Maximum Contraction Amplitude Research Articles

Exploring the characteristics of detrusor after contraction in females with pure urodynamic stress incontinence

PurposeThis study aims to evaluate detrusor after contraction (DAC) characteristics in females with pure urodynamic stress incontinence (USI).MethodsWe examined the urodynamics database from our urodynamic study center. Urodynamic data from pure USI cases with and without DAC were compared. DAC was categorized based on morphological features, and urodynamic parameters in different subgroups were analyzed.ResultsA total of 61 female pure USI patients met all the study requirements. Among them, there were 27 cases of pure USI with DAC and 34 cases of pure USI without DAC. The incidence of pure USI with DAC in the overall female sample was 2.5%.Significant differences were observed in Qmax between pure USI with DAC and pure USI without DAC (20.1 ± 7.2 vs. 13.0 ± 6.8, p = 0.00), as well as in Pdetqmax (24.3 ± 15.1 vs. 16.3 ± 9.8, p = 0.02). Comparing parameters among the three subtypes of DAC revealed statistical differences in uroflow time: Type 1 DAC vs. Type 2 DAC vs. Type 3 DAC [21(20,22.5) vs. 22(16,27) vs. 30(26.8,30.8), p = 0.02], and in the maximum DAC contraction amplitude [64(46.5,107) vs. 39(25.5,48) vs. 45.5(24,74.8), p = 0.03]. Additionally, DAC was categorized into three subgroups: Type 1, Type 2, and Type 3.ConclusionsThis study offers an initial exploration of morphological and mathematical aspects of DAC in urodynamics involving females with pure USI. The findings also suggest DAC may serve as a potential new indictor of bladder function in females with pure USI.Trial registrationNot applicable.

PupilMetrics: a support system for preprocessing of pupillometric data and extraction of outcome measures

The rapid pupillary constriction to an abrupt light stimulus is signaled through an oligosynaptic neural pathway that dominates over other supranuclear influences on pupillary movement. A pupillometric recording of the pupil light reflex shows the steep change in pupil size from baseline to maximal constriction. However, when the pupil is recorded in darkness in the phase after light stimulation or in response to non-light stimuli like a sudden noise or cognitive activity, pupil size changes are small and slow. In such cases, pre-processing of pupil recordings to reduce the noise due to intrusion of various artifactual and non-evoked pupillary movements is particularly important but may be time-consuming. To address the paucity of automated tools for pupil light reflex analysis in pupillometry, we aimed to develop a software for automated, user-guided pupillometric data analysis. We identified two types of commonly observed artifacts on pupil recordings. We designed a software, called PupilMetrics, which imports and displays raw pupil data, detects and removes these two types of artifacts, and quantifies outcome measures like pupil size, response time, maximal contraction amplitude and PIPR. The right pupil of 29 healthy adults was recorded using a Neurolight pupillometer (IDMed, Marseilles) in response to 9 different light stimuli. Data analysis of the total 261 pupil responses were performed manually or automatically using PupilMetrics. High correlation was observed between PupilMetrics and manual analysis outcome measures across all stimuli (average R2 = 0.9891 and p < 0.0001) with a near 1-to-1 correspondence (Beta = 0.9940). PupilMetrics reduced the total analysis time from 30 h to under 1 h. PupilMetrics offers a time-efficient alternative to manual processing and delivers comparable results. Such software can facilitate standardization of pupillometry for clinical and research uses.

The role of adipose tissue cell elements in the regulation of the nitroxidergic system and possible ways of pharmacological modulation

Endothelial dysfunction is characterized by a decrease in the bioavailability of the vasodilator – nitric oxide (NO), and an increase in the level of vasoconstrictor substances. This imbalance leads to vasoconstriction, leukocyte attachment and inflammatory reactions in the vascular wall, atherosclerosis and thrombosis. The aim: to evaluate the role of adipose tissue elements in the regulation of parameters of the nitroxidergic system under hypoxia conditions. Materials and methods. The studies were carried out on 30 adult white male Wistar rats. All animals were randomly assigned and divided into groups: a control group (15 rats), type 2 diabetes mellitus (T2DM) was induced in the animals of the second group (15 rats). Isolated fragments of the popliteal arteries (PA) and intrapulmonary artery (IPA) were cleared of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+) and cut into rings. The simulation of acute hypoxia with further study of medical agents were performed. Results. The PA and IPA with PVAT responded to acute hypoxia with vasoconstriction – an increase in the amplitude of contraction in the first and second phases, and after removing PVAT, they responded with a decrease in the maximum amplitude of contraction by 3.4 times in the 1st phase and an increase in amplitude by 1.8 times in the 2nd phase. Perfusion with Angiolin reduced 2nd phase of HV of the PA and IPA. Adding a combination of Thiotriazoline and L-arginine (1:4) to a solution for perfusion of fragments of arteries of animals with T2DM, causes a significant increase in constrictor reactions in both the 1st and 2nd phases of HV, regardless of presence of perivascular adipose tissue. Conclusions. The presence of PVAT affects the HV of arteries, both in normal and in T2DM. The possibilities of ways of pharmacological modulation of the nitroxidergic system depending on the state of PVAT were determined.

