醋酸环丙孕酮／炔雌醇复方片剂在人体的药代动力学

目的建立人血浆中醋酸环丙孕酮的HPLC—ESI—MS测定方法和丹酰氯衍生化血浆中炔雌醇的HPLC—APCI—MS测定方法,测定女性志愿者口服复方醋酸环丙孕酮片1片后的药代动力学参数,并对受试制剂和参比制剂的生物等效性进行评价。方法血浆样品中的炔雌醇以乙酸乙酯提取后,与丹酰氯发生衍生化反应,进行HPLC—APCI—MS分析,流动相为10mmol·L-1乙酸铵缓冲液（1％甲酸）-甲醇（3：97）。检测离子分别为m／z530．3（炔雌醇的丹酰氯衍生物）、m／z404．3（内标,对羟基联苯的丹酰氯衍生物1。结果在10．43～625．8Pg·ml-1范同内炔雌醇的丹酰氯衍生物与内标的丹酰氯衍生物峰面积比值与浓度呈良好的线性关系,最低定量限为10．43pg·ml-1结论本实验建立的分析方法灵敏、准确、简便,且统计学结果表明两种制剂生物等效。     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Progress in understanding oral health and HIV/AIDS

Over the last 30 years, there have been significant advances in our scientific knowledge of HIV disease, including prevention, detection, medical management, and attempts at cure. Investigations and observations of the oral cavity in individuals with HIV disease have contributed substantially to scientific discovery and innovation. Challenges remain for managing existing and emerging oral diseases associated with HIV and understanding the contribution of latent oral mucosal reservoirs to HIV eradication.     

The incidence and natural history of knee osteoarthritis in the elderly,the framingham osteoarthritis study

Objective. To determine the incidence of radiographic knee osteoarthritis (OA) and symptomatic OA (symptoms plus radiographic OA), as well as the rate of progression of preexisting radiographic OA in a population-based sample of elderly persons. Methods. Framingham Osteoarthritis Study subjects who had knee radiographs and had answered questions about knee symptoms in 1983–1985 were reexamined in 1992–1993 (mean 8.1-year interval) using the same protocol. Subjects were defined as having new (incident) radiographic OA if they developed grade ≤2 OA (at least definite osteophytes or definite joint space narrowing). New symptomatic OA was present if subjects developed a combination of knee symptoms and grade ≤2 OA. Progressive OA was diagnosed when radiographs showing grade 2 disease at baseline showed grade ≤3 disease on followup. Results. Of 1,438 participants in the original study, 387 (26.9%) died prior to followup. Of the 1,051 surviving subjects, 869 (82.7%) participated in the followup study (mean ± SD age 70.8 ± 5.0 at baseline). Rates of incident disease were 1.7 times higher in women than in men (95% confidence interval [CI] 1.0–2.7), and progressive disease occurred slightly more often in women (relative risk = 1.4; 95% CI 0.8–2.5) but rates did not vary by age in this sample. Among women, approximately 2% per year developed incident radiographic disease, 1% per year developed symptomatic knee OA, and about 4% per year experienced progres- sive knee OA. Conclusion. In elderly persons, the new onset of knee OA is frequent and is more common in women than men. However, among the elederly, age may not affect new disease occurrence or progression.     

Investigation of the biological activity,mechanical properties and wound healing application of a novel scaffold based on lignin–agarose hydrogel and silk fibroin embedded zinc chromite nanoparticles

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles. Considering the cell viability technique, red blood cell hemolysis in addition to anti-biofilm assays, it was determined that after three days, the toxicity of the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite was less than 13%. Moreover, the small hemolytic effect (1.67%) and high level of prevention in forming a P. aeruginosa biofilm with low OD value (0.18) showed signs of considerable hemocompatibility and antibacterial activity. Besides, according to an in vivo assay study, the wounds of mice treated with the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite scaffold were almost completely healed in five days. Aside from these biological tests, the structural features were evaluated by FT-IR, EDX, FE-SEM, and TG analyses, as well as swelling ratio, rheological, and compressive mechanical study tests. Additionally, it was concluded that adding silk fibroin and ZnCr₂O₄ nanoparticles could enhance the mechanical tensile properties of cross-linked lignin–agarose hydrogel, and also an elastic network was characterized for this designed nanobiocomposite.

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles.     

Effect of transforming growth factor-beta 1 on proliferation and induction of hemoglobin accumulation in K-562 cells

The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF- beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility of hemoglobinization by TGF-beta 1. One high response clone (no. 1) and one low response clone (no. 8) were studied in detail. Hemoglobin accumulation peaked on day 5 of culture in the presence of TGF-beta 1 (0.5 ng/mL, 20 pmol/L), when 90% of clone 1 cells, 55% of parent line cells, and less than 10% of clone 8 cells contained hemoglobin. There was a concomitant reduction in proliferation of 60% for clone 1, 40% for the parent line, and 30% for the clone 8 on day 5 of culture. Quantitative analysis showed that the hemoglobin contents in clone 1 after 5-day induction by TGF-beta 1 and hemin were 1.0 pg/cell and 2.9 pg/cell, respectively. The hemoglobin induced by TGF-beta 1 showed the same electrophoretic characteristics as the hemoglobin induced by hemin. The expression of epsilon-globin mRNA was minimally detectable in control cells and was induced in both TGF-beta 1 and hemin treated cells. Other cytokines with potential effects on K-562 cell proliferation and differentiation were also studied. Interleukin-1, interleukin-3, interferon alpha, interferon gamma, and inhibin, tested as single agents, showed minimal effects on proliferation. None of these agents could induce hemoglobinization or inhibit the hemoglobinization induced by TGF-beta 1.     

Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging

OBJECTIVE: Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain. METHODS: Subjects ages 50-79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain. RESULTS: Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5-6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83). CONCLUSION: Development of knee pain is associated with an increase in BMLs as revealed on MRI.     

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.