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Background: The effects of laparoscopic adjustable gastric band (LAGB) placement on upper gastrointestinal tract function in obese adolescents are unknown. Therefore, our aim was to determine the short-term effects of LAGB on esophageal motility, gastroesophageal reflux, gastric emptying, appetite-regulatory hormones, and perceptions of post-prandial hunger and fullness.Methods: This study was part of a prospective cohort study (March 2009-December 2015) in one tertiary referral hospital. The study included obese adolescents (14-18 years) with a body mass index (BMI) > 40 (or ≥ 35 with comorbidities). Gastric emptying was assessed by 13C-octanoic acid breath test, pharyngeal, and esophageal motor function by high-resolution manometry with impedance (HRIM), and appetite and other perceptions using 100-mm visual analogue scales. Dysphagia symptoms were scored using a Dakkak questionnaire. Data were compared pre- and post-LAGB placement and at a 6-month follow-up.Results: Based upon analysis of 15 adolescents, at the 6-month follow-up, LAGB placement: (i) led to a significant reduction in weight and BMI; (ii) increased fullness and decreased hunger post-meal; (iii) increased symptoms of dysphagia after solid food; and, despite these effects, (iv) caused little or no changes to appetite hormones, while (v) effects on gastric emptying, esophageal motility, esophageal bolus transport, and esophageal emptying were not significant.Conclusion: In adolescents, LAGB improved BMI and altered the sensitivity to nutrients without significant effects on upper gastrointestinal tract physiology at the 6-month follow-up. [ABSTRACT FROM AUTHOR]

Background. An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies. Objective. To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2. Methods. Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study. Effects on weight loss, HbA1c, fasting blood glucose, and BP were evaluated at 1 week to 12 months. Results. 26 subjects (17 females/9males, 51 ± 2 years, BMI 37 ± 1 kg/m2, mean ± SEM) completed 12 months followup. One serious adverse event (pain at implant site) was easily resolved. At 1 week and 12 months, mean excess weight loss percentages (% EWL) were 9 ± 1% and 25 ± 4% (p < 0.0001), and HbA1c declined by 0.3 ± 0.1% and 1.0 ± 0.2% (P = 0.02, baseline 7.8 ± 0.2%). In DM2 subjects with elevated BP (n = 15), mean arterial pressure reduced by 7 ± 3 mmHg and 8 ± 3 mmHg (P = 0.04, baseline 100 ± 2 mmHg) at 1week and 12months.All subjects MAP decreased by 3 ± 2 mmHg (baseline 95 ± 2 mmHg) at 12months. Conclusions. VBLOC was safe in obese DM2 subjects and associated with meaningful weight loss, early and sustained improvements in HbA1c, and reductions in BP in hypertensive DM2 subjects. [ABSTRACT FROM AUTHOR]

Years of effort have failed to establish a generally-accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse-perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine-induced responses of CA1 cells studied in vitro. [ABSTRACT FROM AUTHOR]

Aim: Hepatic steatosis affects up to 30% of the population. After weight loss, monitoring of the change in hepatic steatosis is not routinely performed. This study aimed to define the closest associates of change in liver fat content in a population of obese females following laparoscopic gastric banding surgery. Methods: Before and 3 months after surgery, proton magnetic resonance spectroscopy and magnetic resonance imaging were used to estimate the amount of lipid contained within the liver and abdominal subcutaneous and visceral compartments of 29 obese [mean body mass index (BMI) 39 ± 5 kg/m2], non-diabetic women aged between 20 and 62 years. Liver enzymes, fasting plasma glucose and insulin were also measured as well as body weight, BMI and waist circumference. Insulin sensitivity was estimated using homeostasis model assessment insulin resistance index. Results: Significant reductions occurred in body weight (p < 0.001), abdominal fat volumes (p < 0.001) and liver fat (p = 0.037) 3 months after surgery. Change in liver fat content more closely associated with change in serum gamma-glutamyl transferase (GGT; r = 0.71, p < 0.001) than with changes in weight (r = 0.10, p = 0.612) and waist circumference (r = 0.15, p = 0.468). Conclusions: Our findings suggest that obese non-diabetic female patients who have undergone significant weight loss over 3 months can be better assessed for the regression of excess liver fat content by monitoring changes in serum GGT levels rather than changes in simple anthropometry. [ABSTRACT FROM AUTHOR]

