The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.
The mechanism of the contractile response of longitudial muscle of rabbit ileum to substance P (SP) has been investigated. The contractions in rabbit ileum under various conditions were recorded isometrically The following results were obtained. 1) The contractions by SP increased according to concentrations. SP·induced contraction was not sustained but faded rapidly at $10^{-7}M$. The response to the commutative addition of SP was decreased in comparison to the response to separate administration of each concentration . 2) The response to $10^{-8}M$ SP after 5 min application cf $10^{-7}M$ SP was increased with increasing the time interval between the administration of $10^{-7}$ and $10^{-8}M$ SP. 3) The treatment of rabbit ileum by $10^{-7}M$ SP for 5 min didn't decrease the response to $10^{-6}M$ acetylcholine. 4) $10^{-6}M$ atropine had no effect of the contractile response to $10^{-7}M$ SP. The response to $10^{-7}M$ SP was normal or subnormal in the presence of 3 mM tetraethylammonium(TEA). 5) 100k solution, $10^{-4}M$ ouabain, and Na-free solution inhibited the response to $10^{-8}M$ SP and 3 mM TEA completely, and to $10^{-7}M$ SP incompletely. 3 mM TEA induced a considerable contraction in K-free solution, but $10^{-8}M$ SP didn't induce the contraction. $10^{-6}M$ norepinephrine decreased the contractile responses to SP and TEA. 6) The contractile response to $10^{-7}M$ SP was dependent on the extracellular $Ca^{2+}$ concentrations to 1.8 mM. 7) The contractile response to $10^{-7}M$ SP remained 15% of the maximal response after bathing the ileum in a Ca-free solution for 2.5 min. 8) The responsiveness to SP was completely lost within 10 min of bathing in Ca-free solution, but was restored by the exposure to $Ca^{2+}$. The restorative effect of $Ca^{2+}$ depended on the concentration of $Ca^{2+}$, and on time for which the tissue exposed to this $Ca^{2+}$ concentration. These results suggest that there are two mechanisms of the action by which the low concentrations of substance P causes the contraction of intestinal smooth muscle: the reduction of K conductance and a mechanism dependent on the extracellular $Ca^{2+}$, and that high concentration of SP may elicit a contraction by releasing $Ca^{2+}$ from an intracellular store, which is not as sensitive to removal of extracellular $Ca^{2+}$ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane.
Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD $(days)=0.26{\times}D$ (Gy)+0.13 in the radiation alone group, and the TGD $(days)=0.30{\times}D$ (Gy)+0.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 ($95\%$ confidence interval; $1.13\~1.27$). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.005) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor $(0.5\%\;vs.\;5.2\%,\;p=0.005)$. The blood flow was not changed with the GBE in normal muscle, but was increased by $23.5\%$ ( p=0.0004) in the tumor. Conclusion : Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.
Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.
The expansion of air transport on a global scale with ever increasing traffic densities has brought about problems that must be solved through new multilateral mechanisms. Looking to the immediate future, air transport will require new forms of international cooperation in technical and economic areas. Air transport by its very nature should have been a counterforce to nationalism. Yet, the regulatory system in civil aviation is still as firmly rooted in the principle of national sovereignty as when it was first proclaimed at t-11e Paris Convention of 1919 and reaffirmed in the Chicago Convention. Sovereignty over the airspace has remained the cornerstone of relations between states in all respects of air transport. The importance of sovereignty over air space embodied in article 1 of the Chicago Conrenton also is responsible for restricting the authority of ICAO as an intergovernmental regulatory agency. The Orgenization, for all its extensive efforts, has only limited authority. ICAO sets standards but cannot enforce them; it devises solutions but cannot impose them. To implement its rules ICAO most rely not so much on legal requirements as on the goodwill of states. It has been forty-eight years since international community set the foundations of the international system in civil aviation action. Profound political, economic and technological changes have taken place in air transport. The Chicago Convention is living proof that staes can work together to make air transport a safe mode of travel. The law governing international civil auiation is principally based on international treaties and on other regulation agreed to by governments, for the most part through the mechanism of ICAO. The role of ICAO international standards and recommended practices and procedures dealing with a broad range of technical matters could hardly be overestimated. The organization's ability to develop these standards and procedures, to adapt them continuously to the rapid sate of change and development of air transport, should be particularly stressed. The role of ICAO in the area of the development of multilateral conventions on international air law has been successful but to a certain degree. From the modest starting-point of the Tokyo Convention, we have seen more adequate international instruments prepared within the scope of ICAO activities, adopted: the Hague Convention of 1970 for the suppression of Unlawful Seizure of Aircraft and the Montreal Convention of 1971 for the Suppression of Unlawful Acts against the Safety of Civil Aviation. The work of ICAO in the new domain of international law conventions concerning what has been loosely termed above as the criminal problems