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51.
Intramuscular injections with botulinum toxin A (BTX-A) lead to a rapid decrease in muscle mass and force, but the effect of this drug on bone development is unclear. In the present pilot study we evaluated the effect of a one-time injection of BTXA in growing rabbits. Twelve young (weight 1.5 kg) New Zealand rabbits were randomly assigned to receive either BTX-A (total dose 8 units per kg body weight) or sodium chloride 0.9% injections into the left quadriceps and gastrocnemius muscles. Both groups continued to gain weight in a similar manner following the injection. However, when the animals were sacrificed at five weeks after the injection, the group receiving BTX-A had a significant deficit (of 10%) in gastrocnemius muscle mass on the injected side, whereas no significant side-difference was found for the quadriceps. BTX-A injections did not affect the length of the tibia. Nevertheless, bone mineral content of the whole tibia, as measured by dual-energy X-ray absorptiometry, was 7% lower in the BTX-A injected side than on the contralateral side. Peripheral quantitative computed tomography showed that this bone mass deficit was larger in the metaphysis than in the epiphysis or diaphysis. In the diaphysis, the bone mass deficit was due to a reduction in cross-sectional bone dimensions, which equally affected the cross-section of the entire bone, the cortical compartment and the marrow space. BTX-A injections did not have a detectable effect on cortical bone mineral density. The bone mass deficit in the diaphysis thus appeared to be caused by a lack of periosteal bone apposition rather than increased endocortical or intracortical resorption. These preliminary data suggest that intramuscular BTX-A injections can have a deleterious effect on the development of bones that are loaded by the injected muscles. 相似文献
52.
Harris ML Hobson AR Hamdy S Thompson DG Akkermans LM Aziz Q 《American journal of physiology. Gastrointestinal and liver physiology》2006,291(5):G950-G958
Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in the neurophysiological characterization of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess the reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in the anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials. Healthy subjects (n = 8, median age 33 yr) were studied on three separate occasions. Variability, tolerance, and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring rectal evoked potential whereas RBD in all cases induced the strong urge to defecate. Rectal intraclass correlation coefficient (ICC) for ES and RBD (0.82 and 0.72, respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not at sensory threshold. Only sphincter ICC for ES at pain showed acceptable between-study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES (P < 0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into the physiological characteristics of visceral afferent pathways in health and disease. 相似文献
53.
Mistry S Rothwell JC Thompson DG Hamdy S 《American journal of physiology. Gastrointestinal and liver physiology》2006,291(4):G666-G671
Human swallowing involves the integration of sensorimotor information with complexities such as taste; however, the interaction between the taste of food and its effects on swallowing control remains unknown. We assessed the effects of pleasant (sweet) and aversive (bitter) tastes on human cortical swallowing motor pathway excitability. Healthy adult male volunteers underwent a transcranial magnetic stimulation (TMS) mapping study (n = 9, mean age: 34 yr) to assess corticobulbar excitability before and up to 60 min after 10-min liquid infusions either 1) as swallowing tasks or 2) delivered directly into the stomach. Infusions were composed of sterile water (neutral), 10% glucose (sweet), and 0.5 mM quinine hydrochloride (bitter). The order of delivery was randomized, and each infusion was given on separate days. Pharyngeal motor-evoked potentials (PMEPs) were recorded from an intraluminal catheter as a measure of corticobulbar excitability and compared using repeated-measures and one-way ANOVA. After the swallowing task (water, glucose, or quinine), repeated-measures ANOVA revealed a significant time interaction across tastants (P = 0.01). One-way ANOVA for each taste showed changes in PMEP amplitudes for both quinine (P = 0.001) and glucose (P = 0.009) solutions but not for water (P = 0.1). Subsequent t-tests showed that glucose and quinine reduced PMEPs by 47% (SD 34) and 37% (SD 54), respectively, at 30 min (P = 0.03). No changes were observed after the infusion of any solution directly into the stomach (P = 0.51). In conclusion, cortical swallowing pathways are similarly modulated by both sweet and bitter tasting stimuli. Changes likely reflect a close interaction between taste and swallowing activity mediated in the central nervous system. 相似文献
54.
55.
Pilet H Vachiéry N Berrich M Bouchouicha R Durand B Pruneau L Pinarello V Saldana A Carasco-Lacombe C Lefrançois T Meyer DF Martinez D Boulouis HJ Haddad N 《Journal of microbiological methods》2012,88(2):205-211
Ehrlichia ruminantium (ER) is a member of the order Rickettsiales transmitted by Amblyomma ticks. This obligatory intracellular bacterium is the causative agent of a fatal disease in ruminants, named heartwater. It represents a constraint on breeding development in sub-Saharan Africa and in the Caribbean. The genetic diversity of the strains of ER, which could be a limiting factor to obtain effective vaccines, needs to be better characterized. For this purpose, we developed a molecular typing technique based on the polymorphism of variable number tandem repeat (VNTR) sequences, MLVA (multiple locus VNTR analysis).Eight (out of 21) VNTR candidates were validated using 17 samples representing a panel of ER strains from different geographical origins from West, South Africa, and Caribbean areas and in ER infected ticks and goat tissues. This result demonstrated the ability of these VNTRs to type a wide range of strains. The stability of the selected VNTR markers was very good, at the time scale needed for epidemiological purposes: in particular, no difference in the VNTR profiles was observed between virulent and attenuated strains (for Gardel and Senegal strains) and between strains (Gardel and Blonde strains) isolated in the same area 19 years apart. We validated the strong discriminatory power of MLVA for ER and found a high level of polymorphism between the available strains, with 10 different profiles out of 13 ER strains.The MLVA scheme described in this study is a rapid and efficient molecular typing tool for ER, which allows rapid and direct typing of this intracellular pathogen without preliminary culture and gives reliable results that can be used for further epidemiological studies. 相似文献
56.
