It is generally accepted that environmental factors can significantly influence respiratory system. Cold is one of these factors. Understanding of the reaction of airways to cold air is very important tool leading to ...It is generally accepted that environmental factors can significantly influence respiratory system. Cold is one of these factors. Understanding of the reaction of airways to cold air is very important tool leading to improvement in management of cold induced rhinitis, cold induced asthma, exercise induced asthma, and exacerbation of chronic airway diseases induced by cold exposure. Despite the airways are protected against cold air by powerful heat and moisture exchanging counter current system within the nose, they are still at the risk of onset and development of cold induced symptoms mainly if this mechanism is insufficient, exposed person hyperventilates or is breathing subfreezing air. Some of the mechanisms involved in cold air induced reactions are understood quite well, but some of them are still discussed as they have not been satisfactorily explained, yet. Most discussed mechanisms by which cold air may induce respiratory symptoms include direct cooling and exsiccation of mucosal surface with subsequent hyper-tonicity of superficial fluid layer and interactions between the trigeminal and the vagus nerve at the central level. Molecular background for such a reaction may rely on the presence of thermo sensitive channels, mainly TRPM8, expressed on airway afferent nerves, which initiate response to cold air, giving a rise to autonomic responses like bronchoconstriction, cough, dyspnoea, chest tightness, mucus secretion and mucosal swelling. Identification of targets for cold action in the airway may help to identify potent antagonists which may prevent or reverse cold induced reactions sharing possibility for clinical application.展开更多
In this study, we aimed to examine the electrophysio- logical properties of β-cells in Kir6.2-/- mice using fresh pancreatic tissue slice preparation. This prepa-ration is advantageous since it preserves socio-cellul...In this study, we aimed to examine the electrophysio- logical properties of β-cells in Kir6.2-/- mice using fresh pancreatic tissue slice preparation. This prepa-ration is advantageous since it preserves socio-cellular context of the β-cells. Using this novel approach we revisited basic morphology and used whole-cell patch-clamp to study electrical excitability as well as to assess the modulation of the late steps of the exocy-totic activity of β-cells by cytosolic [Ca2+] changes in control and Kir6.2-/- mice. We found that young Kir6.2-/- mice (2 - 4 weeks old) were hypoglycaemic while aged Kir6.2-/- mice (5 - 60 weeks old) were normo- or even hyper- glycaemic. Membrane ca-pacitance measurements show- ed more efficient Ca2+-secretion coupling in young Kir6.2-/- mice, but this coupling is significantly reduced in older Kir6.2-/- mice. We have found increased exo- cytotic efficacy induced by repetitive trains of depo- larization pulses which may result from higher cyto- solic [Ca2+] due to hyperexcitability in Kir6.2-/- mice. This condition in turn resulted in the reduced β-cell number and func-tion in the following weeks. Detailed assessment of the efficacy of Ca2+ dependent exocyto- sis in β-cell from Kir6.2-/- mice may contribute to our understanding of the pathophysiology of persistent hyperinsulinemia hypoglycemia of infancy (PHHI) and suggest potential alternative therapeutic approaches for PHHI patients.展开更多
Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physi...Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the ac- tivity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.展开更多
Terminals of the trigeminal afferents innervating nasal mucosa are called gate keepers, since these fibres detect substances entering the airways. Trigeminal excitation by irritants initiates airway defensive mechanis...Terminals of the trigeminal afferents innervating nasal mucosa are called gate keepers, since these fibres detect substances entering the airways. Trigeminal excitation by irritants initiates airway defensive mechanisms, and it is also attributed to the influence of lower airways resistance in a term of nasobronchial reflex. This phenomenon is frequently under debate, because some investigators were unable to confirm its existence. The aim of our study was to determine, whether pharmacological approach could be useful to reach high accuracy and better interpretation of the data obtained by Pennock’s method. Pennock’s method, which is frequently used to measure airway resistance in vivo (Raw) in fact measures total airway resistance, however, the data are usually interpreted in a terms of bronchomotor response. The upper airway component, which represents approximately 40% of Raw, is commonly not considered as being important in this method. 30 Dunkin Hartley guinea pigs were exposed to nasal stimuli (TRPA1 agonist—irritant allylisothiocyanate (10 mM, AITC), TRPM8 agonist with cooling potential menthol (10-3 M) and saline as a control). Raw was measured pre challenge as baseline, after nasal provocation and further, after nasal inhalation of histamine and methacholine (10-6 M) each. The data showed rise of Raw only after nasal AITC challenge, with further increased responsiveness to histamine and methacholine (5.3 vs 10.18 vs 11.26 vs 17.32 cmH2O.s-1, p 0.05). No significant changes were detected after saline, or menthol respectively. Data obtained in further experiment and its analysis showed that pre-treatment with nasal administration of 1% oxymetazoline but without salbutamol inhalation prevented the rise of Raw after nasal irritant challenges. Raw after nasal irritant challenges rises rather due to nasal response than due to narrowing of the lower airways.展开更多
The aim of the present study was to investigate the status of oxidative stress in the serum of children affected with autism spectrum disorder. Twenty autistic children aged 3 to 12 years, were gender and age-matched ...The aim of the present study was to investigate the status of oxidative stress in the serum of children affected with autism spectrum disorder. Twenty autistic children aged 3 to 12 years, were gender and age-matched with 20 typically developing children. Changes in the levels of the redox-sensing transcription factor nuclear factor-kappa B (NF-κB) was measured in serum of autistic children and controls. Other oxidative stress biomarkers such as malondialdehyde, reduced glutathione, total antioxidant capacity, catalase activity, and paraoxonase 1 activity were determined in serum as well. Significant increase was observed in serum NF-κB of autistic children compared to that in controls (by 138.6%). There was also marked increase in malondialdehyde level by 87.3% in autistic patients. Meanwhile, there were significant decreases in reduced glutathione (by 24%), catalase activity (by 40.8%), paraoxonase 1 activity (by 36.6%), and total antioxidant capacity (by 36.5%) compared to the control group. These data clearly demonstrate increased oxidative stress in serum of autistic children and suggest that the NF-κB signaling pathway is activated in autism, possibly due to increased oxidative burden.展开更多