connected with international air transport, in particular the problem of armed aggression against aircraft, should be positively appreciated. But ICAO records in the domain of developing a uniform legal system of international carriage by air are rather disappointing. The problem of maintaining and developing the uniformity of this regulation exceeds the scope of interest and competence of governmental transport agencies. The expectations of mankind linked to it are too great to give up trying to restore the uniform legal system of international air carriage that would create proper conditions for its further growth. It appears that ICAO has, at present, a good opportunity for doing this. The hasty preparation of ICAO draft conventions should be definitely excluded. Every Preliminary draft convention ought to be sent to Governments of all member-States for consideration, So that they could in form ICAO in due time of their observation. The problom of harmonizing a uniform law of international air carriage with that of other branches of international transport should demand more and more of its attention. ICAO cooperation with other international arganization, especially these working in the field of international transport, should be strengthened. ICAO is supposed to act as a link and a mediator among, at times the conflicting interests of member States, serving the happiness and peace of all of the world. The transformation of the contemporary world of developing international relations, stimulated by steadily growing international cooperation in its various dimensions, political, economic, scientific, technological, social and cultural, continuously confronts ICAO with new task.
During the last decade extensive studios on catecholamines have evolved new knowledge in the physiology and biochemistry of adrenergic mechanism. Cardiac muscle, receiving adrenergic fibres from the stellate, cervical and thoracic ganglia, has been repeatedly shown to have a specific capacity to uptake and to store catecholamines. The catecholamine stores in cardiac muscle have also been shown to be important sites for the action of numerous drugs. Under normal condition, a certain level of catecholamines is maintained in the stores and serves as the basis for studying the changes in the catecholamine content of the heart. Because myocardial catecholamines play such important role in the patho-physiology of the heart, it would be interesting to compare the normal level of myocardial catecholamines among various species of animals. An occasional study has dealt with myocardial catecholamines of several species add ages of animals but these have been insufficiently comprehensive to afford a basis for an understanding of the importance of these amines as related to species and ages. The present investigation was undertaken to determine whether or not there is any significance of myocardial catecholamines in the course of the evolution and development of animals. Seasonal changes, sex difference and regional and subcellular distribution of myocardial catecholamines were also examined. The concentration of cardiac catecholamines was determined by the spectrophotofluorometric procedure described by Shore and Olin. The results obtained were summarized as follows: 1. As animals phylogenetically progressed larger amounts of catecholamines were resent in their hearts. A negligibly small amount of catecholamine was present in the hearts of the clam, a non-vertebrate. Among the vertebrates, cold-blooded animals (snake, turtle, frog, eel and fish) had less myocardial catecholamines than warm-blooded animals, of which aves (fowl and duck) had less than mammalia (cat, dog, rabbit, rat, cow and pig). The ratio of norepinephrine to epinephrine also was greater as the animals progress phylogenetically. 2. Examination of the regional distribution of cardiac catecholamines in warm-blooded animals showed that the content of the auricle was generally higher than that of the septum and considerably than that of the ventricle, but the differences of contents among these regions were not so marked. 3. In the embryonic chick, cardiac catecholamines were firstly detected on the 4th day of incubation, the time before the cardiac innervation of sympathetic nerves. The concentrations of these catecholamines increased but not markedly on the 6th day of incubation, soon after the innervation of sympathetic nerves to the heart. The level of the cardiac catecholamines fluctuated throughout the remainder of embryonic development. 4. In newborn rat hearts, a considerable amount of catecholamines was present. With the development of the rats, the concentrations of myocardial catecholamines increased. The ratio of epinephrine and norepinephrine fluctuated within the range of 40 to 60 pervent. However, as development progressed, the percentage of norepinephrine continued to rise, attaining the adult value of $80{\sim}90%$ after $45{\sim}60$ days. In contrast, the total amount of epinephrine remained fairly constant throughout the animal's development. 5. No significant sexual differences were observed in the concentration of myocardial catecholamines in the developing rat. 6. The catecholamines in the rabbit hearts increased during the summer season (from May to August) and maintained a fairly constant level in the other seasons of the year. 7. The subcellular distribution of cardiac catecholamines was examined by differential centrifugation of homogenates of cardiac muscles in rabbits, cats and rats. The catecholamines were found to be present approximately 20% in particles of mitochondrial fraction, 45% in particles of microsomal fraction and 35% in soluble supernatant fraction. The particle containing catecholamines in cardiac muscle appears to be two different sizes.