EMG-CHARACTERISTICS OF MASTICATORY MUSCLES IN SUBJECTS WITH BRUXISM

Today, bruxism is a fairly common phenomenon. Bruxism is often defined as the parafunctional activity of the masticatory and facial muscles. Parafunction is called increased inappropriate activity, tension or even spasm of the masticatory and facial muscles, as well as the muscles of the tongue. However, the peculiarity of the work of masticatory muscles during the day in patients with signs of bruxism remains insufficiently studied.&#x0D; The aim of our study was to determine the features of EMG-activity of masticatory muscles in patients with bruxism.&#x0D; Materials and methods of research. We performed a clinical examination and superficial electromyography (EMG) of the masticatory muscles in 13 subjects aged 25 to 43 years. There were 7 women (53.8%), 6 men (46.2%). All examined subjects were somatically healthy, had no bad habits and defects of the dental arches. The mean age of the subjects was 32.5 ± 5.4 years. In the sample of patients, there were clinical signs of bruxism such as pathological abrasion of the hard tissues of the teeth; point dentin exposure; cracks in tooth enamel; hyperesthesia; pain or feeling of tension and discomfort in the masticatory muscles. All patients were performed superficial electromyography of the anterior temporal and masseter muscles using a 4-channel computerized electromyograph, according to the recommendations by Ferrario V., Sforza C. Electrical biopotentials of masticatory muscles were registered in tests lasting 10 s each: maximum bilateral teeth clenching, clenching of teeth on the left side; clenching of teeth on the right side. The data obtained during the EMG were processed using Synapsis software from Neurotech. We analyzed the indicators of maximum amplitude, mean amplitude (μV) of each muscle in every test. For objective evaluation of the results, we performed electromyography of masticatory muscles of 15 subjects comparable in age and sex without clinical signs of bruxism (control group, mean age was 33.4 ± 6.1 years).&#x0D; Research results. We determined the characteristics of EMG-activity of masticatory muscles in the control group in the test of bilateral maximum teeth clenching: symmetrical activity of masseter and temporal muscles on the left and right sides (p&gt; 0.05), the value of maximum amplitude of contractions did not exceed 1200 μV. It was found higher EMG-activity of the masseter and temporal muscles on a working side, compared to a balancing one in the test of unilateral teeth clenching, that was statistically confirmed (p&lt;0,05).&#x0D; In patients with bruxism, the EMG-activity of the masticatory muscles differed from the control group. Thus, the maximum amplitude of muscle contractions in all tests was significantly higher (p &lt;0.05) among people with bruxism. EMG-activity of masseter muscles in the majority of cases (10 subjects – 76.9%) was greater than the temporal. In tests of unilateral teeth clenching, the EMG-activity of the temporal and masseter muscles was slightly higher on the working side, but the difference with the indicators on the balancing side was not statistically confirmed (p&gt; 0.05). We found the peculiarity of the EMG-activity of the masticatory muscles in subjects with bruxism: the presence of pathological rhythmic peaks of activity in the resting phase. Differences in the indicators of EMG-activity between the subjects with bruxism and control group were evaluated using analyses of Student’s paired t-test. The hypotheses were verified at the level of significance p&lt;0,05.&#x0D; Conclusions. Bruxism is a complex problem of the whole human body, characterized by neuromuscular activity. In our study, some features of EMG-activity of masticatory muscles were studied and established. Patients with clinical signs of bruxism had significantly higher values of maximum, mean amplitude, which are 2.3-3.5 times higher than normal. In most cases, the EMG-activity of the masseter muscles was higher than the temporal. Presence of pathological rhythmic peaks of activity in the resting phase was found. In the future, it is planned to study individual changes in EMG-activity of masticatory muscles in patients with bruxism at different stages of total dental rehabilitation.

