OBJECTIVETo study the selective dilatation effects of iptakalim (Ipt) on basilar and pulmonary arterioles, and endothelial cell function of these arterioles in hypoxic rats.

METHODSSD male rats were divided into 2 groups:control and hypoxic group fed in normobaric hypoxic environment (O2 7.8%, 8 h). Arteriole rings about (204 + 5) pm were isolated and the tension of hypoxic arterioles pre-contracted by 6 nmol/L endothelin-1 (ET-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.

RESULTS10(5) mol/L acetylcholine (ACh)-mediated vasodilatation of basilar and pulmonary arterioles was greatly reduced in the hypoxic group than those in control group (P < 0.05). Compared with normal group, a novel ATP-sensitive potassium channel opener Ipt at the concentration ranging from 10(-11) mol/L to 10(3) mol/L, caused stronger dose dependent vasodilatation on hypoxic pulmonary arterioles, and there was no significant difference between control and hypoxic basilar arterioles.

CONCLUSIONThe endothelial function of basilar and pulmonary arterioles was damaged under hypoxic state, and Ipt selectively increased dilatation effects on hypoxic pulmonary arterioles, but not on hypoxic basilar arterioles which could improve high altitude pulmonary edema pathological state and be the novel drug in the treatment of pulmonary hypertension.

Acetylcholine ; pharmacology ; Altitude ; Altitude Sickness ; physiopathology ; Animals ; Arterioles ; drug effects ; Dilatation ; Endothelin-1 ; pharmacology ; Hypoxia ; KATP Channels ; drug effects ; Male ; Propylamines ; pharmacology ; Rats ; Vasodilation ; Vasodilator Agents ; pharmacology

A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved significantly after solidified by oral fast dissolving film technology without pharmacodynamic properties changed significantly.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Cell Line, Tumor ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Humans ; Male ; Mice ; Neoplasms ; drug therapy ; Phospholipids ; chemistry ; Solubility ; Triterpenes ; administration & dosage ; chemistry

Abstract: Objective　To investigate the distribution and drug resistance characteristics of pathogenic bacteria in patients with neutropenic acute leukemia (AL) and bloodstream infections (BSI). Methods　The clinical data of 258 neutropenic acute leukemia patients with bloodstream infections, who admitted to Shengjing Hospital of China Medical University from January 2016 to December 2021, were collected and analyzed for pathogenic bacteria and drug resistance. Results A total of 268 strains of pathogenic bacteria were isolated from 258 patients, including 180 strains of gram-negative bacteria (67.16%), 61 strains of gram-positive bacteria (22.76%), and 27 strains of fungi (10.07%). Gram-negative bacteria were mainly Klebsiella pneumoniae (53/268, 19.78%), Escherichia coli (49/268, 18.28%) and Pseudomonas aeruginosa (41/268, 15.30%). Gram-positive bacteria were mainly coagulase negative Staphylococcus (31/268, 11.57%) and Staphylococcus aureus(17/268, 6.34%). The main fungi were Candida tropicalis (25/268, 9.33%). Escherichia coli (33/268, 12.31%) was the most common pathogen isolated from acute myeloid leukemia (AML), followed by Pseudomonas aeruginosa (25/268, 9.33%), coagulase-negative Staphylococcus (18/268, 6.72%) and Candida tropicalis (18/268, 6.72%). Klebsiella pneumoniae (35/268, 13.06%) was the most common pathogen isolated from acute lymphoblastic leukemia (ALL),followed by Pseudomonas aeruginosa (15/268, 5.60%) and Escherichia coli (14/268, 5.22%). The resistance of Gram-negative bacteria to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, meropenem, ertapenem, amikacin, cefoxitin, amoxicillin/clavulanic acid was low. Gram-positive bacteria were sensitive to linezolid and vancomycin. Candida was sensitive to flucytosine, amphotericin B and itraconazole. Conclusions　In patients with granulosa after AL chemotherapy combined with BSI, the pathogenic bacteria isolated from AML are diverse, and the pathogenic bacteria isolated from ALL are mainly gram-negative bacteria. Pathogenic bacteria have different degrees of drug resistance to commonly used antibacterial drugs, so it is important to strengthen the monitoring of the distribution of pathogenic bacteria and the change of drug resistance and rational use of antibacterial drugs to minimize the death of patients.

0.05).There was significant difference between normal control group and group A and B(P0.05 ).Neuron counting was significantly higher in group B than that in group A 4 weeks after treatment(P

OBJECTIVETo compare the effects and complications of subinguinal microscopic ligation, laparoscopic transperitoneal varicocelectomy, laparoscopic retroperitoneal varicocelectomy, open retroperitoneal high ligation, and interventional embolotherapy in the treatment of varicocele.

