Recombinant bovine growth hormone-induced reduction of atrial natriuretic peptide is associated with improved left ventricular contractility and reverse remodeling in cardiomyopathic UM-X7.1 hamsters with congestive heart failure.

OBJECTIVE: To assess the effect of short-term treatment with GH on left ventricular contractility and remodeling, after the development of heart failure in cardiomyopathic hamsters (CMH). DESIGN: Two groups of 200-day-old UM-X7.1 CMH received daily subcutaneous injections of recombinant bovine (rb) GH (1mg/kg/day) or 0.9% NaCl for 40 days. Golden Syrian hamsters (GSH) were used as controls. At 240-day-old, the hamsters were randomly subjected to (i) assessment of left ventricular systolic function in a Langendorff perfused mode followed by the determination of the passive diastolic pressure-volume relationship and morphometric measurements; (ii) assessment of left ventricular mRNA expression of genes belonging to the fetal gene program including atrial (ANP) and brain (BNP) natriuretic peptides and cardiac myosin heavy chain isoforms and of the circulating levels of the natriuretic peptides. RESULTS: Hearts from CMH were hypertrophied and dilated (p<0.05) compared to hearts from GSH, along with a approximately 10-fold increase in the circulating ANP and BNP levels. Left ventricular BNP and ANP mRNAs were elevated by 2- and 3-fold, respectively, compared to GSH. rbGH reduced both ANP mRNA and ANP circulating levels by 34% (p<0.01) but did not significantly modulate BNP levels. This effect was associated with a preserved systolic function and reverse remodeling as assessed by a leftward shift of the passive diastolic pressure-volume relationship indicating reduced ventricular dilatation. CONCLUSIONS: The data show that a short-term administration of GH in the terminal phase of the disease confers cardioprotection by attenuating systolic dysfunction and by inducing beneficial reverse remodeling.     

Immunohistochemical localization of 3'': 5''-cyclic AMP and 3'': 5''-cyclic GMP in rat liver, intestine, and testis.

Cyclic GMP and cyclic AMP have been localized in rat liver, small intestine, and testis by a fluorescent immunocytochemical procedure. In liver, cyclic AMP is distributed along sinusoids predominantly, and increased fluorescence is seen sinusoidal areas after glucagon administration. Cyclic GMP is located in nuclear elements and on the plasma membranes of hepatocytes. In jejunum, cyclic AMP is found predominantly at the basal and lateral sides of brush border cells and in the lamina propria, while cyclic GMP is located to the brush border membrane, smooth muscle, and nuclear elements. In testis, cyclic AMP is found in cytoplasm of cells at the perimeter of the seminiferrous tubules and in interstitial cells, while cyclic AMP is visualized on the plasma membrane of the cells lining the tubules. Cyclic GMP is also seen on chromosomes of premeiotic spermatocytes and in sperm. These data provide histological evidence implicating diverse roles for the nucleotides in these tissues. The nuclear localization of cyclic GMP in all of these tissues suggests a role for the nucleotide in nucleus-directed events.     

A Multiple Indicators Multiple Cause (MIMIC) Model of Respiratory Health and Household Factors in Chinese Children: The Seven Northeastern Cities (SNEC) Study

In China, with the rapid economic development and improvement of living standards over the past few decades, the household living environment has shifted dramatically. The aim of the present study is to assess the impact of home environment factors on respiratory symptoms and asthma in Chinese children. Investigators analyzed data collected in the 25 districts from the seven Northeastern cities to examine health effects on respiratory symptoms and asthma in 31,049 children aged 2–14 years. Factor analysis was used to reduce 33 children’s lifestyle and household variables to six new ‘factor’ variables. The multiple indicators multiple causes approach was used to examine the relationship between indoor air pollution and respiratory health status, controlling for covariates. Factor analyses generated six factor variables of potential household risk factors from an original list of 33 variables. The respiratory symptoms and asthma were significantly associated with the recent home renovation factor (estimate = 0.076, p < 0.001), pet ownership factor (estimate = 0.095, p < 0.001), environmental tobacco smoke (ETS) exposure factor (estimate = 0.181, p < 0.001) and PVC-flooring factor (estimate = 0.031, p = 0.007). Home ventilation factor was not related to any respiratory condition (estimate = 0.028, p = 0.074). Independent respiratory health effects existed for multiple household environmental factors recent home renovation, pet ownership, ETS, and PVC-flooring.     

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis

Background

Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement.

Materials and methods

Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand.

Results

ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10⁻⁷ mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1β and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells.

Conclusions

ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.     

Aging aggravates long-term renal ischemia-reperfusion injury in a rat model

Aim

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI.

Materials and methods

Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed.

Results

Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI.

Conclusion

Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI.