Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry

Objective To observe the metabolism and distribution of arsenic in liver and brain of offspring rata by exposure to arsenic of pregnant rats or lactation dams and weaned pups,and explore if arsenic could penetrate the placental barrier,lactation barrier and blood brain barrier. Methods The Wistar female rots were randomly divided into four groups according to body weights,12 in each group,and were fed with drinking water that contained arsenic(NaAsO_2) 0,10,50,100 mg/L beginning from the gestafional day 6 until pups 42 days old. Pups were separately sacrificed on postnatal day(PND) 0,15,28,42. Arsenic in liver and brain of offspring rots and in breast milk was examined by atomic absorption speetrophotometer with an arsenic speeiation pretreatment system. Results Concentration of iAs,MMA,DMA of brain in 50,100 mg/L groups were higher than that of 0 mg/L group[0,0,0,(7.3±6.6),0,(44.2±27.4)ng/g]on PND 0,42[iAs: (120.0±46.0),(195.5±125.3),(216.5±278.4),(176.6±151.8) ng/g; M MA: (47.2±18.1),(199.6±389.1),(47.4±55.2),(82.7±79.2) ng/g; DMA: (984.3±377.4),(2222.1±1433.2),(998.1±368.3),(1781.3±715.7)ng/g,all P < 0.05]. Concentration of DMA of brain in 50,100 mg/L groups were higher than that of 0 mg/L group[(13.9±18.1),(50.6±98.3)ng/g]on PND 15,28 [(270.3±73.1),(323.9±72.7),(758.7±245.9),(1020.6±383.6) ng/g,all P < 0.05]. Concentration of iAs,DMA of liver in 10,50,100 mg/L groups were higher than that of 0 mg/L group [(1.4±3.5),(49.7± 47.1),0,(100.4±30.2)ng/g]on PND 28,42 [iAs: (37.5±28.1),(268.8±246.4),(307.2±339.9),(15.4±9.4),(479.1±161.1),(408.4±51.9)ng/g;DMA: (594.5±148.8),(3181.9±519.0),(4834.2±2568.4),(1061.8± 85.2),(3697.1±553.7),(4120.0±732.8) ng/g,all P < 0.05]. Concentration of DMA of liver in 10,50,100 mg/L groups were higher than that of 0 mg/L group[(13.2±20.5)ng/g]on PND 15[(182.0±60,2),(637.6±90.0),(1458.7±196.3)ng/g,all P < 0.05]. Concentration of arsenicals of liver and brain showed a dose-dependent increase. The concentrations of DMA of breast milk in 50,100 mg/L groups were also higher than that of 0 mg/L group[(9.8±13.4),0 ng/g]on PND 0,15 [(182.3±85.9),(372.2±203.9),(124.2±33.1),(244.4±196.5)ng/g,all P < 0.05]. In the analysis of the change of arsenic on different postnatal day,we found the concentration of iAs,MMA,DMA,TMA in liver and brain of pups all decreased on postnatal day 15,and was lower than that on PND 0,28 and 42. Conclusions The distribution of arsenic and methyl-metabolism in liver and brain of pups is related with arsenic exposure dose. Arsenic can penetrate the placenta and blood brain barrier easily and lactation can hinder arsenic intake in some extent.

Animals ; Arsenic ; toxicity ; Comet Assay ; DNA Damage ; drug effects ; Lymphocytes ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Wistar ; Tobacco Smoke Pollution ; adverse effects

Abstract: Objective　To analyze the laboratory microscopic re-examination results of malaria cases in Nantong of the National Notifiable Disease Report System from 2014 to 2021 by Nantong Malaria Diagnostic Reference Laboratory, so as to evaluate the malaria diagnosis ability of Nantong Malaria Diagnostic Reference Laboratory. Methods　The blood smear and blood samples of malaria cases in Nantong from 2014 to 2021 of the National Notifiable Disease Report System were collected. Nantong Malaria Diagnostic Reference Laboratory and Jiangsu Institute of Parasitic Diseases carried out the re-examination of municipal and provincial laboratories, taking the results of provincial laboratory as the standard to compare and analyze the re-examination results of Nantong Malaria Diagnostic Reference Laboratory. Results　From 2014 to 2021, the two-level laboratories in Nantong city and Jiangsu Province re-examined the blood samples of 297 malaria cases. The microscopic examination and PCR re-examination results at the provincial level were the same：292 positive cases and 5 negative cases. The qualitative coincidence rate between Nantong microscopic re-examination results and the provincial re-examination results was 100% (297/297), without misjudgment and omission. The coincidence rate of Plasmodium typing was 96.23% (281/292). The coincidence rate of P. falciparum, P. vivax, P. ovale and P. malaria were 99.57% (234/235), 62.50% (5/8), 89.47% (34/38) and 72.73% (8/11) respectively. The consistency test results showed that the Kappa value of Plasmodium typing results between municipal and provincial laboratories was 0.89. The Kappa values of P. falciparum, P. vivax， P. ovale and P. malaria were 0.98, 0.58, 0.87 and 0.79 respectively. Conclusion　The malaria diagnosis ability of Nantong Malaria Diagnostic Reference Laboratory is generally good, and it is necessary to improve the ability of Plasmodium typing.

