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Objective:To introduce the early results of total aortic arch replacement (TAA) without cardiopulmonary bypass (CPB) and without interruption of cerebral blood supply, using the technique of arch branches preferential reconstruction and whole brain perfusion for brain protection.Methods:Between June 2020 and March 2021, a total of 9 Stanford type A aortic dissection patients we performed total arch replacement by using the technique of arch branches preferential reconstruction and whole brain perfusion without cardiopulmonary bypass and without interruption of blood supply to the brain. The method of this reconstruction technique is as follows: A 24F aortic cannula was inserted into the true lumen at the root of the transverse innominate artery (IA) to connect one end of the artery for cardiopulmonary bypass. The access was connected to 14F artery via Y-connector and inserted into IA cavity to maintain blood supply to brain. Without cardiopulmonary bypass, the 10 mm branch of the four branch artificial blood vessel was anastomosed with the innominate artery IA. The perfusion collateral was connected to the second end of the artery of CPB (single pump and double tubes) to continue to supply blood for IA. The left common carotid artery (LCA) and left subclavian artery (LSCA) were reconstructed by the same method. When IA and LCA were anastomosed, the distal blood supply was not interrupted. After the three branches of the aortic arch were anastomosed, we started to turn the machine, then cooled down and blocked the ascending aorta to further complete the operation of the aortic root and arch. During the period of lower body circulatory arrest, the whole brain was perfused with low flow.Results:No intraoperative death or perioperative complications occurred in all patients, and they were discharged smoothly. The cardiopulmonary bypass time was (192.4±58.1) min, the aortic clamping time was (128.3±52.4) min, the lower body circulatory arrest time was (29.1±1.3) min, and the postoperative awake time was (8.2±3.7) h.Conclusion:Off-pump arch branches preferential reconstruction can provide physiological whole brain perfusion, shorten the cardiopulmonary bypass time and aortic occlusion time, and the operation is safe and effective.
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<p><b>OBJECTIVE</b>To investigate the effect of oral bosentan in the treatment of congenital heart disease-associated pulmonary arterial hypertension.</p><p><b>METHODS</b>24 patients with congenital heart disease-associated pulmonary arterial hypertension, including 4 receiving heart surgery and 20 with surgical contraindications, were enrolled in this study. All the patients were given oral bosentan and followed up regularly for analyzing the outcomes and side effects.</p><p><b>RESULTS</b>One patient was lost to follow up and one patient died. Systolic pulmonary artery pressure showed no significant changes at 2 (93.6 ± 17.2 mmHg) and 4 months (85.7 ± 25.5 mmHg) of bosentan treatment compared to that before the medication (97.8 ± 14.9 mmHg) (P=0.096), but decreased significantly after a 6-month therapy (80.9 ± 25.0 mmHg, P=0.029). The 6-minute walking distance increased significantly after a 2, 4, and 6-month therapy [(488 ± 98.8, 496.3 ± 89.0, and 491.3 ± 114.2 m, respectively; P=0.004, 0.003, and 0.004 vs the distance before medication (317.0 ± 134.1)]. The New York heart functional classification was improved significantly after a 2, 4, and 6-month therapy [(2.0 ± 0.5, 1.8 ± 0.4, and 1.7 ± 0.5, respectively; P<0.001 vs pre-medication score (2.9 ± 0.5)). Hepatic and renal function remained normal, and ALT and AST showed no significant variations during the medication (P>0.05).</p><p><b>CONCLUSION</b>Oral bosentan can effectively relieve the symptoms, decrease pulmonary artery hypertension, and improve exercise tolerance and cardiac function classification in patients with pulmonary artery hypertension associated with congenital heart disease with good safety and mild side effects.</p>
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Humanos , Administración Oral , Antihipertensivos , Usos Terapéuticos , Cardiopatías Congénitas , Hipertensión Pulmonar , Quimioterapia , Sulfonamidas , Usos TerapéuticosRESUMEN
