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Comprehensive programmes to help reduce substance misuse/mental illness in youth should combine Screening, Brief Intervention, and Referral to Treatment (SBIRT). EMPATHY, an SBIRT programme, was part of a school-based prevention initiative to reduce symptoms of substance misuse in youth in Grades 6-12, along with reducing symptoms of depression, suicidal thinking, and anxiety. To better understand the feasibility of school-based SBIRT, we retrieved perspectives of administrators primarily through interviews. The level of engagement and interest of youth in the programme was high; however, two significant barriers were: (1) the need for parental consent/involvement; and (2) a systemic gap in treatment choices for youth with mild to moderate symptomology. Therapeutic alliance with students was reportedly a significant factor contributing to benefits.

Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue (1,2), but its thermogenic potential is reduced with obesity and type 2 diabetes (3-5) for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in nonneuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively (6-8). Recent findings suggest that increased peripheral serotonin (9) and polymorphisms in TPH1 are associated with obesity (10); however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts β-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities., Serotonin is a primal signaling molecule conserved across phyla that is implicated in the control of energy balance (11). Central serotonin is known to regulate energy balance by decreasing appetite [...]

Aside from its established immunologic and hematologic functions, the spleen also plays an important role in cardiovascular regulation. This occurs through changes in intrasplenic microvascular tone, as well as through splenic neurohormonal modulation of the renal and mesenteric vascular beds. Splenic regulation of blood volume occurs predominantly through fluid extravasation from the splenic circulation into lymphatic reservoirs; this is controlled by direct modulation of splenic pre- and postcapillary resistance by established physiologic agents such as atrial natriuretic peptide (ANP), nitric oxide (NO), and adrenomedullin (ADM). In addition to physiologic fluid regulation, splenic extravasation is a key factor in the inability to maintain adequate intravascular volume in septic shock. The spleen also controls renal microvascular tone through reflex activation of the splenic afferent and renal sympathetic nerves. This splenorenal reflex not only contributes to the physiologic regulation of blood pressure, but also contributes to the cardiovascular dysregulation associated with both septic shock and portal hypertension. In septic shock, the splenorenal reflex protectively limits splenic extravasation and potentially promotes renal sodium and water reabsorption and release of the vasoconstrictor angiotensin II; this function is eventually overwhelmed as shock progresses. In portal hypertension, on the other hand, the splenorenal reflex-mediated reduction in renal vascular conductance exacerbates sodium and water retention in the kidneys and may eventually contribute to renal dysfunction. Preliminary evidence suggests that the spleen also may play a role in the hemodynamic complications of portal hypertension via neurohormonal modulation of the mesenteric vascular bed. Lastly, the spleen itself may be a source of a vasoactive factor. Key words: blood volume, extravasation, renal sympathetic nerve activity, portal hypertension, septic shock, splenorenal reflex, splanchnic, microvascular regulation. Resume : Outre ses fonctions immunologiques et hematologiques, la rate joue aussi un role important dans la regulation cardiovasculaire. Ce role se manifeste a travers les modifications du tonus microvasculaire intrasplenique et la modulation neurohormonale splenique des lits vasculaires renal et mesenterique. La regulation splenique du volume sanguin se produit principalement par l'intermediaire de l'extravasation de liquide depuis la circulation splenique jusqu'aux reservoirs lymphatiques; cet effet est regule par la modulation directe de la resistance pre et postcapillaire splenique par des agents physiologiques etablis comme le peptide natriuretique auriculaire (PNA), le monoxyde d'azote (NO) et l'adrenomedulline (ADM). En plus de reguler le liquide physiologique, l'extravasation est un facteur cle dans l'incapacite de maintenir un volume intravasculaire adequat dans le choc septique. La rate regule aussi le tonus microvasculaire renal par l'activation reflexe des nerfs afferents spleniques et sympathiques renaux. Ce reflexe splenorenal contribue non seulement a la regulation physiologique de la pression arterielle, mais aussi a la dysregulation cardiovasculaire associee au choc septique et a l'hypertension portale (HP). Dans le choc septique, le reflexe splenorenal limite l'extravasation splenique de facon a assurer une protection et favorise potentiellement la reabsorption renale d'eau et de sodium et la liberation du vasoconstricteur angiotensine Il; cette fonction s'amenuise et devient negligeable a mesure que le choc progresse. A l'oppose, dans l'HP, la diminution de la conductance vasculaire renale vehiculee par le reflexe splenorenal amplifie la retention renale de sodium, et d'eau et pourrait contribuer a la dysfonction renale. Des resultats preliminaires donnent a penser que la rate pourrait aussi jouer un role dans les complications hemodynamiques de l'HP par la modulation neurohormonale du lit vasculaire mesenterique. Enfin, la rate pourrait etre une source de facteur vasoactif. Mots-cles : volume sanguin, extravasation, activite nerveuse sympathique renale, hypertension portale, choc septique, reflexe splenorenal, splanchnique, regulation microvasculaire. [Traduit par la Redaction], Introduction Historically, the spleen has been viewed as an important organ for blood filtration and immunologic functions. Because it is not critical for survival, the significance of the spleen in [...]

