The Pathogenetic Role of Reactive Oxygen Species in Aminonucleoside Nephrosis

We studied the pathogenetic role of reactive oxygen species (ROS) in rats with puromycin aminonucleoside nephrosis (PAN). Heavy albuminuria with markedly decreased density of the anionic sites (AS) on glomerular basement membrane (GBM) (2. 6 ± O. 98 compared to 20. 0 ± 1. 61 AS/l,OOOnm GBM in control) developed 7 days after PA injection. The malondialdehyde (MDA) levels in kidney homogenates increased gradually (1. 16 ± O. 18 at day -1 to 1. 97 ± O. 23/g protein at day 5). While catalase or dimethyl sulfoxide, administered with PA, did not affect the course of PAN. superoxide dismutase and allopurinol reduced proteinuria and decreased loss of the AS (11. 7 ± 2. 80 and 13, 7 ± 1. 27 AS/l.000nm GBM, reo spectively) at day 7. These findings suggest that proteinuria in PAN results from the loss of GBM AS. in which ROS generated by xanthine oxidase system plays an import. ant role

Glycaemic status, insulin resistance, and risk of infection-related mortality:a cohort study

Importance: the impact of non-diabetic hyperglycaemia and insulin resistance on infection-related mortality risk remains unknown.Objective: we investigated the association of glycaemic status and insulin resistance with infection-related mortality in individuals with and without diabetes.Design: cohort study based on Kangbuk Samsung Health Study and national death records.Participants: about 666 888 Korean adults who underwent fasting blood measurements including glucose, glycated haemoglobin (HbA1c), and insulin during health-screening examinations were followed for up to 15.8 years.Main outcome and measures: infection-related mortality, therefore we used Cox proportional hazards regression analyses to estimate hazard ratios (HRs) and 95% CIs for infection-related mortality. Vital status and infection-related mortality were ascertained through national death records. Variable categories were created based on established cut-offs for glucose and HbA1c levels and homeostatic model assessment of insulin resistance (HOMA-IR) quintiles.Results: during a median follow-up of 8.3 years, 313 infectious disease deaths were dentified. The associations of glucose and HbA1c levels with infection-related mortality were J-shaped (P for quadratic trend&lt;.05). The multivariable-adjusted HR (95% CIs) for infection-related mortality comparing glucose levels &lt;5, 5.6-6.9, and ≥7.0 mmol/L to 5.0–5.5 mmol/L (the reference) were 2.31 (1.47–3.64), 1.65 (1.05–2.60), and 3.41 (1.66–7.00), respectively. Among individuals without diabetes, the multivariable-adjusted HR for infection-related mortality for insulin resistance (HOMA-IR ≥75th centile versus &lt;75th centile) was 1.55 (1.04–2.32).Conclusions and relevance: both low and high glycaemic levels and insulin resistance were independently associated with increased infection-related mortality risk, indicating a possible role of abnormal glucose metabolism in increased infection-related mortality.<br/

Extreme Drug Resistance in Acinetobacter baumannii Infections in Intensive Care Units, South Korea

BACKGROUND: Difference in adaptability responses to stress has been observed amongst bird species, strains, and individuals. Components of the HPA axis, one of the internal systems involved in homeostasis re-establishment following stress, could play a role in this variability of responses. The aim of the present study was 1) to identify genes involved in the regulation of adrenal activity following ACTH stimulation and 2) to examine adrenal genes differentially expressed in individuals with high and low plasma corticosterone response following ACTH treatment. RESULTS: Analysis with 21 K poultry oligo microarrays indicated that ACTH treatment affected the expression of 134 genes. Several transcripts assigned to genes involved in the adrenal ACTH signaling pathway and steroidogenic enzymes were identified as differentially expressed by ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and StAR. Only 4 genes revealed to be differentially expressed between higher and lower adrenal responders to ACTH treatment. CONCLUSION: The results from the present study reveal putative candidate genes; their role in regulation of adrenal functions and adaptability to stress should be further investigated

