Do Leptin Levels Predict Weight Gain?—A 5-Year Follow-Up Study in Mauritius

Objective : To investigate whether relative baseline leptin levels predict long-term changes in adiposity and/or its distribution. Research Methods and Procedures : In a longitudinal study of 2888 nondiabetic Mauritians aged 25 years to 74 years who participated in population-based surveys in 1987 and 1992, changes in body mass index (BMI), waist/hip ratio (WHR), and waist circumference were compared between “hyperleptinemic,” “normoleptinemic,” and “hypoleptinemic” groups. “Relative leptin levels” were calculated as standardized residuals from the regression of log₁₀ leptin on baseline BMI to provide a leptin measure independent of BMI. Analyses were performed within each sex. A linear regression model was used to assess the effect of standardized residuals on changes in BMI, WHR, and waist circumference, independent of baseline BMI, age, fasting insulin, and ethnicity. Results : After adjusting for age and baseline BMI by analysis of covariance, there was no difference in changes in BMI, WHR, or waist circumference between men with low, normal, or high relative leptin levels. Among women, there was a significant difference in ΔWHR across leptin groups, such that the largest increase occurred in the “normal” leptin group. For both men and women, the linear regression models explained ?10% of variation in dependent variables, and the only significant independent variables were age, BMI, and being of Chinese origin, compared with Indian origin. Discussion : These findings do not support a role for leptin concentration in predicting weight gain or changes in fat distribution in adults over a 5-year period.     

Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance

Walshe, Andrew D., Greg J. Wilson, and Gertjan J. C. Ettema.Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance. J. Appl. Physiol. 84(1): 97-106, 1998.To isolateany difference muscular contraction history may have on concentric workoutput, 40 trained male subjects performed three separate isokineticconcentric squats that involved differing contraction histories:1) a concentric-only (CO) squat, 2) a concentric squat preceded by anisometric preload (IS), and 3) astretch-shorten cycle (SSC) squat. Over the first 300 ms of theconcentric movement, work output for both the SSC and IS conditions wassignificantly greater (154.8 ± 39.8 and 147.9 ± 34.7 J, respectively; P < 0.001) comparedwith the CO squat (129.7 ± 34.4 J). In addition, work output afterthe SSC test over the first 300 ms was also significantly larger thanthat for the corresponding period after the IS protocol(P < 0.05). There was no difference in normalized, integrated electromyogram among any of the conditions. It was concluded that concentric performance enhancement derived from apreceding stretch of the muscle-tendon complex was largely due to theattainment of a higher active muscle state before the start of theconcentric movement. However, it was also hypothesized that contractileelement potentiation was a significant contributor to stretch-inducedmuscular performance under these conditions.

     

Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure

In congestive heart failure (CHF), themechanisms of exercise-induced sympathoexcitation are poorly defined.We compared the responses of sympathetic nerve activity directed tomuscle (MSNA) and to skin (SSNA, peroneal microneurography) duringrhythmic handgrip (RHG) at 25% of maximal voluntary contraction andduring posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similarin both groups (CHF patients, n = 12;controls, n = 10). However, duringPHG-CA, in the controls MSNA returned to baseline, whereas it remainedelevated in CHF patients (P < 0.05).Similarly, at end exercise, the increase in SSNA was comparable in bothgroups (CHF patients, n = 11;controls, n = 12), whereas SSNAremained elevated during PHG-CA in CHF patients but not in the controls (P < 0.05). In a separate controlgroup (n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNAduring PHG-CA. ³¹P-nuclear magneticresonance spectroscopy during RHG demonstrated significant muscleacidosis and accumulation of inorganic phosphate in CHF patients(n = 7) but not in controls(n = 9). We conclude that in CHFpatients rhythmic forearm exercise leads to premature fatigue andaccumulation of muscle metabolites. The prominent PHG-CA response ofMSNA and SSNA in CHF patients suggests activation of the musclemetaboreflex. Because, in contrast to controls, in CHF patients bothMSNA and SSNA appear to be under muscle metaboreflex control, themechanisms and distribution of sympathetic outflow during exerciseappear to be different from normal.

     

Patch Defence in the Parasitoid Wasp Trissolcus basalis (Insecta: Scelionidae): The Time Structure of Pairwise Contests,and the ‘Waiting Game’

Aggressive defence of host patches has been reported in many parasitoid wasps, but rarely examined in quantitative detail. One aspect of interest is that foraging female parasitoids do not simply consume resource patches, they invest offspring in them. Therefore, patch defence in parasitoids can involve not only resource defence prior to oviposition, but also postoviposition defence of offspring (maternal care). In this paper, the time-structure and sequence of pairwise agonistic contests between females of the parasitoid Trissolcus basalis (Wollaston) (Hymenoptera: Scelionidae) are analysed. Three main periods were evident in contests. In the first period, both females exploited the patch with no aggression. After the initiation of fighting, they entered a ‘contest period’, during which resident and intruder roles became clearly resolved. The resident then usually guarded the patch for up to several hours before leaving. This signalled the beginning of the third period, in which the intruder returned to superparasitise the patch. During the contest period, resident behaviour initially reflected the trade-off between exploiting fresh hosts, and defending those it had already parasitised from the intruder, which persistently returned to the patch to try and oviposit, with some success. However, when the patch became fully parasitised, both resident and intruder switched to a ‘waiting game’, in which they sat motionless for extended periods, the resident on the patch and the intruder at a distance. These stand-offs were punctuated by occasional aggressive patrolling by the resident, and cryptic returns to the palch by the intruder. This waiting game appears to be an informational war of attrition, suggesting a conceptual basis for modelling patch-leaving decisions using evolutionary game theory.     