Effect of the level of magnesium in drinking water on the state of the cardiovascular system of spontaneous hypertensive rats

INTRODUCTION. Magnesium is the second most common intracellular cation, is a cofactor for more than 300 enzymes, affects the functional state of the cardiovascular system through various mechanisms, in particular, through the action on the smooth muscle cells of the vessels, modulation of the renin-angiotensin-aldosterone system, regulation of sodium and calcium homeostasis. Therefore, maintaining a normal level of magnesium in the blood is an urgent task, and the consumption of drinking water enriched with magnesium can be considered as a method of correcting an insufficient intake of exogenous magnesium.THE AIM. The purpose of the study was determined – to evaluate the effect of drinking water with different contents of magnesium ions and a complex of magnesium with calcium on the state of the cardiovascular system of rats with genetically determined arterial hypertension. MATERIALS AND METHODS. From 6–7 weeks of age, male SHR rats received drinking water of various compositions for two months: in the first group (hCа+Mg) – with increased content of calcium and magnesium (120 mg/l Ca2+ and 45 mg/l Mg2+), the second (nCа+Mg) – drinking water normalized by mineral composition (60 mg/l Ca2+ and 25 mg/l Mg2+), in the third (hMg) – enriched Mg2+ (45 mg/l), the fourth (control) control group – St. Petersburg tap water with a low mineral content (8 mg/l Ca2+ and 3 mg/l Mg2+). WKY rats were divided into 2 groups: one group (hMg) received water enriched with Mg2+ (45 mg/l), the control WKY (control) group received water with a low mineral content (8 mg/l Ca2+ and 3 mg/l Mg2+). After 2 months, the blood pressure of rats on the tail was measured by the cuff method, the level of urea, cholesterol, total calcium, and albumin in the blood serum was analyzed, left ventricular mass index (LVMI) and myocardial mass index (MMI) were calculated. The spontaneous contractile activity of the portal vein (PV) was recorded by myography (in vitro) in isometric mode. The following were analyzed: frequency, total and maximum amplitude of phase-tonic contractions, the area under the contraction curve in 1 min, which characterizes the work performed by the vein. %). RESULTS. Enrichment of drinking water with Ca2+ and Mg2+ had a more pronounced antihypertensive effect in SHR rats compared with the hMg2+ group. In WKY rats, magnesium enrichment of water did not affect blood pressure. Modification of the mineral composition of drinking water did not affect MMI and LVMI in both SHR and WKY rats. Interlinear differences were found in the contractile activity of PV in control rats (the amplitude of PV contractions in SHR rats was greater than WKY. Consumption of water enriched with minerals decreased the amplitude of PV contractions, the largest decrease was in the hMg2+ group (in SHR, 2.6 times, in WKY, 1.5 times as compared to the control of the corresponding line). The value of the work performed by the PV in the control SHR rats was greater than in the control rats of the WKY line, and the enrichment of water with magnesium caused a decrease in the work performed by the PV only in rats SHR lines (by 55.6 %), but not for WKY. CONCLUSIONS. In rats, the consumption of drinking water enriched only with magnesium has an antihypertensive effect; however, it suppresses the spontaneous contractile activity of PV. It is advisable to use a complex of magnesium with calcium, which lowers blood pressure, but maintains an adequate level of contractile activity of the PV.

Sampling reflex: pathogenic role in functional defecation disorder.

