抗癌抗生素C1027与单克隆抗体Fab片段偶联物的抗肝癌作用

抗人肝癌单克隆抗体(单抗)3A₅用木瓜蛋白酶消化得到Fab片段。单抗3A₅和Fab片段分别与抗癌抗生素C1027偶联,偶联物经克隆生成法测定对肝癌细胞有很强的杀伤作用,C1027,Fab-C1027和3;3A₅-C1027的IC₅₀分别为6.5×10^-16,8.6×10^-16和4.2×10^-14mol·L^-1;Fab-C1027偶联物对非靶细胞(KB)的IC₅₀值为1.4×10^-13mol·L^-1,与靶细胞(BEL-7402)的IC₅₀值相比,两者相差160倍。说明Fab-C1027的杀伤活性强于3A₅-C1027,并对靶细胞呈选择性杀伤作用。给皮下移植人肝癌的裸鼠iv剂量0.1 mg·kg^-1,结果C1027和Fab-C1027的抑瘤率分别为59和85%,说明Fab片段与C1027偶联物比游离C1027的疗效更高。     

盐酸地芬尼多片溶出度考察

目的：对盐酸地芬尼多片进行溶出度测定,以考察其质量。方法：采用高效液相色谱法测定了盐酸地芬尼多片的溶出度,色谱柱,YWG－C18柱,流动相：甲醇－0．5％三乙胺溶液（磷酸调PH值为3．5）（62：38）,检测波长;215nm。结果：各（厂）批产品溶出参数（T50,Td,m)有极显著差异（P＜0．01）,结论：有必要增加盐酸地芬尼多片溶出度检查以控制其质量。     

1，1－二烷基－4－（3－溴丙酰基）－哌嗪溴化物的合成及生物活性研究

设计合成了七种新的１，１－二烷基－４－（３－溴丙酰基）哌嗪季铵盐溴化物，通过ＩＲ，￣１ＨＮＭＲ和元素分析证实其结构。初步生物活性试验结果表明，Ⅵａ，Ⅵｃ和Ⅵｅ～ｇ有明显的镇痛活性，Ⅵｅ～ｇ还有较好的抗氧化ＳＯＤ活性，但未发现有抗肿瘤作用。     

Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group

To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cells and platelets. Quality control of bedside filtration was explored by sequential sampling downstream of the filter, but this did not predict the total number of leucocytes transfused. After exclusions, 123 evaluable patients were assessed every two weeks until the end of therapy. HLA antibodies developed in 21 of 56 (37.5%) nonfilter (NF) and 15 of 67 (22%) filter (F) patients (risk ratio estimate, 0.60 [95% confidence interval, 0.34 to 1.05]; P = .07). Patients with acute myeloid leukemia (AML; n = 53) had higher alloimmunization rates in both arms of the study, with a greater effect of filtration (62.5% NF and 31.0% F; P = .025). Bedside filtration did not affect the overall incidence of febrile transfusion reactions (FTRs; 37% NF and 34% F; P = .71) or of platelet refractoriness assessed in 50 patients (30% NF and 26% F), despite an association between broad HLA reactivity and both FTRs and refractoriness. However, FTRs were also seen in 28 patients without HLA antibodies. Five alloimmunized refractory patients (2 F and 3 NF) required HLA-selected platelets. This report, the first prospective study of bedside filtration, has failed to show clear clinical benefit. Methodological limitations may account in part for this failure, notably the difficulties in accurately assessing the number of leucocytes transfused.     

A simple approach to prenatal diagnosis of beta-thalassemia in a geographic area where multiple mutations occur

We describe a simple approach for detecting beta-thalassemia mutations in geographic areas such as southern China where multiple mutations are known to occur. Segments of the beta-globin gene were amplified in vitro by using the polymerase chain reaction. Dot blot hybridization of the amplified DNA with oligonucleotide probes corresponding to the six mutations found in southern China could directly identify the mutations causing beta-thalassemia in the affected families. The increased number of target sequences after amplification allows the use of 35S-labeled probes, which are reusable for up to 3 months. The mutations can be determined in two days.     

Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

Aim

To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress.

Methods

Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed.

Results

Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033).