METHODSWe conducted a retrospective study that included 632 varicocele patients treated by subinguinal microscopic ligation (group A, n = 79), laparoscopic transperitoneal varicocelectomy (group B, n = 120), laparoscopic retroperitoneal varicocelectomy (group C, n =137), open retroperitoneal high ligation (group D, n = 283), and interventional embolotherapy (group E, n = 13). We compared the baseline and 3-month postoperative semen parameters, postoperative complications, and pregnancy rate among the five groups of patients.

RESULTSThe operation time was longer in groups A ([2.02 ± 1.25] h) and E ([2.17 ± 1.02] h) than in the other three groups, while the postoperative hospital stay was the shortest in group E ([1.1 ± 0.1] d). Intestinal injury or incision bleeding occurred intraoperatively in 2 cases in group B and 1 case in group E. Postoperative scrotal edema developed in 3.7, 17, 10, and 19% of the patients in groups A, B, C, and D, respectively, but not in group E. The rate of 1-year recurrence was the lowest in group A (1.6%) and highest in group E (22%). Sperm concentration and the percentages of progressively motile sperm and morphologically normal sperm were improved postoperatively in all the patients (P < 0. 05), but there were no statistically significant differences among the five groups either in the above three parameters or in the postoperative pregnancy rate (P > 0. 05).

CONCLUSIONIn the surgical treatment of varicocele, laparoscopic retroperitoneal approach involves short operation time and few complications, subinguinal microscopic ligation has the advantages of little injury, rapid recovery, and few complications but requires specialized microsurgical techniques, and interventional embolotherapy leaves no incision scar and needs only local anesthesia and 1-day postoperative hospital stay, which is uitable for those with a contraindication to anesthesia.

Embolization, Therapeutic ; adverse effects ; methods ; Female ; Humans ; Laparoscopy ; adverse effects ; methods ; Length of Stay ; Ligation ; adverse effects ; methods ; Male ; Operative Time ; Postoperative Complications ; Postoperative Hemorrhage ; Pregnancy ; Pregnancy Rate ; Recurrence ; Retroperitoneal Space ; Retrospective Studies ; Sperm Count ; Urogenital Surgical Procedures ; adverse effects ; Varicocele ; surgery ; Vascular Surgical Procedures ; adverse effects ; methods

OBJECTIVETo investigate the changes of vasoconstriction and vasodilatation under different temperature conditions and the protective effects of Vitamin E (Vit E) against endothelial injury induced by hypothermia.

METHODSThe tail arterial rings were prepared for isometric tension recording using multi wire myograph system. The effect of temperature on relaxation and construction was evaluated. Incubate the arterial rings with different concentration of Vit E when they were exposed to hypothermia, then acetylcholine (ACh)-induced endothelium-dependent relaxation was investigated to evaluate the activity of endothelial.

RESULTS(1) The hypothermia could enhanced the dose-dependent construction induced by PE in mice tail artery. (2) Exposure to hypothermia also resulted in increase of sodium nitroprusside (SNP)-induced re-After incubation with Vit E, the vascular relaxation responses to ACh increased in an endothelium-dependent manner, when compared with the hypothermia-treated group.

CONCLUSIONThe vascular function of constriction was attenuated by hypothermia, while the relaxation was increased. Vit E could prevent the hypothermia-induced decrease in vascular endothelial cells.

Animals ; Arteries ; drug effects ; physiology ; Cold Temperature ; Hypothermia ; In Vitro Techniques ; Male ; Mice ; Prazosin ; pharmacology ; Solanaceous Alkaloids ; pharmacology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; Vitamin E ; pharmacology

Carcinoma ; epidemiology ; mortality ; Esophageal Neoplasms ; epidemiology ; mortality ; Humans ; Water Supply

OBJECTIVETo study the impact of left varicocele (VC) and varicocelectomy (VCT) on the apoptosis of spermatogenic cells and the levels of nitrogen monoxidum (NO) and interleukin 1 (IL-1) in the rat testis.

METHODSWe randomly divided 60 adolescent male SD rats into four groups of equal number: sham operation control, VC model 1 (VC1), VC model 2 (VC2), and VCT. We determined the semen quality and levels of NO and IL-1 in the testis tissue, detected the apoptosis of spermatogenic cells by TUNEL, and compared the indexes obtained among different groups.