Portal hypertension initiates a splenorenal reflex, whereby increases in splenic afferent nerve activity and renal sympathetic nerve activity cause a decrease in renal blood flow (RBF). We postulated that mesenteric vascular congestion similarly compromises renal function through an intestinal-renal reflex. The portal vein was partially occluded in anesthetized rats, either rostral or caudal to the junction with the splenic vein. Portal venous pressure increased (6.5 [+ or -] 0.1 to 13.2 [+ or -] 0.1 mmHg; n = 78) and mesenteric venous outflow was equally obstructed in both cases. However, only rostral occlusion increased splenic venous pressure. Rostral occlusion caused a fall in RBF (-1.2 [+ or -] 0.2 ml/min; n = 9) that was attenuated by renal denervation (-0.5 [+ or -] 0.1 ml/min; n = 6), splenic denervation (-0.2 [+ or -] 0.1 ml/min; n = 11), celiac ganglionectomy (-0.3 [+ or -] 0.1 ml/min; n = 9), and splenectomy (-0.5 [+ or -] 0.1 ml/min; n = 6). Caudal occlusion induced a significantly smaller fall in RBF (-0.5 [+ or -] 0.1 ml/min; n = 9), which was not influenced by renal denervation (-0.2 [+ or -] 0.2 ml/min; n = 6), splenic denervation (-0.1 [+ or -] 0.1 ml/min; n = 7), celiac ganglionectomy (-0.1 [+ or -] 0.3 ml/min; n = 8), or splenectomy (-0.3 [+ or -] 0.1 ml/min; n = 7). Renal arterial conductance fell only in intact animals subjected to rostral occlusion (-0.007 [+ or -] 0.002 ml x [min.sup.-1] x mm[Hg.sup.-1]). This was accompanied by increases in splenic afferent nerve activity (15.0 [+ or -] 3.5 to 32.6 [+ or -] 6.2 spikes/s; n = 7) and renal efferent nerve activity (32.7 [+ or -] 5.2 to 39.3 [+ or -] 6.0 spikes/s; n = 10). In animals subjected to caudal occlusion, there were no such changes in renal arterial conductance or splenic afferent/renal sympathetic nerve activity. We conclude that the portal hypertension-induced fall in RBF is initiated by increased splenic, but not mesenteric, venous pressure, i.e., we did not find evidence for intestinal-renal reflex control of the kidneys. portal hypertension; spleen; renal sympathetic nerve activity

Hamza, Shereen M., and Susan Kaufman. A vibrator prevents streaming during close-arterial infusion into the kidney. Am J Physiol Renal Physiol 286: F643-F646, 2004. First published December 2, 2003; 10.1152/ajprenal.00290.2003.--Close-arterial infusion of test substances allows one to study the responses of a selected vascular bed without inducing confounding systemic effects. Unfortunately, laminar flow patterns within the artery cause streaming of the injected factor, so that distribution within the target organ is not homogeneous. We describe a reliable method of overcoming these problems. Specifically, we attach a vibrator (i-Vibe egg) to the syringe containing the test substance. We showed that, without vibration, infusion of a solution of Evans blue (0.5% wt/vol) results in uneven distribution of the dye in the kidney. Vibration of the syringe during infusion allows for uniform coloration of the kidney surface. There is also functional improvement of drug distribution during vibration. Renal blood flow was measured during intrarenal infusion of phenylephrine (150 [micro]l, 0.05-0.5 [micro]g). Vibration caused a significant leftward shift in the dose-response curve, i.e., the phenylephrine-induced reduction in renal blood flow was enhanced by vibration. This cheap, simple method for ensuring adequate mixing of intra-arterially infused substances will facilitate not only the study of renal function in the rat but also infusion of test and therapeutic substances into other organs. renal artery; laminar flow