A clinico-genetic study of renal coloboma syndrome in children

Renal coloboma syndrome (RCS) is an autosomal dominant disorder caused by PAX2 gene mutations and characterized by renal hypoplasia and optic disc coloboma. The clinical findings were retrospectively reviewed, and all coding regions of the PAX2 gene were sequenced, in six children with RCS. A c.619_620insG mutation was detected in five patients, including two siblings, and a novel p.Arg104X mutation was detected in one patient. All the patients had progressive renal dysfunction and bilateral hypoplastic kidneys without vesicoureteral reflux (VUR), but the rate of progression to end-stage renal disease showed some diversity. The ocular manifestations showed wide variability, ranging from subtle optic disc anomalies to microphthalmia. In one family with two affected siblings, maternal germline mosaicism was suggested by an intragenic microsatellite marker study. In conclusion, there are variable renal and ocular manifestations in RCS without significant phenotype-genotype correlations. VUR is not a cardinal renal manifestation of RCS. The possibility of germline mosaicism should be considered during molecular diagnosis and genetic counseling for PAX2 mutations

Emergence of serotype K1 Klebsiella pneumoniae ST23 strains co-producing the plasmid-mediated AmpC beta-lactamase DHA-1 and an extended-spectrum beta-lactamase in Korea

Abstract Background Serotype K1 Klebsiella pneumoniae has emerged as an important community pathogen causing various infections, including liver abscesses. Although serotype K1 K. pneumoniae community isolates have been reported as susceptible to most classes of antimicrobial agents, a few cases of infection caused by extended-spectrum beta-lactamase (ESBL)-producing serotype K1 K. pneumoniae have recently been reported in Asian countries. We identified three ESBL-producing strains of serotype K1 K. pneumoniae and conducted a molecular characterization of their drug resistance. Methods Three ESBL-producing serotype K1 K. pneumoniae ST23 strains were identified from strains in the Asian Bacterial Bank. Antimicrobial susceptibility testing was performed using the broth microdilution method, and ESBL production was tested by the double-disk synergy test and a confirmatory test. PCR was performed to detect the genes for plasmid-mediated ESBL and AmpC beta-lactamases. Results All three strains were resistant to cefotaxime, ceftazidime, and piperacillin/tazobactam, and all were determined to be ESBL-producers. No known ESBL genes, including bla SHV, bla TEM, bla CTX-M, bla GES, bla PER, and bla VEB, were detected among the three strains. Of all plasmid-mediated AmpC beta-lactamase (PAB) genes, including bla DHA-1, bla CMY, bla FOX, and bla MOX, the bla DHA-1 gene was detected in two of the strains. The PFGE patterns revealed that the two isolates carrying bla DHA-1 were closely related (84% similarity). Conclusions No ESBL genes were detected among three ESBL-producing serotype K1 K. pneumoniae ST23 strains. Two strains contained the PAB gene bla DHA-1. The emergence of resistant strains of community-origin serotype K1 K. pneumoniae has important implications for effective treatment and infection control practices

Gut Microbiota and Risk of Persistent Nonalcoholic Fatty Liver Diseases

Gut dysbiosis is regarded as a pathogenetic factor of nonalcoholic fatty liver disease (NAFLD), but its role in NAFLD persistence is unknown. We investigated the influence of the gut microbiota on persistent NAFLD. This cohort study included 766 subjects with 16S ribosomal RNA (rRNA) gene sequencing data from fecal samples at baseline who underwent repeated health check-up examinations. Fatty liver was determined using ultrasound at baseline and follow-up. Participants were categorized into four groups: none (control), developed, regressed, or persistent NAFLD. The persistent NAFLD group had lower richness compared with the control group. Significant differences were also found in both non-phylogenic and phylogenic beta diversity measures according to NAFLD persistence. Pairwise comparisons indicated that taxa abundance mainly differed between the control and persistent NAFLD groups. A relative high abundance of Fusobacteria and low abundance of genera Oscillospira and Ruminococcus of the family Ruminococcaceae and genus Coprococcus of the family Lachnospiraceae were found in the persistent NAFLD group. Based on the functional predictions, pathways related to primary and secondary bile acid biosynthesis were highly detected in the persistent NAFLD group compared with the control group. These findings support that the composition of the gut microbiome associated with dysregulation of bile acid biosynthetic pathways may contribute to the persistence of NAFLD. This is the first cohort study to demonstrate the influence of microbiota on persistent NAFLD. Our findings may help identify potential targets for therapeutic intervention in NAFLD