The effect of acute and chronic cold exposure on heart rate (HR) and neuronal function in crayfish Procambarus clarkii and prawns Macrobrachium rosenbergii was addressed. This is particularly important since prawn far...The effect of acute and chronic cold exposure on heart rate (HR) and neuronal function in crayfish Procambarus clarkii and prawns Macrobrachium rosenbergii was addressed. This is particularly important since prawn farms of this species are used for aquaculture in varied climates world wide. The success of P. clarkii as an invasive species throughout the world may in part be due to their ability to acclimate to cold and warm habitats. A set of experiments was devised to address the physiological abilities of these species in managing rapid changes to cold environments as well as their ability to respond to sensory stimuli by using behavior and a bioindex of HR. Prawns died within 2 hrs when moved from 21℃ to 5℃. Crayfish reduced their HR but survived for at least a week with this rapid change. Changes in temperature of 5℃ each week resulted in death of the prawns when 10℃ was reached. Some died at 16℃ and some lasted at 10℃ for 1 day before dying. Crayfish remained responsive to sensory stimuli and survived with either rapid or slow changes in temperature from 21℃ to 5℃. Primary sensory neurons were rapidly inhibited in prawns with an acute change to 5℃, where as in crayfish the activity was reduced but not completely inhibited. An induced sensory-CNS-motor circuit elicited activity at neuromuscular junctions in prawns and crayfish at 21℃ but with acute changes to 5℃only in crayfish was the circuit functionally intact. The ability to survive rapid environmental temperature changes will impact survival and in time the distribution of a species. The significance of these findings is that they may account, in part, for the wide ecological distribution of P. clarkii as compared to M. rosenbergii. The invasiveness of organisms, as for P. clarkii, is likely linked to the physiological robustness to acute and chronic temperature changes of habitats.展开更多
The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH...The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH (pHi) acidification by exposure to20 mMNH4Cl for 2 min in a Na+-free solution containing Schering 28080, conditions under which H+-AT-Pase is the only cell mechanism for pHi recovery. Using the acridine orange fluorescent probe (5mM) and confocal microscopy, the vesicle movement was quantified by determining, for each experimental group, the mean slope of the line indicating the changes in apical/basolateral fluorescence density ratio over time during the first 5.30 min of the pHi recovery period. Under the control conditions, the mean slope was 0.079 ± 0.0033 min-1 (14) and it increased significantly with ANG II [10-12 and 10-7 M, respectively to 0.322 ± 0.038 min-1 (13) and 0.578 ± 0.061 min-1 (12)] or AVP [10-12 and 10-6 M, respectively to 0.301 ± 0.018 min-1 (12) and 0.687 ± 0.049 min-1 (11)]. However, in presence of ANP (10-6 M, decreases cytosolic free calcium), dimethyl-BAPTA/AM (5 × 10-5 M, chelates intracellular calcium) or colchicine (10-5 M, 2-h preincubation;inhibits microtubule-dependent vesicular trafficking) alone or plus ANG II or AVP the mean slopes were similar to the control values, indicating that such agents blocked the stimulatory effect of ANG II or AVP on vesicle trafficking. The results suggest that the pathway responsible for the increase in cytosolic free calcium and the microtu-bule-dependent vesicular trafficking are involved in this hormonal stimulating effect. Whether cytosolic free calcium reduction represents an important direct mechanism for ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking, or is a side effect of other signaling pathways which will require additional studies.展开更多
Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks dow...Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks down is fundamental to solving the problem of asthma. In this paper we have proposed a stochastic modeling the airway smooth muscle bundle for reproducing AHR such as an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to agonist. A large number N of contractile muscle cells was assumed to repeat themselves in between contraction and relaxation asynchronously. Dynamic equilibrium of statistic physics was applied to the system of ASM bundle. Thus, the relation of dose to response of a piece of ASM bundle was described by Φ=tanh(βH) , where β was Boltzman factor and H represented energy of contraction induced by constrictor agents. Each of adjacent pair contractile cells was assumed to have Ising-type of antimagnetic interactions of preference energy J (for the condition of contraction-relaxation) between them. A motion equation for a piece of ASM bundle was described by Φ=N(H-zJΦ , which explained existence of combined tonic and phasic contractions. Based on observations of Venegas et al. [4], airway responsiveness was assumed to be assessable by total volume of the ventilation defects (TVD) of 13NN PET-CT images. Interactions via propagation of Ca ion waves between ASM bundles would cause percolation probability by PΦ=(1+tanh(βH))2/4 along the tree, then the relation of dose βH to TVD was described by TVD=PΦ[1-(1-PΦ)3/PΦ3]-TVD0. TVD0 represented the protection mechanism against excessive airway narrowing, which was determined by the ratio of amplitudes between tonic and phasic contractions, thus the balance of amplitudes between tonic and phasic contractions of peripheral lobular smooth muscles would be the determinant of AHR.展开更多
A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circu- lating human lymphocytes leading to lipid peroxide- tion, DNA damage, mitochondrial perturbations, and protein...A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circu- lating human lymphocytes leading to lipid peroxide- tion, DNA damage, mitochondrial perturbations, and protein oxidation. In a training experiment, Wistar rats were divided into control group (CG) and exer- cise group (EG). After a running level exercise until exhaustion, we observed an increase in the mRNA content and protein expression of SIRT1 and SIRT7 in the EG compared to the CG. Moreover, such train- ing exercise did not change mRNA transcripts and protein expression of FOXO3A and GADD45. We also observed an increase of pro-apoptotic protein bax and a decrease of the anti-apoptotic protein bcl-2 in the EG. Accordingly, we observed a caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage only in EG rats. Statistical analysis of the data showed a significant correlation between SIRT1 and SIRT7 expression and apoptotic proteins such as bax, bcl-2 in both tissues. We conclude that, in both muscle, such exercise activates both a damaging apoptotic mecha- nism with bax increase and bcl-2 decrease and a counterbalancing protective mechanism with SIRT1 and SIRT7 increase.展开更多
