Damaged male germ cells induce epididymitis in mice.

Epididymitis can be caused by infectious and noninfectious etiological factors. While microbial infections are responsible for infectious epididymitis, the etiological factors contributing to noninfectious epididymitis remain to be defined. The present study demonstrated that damaged male germ cells (DMGCs) induce epididymitis in mice. Intraperitoneal injection of the alkylating agent busulfan damaged murine male germ cells. Epididymitis was observed in mice 4 weeks after the injection of busulfan and was characterized by massive macrophage infiltration. Epididymitis was coincident with an accumulation of DMGCs in the epididymis. In contrast, busulfan injection into mice lacking male germ cells did not induce epididymitis. DMGCs induced innate immune responses in epididymal epithelial cells (EECs), thereby upregulating the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), as well as the chemokines such as monocyte chemotactic protein-1 (MCP-1), monocyte chemotactic protein-5 (MCP-5), and chemokine ligand-10 (CXCL10). These results suggest that male germ cell damage may induce noninfectious epididymitis through the induction of innate immune responses in EECs. These findings provide novel insights into the mechanisms underlying noninfectious epididymitis, which might aid in the diagnosis and treatment of the disease.

[Value of dynamic arterial elastance in the predication of arterial pressure response to volume loading in shock patients].

OBJECTIVE: To explore the value of dynamic arterial elastance (Eadyn) in the predication of arterial pressure response to volume loading in shock patients. METHODS: A total of 32 patients with pulse indicator continuous cardiac output (PICCO) monitoring at our intensive care unit from January 2011 to December 2012 were retrospectively studied. The decision of fluid replacement was based upon the presence of shock (mean arterial pressure (MAP) ≤ 65 mm Hg, systolic arterial pressure <90 mm Hg or a decrease of 40 mm Hg from baseline) and preserved volume responsiveness condition with a stroke volume variation (SVV) value ≥ 10%. According to the MAP increase after volume loading, they were classified into MAP responders (≥ 15%) and MAP nonresponders (<15%) respectively. The goal was to investigate the influencing factors of the changes of MAP after volume loading and predict the arterial pressure response to volume loading. RESULTS: Significantly different between MAP responders and MAP nonresponders, baseline Eadyn was an effective predictor of MAP increase after volume loading. The area under the ROC curve was 0.95 for the prediction of volume loading on MAP for Eadyn at baseline (P < 0.01). A baseline Eadyn value >0.85 predicted a MAP increase after volume administration with a sensitivity of 89.5% and a specificity of 92.3%. CONCLUSION: Baseline Eadyn may predict accurately arterial pressure response in MAP to volume loading in shock patients.

Effects and mechanisms of PPARalpha activator fenofibrate on myocardial remodelling in hypertension.

Although peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the heart, the effects of PPARalpha on cardiac remodelling and the underlying mechanisms are unclear. The present study was undertaken to test the hypothesis that PPARalpha activator fenofibrate plays a key role in left ventricular hypertrophic remodelling via the formation of c-fos/c-jun heterodimers in spontaneous hypertensive rats (SHRs). Twenty-four male 8-week-old SHRs were randomly divided into two groups, one group treated with oral saline (n= 10) and another treated with oral fenofibrate (60 mg.kg-1.d-1, n= 14). Ten same-aged Wistar-Kyoto (WKY) rats were selected as a normal control group. Using echocardiography, immunohistochemistry, co-immunoprecipitation, Western blot analysis and real-time RT-PCR, we showed that the left ventricular wall thickness and significantly reduced and left ventricular diastolic function improved in SHRs treated with fenofibrate compared with SHRs treated with saline. Similarly, the excessive collagen deposition and the up-regulation of collagen I, collagen III, c-fos and c-jun seen in SHRs receiving saline were significantly attenuated in SHRs receiving fenofibrate. In addition, fenofibrate markedly decreased the expression of AP-1 and c-fos/c-jun heterodimers (P < 0.01). These results demonstrated that PPARalpha activator fenofibrate may exert a protective effect on cardiac remodelling in SHRs by decreasing the expression of c-fos and c-jun and suppressing the formation of c-fos/c-jun heterodimers, which may further inhibit transcription of the downstream genes involved in the pathogenesis of left ventricular hypertrophy induced by hypertension.