Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves.

Renal denervation (RDN) is a potential therapy for drug-resistant hypertension. However, whether its effects are mediated by ablation of efferent or afferent renal nerves is not clear. Previous studies have implicated that renal inflammation and the sympathetic nervous system are driven by the activation of afferent and efferent renal nerves. RDN attenuated the renal inflammation and sympathetic activity in some animal models of hypertension. In the 2 kidney,1 clip (2K1C) model of renovascular hypertension, RDN also decreased sympathetic activity; however, mechanisms underlying renal and central inflammation are still unclear. We tested the hypothesis that the mechanisms by which total RDN (TRDN; efferent + afferent) and afferent-specific RDN (ARDN) reduce arterial pressure in 2K1C rats are the same. Male Sprague-Dawley rats were instrumented with telemeters to measure mean arterial pressure (MAP), and after 7 days, a clip was placed on the left renal artery. Rats underwent TRDN, ARDN, or sham surgery of the clipped kidney and MAP was measured for 6 wk. Weekly measurements of water intake (WI), urine output (UO), and urinary copeptin were conducted, and urine was analyzed for cytokines/chemokines. Neurogenic pressor activity (NPA) was assessed at the end of the protocol calculated by the depressor response after intraperitoneal injection of hexamethonium. Rats were euthanized and the hypothalamus and kidneys removed for measurement of cytokine content. MAP, NPA, WI, and urinary copeptin were significantly increased in 2K1C-sham rats, and these responses were abolished by both TRDN and ARDN. 2K1C-sham rats presented with renal and hypothalamic inflammation and these responses were largely mitigated by TRDN and ARDN. We conclude that RDN attenuates 2K1C hypertension primarily by ablation of afferent renal nerves which disrupts bidirectional renal neural-immune pathways.NEW & NOTEWORTHY Hypertension resulting from reduced perfusion of the kidney is dependent on renal sensory nerves, which are linked to inflammation in the kidney and hypothalamus. Afferent renal nerves are required for chronic increases in both water intake and vasopressin release observed following renal artery stenosis. Findings from this study suggest an important role of renal sensory nerves that has previously been underestimated in the pathogenesis of 2K1C hypertension.

Association between Vitamin D Levels and Nonalcoholic Fatty Liver Disease: Potential Confounding Variables.

Nonalcoholic fatty liver disease (NAFLD), historically considered to be the hepatic component of the metabolic syndrome, is a spectrum of fat-associated liver conditions, in the absence of secondary causes, that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Disease progression is closely associated with body weight or fatness, dyslipidemia, insulin resistance, oxidative stress, and inflammation. Recently, vitamin D deficiency has been linked to the pathogenesis and severity of NAFLD because of vitamin D "pleiotropic" functions, with roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. Indeed, several studies have reported an association between vitamin D and NAFLD/NASH. However, other studies have failed to find an association. Therefore, we sought to critically review the current evidence on the association between vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables that may interfere with this evaluation, such as host-, environment-, and heritability-related factors regulating vitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respect to skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D; and methods of diagnosing NAFLD as well as quantifying adiposity, the cardinal link between vitamin D deficiency and NAFLD.

Highlights from the third annual Mayo Clinic conference on systems engineering and operations research in health care.

In August 2010, the Third Annual Mayo Clinic Conference on Systems Engineering and Operations Research in Health Care was held. The continuing mission of the conference is to gather a multidisciplinary group of systems engineers, clinicians, administrators, and academic professors to discuss the translation of systems engineering methods to more effective health care delivery. Education, research, and practice were enhanced via a mix of formal presentations, tutorials, and informal gatherings of participants with diverse backgrounds. Although the conference promotes a diversity of perspectives and methods, participants are united in their desire to find ways in which systems engineering can transform health care, especially in the context of health care reform and other significant changes affecting the delivery of health care.

Percutaneous laser ablation in patients with isolated unresectable liver metastases from colorectal cancer: Results of a phase II study.

We prospectively evaluated the safety, local tumor control, and impact on survival parameters of percutaneous laser ablation (PLA) in patients with colorectal liver metastases not amenable to surgical resection. The study included 44 individuals with 75 unresectable liver metastases and no known extrahepatic disease. The median number of metastases treated for each patient was one, with a range of 1-4. Metastases had a median diameter of 3.4 cm (range 0.5-9 cm), and a median volume of 16.8 cm(3) (range 0.4-176.4 cm(3)). All patients also received systemic chemotherapy with modalities that differed according to the type of response to PLA. After treatment, 61% (46/75) of the tumors were ablated completely. The likelihood of achieving a complete ablation was significantly higher when metastases had a diameter <3.0 cm (p = 0.004). Overall survival was 30.0+/-12.7 months in patients with a complete ablation, and 20.2+/-10.2 months in those with a partial ablation (p = 0.002). There were no major complications during or after PLA, the most frequent side effect being abdominal pain that required analgesics. These findings indicate that PLA can be safely used as an adjunct to chemotherapy in unresectable colorectal liver metastases, and may have a positive impact on survival.