RESULTSAn experimental VC model was successfully established by partially ligating the left renal vein of the rats. Sperm concentration and motility were significantly decreased in the VC1 ([1.54 ± 1.16] x 10⁶/ml and [44.23 ± 15.46]%) as compared with those in the sham operation group ([2.80 ± 1.62] x 10⁶/ml and [72.34 ± 12.62]%) (P < 0.05), but remarkably higher in the VCT ([1.82 ± 1.34] x 10⁶/mI and [51.21 ± 12.62]%) than in the VC2 group ([1.04 ± 1.21] x 10⁶/ml and [39.23 ± 13.21]%) (P < 0.05). The levels of NO and IL-1 in the left testes were markedly elevated in the VC1 ([0.172 ± 0.030] ng/ml and [1.468 ± 0.080 ] mg/ml) in comparison with those in the sham operation group ([0.134 ± 0.021] ng/ml and [0.782 ± 0.079 ] mg/ml) (P < 0.05), and significantly higher in the VC2 ([0.198 ± 0.020] ng/ml and [1.994 ± 0.090] mg/ml) than in the VCT group ([0.141 ± 0.010] ng/ml and [0.781 ± 0.036] mg/ml) (P < 0.05). However, the NO and IL-1 levels in the right testis showed no statistically significant differences between the two groups, and the two levels were positively correlated (r = 0.492, P < 0.01). The rats of the VC1 group exhibited remarkable apoptosis of spermatogenic cells in the bilateral testes, with significant differences in the apoptosis index ( AL) between the two sides (P < 0.05) as well as in the same side in comparison with the sham operation group (P < 0.01). The Als of spermatogenic cells in the bilateral testes showed statistically significant differences in the VCT (P < 0.05) but not in the VC2 group (P > 0.05), and those in the same side manifested dramatic differences between the VCT and VC2 groups (P < 0.01).

CONCLUSIONVaricocele induces changes of the NO and IL-1 levels in the testis tissue and increases the apoptosis of spermatogenic cells, which might be one of the causes of testis damage and spermatogenic dysfunction.

Animals ; Apoptosis ; Germ Cells ; pathology ; In Situ Nick-End Labeling ; Interleukin-1 ; analysis ; Ligation ; Male ; Nitrogen ; analysis ; Random Allocation ; Rats ; Semen Analysis ; Spermatogenesis ; Testis ; chemistry ; Varicocele ; complications ; surgery

OBJECTIVETo observe the effects of electroacupuncture (EA) on circadian rhythm of temperature and melatonin (MT) in depression rats model induced by chronic stress, so as to explore the biological mechanism of EA for depression.

METHODSTwenty-four SD rats were randomly divided into a control group, a model group and an EA group, 8 cases in each one. Rats in the control group were treated with normal diet for 21 days without any treatment. In the model and EA group, rat model was established by chronic unpredictable stress combined with solitarily feeding method, and rats in the EA group was treated with EA at "Baihui" (GV 20), "Yintang" (GV 29) 1 h before stress stimulation everyday, 2 Hz in frequency and intensity was favorable with the head of rat slightly shivering. The needles were retained for 20 min, once a day for totally 21 days. After EA treatment, open-field experiment was adopted to observe the behavioral improvement; the rats temperatures were monitored at six time points (2:00, 6:00, 10:00, 14:00, 18:00, 22:00) and orbital blood sampling was collected. The level of serum MT was tested by enzyme linked immunosorbent assay. The circadian rhythm changes of temperature and serum MT in each group were compared.

RESULTSThe numbers of horizontal movement and vertical movement in the model group were obviously lower than those in the control group (both P < 0.05), while those in the EA group were significantly improved compared with those in the model group (both P < 0.01). The circadian rhythm of temperature and MT disappeared in the model group, which was improved into normal level after EA treatment.

CONCLUSIONThe electroacupuncture has regulation effects on circadian rhythm of temperature and melatonin in depression rat model induced by chronic stress.

Animals ; Circadian Rhythm ; Depression ; metabolism ; physiopathology ; therapy ; Electroacupuncture ; Humans ; Male ; Melatonin ; metabolism ; Rats ; Rats, Sprague-Dawley

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.
Aconitine ; analogs & derivatives ; isolation & purification ; Aconitum ; chemistry ; Alkaloids ; isolation & purification ; Chromatography, High Pressure Liquid ; Drug Stability ; Drugs, Chinese Herbal ; isolation & purification ; Hot Temperature ; Plant Extracts ; isolation & purification ; Steam ; Tandem Mass Spectrometry ; Time Factors