We investigated the effects of dual renin-angiotensin system (RAS) blockade on angiotensin-converting enzyme-2 (Ace2) expression, hypertension, and renal proximal tubular cell (RPTC) apoptosis in ...type 1 diabetic Akita angiotensinogen (Agt)-transgenic (Tg) mice that specifically overexpress Agt in their RPTCs. Adult (11 wk old) male Akita and Akita Agt-Tg mice were treated with two RAS blockers (ANG II receptor type 1 blocker losartan, 30 mg·kg(-1)·day(-1)) and angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg·kg(-1)·day(-1)) in drinking water. Same-age non-Akita littermates and Agt-Tg mice served as controls. Blood pressure, blood glucose, and albuminuria were monitored weekly. The animals were euthanized at age 16 wk. The left kidneys were processed for immunohistochemistry and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess gene and protein expression. Urinary ANG II and ANG 1-7 were quantified by ELISA. RAS blockade normalized renal Ace2 expression and urinary ANG 1-7 levels (both of which were low in untreated Akita and Akita Agt-Tg), prevented hypertension, albuminuria, tubulointerstitial fibrosis and tubular apoptosis, and inhibited profibrotic and proapoptotic gene expression in RPTCs of Akita and Akita Agt-Tg mice compared with non-Akita controls. Our results demonstrate the effectiveness of RAS blockade in preventing intrarenal RAS activation, hypertension, and nephropathy progression in diabetes and support the important role of intrarenal Ace2 expression in modulating hypertension and renal injury in diabetes.
Neuronal nitric oxide synthase (nNOS) is concentrated at synaptic junctions in brain and motor endplates in skeletal muscle. Here, we show that the N-terminus of nNOS, which contains a PDZ protein ...motif, interacts with similar motifs in postsynaptic density-95 protein (PSD-95) and a related novel protein, PSD-93. nNOS and PSD-95 are coexpressed in numerous neuronal populations, and a PSD-95/nNOS complex occurs in cerebellum. PDZ domain interactions also mediate binding of nNOS to skeletal muscle syntrophin, a dystrophin-associated protein. nNOS isoforms lacking a PDZ domain, identified in nNOS super( Delta / Delta ) mutant mice, do not associate with PSD-95 in brain or with skeletal muscle sarcolemma. Interaction of PDZ-containing domains therefore mediates synaptic association of nNOS and may play a more general role in formation of macromolecular signaling complexes.
Background Lead in blood can stimulate lipid oxidation in phosphatidylcholine and increase peroxidation in lipids. Metallothionein (MT) is a cysteine-rich protein that can influence the ...detoxification of heavy metals and scavenge oxidative stress for free radicals. One of the most expressive functional genes in humans is the MT2A gene. Objective This study aims to determine if the association of the blood lead level and lipid biomarkers was influenced by MT2A polymorphisms. Methods We recruited 677 participants after informed consent was obtained. All the samples collected were analyzed for lipid biomarkers and blood lead levels and were genotyped for MT2A polymorphisms by reverse transcription polymerase chain reaction. A short questionnaire collected the medical history and alcohol and cigarette consumption information. The data were used for descriptive analyses and linear regression models. Results The investigation revealed that lead elevated concentration increased low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol (HDL-C) by multiple linear models. The carriers of the rs10636 GC-rs28366003 AA genetic combination may be less susceptive to lead elevated concentration on HDL-C than other types. Conclusion In conclusion, the association of the blood lead level and HDL-C may be modified by the MT2A genetic combination: the rs10636 GC-rs28366003 AA genotype could play a protective role in lead elevated concentration on HDL-C in humans.
Aims/hypothesis: We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF- beta 1 signalling, TGF- beta 1 inhibition of Ace-2 ...gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. Methods: Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied. Results: Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf- beta 1, TGF- beta receptor II Tgf- beta rII) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1-7 receptor MasR) expression, and normalised urinary Ang 1-7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf- beta 1 and Tgf- beta rII gene expression. Furthermore, hnRNP F overexpression prevented TGF- beta 1 signalling and TGF- beta 1 inhibition of Ace-2 gene expression. Conclusions/interpretation: These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF- beta 1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.
The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard ...imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.
The OncoDB.HCC (http://oncodb.hcc.ibms.sinica.edu.tw) is based on physical maps of rodent and human genomes containing quantitative trait loci of rodent HCC models and various human HCC somatic ...aberrations including chromosomal data from loss of heterozygosity and comparative genome hybridization analyses, altered expression of genes from microarray and proteomic studies, and finally experimental data of published HCC genes. Comprehensive integration of HCC genomic aberration data avoids potential pitfalls of data inconsistency from single genomic approach and provides lines of evidence to reveal somatic aberrations from levels of DNA, RNA to protein. Twenty-nine of 30 (96.7%) novel HCC genes with significant altered expressions in compared between tumor and adjacent normal tissues were validated by RT-PCR in 45 pairs of HCC tissues and by matching expression profiles in 57 HCC patients of re-analyzed Stanford HCC microarray data. Comparative mapping of HCC loci in between human aberrant chromosomal regions and QTLs of rodent HCC models revealed 12 syntenic HCC regions with 2 loci effectively narrowed down to 2 Mb. Together, OncoDB.HCC graphically presents comprehensive HCC data integration, reveals important HCC genes and loci for positional cloning and functional studies, and discloses potential molecular targets for improving HCC diagnosis and therapy.
