60 research outputs found
Fibrosis in the kidney: is a problem shared a problem halved?
Fibrotic disorders are commonplace, take many forms and can be life-threatening. No better example of this exists than the progressive fibrosis that accompanies all chronic renal disease. Renal fibrosis is a direct consequence of the kidney's limited capacity to regenerate after injury. Renal scarring results in a progressive loss of renal function, ultimately leading to end-stage renal failure and a requirement for dialysis or kidney transplantation
Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice
A novel approach was employed to assess the contribution of the renin-angiotensin system (RAS) to obstructive nephropathy in neonatal mice having zero to four functional copies of the angiotensinogen gene (Agt). Two-day-old mice underwent unilateral ureteral obstruction (UUO) or sham operation; 28 days later, renal interstitial fibrosis and tubular atrophy were quantitated. In all Agt genotypes, UUO reduced ipsilateral renal mass and increased that of the opposite kidney. Renal interstitial collagen increased after UUO linearly with Agt expression, from a fractional area of 25% in zero-copy mice to 54% in two-copy mice. Renal expression of transforming growth factor-β1 was increased by ipsilateral UUO in mice expressing Agt, but not in zero-copy mice. However, the prevalence of atrophic tubules due to UUO did not vary with Agt expression. Blood pressure was not different in all groups, except for a reduction in sham zero-copy mice. We conclude that a functional RAS is not necessary for compensatory renal growth. This study demonstrates conclusively that angiotensin regulates at least 50% of the renal interstitial fibrotic response in obstructive nephropathy, an effect independent of systemic hemodynamic changes. Angiotensin-induced fibrosis likely is a mechanism common to the progression of many forms of renal disease
Mechanisms of progression of chronic kidney disease
Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin–angiotensin–aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number
1110 Preliminary experience of laparoscopic simultaneous bilateral adrenalectomy for patients with aldosterone-producing adenoma
Vertical distributions of N<sub>2</sub>O isotopocules in the equatorial stratosphere
Vertical profiles of nitrous oxide (N2O) and its
isotopocules, isotopically substituted molecules, were obtained over the
Equator at altitudes of 16–30 km. Whole air samples were collected using
newly developed balloon-borne compact cryogenic samplers over the eastern
equatorial Pacific in 2012 and Biak Island, Indonesia, in 2015. They were
examined in the laboratory using gas chromatography and mass spectrometry.
The mixing ratio and isotopocule ratios of N2O in the equatorial
stratosphere showed a weaker vertical gradient than the previously reported
profiles in the subtropical and mid-latitude and high-latitude stratosphere.
From the relation between the mixing ratio and isotopocule ratios, further
distinct characteristics were found over the Equator: (1) observed
isotopocule fractionations (ε values) in the middle stratosphere
(25–30 km or [N2O] < ca. 260 nmol mol−1) are almost equal to
ε values reported from broadband photolysis experiments
conducted in the laboratory; (2) ε values in the lower
stratosphere (< ca. 25 km or [N2O] > ca. 260 nmol mol−1)
are about half of the experimentally obtained values, being slightly larger
than those observed in the mid-latitude and high-latitude lower stratosphere
([N2O] > ca. 170 nmol mol−1). These results from the deep
tropics suggest the following. (i) The timescale for quasi-horizontal mixing
between tropical and mid-latitude air in the tropical middle stratosphere is
sufficiently slow relative to the tropical upwelling rate that isotope
fractionation approaches the Rayleigh limit for N2O photolysis. (ii) The
air in the tropical lower stratosphere is exchanged with extratropical air on
a timescale that is shorter than that of photochemical decomposition of
N2O. Previously observed ε values, which are invariably
smaller than those of photolysis, can be explained qualitatively using a
three-dimensional chemical transport model and using a simple model that
assumes mixing of aged tropical air and extratropical air during residual
circulation. Results show that isotopocule ratios are useful to examine the
stratospheric transport scheme deduced from tracer–tracer relations
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