Recombinant human growth hormone, but not insulin-like growth factor-I, enhances central fat loss in postmenopausal women undergoing a diet and exercise program

We examined the effect of recombinant human growth hormone (rhGH) and/or recombinant human insulin-like growth factor-I (rhIGF-I) on regional fat loss in postmenopausal women undergoing a weight loss regimen of diet plus exercise. Twenty-seven women aged 59-79 years, 20-40% above ideal body weight, completed a 12-week program consisting of resistance training 2 days/week and walking 3 days/week, while consuming a diet that was 500 kcal/day less than that required for weight maintenance, Participants were randomly assigned in a double-blind fashion to receive rhGH (0.025 mg/kg BW/day: n=7), rhIGF-I (0.015 mg/kg BW/day: n=7), rhGH + rhIGF-I (n = 6), or placebo (PL: n = 7). Regional and whole body fat mass were determined by dual X-ray absorptiometry. Body fat distribution was assessed by the ratios of trunk fat-to-limb fat (TrF/LimbF) and trunk fat-to-total fat (TrF/TotF), Limb and trunk fat decreased in all groups (p < 0.01). For both ratios of fat distribution, the rhGH treated group experienced an enhanced loss of truncal compared to peripheral fat (p less than or equal to 0.01), with no significant change for those administered rhIGF-I or FL. There was no association between change in fat distribution and indices of cardiovascular disease risk as determined by serum lipid/lipoprotein levels and maximal aerobic capacity. These results suggest that administration of rhGH facilitates a decrease in central compared to peripheral fat in older women undertaking a weight loss program that combines exercise and moderate caloric restriction, although no beneficial effects are conferred to lipid/lipoprotein profiles, Further, the effect of rhGH is not enhanced by combining rhCH with rhIGF-I administration. In addition, rhIGF-I does not augment the loss of trunk fat when administered alone.

Movement-related potentials in Huntington's disease: movement preparation and execution

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD. particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

Contraction of the pelvic floor muscles during abdominal maneuvers

Objective: To determine whether voluntary abdominal muscle contraction is associated with pelvic floor muscle activity. Design: Pelvic floor muscle activity was recorded during contractions of the abdominal muscles at 3 different intensities in supine and standing positions. Setting: Research laboratory. Participants: Six women and 1 man with no histories of lower back pain. Interventions: Not applicable. Main Outcome Measures: Electromyographic activity of the pelvic floor muscles was recorded with surface electrodes inserted into the anus and vagina. These recordings were corroborated by measurements of anal and vaginal pressures. Gastric pressure was recorded in 2 subjects. Results: Pelvic floor muscle electromyography increased with contraction of the abdominal muscles. With strong abdominal contraction, pelvic floor muscle activity did not differ from that recorded during a maximal pelvic floor muscle effort. The pressure recordings confirmed these data. The increase in pressure recorded in the anus and vagina preceded the pressure in the abdomen. Conclusions: In healthy subjects, voluntary activity in the abdominal muscles results in increased pelvic floor muscle activity. The increase in pelvic floor pressure before the increase in the abdomen pressure indicates that this response is preprogrammed. Dysfunction of the pelvic floor muscles can result in urinary and fecal incontinence. Abdominal muscle training to rehabilitate those muscles may be useful in treating these conditions.

