Active Harmonic Compensation and Stability Improvement in High-Power Grid-Connected Inverters Using Unified Power Quality Conditioner

Multifunctional features of grid-connected inverters can be used for harmonic compensation of local load voltage and grid-injected current. But, in high-power grid-connected inverters, there is a challenge due to low switching frequency. On the other hand, simultaneous compensation of local load voltage and grid-injected current harmonics is an important issue in grid-connected inverters. Using a Unified Power Quality Conditioner (UPQC) at the Point of Common Coupling (PPC), an improved active harmonic compensation method is proposed which is appropriate for high-power low-frequency grid-connected inverters. The UPQC operates as a combination of a negative shunt virtual admittance and a negative series virtual impedance at the PCC. It suppresses the disturbances caused by local load variation and grid impedance change. Using a low-power, high-frequency UPQC, local load voltage and grid-injected current harmonics up to higher-order components are simultaneously compensated despite grid impedance changes and nonlinear local load variations. The control system is designed according to the impedance-based stability criterion to ensure the system's stability. The theoretical results are validated using different case study simulations in MATLAB/Simulink software

Identification of myoelectric signals of pregnant rat uterus: new method to detect myometrial contraction

Aim To develop an electromyography method for pregnant rat uterus in vivo and to separate myometrial signals from the gastrointestinal tract signals. Methods: Pregnant Sprague-Dawley rats (n = 8) were anaesthetized and their stomach, small intestine, and large intestine were removed from the abdomen. A pair of thread electrodes was inserted into the uterus, while a pair of disk electrodes was placed subcutaneously above the myometrium. Additionally, a strain gauge sensor was fixed on the surface of the myometrium and cecum for the parallel detection of mechanical contractions in rats (n = 18) with intact gastrointestinal tract. The filtered electric signals were amplified and recorded by an online computer system and analyzed by fast Fourier transformation. The frequency of the electric activity was characterized by cycle per minute (cpm), the magnitude of the activity was described as power spectrum density maximum (PsDmax). Results: The frequency of the pregnant uterine activity was 1-3 cpm, which falls within the same range as that of cecum. Measuring by both electrodes, oxytocin (1 μg/kg) increased and terbutaline (50 μg/kg) decreased the PsDmax by 25%-50% (P < 0.001) and 25%-40% (P < 0.01), respectively. We found a strong positive correlation between the alterations of PsDmax values and the strain gauge sensordetected mechanical contractions (area under curve). The GI specific compounds (neostigmine, atropine) mainly affected the cecal activity, while myometrium specific drugs (oxytocin, terbutaline) influenced the myometrial signals only. Conclusion: Our method proved to be able to detect the myoelectric activity that reflects the mechanical contraction. The overlapping myometrial and cecal signals are not separable, but they can be distinguished based on the much higher activity and different pharmacological reactivity of the pregnant uterus. Thus, the early signs of contractions can be detected and labor may be predicted in a fast and sensitive way

Smooth muscle electromyography for detecting major alterations in the estrus cycle in rats

Determining the female animal cycle is crucial in preclinical studies and animal husbandry. Changes in hormone levels during the cycle affect physiological responses, including altered contractility of the visceral smooth muscle. The study aimed to identify estrus and anestrus using smooth muscle electromyographic (SMEMG) measurements, in vivo fluorescent imaging (IVIS) and in vitro organ contractility of the uterus and cecum. The study involved sexually mature female Sprague-Dawley rats, aged 10–12 weeks. The rats received a daily injection of cetrorelix acetate solution for 7 days, while another group served as the control. The animals were subjected to gastrointestinal and myometrial SMEMG. The change in αvβ3 integrin activity was measured with IVIS in the abdominal cavity. Contractility studies were performed in isolated organ baths using dissected uterus and cecum samples. Plasma samples were collected for hormone level measurements. A 3-fold increase in spontaneous contraction activity was detected in SMEMG measurements, while a significant decrease in αvβ3 integrin was measured in the IVIS imaging procedure. Cetrorelix reduced the level of LH and the progesterone / estradiol ratio, increased the spontaneous activity of the cecum rings, and enhanced KCl-evoked contractions in the uterus. We found a significant change in the rate of SMEMG signals, indicating simultaneous increases in the contraction of the cecum and the non-pregnant uterus, as evidenced by isolated organ bath results. Fluorescence imaging showed high levels of uterine αvβ3 integrin during the proestrus-estrus phase, but inhibiting the sexual cycle reduced fluorescence activity. Based on the results, the SMEMG and IVIS imaging methods are suitable for detecting estrus phase alterations in rats

