Oxytocin Reduces Reward-Driven Food Intake in Humans

Experiments in animals suggest that the neuropeptide oxytocin acts as an anorexigenic signal in the central nervous control of food intake. In humans, however, research has almost exclusively focused on the involvement of oxytocin in the regulation of social behavior. We investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 min after neuropeptide administration, followed by the assessment of olfaction and reward-driven snack intake in the absence of hunger. Energy expenditure was registered by indirect calorimetry, and blood was repeatedly sampled to determine concentrations of blood glucose and hormones. Oxytocin markedly reduced snack consumption, restraining, in particular, the intake of chocolate cookies by 25%. Oxytocin, moreover, attenuated basal and postprandial levels of adrenocorticotropic hormone and cortisol and curbed the meal-related rise in plasma glucose. Energy expenditure and hunger-driven food intake as well as olfactory function were not affected. Our results indicate that oxytocin, beyond its role in social bonding, regulates nonhomeostatic, reward-related energy intake, hypothalamic-pituitary-adrenal axis activity, and the glucoregulatory response to food intake in humans. These effects can be assumed to converge with the psychosocial function of oxytocin and imply possible applications in the treatment of metabolic disorders.The hypothalamic nonapeptide oxytocin is released into the circulation by axonal terminals in the posterior pituitary and, moreover, acts directly on central nervous receptors. Oxytocin, which has been highly preserved during mammalian evolution, regulates physiological functions related to reproduction and mother-infant interaction, such as lactation, and in recent years, has been shown to modulate affiliative behavior (1). Research in humans has almost exclusively focused on the role of oxytocin in the regulation of prosocial behavior, including trust, attachment, and sexual behavior (2–5), largely ignoring potential effects of the neuropeptide on ingestive behavior and metabolism. In fact, evidence from rodent studies indicates that the neuropeptide acts as a strong inhibitor of food intake and affects energy expenditure and glucose homeostasis (6–9). Oxytocinergic neurons in the hypothalamic paraventricular nucleus are assumed to mediate the food intake–limiting effect of leptin, an adipokine that provides the brain with negative feedback on body fat stores and sensitizes caudal brainstem nuclei to satiety factors such as cholecystokinin (10). Hypothalamic oxytocin signaling, moreover, mediates anorexigenic effects of the satiety factor nesfatin-1 in a leptin-independent manner (11). Importantly, oxytocin reduces food intake not only in normal-weight rodents but also in animals with diet-induced obesity (8,12,13), so oxytocinergic pathways might be a promising target of clinical interventions in obese patients.The direct manipulation of neuropeptidergic central nervous signaling pathways can be achieved via the intranasal administration of peptides, which is known to bypass the blood–brain barrier and result in significant cerebrospinal fluid elevations in substance levels within 40 min, without the need for systemic infusion (14,15). This approach has been validated, among others, for vasopressin, a close homolog of oxytocin (14), and intranasal oxytocin administration has been shown to reliably modulate neuropsychological functions in a series of studies (2–5) in the absence of relevant side effects (16). Surprisingly, however, the effect of intranasal oxytocin on energy metabolism, including ingestive behavior, has not been investigated in humans so far. The assessment of respective effects of intravenous oxytocin (17) is hampered because peripheral oxytocin is not readily transported across the blood–brain barrier (18).In the present experiments, we studied the contribution of oxytocin signaling to the control of ingestive behavior and energy expenditure in normal-weight, healthy men, with a particular view to endocrine regulators of metabolism, such as ghrelin and insulin, as well as hypothalamic-pituitary-adrenal (HPA) axis secretory activity. Ingestive behavior is not only regulated homeostatically (i.e., by central nervous pathways that respond to energy depletion) but also by nonhomeostatic brain circuits that process the reward-related, “hedonic” qualities of food intake (19). Therefore, we applied a twofold assessment of food intake that relied, on the one hand, on a large breakfast buffet after an overnight fast to investigate homeostatic, primarily hunger-driven energy intake (20–22), and on the other hand, on a collection of snacks of varying palatability offered after breakfast intake for the measurement of reward-driven food intake (22–24).     

Chloride: The queen of electrolytes?

BackgroundChannelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general do not allocate chapters exclusively on hypochloremia or hyperchloremia and information on chloride other than channelopathies is scattered in the literature.Study designTo systematically review the function of chloride in man, data for this review include searches of MEDLINE, PubMed, and references from relevant articles including the search terms “chloride,” “HCl,” “chloride channel” “acid-base,” “acidosis,” “alkalosis,” “anion gap” “strong anion gap” “Stewart,” “base excess” and “lactate.” In addition, internal medicine, critical care, nephrology and gastroenterology textbooks were evaluated on topics pertaining the assessment and management of acid-base disorders, including reference lists from journals or textbooks.ConclusionChloride is, after sodium, the most abundant electrolyte in serum, with a key role in the regulation of body fluids, electrolyte balance, the preservation of electrical neutrality, acid-base status and it is an essential component for the assessment of many pathological conditions. When assessing serum electrolytes, abnormal chloride levels alone usually signify a more serious underlying metabolic disorder, such as metabolic acidosis or alkalosis. Chloride is an important component of diagnostic tests in a wide array of clinical situations. In these cases, chloride can be tested in sweat, serum, urine and feces. Abnormalities in chloride channel expression and function in many organs can cause a range of disorders.     