BACKGROUND:celltherapy by the implantation of autologous bone marrow cells has been used for the treatment of ischemic heart diseases in clinical trials for decade. However, as the outcomes of celltransplantation obviously vary among patients, it is essential to identify the risk factors that may influence the level and function of progenitor cells in bone marrow, in order to identify the patients who would benefit the most from this treatment. OBJECTIVE:To observe the impact of perioperative cardiovascular risk factors on number and function of bone marrow progenitor cells from patients undergoing coronary artery bypass grafting surgery. METHODS:We col ected clinical and laboratory data from 44 patients scheduled to undergo sternotomy for coronary artery bypass grafting procedures. Bone marrow was aspirated from the sternum during the operation and bone marrow mononuclear cells were isolated by density centrifugation with Ficol lymphoprep and then detected using trypan blue exclusion method. Levels of progenitor cells in bone marrow were evaluated using flow cytometry. Function of bone marrow progenitor cells were assessed by clonogenic and migration assays. RESULTS AND CONCLUSION:We assessed the number of bone marrow mononuclear cells out of 20 mL bone marrow in duplicate samples from patients with coronary heart disease scheduled for coronary artery bypass grafting that was (10-89)×106 cells with over 95%activity. A negative correlation was observed between the number of bone marrow mononuclear cells and the age (n=44, r=-0.788, P=0.001). Levels of CD34+, CD133+, and CD34+CD133+cells in bone marrow mononuclear cells was (0.94±0.39)%, (0.46±0.28)%, and (0.53±0.26)%. Levels of CD34+cells and CD133+cells in patients with diabetes were significantly lower than those in patients without diabetes. Female, advanced age and poor heart function were related with reduced colony-forming ability of progenitor cells. A positive correlation was observed between level of CD34+cells and migration ability of bone marrow mononuclear cells. The results show that by density gradient centrifugation, we can harvest a sufficient number of bone marrow mononuclear cells in the treatment for ischemic heart disease. Age, gender, diabetes, heart function are correlated with bone marrow mononuclear cellnumber and functions.
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Objective: To study the effects of triptolide-medicated serum on secretory function of adrenocortical cells isolated from rats. Methods: Thirty SD rats were randomly divided into control group, prednisone group, and low-, medium- and high-dose triptolide groups. Rats were administered with normal saline, prednisone and low-, medium- and high-dose triptolide respectively by gastrogavage to prepare sera containing drugs. Primary adrenocortical cells were isolated from normal male rats and cultured with sera containing drug for 48 hours. Expression of proliferating cell nuclear antigen (PCNA) was observed by immunohistochemical method and number of PCNA-positive cells was counted. Ultrastructure of adrenocortical cells was observed under a transmission electron microscope. Content of corticosterone in supernatant of adrenocortical cell culture was detected by enzyme-linked immunosorbent assay, and real-time fluorescence quantitative polymerase chain reaction (PCR) was employed to investigate the expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA. Results: As compared with the control group, content of corticosterone in supernatant of adrenocortical cell culture and expression of 3beta-HSD mRNA were significantly increased in the triptolide-treated groups, and the numbers of PCNA-positive cells were increased in the medium- and high-dose triptolide groups, however, they were decreased in the prednisone group. Conclusion: Triptolide-medicated serum can increase the secretion of corticosterone in rat adrenocortical cells in vitro.
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OBJECTIVE: To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro. METHODS: Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5x10(5) or 5x10(6) tumor cells in the right flank, respectively. RESULTS: KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (< or = 1.18 g/kg). No adverse reactions were observed. CONCLUSION: These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.
