This study taking gestodene (GEST) as a model, investigated the factors affecting reservoir-type intravaginal ring (IVR)'s drug release. This paper reported a gestodene intravaginal ring of reservoir design, comprising a gestodene silicone elastomer core encased in a non-medicated silicone sheath, separately manufactured by reaction injection moulding at 80 degrees C and heating vulcanization at 130 degrees C is reported. The test investigated the factors affecting drug release through a single variable method, taking the drug release rates of 21 days as standards. When changing the thickness of the controlling sheath outside, the ratio of the first day of drug release and mean daily release (MDR), named the relatively burst effect, is closing to 1 with the thickness of controlling sheath increasing, while the 1.25 mm sheath corresponding to 1.04 controlled the burst release effectively; a positive correlation (r = 0.992 2) existed between the average drug release (Q/t) and drug loading (A) within a certain range. The C6-165 controlling sheath with high solubility of GEST is easier to achieve controlled release of the drug; GEST crystalline power is more effective to implement controlled release of drugs among difficent states of the drug. A 1/4 fractional segment core gives a relatively burst effect of 1.76, while the 1/1 and 1/2 are 1.93 and 1.87 separately, at the same drug loading, concluding that use of a fractional segment core would allow development of a suitable GEST reservoir IVR. In summary, GEST reservoir-type IVR could be adjusted by the thickness of controlling sheath, the loading of drug, the material properties of controlling sheath, the dispersion state of drug, the additive composition and structure of intravaginal ring, to control the drug release behavior and achieve the desired drug release rate.
Administration, Intravaginal ; Contraceptive Agents, Female ; administration & dosage ; Contraceptive Devices, Female ; Delayed-Action Preparations ; Drug Delivery Systems ; methods ; Norpregnenes ; administration & dosage ; chemistry ; Silicone Elastomers ; chemistry ; Solubility

OBJECTIVETo study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats.

METHODRats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters.

RESULTAfter oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group.

CONCLUSIONPhenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.

Administration, Oral ; Animals ; Drug Interactions ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Isoflavones ; administration & dosage ; pharmacokinetics ; Male ; Phenformin ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Vasodilator Agents ; administration & dosage ; pharmacokinetics

Objective To analyze the clinical outcome and prognostic factors of concurrent radiochemotherapy (CRCT) or radiotherapy (RT) alone followed by radical hysterectomy in cervical cancer.MethodsBetween April 2006 and June 2011,182 patients with FIGO ⅠB2-ⅢB cervical carcinoma were treated with preoperative CRCT ( 123 patients) or RT alone ( 59 patients) followed by radical surgery.Weekly cisplatin (40 mg/m2)were administered during radiotherapy for patients treated with CRCT.Preoperative RT doses were 40-50 Gy in 20-25 fractions.Total hysterosalpingo-oophorectomy and pelvic lymph node dissection was performed 2-3 weeks after neoadjuvant therapy.The prognostic factors were analyzed by Cox-regression method.ResultsSixty-nine patients were followed up for 3 years.For patients with tumor ≥4.5 cm,there were no significant differences in the 3-year progression-free survival (PFS) and overall survival (OS) rates between CRCT and RT alone ( x2 =1.84 and 1.56,P =0.176 and 0.221 ).For patients with tumor ＜ 4.5 cm,CRCT group had higher PFS and OS rates than RT alone ( x2 =5.22 and 4.81,P=0.022 and 0.018).The 3-year PFS and OS rates were 92.0％ and 93.8％.By multivariate analysis,tumor diameter ( ≥6 cm vs.＜ 6 cm) was significant prognostic factor for PFS and OS (x2 =2.56,P =0.011 ;x2 =4.06,P =0.007 ),age ( ＜ 48 vs.≥ 48 years) was significant prognostic factor for OS (x2=4.86,P =0.046),and postoperative lymph node status (positive vs.negative) was significant prognostic factor for PFS ( x2 =1.04,P =0.010).ConclusionsTreatment with CRCT or RT followed by radical surgery has achieved good OS and PFS for patients with FIGOⅠB2-ⅢB cervical cancer.Tumor diameter,age and postoperative lymph node status are important prognostic factors for survival.