To reveal the characterization of interaction between Chinese and western medicinal injections, isothermal titration calorimetry (ITC) was applied to evaluating the interaction of Yiqi Fumai injection (YQFM, as mode drug) with epinephrine hydrochloride injection (YS) and 5% glucose injection (5% GS). The diversification of Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) were determined to judge the reaction types of colliquefaction procedures of different injections. Meanwhile, the fingerprints of YQFM before and after combined with the various injections were compared to validate the results. This work demonstrated that during the titration procedure of YQFM and YS, [ΔH] > T [ΔS] , that was to say the reaction was enthalpy-driving. And the reactive profile indicated that a great deal of heat gave out during the procedure. Obviously, chemical reactions happened and the internal component changed. On the other side, the reaction of YQFM combined with 5% GS was entropy-driving, because [ΔH] < T [ΔS]. The reactive profile showed there was only a little heat released. So non-chemical reactions happened and the major ingredients did not change. ITC could be applied to the evaluation on compatibility of other kinds of Chinese and western medicinal injection combination.
Calorimetry ; Drug Interactions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Entropy ; Epinephrine ; chemistry ; pharmacology ; Glucose ; chemistry ; pharmacology ; Injections ; Thermodynamics

Objective To study the effects of fluorine and aluminum on index of hematologic tests of rats. Methods According to body mass,56 Wistar rats of 130-200 g were randomly divided into control,low-fluorine (F),middle-F,high-F,low-F + aluminum(Al),middle-F + Al,high-F + Al group,8 rats in each group were given a series of doses of fluoride and aluminum,which were (0 + 0),(100 + 0),(200 + 0),(300 + 0),(100 + 10),(200 + 10),(300 + 10)mg/L After 90-day intragastrie administration,blood samples were collected on eyes of rats to undergo blood routine test,including red blood cell (RBC),lymphocyte (LYM),platelet (PLT),hemoglobin (HGB),white blood cell (WBC),hematocrit (HCT),mean corpuscular hemoglobin (MCH),mean corpuscular-hemoglobin concentration(MCHC),mean corpuscular volume(MCV),and at the same time some blood biochemistry indicators related to functio ns of liver and kidney were determined such as aspartic acid aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),Crea(Cr) and Urea. Organ coefficient of liver and kidney were calculated. Results The difference of RBC,HCT,MCV among all groups of rats was statistically significant(F = 3.202,3.316,2.915,P < 0.05). The RBC,HCT of the low-F group[(7.59± 2.40)×10~(12)/L,0.51±0.11],the middle-F group[(8.60±1.16)×10~(12)/L,0.55±0.05],the high-F group[(9.23± 0.60)×10~(12)/L,0.54±0.03],the low-F + Al group[(9.25±0.79)×10~(12)/L,0.53±0.04],the middle-F + Al group[(7.98±2.14)×10~(12)/L,0.49±0.08]and the high-F + Al group[(7.61±3.17)×10~(12)/L,0.49±0.16]were significantly higher than that in the control group[(4.46±3.10)×10~(12)/L,0.31±0.16,P< 0.05 or < 0.01)]. The MCV of the middle-F group[(64.06±6.51)fl],high-F group[(58.67±1.13)fl],low-F + Al group[(57.78± 1.57)fl]and the middle-F + Al group[(63.04±10.64)fl]were significantly higher than the control group[(78.54± 15.57)fl,P < 0.05 or < 0.01]. The difference of AST and Urea among all the groups of mrs serum was statistically significant(F= 2.847,5.549,P < 0.05 or < 0.01). The serum AST of low-F group[(399.00±54.99)U/L],the middle-Fgroup[(465.60±76.99)U/L],the high-F group[(465.80±75.41)U/L],the low-F + Al group[(346.00±69.26) U/L],the middle-F + Al group[(437.40±68.31)U/L]and the high-F + Al group[(403.00±30.61)U/L]were all significantly higher than that in the control group[(336.67±94.34)U/L,P < 0.05],and the high-F group significantly higher than the high-F + Al group(P < 0.05). The serum Urea of the middle-F group[(7.70±0.52)mmol/L],the high-F group[(8.44±1.30)mmol/L],the low-F + Al group[(7.83±0.62)mmol/L],the middle-F + Al group [(7.73±0.47)mmol/L],and the high fluoride + aluminum group[(7.70±0.21)mmol/L]were all significantly higher than that in the control group[(6.55±0.50)mmol/L,P< 0.05 or < 0.01],and the low-F group was significantly lower than the low-F + Al group(P < 0.01),however the high-F group was significantly higher than that in the high-F + Al group(P< 0.05). The liver organ coefficient of the low-F group(2.94±0.36) was higher than the low-F + Al group (2.60±0.15,P < 0.05). Conclusions Fluorine and combination of aluminum and fluorine have toxicity on rats to a certain extent,including the proliferation of crythrocytes of rat,while the cell size gets smaller and the cell quality is deteriorated,meanwhile functions of liver and kidney are impaired. Aluminum shows different joint action in different concentrations of fluorine.