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AIM: To investigate the effect of soybean isoflavones (SI) on ventricular remodeling induced by myocardial infarction (MI). METHODS: MI was induced by permanent ligation of the left anterior descending coronary artery (LAD) in male Sprague-Dawley (SD)rats. Rats were randomly divided into six groups: shamThree hours after the operation, the drugs or solvent were administrated ig qd for 35 d. Twenty-four hours after the last administration, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), peak systolic left ventricular pressure (Peak), maximal rate of left ventricular pressure rising (+dp/dtmax), maximal rate of left ventricular pressure declining (-dp/dtmax) and myocardial maximal shortening velocity (Vmax) were measured. After above hemodynamic parameters were measured, hearts were extracted. The ratio of total ventricle weight to body weight(TVW/BW) was calculated. Myocardial collagen was shown with the collagen-specific picrosirius red stain,myocardial interstitial collagen volume fraction(ICVF), perivascular collagen volume fraction(PCVF), infarct size,septal thickness (ST) and left ventricular diameter (LVD) were measured by image analysis system. RESULTS:(31 ± 5) %, respectively, all of which were significantly smaller than that in MI group (( 38.9 ± 2.9) %, P ＜ 0.01 ).In MI group, TVW/BW, LVD, ICVF and PCVF were remarkably increased compared with those in sham group (P ＜ 0.01 ). The increased TVW/BW, LVD, ICVF and PCVF were significantly reduced by treatment with eaprats in MI group was significantly decreased than that in sham group (P ＜ 0.01 ). The reduced ST could be in-dp/dtmax and Vmax were decreased (P ＜ 0.01 ), while LVEDP was increased (P ＜ 0.01 ), significantly. The reSION: SI can improve cardiac function and ventricular remodeling induced by myocardial infarction in the rat.
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Objective:To explore the protective effects and mechanisms of salidroside on cerebral ischemia-reperfusion injury in middle cerebral artery occlusive(MCAO)rats.Methods:Focal cerebral ischemia in rats was produced by 1.5 h occlusion of the middle cerebral artery and 24 h reperfusion.Salidroside was administered intravenously immediately after occlusion and reperfusion respectively.The neurologic deficit scores were investigated according to Zea-Longa's Standard.The infarct areas were assessed with software Imagepro Plus 6.0 after TTC staining.And the activities of inducible nitric oxide synthase(iNOS)as well as glutathione peroxidase(GSH-Px)were determined by specific kit.The levels of B cell lymphoma/lewkmia-2(Bcl-2)and Bcl-2 assaciated X protein(Bax)in central neutral system were assessed by western blot.Results:Compared with the model group,salidroside could decrease the neurologic deficit score,reduced the infarct areas of the brain in MCAO-I/R rats,increased the activity of GSH-Px and decreased the activity of iNOS,enhanced the expression of Bcl-2,depressed the expression of Bax.Conclusion:Salidroside has a protective effect on cerebral ischemia-reperfusion injury and this effect is related to attenuating lipid peroxidation,enhancing the expression of Bcl-2 and diminishing Bax expression.
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AIM: To study the inhibitory effects of domestic leuprolide acetate microsphere (LE-ms) on the growth of explanted endometrium in the rat models of EMT and its possible mechanisms. METHODS: The 60 rats models of EMT were induced surgically by the Jones method. Then the animals were treated with LE (20 ?g? -1?d -1,28 d,sc) , enanton(20 ?g? -1?d -1,sc) and domestic LE-ms (2, 20, and 200 ?g㎏ -1?d -1,sc), respectively; another 30 rats were divided into sham group(N.S, 1 ml?kg -1?d -1,21 d,sc), EMT+ LE group(100 ?g?kg -1?d -1,21 d,sc)and EMT group(N.S, 1 ml?kg -1?d -1,21 d,sc). At the same time, estrous cycle was monitored daily by examination of vaginal cytologic smears. After 3 weeks, blood was drawn and the serum estradiol concentration was assayed. The volume of endometrial implant was assessed. Lateral uterus, bilateral ovary, thymus and spleen were weighed. The NK cell cytotoxicity in the spleen was evaluated with lactate dehydrogenase (LDH) release assay. RESULTS: Implants in control group continued to grow, while those in groups treated with the drugs showed remarkable atrophy. The inhibitory rates were 87.2%, 78.3%, 57.3%, 89.0% and 94.7%, respectively. The regular estrous cycle of the model rats was abolished and serum estradiol reduced (P0.05); and the NK cells activity was enhanced(P
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AIM: To study the effect of genistein on c-myc mRNA expression induced by oxidized low density lipoprotein (ox-LDL) in human vascular endothelial cells (ECV304). METHODS: LDL were isolated from healthy human plasma by gradient ultracentrifugation and oxidized by CuSO4. ECV304 cells were exposed to ox-LDL 200 mg*L-1 in the presence or absence of genistein 100 μmol*L-1 for 1, 2, and 4 h in vitro. Northern blot was employed to measure c-myc mRNA levels of ECV304. RESULTS: In response to ox-LDL 200 mg*L-1, c-myc mRNA expression in ECV304 increased by 3 fold for 1h and 3.3 fold for 2 h and decreased below the control level at 4 h. Expressions of c-myc stimulated by ox-LDL in the presence of genistein 100 μmol*L-1 for 1 h and 2 h were separately 80 percent and 60 percent of that in the absence of genistein 100 μmol*L-1. CONCLUSION: Genistein can effectively inhibit c-myc mRNA expression in ECV304 induced by ox-LDL.