To report a case of abscess formation in bilateral ovarian endometriomas after failure of mifepristone-induced abortion.
A-36-year-old multiparous woman with bilateral ovarian endometriomas conceived ...spontaneously and received mifepristone to induce an abortion at 35 days' gestation. Fever and lower abdominal pain occurred 28 days after the abortion. The patient then underwent surgical curettage for an incomplete abortion complicated by endometritis. Her symptoms and signs became aggravated, and computed tomography showed a large ovarian abscess. She underwent laparoscopic drainage of the abscess plus the enucleation of the ovarian endometriomas, and received intravenous antibiotic treatment. She resumed menstruation one month later and was doing well at the 11-month follow-up.
This case demonstrates the importance of combining antibiotic therapy with mifepristone to induce abortions in women with known ovarian endometriomas.
Varicocele is a common condition seen in adolescence and associated with adult subfertility. Numerous types of intervention have been described with differences in success and complication rates. ...This study aims to review and compare the surgical outcomes of laparoscopic Palomo surgery and scrotal antegrade sclerotherapy at our center.
A retrospective analysis was done of all patients younger than 18 years old with idiopathic varicocele treated operatively between February 2001 and December 2016. Demographics such as age at operation, side, varicocele grade, operative date, and types of operation were collected. Primary outcomes were clinical recurrence, defined as any grading noted on follow-up within 1 year post-op and post-operative hydrocele. Secondary outcomes were operative time, length of stay, and other surgical complications. Mann–Whitney U test, independent t test and chi-square tests were used for analysis. All p-values were two-sided and considered statistically significant at p ≤ 0.05.
A total of 119 patients fit the criteria, of whom 117 patients were included in data analysis (Table). Sixty-two patients had laparoscopic Palomo surgery (LPS) and 55 had scrotal antegrade sclerotherapy (SAS). Clinical recurrence (grade 2–3) within 1 year was similar between the two groups, with four out of 48 patients in the SAS group and six out of 62 patients in the LPS group (8.4% in SAS vs. 9.7% in LPS, p = 1.00). Of the 11 patients who had recurrence in the SAS group, seven had grade 1 recurrence (14.5%), two (4.2%) had grade 2 recurrence, and two (4.2%) had grade 3 recurrence. For the LPS group, 17 out of 62 patients had clinical recurrence within 1 year, of whom 11 (17.7%) had grade 1 recurrence, one (1.6%) had grade 2, and five (8.1%) had grade 3 recurrence. Post-operative hydrocele was significantly higher in the LPS group; there was none in the SAS group but 11 patients in the LPS group (0% in SAS vs. 17.7%, p = 0.002). Three patients had clinically significant hydrocele requiring Jaboulays' procedure. Complications other than hydrocele were noted in three patients in the SAS group and one patient in the LPS group (5.5% in SAS vs. 1.6% in LPS, p = 0.158). None required operative intervention. No conversion to open procedure was seen in the LPS group and there were no perioperative complications. Mean operative time was 62.9 min in the SAS group and 60.7 min in the LPS group (p = 0.624). Mean length of stay was 17.5 h in the SAS group and 31.7 h in the LPS group (p < 0.001).
Both SAS and LPS are safe procedures for treatment of adolescent varicocele with similar clinical recurrence rate within 1 year. SAS has a significantly lower rate of post-operative hydrocele.TableSummary of clinical recurrence between two groups.TableSASLPSp valueTotal = 1175562Clinical recurrence (grade 2–3) within 1 year8.4% (n = 4/48)9.7% (n = 4/62)1.00Grade 114.5% (n = 7/48)17.7% (n = 11/62)1.00Grade 24.2% (n = 2/48)1.6% (n = 1/62)0.54Grade 34.2% (n = 2/48)8.1% (n = 5/62)0.67Post-op hydrocele0% (n = 0/48)17.7% (n = 11/62)0.002Complication rate (other than hydrocele)5.5% (n = 3/55)1.6% (n = 1/62)0.158SAS = scrotal antegrade sclerotherapy, LPS = laparoscopic Palomo surgery.
Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 ...infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy‐proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon α‐2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon α‐2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent‐to‐treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG‐IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non‐1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG‐IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non‐1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG‐IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG‐IFNα2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non‐1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG‐IFNα2b ribavirin.
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