The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation o...The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2;this may clarify the role of endothelium in the vasodilatory mechanism of SO2.展开更多
Seven percent voluntary body weight decrease by boxers requires 21 days while 4.4 percent increase needs only one day. Energy and fluid intakes reduction does not affect boxers punching force. Boxers effective punch m...Seven percent voluntary body weight decrease by boxers requires 21 days while 4.4 percent increase needs only one day. Energy and fluid intakes reduction does not affect boxers punching force. Boxers effective punch masses and body weights correlate. Wrist girths and competition rankings of boxers correlate. Boxers show leanness body fat percentage. Boxers, generally highly mesomorphic, with increasing body weight, show ectomorphy decreases but endomorphy and mesomorphy increases. Vibration treatment enhances power in boxers arm flexors. Presence, nature and thickness of bandages and gloves donned influence boxers punch force. Stance posture adopted by boxers ends in locomotion functional parameters adaptations. Muscular recruitment sequence during rear straight punches may be influenced by the target height (head or body levels) and the boxer intention (produce maximal force or maximal speed). Handgrip strength: 1) increases from younger to older and from lighter to heavier boxers, and 2) correlates with competition ranking. Rear knee extension increases rear straight punching force to the head. Compared to uppercut and straight punches, the hook produces the highest change in hand velocity. Maximal forces are larger for the rear than the lead hand, and greater in more than in less experienced boxers. Hook punch force is greater than those of uppercut and straight punches. Boxer aim (produce maximum force or maximum speed) influence his punching force. Massage neither prevents a decrement in repeated performance nor has detrimental effects on performance, but increases recovery perceptions, compared with the passive rest intervention.展开更多
Prostaglandins (PGs) mediate cervical ripening leading to parturition. PGs are used successfully to induce cervical ripening. However, the cell type specific expression of PG receptor subtypes and various stromal fact...Prostaglandins (PGs) mediate cervical ripening leading to parturition. PGs are used successfully to induce cervical ripening. However, the cell type specific expression of PG receptor subtypes and various stromal factors important for cervical ripening in human cervix is not known. Our objective was to investigate the expression and localization of PG receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin ?B, ALOX12 (arachidonate 12-lipooxy-genase) and ALOX15 in human cervical tissue from pregnant and non-pregnant women. Cervical biopsies were obtained from non-pregnant (NP), term pregnant (TP) and post-partum (PP) women. The mRNA expression was determined with real-time PCR, protein expression and localization with immunohistochemistry. Our results show that the EP2 mRNA level was higher in the PP group as compared to TP, whereas the EP4 mRNA level was lower in the TP group as compared to NP. Concomitantly stromal EP2 and epithelial EP3 immunoreactivity was higher in the TP as compared to the NP group, while the EP4 immunostaining in glands was lower in the TP as compared to the PP group. Immunostaining of endothelial CTGF, smooth muscle furin and ALOX12, were all lower in the TP group as compared to NP, for CTGF also the PP group was lower than NP. Endothelial calgranulin B immunoreactivity was higher in the PP group than the NP group. PG receptors and stromal factors exhibit differential expression in the cervix from women in non-pregnant and pregnant states, implying their involvement in the process of cervical ripening.展开更多
Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, r...Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, renal dysfunction, and/or rejection. Treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following ischemia/reperfusion injury. The present study tests the hypothesis that an antioxidant-fortified diet given to rats before and after renal ischemia/reperfusion injury will reduce the kidney damage that results and improve renal function. Endothelial and inducible nitric oxide synthases may change with tissue injury, including ischemia/ reperfusion. Materials and Methods: Male Wistar rats were subjected to ischemia/reperfusion injury at 7 or 19 weeks of age with or without dietary antioxidant supplementation. One week later, glomerular filtration rate, mean arterial pressure and urinary nitric oxide were measured, and renal endothelial and inducible nitric oxide synthases examined. Results: The glomerular filtration rate was elevated more than two-fold above the normal range? at 8 weeks in animals on the regular diet exposed to ischemia/reperfu- sion, while in the 8 week antioxidant-fortified diet group the glomerular filtration rate was normal. Also, in 8 week rats, levels of endothelial nitric oxide synthase protein in cortex were higher on the regular than on the antioxidant-fortified diet. Conclusion: Early after ischemia/reperfusion injury renal endothelial nitric oxide synthase levels rise, possibly contributing to vascular dilation and hyperperfusion, and an antioxidant-fortified diet can ameliorate these changes in the younger age group.展开更多
The aim of this study is to evaluate the skin elasticity in individuals who practise spinning. Mechanical eva- luations were conducted, under environmental and physical established conditions, during a physical traini...The aim of this study is to evaluate the skin elasticity in individuals who practise spinning. Mechanical eva- luations were conducted, under environmental and physical established conditions, during a physical training period. A total of 12 volunteers aged 35 ± 5 years were enrolled in this study, (60 min) before (control) and (60 min) after practicing spinning. Skin elasticity and area were measured by a Skin Meter and analysed with the Skin Meter software 1.3. In subjects who practiced spinning, the data shown a sig-nificant effect: on elasticity, evaluated as the ratio of final retraction (UA) and final distension (UF), on viscoelasticity express as the ratio delayed distension (UV) and immediate distension (UE);and on measurements of skin area vs control subjects. Skin Meter can be useful for a non-invasive screening of skin condition with also a potential extension in subjects with skin pathologies or to monitor skin oxidative stress in sportive subjects.展开更多