The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients

Studies on pharmacokinetics and pharmacodynamics of high-dose methotrexate chemotherapy (HD-MTX) in elderly primary central nervous system lymphoma (PCNSL) patients are rare. MTX exposure time has recently been proposed as an outcome determining factor in PCNSL. We investigated 49 immunocompetent PCNSL patients (female N=30, male N=19, median age 73 years) who were treated according to HD-MTX-based protocols. A two-compartment pharmacokinetic model was used to describe the MTX clearance. Response to treatment was assessed by MRI. We used multivariable models to investigate the association between MTX exposure and tumor response as well as survival. Dose normalized MTX peak serum levels [C (max), μmol/L g] and dose normalized area under the curve [AUC(dn), μmol h/L g] were higher in females than in males, respectively [59.4 (f) vs. 48.1 (m), P<0.001; 373.2 (f) vs. 271.9 (m), P=0.008]. Increasing AUC was inversely correlated with tumor response. AUC values above 2,126 h?μmol/L were independently associated with shorter overall and progression-free survival [hazard ratio (HR), 4.56, 95 % CI 1.74-11.94; HR 2.87, 95 % CI 1.18-7.00]. Exceedingly high MTX AUC levels can have a negative impact on progression-free and overall survivals in elderly PCNSL patients.     

Medium-term results after complex intra-articular fractures of the tibial plateau

Background

To present the medium-term results of intra-articular, bicondylar AO/OTA classification type C fractures of the tibial plateau in a retrospective study at a level-1 trauma center in 22 patients with 23 fractures.

Methods

Demographic data for the patients and details of current clinical and radiological follow-up findings were obtained to assess range of motion, clinical stability and alignment of the knee, and posttraumatic arthrosis (Kellgren/Lawrence score). Functional outcomes were assessed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) form.

Results

Patients’ mean age was 46 years (range 20–67 years). Leading causes of the fractures were high-energy traffic accidents and falls. There were seven C1, seven C2, and nine C3 fractures. ORIF was performed in 20 patients; in two patients an external fixator and in one patient cannulated screws alone were used. In 13/22 patients, an angle-stable locking plate (Less Invasive Stabilization System, LISS©) was used for osteosynthesis. The mean follow-up period was 67 months (range 36–109 months). The overall complication rate was 39.1 %, including four infections and four cases of pseudarthrosis (17.4 %). The average flexion of the injured knee was significantly lower in comparison with the contralateral side (124.9° vs. 135.2°). Knee stability did not differ statistically significantly. Current radiographs revealed no signs of posttraumatic arthrosis in 30.4 % of cases, mild signs in 34.8 %, clear signs in 26.1 %, and severe signs in 13 % using the Kellgren and Lawrence scale. The average Lysholm score was 66.2 points, and the average KOOS score was 67.84. One patient was in category A, and 2 were in category B in the IKDC overall categories, whereas 5 patients were in category C and 14 were even in category D.

Conclusions

Complex articular tibial plateau fractures are associated with a high rate of complications, continue to have a severe impact on function in the injured knee, lead to early post-traumatic arthrosis, and result in long-lasting subjective symptoms for the patients.     

Influence of Preoperative and Postoperative Pelvic Floor Muscle Training (PFMT) Compared with Postoperative PFMT on Urinary Incontinence After Radical Prostatectomy: A Randomized Controlled Trial

Background

The efficacy of preoperative pelvic floor muscle training (PFMT) for urinary incontinence (UI) after open radical prostatectomy (ORP) and robot-assisted laparoscopic radical prostatectomy (RARP) is still unclear.

Objective

To determine whether patients with additional preoperative PFMT regain urinary continence earlier than patients with only postoperative PFMT after ORP and RARP.

Design, setting, and participants

A randomized controlled trial enrolled 180 men who planned to undergo ORP/RARP.

Intervention

The experimental group (E, n = 91) started PFMT 3 wk before surgery and continued after surgery. The control group (C, n = 89) started PFMT after catheter removal.

Outcome measurements and statistical analysis

The primary end point was time to continence. Patients measured urine loss daily (24-h pad test) until total continence (three consecutive days of 0 g of urine loss) was achieved. Secondary end points were 1-h pad test, visual analog scale (VAS), International Prostate Symptom Score (IPSS), and quality of life (King's Health Questionnaire [KHQ]). Kaplan-Meier analysis and Cox regression with correction for two strata (age and type of surgery) compared time and continence. The Fisher exact test was applied for the 1-h pad test and VAS; the Mann-Whitney U test was applied for IPSS and KHQ.

Results and limitations

Patients with additional preoperative PFMT had no shorter duration of postoperative UI compared with patients with only postoperative PFMT (p = 0.878). Median time to continence was 30 and 31 d, and median amount of first-day incontinence was 108 g and 124 g for groups E and C, respectively. Cox regression did not indicate a significant difference between groups E and C (p = 0.773; hazard ratio: 1.047 [0.768–1.425]). The 1-h pad test, VAS, and IPSS were comparable between both groups. However, “incontinence impact” (KHQ) was in favor of group E at 3 mo and 6 mo after surgery.

Conclusions

Three preoperative sessions of PFMT did not improve postoperative duration of incontinence.

Trial registration

Netherlands Trial Register No. NTR 1953.