Objective　To study the effects of ACE1 on amount and mRNA expression of Ca2+ release channels(RyR2) of myocardial sarcoplasmic reticulum(SR) in prevention and treatment of chronic heart failure.Methods　After the model of chronic heart failure was established with ligation of left corongary artery in rats,the animals were prevented and treated with Perindopril. Hemodynamic parameters, Bmax and Kd of ［3H］－ryanodine binding to RyR2、RyR2 mRNA content were determined.Results　Compared with the control group(group C),LVEDP in the heart faliure group (group F)increased(P<0.01),while+dp/dtmax and -dp/dtmaxdecreased significantly(P<0.01).LVEDP was lower but +dp/dtmax and -dp/dtmaxsignificantly higher in the Perindopril treated group(group P)than those in group F(P<0.01).Bmaxof ［3H］－ryanodine binding to RyR2 and mRNA content of RyR2 in group F were lower than those in group C(P<0.01),and these in group P were higher than those in group F(P<0.01). There were no significant difference of Kd among the three groups(P>0.05).Conclusion　The amount and mRNA expression of RyR2 of myocardial sarcoplasmic reticulum(SR) decreased in chronic heart failure.Perindopril can improve mRNA expression and amount of RyR2 of myocardial SR in prevention and treatment of chronic heart failure, thus contributing to the improvement of myocardial function.

BACKGROUND:At present, spleen tyrosine kinase is the new target of studying and treating rheumatoid arthritis. OBJECTIVE:To study the influence of smal molecule tyrosine kinase inhibitor HL131078 on the inflammatory cel infiltration and cartilage destruction of the knee joint of mice with col agen-induced arthritis. METHODS:Forty DBA/1 mice were randomly and evenly divided into blank, model, positive and experimental groups. Col agen type II (CII) solution and Freund’s complete adjuvant (including mycobacterium tuberculosis) were injected into the mice of the latter three groups through the tail to establish mouse models of col agen-induced arthritis. At 2 weeks after the the first immunization with CII, the mice in the positive group were intragastrical y given R406 (10 mg/kg), once a day, for 28 consecutive days. The mice in the experimental group were intragastrical y given HL131078 (10 mg/kg), once per day, for 28 consecutive days. RESULTS AND CONCLUSION:Compared with the model group, the mean arthritis indexes of mice in the experimental and positive groups started to decline at 29 and 26 days. In the experimental group, the cartilage destruction of mouse knee joint was obviously reduced and the inflammatory cel infiltration in the knee joints was obviously reduced, which was close to that in the positive group. The results demonstrate that the smal molecule tyrosine kinase inhibitor HL131078 can effectively reduce inflammatory cel infiltration and cartilage destruction in the knee joints of mice with col agen-induced arthritis.

Objective To evaluate the effect of neurectomy and chemodenervation of the masseter muscle on mandible bone mineral density.Methods Thirty 28-day-old Wistar rats were divided into four groups:operation groups 1 and 2,botulinum toxin group and control group.The main trunk and initial branches of masseteric nerve on the right side were resected in the operation group 1.The nerve was exposed,but not resected in the operation group 2.The right side of masseter muscle was injected with botulinum toxin type A and the left side was injected with sterile saline in botulinum toxin group when the rats were 28 days old.The control group was only anaesthetised.Bilateral mandibles of all four groups were scanned by GE lunar prodigy bone densitometer when the rats were 75 days old.Results BMD was (0.184±0.012) g/cm2 on the left side and (0.184±0.026) g/cm2on the right side in operation group 1.BMD was (0.179±0.022) g/cm2 on the left side and (0.173±0.019) g/cm2 on the right side in operation group 2.BMD was (0.165±0.061) g/cm2 on the left side and (0.158±0.051) g/cm2 on the right side in botulinum toxin group.BMD was (0.196±0.026) g/cm2 on the left side and (0.185±0.022) g/cm2 on the right side in control group.The variance of BMD between two sides of each group was not significant difference.The variances of BMD among the right side of the four groups were not significant difference.Conclusions No pathological changes in mandibular bone mineral density after denervation and chemodenervation of the massetermuscle are observed in this study.