Control pigs required 109.9 ug/kg/min and MHS pigs required 72.4 ug/kg/min infusion of Organon 9426 to maintain a 90% block. It appears that Organon 9426 is only one-third to one-half as potent as Vecuronium in pigs. ...Control pigs required 109.9 ug/kg/min and MHS pigs required 72.4 ug/kg/min infusion of Organon 9426 to maintain a 90% block. It appears that Organon 9426 is only one-third to one-half as potent as Vecuronium in pigs. The fact that MHS pigs only require 66% of the infusion dose to maintain a 90% block suggests that there is difference in the neuromuscular effect of Organon 9426 in MHS vs. control pigs. A linear regression analysis of the dose response data to Organon 9426 in MHS pigs indicated that 427.033 ug/kg would be required to produce a 100% neuromuscular blockade vs. 586.31 ug/kg in control pigs. Nine of the ten MHS pigs did not develop MH or show any signs of impending MH during the halothane and succinylcholine challenge at the end of the infusion period. Organon 9426 is the first muscle relaxant to offer significant protective action at a clinical dose. This suggests that there is an allosteric site on the sodium channel (acetylcholine receptor) which regulates the flow of sodium ions through the sodium channel. Organon 9426 may be therapeutically effective in an active MH case [1].展开更多
During exercise, phosphorylase kinase (PhK) is the key regulatory enzyme responsible for maintaining glycogenolytic flux to sustain muscle contraction. The absence of PhK in skeletal muscle results in glycogen storage...During exercise, phosphorylase kinase (PhK) is the key regulatory enzyme responsible for maintaining glycogenolytic flux to sustain muscle contraction. The absence of PhK in skeletal muscle results in glycogen storage disease (GSD) Type IX which is characterized by muscle weakness and rapid fatigue upon exercise. In this study, we have used the phka1 deficient I/LnJ mouse model of GSD to investigate the physiological and genetic adaptations that occur in response to voluntary exercise. When quantified over training periods of either 1, 2, or 5 weeks, I/LnJ mice ran significantly less time/day and distance/day than agematched C57/Bl6 mice. Cumulatively after five weeks, adult I/LnJ mice ran ~1/2 the total time and distance of wild-type mice, 116 ± 6 hours and 211 ±23 kmversus 194 ± 3 hours and 418 ±4 km, respectively. After 5 weeks, C57/Bl6 mice demonstrated an increase in endurance as a result of aerobic training;this observed physiological adaptation was not present in I/LnJ mice. The decrease in total distance run by I/LnJ mice was not due to a reduction in speed;juvenile and adult I/LnJ mice ran ~75% - 80% as fast as C57/Bl6 mice. When transcription of glycolytic genes glucose transporter 4 (scla1), pyruvate dehydrogenase (pdha1), and phosphofructokinase (pfk) were quantified at the end of each training period, no significant differences in expression levels were found between mouse strains, suggesting that non-glycolytic mechanisms work to maintain the muscle function observed in the I/LnJ mice.展开更多
The cardio-ankle vascular index (CAVI) is a new index of arterial stiffness that can be measured with a VaSera VS-1000 device. An association between certain arterial stiffness indices and cardiac function has been fo...The cardio-ankle vascular index (CAVI) is a new index of arterial stiffness that can be measured with a VaSera VS-1000 device. An association between certain arterial stiffness indices and cardiac function has been found but has not yet been validated. The aim of this study was to establish whether any significant relationship exists between cardiac index (CI) and CAVI. Twenty healthy male volunteers with a mean age of 30 ± 5 years and a mean BMI of 23.1 ± 1.1 kg/m2 participated in the study. CO was estimated using a Doppler technique, and CAVI was measured with a VaSeraVS-1000 device. A motorised tilting table was used to achieve head-up tilt (HUT) angles of 0°, 30°and 60°, to modify the peripheral sympathetic outflow. We found that there was a significant inverse correlation between CI and the degree of head-up tilt, ( for 0°and 30°;for 0° and 60°, p for both;for 30° and 60°, ). CAVI showed a significant positive correlation relative with the degree of HUT, ( for 0° and 30°;for 0° and 60°;for 30° and 60°, for all). A significant negative correlation was found between CI and CAVI r = - 0.47, p Additionally, a significant p increase in PVR values was observed for increasing HUT values. In conclusion: An inverse relationship between CI and CAVI was shown;a decrease in cardiac output is associated with an increase in CAVI values at different degrees of HUT. This association provides further insight into the postural link between cardiac output and arterial compliance.展开更多
Apparent motion stimulus induces visual perception of smooth motion even though there is no speed information. We examined whether human brain response as measured by magnetoencephalography carries direction informati...Apparent motion stimulus induces visual perception of smooth motion even though there is no speed information. We examined whether human brain response as measured by magnetoencephalography carries direction information in the visually presented apparent motion of a randomdot pattern in a similar manner as continuous motions that have speed and direction information. Although there was no significant effect of motion direction on the peak response latency and amplitude, mutual information entropy (IE) significantly increased after the motion onset at approximately 36 ms after the response latency in 41% of the evaluations. Detailed analysis of the data from five subjects who participated in both the present apparent motion and our previous coherent motion studies revealed that the maximum IE latency (delay) for apparent motion was significantly longer than that for coherent motion, although the mean maximum IE was the same. The results indicate that direction is represented in the response waveform evoked by apparent motion but the manner is different from that for coherent motion probably due to the distinct neural processes engaged only for the apparent motion perception. We consider that direction and speed can be processed separately in the human brain because direction information was generated without speed information for the perception of apparent motion.展开更多