Abstract?AIM:To study the Influence and outcomes of eye healthcare information teaching for the visual development of children under“combination of medicine and education” in kindergartens.?METHODS:The children(5-6 years old) were randomly selected from 6 kindergartens in Nanjing, 3 in Yuhua District as the experimental group, and the other 3 in Jianye District as the control group.A one-year follow-up was conducted to evaluate the difference of visual development, including the rate of low vision, rate of referral caused by refractive abnormality, rate of astigmatism, the average of the equivalent spherical lens and the rate of lacking physiological hypermetropia, between the experimental group and the control group children.?RESULTS:One school year later,the rate of low vision, rate of referral caused by refractive abnormality and the rate of astigmatism, were significantly lower (P<0.05)in the experimental group under the mode of“combination of medicine and education”, which were also lower than those before experiment(P<0.05).The average of the equivalent spherical lens of experimental group increased and the rate of lacking physiological hypermetropia decreased significantly, compared with the control group ( P <0.05 ) and with those before experiment(P<0.05).?CONCLUSION:Using “combination of medicine and education” eye health care model,is good for children's visual development,so as to reduce the rate of low vision and delay the occurrence of myopia.

OBJECTIVETo study on clinical role of acupuncture at Tanzhong (CV 17) for treatment of postpartum hypolactation and to provide clinical basis for indications of acupoints.

METHODSThis was a single blind randomized controlled multi-center study by Beijing obstetrical and gynecological hospital, Beijing Mother and Child health institute and Haidian Mother and Child health institute, 276 cases of postpartum hypolactation were randomly divided into an acupuncture group and a Chinese drug group. The acupuncture group were treated with acupuncture at Tanzhong (CV 17) and the Chinese drug group with traditional drug Tongre Decoction. Degree of breast engorge, lactating volume, prolactin, neonate body weight, artificial feeding frequency and volume, urination frequency and crying time of neonate were recorded for comparison of therapeutic effects.

RESULTSAfter treatment, degree of breast engorge, lactating volume, neonate body weight, artificial feeding frequency and volume, urination frequency and crying time of neonate were significantly improved in the two groups, with no significant difference between the two groups.

CONCLUSIONAcupuncture at Tanzhong (CV 17) can effectively promote lactation with a same therapeutic effect as the traditional Chinese drug Tongru Decocnon.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Female ; Humans ; Lactation Disorders ; therapy ; Puerperal Disorders ; therapy ; Single-Blind Method

AIMThe interactions between diorganotin (IV) complexes of 1,3-dimethyl-4-acetyl-5-pyrazolone (HL1) and mono-nucleotides together with DNA near physiological condition were investigated.

METHODSThe mode of action of the diorganotin (IV) complexes with mononucleotides and DNA under different conditions and different times were investigated by high resolution NMR technology and UV spectra.

RESULTSThe interaction of [(L1)2SnEt2] with AMP was shown to result in significant change of chemical shift of H(8), H(2) and 31P of AMP. Hyperchromic effect of DNA could be observed due to the interaction of; [(L1)2SnEt2] with DNA, while interaction of [(L1)2SnMe2] with AMP and DNA could only cause obvious change of chemical shift of 31P and lead to hypochromic effect of DNA.

CONCLUSIONThe results indicate that [(L1)2SnEt2] can selectively bind to the N1 atom of the base and the phosphate oxygen atom of AMP and may further destroy the helical structure of DNA, while the dimethyltin (IV) compound of 1,3-dimethyl-4-acetyl-5-pyrazolone [(L1)2SnMe2] merely binds to the the phosphate oxygen atom of AMP and causes the contraction of DNA helical structure.

Antineoplastic Agents ; chemistry ; DNA ; chemistry ; Nucleotides ; chemistry ; Organotin Compounds ; chemistry ; Porphyrins ; chemistry

