/m2/ day, P=0.007). The protein permeability of the peritoneal membrane measured by the ratio of total protein concentration in dialysate to plasma was twice as high in SRNS patients as the non-SRNS (1.06+/-0.46% vs. 0.58+/-0.43%, P=0.010). After 1 year, peritoneal protein loss increased in both patient groups, but to a significantly greater degree in non-SRNS patient (P=0.023). CONCLUSION: The results of our study support the notion that in nephrotic syndrome there are some 'circulating factors' with the systemic effect. Since the greater protein loss through peritoneal membrane in SRNS was confirmed in this study, more meticulous nutritional support and close monitoring on the nutrition are required in these patients.

Chronic Renal Failure in Russell-Silver Syndrome

The Russell-Silver syndrome (RSS) is a disease characterized by intrauterine growth retardation with preserved head circumference, facial dysmorphism and short stature. Reported renal and urinary manifestations of RSS include horseshoe kidney, renal tubular acidosis, hydronephrosis, ureteropelvic obstruction and vesicoureteral reflux. Here we report a case of end-stage renal disease associated with RSS, which, to the best of our knowledge, has not been reported yet.

Relaxation Effect of Synthetic Ceramide Analogues in Cat Esophageal Smooth Muscle Cells

Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. C2- ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the C2-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited C2-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the C2- ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit C2-ceramide induced contraction via PKC and MAPK dependent pathway.