Objective To probe into the impact on sperm motility in male rat induced by fluorine poisoning, and provide experimental basis to further research for reproductive toxicity of fluoride. Methods According to bodyweight, 32 male Wistar rats were randomly divided into control group, the low-dose, medium-dose and high-dose group( 100,200,300 mg·kg~(-1)·d~(-1) NaF), and were treated by intragastric administration for 90 days, and the weight of the rats was observed each day. After the last intragastric administration, all rats were killed. The relative weight of liver, kidney and testis was calculated. Rat epididymides were plucked off and spermatozoa released from it. Sperm motility parameters were measured by WLJY-9000 color-detection system of sperm quality. Results Compared with high-dose group[(206.00 ± 18.16)g], the weight of low-dose and medium-dose group [ (235.00 ± 14.56), (235.44 ± 24.99)g] in 30 days were statistically significant increased(all P < 0.05) ; there were no significant differences between the groups in 60 days and in 90 days(F = 0.578,1.893, all P > 0.05). Comparison of organ coefficient of liver, kidney and testis among three groups showed no significant difference(F = 2.148,0.907, 1.801, all P > 0.05). The average path velocity(VAP) of the high-dose group[ (25.04 ± 4.59)μm/s] showed significant increase compared with control group[ (20.22 ± 3.29)μm/s] ; the straight line velocity(VSL) of the low- dose, medium-dose and high-dose group[ (18.82± 3.19), (17.84 ± 4.54), (16.46 ± 2.63)μm/s] showed significant increase compared with control group[ ( 12.48 ± 1.73 ) μm/s ] ; linearity (LIN) of the low-dese, medium-dose and high.dose group[(23.84±1.58)%,(24.99±3.37)%,(26.75±5.07)%]showed significant decrease compared with control group[(33.29±4.00)%];wobble(WOB)of the medium-dose and high-dose group[(47.03±3.98)%,(4921±723)%]showed significant increase compared with control group[(38.09±0.48)%];mean angular deviation (MAD)of the low-dose group[(68.29±5.71)radian/s]showed significant decrease compared with control group [(81.57±8.44)radian/s];beat cross frequency(BCF)ofthe high-dose group[(117±0.61)/s]showed significant increase compared with control group[(9.49±0.34)/s];sperm density(p)of the low-dose and medium-dose group [(1.26±0.24)×10~9/L,(1.84±0.50)×10~9/L]showed significant decrease compared with control group [(3.94±1.10)×10~9/L,all P<0.05].Comparison of the eurvilinearvelocity(VCL),straightness(STR),amplitude of lateral head displacement(ALH)among three groups showed no significant difference(F=0.264,2.209,1.667, all P>0.05).Conclusion Fluorine poisoning could change sperm motility parameters of the rat,reduce the sperm density and cau8e damage to the reproductive system.

OBJECTIVETo investigate the relationship between lamivudine-resistant mutants of hepatitis B virus (HBV) and serum HBV DNA loading before antiviral therapy.

METHODSThis study involved 106 patients with hepatitis B receiving lamivudine treatment for an average of 32 months (rang 12-48 months). Serum HBV DNA loadings were measured with PCR before and every 4 to 6 months during lamivudine therapy. HBV YMDD mutants were detected using mismatched PCR-restriction fragment length polymorphism (PCR-RFLP) during lamivudine treatment.