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

Aim To assess the effect of 17β-estradiol pretreatment on the function and expression of α2- adrenergic receptors (ARs) subtypes in late pregnancy in rats. Methods Sprague-Dawley rats (n = 37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α2-AR subtypes was determined by real time polymerase chain reaction and Western blot analysis. In vitro contractions were stimulated with (-)-noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α2A), ARC 239 (α2B/C), and spiroxatrine (α2A). The cyclic adenosine monophosphate (cAMP) accumulation was also measured. The activated G-protein level was investigated by guanosine 5’-O-[gamma-thio]triphosphate (GTPγS) binding assay. Results 17β-estradiol pretreatment decreased the contractile effect of (-)-noradrenaline via the α2-ARs, and abolished the contractile effect via the α2B-ARs. All the α2-AR subtypes’ mRNA was significantly decreased. 17β-estradiol pretreatment significantly increased the myometrial cAMP level in the presence of BRL 44408 (P = 0.001), ARC 239 (P = 0.007), and spiroxatrine (P = 0.045), but did not modify it in the presence of spiroxatrine + BRL 44408 combination (P = 0.073). It also inhibited the G-protein-activating effect of (-)-noradrenaline by 25% in the presence of BRL 44408 + spiroxatrine combination. Conclusions The expression of the α2-AR subtypes is sensitive to 17β-estradiol, which decreases the contractile response of (-)-noradrenaline via the α2B-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the α2-AR

Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility

Obesity is a global health problem even among pregnant women. Obesity alters quality of labor, such as preterm labor, prolonged labor, and higher oxytocin requirements in pregnant women. The most important factors to play a role in the altered gestational period and serve as drug targets to treat the consequences are female sexual hormones, calcium channels, adrenergic system, oxytocin, and prostaglandins. However, we have limited information about the impact of obesity on the pregnant uterine contractility and gestation time. Adipose tissue, which is the largest endocrine and paracrine organ, especially in obesity, is responsible for the production of adipokines and various cytokines and chemokines, and there are no reliable data available describing the relation between body mass index, glucose intolerance, and adipokines during pregnancy. Recent data suggest that the dysregulation of leptin, adiponectin, and kisspeptin during pregnancy contributes to gestational diabetes mellitus and pre-eclampsia. A preclinical method for obese pregnancy should be developed to clarify the action of adipokines and assess their impact in obesity. The deeper understanding of the adipokines- induced processes in obese pregnancy may be a step closer to the prevention and therapy of preterm delivery or prolonged pregnancy. Gestational weight gain is one of the factors that could influence the prenatal development, birth weight, and adiposity of newborn

Development of targeted LC-MS/MS method for analysis of diclofenac and its main metabolites in rat liver perfusion solution obtained by new type of ex vivo perfusion system

Isolated perfused rat liver (IPRL) is used as ex vivo simulation for more accurate evaluation of pharmacokinetic parameters of target drugs, production of their metabolites and their excretion in the bile. Compared to in vivo systems, IPRL avoids the clearance of any other organ and permits the control over the factors that may affect the hepatic metabolism, for example, the flow rate of the perfusate, pH, pressure, and concentration of chemicals. This simple experimental technique, unlike the cultured cells, keeps the intactness of the liver, in other words, cells other than hepatocytes, drug transporters' distribution, as well as enzymes, are still affecting the metabolism which gives a realistic picture [1-2]. The portal vein of the anesthetized rat was cannulated and the perfusion solution saturated with carbogen (95% O2 and 5% CO2) was pumped through it. The solution was directed through the transected abdominal vein to the waste. A cannula was inserted into the inferior vena cava through the right heart atrium through which the perfusate leaved the liver after the ligation of the abdominal vein. The isolated liver was then placed into the buffer vapour chamber of the recirculated perfusion system and the perfusate samples were collected during different time intervals. The main goal of our work was the development of targeted reversed-phase LC-MS/MS analytical method for the analysis of diclofenac (DF) and its main metabolites namely diclofenac-O-acyl glucuronide (Glu-DF) and 4-hydroxydiclofenac (4´OH-DF) in the perfusion solution of rat liver. We are planning to use diclofenac as a reference compound in the future investigation of metabolism of designer drugs. DF and its metabolites were extracted by the optimized liquid-liquid extraction procedure. LC separation was achieved by gradient elution of the mobile phase consisted of 0.1% formic acid in water and 0.1% of formic acid in acetonitrile on a Luna Phenyl-Hexyl column at 50˚ C with a run time of 10 minutes. The Agilent 1100 LC system was coupled to the triple quadrupole TSQ 7000 mass spectrometer. The appropriate transitions were monitored during the region of elution of each analyte. The linearity range of DF was between 100 ng/mL and 40 μg/mL. The related matrix effect, recovery and process efficiency were successfully evaluated

Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates

Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation. © 2016 Informa UK Limited, trading as Taylor &amp; Francis Group

Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Ca 2.2 Blocker Multitarget Ligands.

N-type voltage-dependent Ca2+ channels (CaV 2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.2 blockers such as the omega-conotoxin MVIIA (Prialt) are analgesic and have opioid-sparing effects. With the aim to develop new multitarget analgesic compounds, we designed the first omega-conotoxin/opioid peptidomimetics based on the enkephalin-like sequence Tyr-D-Ala-Gly-Phe (for the opioid portion) and two fragments derived from the loop-2 pharmacophore of omega-conotoxin MVIIA. Antinociceptive activity evaluated in vitro and in vivo revealed differential affinity for CaV 2.2 and opioid receptors and no significant synergistic activity