The sampling reflex is necessary to begin defecation or flatulence. It consists of a simultaneous rectoanal inhibitory reflex (RAIR) mediated by relaxation of the internal anal sphincter and rectoanal excitatory reflex (RAER) mediated by contraction of the external anal sphincter. The aim of this study was to evaluate the sampling reflex in patients with functional defecation disorder (FDD). A prospective cohort study was conducted on 58 obstructed defecation syndrome (ODS) patients with FDD. All 58 patients and 20 controls were evaluated with anorectal manometry to study the sampling reflex. Quantitative RAIR (total duration of reflex; maximal amplitude of relaxation; residual pressure at the lowest point of the RAIR) and RAER data (maximal amplitude of contraction; duration) were obtained. The straining test on manometry was considered positive for FDD if there was a muscle contraction/lack of relaxation or an insufficient pressure gradient for the passage of feces. Defecography was performed on all the patients with assessment of the anorectal angle and persistence or increase of puborectalis indentation. Fifty (86.2%) FDD patients had an altered sampling reflex, showing incomplete/short duration of RAIR and excessive contraction/duration of RAER. More specifically, there was a correlation between a positive straining test and a short total duration of RAIR (ρ 0.92) as well as with excessive duration of RAER (ρ 0.89). There was also a correlation between lack of muscle relaxation on defecography and short total duration of RAIR ((ρ 0.79) and between lack of muscle relaxation on defecography and excessive duration of RAER (ρ 0.83). Altered maximal amplitude relaxation had the highest sensitivity in detecting impairment of RAIR (87.9) while maximal amplitude contraction had the highest sensitivity in detecting impairment of RAER (89.6). High residual pressure at the lowest point of RAIR had the highest specificity in detecting impairment of RAIR (80.0) while RAER duration had the highest specificity in detecting impairment of RAER (77.7). The sampling reflex is impaired in patients with FDD. This finding provides an important insight into the pathogenesis of obstructed functional defecation.

Біологічно активні композиції, які містять нейротрофічні фактори, змінюють скоротливу активність детрузора щурів iз iнфравезiкальною обструкцією

The contractile activity of urinary bladder (UB) after introduction of biologically active compositions (BAC) containing neurotrophic factors in female rats with infravesical obstruction, which was modeled by a ligature to the urinary tract distal part, was investigated. Cryoextract of the spinal ganglia (SG), conditioned culture media of native and cryopreserved mantle gliocytes (MG), the bulk medium, the drug Cortexin were used as BAC. Animals were injected with BAC for 10 days and the contractile activity (CA) of isolated UB strips was determined by measuring KCl-induced and agonist-dependent responses. The use of BAC, in addition to Cortexin, contributed to the CA restoration. The conditioned culture medium of cryopreserved MG and cryoextract of SG increased the agonist-dependent response by 4.6 and 2.5 times, respectively, compared to the CA of the control animals. The rats in these groups showed the highest indices of maximal amplitude of contraction, similar to the control ones. Probl Cryobiol Cryomed 2020; 30(2): 188-198

Effects of maternal parity on response of human myometrium to oxytocin and ergometrine in vitro

ObjectiveThe aim of this study was to compare the effects of oxytocin and ergometrine on the intrinsic contractile parameters of human uterine smooth muscle at term between primiparous and multiparous women. Study designMyometrial biopsies were obtained from women undergoing planned caesarean section at term. The biopsies were dissected into eight uniform strips and mounted in tissue baths for isometric recording. The strips were challenged with increasing concentrations of oxytocin and ergometrine. Parameters of contractile activity, including mean contractile force (MCF) and maximum amplitude of contractions (MAMP) were recorded and analysed. Results were compared between primiparous (Group 1) and multiparous (Group 2) women. ResultsMyometrial biopsies were obtained from n = 11 donors (88 tissue strips), of which n = 5 were Group 1 and n = 6 were Group 2. In relation to oxytocin, the MAMP value observed was significantly greater in Group 2 than in Group 1 (151 ± 18mN vs 67 ± 14mN, P < 0.01). Regarding ergometrine, the MCF response was greater in Group 2 samples (24 ± 10 mN) than that in Group 1 (18 ± 2mN) (P < 0.05). ConclusionOur findings highlight that women in a first pregnancy have a decreased response to both oxytocin and ergometrine in an in vitro setting when compared with women in a subsequent pregnancy, and this may have clinical implications regarding the management of postpartum haemorrhage in this cohort.

Spontaneous Human Myometrial Contractility in the Third Trimester of Pregnancy in Relation to Past Mode of Delivery.

It is well established that women with a previous vaginal delivery have higher success rates in relation to vaginal birth after cesarean than those without. The aim of this study was to examine the effect of past mode of delivery on contractile parameters of human myometrium in vitro. Myometrial strips were excised from 64 women at cesarean delivery (CD) and recordings of spontaneous contractile activity analyzed and compared across three clinical groups: (1) women with no previous delivery (Group 1); (2) women with CD only (Group 2); and (3) women with a history of vaginal delivery and CD (Group 3). Myometrial samples from women in Group 3, women who had a previous vaginal delivery, had a significantly greater maximum amplitude of contractions (p < 0.05), a greater force (mean contractile force) of contractions (p < 0.01), and a faster rate of rise (p < 0.01) and relaxation of contractions (p < 0.05) than those in Groups 1 and 2. Many of the functional parameters of human uterine contractions are altered, or enhanced, in the women who have had a previous vaginal delivery, when compared with those without. This may partly explain the clinical differences observed in labor.