A cDNA clone SSJ337 (accession no. AF161253) of 1230 bp, encoding a catalytic subunit of protein phosphatase 4, was selected as one of the clones expressed specifically in prestalk cells from a cDNA library of D. disc...A cDNA clone SSJ337 (accession no. AF161253) of 1230 bp, encoding a catalytic subunit of protein phosphatase 4, was selected as one of the clones expressed specifically in prestalk cells from a cDNA library of D. discoideum slugs. Cells transformed with a knockout construct of SSJ337 showed an aberrant and tiny fruiting-body formation with a short stalk. A knockout mutant, SSJ337KO was allowed to develop much slower than a wild-type AX2 after the post-aggregation stage. This suggested that the SSJ337 cDNA clone has played an important role especially in the later development of Dictyostelium discoideum. Results from Northern blotting, analysis showed that transcripts for SSJ337 were accumulated at 16 h to 24 h after starvation began.展开更多
Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for mo...Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for most (mitochondria) or all (peroxisome) of them, synthesized in the cytosol from the nuclear genome. Nevertheless, the membrane structures and the DNA content differ between these two organelles. Mitochondria possess a small circular genome while peroxisomes don’t. The control of their dynamic is dependent on specific factors even if some of those are able to affect both. These two organelles are metabolically connected: they are both involved in lipid metabolism. They are both able to beta oxidize fatty acids and are implicated in ROS production. However, their precise function in these metabolic pathways and their physiological functions are different. While mitochondrial metabolism is closely related to energy production, peroxisome does not seem to be associated with energy production but with the production of bioactive molecules and in detoxification processes.展开更多
文摘It is generally accepted that environmental factors can significantly influence respiratory system. Cold is one of these factors. Understanding of the reaction of airways to cold air is very important tool leading to improvement in management of cold induced rhinitis, cold induced asthma, exercise induced asthma, and exacerbation of chronic airway diseases induced by cold exposure. Despite the airways are protected against cold air by powerful heat and moisture exchanging counter current system within the nose, they are still at the risk of onset and development of cold induced symptoms mainly if this mechanism is insufficient, exposed person hyperventilates or is breathing subfreezing air. Some of the mechanisms involved in cold air induced reactions are understood quite well, but some of them are still discussed as they have not been satisfactorily explained, yet. Most discussed mechanisms by which cold air may induce respiratory symptoms include direct cooling and exsiccation of mucosal surface with subsequent hyper-tonicity of superficial fluid layer and interactions between the trigeminal and the vagus nerve at the central level. Molecular background for such a reaction may rely on the presence of thermo sensitive channels, mainly TRPM8, expressed on airway afferent nerves, which initiate response to cold air, giving a rise to autonomic responses like bronchoconstriction, cough, dyspnoea, chest tightness, mucus secretion and mucosal swelling. Identification of targets for cold action in the airway may help to identify potent antagonists which may prevent or reverse cold induced reactions sharing possibility for clinical application.
基金the Growbeta EU grant (5th framework, No. QLG1-CT-2001-02233)The European Neuroscience Institute Gottingen (ENI-G)+1 种基金 Gottingen University Medical School the Max-Planck-Society and Schering AG
文摘In this study, we aimed to examine the electrophysio- logical properties of β-cells in Kir6.2-/- mice using fresh pancreatic tissue slice preparation. This prepa-ration is advantageous since it preserves socio-cellular context of the β-cells. Using this novel approach we revisited basic morphology and used whole-cell patch-clamp to study electrical excitability as well as to assess the modulation of the late steps of the exocy-totic activity of β-cells by cytosolic [Ca2+] changes in control and Kir6.2-/- mice. We found that young Kir6.2-/- mice (2 - 4 weeks old) were hypoglycaemic while aged Kir6.2-/- mice (5 - 60 weeks old) were normo- or even hyper- glycaemic. Membrane ca-pacitance measurements show- ed more efficient Ca2+-secretion coupling in young Kir6.2-/- mice, but this coupling is significantly reduced in older Kir6.2-/- mice. We have found increased exo- cytotic efficacy induced by repetitive trains of depo- larization pulses which may result from higher cyto- solic [Ca2+] due to hyperexcitability in Kir6.2-/- mice. This condition in turn resulted in the reduced β-cell number and func-tion in the following weeks. Detailed assessment of the efficacy of Ca2+ dependent exocyto- sis in β-cell from Kir6.2-/- mice may contribute to our understanding of the pathophysiology of persistent hyperinsulinemia hypoglycemia of infancy (PHHI) and suggest potential alternative therapeutic approaches for PHHI patients.
文摘Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the ac- tivity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.
文摘Terminals of the trigeminal afferents innervating nasal mucosa are called gate keepers, since these fibres detect substances entering the airways. Trigeminal excitation by irritants initiates airway defensive mechanisms, and it is also attributed to the influence of lower airways resistance in a term of nasobronchial reflex. This phenomenon is frequently under debate, because some investigators were unable to confirm its existence. The aim of our study was to determine, whether pharmacological approach could be useful to reach high accuracy and better interpretation of the data obtained by Pennock’s method. Pennock’s method, which is frequently used to measure airway resistance in vivo (Raw) in fact measures total airway resistance, however, the data are usually interpreted in a terms of bronchomotor response. The upper airway component, which represents approximately 40% of Raw, is commonly not considered as being important in this method. 30 Dunkin Hartley guinea pigs were exposed to nasal stimuli (TRPA1 agonist—irritant allylisothiocyanate (10 mM, AITC), TRPM8 agonist with cooling potential menthol (10-3 M) and saline as a control). Raw was measured pre challenge as baseline, after nasal provocation and further, after nasal inhalation of histamine and methacholine (10-6 M) each. The data showed rise of Raw only after nasal AITC challenge, with further increased responsiveness to histamine and methacholine (5.3 vs 10.18 vs 11.26 vs 17.32 cmH2O.s-1, p 0.05). No significant changes were detected after saline, or menthol respectively. Data obtained in further experiment and its analysis showed that pre-treatment with nasal administration of 1% oxymetazoline but without salbutamol inhalation prevented the rise of Raw after nasal irritant challenges. Raw after nasal irritant challenges rises rather due to nasal response than due to narrowing of the lower airways.
