Hypertrophic muscle growth and metabolic efficiency were impaired by chronic heat stress, improved by zilpaterol supplementation, and not affected by ractopamine supplementation in feedlot lambs1.

Feedlot performance is reduced by heat stress and improved by ß adrenergic agonists (ßAA). However, the physiological mechanisms underlying these outcomes are not well characterized, and anecdotal reports suggest that ßAA may confound the effects of heat stress on wellbeing. Thus, we sought to determine how heat stress and ßAA affect growth, metabolic efficiency, and health indicators in lambs on a feedlot diet. Wethers (38.6 ± 1.9 kg) were housed under thermoneutral (controls; n = 25) or heat stress (n = 24) conditions for 21 d. In a 2 × 3 factorial, their diets contained no supplement (unsupplemented), ractopamine (ß1AA), or zilpaterol (ß2AA). Blood was collected on days -3, 3, 9, and 21. On day 22, lambs were harvested and ex vivo skeletal muscle glucose oxidation was determined to gauge metabolic efficiency. Feet and organ tissue damage was assessed by veterinary pathologists. Heat stress reduced (P < 0.05) feed intake by 21%, final bodyweight (BW) by 2.6 kg, and flexor digitorum superficialis (FDS) muscle mass by 5%. ß2AA increased (P < 0.05) FDS mass/BW by 9% and average muscle fiber area by 13% compared with unsupplemented lambs. Blood lymphocytes and monocytes were greater (P < 0.05) in heat-stressed lambs, consistent with systemic inflammation. Plasma insulin was 22% greater (P < 0.05) and glucose/insulin was 16% less (P < 0.05) in heat-stressed lambs than controls. Blood plasma urea nitrogen was increased (P < 0.05) by heat stress on day 3 but reduced (P < 0.05) on days 9 and 21. Plasma lipase and lactate dehydrogenase were reduced (P < 0.05) by heat stress. Glucose oxidation was 17% less (P < 0.05) in muscle from heat-stressed lambs compared with controls and 15% greater (P < 0.05) for ß2AA-supplemented compared with unsupplemented lambs. Environment and supplement interacted (P < 0.05) for rectal temperature, which was increased (P < 0.05) by heat stress on all days but more so (P < 0.05) in ß2AA-supplemented lambs on days 4, 9, and 16. Heat stress increased (P < 0.05) the frequency of hoof wall overgrowth, but ßAA did not produce any pathologies. We conclude that reduced performance in heat-stressed lambs was mediated by reduced feed intake, muscle growth, and metabolic efficiency. ß2AA increased muscle growth and improved metabolic efficiency by increasing muscle glucose oxidation, but no such effects were observed with ractopamine. Finally, ßAA supplementation was not detrimental to health indicators in this study, nor did it worsen the effects of heat stress.

EFFECT OF ASTRAGALOSIDE ON VITAMIN D-RECEPTOR EXPRESSION AFTER ENDOTHELIN-1-INDUCED CARDIOMYOCYTE INJURY.

BACKGROUND: Astragaloside, which is one of the main components of Astragalus membranaceus, has been widely used in the treatment of congestive heart failure in China, and it can protect cardiomyocytes. Its mechanism of action remains unclear. Therefore, the present study was carried out to investigate the influence of astragaloside on rat cardiomyocytes stimulated with endothelin-1 (ET-1), and explored the underlying mechanism. MATERIALS AND METHODS: ET-1 was used to stimulate primary rat cardiomyocytes and establish a cardiomyocyte hypertrophy model. Different astragaloside doses were administered in combination with ET-1. Cardiomyocyte hypertrophy and apoptosis were examined using transmission electron microscopy (TEM) and flow cytometry, respectively. The molecular mechanism was explored by analyzing the mRNA of the vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1(CYP27B), cytochrome P450 family 24 subfamily A member 1(CYP24A) and renin mRNA levels by quantificational real-time polymerase chain reaction(qRT-PCR). RESULTS: Rat cardiomyocyte hypertrophy model was established successfully. Astragaloside administration significantly affected cell apoptosis and significantly inhibited ET-1-induced cardiomyocyte hypertrophy in a dose-dependent manner. Astragaloside treatment affected the expression of signaling molecules in the vitamin D axis. CONCLUSION: Astragaloside inhibits ET-1-induced cardiomyocyte hypertrophy. This effect can be reversed by regulating the levels of the relevant factors in the vitamin D axis.