Objective To investigate the conventional MRI and DWI features of prostatic abscess.Methods 8 patients with path-ologically and clinically proved prostatic abscess who were performed MRI examination in our institution were enrolled in this study. Among them,2 patients underwent CT examination and 7 patients were performed DWI examination (b = 0 and 1 000 s/mm2 ). Their CT,conventional MRI and DWI features were retrospectively analyzed.The ADC value between prostatic abscess and normal prostate tissues were compared by using paired t test.Statistical significance was inferred at P <0.05.Results 2 patients with 3 fo-cal abscesses,2 patients with 2 focal abscesses,and 4 patients with only one focal abscess.4 abscesses perforated the prostate cap-sule and involved the fat gap in front of the rectum.Prostatic abscess showed low hypointensity on T1 WI,hyperintensity on T2 WI and DWI.2 focal abscesses with low signal areas consistent both on T1 WI and T2 WI of gas.The mean ADCs of prostatic abscess were (0.854±0.223)×10 -3 mm2/s ,which were significantly lower than those of prostate tissues (1.41 6±0.1 68 )×10 -3 mm2/s (P <0.05).Conclusion Prostatic abscess has characteristic feature on MRI,and shows restricted diffusion on DWI.MRI can clearly display their size,number and invasive condition of the circumambient organs.Thus should be considered as an optimal method in the diagnosis of prostatic abscess.

Objective To determine the influence of intense pulsed light (IPL) on the secretion of TGF-β1 in cultured human fibroblasts and the intervention of JNK inhibitor.Methods The callan foreskin fibroblasts were cultured and divided into 2 groups. In the IPL treatment group, cells were irradiated with IPL with fluences of0 (negative control), 10, 18, 27, 36, and 36 J/cm2 × 2 (irradiated with IPL with fluences of 36 J/cm2 twice). In the IPL + inhibitor group, cells were irradiated with IPL with fluences of 36 J/cm2 after incubation with the inhibitor SP600125 for 2 h. TGF-β1 in the culture supernatant was evaluated 48 h after the irradiation using enzyme-linked immunosorbent assay. Results Compared with the negative control, TGF-β1 in the culture supernatant decreased at the IPL irradiation of 10, 18, 27, and 36 J / cm2, whereas TGF-β1 increased at the IPL irradiation of 36 J/cm2× 2. In the IPL + inhibitor group, the concentration of TGF-β1 in the culture supernatant decreased compared with the controls (P<0.05). Conclusion IPL can suppress the secretion of TGF-β1 at the lower fluence and promote the secretion at a higher fluence. JNK inhibitor may play an inhibitive role when IPL regulates the TGF-β1 secretion in cultured human fibroblasts. IPL may stimulate TGF-β1 secretion of the fibroblast cells in human skin via JNK signal pathway.

OBJECTIVETo explore the relationship between hypoxia and the apoptosis of corpus cavernosum smooth muscle cells (CCSMC) in SD rats.

METHODSCCSMCs were cultured in vitro and identified by immunohistochemistry, and then underwent hypoxia interference at the concentration of 1% O2 for 12, 24, 48 and 72 hours, with normal oxygen concentration as the control. Flow cytometry was used to determine the cycles and apoptosis of the cells.

RESULTSThe cultured CCSMCs grew well, positive for anti-smooth muscle alpha-actin monoclonal antibody immunohistochemical staining. Flow cytometry showed that the number of CCSMCs in G0/G1 was gradually increased within 48 hours and then decreased, just opposite to the proportion of the S phase cells. But no regular change was found in the proportion of the cells in the G2/M phase.

CONCLUSIONHypoxia promotes the apoptosis of CCSMCs in a time-dependent manner, to the maximum at 48 hours, and then cell lysis may occur, but with no further apoptosis.

Animals ; Apoptosis ; Cell Hypoxia ; Cells, Cultured ; Male ; Muscle, Smooth, Vascular ; cytology ; Penis ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of hypoxia on the fibrosis of corpus cavernosum smooth muscle cells (CCSMC) in SD rats.

METHODSCCSMCs were cultured in vitro, identified by immunohistochemistry, and then exposed to hypoxia at the concentration of 1% O2 for 12, 24, 48 and 72 hours. Those exposed to normal oxygen concentration for the corresponding lengths of time were used as the control. The relative expressions of TGF-131, type I collagen and type DI collagen were determined by RT-PCR.

RESULTSThe in vitro cultured CCSMCs grew well, and the anti-a-smooth muscle actin monoclonal antibodies were positive on immunohistochemical staining. The relative expression levels of TGF-beta1, type I collagen and type mI collagen were positively correlated with the time of hypoxia interference within 48 hours, and did not increase further with prolonged exposure.

CONCLUSIONWhen exposed to hypoxia, the relative expressions of TGF-beta1, type I collagen and type mI collagen in the CCSMCs of SD rats increased with the length of time, and reached the peak at 48 hours. Hypoxia can cause fibrosis of CCSMCs in SD rats.