文摘The aim of the present study was to investigate the status of oxidative stress in the serum of children affected with autism spectrum disorder. Twenty autistic children aged 3 to 12 years, were gender and age-matched with 20 typically developing children. Changes in the levels of the redox-sensing transcription factor nuclear factor-kappa B (NF-κB) was measured in serum of autistic children and controls. Other oxidative stress biomarkers such as malondialdehyde, reduced glutathione, total antioxidant capacity, catalase activity, and paraoxonase 1 activity were determined in serum as well. Significant increase was observed in serum NF-κB of autistic children compared to that in controls (by 138.6%). There was also marked increase in malondialdehyde level by 87.3% in autistic patients. Meanwhile, there were significant decreases in reduced glutathione (by 24%), catalase activity (by 40.8%), paraoxonase 1 activity (by 36.6%), and total antioxidant capacity (by 36.5%) compared to the control group. These data clearly demonstrate increased oxidative stress in serum of autistic children and suggest that the NF-κB signaling pathway is activated in autism, possibly due to increased oxidative burden.
文摘The effect of acute and chronic cold exposure on heart rate (HR) and neuronal function in crayfish Procambarus clarkii and prawns Macrobrachium rosenbergii was addressed. This is particularly important since prawn farms of this species are used for aquaculture in varied climates world wide. The success of P. clarkii as an invasive species throughout the world may in part be due to their ability to acclimate to cold and warm habitats. A set of experiments was devised to address the physiological abilities of these species in managing rapid changes to cold environments as well as their ability to respond to sensory stimuli by using behavior and a bioindex of HR. Prawns died within 2 hrs when moved from 21℃ to 5℃. Crayfish reduced their HR but survived for at least a week with this rapid change. Changes in temperature of 5℃ each week resulted in death of the prawns when 10℃ was reached. Some died at 16℃ and some lasted at 10℃ for 1 day before dying. Crayfish remained responsive to sensory stimuli and survived with either rapid or slow changes in temperature from 21℃ to 5℃. Primary sensory neurons were rapidly inhibited in prawns with an acute change to 5℃, where as in crayfish the activity was reduced but not completely inhibited. An induced sensory-CNS-motor circuit elicited activity at neuromuscular junctions in prawns and crayfish at 21℃ but with acute changes to 5℃only in crayfish was the circuit functionally intact. The ability to survive rapid environmental temperature changes will impact survival and in time the distribution of a species. The significance of these findings is that they may account, in part, for the wide ecological distribution of P. clarkii as compared to M. rosenbergii. The invasiveness of organisms, as for P. clarkii, is likely linked to the physiological robustness to acute and chronic temperature changes of habitats.
文摘The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH (pHi) acidification by exposure to20 mMNH4Cl for 2 min in a Na+-free solution containing Schering 28080, conditions under which H+-AT-Pase is the only cell mechanism for pHi recovery. Using the acridine orange fluorescent probe (5mM) and confocal microscopy, the vesicle movement was quantified by determining, for each experimental group, the mean slope of the line indicating the changes in apical/basolateral fluorescence density ratio over time during the first 5.30 min of the pHi recovery period. Under the control conditions, the mean slope was 0.079 ± 0.0033 min-1 (14) and it increased significantly with ANG II [10-12 and 10-7 M, respectively to 0.322 ± 0.038 min-1 (13) and 0.578 ± 0.061 min-1 (12)] or AVP [10-12 and 10-6 M, respectively to 0.301 ± 0.018 min-1 (12) and 0.687 ± 0.049 min-1 (11)]. However, in presence of ANP (10-6 M, decreases cytosolic free calcium), dimethyl-BAPTA/AM (5 × 10-5 M, chelates intracellular calcium) or colchicine (10-5 M, 2-h preincubation;inhibits microtubule-dependent vesicular trafficking) alone or plus ANG II or AVP the mean slopes were similar to the control values, indicating that such agents blocked the stimulatory effect of ANG II or AVP on vesicle trafficking. The results suggest that the pathway responsible for the increase in cytosolic free calcium and the microtu-bule-dependent vesicular trafficking are involved in this hormonal stimulating effect. Whether cytosolic free calcium reduction represents an important direct mechanism for ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking, or is a side effect of other signaling pathways which will require additional studies.
文摘Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks down is fundamental to solving the problem of asthma. In this paper we have proposed a stochastic modeling the airway smooth muscle bundle for reproducing AHR such as an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to agonist. A large number N of contractile muscle cells was assumed to repeat themselves in between contraction and relaxation asynchronously. Dynamic equilibrium of statistic physics was applied to the system of ASM bundle. Thus, the relation of dose to response of a piece of ASM bundle was described by Φ=tanh(βH) , where β was Boltzman factor and H represented energy of contraction induced by constrictor agents. Each of adjacent pair contractile cells was assumed to have Ising-type of antimagnetic interactions of preference energy J (for the condition of contraction-relaxation) between them. A motion equation for a piece of ASM bundle was described by Φ=N(H-zJΦ , which explained existence of combined tonic and phasic contractions. Based on observations of Venegas et al. [4], airway responsiveness was assumed to be assessable by total volume of the ventilation defects (TVD) of 13NN PET-CT images. Interactions via propagation of Ca ion waves between ASM bundles would cause percolation probability by PΦ=(1+tanh(βH))2/4 along the tree, then the relation of dose βH to TVD was described by TVD=PΦ[1-(1-PΦ)3/PΦ3]-TVD0. TVD0 represented the protection mechanism against excessive airway narrowing, which was determined by the ratio of amplitudes between tonic and phasic contractions, thus the balance of amplitudes between tonic and phasic contractions of peripheral lobular smooth muscles would be the determinant of AHR.