C Treins S Alliouachene R Hassouna Y Xie MJ Birnbaum M Pende 《Molecular and cellular biology》2012,32(19):4001-4011
Signaling downstream of mechanistic target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) controls specific and distinct aspects of insulin action and nutrient homeostasis in an interconnected and as yet unclear way. Mice lacking the mTORC1 substrate S6 kinase 1 (S6K1) maintain proper glycemic control with a high-fat diet. This phenotype is accompanied by insulin hypersensitivity, Akt- and AMP-activated kinase upregulation, and increased lipolysis in adipose tissue and skeletal muscle. Here, we show that, when S6K1 inactivation is combined with the deletion of the mTORC2 substrate Akt2, glucose homeostasis is compromised due to defects in both insulin action and β-cell function. After a high-fat diet, the S6K1(-/-) Akt2(-/-) double-mutant mice do not become obese, though they are severely hyperglycemic. Our data demonstrate that S6K1 is required for pancreatic β-cell growth and function during adaptation to insulin resistance states. Strikingly, the inactivation of two targets of mTOR and phosphatidylinositol 3-kinase signaling is sufficient to reproduce major hallmarks of type 2 diabetes. 相似文献
57.
58.
Rim Lajnef Mejdi Snoussi Jesús López Romalde Cohen Nozha Abdennaceur Hassen 《World journal of microbiology & biotechnology》2012,28(12):3345-3363
The antibiotic resistance patterns and the plasmids profiles of the predominant etiological agent responsible for vibriosis in Tunisia, V. alginolyticus were studied to contribute to control their spread in some Mediterranean aquaculture farms and seawater. The sixty-nine V. alginolyticus strains isolated from different marine Tunisian biotopes (bathing waters, aquaculture and conchylicole farms and a river connected to the seawater during the cold seasons) were multi-drug resistant with high resistance rate to ampicillin, kanamycin, doxycyclin, erythromycin, imipinem, and nalidixic acid. The multiple resistance index ranged from 0.3 to 0.7 for the isolates of Khenis, from 0.5 to 0.8 for those of Menzel Jmil, from 0.5 to 0.75 (Hergla) and from 0.3 to 0.7 for the isolates of Oued Soltane. The high value of antibiotic resistance index was recorded for the V. alginolyticus population isolated from the fish farm in Hergla (ARI?=?0.672) followed by the population isolated from the conchylicole station of Menzel Jmil (ARI?=?0.645). The results obtained by the MIC tests confirmed the resistance of the V. alginolyticus to ampicillin, erythromycin, kanamycin, cefotaxime, streptomycin and trimethoprim. Plasmids were found in 79.48?% of the strains analyzed and 30 different plasmid profiles were observed. The strains had a high difference in the size of plasmids varying between 0.5 and 45?kb. Our study reveals that the antibiotic-resistant bacteria are widespread in the aquaculture and conchylicole farm relatively to others strains isolated from seawater. 相似文献
59.
Jérémie Fournier-Dit-Chabert Victoria Vinader Ana Rita Santos Mariano Redondo-Horcajo Aurore Dreneau Ramkrishna Basak Laura Cosentino Gemma Marston Hamdy Abdel-Rahman Paul M. Loadman Steven D. Shnyder José Fernando Díaz Isabel Barasoain Robert A. Falconer Klaus Pors 《Bioorganic & medicinal chemistry letters》2012,22(24):7693-7696
Colchicine was modified at the 10-OCH3 position of the C-ring by reaction with heterocyclic amines or commercially available amines to afford a library of target colchicinoids in high yields (62–99%). Molecular modeling revealed that the incorporation of the linker groups led to a reduction in entropy and therefore binding affinity when compared with colchicine. Some colchicinoids were shown to be equicytotoxic with colchicine when evaluated in the DLD-1 colon cancer cells and retained activity in resistant A2780AD or HeLa cells with mutant Class III β-tubulin. Importantly, unlike colchicine, the analogues in this study are amenable for prodrug derivatisation and with potential for tumor-selective delivery. 相似文献
60.
Moo Rim Kang Glen Yang Klaus Charisse Hila Epstein-Barash Muthiah Manoharan Long-Cheng Li 《Journal of visualized experiments : JoVE》2012,(65)
We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. The mouse model is established by urethral catheterization under inhaled general anesthetic. Chemical burn is then introduced to the bladder mucosa using intravesical silver nitrate solution to disrupt the bladder glycosaminoglycan layer and allows cells to attach. Following several washes with sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder tumors is confirmed and monitored by in vivo bladder ultrasound and bioluminescent imaging. The tumors are then treated intravesically with saRNA formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with ultrasound and bioluminescence. All steps of this procedure are demonstrated in the accompanying video. 相似文献