Even though the anticarcinogenic effect of dietary factors especially beta - carotene has been reported by various investigators, the mechanism of the action of ${\beta}-carotene$ has not yet been identified. We carried out the present study to determine the possibilities of relative cancer risk related to dietary intake of vitamin A ( both ${\beta}-carotene$ and retinol ) and blood levels of vitamin A among Koreans. The subjects were divided into two groups; cancer patients and controls. Blood levels for ${\beta}-carotene$ and retinol were analyzed by alumina column chromatography and colorimetry. Dietary intake was examined by food profile and convenient method for evaluating nutritional status through recalling 10 years of food habits. The results obtained are as follows : 1 ) Calorie, protein, fat, and carbohydrate intakes of cancer patient were lower than those of control. Calorie and carbohydrate intakes showed no significant difference but protein and fat intakes were significantly lower in cancer patients. According to cancer sites, in stomach cancer only fat intake was significantly lower than that of control. In lung and larynx cancer calorie, protein, fat and carbohydrate intakes showed similar trend as in control. 2 ) Vitamin A intake of cancer patient was significantly lower than that of control. It was estimated that 83.6% of total Vitamin A intake were provided by ${\beta}-carotene$ for control and cancer patient respectively. 3 ) The mean intake of dietary ${\beta}-carotene$ in cancer patient was significantly lower than that in control ( $7002\;\mu}g/day$ versus $10326\;{\mu}g/day$ ) According to cancer sites in mean intake of dietary ${\beta}-carotene$ was significantly lower in all but stomach cancer compared with that of control. Lung and larynx cancer showed lowest ${\beta}-carotene$ intake with mean value of $5855{\mu}g/day$ and $5492{\mu}g/day$ respectively. 4 ) The mean intake of dietary retinol in cancer patient was significantly lower than that in control ( $245{\mu}g/day$ versus $338{\mu}g/day$ ), but the difference was not significant. 5 ) The relative risk of all cancers in the first (lowest) to the forth quartile level of ${\beta}-carotene$ consumption such as $0-5999{\mu}g/day$. $6000-8999{\mu}g/day$, $9000-11999{\mu}g/day$/ day and $12000-20000{\mu}g/day$ was 85 : 1.7 : 20 : 1.0. The relative risk of all cancers in the first (lowest) to the forth quartile level of retinol consumption, such as $0-299{\mu}g/day$, $300-599{\mu}g/day$, 600-899${\mu}g/day$, and $900-1200{\mu}g/day$, was 1.14 : 067 : 0.21 : 1.0. 6 ) The various food group consumption of cancer patient were significantly lower than those of control in green leafy vegetables, fruits, sea weeds, milk and cheese and eggs. But the Kimchie consumption in cancer patient was three fold higher than that of control ( $1840\;{\mu}g/day$ versus $562\;{\mu}g/day$ ) and in the stomach cancer, Kimchie consumption was the highest, ( $1890\;{\mu}g/day$) According to cancer sites, the consumption of green leafy vegetables was significantly lower in all but stomach cancer compared to control and other vegetables showed no difference between two. In lung and larynx cancer, green leafy vegetables consumption was lowest ( $6094{\mu}g/day$$5921{\mu}g/day$) and milk and cheese consumption was also( $5\;{\mu}g/day$ and $11{\mu}g/day$) 7 ) The recovery of ${\beta}-carotene$ from human serum by alumina column chromatography was $94.4{\pm}2.3%$. 8 ) Cancer patients showed significantly lower serum retinol ($56.4{\pm}18.1\:{\mu}g/100ml$ versus $72.2{\pm}21.8\:{\mu}g/100ml$) and ${\beta}-carotene$ ($48.9{\pm}33.8\:{\mu}g/100ml$ versus $72.2{\pm}42.6\:{\mu}g/100ml$) concentrations than in controls. 9 ) But breast cancer patients were not significantly different from controls in their serum retinol and ${\beta}-carotene$ concentrations.