文摘A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circu- lating human lymphocytes leading to lipid peroxide- tion, DNA damage, mitochondrial perturbations, and protein oxidation. In a training experiment, Wistar rats were divided into control group (CG) and exer- cise group (EG). After a running level exercise until exhaustion, we observed an increase in the mRNA content and protein expression of SIRT1 and SIRT7 in the EG compared to the CG. Moreover, such train- ing exercise did not change mRNA transcripts and protein expression of FOXO3A and GADD45. We also observed an increase of pro-apoptotic protein bax and a decrease of the anti-apoptotic protein bcl-2 in the EG. Accordingly, we observed a caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage only in EG rats. Statistical analysis of the data showed a significant correlation between SIRT1 and SIRT7 expression and apoptotic proteins such as bax, bcl-2 in both tissues. We conclude that, in both muscle, such exercise activates both a damaging apoptotic mecha- nism with bax increase and bcl-2 decrease and a counterbalancing protective mechanism with SIRT1 and SIRT7 increase.
文摘The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2;this may clarify the role of endothelium in the vasodilatory mechanism of SO2.
文摘Seven percent voluntary body weight decrease by boxers requires 21 days while 4.4 percent increase needs only one day. Energy and fluid intakes reduction does not affect boxers punching force. Boxers effective punch masses and body weights correlate. Wrist girths and competition rankings of boxers correlate. Boxers show leanness body fat percentage. Boxers, generally highly mesomorphic, with increasing body weight, show ectomorphy decreases but endomorphy and mesomorphy increases. Vibration treatment enhances power in boxers arm flexors. Presence, nature and thickness of bandages and gloves donned influence boxers punch force. Stance posture adopted by boxers ends in locomotion functional parameters adaptations. Muscular recruitment sequence during rear straight punches may be influenced by the target height (head or body levels) and the boxer intention (produce maximal force or maximal speed). Handgrip strength: 1) increases from younger to older and from lighter to heavier boxers, and 2) correlates with competition ranking. Rear knee extension increases rear straight punching force to the head. Compared to uppercut and straight punches, the hook produces the highest change in hand velocity. Maximal forces are larger for the rear than the lead hand, and greater in more than in less experienced boxers. Hook punch force is greater than those of uppercut and straight punches. Boxer aim (produce maximum force or maximum speed) influence his punching force. Massage neither prevents a decrement in repeated performance nor has detrimental effects on performance, but increases recovery perceptions, compared with the passive rest intervention.
文摘Prostaglandins (PGs) mediate cervical ripening leading to parturition. PGs are used successfully to induce cervical ripening. However, the cell type specific expression of PG receptor subtypes and various stromal factors important for cervical ripening in human cervix is not known. Our objective was to investigate the expression and localization of PG receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin ?B, ALOX12 (arachidonate 12-lipooxy-genase) and ALOX15 in human cervical tissue from pregnant and non-pregnant women. Cervical biopsies were obtained from non-pregnant (NP), term pregnant (TP) and post-partum (PP) women. The mRNA expression was determined with real-time PCR, protein expression and localization with immunohistochemistry. Our results show that the EP2 mRNA level was higher in the PP group as compared to TP, whereas the EP4 mRNA level was lower in the TP group as compared to NP. Concomitantly stromal EP2 and epithelial EP3 immunoreactivity was higher in the TP as compared to the NP group, while the EP4 immunostaining in glands was lower in the TP as compared to the PP group. Immunostaining of endothelial CTGF, smooth muscle furin and ALOX12, were all lower in the TP group as compared to NP, for CTGF also the PP group was lower than NP. Endothelial calgranulin B immunoreactivity was higher in the PP group than the NP group. PG receptors and stromal factors exhibit differential expression in the cervix from women in non-pregnant and pregnant states, implying their involvement in the process of cervical ripening.
文摘Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, renal dysfunction, and/or rejection. Treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following ischemia/reperfusion injury. The present study tests the hypothesis that an antioxidant-fortified diet given to rats before and after renal ischemia/reperfusion injury will reduce the kidney damage that results and improve renal function. Endothelial and inducible nitric oxide synthases may change with tissue injury, including ischemia/ reperfusion. Materials and Methods: Male Wistar rats were subjected to ischemia/reperfusion injury at 7 or 19 weeks of age with or without dietary antioxidant supplementation. One week later, glomerular filtration rate, mean arterial pressure and urinary nitric oxide were measured, and renal endothelial and inducible nitric oxide synthases examined. Results: The glomerular filtration rate was elevated more than two-fold above the normal range? at 8 weeks in animals on the regular diet exposed to ischemia/reperfu- sion, while in the 8 week antioxidant-fortified diet group the glomerular filtration rate was normal. Also, in 8 week rats, levels of endothelial nitric oxide synthase protein in cortex were higher on the regular than on the antioxidant-fortified diet. Conclusion: Early after ischemia/reperfusion injury renal endothelial nitric oxide synthase levels rise, possibly contributing to vascular dilation and hyperperfusion, and an antioxidant-fortified diet can ameliorate these changes in the younger age group.
文摘The aim of this study is to evaluate the skin elasticity in individuals who practise spinning. Mechanical eva- luations were conducted, under environmental and physical established conditions, during a physical training period. A total of 12 volunteers aged 35 ± 5 years were enrolled in this study, (60 min) before (control) and (60 min) after practicing spinning. Skin elasticity and area were measured by a Skin Meter and analysed with the Skin Meter software 1.3. In subjects who practiced spinning, the data shown a sig-nificant effect: on elasticity, evaluated as the ratio of final retraction (UA) and final distension (UF), on viscoelasticity express as the ratio delayed distension (UV) and immediate distension (UE);and on measurements of skin area vs control subjects. Skin Meter can be useful for a non-invasive screening of skin condition with also a potential extension in subjects with skin pathologies or to monitor skin oxidative stress in sportive subjects.