Conclusion

Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males.Maintaining homeostasis is often challenged by different types of stressors (1). Homeostasis is regulated by a complex endocrine processes engaging the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic autonomic system (2-4). Stress can occur either in acute or chronic form with different consequences – the acute stress mostly induces the ˝fight or flight˝ response, while chronic stress promotes long term changes, which can lead to a variety of diseases (5,6). If stress is of sufficient magnitude and duration, the action of HPA is unsuppressed and results in prolonged elevation of cortisol (7), induced production of energy, vasoconstriction, lipolysis, proteolysis, immunosuppression, and suppression of reproductive function to save energy and retain overall homeostasis (8). Women are generally less susceptible to chronic stress up to the period of menopause, when the loss of protective hormones, estrogen and progesterone, occurs and thus they become prone to development of depression, anxiety, or schizophrenia (9). In contrast, men are generally more susceptible and sensitive to chronic stress, showing changes in feeding habits and decreased body weight (10,11).Chronic stress can cause the development of cardiovascular disorder, obesity, and diabetes, which can be reflected in serum cholesterol, glucose, and decreased glucose tolerance (12-14). There is a strong correlation between stress and sexual hormones, but the mechanisms by which estrogen, testosterone, and progesterone exert their possible protective role under stress conditions are not fully explored. Sexual hormones affect stress outcome and stress hormones affect the levels of sexual hormones (15-17). Testosterone is activated during stress response in rats and humans (18,19) and tends to increase more in men than women (20). Estrogen lowers the stress-induced response in women and men (9,21). Estrogens and progesterone are produced even after ovariectomy by adrenal glands (22) but it is not known if such compensation can withstand additional challenge like stress. Another possible player in stress response is leptin (Ob), hormone responsible for maintaining body weight, which is synthesized and secreted by adipose tissue (23), exerting its effects through the leptin receptor (Ob-R) (24). Chronic stress models imply a direct link between stress response and leptin (25,26). Receptors for leptin are present in the adrenal gland (27). The aim of this study was to investigate cardiovascular risk parameters and changes in leptin and sexual hormone receptors in adrenal gland during chronic stress. There is a clinically relevant change in the onset of cardiometabolic risk between healthy women and women with premature ovarian failure (28) and because of that ovariectomized female rats were included in the study.     

Antioxidant effects of flavonoid from Croatian Cystus incanus L. rich bee pollen

Oxidant/antioxidant status, estrogenic/anti-estrogenic activity and gene expression profile were studied in mice fed with Cystus incanus L. (Cistaceae) reach bee pollen from location in Central Croatia’s Dalmatia coast and offshore islands. Seven phenolic compounds (out of 13 tested) in bee pollen sample were detected by high performance liquid chromatography (HPLC) analysis. Phenolics detected in C. incanus L. bee pollen belong to flavonol (pinocembrin), flavanols (quercetin, kaempferol, galangin, and isorhamnetin), flavones (chrysin) and phenylpropanoids (caffeic acid). Bee pollen as a food supplement (100 mg/kg bw mixed with commercial food pellets) compared to control (commercial food pellets) modulated antioxidant enzymes (AOE) in the mice liver, brain and lysate of erythrocytes and reduced hepatic lipid peroxidation (LPO). Bee pollen induced 25% of anti-estrogenic properties while no estrogenic activity was found. Differential gene expression profile analyses after bee pollen enriched diet identify underexpressed gene Hspa9a, Tnfsf6 (liver) and down-regulated gene expression of Casp 1 and Cc121c (brain) which are important in the apoptosis pathway and chemotaxis. These results indicate that used bee pollen possess a noticable source of compounds with health protective potential and antioxidant activity.     

Aspects of complex oral rehabilitation with oral osseointegrated implants

Dentists and patients become increasingly aware of the complex and predictible results offered by implant-supported dentures. These alternatives fulfill the demands of modern dentistry to rehabilitate the oral health condition according to the highest standards. A deficient residual crest represents a great challenge for the healing and osseointegration of the implants. Dental implants have an essential effect on stopping bone atrophy in the edentulous crest and preserving its condition. Function and esthetics and the patients comfort can be rehabilitated within normal limits. The prosthetic reconstruction based on osseointegration implants has better long-term prognosis if the therapeutic option is judiciously selected. The risk of relative movements at the bone-implant interface decreases according to the difference in value between the elasticity module of the implant and the bone. Prosthetic reconstruction based on implants has a better long-term prognosis if the therapeutic option is judiciously selected from all possibilities according to the osteointegration of an adequate number of implants.