The present study evaluated the susceptibility of field populations of Plutella xylostella and Spodoptera exigua larvae to four diamide insecticides-chlorantraniliprole, cyantraniliprole, cyclaniliprole, and flubendiamide. All the four diamide insecticides induced 100% mortality in the populations from Seongju (SJ) and Geochang (GC) when treated at a concentration recommended for P. xylostella. However, a very low insecticidal activity was observed in the population from Pyeongchang (PC) with 42.3% 3 d after treatment with chlorantraniliprole. The relative resistance ratio of P. xylostella to cyclaniliprole was similar or low (0.1-6.3 folds) in all the four areas. However, the population from PC exhibited a high resistance ratio to chlorantraniliprole (1,196.3 folds), cyantraniliprole (105.6 folds), and flubendiamide (191.6 folds) compared with that of the susceptible strain P. xylostella. Further, the populations of S. exigua from Cheongju (CJ), Jindo (JD), and Yeonggwang (YG) were not completely controlled by the 4 diamide insecticides. These populations also showed high relative resistance ratio when compared with that of the susceptible strain S. exigua. In particular, the populations from CJ and JD showed 100,000-fold higher resistance ratio to flubendiamide. A comparison of susceptibility of S. exigua larvae to chlorantraniliprole between 2014 and 2017 showed that chlorantraniliprole induced 100% mortality in all populations in 2014, whereas a very low insecticidal activity was observed among the populations in 2017. The results of the present study indicate that the insect pests rapidly develop resistance to diamide insecticides. Therefore, alternative insecticides with a different mechanism of action and comprehensive control strategy are needed. This study can serve as a basis to control pests effectively using diamide insecticides.
Park, Sang Eun;Lee, Su Young;Shin, Dong Yeok;Jeong, Jin-Woo;Jin, Myung Ho;Park, Seon Young;Chung, Yoon Ho;Hwang, Hye Jin;Hong, Sang Hoon;Choi, Yung Hyun
Journal of Life Science
/
v.23
no.3
/
pp.389-398
/
2013
Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.
Journal of the korean academy of Pediatric Dentistry
/
v.35
no.1
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pp.47-56
/
2008
Risperidone is a widely prescribed atypical antipsychotic agent. Approved by the FDA as the first drug to treat irritability associated with autism in children, it is also used to treat tic disorder and Tourette's syndrome. Its adverse reactions related to dentistry include dry mouth, the mechanism of which is yet to be identified. The aim of this study is to identify, at the cellular level, how and to what extent risperidone affects intracellular free calcium concentration ($[Ca^{2+}]_i$), an primary intracellular factor in the regulation of fluid secretion in salivary gland cells. The human salivary gland cell line (HSG) was grown in MEM supplemented with 10% BCS. In order to measure $[Ca^{2+}]_i$, Fura-2/AM was loaded in the HSG, and fluorescence at 340 nm/380 nm excitation was measured in the 500 nm emission ratio. After every experiment, a calibration experiment was conducted in order to readjust the ratio to the actual $[Ca^{2+}]_i$. Changes in $[Ca^{2+}]_i$ were measured in the presence of carbachol, ATP and histamine. The researcher then explored how the pretreatment of risperidone affected such changes. Findings of this study include: 1. In HSG, $[Ca^{2+}]_i$ increased due to the addition of carbachol, ATP and histamine. The presence of risperidone inhibited the action of histamine on this process, while making little effect on that of carbachol and ATP. 2. A quantification of $[Ca^{2+}]_i$ in relation to histamine of different concentrations indicates that the effect of histamine was concentration dependent with an $EC_{50}$ of $3.3{\pm}0.5\;{\mu}M$. 3. The inhibitory effect of risperidone on histamine-induced $[Ca^{2+}]_i$ was concentration-dependent with an $IC_{50}$ of $104.4{\pm}14\;nM$. 4. Risperidone inhibits histamine-induced Ca2+ release from endoplasmic reticulum and influx of extracellular $Ca^{2+}$ in HSG cells(p<0.05).
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