Oestradiol actions in the hypothalamus play an important role in reproductive behaviour. Oestradiol treatment in vivo induces α1b-adrenoceptor mRNA and increases the density of α1B-adrenoceptor binding in the hypothalamus. Oestradiol is also known to modulate neuronal excitability, in some cases by modulating calcium channels. We assessed the effects of phenylephrine, an α1-adrenergic agonist, on low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium channels in ventromedial hypothalamic (VMN) neurones from vehicle- and oestradiol-treated female rats. Whole-cell and gramicidin perforated-patch recordings were obtained, with barium as the charge carrier. In the absence of phenylephrine, oestradiol treatment increased the magnitude of LVA currents compared to controls, but had no effect on HVA currents. Phenylephrine enhanced HVA currents in a significantly greater proportion of neurones from oestradiol-treated rats (76%) than from vehicle-treated (41%) rats. The L-channel blocker nifedipine abolished this oestradiol effect on phenylephrine-enhanced HVA currents. Preincubating slices with the N-type channel blocker omega-conotoxin GVIA completely blocked the phenylephrine response, suggesting that the N-type channel is essential. Phenylephrine also stimulated LVA currents in approximately two-thirds of neurones in slices from both vehicle- and oestradiol-treated rats. Our data show that oestradiol increases LVA currents in the VMN. Oestradiol also amplifies α1-adrenergic signalling by increasing the proportion of neurones showing phenylephrine-stimulated HVA currents mediated by N- and L-type calcium channels. In this way, oestradiol may increase excitatory responses to arousing adrenergic inputs to VMN neurones governing oestradiol-dependent reproductive behaviour. [ABSTRACT FROM AUTHOR]

Regulated gene expression in single neurons can be linked to biophysical events and behavior in the case of estrogen-regulated gene expression in neurons in the ventrolateral portion of the ventromedial nucleus (VMN) of the hypothalamus. These cells are essential for lordosis behavior. What genes are coexpressed in neurons that have high levels of mRNAs for estrogen receptors (ERs)? We have been able to isolate and measure certain mRNAs from individual VMN neurons collected from rat hypothalamus. Large numbers of neurons express mRNA for ERα, but these neurons are not identical with the population of VMN neurons expressing the likely gene duplication product, ERβ. An extremely high proportion of neurons expressing either ER also coexpress mRNA for the oxytocin receptor (OTR). This fact matches the known participation of oxytocin binding and signaling in sexual and affiliative behaviors. In view of data that ER and OTR can signal through PKCs, we looked at coexpression of selected PKCs in the same individual neurons. The most discriminating analysis was for triple coexpression of ERs, OTR, and each selected PKC isoform. These patterns of triple coexpression were significantly different for male vs. female VMN neurons. Further, individual neurons expressing ERa could distribute their signaling across the various PKC isoforms differently in different cells, whereas the reverse was not true. These findings and this methodology establish the basis for systematic linkage of the brain's hormone-sensitive signaling pathways to biophysical and behavioral mechanisms in a well studied mammalian system. [ABSTRACT FROM AUTHOR]

Compared to results from a generation of neuropharmacological work, the phenotype of mice lacking the oxytocin (OT) peptide gene was remarkably normal. An important component of the current experiments was to assay OT-knockout (OTKO) and wild-type (WT) littermate control mice living under controlled stressful conditions designed to mimic more closely the environment for which the mouse genome evolved. Furthermore, our experimental group was comprised of an all-female population, in contrast to previous studies which have focused on all-male populations. Our data indicated that aggressive behaviors initiated by OTKO during a food deprivation feeding challenge were considerably more intense and diverse than aggressive behaviors initiated by WT. From the measures of continuous social interaction in the intruder paradigm, it emerged that OTKO mice were more offensively aggressive (attacking rumps and tails) than WT. In a test of parental behaviors, OTKO mice were 100% infanticidal while WT were 16% infanticidal and 50% maternal. Finally,‘alpha females’ (always OTKO) were identified in each experiment. They were the most aggressive, the first to feed and the most dominant at nesting behaviors. Semi-natural environments are excellent testing environments for elucidating behavioral differences between transgenic mice and their WT littermates which may not be ordinarily discernible. Future studies of mouse group behavior should include examining female groupings in addition to the more usual all-male groups. [ABSTRACT FROM AUTHOR]

Background: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has been practised widely over the last 20 years, and it has revolutionized the diagnosis and management of biliary and pancreatic conditions. More recently newer techniques (magnetic resonance imaging) for diagnosis and therapy (laparoscopic biliary surgery) have evolved. The present paper evaluates the risks of ERCP procedures in a modern setting. Methods: A prospective audit of all ERCP carried out by a single unit across two campuses over 12 months was undertaken. All procedures were included and predetermined morbidity criteria were recorded and evaluated by independent observers who did not perform the procedures. Results: During this period 372 procedures were performed. A total of 9.4% of procedures failed to achieve the preprocedure-stated goal. There were five deaths (30-day mortality of 1.3%) and in 16 patients complications were recorded (morbidity of 4.3%). Two clinical and two technical factors were shown to be associated with the morbidity and mortality by multiple logistic regression analysis: diagnosis of sphincter of Oddi dysfunction; presence of jaundice; need to perform percutaneous transhepatic drainage of an obstructed biliary system after a failed endoscopic approach; and multiple ERCP. Conclusions: These results compare favourably with results from other reported series and serve to illustrate the relative safety of diagnostic and therapeutic ERCP. [ABSTRACT FROM AUTHOR]