The hematopoietic system of the mouse arises from extraembryonic mesoderm that migrate through primitive streak to the presumptive yolk sac at day 7.0 of gestation. However, the mechanisms regulating mesoderm commitment to hematopoietic lineages remain poorly understood. Previous studies demonstrated that the development kinetics and growth factor responsiveness of hematopoietic precursors derived from embryonic stem cells (ES cells) is similar to that found in the yolk sac, indicating that the onset of hematopoiesis within the embryoid bodies (EBs) parallels that found in the embryo. Furthermore, in vitro differentiation of ES cells to hematopoietic cells is valuable for establishment of therapeutic clone against a variety of hematological disorders. Despite the identification of multipotential hematopoietic progenitors in EBs, a subset of more primitive progenitors, identical to the high proliferative potential colony-forming cells (HPP-CFC) derived from human and murine hematopoietic tissues, have not been clearly identified regarding particular their replating potential in vitro. HPP-CFC is among the most primitive hematopoietic multipotent precursors cultured in vitro. In this study, our aim was to investigate the in vitro and in vivo hematopoietic capacity of HPP-CFC within the day 12 EBs, rather than the expansion of more committed progenitors. In this study the HPP-CFC could be detected within EBs differentiated for 5 to 14 days of murine ES cells, but the development dynamics of the HPP-CFC differed greatly among distinct serum lots. Qualitatively HPP-CFC is capable of forming secondary colonies. As to our expectation the ES cells-derived HPP-CFC demonstrated similar regeneration capacity to those from yolk sac, giving rise to secondary granulocyte, erythrocyte, macrophage and mast cells, however largely differed from the counterparts of adult bone marrow. In addition, by RT-PCR ES cells-derived HPP-CFC were found to express transcription factors associated closely with stem cell proliferation including SCL, GATA-2 and AML1 as well as various receptors of hematopoietic growth factors such as c-kit, GM-CSF receptor and interleukin 3 receptor et al. Finally, in order to understand the in vivo hematopoietic capacity of the ES cells-derived HPP-CFC, spleen colony-forming unit (CFU-S) assay was performed. Nevertheless, typical CFU-S was not observed after transplantation of the day 12 EB cells or HPP-CFC colonies into lethally irradiated adult murine. In conclusion the HPP-CFC differentiated from murine ES cells displayed robust hematopoietic activity in vitro, however their in vivo reconstitution ability was not detected. The difference between in vitro and in vivo hematopoietic activities of ES cells-derived primitive hematopoietic precursors deserves further investigation.
Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Cell Differentiation ; genetics ; physiology ; Colony-Forming Units Assay ; Core Binding Factor Alpha 2 Subunit ; genetics ; Embryonic Stem Cells ; cytology ; GATA2 Transcription Factor ; genetics ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Mice ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; Receptors, Interleukin-3 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; T-Cell Acute Lymphocytic Leukemia Protein 1

OBJECTIVETo evaluate the roles of plasma mast cell carboxypeptidase and chymase in the diagnosis of allergic diseases by measuring the contents of both in children.

METHODSA total of 59 children with allergic diseases and 53 healthy children were recruited into the study. Plasma levels of mast cell carboxypeptidase and chymase were measured using ELISA.

RESULTSThe plasma levels of mast cell carboxypeptidase and chymase in children with allergic children were 1.089 ± 0.752 ng/mL and 0.905(0.375-2.318) ng/mL, respectively, which were significantly higher than those in healthy children [0.593 ± 0.380 ng/mL and 0.454 (0.097-1.077) ng/mL respectively; P<0.05]. There was a significantly positive correlation between plasma mast cell carboxypeptidase and chymase levels in children with allergic diseases (r=0.684, P<0.01).

CONCLUSIONSPlasma levels of mast cell carboxypeptidase and chymase increase in children with allergic diseases, suggesting that mast cell carboxypeptidase and chymase may serve as the indexes for the diagnosis of allergic diseases.

Adolescent ; Carboxypeptidases ; blood ; Child ; Child, Preschool ; Chymases ; blood ; Female ; Humans ; Hypersensitivity ; diagnosis ; enzymology ; Infant ; Infant, Newborn ; Male ; Mast Cells ; enzymology

OBJECTIVETo discuss the perioperative management of hemophiliacs A with orthopaedic complications.

METHODSTo regulate the injection of factor VIII concentrate in peroperative period by testing the level of factor VIII:C in 27 cases. The lever of factor VIII:C was improved to 30% - 50% at the day before the operation. To the severe patients, it was maintained at 58.5% - 89.3% during the operation and at 47.0% - 78.4% in postoperation. While to the gentle, it was maintained at 38.5% - 52.5% during the operation and at 29.2% - 52.3% in postoperation. The individualized surgical procedures were carried out, such as arthrocentesis, open knee synovectomy or arthroscopic synovectomy, evacuation or curettage of haematoma, debridements, internal fixation.

RESULTSAll patients were cured in 14 - 105 days by regulating the injection of factor VIII during the peroperative period. The usage of factor VIII was 1 200 - 70 250 IU.

CONCLUSIONWhile the hemophiliacs have orthopaedic complications, it is necessary to promise the factor VIII:C being maintained at the lever of hemostasis during the peroperative period. The hemophiliacs are endurable to the operation.

Adolescent ; Adult ; Factor VIII ; administration & dosage ; Fractures, Bone ; complications ; surgery ; Hemarthrosis ; etiology ; surgery ; Hematoma ; etiology ; surgery ; Hemophilia A ; blood ; complications ; drug therapy ; Humans ; Male ; Perioperative Care ; Postoperative Complications ; blood

Animals ; Dietary Fats ; Fatty Liver ; diet therapy ; etiology ; pathology ; Female ; Male ; Mollusca ; Rabbits ; Random Allocation