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AIM: To analyse quantitatively the interactions among ethanol, chloral hydrate and naloxone with isobologram, Q-test and multiple logistic regression methods. METHODS: The hypnotic effects of the three drugs on Kunming mice were observed. In two drugs interaction study, chloral hydrate and ethanol were given at different ratios (25∶75, 50∶50, 78∶22 and 80∶20). In three drugs interactions study, 15 min after treatment of naloxone at fixed dose (0.5 mg*kg-1 and 0.2 mg*kg-1) the mixture of chloral hydrate and ethanol (at 1∶1 and 1∶3 ratio) was given to induce sleep. The ED50 for hypnotic action (righting reflex loss) of chloral hydrate, ethanol, naloxone and their mixtures were calculated by use of isobologram, interaction Q-index test and multivariate logistic regression analysis. RESULTS: The mixtures of ethanol and chloral hydrate in all ratios revealed partial but significant synergism. But in addition with naloxone the three agents showed different natures of interactions according to different naloxone levels. CONCLUSION: There are synergistic interactions in hypnotic ED50s between ethanol and chloral hydrate at different ratios and antagonistic interaction in adding a fixed dose of naloxone. The results coincide with the pharmacologistic mechanism discussed in this paper.
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Directing at the cultivating aims of the students in major of basic medical science,the article expounds some instruction innovations in teaching pharmacology.We introduce some social practical problems and some research fields which evolve rapidly to the teaching class by compiling the teaching materials,conducting lectures and giving discussion lessons.In addition,we incorporate the cultivation of students' capability of doing scientific research to the teaching work through guiding them how to read references,directing them to finish independently the project of experiment designed by themselves and operating group activities instructed by their supervisors in the department of pharmacology.
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10 mg?kg -1?d -1? 5 d. The inhibitory rate of ZD1694( 0.001- 1 000 mmol?L -1)on SGC-7901 cells were increased in concentration and time-dependent manner. The cell numbers in G_0-G_1 phase in SGC-7901 cells were raised by ZD1694 as well. CONCLUSION: ZD1694 can take obvious antitumor effects on S180-bearing mice. The antitumor rate of ZD1694 is in a dose-dependent manner, and it is higher when the total dosage is administered in one day than that the total dosage was divided into 5 consecutive days. ZD1694 can inhibit the growth of SGC-7901 cells and block the cells in G_1 phase in vitro.
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Aim To examine the protective effects of allopregnanolone against seizure on different animal models.Methods The protective effects of allopregnanolone against maximal electrical seizure (MES) and picrotoxin-induced seizure were studied in C57 mice 15 minutes after vehicle or drug intraperitoneal administration.Results In the MES test, we found that pretreatment with the phenobarbital or allopregnanolone produced a dose-dependent protective effect against seizure. The potency (ED50 value) of phenobarbital in the MES test was 2.40 mg·kg-1, with 95% confidence interval range from 1.22 to 4.72 mg·kg-1. The potency (ED50 value) of allopregnanolone in the MES test was 0.086 mg·kg-1, with 95%confidence interval range from 0.037 to 0.201 mg·kg-1, which was significantly higher than that of phenobarbital (P<0.01). The combination study of half ED50 values of phenobarbital and allopregnanolone resulted in a 80% of protective effect in MES test, which was higher than 50% produced by either phenobarbital or allopregnanolone at their ED50 values respectively. This result indicated that there was a synergism between phenobarbital and allopregnanolone in their anticonvulsant activities. In the picrotoxin test, we found that pretreatment with the allopregnanolone also produced a dose-dependent protective effect against picrotoxin-induced seizure. The potency of allopregnanolone in the picrotoxin seizure test was 0.123 mg·kg-1, with 95% confidence interval range from 0.058 to 0.263 mg·kg-1.Conclusion Allopregnanolone(ip) could protect different seizures in a dose-dependent manner,had a higher potency than phenobarbital,and had synergism with phenobarbital in the MES test.