Aims: Gastric bypass and vertical banded gastroplasty (VBG) are currently the most commonly performed bariatric procedures but neither are ideal. The results of the first 56 patients who had laparoscopic Swedish adjustable gastric banding (SAGB) are presented. Methods: All patients referred for bariatric surgery were considered for SAGB. Each was given the alternative of gastric bypass. Patients with a body mass index of less than 35, large hiatus hernia, under 18 years of age, gastric pathology and significant psychiatric illness were excluded. Preoperative gastroscopy, ultrasonographic examination of the gallbladder and specialist anaesthetic assessment were arranged. All but five patients had attempted laparoscopic procedures. Patients were discharged when they were mobile and could tolerate 1500 ml fluid per day. Patients were given a liquidized diet for 6 weeks. Assessments were made at 6 weeks and 3, 6, 9 and 12 months. Results: Some 56 consecutive patients were followed for up to 12 months. The conversion rate fell from 52 per cent for the first 25 patients to 20 per cent for the last 20. Conversion rates were higher in men and in superobese patients. The duration of a laparoscopic operation fell significantly with experience but was still significantly longer than that of an open procedure (P < 0·004). The length of hospital stay was significantly shorter for laparoscopic procedures (P < 0·001). There was no death and little morbidity. Two bands had to be removed (easily) by open surgery, one for infection and one for a recurrence of gastric herniation. The mean excess weight loss was 60 per cent at 12 months. Greater than 50 per cent of excess body-weight was lost by 48 per cent of patients at 6 months and 69 per cent at 12 months. Band adjustments in most patients achieved further weight loss to compensate for late pouch dilatation. Most failures were in patients who failed to attend. Conclusions: SAGB appears to have many advantages ov... [ABSTRACT FROM AUTHOR]

Functional and neurochemical evidence suggests significant GABA participation in the basomedial hypothalamus. We have investigated electrophysiological effects of GABA using in vitro recording from hypothalamic tissue slices. Exogenous GABA inhibited 94 out of 121 ventromedial hypothalamic (VMN) neurons tested. In sixty-one percent of these GABA-responsive neurons, the inhibitory action of GABA was blocked by GABA antagonists, bicuculline methiodide (BMI) and picrotoxin (PTX). Nevertheless, many (27/69) GABA-responsive neurons were not sensitive to GABA blockers: BMI and PTX failed to antagonize inhibitory action of GABA. Most, if it not all, of these inhibitions can be accounted for by GABA effects, since baclofen powerfully inhibited 42 of 44 neurons tested. In addition to blocking the inhibitory action of exogenous GABA, BMI (55%) and PTX (36%) also caused changes of neuronal activity indicating blockade of intrinsic GABA-ergic action. Altogether, our results showed that, in the VMN, GABA acts through not only GABA but also GABA receptors to inhibit neuronal activity, and that there is tonic inhibition by intrinsic GABA neurons. These GABA actions may participate in behaviorallyrelevant VMN hypothalamic mechanisms. [ABSTRACT FROM AUTHOR]

Electrical activity of neurons in rat hypothalamic ventromedial nucleus was recorded in tissue slices, to investigate central neural mechanisms underlying reduction of food intake caused by TRH and its metabolite, cyclo(His-Pro) [cHP]. Application of TRH had two actions: stimulation of neuronal activity, which was desensitized on closely repeated applications; and modulation of neuronal responses to neurotransmitters, even in the absence of the stimulatory action. The neuromodulatory but not the direct stimulatory action could also be achieved by cHP. The neuromodulatory action is more likely to be a neural mechanism underlying the inhibition of feeding, while other biological functions, unique to TRH, may depend on direct stimulation. In this way, TRH could achieve different biological results through different modes of action on hypothalamic neurons. [ABSTRACT FROM AUTHOR]

The medial medullary reticular formation (mMRF) is probably involved in controlling lordosis, a feminine mating reflex which requires both estrogen priming and appropriate somatosensory input(s). We have recorded single-unit activity of antidromically identified reticulospinal (RS) and unidentified (UI) neurons in mMRF of ovariectomized rats with or without estrogen treatment to investigate neurohormonal mechanisms regulating lordosis. The units were recorded in both acute and chronic preparations, the latter involving implanted 'floating' wire electrodes to allow the influence of estrogen on a particular unit to be followed for several days. A substantial number of RS and UI units in both acute and chronic preparations were either excited or inhibited by a lordosis-eliciting somatosensory stimulation, indicating that the lordosis-eliciting sensory inputs did reach mMRF. The majority of these units responded promptly to the stimulation, and could participate in triggering the short-latency lordosis reflex. Electrical stimulation of several brainstem locations revealed that there was an extensive and specific convergence on mMRF neurons between inputs from the lordosis-eliciting stimulation and mesencephalic central gray, which has been shown to relay lordosis-inducing estrogen influence from hypothalamus to lower brainstem. Therefore, mMRF neurons can receive both the estrogen influence and the lordosis-eliciting inputs and integrate them. Although no apparent estrogen influence was detected in chronic preparations, statistical comparisons of results from acute preparations with or without estrogen treatment suggest that estrogen can increase the proportion of the neurons excited by the lordosis-eliciting stimulation and facilitate neuronal excitability. Both effects are consistent with the prevailing notion that the net lordosis-inducing influence of estrogen is facilitatory, and they may be mechanisms for making lordosis elicitable. [ABSTRACT FROM AUTHOR]