C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis

C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72) in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05). Reduction in albuminuria was also reported in the C-peptide group (p<0.05). In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001) reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05), glomerular volume (p<0.00001), and mesangial matrix area (p<0.00001) in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472)     

The Vaginal Microbiota over an 8- to 10-Year Period in a Cohort of HIV-Infected and HIV-Uninfected Women

BackgroundWe identified predominant vaginal microbiota communities, changes over time, and how this varied by HIV status and other factors in a cohort of 64 women.MethodsBacterial DNA was extracted from reposited cervicovaginal lavage samples collected annually over an 8–10 year period from Chicago Women’s Interagency HIV Study participants: 22 HIV-negative, 22 HIV-positive with stable infection, 20 HIV-positive with progressive infection. The vaginal microbiota was defined by pyrosequencing of the V1/V2 region of the 16S rRNA gene. Scheduled visits included Bacterial vaginsosis (BV) screening; clinically detected cases were referred for treatment. Hierarchical clustering identified bacterial community state types (CST). Multinomial mixed effects modeling determined trends over time in CST, by HIV status and other factors.ResultsThe median follow-up time was 8.1 years (range 5.5–15.3). Six CSTs were identified. The mean relative abundance (RA) of Lactobacillus spp. by CST (with median number of bacterial taxa) was: CST-1–25.7% (10), CST-2–27.1% (11), CST-3–34.6% (9), CST-4–46.8% (9), CST-5–57.9% (4), CST-6–69.4% (2). The two CSTs representing the highest RA of Lactobacillus and lowest diversity increased with each additional year of follow-up (CST-5, adjusted odds ratio (aOR) = 1.62 [95% CI: 1.34–1.94]; CST-6, aOR = 1.57 [95 CI: 1.31–1.89]), while the two CSTs representing lowest RA of Lactobacillus and higher diversity decreased with each additional year (CST-1, aOR = 0.89 [95% CI: 0.80–1.00]; CST-2, aOR = 0.86 [95% CI: 0.75–0.99]). There was no association between HIV status and CST at baseline or over time. CSTs representing lower RA of Lactobacillus were associated with current cigarette smoking.ConclusionsThe vaginal microbial community significantly improved over time in this cohort of women with HIV and at high risk for HIV who had regular detection and treatment referral for BV.     

A Four-Compartment Metabolomics Analysis of the Liver,Muscle, Serum,and Urine Response to Polytrauma with Hemorrhagic Shock following Carbohydrate Prefeed

Objective

Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

Methods

Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

Results

Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

Conclusions

Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.     

Comparison of Isoflurane and α-Chloralose in an Anesthetized Swine Model of Acute Pulmonary Embolism Producing Right Ventricular Dysfunction

Pulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO_2, end-tidal CO_2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO₂ (98% ± 3% compared with 95% ± 1%), end-tidal CO₂ (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE.Abbreviations: LV, left ventricle; PAP, pulmonary arterial pressure; PE, pulmonary embolism; RV, right ventriclePulmonary embolism (PE) is one of the leading causes of noncardiac sudden death in Western nations and is the third most common cause of cardiovascular morbidity.^4,6,7,18 In survivors, severe PE damages the right heart, leading to a clinical course complicated by hypotension and circulatory shock, suggesting acute right heart failure in about 10% of patients and followed by persistent pulmonary hypertension or right ventricular dysfunction and dyspnea in at least 15% of patients.^{9,15,16,23,29} To test treatments to reduce right heart failure, a standardized model that is repeatable, accurate, and precise and that mimics the gross pathologic, cardiovascular, pulmonary, autonomic, hematologic, biochemical, and cellular characteristics of PE in humans with disease is needed.⁸Three lines of rationale favor domestic pigs as a model for PE. Several publications, using different methods of anesthesia, have found that swine manifest hemodynamic responses similar to those of humans in the presence of autologous PE, including elevated heart rate, decreased cardiac output, and reduced oxygen saturation.^2,12,30 Swine have similar platelet concentrations, and their coagulation profile on thromboelastography has been shown to be similar to humans, with the exception of higher fibrin crosslinking but less fibrin, leading to resistance to plasmin.^5,11,19,34 Market swine, which would otherwise be destined for slaughter, are relatively cost effective compared with other large animals and are of sufficient size for placement of an adult pulmonary arterial catheter for measurement of pulmonary vascular resistance in a closed-chest preparation.In view of the differences in the hemodynamic effects of different anesthetic agents, the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. However, current literature lacks a methodologic publication that compares the cardiovascular, right ventricular, pulmonary, and hematologic responses to PE in closed-chest swine models incorporating different anesthetic regimens.Figure 1 presents features of an ideal animal model for the purpose of testing treatments for PE. To develop a swine model of PE that closely resembles this physiologic ideal model, we induced PE in swine maintained in a surgical plane of anesthesia with either isoflurane or α-chloralose. Each of these agents has potential advantages and disadvantages. Isoflurane can be titrated minute by minute but causes undesirable vasodilation, whereas α-chloralose is believed to preserve cardiovascular reflexes but requires heating to dissolve and continuous infusion or repeated boluses.^26,35 We hypothesized that, compared with isoflurane, α-chloralose would meet more of the features described in Figure 1.Open in a separate windowFigure 1.Desirable features of large animal model of severe submassive PE designed for translational research.