A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.

[Contrast study of acupuncture anesthesia and local anesthesia: their effects on the blood pressure and the heart rate in chronic rhinitis patients accompanied inferior turbinate hypertrophy in low temperature radiofrequency ablation].

OBJECTIVE: To compare the effects of acupuncture anesthesia (AA) and local anesthesia (LA) on the blood pressure (BP) and the heart rate (HR) in chronic rhinitis patients accompanied inferior turbinate hypertrophy in low temperature radiofrequency ablation (RFA). METHODS: Totally 61 chronic rhinitis patients accompanied inferior turbinate hypertrophy were randomly assigned to the AA group (31 cases) and the control group (30 cases). All patients received RFA respectively under AA and RA. Their heart rate (HR), systolic pressure (SP), diastolic pressure (DP), and mean pressure (MP) were recorded and compared at 10 minutes after their entry into the operating room, immediately before surgery, intraoperation, and 5 min after operation. RESULTS: When compared with the control group at the same time points, the SP, DP, MP, and HR all decreased at intraoperation and 5 min after operation in the AA group. There was statistical difference in the SP on the right side at the 2nd melting point and the HR on the left side at the 2nd melting point between the two groups (P < 0.05). Compared with the same group at 10 min after entry into the operating room, the SP on the right side at the 1st melting point, the SP, DP, and MP on the right side at the 2nd melting point, the SP, DP, and MP on the left side at the 1st melting point, and the SP on the left side at the 2nd melting point all obviously increased with statistical difference (P < 0.05, P < 0.01). When compared with the same group at 10 min after entry into the operating room and immediately before surgery, there was no statistical difference in the SP, DP, MP, or HR of the AA group at intraoperation and 5 min after operation (P > 0.05). When compared with the same group at 10 min after entry into the operating room and immediately before surgery, there was no statistical difference in HR of the control group at intraoperation and 5 min after operation (P > 0.05). CONCLUSION: Patients undergoing AA had less fluctuation of the BP and the HR, indicating AA had better analgesic effects.

Gαq-protein carboxyl terminus imitation polypeptide GCIP-27 attenuates proliferation of vascular smooth muscle cells and vascular remodeling in spontaneously hypertensive rats.

Gq-protein is located at the convergent point in signal transduction pathways leading to vascular remodeling. The carboxyl terminus of Gα-subunit plays a vital role in G-protein-receptor interaction. The present study was designed to explore the effects of a synthetic Gαq carboxyl terminus imitation peptide, namely GCIP-27, on vascular smooth muscle cells (VSMC) in vitro and vascular remodeling in spontaneous hypertensive rats (SHR). Hyperplasia and hypertrophy of VSMC wre determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, [(3)H]-thymidine and [(3)H]-leucine incorporation, and [Ca(2+)](i) was measured with Fluo-3/AM staining. Systolic blood pressure (SBP), the ratio of media thickness to lumen diameter (MT/LD) of aorta, collagen content, and phospholipase C activity in aorta were measured in SHR. GCIP-27 (3-100 µg/l) significantly decreased proliferation activity, protein content, incorporation of [(3)H]-thymidine and [(3)H]-leucine, and [Ca(2+)](i) level in VSMC. SBP, MT/LD, collagen content, and phospholipase C activity in aorta of SHR were decreased significantly in GCIP-27 (7, 20, 60 µg/kg)-treated groups and losartan (6 mg/kg) group compared with vehicle group. In conclusion, GCIP-27 could inhibit vascular remodeling effectively in vitro and in vivo.

Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload.