Long-term survival of women with breast cancer in New South Wales

Several long-term studies of breast cancer survival have shown continued excess mortality from breast cancer up to 20-40 years following treatment. The purpose of this report was to investigate temporal trends in long-term survival from breast cancer in all New South Wales (NSW) women. Breast cancer cases incident in 1972-1996 (54,228) were derived from the NSW Central Cancer Registry a population-based registry which began in 1972. All cases of breast cancer not known to be dead were matched against death records. The expected survival for NSW women was derived from published annual life tables. Relative survival analysis compared the survival of cancer cases with the age, sex and period matched mortality of the total population. Cases were considered alive at the end of 1996, except when known to be dead. Proportional hazards regression was employed to model survival on age, period and degree of spread at diagnosis. Survival at 5, 10, 15, 20 and 25 years of follow-up was 76 per cent, 65 per cent, 60 per cent, 57 per cent and 56 per cent. The annual hazard rate for excess mortality was 4.3 per cent in year 1, maximal at 6.5 per cent in year 3, declining to 4.7 per cent in year 5, 2.7 per cent in year 10, 1.4 per cent in year 15, 1.0 per cent for years 16-20, and 0.4 per cent for years 20-25 of follow-up. Relative survival was highest in 40-49 year-olds. Cases diagnosed most recently (1992-1996) had the highest survival, compared with cases diagnosed in previous periods. Five-year survival improved over time, especially from the late 1980s for women in the screening age group (50-69 years). Survival was highest for those with localised cancer at diagnosis: 88.4 per cent, 79.1 per cent, 74.6 per cent, 72.7 per cent and 72.8 per cent at 5, 10, 15, 20 and 25 years follow-up (excluding those aged greater than or equal to 70 years). There was no significant difference between the survival of the breast cancer cases and the general population at 20-25 years follow-up. Degree of spread was less predictive of survival 5-20 years after diagnosis, compared with 0-5 years after diagnosis, and was not significant at 20-25 years of follow-up. Relative survival from breast cancer in NSW women continues to decrease to 25 years after diagnosis, but there is little excess mortality after 15 years follow-up, especially for those with localised cancer at diagnosis, and the minimal excess mortality at 20-25 years of follow-up is not statistically significant. (C) 2002 Elsevier Science Ltd. All rights reserved.

Reproducibility of the cycling time to exhaustion at VO(2)peak in highly trained cyclists

The purpose of the present study was to examine, in highly trained cyclists, the reproducibility of cycling time to exhaustion (T-max) at the power output equal to that attained at peak oxygen uptake ((V) over dot O(2)peak) during a progressive exercise test. Forty-three highly trained male cyclists (M +/- SD; age = 25 +/- 6yrs; weight = 75 +/- 7 kg; (V) over dot(2)peak = 64.8 +/- 5.2 ml.kg(-1) . min(-1)) performed two T-max tests one week apart. While the two measures of T-max were strongly related (r = 0.884; p < 0.001), T-max from the second test (245 +/- 57 s) was significantly higher than that of the first (237 +/- 57 s; p = 0.047; two-tailed). Within-subject variability in the present study was calculated to be 6 +/- 6%, which was lower than that previously reported for Tmax in sub-elite runners (25%). The mean T-max was significantly (p < 0.05) related to both the second ventilatory turnpoint (VT2; r = 0.38) and to (V) over dot O(2)peak (r = 0.34). Despite a relatively low within-subject coefficient of variation, these data demonstrate that the second score in a series of two T-max tests may be significantly greater than the first. Moreover the present data show that T-max in highly trained cyclists is moderately related to VT2 and (V) over dot O(2)peak.

The force-velocity relationship of the human soleus muscle during submaximal voluntary lengthening actions