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To compare the anxiolytic effects of reduced metabolite of progesterone and benzodiazepine.Methods The effects of allopregnanolone and diazepam on spontaneous locomotor activity and on exploration in the elevated plus-maze were studied in C57 mice 20 min after vehicle or drug intraperitoneal administration.Results Allopregnanolone (0.1 mg.kg-1,ip) elicited marked anxiolytic effects in terms of significantly reducing the latency to enter the open arm from (31.30±8.39)s to (8.80±6.00)s,(P<0.001),and significantly increasing both the number of open arm entries from 1.20 ± 0.42 to 4.80 ±1.75,(P<0.001) and the proportion of total time spent on the open arm from 7.13％ to 32.50％,(P<0.001).Meanwhile,the diazepam (0.25 mg·kg-1) produced a lower anxiolytic effect comparing to that of the allopregnanolone.Analysis of spontaneous locomotor activity showed while 0.5 mg·kg-1 of diazepam decreased the locomotor activity (P<0.01),neither 0.1 mg·kg-1 of allopregnanolone nor 0.25 mg·kg-1 of diazepam affect the locomotor activity score.Conclusion Together,these results provide evidence for differential behavioral actions of the neurosteroids and benzodiazepines.Since the allopregnanolone produce a selective anxiolytic effect without affecting the spontaneous locomotor activity,the allopregnanolone may be a better alternative for diazepam in treating anxiety.
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Aim To study the effect of leuprorelin acetate microspheres (LE ms) on endometriosis in rats, and compare the efficacy of material drug (LE), domestic and imported LE ms (enanton). Methods Endometriosis was induced by endometrial implant in rats. Then the animals were treated with LE (20 ?g?kg -1 ?d -1 ? 28 d ,sc), enanton(20 ?g?kg -1 ?d -1 ,sc)and domestic LE ms ( 2,20,200 ?g?kg -1 ?d -1 ,sc). Results Implants in control group continued to grow, while those in groups treated with drugs shrinked significantly, and domestic LE ms could produce dose dependent inhibitory effect on the growth of endometrial implant in rats. Conclusion The domestic LE ms at the single dose of 20 ?g?kg -1 ?d -1 has the same effectiveness as enanton and routine injection with the same does of LE for 28 days.
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AIM: To observe the anticonvulsant action of L-histidine in mice. METHODS: The anticonvulsant effect of L-histidine, and the antagonism of dl-chlorpheniramine to L-histidine were observed in convulsion mice induced by pentylenetetrazole (PTZ) and electric stimulation. RESULTS: L-histidine exerted remarkable anticonvulsant action with dose-response relationship in convulsion mice induced by pentylenetetrazole and electric stimulation, and the action was partly antagonized by dl-chlorpheniramine. CONCLUSION: L-histidine has anticonvulsant effect, and the action was partly antagonized by dl-chlorpheniramine, suggesting that L-histidine can pass the BBS and enter the central nervous system.
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AIM: To compare the effects of histamine and its antagonists on tension of isolated rabbit basilar and mesenteric artery in vitro, and to observe the role of Ca 2+ in histamine induced response. METHODS: The dose response curves induced by histamine were recorded on the isolated rabbit central and peripheral arteries in different doses of diphenhydramine, cimitidine, and nifidipine. RESULTS: Histamine could cause contraction of basilar and mesenteric isolated arteries. Diphenhydramine and nifidipine antagonized these effects, while cimitidine enhanced this effect. CONCLUSION: There may be different receptors densities in different rabbit arteries; histamine shows the vasoconstrictive effect on both brain and mesenteric arteries; and the vasoconstrictive effect mainly produces via Ca 2+ inflax.