Muscle activation during maximum voluntary contraction and m-wave related in healthy but not in injured conditions: Implications when normalizing electromyography

BackgroundElectromyography signal amplitude is influenced by a variety of factors. Normalization strategies aimed at decreasing signal variability include using peak electromyography signal during a maximum voluntary contraction and peak-to-peak M-wave amplitude. However, whether these normalization methods are comparable has not been investigated in injured populations. This study investigated the relationship between peak signal during maximum voluntary contraction and M-wave amplitude in individuals with a unilateral Achilles tendon rupture. Secondarily, we observed whether the two normalizations strategies would yield similar results when evaluating between limb differences in muscle activity during a jump task. MethodsEleven individuals 1–3 years after a unilateral Achilles tendon rupture were included in this study. Surface electromyography was used on the medial and lateral gastrocnemii bilaterally. Peak maximum voluntary contraction, M-wave amplitude, and electromyography during a jumping task were collected. FindingsA strong relationship was observed between peak maximum voluntary contraction and M-wave amplitude on the uninjured (r = 0.71–0.88, P < 0.05) but not on the ruptured side (r = 0.41–0.44, P > 0.05). The two normalization techniques did not produce different results when comparing the uninjured and ruptured sides. InterpretationThe findings of this study suggest that M-wave normalization yields similar results as peak maximum voluntary contraction-normalized electromyography in uninjured conditions. M-wave normalization may be a useful strategy in an injured population where a maximal muscle contraction is unsafe or impaired.

Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats

IntroductionAlthough premature ejaculation (PE) is the most common sexual dysfunction in young men, its true pathophysiology has not yet been clearly elucidated. AimTo investigate the quantitative changes that occurred in an ejaculation model induced by para-chloroamphetamine (PCA) after botulinum-A toxin injection into the bulbospongiosus (BS) muscle in rats. MethodsA total of 21 male rats weighing 300 to 350 grams were used in the study. The animals were divided into 3 groups: control, 1 unit of botulinum-A toxin injected, and 5 units of botulinum-A toxin injected. The botulinum-A toxin was percutaneously injected into the BS muscle, and the experiment was carried out 96 hours (5 days) after the injection. Main Outcome MeasureThe seminal vesicle (SV) was cannulated, and the BS muscle was dissected and connected to an amplifier (Biopac; Goleta, CA) to record the pressure and electromyography measurement. The ejaculation parameters were obtained after the PCA injection. ResultsThe ejaculation latency time of the group receiving 5 units of botulinum-A toxin was statistically significantly longer (1092 ± 657 seconds) compared to the control group (298 ± 81 seconds) and the group receiving 1 unit of botulinum-A toxin (439 ± 100 seconds) (P = .003). Furthermore, the BS EMG area under the curve values for the group receiving 5 units of botulinum-A toxin were significantly lower (7.4 ± 1.2 V/s × 10–4) than those of the control group (13.6 ± 4.0 V/s × 10–4) and the group receiving 1 unit of botulinum-A toxin (13.6 ± 5.0 V/s × 10–4) (P = .009). No statistically significant difference was found between the groups in terms of the basal SV pressure, number of SV phasic contractions, maximum amplitude of the SV phasic contraction, and intervals between the SV phasic contractions and the BS muscle contractions. Clinical ImplicationsBotulinum-A toxin injection is a potential treatment option for PE and should be further investigated by future clinical studies. Strengths and LimitationsEase of administration and prolonged duration of botulinum-A toxin are advantages of the existing treatment options. The risk of anejaculation due to the dosage should be kept in mind. ConclusionsInjection of botulinum-A toxin into the BS muscle in rats significantly delayed the ejaculation latency time and affected the expulsion phase.Ongün S, Acar S, Koca P, et al. Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats. J Sex Med 2019;16:1338–1343.