BACKGROUND: Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats. METHODS AND RESULTS: Male Wistar rats (aged 3-4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham operation (Sham). Experiments were performed on excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin43, was markedly reduced in AoB compared with Sham hearts. CONCLUSIONS: Using a small-animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin43 expression, and marked conduction abnormalities.

Attenuation of renal dysfunction by anti-hyperglycemic compound isolated from fruit pulp of Eugenia jambolana in streptozotocin-induced diabetic rats.

The renal protective effect of an active principle isolated from the aqueous extract of fruit pulp of Eugenia jambolana was investigated in streptozotocin (45 mg/kg body weight)-induced severely diabetic rats (FBG > or = 300 mg/dl). For isolation of active principle, crude aqueous extract of E. jambolana fruit pulp was subjected to purification by ion-exchange column chromatography, which yielded a partially purified compound (FII), which on further purification by rechromatography gave a purified active compound (FIIc). Purity of FIIc was confirmed by high pressure liquid chromatography. Detailed UV, NMR, IR spectra suggested that FIIc is a small aliphatic organic compound having molecular formula C4H7O4N. Oral administration of FIIc to diabetic rats (10, 15 and 20 mg/kg body weight per day for a period of 60 days) produced significant (P<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with FIIc (15 mg/kg body wt.) showed significant (P<0.001) improvement in body weight, blood urea, plasma creatinine levels, urinary volume, urinary sugar and microalbuminuria. Renal hypertrophy, assessed as the ratio of the weight of the two kidneys to total body weight was also significantly (P<0.05) improved after treatment with FIIc. The above results suggest that FIIc possesses significant nephroprotective activity.

Gray matter changes related to chronic posttraumatic headache.

BACKGROUND: Although up to 15% of patients with whiplash injury develop chronic headache, the basis and mechanisms of this posttraumatic headache are not well understood. METHODS: Thirty-two patients with posttraumatic headache following whiplash injury were investigated within 14 days after the accident and again after 3 months using magnetic resonance-based voxel-based morphometry. Twelve patients developed chronic headache lasting longer than 3 months and were studied a third time after 1 year. RESULTS: Patients who developed chronic headache revealed decreases in gray matter in the anterior cingulate and dorsolateral prefrontal cortex after 3 months. These changes resolved after 1 year, in parallel to the cessation of headache. The same patients who developed chronic headache showed an increase of gray matter in antinociceptive brainstem centers, thalamus, and cerebellum 1 year after the accident. CONCLUSION: We demonstrate adaptive gray matter changes of pain processing structures in patients with chronic posttraumatic headache in regard to neuronal plasticity, thus providing a biologically plausible basis for this common, disabling problem.

Decongestion test in patients with allergic rhinitis: functional evaluation of nasal airflow.

BACKGROUND: Rhinomanometry measures nasal airflow that is frequently impaired in allergic rhinitis. Decongestion tests consist of spraying an intranasal vasoconstrictor drug to evaluate the reversibility of nasal airflow limitation. The aim of this study was to evaluate the decongestion test in patients with seasonal allergic rhinitis (SAR) caused by pollen sensitization, perennial allergic rhinitis (PAR) caused by sensitization to perennial allergens only, or mixed allergic rhinitis (MAR) caused by sensitization to both allergens. METHODS: One hundred twenty-three subjects (112 men and 11 women, mean age, 22.9 +/- 5.7 years) were studied; 40 subjects had PAR, 43 subjects had MAR, and 40 subjects had SAR. Total symptom score (including: nasal itching, sneezing, rhinorrhea, and nasal obstruction) was assessed. Rhinomanometry and decongestion tests were performed in all subjects. RESULTS: Nasal symptom severity was superimposable in the three groups (p was not significant). After decongestion tests, an increase of nasal airflow and a decrease of nasal resistance was shown in PAR (p < 0.01), MAR (p < 0.001), and SAR subjects (p < 0.001). The intergroup analysis showed that SAR patients had less reversibility than PAR (p < 0.01). CONCLUSION: This study provides the first evidence of the different response to decongestion tests, taking into consideration the causal allergens.

Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation.

OBJECTIVE: To investigate the role of nitric oxide (NO) and interleukin-1 in (IL-1) joint inflammation and cartilage destruction during zymosan-induced gonarthritis (ZIA). METHODS: Monarticular arthritis was elicited by intraarticular injection of zymosan. The effect of NO deficiency on arthritis was studied in mice with genetically disrupted NOS2. The role of IL-1 was examined by treating wild-type mice with neutralizing anti-murine IL-1(alpha+beta) antibodies. Joint swelling was measured externally by the increased uptake of circulating 99mtechnetium pertechnetate. Proteoglycan (PG) synthesis was assessed using 35S-sulfate incorporation into patellae ex vivo. Histology evaluated exudation and infiltration of leukocytes and the extent of cartilage destruction. RESULTS: The proinflammatory mediators NO, IL-1, and IL-6 were released by the articular tissues during the first hours of inflammation. Interestingly, anti-IL-1 treatment moderately reduced, and NOS2 deficiency moderately enhanced, joint swelling. However, the influx of neutrophils into the joint occurred independently of IL-1 and NOS2 activities. In the first week of inflammation, chondrocyte PG synthesis was significantly suppressed and chondrocytes became unresponsive to their essential anabolic factor, insulin-like growth factor 1 (IGF-1). Anti-IL-1 treatment or NOS2 deficiency prevented the inhibition of PG synthesis, and the chondrocytes remained IGF-1 responsive. Intraarticular injections of IL-1alpha into NOS2-deficient mice did not affect PG synthesis, thus proving that NO mediated this IL-1 effect in vivo. Furthermore, histology showed that cartilage PG loss was markedly ameliorated in NOS2-deficient and anti-IL-1-treated mice. Intermediate cartilage pathology was found in mice that were heterozygous for disrupted NOS2. CONCLUSION: IL-1 and NO play a minor role in edema and neutrophil influx, but a major role in cartilage destruction of ZIA. In this model of murine arthritis, cartilage destruction was, for the most part, caused by pronounced suppression of PG synthesis and IGF-1 unresponsiveness of the chondrocytes, which were induced by de novo-synthesized IL-1 and were mediated by NOS2 activation.

Influence of neck muscles on mouth pressure response to cervical magnetic stimulation.

Measurement of mouth pressure (Pm) in response to electrical phrenic nerve stimulation (Es) provides a simple noninvasive means to assess diaphragm function. An even simpler measure would be to use the Pm twitch response (Pm,t) to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects diaphragm function only if the corresponding INM contraction does not produce inspiratory pressures by itself. In patients with recent-onset bilateral diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero; however, INM hypertrophy could change this situation and lead CMS-Pm,t to overestimate the performance of the diaphragm. To address this issue, we studied nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of inspiratory neck muscles. The response to CMS was described in terms of diaphragm electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG response to CMS could be observed in most cases, and CMS was always associated with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck muscle hypertrophy can significantly influence the Pm response to CMS. This should be taken into account when using the CMS-Pm combination in patients with possible chronic diaphragm dysfunction.

Compensatory hypertrophy and adaptation in the cortical collecting duct.

The cortical collecting duct (CCD) undergoes hypertrophy and functional adaptation following reduction of renal mass. The nature and mechanisms of these changes have been investigated using microperfusion of isolated CCD from rabbit remnant kidneys. By 1 week after reduction of renal mass, tubule hypertrophy and increased sodium transport are fully developed. The transport adaptations are specific or selective, since bicarbonate transport in these CCD is unchanged. Mineralocorticoids may play an important role in the hypertrophy and increased sodium transport, since plasma aldosterone increases early after reduction of renal mass. Also, adrenalectomy abolishes the changes in size and sodium transport, even with supplementation of aldosterone to unstressed physiologic levels. Epidermal growth factor also has immediate effects on CCD sodium transport; however, the direction of the effect is opposite--an inhibition of transport.