Early insulin sensitivity after restrictive bariatric surgery,inconsistency between HOMA-IR and steady-state plasma glucose levels

BackgroundThe low-grade inflammatory condition present in morbid obesity is thought to play a causative role in the pathophysiology of insulin resistance (IR). Bariatric surgery fails to improve this inflammatory condition during the first months after surgery. Considering the close relation between inflammation and IR, we conducted a study in which insulin sensitivity was measured during the first months after bariatric surgery. Different methods to measure IR shortly after bariatric surgery have given inconsistent data. For example, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels have been reported to decrease rapidly after bariatric surgery, although clamp techniques have shown sustained insulin resistance. In the present study, we evaluated the use of steady-state plasma glucose (SSPG) levels to assess insulin sensitivity 2 months after bariatric surgery.MethodsInsulin sensitivity was measured using HOMA-IR and SSPG levels in 11 subjects before surgery and at 26% excess weight loss (approximately 2 months after restrictive bariatric surgery).ResultsThe SSPG levels after 26% excess weight loss did not differ from the SSPG levels before surgery (14.3 ± 5.4 versus 14.4 ± 2.7 mmol/L). In contrast, the HOMA-IR values had decreased significantly (3.59 ± 1.99 versus 2.09 ± 1.02).ConclusionDuring the first months after restrictive bariatric surgery, we observed a discrepancy between the HOMA-IR and SSPG levels. In contrast to the HOMA-IR values, the SSPG levels had not improved, which could be explained by the ongoing inflammatory state after bariatric surgery. These results suggest that during the first months after restrictive bariatric surgery, HOMA-IR might not be an adequate marker of insulin sensitivity.     

The development and initial validation of the narrative foreclosure scale

Objectives: As people grow older, identity development in later life becomes a more and more relevant topic. Studying processes that hinder or promote identity development in later life is of importance. Within this broader field, there has been a growing interest in narrative foreclosure. Our goal was to develop a short, reliable and easy–to-use instrument measuring narrative foreclosure and to validate this instrument in two samples.Methods: The narrative foreclosure scale (NFS) was validated in two studies with a sample of middle-aged adults (n = 319) and a sample with older adults (n = 174). Several analyses were conducted to assess the psychometric properties, the factor-structure and incremental validity of the scale.Results: Confirmatory factor analyses generally showed an acceptable fit of the two-factor (NF-Future and NF-Past) model to the data in both samples. Both factors of the NFS demonstrated adequate to good internal consistency, with alpha coefficients ranging from .79 for NF-Past in study 2 to .88 for NF-Future in study 1. Construct validity was good as shown by moderate to large correlations to related constructs. The scale adds a unique portion of explained variance to positive mental health, thereby showing the incremental validity of the NFS.Conclusion: A reliable scale is now available that allows to study the premature hindering of identity development in older populations. The use of the NFS as a process measure in studies on the effectiveness of interventions aiming at meaning making and identity development, such as life-review therapy and narrative therapy, is also recommended.     

Long-term exposure to telmisartan as monotherapy or combination therapy: efficacy and safety

This multicentre, open-label extension study to four controlled trials involved 888 patients with mild-to-moderate primary hypertension. Patients received telmisartan 40-80 mg once daily with add-on hydrochlorothiazide (HCTZ; 12.5-25 mg) if necessary and/or other antihypertensives to achieve diastolic blood pressure (DBP) control (<90 mmHg). Treatment continued for up to 4 years. At treatment end, 578 (65.1%) patients were on telmisartan monotherapy, 106 (11.9%) were on telmisartan + HCTZ 12.5 mg, 101 (11.4%) were on telmisartan + HCTZ 25 mg, and 103 (11.6%) were on telmisartan + another antihypertensive + HCTZ. Overall, 84.4% (746/884) patients achieved DBP control. The highest proportion of responders was in the telmisartan monotherapy (40 or 80 mg) treatment category (89.0% 1,511/574 patients]). The mean change in systolic blood pressure (SBP)/DBP from the previous trial baseline to last available trough was -21.2/-17.3 mmHg with telmisartan alone, -24.6/-16.7 mmHg with telmisartan + HCTZ, and - 18.7/-14.9 mmHg with telmisartan + another antihypertensive +/- HCTZ. Most adverse events were of mild-to-moderate intensity and unrelated to treatment. The proportions of patients discontinuing the study due to adverse events, by treatment at onset, were 7.3% (65/888) with telmisartan monotherapy, 6.6% (20/304) with telmisartan + HCTZ and 2.9% (3/103) with telmisartan + another antihypertensive +/- HCTZ. There were 15 deaths during the study, but none was considered drug related. Thus, telmisartan alone or in combination with other antihypertensives achieved and maintained clinically relevant reductions in DBP and SBP. This long-term analysis supports the favourable efficacy and safety profile of telmisartan both as monotherapy and in combination with other antihypertensive drugs.     

On the perceived location of global motion

We measured the effects of coherent motion of one set of dots on the perceived location of Gaussian envelopes formed by luminance modulation of a second set of dots. Perceived shifts in envelope location in the direction of coherent motion were obtained even when the dots forming the envelopes did not physically move in the direction of coherent motion. In such cases, perceived shifts coincided with stimulus configurations that permitted motion integration of the envelope dots with the coherently moving dots, for example, when envelope dots moved in random directions as opposed to being static. In subsequent experiments we explored the type of motion integration underlying the positional shifts obtained. We discounted the possibility that the visual system incorrectly attributes motion signals associated with coherently moving dots to envelope dots by demonstrating that positional shifts could be obtained even when the coherent dots were laterally displaced to either side of the envelope dots such that the regions occupied by the dots did not overlap. We also discounted spatio-temporal summation within the receptive fields of low-spatial-frequency motion-sensitive mechanisms by demonstrating that positional shifts persisted even when the dot displays were high-pass filtered. These results, coupled with the observation that the proportion of coherently moving dots required to produce positional shifts correlated well with global motion thresholds measured for the same dot configurations, suggests that visual processes which underlie motion-dependent positional shifts are based at least in part on cooperative interactions of the type implicated in global motion.     

Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat

The tryptophan (TRP) depletion method has been used as a tool to investigate the effects of acute lowered serotonin levels in the brain. In the present study, the effects of this treatment were investigated in rat models of anxiety (open field test, home cage emergence test), depression (forced swimming test, sucrose preference test) and cognition (spatial discrimination learning, sustained attention). It was found that the repeated TRP depletion increased anxiety-related behaviour in the open field test and increased immobility in the forced swimming test. The other behavioural tests did not reveal effects of treatment. TRP levels were decreased in plasma (34%) and hippocampus (33%) but not in the cortex. Stress-induced corticosterone levels were not affected after TRP depletion. The present findings indicate that repeated moderate TRP depletion leads to anxiogenic and depressive-like behaviour in the rat and corroborates the notion of the involvement of serotonin in these behaviours.     

Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study

BACKGROUND: Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD. OBJECTIVE: To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography. SETTING: University and Veterans' Administration medical center.Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity. MAIN OUTCOME MEASURES: Cerebral AChE activity. RESULTS: Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001). CONCLUSION: Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.     

Overexpression of arginase I in enterocytes of transgenic mice elicits a selective arginine deficiency and affects skin,muscle, and lymphoid development

BACKGROUND: Arginine is required for the detoxification of ammonia and the synthesis of proteins, nitric oxide, agmatine, creatine, and polyamines, and it may promote lymphocyte function. In suckling mammals, arginine is synthesized in the enterocytes of the small intestine, but this capacity is lost after weaning. OBJECTIVE: We investigated the significance of intestinal arginine production for neonatal development in a murine model of chronic arginine deficiency. DESIGN: Two lines of transgenic mice that express different levels of arginase I in their enterocytes were analyzed. RESULTS: Both lines suffer from a selective but quantitatively different reduction in circulating arginine concentration. The degree of arginine deficiency correlated with the degree of retardation of hair and muscle growth and with the development of the lymphoid tissue, in particular Peyer's patches. Expression of arginase in all enterocytes was necessary to elicit this phenotype. Phenotypic abnormalities were reversed by daily injections of arginine but not of creatine. The expression level of the very arginine-rich skin protein trichohyalin was not affected in transgenic mice. Finally, nitric oxide synthase-deficient mice did not show any of the features of arginine deficiency. CONCLUSIONS: Enterocytes are important for maintaining arginine homeostasis in neonatal mice. Graded arginine deficiency causes graded impairment of skin, muscle, and lymphoid development. The effects of arginine deficiency are not mediated by impaired synthesis of creatine or by incomplete charging of arginyl-transfer RNA.     

L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia

BACKGROUND: Accumulating evidence suggests that L-arginine, under conditions of septicemia, not only enhances immune function but also improves protein metabolism. OBJECTIVE: Because the effect of L-arginine administration on the protein metabolism of different organs is unknown, the aim of the study was to elucidate the effects of exogenous supplementation of L-arginine during endotoxemia on the in vivo protein metabolism of individual organs and at the whole-body level. DESIGN: Female pigs were cannulated with catheters in the aorta and the splenic, caval, portal, hepatic, and renal veins, enabling measurements across the hindquarter, portal-drained viscera, liver, and kidneys. Endotoxemia was induced by a 24-h continuous intravenous infusion of endotoxin (3 microg x kg body wt(-1) x h(-1)). At 8 h, an intravenous infusion of L-arginine was started (n = 8). Control pigs (n = 6) received L-alanine. At 24 h, blood was sampled. After cessation of the endotoxin infusion, L-arginine and L-alanine infusions were continued as a supplement in the enterally infused diet. At 48 h, blood samples were obtained during the postendotoxemic and nutritionally supported conditions. Stable isotopes were used to assess protein metabolism and phenylalanine hydroxylation. RESULTS: Both during and after the endotoxin challenge, L-arginine administration enhanced protein synthesis and degradation across the hindquarter and simultaneously reduced protein synthesis and degradation in the liver at equal rates. Protein turnover across the kidneys and portal-drained viscera remained unaffected. After endotoxemia, L-arginine infusion decreased whole-body protein turnover without affecting the net protein balance. CONCLUSION: L-Arginine administration affects protein turnover of the muscle area and the liver oppositely.     

Mapping the oculomotor system: the power of transneuronal labelling with rabies virus

Neuronal networks underlying and related to horizontal eye movements were visualized by retrograde transneuronal tracing with rabies virus from the left medial rectus muscle in guinea pigs. Time-sequenced labelling revealed distinct circuitries involved in particular oculomotor functions, i.e. vestibulo-ocular reflex and saccade generation (brainstem circuitry), adaptive plasticity (cerebellar modules) and possibly motivation and navigation (limbic, hippocampal and cortical structures). Our results provide a first comprehensive road map of the oculomotor system that is unsurpassed by any previous tracing study. We report a number of unexpected findings that illustrate a much vaster and more complicated network for the control of the relatively simple horizontal eye movements than had been envisioned previously.