Mechanical analysis of intestinal contractility in a neonatal maternal deprivation irritable bowel syndrome rat model

The aims of the present study are to investigate biomechanical properties and provide mechanical analysis of contractility in ileum and colon in a neonatal maternal deprivation (NMD) irritable bowel syndrome (IBS) rat model. Mechanical testing was done on segments from ileum and colon in 25 IBS rats and 13 Control rats. Morphometric data were obtained from digitized images of the segments at no-load and zero-stress states. Pressure and diameter changes were measured during flow and ramp distensions under active and passive experimental conditions. Circumferential stresses (force per area) and strains (deformation) were computed with referenced to the zero-stress state. The contraction frequency was analyzed. Contraction thresholds and maximum contraction amplitude were calculated in terms of mechanical stress and strain. Compared with controls, the IBS rats had lower body weight (P < 0.01), smaller colonic opening angle (P < 0.05), higher colonic contraction frequency (P < 0.05 and P < 0.01) and lower contraction thresholds of pressure, stress and strain in both ileum and colon (P < 0.05 and P < 0.01). The maximum contraction pressure, stress and strain did not differ between IBS and Control groups (P > 0.05). In conclusion, the pressure, stress, and strain to evoke contractility in ileum and colon were lower whereas the frequency of induced colon contractions was higher in NMD IBS rats compared to normal rats. Furthermore, zero-stress state remodeling occur in colon in NMD IBS rats. Further studies on the association between intestinal biomechanical properties, hypersensitivity and afferent signaling in the IBS animal models are warranted.

Stress-strain analysis of duodenal contractility in response to flow and ramp distension in rabbits fed low-fiber diet.

Previously we demonstrated that low-fiber diet in rabbits affects the passive mechanomorphological properties in the small intestine, resulting in reduced intestinal wall thickness and collagen content, as well as intestinal wall softening. The aim of the present study was to evaluate the contractility in rabbits on long-term low-fiber diet and specifically to compare the contraction threshold, the frequency, and the amplitude of flow-induced and distension-induced contractions in the duodenum between rabbits on normal diet and on long-term low-fiber diet. Ten rabbits were fed a low-fiber diet for 5months (Intervention group), and five rabbits were fed normal diet (Control group). The duodenal segments were used for determination of mechanical parameters for analyses of contractility. The duodenal experiments were carried out in organ baths containing physiological Krebs solution. Pressure and diameter changes induced by contractions in response to flow and ramp distension were measured. The frequencies and amplitude of contractions were analyzed. Distension-induced contraction thresholds and maximum contraction amplitude of flow-induced contractions were calculated in terms of mechanical stress and strain. Multiple linear regression analyses were applied to study dependencies between contractility parameters and wall thickness, wall area, and muscle layer thickness. During distension, the pressure, stress, and strain thresholds for induction of phasic contraction were biggest in the Intervention Group (P<0.05). In addition, the contraction frequencies during flow-induced contraction were highest in the Intervention Group (P<0.05), whereas the maximum contraction amplitudes in terms of pressure, diameter, stress, and strain were lowest in the Intervention Group (P<0.05). The contraction thresholds and contraction frequencies were negatively associated with the wall thickness, wall area, and muscle layer thickness, whereas maximum contraction amplitudes were positively associated with the wall thickness, wall area, and muscle layer thickness. Duodenal contractility in rabbits fed with long-term low-fiber diet exhibited low contraction amplitudes and high contraction thresholds and frequencies. The changes were associated with the low-fiber diet-induced histomorphological remodeling. Studies on detailed structural and functional diet-induced changes in smooth muscle and intestinal nerves are needed for better understanding the remodeling mechanisms.

The effects and possible mechanism of β2AR gene expression in cardiocytes of canines with heart failure.

The objective of the present study was to observe the changes of β2-adrenergic receptor (β2AR) protein expression in a canine model of heart failure (HF), and the function of cardiocytes after transfection with Adv-β2AR. The canine model of chronic HF was induced by rapid right ventricular pacing and cardiocytes were isolated with collagenase II. Cardiocytes were transfected with Adv-β2AR to observe contractile function with a motion edge-detection system of single cells. Expression of β2AR protein in cardiocytes was measured by immunoblotting and the levels of intracellular cAMP were measured by ELISA. Compared with the control group (the sham group), the expression of β2AR protein in HF cardiocytes did not change, but the basal (1 mM Ca2+) contraction amplitude percentage (1.809±0.922 vs. 1.120±0.432%, P<0.05), the maximum contraction amplitude percentage (14.855±2.377 vs. 10.784±2.675%, P<0.01) and the basal levels of intracellular cAMP (9.39±2.54 vs. 5.26±0.95 pmol/ml, n=6, P<0.05) of HF cardiocytes were significantly decreased. However, when HF cardiocytes were transfected with Adv-β2AR and cultured for 48 h, compared with the non-transfected group, the basal contraction amplitude percentage (0.851±0.324 vs. 1.629±0.522%, P<0.05), the maximum contraction amplitude percentage (9.260±2.208% vs. 12.205±1.437%, P<0.01) and the basal levels of intracellular cAMP (5.26±0.95 vs. 9.03±1.03 pmol/ml, n=6, P<0.05) of cardiocytes in the transfected group were significantly increased. In conclusion, the expression of β2AR protein in HF cardiocytes did not change, but contraction function was impaired. The moderate overexpression of β2AR gene in the HF cardiocytes increased the levels of intracellular cAMP and improved contraction function.

Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed Vermiform Appendix.

Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix. Contractions of the longitudinal muscle strips of inflamed appendix were recorded in vitro at 37±0.5°C. Control contractions were recorded for 30 min after an initial tension of 0.5 gram. Initially dose-response experiments of agonists (acetylcholine, serotonin and histamine) were performed separately and the dose that produced maximum contraction was determined with each agonist. This maximal dose of agonist was used to elicit contractions in next series of experiments before and after pre-treatment with appropriate antagonists like atropine, ondansetron (5-HT3 antagonist) and chlorpheniramine maleate respectively. Acetylcholine (ACh) and serotonin (5-HT) elicited maximum amplitude of contraction at 10 µM and 1 µM concentration respectively. These contractions were significantly blocked by prior exposure of muscle strips with atropine (100 µM) and ondansetron (10 µM). Histamine produced very low amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose-response relations. The histamine induced contractions were blocked by H1 antagonist chlorpheniramine maleate (100 µM). The observations suggested that the contractility of longitudinal muscle strips of inflamed vermiform appendix in human beings was predominantly mediated by muscarinic and serotonergic (5-HT3) mechanisms, whereas, histaminergic mechanisms played a minor role in mediating the contractility.

Short-term effects of β2-AR blocker ICI 118,551 on sarcoplasmic reticulum SERCA2a and cardiac function of rats with heart failure.

The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured. The results showed that compared with the Sham group, the survival rate, percentage of basic contraction and maximum contraction amplitude percentage of cardiac muscle cells with heart failure decreased, Gi protein expression increased while Gs and SERCA2a protein expression decreased. Compared with the HF group, the maximum contraction amplitude percentage of cardiac muscle cells in group HF+ICI 50 nM decreased, the Gi protein expression level increased while the SERCA2a protein expression level decreased. Following the stimulation of Ca2+ and ISO, the maximum contraction amplitude percentage of cardiac muscle cells in the HF+ICI 50 nM group was lower than that in group HF. This indicated that ICI 118,551 has negative inotropic effects on cardiac muscle cells with heart failure, which may be related to Gi protein. Systolic function of cardiac muscle cells with heart failure can therefore be reduced by increasing Gi protein expression and lowering SERCA2a protein expression.

Seasonal variation of the pupil light reflex

PurposeVariation of retinal light sensitivity between winter and summer seasons may be a marker for seasonal affective disorder and the basis for response to phototherapy. As the pupil is a marker of retinal light sensitivity and shows a 24‐hour variation that reflects circadian rhythm, we used the pupil as proxy to assess light sensitivity of rods, cones and melanopsin as a function of seasonal light in healthy adults.Methods37 adults were tested during the short (January‐February) and long (July‐August) annual photoperiods. All subjects completed standardized questionnaires of seasonality and sleep. Pupil responses to blue (470 nm) and red (622 nm) light were recorded under dark and light adapted conditions using an automated pupillometer. Main outcome parameters were maximal contraction amplitude and post‐stimulus contraction amplitude.ResultsAll but two subjects reported good sleep quality. One subject was an extreme morning type. Twelve subjects reported a global seasonal variation in sleep, mood and appetite but without dysfunction or disability. Baseline pupil size of light adapted eyes was greater in summer compared to winter. Maximal contraction amplitudes to scotopic and photopic light stimuli were greater in summer. The post‐stimulus pupil contraction was also greater in summer, but only after light adaptation.ConclusionsBaseline pupil size and pupil responses derived from rods, cones and melanopsin photoreception were greater in summer in healthy adults. This seemingly greater retinal sensitivity to light when the photoperiod (daylength) is long suggests a more central basis for seasonal regulation of the pupil light reflex.

