Visfatin Induces Sickness Responses in the Brain

BACKGROUND/OBJECTIVE: Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity. METHODOLOGY: Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated. PRINCIPAL FINDINGS: Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity. CONCLUSIONS: Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain

Impact of Depression on Work Productivity and Its Improvement after Outpatient Treatment with Antidepressants

AbstractObjectiveDepressive disorders influence socioeconomic burden at both the individual and organizational levels. This study estimates the lost productive time (LPT) and its resulting cost among workers with major depressive disorder (MDD) compared with a comparison group. It also estimates the change in productivity after 8 weeks of outpatient psychiatric treatment with antidepressants.MethodsWorking patients diagnosed with MDD without other major physical or mental disorders were recruited (n = 102), along with age- and sex-matched healthy controls from the Seoul Metropolitan area (n = 91). The World Health Organization's Health and Work Performance Questionnaire and the Hamilton Rating Scale for Depression were utilized to measure productivity and severity of depression, respectively, at baseline and at 8 weeks of treatment.ResultsThe LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group. Workers with MDD averaged costs due to LPT at 33.4% of their average annual salary, whereas the comparison group averaged costs of 2.5% of annual salary. After 8 weeks of treatment, absenteeism and clinical symptoms of depression were significantly reduced and associated with significant improvement in self-rated job performance (31.8%) or cost savings of $7508 per employee per year.ConclusionsWe confirmed that significant productivity loss arises from MDD and that this loss can be reduced with psychiatric intervention after a time period as short as 8 weeks. Mental health professionals should work with employers to devise a cost-effective system to provide workers with accessible quality care

Distinct firing activities of the hypothalamic arcuate nucleus neurons to appetite hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

Incidence and Predictive Factors of Benign Renal Lesions in Korean Patients with Preoperative Imaging Diagnoses of Renal Cell Carcinoma

The present study was performed to determine the incidence and predictive factors of benign renal lesions in Korean patients undergoing nephrectomy for presumed renal cell carcinoma on preoperative imaging. We analyzed the pathologic reports and medical records of 1,598 eligible patients with unilateral, nonmetastatic, and nonfamilial renal masses. Of the 1,598 renal masses, 114 (7.1%) were benign lesions, including angiomyolipoma in 47 (2.9%), oncocytoma in 23 (1.4%), and complicated cysts in 18 (1.1%) patients. On univariate analysis, the proportion of benign lesions was significantly higher in female patients, and in patients with smaller tumors, cystic renal masses, and without gross hematuria as a presenting symptom. When renal lesions were stratified by tumor size, the proportion of benign as opposed to malignant lesions decreased significantly as tumor size increased. On multivariate analysis, female gender, smaller tumor size, and cystic lesions were significantly associated with benign histological features. The findings in this large cohort of Korean patients show a lower incidence (7.1%) of benign renal lesions than those of previous Western reports. Female gender, cystic renal lesions, and smaller tumor size are independent predictors of benign histological features

Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling

<p>Abstract</p> <p>Background</p> <p>Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.</p> <p>Methods</p> <p>To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.</p> <p>Results</p> <p>The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.</p> <p>Conclusions</p> <p>The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.</p