Acutely increased renal venous pressure (RVP) impairs renal function, but the long-term impact is unknown. We investigated whether chronic RVP elevation impairs baseline renal function and prevents exacerbation of renal dysfunction and cardiovascular instability upon further RVP increase. RVP elevation (20 –25 mmHg) or sham operation (sham) was performed in rats. After 1 wk (n=17) or 3 wk (n = 22), blood pressure, RVP, renal blood flow (RBF), renal vascular conductance (RVC), and glomerular filtration rate (GFR) were measured at baseline and during superimposed RVP increase. Chronic RVP elevation induced extensive renal venous collateral formation. RVP fell to 6±1 mmHg at 1 wk and 3 ±1 mmHg at 3 wk. Baseline blood pressure and heart rate were unaltered compared with sham. RBF, RVC, and GFR were reduced at 1 wk but normalized by 3 wk. Upon further RVP increase, the drop in mean arterial pressure was attenuated at 3 wk compared with 1 wk (P < 0.05), whereas heart rate fell comparably across all groups; the mean arterial pressure-heart rate relationship was disrupted at 1 and 3 wk. RBF fell to a similar degree as sham at 1 wk (–2.3±0.7 vs. – 3.9 ± 1.2 mL/min, P = 0.066); however, at 3 wk, this was attenuated compared with sham (–1.5 ± 0.5 vs. 4.2± 0.7 mL/min, P < 0.05). The drop in RVC and GFR was attenuated at 1 and 3 wk (P < 0.05). Thus, chronic RVP elevation induced by partial renal vein ligation elicits extensive renal venous collateral formation, and although baseline renal function is impaired, chronic RVP elevation in this manner induces protective adaptations in kidneys of healthy rats, which attenuates the hemodynamic response to further RVP increase. [ABSTRACT FROM AUTHOR]

Increased central venous pressure and renal venous pressure (RVP) are associated with worsening of renal function in acute exacerbation of congestive heart failure. We tested whether an acute isolated elevation of RVP in one kidney leads to ipsilateral renal vasoconstriction and decreased glomerular filtration rate (GFR) and whether this depends on dietary salt intake or activation of renal nerves. Male Lewis rats received a normal (1% NaCl, NS) or high-salt (6% NaCl) diet for ≥14 days before the acute experiment. Rats were then randomized into the following three groups: time control and RVP elevation to either 10 or 20 mmHg to assess heart rate, renal blood flow (RBF), and GFR. To increase RVP, the left renal vein was partially occluded for 120 min. To determine the role of renal nerves, surgical denervation was conducted in rats on both diets. Renal sympathetic nerve activity (RSNA) was additionally recorded in a separate group of rats. Increasing RVP to 20 mmHg decreased ipsilateral RBF (7.5 ± 0.4 to 4.1 ± 0.7 ml/min, P<0.001), renal vascular conductance (0.082 ± 0.006 to 0.060 ± 0.011 ml· min-1 ·mmHg-1 , P<0.05), and GFR (1.28 ± 0.08 to 0.40 ± 0.13 ml/min, P<0.05) in NS rats. The reduction was abolished by high-salt diet but not by renal denervation. Furthermore, a major increase of RVP (1.6 ± 0.8 to 24.7 ± 1.2 mmHg) immediately suppressed RSNA and decreased heart rate (P<0.05), which points to suppression of both local and systemic sympathetic activity. Taken together, acute elevated RVP induces renal vasoconstriction and decreased GFR, which is more likely to be mediated via the renin-angiotensin system than via renal nerves. [ABSTRACT FROM AUTHOR]

Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol. [ABSTRACT FROM AUTHOR]