In experiments on isolated animal muscle, the force produced during active lengthening contractions can be up to twice the isometric force, whereas in human experiments lengthening force shows only modest, if any, increase in force. The presence of synergist and antagonist muscle activation associated with human experiments in situ may partly account for the difference between animal and human studies. Therefore, this study aimed to quantify the force-velocity relationship of the human soleus muscle and assess the likelihood that co-activation of antagonist muscles was responsible for the inhibition of torque during submaximal voluntary plantar flexor efforts. Seven subjects performed submaximal voluntary lengthening, shortening(at angular, velocities of +5, -5, +15, -15 and +30, and -30degrees s(-1)) and isometric plantar flexor efforts against an ankle torque motor. Angle-specific (90degrees) measures of plantar flexor torque plus surface and intramuscular electromyography from soleus, medial gastrocnemius and tibialis anterior were made. The level of activation (30% of maximal voluntary isometric effort) was maintained by providing direct visual feedback of the soleus electromyogram to the subject. In an attempt to isolate the contribution of soleus to the resultant plantar flexion torque, activation of the synergist and antagonist muscles were minimised by: (1) flexing the knee of the test limb, thereby minimising the activation of gastrocnemius, and (2) applying an anaesthetic block to the common peroneal nerve to eliminate activation of the primary antagonist muscle, tibialis anterior and the synergist muscles, peroneus longus and peroneus brevis. Plantar flexion torque decreased significantly (P<0.05) after blocking the common peroneal nerve which was likely due to abolishing activation of the peroneal muscles which are synergists for plantar flexion. When normalised to the corresponding isometric value, the force-velocity relationship between pre- and post-block conditions was not different. In both conditions, plantar flexion torques during shortening actions were significantly less than the isometric torque and decreased at faster velocities. During lengthening actions, however, plantar flexion torques were not significantly different from isometric regardless of angular velocity. It was concluded that the apparent inhibition of lengthening torques during voluntary activation is not due to co-activation of antagonist muscles. Results are presented as mean (SEM).

A medial to lateral shift in premovement cortical activity in hemi-Parkinson's disease: Studies of event-related potentials and whole-scalp magneto encephalography

Cortical activity associated with voluntary movement is shifted from medial to lateral premotor areas in Parkinson's disease. This occurs bilaterally, even for unilateral movements. We have used both EEG and MEG to further investigate medial and lateral premotor activity in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. The CNV, recorded from 21 scalp positions in a Go/NoGo task, was maximal over central medial regions in control subjects. For hemi-Parkinson's disease subjects, activity was shifted more frontally, reduced in the midline and lateralised towards the side of greatest basal ganglia impairment. With 143 channel whole-scalp magneto encephalography (MEG) we are further examining asymmetries in supplementary motor/premotor cortical activity prior to self-paced voluntary movement. In preliminary results, one hemi-Parkinson's disease patient with predominantly left-side symptoms showed strong medial activity consistent with a dominant source in the left supplementary motor area (SMA). Three patients showed little medial activity, but early bilateral sources within lateral premotor cortex. Results suggest greater involvement of lateral premotor rather than the SMA prior to movement in Parkinson's disease and provide evidence for asymmetric function of the SMA in hemi- Parkinson's disease, with reduced activity on the side of greatest basal ganglia deficit.

Neural correlates of the emergence of consciousness of thirst

Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15-20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.

Modulation of cytochrome P450 monooxygenase by cadmium chloride in the mouse liver: Involvement of transcription factor Nrf2.

Modulation of the cytochrome P450 (CYP) monooxygenase system and haem oxygenase by cadmium was investigated in male, adult DBA/2J mice treated with a single dose (16 Amol/kg body weight, i.p.) of cadmium chloride (CdCl2), at various time points. Total CYP content of liver microsomes decreased significantly (P < 0.05) at 12, 18, and 24 hours (22%, 47%, and 56%, respectively) after treatment. In contrast, progressive increases of hepatic coumarin 7-hydroxylase (COH) activity (indicative of CYP2A5 activity) were observed at 8 hrs (2-fold), 12 hrs (3-fold), and 7-fold at 18 and 24 hrs. Simultaneously, haem oxygenase activity increased significantly at 4 hours and continued to increase progressively to more than 50-fold compared to control. Liver CYP2A5 mRNA levels increased maximally 12 hours after treatment and decreased to almost half 6 hours later, while western blot analysis showed 2- and 3- fold increase in CYP2A5 apoprotein at 12 and 24 hours. The CYP2A5 mRNA levels in the liver increased after Cd treatment in Nrf2 +/+ but not in Nrf2 / mouse. This study demonstrates that hepatic haem oxygenase and CYP2A5 are upregulated by cadmium. The upregulation of haem oxygenase precedes that of CYP2A5. The strong upregulation of the CYP2A5 both at mRNA and enzyme activity levels, with a simultaneous decrease in the total CYP concentration suggest an unusual mode of regulation of CYP2A5 in response to cadmium exposure, amongst the CYP enzymes. The observed increase in the mRNA but not in protein levels after maximal induction may suggest involvement of post-transcriptional mechanisms in the regulation. Upregulation of CYP2A5 by cadmium in the Nrf2 +/+ mice but not in the Nrf2 / mice indicates a role for this transcription factor in the regulation.