Animals ; Cell Hypoxia ; Cells, Cultured ; Collagen Type I ; metabolism ; Extracellular Matrix ; Fibrosis ; Male ; Muscle, Smooth ; cytology ; pathology ; Oxygen ; metabolism ; Penis ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

P-glycoprotein (P-gp) located in the apicalmembranes of intestinal absorptive cells is an energy-dependent efflux pump which can reduce the bioavailability of a wide range of substrate drugs. There is increasingly interest in enhancing the bioavailability of these molecules by inhibiting intestinal P-gp. A classification of excipient inhibitors of intestinal P-gp nonionic surfactants, poly (ethylene glycol), derivates of beta-cyclodextrin and thiolated chitosan will be presented and then the inhibition mechanism will be discussed. Compared with traditional P-gp inhibitor, excipient inhibitors appear to have minimal nonspecific pharmacological activity, thus potential side effects can be mostly avoided. These excipient inhibitors, which hold the promise of replacing the traditional ones, will be extensively employed to significantly improve the intestinal absorption of poorly soluble and absorbed drugs as a result of P-gp inhibition, and thus to enhance the bioavailability of these drugs. However, the further studies of both the mechanism and clinical application are urgently needed.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; pharmacokinetics ; Animals ; Biological Availability ; Chitin ; analogs & derivatives ; pharmacology ; Excipients ; pharmacology ; Glycerol ; analogs & derivatives ; pharmacology ; Humans ; Intestinal Absorption ; drug effects ; Polyethylene Glycols ; pharmacology ; Surface-Active Agents ; pharmacology ; beta-Cyclodextrins ; pharmacology

OBJECTIVETo investigate the diagnostic value of FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms) technique, combining immunofluorescence and fluorescence in situ hybridization (FISH), to detect genetic aberrations in multiple myeloma (MM).

METHODSBone marrow samples were collected from 18 MM and 2 plasma cell leukemia (PCL) patients. Probes targeting IgH and MMSET were prepared using a Nick Translation Kit from Bacterial artificial chromosome (BAC) clones. The immunophenotyping was achieved via the CD138 tyramide signal amplification (TSA)-mediated immunofluorescence, followed by FISH with the prepared probes \[t(4;14), t(11;14), t(14;16)\] and the commercial deletion probes (13q and p53) to detect common genetic aberrations in MM.

RESULTSAll the 20 samples were assayed with the probes mentioned above, and revealed 4 cases with t(4;14), 6 with t(11;14), 1 with t(14;16), 3 with p53 deletion; and 8 with 13q deletion. The remaining 4 cases had none of the 5 aberrations.

CONCLUSIONFICTION technique facilitates the detection of genetic abnormalities of MM in situ; enhances both efficiency and sensitivity of positive detection, thus, could be used as the screening test of molecular diagnosis of MM to guide coming-up risk-adapted therapy and evaluate prognosis.

Adult ; Aged ; Aged, 80 and over ; Cytogenetics ; Female ; Fluorescent Antibody Technique ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; genetics

The objective of this study is to compare the differences between self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD) technology used to improve the dissolution rate and bioavailability of vinpocetine (VIP). The formulation of VIP-SMEDDS was composed of Labrafac, oleic acid, Cremophor EL, Transcutol P, and gum acacia which was used as solid absorbent. VIP-SD was prepared using poloxamer F68 as the carrier. In the solubility test, the solubility of VIP in SMEDDS was 17.3 times as much as that in SD. In the dissolution test, SMEDDS had shown better enhancement and stability in dissolving VIP than SD. When compared to VIP crude powder, the bioavailability of VIP in SMEDDS (VIP-SMEDDS) was 1.89-fold higher, and was less affected by food intake. However, the bioavailability of VIP in SD (VIP-SD) was bioequivalent to that of VIP crude powder. The tissue uptake of VIP-SMEDDS in Peyer's patches, intestine and liver after administration for 2 hours was more favorable than that of VIP-SD, which was 3.7 times higher in Peyer's patches, 2.2 times higher in intestine and 1.5 times higher in liver. In Caco-2 tests, the apparent permeability (P(app)) of VIP-SMEDDS was 2.65 times of that of VIP-SD. The width of the cell tight junctions of Caco-2 cell monolayer treated with VIP-SMEDDS were 9.6-fold wider, but there was no significant change after treatment with VIP-SD, when compared to the blank control. In conclusion, SMEDDS was more efficient than the traditional SD technology in increasing solubility, dissolution, intestinal permeability, lymphatic absorption and bioavailability of the insoluble drugs such as VIP, which is less affected by food intake.
Animals ; Biological Availability ; Caco-2 Cells ; Dosage Forms ; Drug Delivery Systems ; Emulsions ; chemistry ; pharmacokinetics ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Solubility ; Vinca Alkaloids ; chemistry ; pharmacokinetics