RESULTSHBV DNA loading was significantly higher in patients infected with HBV YMDD mutants during lamivudine therapy than those infected with HBV without YMDD mutation.

CONCLUSIONHigh viral loading in hepatitis B patients before treatment is associated with high likeliness of HBV YMDD mutation during lamivudine treatment. HBV DNA loading may be indicative for the occurrence of YMDD mutation during lamivudine therapy.

Antiviral Agents ; pharmacology ; DNA, Viral ; blood ; Drug Resistance, Viral ; genetics ; Female ; Hepatitis B ; blood ; Hepatitis B virus ; drug effects ; genetics ; physiology ; Humans ; Lamivudine ; pharmacology ; Male ; Middle Aged ; Mutation ; Viral Load ; genetics

OBJECTIVETo evaluate the effect of meatoplasty with the pedicle flap in the treatment of meatal stenosis secondary to chronic balanitis.

METHODSWe retrospectively analyzed 32 cases of meatal stenosis secondary to chronic balanitis treated by meato- plasty with the pedicle flap. All the patients had a history of chronic balanitis and had received meatal dilatation or simple ventral mea- totomy without significant effect. Their mean maximum urinary flow rate (Qmax) was (4.3 ± 2.4) ml/s. During the operation, A "/\"-shaped incision was made in the healthy epidermis and a flap was harvested from the frenulum. After complete removal of the scar, the flap was placed into the urethral wall, followed by reconstruction of the external urethral orifice.

RESULTSThe patients were fol- lowed up for 6 to 30 months, which revealed smooth urination in all the patients with Qmax of (26.7 ± 4.5) ml/s and normal erectile function and uresiesthesis.

CONCLUSIONWith little invasiveness and few complications, meatoplasty with the pedicle flap is an ideal surgical method for the treatment of meatal stenosis secondary to chronic balanitis. However, there might be some change in the normal appearance of the balanus postoperatively, and its long-term effect needs further observation.

Balanitis ; complications ; Constriction, Pathologic ; etiology ; surgery ; Dilatation ; Humans ; Male ; Postoperative Period ; Reconstructive Surgical Procedures ; Retrospective Studies ; Surgical Flaps ; Urethra ; surgery ; Urethral Stricture ; etiology ; surgery ; Urination

OBJECTIVETo explore the impact of 5-fluorouracil (5-FU) on glucose metabolism and pancreatic pathology.

METHODSTwenty Wistar rats were divided into 5-FU group(n=10, chemotherapy was administered intraperitoneally to animals at a dose of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride was administered intraperitoneally to animals with the same dose at the same time ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by serial measurement of blood glucose before and after an oral glucose load. Plasma insulin concentration was determined by radioimmunoassay. Pancreatic pathology was examined with morphological method and the ultrastructural changes of β cells were observed by transmission electron microscope.

RESULTSFasting blood glucose level was significantly higher in the 5-FU group than that in the control group [(7.6±0.9) mmol/L vs. (4.6±0.6) mmol/L at day 2; (8.9±1.0) mmol/L vs. (4.7±0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the early phase insulin response to glucose load was significantly diminished in animals treated with 5-FU at day 2. Insulin level was significantly lower in the 5-FU group than that in the control group at 30 min (P<0.01). The peak secretion time of plasma insulin in 5-FU group was at 60 min, similar to the control group; and plasma insulin level decreased more slowly. Plasma insulin level was higher in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin level was lower in the 5-FU group than that in the control group on 60 min, and the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin level was significantly increased in 5-FU group than that in control group on 180 min(P<0.01). No gross histopathological damage to the pancreas was observed at day 2 and 7 following administration of 5-FU. The structural changes of mitochondria were mainly the quantities of secretory granule diminished at day 7 under transmission electron microscope. Dilated rough endoplasmic reticula, swollen mitochondria, and the presence of adipose drops in lysosomes were found in few cells.

CONCLUSIONS5-FU-induced hyperglycemia appears to be mediated in part by a relatively deficient insulin secretion to glucose stimulation. A relative deficiency in insulin secretion following 5-FU treatment appears to be related to β cells function impairs with islet cell ultrastructural changes induced by 5-FU.

Animals ; Blood Glucose ; drug effects ; metabolism ; Female ; Fluorouracil ; pharmacology ; Insulin ; blood ; Male ; Pancreas ; drug effects ; pathology ; Rats ; Rats, Wistar