Tumor necrosis factor-α blockade ameliorates diabetic nephropathy in rats.

BACKGROUND: Tubular injury plays a critical role in the development of diabetic nephropathy (DN), but current DN therapies do not combat tubular injury. This study was conducted to investigate if tumor necrosis factor (TNF)-α inhibition protects against tubular injury in diabetic rats and to examine the associated mechanisms. METHODS: Kidney biopsy tissues were collected and analyzed from 12 patients with DN and 5 control subjects. Streptozotocin (STZ)-induced diabetic rats were treated with a TNF-α inhibitor for 12 weeks. Renal function, albuminuria, histological injury, renal TNF-α messenger RNA (mRNA) and the NOD- (nucleotide-binding), LRR- (domain-like receptor) and pyrin domain-containing protein 3 (NLRP3) inflammasome were assessed. RESULTS: Diabetic patients with tubulointerstitial injury (TIN) presented with higher renal tubular expression of TNF-α mRNA and the NLRP3 inflammasome (P < 0.05). TNF-α inhibition reduced albuminuria, glomerular injury and tubular injury in STZ-induced diabetic rats (P < 0.05). Importantly, TNF-α inhibition significantly reduced the NLRP3 inflammasome in tubules (P < 0.05). Moreover, TNF-α inhibition decreased expression of tubular interleukin (IL)-6 and IL-17A mRNA. CONCLUSIONS: TNF-α inhibition protects against TIN by suppressing the NLRP3 inflammasome in DN rats. Future studies may focus on the clinical protective effects of TNF-α inhibition using prospective observation.

Endogenous miR-204 Protects the Kidney against Chronic Injury in Hypertension and Diabetes.

BACKGROUND: Aberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown. METHODS: We used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid-modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury. RESULTS: Kidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti-miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti-miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2. CONCLUSIONS: These findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.

Transient visual impairment in a patient with psychogenic fever: A case report.

BACKGROUND: Psychogenic fever is a stress-related psychosomatic disease and has been recognized clinically since the early twentieth century. It is common in adolescents or young women with acute or persistent elevation in body temperature. Psychogenic fever can be attenuated by anxiolytic, neuroleptic, or by psychotherapy. CASE SUMMARY: A 22-year-old female was diagnosed with psychogenic fever and suffered from fever, headache and transient visual impairment. She had a history of being hit on the head by a rolling gate 10 days prior to visiting our hospital. All examinations showed no abnormal findings. Antipyretic drugs and antibiotics had no effect on reducing her body temperature. The patient was usually nervous at work and became extremely anxious after the injury. Within a week of psychotherapy, her temperature gradually returned to normal and her sight was restored. CONCLUSION: Psychological stress may present with a range of symptoms, including visual impairment. Physicians should consider the diagnosis of psychogenic fever when patients present with fever of unknown origin and no other abnormal findings.

Length-Dependent Electronic Transport Properties of the ZnO Nanorod.

The two-probe device of nanorod-coupled gold electrodes is constructed based on the triangular zinc oxide (ZnO) nanorod. The length-dependent electronic transport properties of the ZnO nanorod was studied by density functional theory (DFT) with the non-equilibrium Green's function (NEGF). Our results show that the current of devices decreases with increasing length of the ZnO nanorod at the same bias voltage. Metal-like behavior for the short nanorod was observed under small bias voltage due to the interface state between gold and the ZnO nanorod. However, the influence of the interface on the device was negligible under the condition that the length of the ZnO nanorod increases. Moreover, the rectification behavior was observed for the longer ZnO nanorod, which was analyzed from the transmission spectra and molecular-projected self-consistent Hamiltonian (MPSH) states. Our results indicate that the ZnO nanorod would have potential applications in electronic-integrated devices.

Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats.

Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats.

Renalase might be associated with hypertension and insulin resistance in Type 2 diabetes.

BACKGROUND AND OBJECTIVES: Renalase, a monoamine oxidase derived from the kidney, can degrade catecholamine (CA) and regulate blood pressure as well as cardiac function. To investigate the changes of serum renalase levels in patients with Type 2 diabetes mellitus (DM) and examine the correlation with other features of T2DM. METHODS: Seventy-five patients with T2DM and 13 healthy volunteers were studied. The levels of serum renalase and CA were measured by enzyme linked immunosorbent assay. Several other biochemical and clinical parameters were measured. RESULTS: Serum levels of CA and renalase as well as renalase/CA (R/C) ratio in the T2DM group were significantly higher than those of the control group (p<0.05). There was a highly positive correlation between the levels of serum renalase and CA (r=0.795, p<0.001). The levels of serum renalase were positively correlated with systolic blood pressure (r=0.217, p=0.042) and serum creatinine (SCr) (r=0.295, p=0.007), and negatively correlated with eGFR (r=-0.222, p=0.044). The R/C ratio was positively correlated with SCr (r=0.347, p=0.001) as well as homeostasis model assessment for insulin resistance (IR) HOMA2-% S (r=0.340, p=0.037). CONCLUSION: Serum levels of renalase and CA were highly correlated in patients with T2DM. The levels of serum renalase and R/C ratio of T2DM patients were significantly higher than those of healthy subjects and appeared correlated with changes in blood pressure, glomerular filtration rate and IR.

Clinical survey on contrast-induced nephropathy after coronary angiography.

OBJECTIVE: To investigate the incidence and risk factors of contrast-induced nephropathy (CIN) in patients receiving coronary angiography (CAG) in a Chinese medical center. METHODS: The medical records of the patients receiving CAG at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University from January 2008 to July 2009 were collected to analyze the incidence of CIN under different conditions and the clinical difference between CIN group and non-CIN group. RESULTS: There were 487 cases enrolled in this study and the total incidence of CIN was 10.5%. Through Mehran risk score stratification, incidence of CIN increased with risk scores and in an extremely high-risk group it was as high as 18.0%. Multi-factor regression analysis showed that preoperative hypotension, heart failure, anemia and low estimated glomerular filtration rate (≤30 mL/min) were risk factors of CIN after CAG. CONCLUSION: CIN post CAG is associated with preoperative hypotension, heart failure, anemia and renal function. Close attention should be paid to CIN in patients receiving CAG.