Subtype-selective noncompetitive or competitive inhibition of human alpha(1)-adrenergic receptors by rho-TIA

The 19-amino acid conopeptide (rho-TIA) was shown previously to antagonize noncompetitively alpha(1B)-adrenergic receptors (ARs). Because this is the first peptide ligand for these receptors, we compared its interactions with the three recombinant human alpha(1)-AR subtypes (alpha(1A), alpha(1B), and alpha(1D)). Radioligand binding assays showed that rho-TIA was 10-fold selective for human alpha(1B)- over alpha(1A)- and alpha(1D)-ARs. As observed with hamster alpha(1B)-ARs, rho-TIA decreased the number of binding sites (B-max) for human alpha(1B)-ARs without changing affinity (K-D), and this inhibition was unaffected by the length of incubation but was reversed by washing. However, rho-TIA had opposite effects at human alpha(1A)-ARs and alpha(1D)-ARs, decreasing KD without changing Bmax, suggesting it acts competitively at these subtypes. rho-TIA reduced maximal NE-stimulated [H-3] inositol phosphate formation in HEK293 cells expressing human alpha(1B)-ARs but competitively inhibited responses in cells expressing alpha(1A)- or alpha(1D)-ARs. Truncation mutants showed that the amino-terminal domains of alpha(1B)- or alpha(1D)-ARs are not involved in interaction with rho-TIA. Alanine-scanning mutagenesis of rho-TIA showed F18A had an increased selectivity for alpha(1B)-ARs, and F18N also increased subtype selectivity. I8A had a slightly reduced potency at alpha(1B)-ARs and was found to be a competitive, rather than noncompetitive, inhibitor in both radioligand and functional assays. Thus rho-TIA noncompetitively inhibits alpha(1B)-ARs but competitively inhibits the other two subtypes, and this selectivity can be increased by mutation. These differential interactions do not involve the receptor amino termini and are not because of the charged nature of the peptide, and isoleucine 8 is critical for its noncompetitive inhibition at alpha(1B)-ARs.

Purification and biochemical characterization of a mycelial glucose- and xylose-stimulated beta-glucosidase from the thermophilic fungus Humicola insolens

A mycelial beta-glucosidase from the thermophilic mold Humicola insolens was purified and biochemically characterized. The enzyme showed carbohydrate content of 21% and apparent molecular mass of 94 kDa, as estimated by gel filtration. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed a single polypeptide band of 55 kDa, suggesting that the native enzyme was a homodimer. Mass spectrometry analysis showed amino acid sequence similarity with a P-glucosidase from Humicola grisea var. thermoidea, with about 22% coverage. Optima of temperature and pH were 60 degrees C and 6.0-6.5, respectively. The enzyme was stable up to I h at 50 degrees C and showed a half-life of approximately 44 min at 55 degrees C. The beta-glucosidase hydrolyzed cellobiose, lactose, p-nitrophenyl-beta-D-glucopyranoside, p-nitrophenyl-beta-D-fucopyranoside, p-nitrophenyl-beta-D-xylopyranoside, p-nitrophenyl-beta-D-galactopyranoside, o-nitrophenyl-beta-D-galactopyranoside, and salicin. Kinetic studies showed that p-nitrophenyl-beta-D-fucopyranoside and cellobiose were the best enzyme substrates. Enzyme activity was stimulated by glucose or xylose at concentrations up to 400 mM, with maximal stimulatory effect (about 2-fold) around 40 mM. The high catalytic efficiency for the natural substrate, good thermal stability, strong stimulation by glucose or xylose, and tolerance to elevated concentrations of these monosaccharides qualify this enzyme for application in the hydrolysis of cellulosic materials. (C) 2009 Elsevier Ltd. All rights reserved.