Role of large conductance calcium-activated potassium channels in vascular hyporesponsiveness in rats with obstructive jaundice

Objective To evaluate the role of large conductance calcium-activated potassium (BKCa) channels in vascular hyporesponsiveness in rats with obstructive jaundice. Methods Eighteen male Sprague-Dawley rats, weighing 180-200 g, were randomly divided into 3 groups (n = 6 each) using a random number table: control group (group C), sham operation group (group S), and bile duct ligation group (group BDL). Obstructive jaundice was produced by common bile duct ligation.At 7 days after surgery, blood samples were collected for determination of the levels of serum total bilirubin (TBL), direct bilirubin (DBL), indirect bilirubin (IBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Thoracic aortic rings were prepared, and the endothelium was removed.The aortic rings were sequentially perfused with different concentrations of norepinephrine (NE) and sodium nitroprusside (SNP), and the maximum amplitude of contraction and dilatation of aortic rings was recorded.The aortic rings were then perfused with BKCa channel blocker Chtx with the final concentration of 10-7 mol/L, followed by perfusion with different concentrations of NE and SNP again, and the maximum amplitude of contraction and dilatation of aortic rings was recorded under each concentration.The percentage of maximum contraction and dilatation (maximum amplitude after Chtx administration÷maximum amplitude before Chtx administration×100%) was calculated. Results Compared with C and S groups, the levels of TBL, DBL, IBL, ALT and AST in serum were significantly increased, the maximum amplitude of NE-induced contraction of aortic rings was decreased, and the percentage of the maximum NE-induced dilatation of aortic rings was increased, the maximum amplitude of SNP-induced contraction of aortic rings was increased, and the percentage of the maximum SNP-induced dilatation of aortic rings was decreased in group BDL. Conclusion Excessive opening of BKCa channels may be involved in the mechanism of vascular hyporesponsiveness in rats with obstructive jaundice. Key words: Jaundice, obstructive; Large-conductance calcium-activated potassium channels; Aorta, thoracic

Comparative Study of Protective Effects of Salbutamol and Beclomethasone against Insulin Induced Airway Hyper-reactivity on Isolated Tracheal Smooth Muscle of Guinea Pig.

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin (10(-7) to 10(-3) M), insulin pretreated with fixed concentration of salbutamol (10(-7) M) and beclomethasone (10(-6) M) were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean ± SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 ± 1.13 mm, 14.55 ± 0.62 mm and 22 ± 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction.

Effect of topical anti-glaucoma medications on late pupillary light reflex, as evaluated by pupillometry.

The late post-illumination pupillary response (PIPR 10-30s ) to blue light is reduced in glaucoma, suggesting that pupillometry can be used in clinical glaucoma evaluation. Since animal studies have indicated that common anti-glaucomatous agents affect the iris muscle, we investigated the short-term effect of the anti-glaucoma drugs on the pupillary light reflex and in particular on the PIPR10-30s. In this randomized, double-masked, crossover trial, pupillometry was performed before and after topical administration of latanoprost, dorzolamide, and timolol in 20 healthy subjects. Stimulus was blue (463 nm) and red light (633 nm) of 2 log (lux). Main outcome was the PIPR10-30s to blue light. Additionally, pupil size, maximal contraction, and the early post-illumination pupillary response (PIPR 0-10s ) to blue and red light were investigated. Pupil response variations between 8 a.m. and 2 p.m. were also assessed. Intraocular pressure (IOP) was measured before and 3.5 h after drug instillation. We found no drug effect on the blue light PIPR10-30s or any other blue light pupil parameters. During the control day, the only significant variation over time was observed for the red light PIPR0-10s (p = 0.02). Pupillary size decreased slightly with timolol (0.1 mm, p = 0.03) and dorzolamide (0.2 mm, p < 0.001), but not with latanoprost. Timolol also reduced the maximal contraction amplitude significantly during red light (p = 0.02). Intraocular pressure was significantly reduced by all three drugs after 3.5 h (p < 0.01), while it remained unchanged during the control day (p = 0.3). Anti-glaucoma medications did not interfere with the blue light elicited PIPR. Dorzolamide reduced pupil size, while timolol reduced both pupil size and maximal contraction to red light, but the effect was minute and not of clinical importance.