Increased central venous pressure and renal venous pressure (RVP) are associated with worsening of renal function in acute exacerbation of congestive heart failure. We tested whether an acute isolated elevation of RVP in one kidney leads to ipsilateral renal vasoconstriction and decreased glomerular filtration rate (GFR) and whether this depends on dietary salt intake or activation of renal nerves. Male Lewis rats received a normal (1% NaCl, NS) or high-salt (6% NaCl) diet for ≥14 days before the acute experiment. Rats were then randomized into the following three groups: time control and RVP elevation to either 10 or 20 mmHg to assess heart rate, renal blood flow (RBF), and GFR. To increase RVP, the left renal vein was partially occluded for 120 min. To determine the role of renal nerves, surgical denervation was conducted in rats on both diets. Renal sympathetic nerve activity (RSNA) was additionally recorded in a separate group of rats. Increasing RVP to 20 mmHg decreased ipsilateral RBF (7.5 ± 0.4 to 4.1 ± 0.7 ml/min, P < 0.001), renal vascular conductance (0.082 ± 0.006 to 0.060 ± 0.011 ml·min -1 ·mmHg -1 , P < 0.05), and GFR (1.28 ± 0.08 to 0.40 ± 0.13 ml/min, P < 0.05) in NS rats. The reduction was abolished by high-salt diet but not by renal denervation. Furthermore, a major increase of RVP (1.6 ± 0.8 to 24.7 ± 1.2 mmHg) immediately suppressed RSNA and decreased heart rate ( P < 0.05), which points to suppression of both local and systemic sympathetic activity. Taken together, acute elevated RVP induces renal vasoconstriction and decreased GFR, which is more likely to be mediated via the renin-angiotensin system than via renal nerves.

Over the past several decades, studies of the sympathetic nervous system in humans, sheep, rabbits, rats, and mice have substantially increased mechanistic understanding of cardiovascular function and dysfunction. Recently, interest in sympathetic neural mechanisms contributing to blood pressure control has grown, in part because of the development of devices or surgical procedures that treat hypertension by manipulating sympathetic outflow. Studies in animal models have provided important insights into physiological and pathophysiological mechanisms that are not accessible in human studies. Across species and among laboratories, various approaches have been developed to record, quantify, analyze, and interpret sympathetic nerve activity (SNA). In general, SNA demonstrates "bursting" behavior, where groups of action potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In humans, it is common to quantify SNA as bursts per minute or bursts per 100 heart beats. This type of quantification can be done in other species but is only commonly reported in sheep, which have heart rates similar to humans. In rabbits, rats, and mice, SNA is often recorded relative to a maximal level elicited in the laboratory to control for differences in electrode position among animals or on different study days. SNA in humans can also be presented as total activity, where normalization to the largest burst is a common approach. The goal of the present paper is to put together a summary of "best practices" in several of the most common experimental models and to discuss opportunities and challenges relative to the optimal measurement of SNA across species.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-measuring-sympathetic-nerve-activity/., (Copyright © 2017 the American Physiological Society.)

Since left ventricular hypertrophy (LVH) increases the susceptibility for the development of other cardiac conditions, pharmacotherapy that mitigates pathological cardiac remodeling may prove to be beneficial in patients with LVH. Previous work has shown that the activation of the energy-sensing kinase AMP-activated protein kinase (AMPK) can inhibit some of the molecular mechanisms that are involved in LVH. Of interest, metformin activates AMPK through its inhibition of mitochondrial complex I in the electron transport chain and can prevent LVH induced by pressure overload. However, metformin has additional cellular effects unrelated to AMPK activation, raising questions about whether mitochondrial complex I inhibition is sufficient to reduce LVH. Herein, we characterize the cardiac effects of a novel compound (R118), which is a more potent complex I inhibitor than metformin and is thus used at a much lower concentration. We show that R118 activates AMPK in the cardiomyocyte, inhibits multiple signaling pathways involved in LVH, and prevents G q protein-coupled receptor agonist-induced prohypertrophic signaling. We also show that in vivo administration of R118 prevents LVH in a mouse model of hypertension, suggesting that R118 can directly modulate the response of the cardiomyocyte to stress. Of importance, we also show that while R118 treatment prevents adaptive remodelling in response to elevated afterload, it does so without compromising systolic function, improves myocardial energetics, and prevents a decline in diastolic function in hypertensive mice. Taken together, our data suggest that inhibition of mitochondrial complex I may be worthy of future investigation for the treatment of LVH. NEW & NOTEWORTHY Inhibition of mitochondrial complex I by R118 reduces left ventricular hypertrophy (LVH) and improves myocardial energetics as well as diastolic function without compromising systolic function. Together, these effects demonstrate the therapeutic potential of complex I inhibitors in the treatment of LVH, even in the presence of persistent hypertension., (Copyright © 2017 the American Physiological Society.)