文摘Control pigs required 109.9 ug/kg/min and MHS pigs required 72.4 ug/kg/min infusion of Organon 9426 to maintain a 90% block. It appears that Organon 9426 is only one-third to one-half as potent as Vecuronium in pigs. The fact that MHS pigs only require 66% of the infusion dose to maintain a 90% block suggests that there is difference in the neuromuscular effect of Organon 9426 in MHS vs. control pigs. A linear regression analysis of the dose response data to Organon 9426 in MHS pigs indicated that 427.033 ug/kg would be required to produce a 100% neuromuscular blockade vs. 586.31 ug/kg in control pigs. Nine of the ten MHS pigs did not develop MH or show any signs of impending MH during the halothane and succinylcholine challenge at the end of the infusion period. Organon 9426 is the first muscle relaxant to offer significant protective action at a clinical dose. This suggests that there is an allosteric site on the sodium channel (acetylcholine receptor) which regulates the flow of sodium ions through the sodium channel. Organon 9426 may be therapeutically effective in an active MH case [1].
文摘During exercise, phosphorylase kinase (PhK) is the key regulatory enzyme responsible for maintaining glycogenolytic flux to sustain muscle contraction. The absence of PhK in skeletal muscle results in glycogen storage disease (GSD) Type IX which is characterized by muscle weakness and rapid fatigue upon exercise. In this study, we have used the phka1 deficient I/LnJ mouse model of GSD to investigate the physiological and genetic adaptations that occur in response to voluntary exercise. When quantified over training periods of either 1, 2, or 5 weeks, I/LnJ mice ran significantly less time/day and distance/day than agematched C57/Bl6 mice. Cumulatively after five weeks, adult I/LnJ mice ran ~1/2 the total time and distance of wild-type mice, 116 ± 6 hours and 211 ±23 kmversus 194 ± 3 hours and 418 ±4 km, respectively. After 5 weeks, C57/Bl6 mice demonstrated an increase in endurance as a result of aerobic training;this observed physiological adaptation was not present in I/LnJ mice. The decrease in total distance run by I/LnJ mice was not due to a reduction in speed;juvenile and adult I/LnJ mice ran ~75% - 80% as fast as C57/Bl6 mice. When transcription of glycolytic genes glucose transporter 4 (scla1), pyruvate dehydrogenase (pdha1), and phosphofructokinase (pfk) were quantified at the end of each training period, no significant differences in expression levels were found between mouse strains, suggesting that non-glycolytic mechanisms work to maintain the muscle function observed in the I/LnJ mice.
文摘The cardio-ankle vascular index (CAVI) is a new index of arterial stiffness that can be measured with a VaSera VS-1000 device. An association between certain arterial stiffness indices and cardiac function has been found but has not yet been validated. The aim of this study was to establish whether any significant relationship exists between cardiac index (CI) and CAVI. Twenty healthy male volunteers with a mean age of 30 ± 5 years and a mean BMI of 23.1 ± 1.1 kg/m2 participated in the study. CO was estimated using a Doppler technique, and CAVI was measured with a VaSeraVS-1000 device. A motorised tilting table was used to achieve head-up tilt (HUT) angles of 0°, 30°and 60°, to modify the peripheral sympathetic outflow. We found that there was a significant inverse correlation between CI and the degree of head-up tilt, ( for 0°and 30°;for 0° and 60°, p for both;for 30° and 60°, ). CAVI showed a significant positive correlation relative with the degree of HUT, ( for 0° and 30°;for 0° and 60°;for 30° and 60°, for all). A significant negative correlation was found between CI and CAVI r = - 0.47, p Additionally, a significant p increase in PVR values was observed for increasing HUT values. In conclusion: An inverse relationship between CI and CAVI was shown;a decrease in cardiac output is associated with an increase in CAVI values at different degrees of HUT. This association provides further insight into the postural link between cardiac output and arterial compliance.
文摘Apparent motion stimulus induces visual perception of smooth motion even though there is no speed information. We examined whether human brain response as measured by magnetoencephalography carries direction information in the visually presented apparent motion of a randomdot pattern in a similar manner as continuous motions that have speed and direction information. Although there was no significant effect of motion direction on the peak response latency and amplitude, mutual information entropy (IE) significantly increased after the motion onset at approximately 36 ms after the response latency in 41% of the evaluations. Detailed analysis of the data from five subjects who participated in both the present apparent motion and our previous coherent motion studies revealed that the maximum IE latency (delay) for apparent motion was significantly longer than that for coherent motion, although the mean maximum IE was the same. The results indicate that direction is represented in the response waveform evoked by apparent motion but the manner is different from that for coherent motion probably due to the distinct neural processes engaged only for the apparent motion perception. We consider that direction and speed can be processed separately in the human brain because direction information was generated without speed information for the perception of apparent motion.
文摘A cDNA clone SSJ337 (accession no. AF161253) of 1230 bp, encoding a catalytic subunit of protein phosphatase 4, was selected as one of the clones expressed specifically in prestalk cells from a cDNA library of D. discoideum slugs. Cells transformed with a knockout construct of SSJ337 showed an aberrant and tiny fruiting-body formation with a short stalk. A knockout mutant, SSJ337KO was allowed to develop much slower than a wild-type AX2 after the post-aggregation stage. This suggested that the SSJ337 cDNA clone has played an important role especially in the later development of Dictyostelium discoideum. Results from Northern blotting, analysis showed that transcripts for SSJ337 were accumulated at 16 h to 24 h after starvation began.
文摘Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for most (mitochondria) or all (peroxisome) of them, synthesized in the cytosol from the nuclear genome. Nevertheless, the membrane structures and the DNA content differ between these two organelles. Mitochondria possess a small circular genome while peroxisomes don’t. The control of their dynamic is dependent on specific factors even if some of those are able to affect both. These two organelles are metabolically connected: they are both involved in lipid metabolism. They are both able to beta oxidize fatty acids and are implicated in ROS production. However, their precise function in these metabolic pathways and their physiological functions are different. While mitochondrial metabolism is closely related to energy production, peroxisome does not seem to be associated with energy production but with the production of bioactive molecules and in detoxification processes.