Regulation by the exogenous polyamine spermidine of Na,K-ATPase activity from the gills of the euryhaline swimming crab Callinectes danae (Brachyura, Portunidae)

Euryhaline crustaceans rarely hyporegulates and employ the driving force of the Na,K-ATPase, located at the basal surface of the gill epithelium, to maintain their hemolymph osmolality within a range compatible with cell function during hyper-regulation. Since polyamine levels increase during the adaptation of crustaceans to hyperosmotic media, we investigate the effect of exogenous polyamines on Na,K-ATPase activity in the posterior gills of Callinectes danae, a euryhaline swimming crab. Polyamine inhibition was dependent on cation concentration, charge and size in the following order: spermine > spermidine > putrescine. Spermidine affected K-0.5 values for Na+ with minor alterations in K-0.5 values for K+ and N-H-4(+), causing a decrease in maximal velocities under saturating Na+, K+ and NH4+ concentrations. Phosphorylation measurements in the presence of 20 mu M ATP revealed that the Na,K-ATPase possesses a high affinity site for this substrate. In the presence of 10 mM Na+, both spermidine and spermine inhibited formation of the phosphoenzyme; however, in the presence of 100 mM Na+, the addition of these polyamines allowed accumulation of the phosphoenzyme. The polyamines inhibited pumping activity, both by competing with Na+ at the Na+-binding site, and by inhibiting enzyme dephosphorylation. These findings suggest that polyamine-induced inhibition of Na,K-ATPase activity may be physiologically relevant during migration to fully marine environments. (c) 2008 Elsevier Inc. All rights reserved.

Chronic absence of baroreceptor inputs prevents training-induced cardiovascular adjustments in normotensive and spontaneously hypertensive rats

We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (similar to 9% in WKY and SHR) and MAP reductions (-8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (-13%) and arteriolar wall/lumen ratio (-35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

Genetic polymorphism in an inflammasome component, cervical mycoplasma detection and female infertility in women undergoing in vitro fertilization

The inflammasome is an inducible cytoplasmic structure that is responsible for production and release of biologically active interleukin-1 (IL-1). A polymorphism in the inflammasome component NALP3 has been associated with decreased IL-1 levels and increased occurrence of vaginal Candida infection. We hypothesized that this polymorphism-induced variation would influence susceptibility to infertility. DNA was obtained from 243 women who were undergoing in vitro fertilization (IVF) and tested for a length polymorphism in intron 2 of the gene coding for NALP3 (gene symbol CIAS1). At the conclusion of testing the findings were analyzed in relation to clinical parameters and IVF outcome. The frequency of the 12 unit repeat allele, associated with maximal inflammasome activity, was 62.3% in cases of female infertility vs. 75.6% in cases where only the male partner had a detectable fertility problem (p = 0.0095). Conversely, the frequency of the 7 unit repeat allele was 28.9% in those with a female fertility problem, 17.0% in women with infertile males and 18.4% in idiopathic infertility (p = 0.0124). Among the women who were cervical culture-positive for mycoplasma the frequency of the 7 unit repeat was 53.7% as opposed to 19.5% in those negative for this infection (p < 0.0001). We conclude that the CIAS1 7 unit repeat polymorphism increases the likelihood of mycoplasma infection-associated female infertility. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT = 6 ml/kg and positive end-expiratory pressure (PEEP) = 5 cmH(2)O for 1 h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40 s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP = 40 cmH(2)O), with interposed periods of PIP = 10 cmH(2)O above a PEEP = 15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury. (C) 2009 Elsevier BLV. All rights reserved.