Spray coated pellets as carrier system for mucoadhesive drug nanocrystals.

High pressure homogenization can be employed to produce drug nanocrystals with a number of advantages, like improved solubility behaviors, better drug targeting or even increased mucoadhesiveness. To obtain a controlled drug delivery system it is necessary to transform the resulting nanosuspension into a solid dosage form. The present study shows the feasibility to use a mucoadhesive nanosuspension of poorly soluble hydrocortisone acetate produced by high pressure homogenization as layering dispersion in a fluidized bed process, followed by the application of an enteric coating to achieve a controlled drug release. To point out the advantages of drug nanocrystals the new fomulation was compared with a formulation containing micronized drug. Both formulations were characterized with regard to their particle size and crystallinity by using laser diffractometry, photon correlation spectroscopy and X-ray diffraction. The pellet morphology was characterized by using the environmental scanning electron microscopy (ESEM). In the in vitro dissolution tests an accelerated dissolution velocity and an increased drug release could be shown for the pellets containing drug nanocrystals.     

Social phobia, fear of negative evaluation and harm avoidance.

This naturalistic, prospective investigation examined the role of fear of negative evaluation and the personality trait of harm avoidance in the anxiety levels of treated social phobia patients. One hundred and fifty-seven patients with DSM-IV social phobia were assessed before starting treatment and were then followed for up to two years. As expected, greater fear of negative evaluation and higher scores of harm avoidance were associated with greater anxiety at the 6 month follow-up, and harm avoidance remained a significant predictor at 24 months. However, no evidence was found for an interaction between the personality and cognitive variables examined. The findings are discussed in terms of the relative independence of these factors, as well as their potential implications for the treatment of this disorder.     

Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis.

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.     

三维骨建模在全膝关节置换术中韧带平衡的作用

目的探讨以三维骨建模为基础、无需影像的计算机辅助系统在人工全膝关节置换术(totalknee arthroplasty,TKA)中韧带平衡的作用。方法2002年11月～2003年6月,采用后稳定型人工全膝关节,在Ceravision无需影像资料的三维骨建模系统导航监控下,辅助完成TKA21例。男5例,女16例,年龄64～79岁,平均72.4岁。其中2例既往行胫骨近端截骨术,1例行股骨远端截骨术。14例膝内翻,7例膝外翻。术前下肢全长X线正位片测量,内翻13°～外翻13°,平均2.36°;膝关节X线正位片测量,应力下内翻平均8.47°(内翻2°～内翻20°),应力下外翻平均3.63°(内翻7°～外翻12°)。结果术中导航系统测量,额面内翻12°～外翻10°,平均3.33°,与术前比较差异有统计学意义(P<0.05);额面应力下内翻平均6.47°(内翻0°～内翻24°),应力下外翻平均4.32°(内翻8°～外翻15°),与术前比较差异有统计学意义(P<0.05)。术毕导航系统测得膝内外翻平均0.175°(内翻2°～外翻3°),而术后下肢全长X线正位片测量平均0.3°(内翻3.5°～外翻1.5°),二者差异无统计学意义(P>0.05)。术后3个月关节活动度为105～130°,平均115°,膝关节额面松弛度0.2～0.5cm,平均0.27cm。人工膝关节胫、股骨假体取得满意的对位置入和韧带平衡,无关节失稳和髌骨脱位等并发症发生。结论以三维骨建模为基础、无需影像的Ceravision系统,具有三维立体定位、优化截骨,并通过旋转对位和韧带松解获得伸屈膝关节等距间隙与韧带平衡稳定的作用,近期临床疗效满意,可在TKA中常规使用。     

Risk factors for oral hairy leukoplakia in HIV-infected adults of Brazil

BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells.

Placenta is an important source of leptin during pregnancy that contributes to the high plasma leptin levels in pregnant women. Leptin and its functional receptors are synthesized in trophoblast cells that, in turn, secrete gestational hormones supporting a paracrine or autocrine role for leptin in the endocrine activity of the placenta. In the present study we examined the effect of leptin on in vitro release of gestational hormones (human chorionic gonadotropin (hCG), human placental lactogen (hPL), progesterone, estrogens and testosterone) by human term placental cells in culture. Placentas at term were obtained immediately after delivery from mothers with uncomplicated pregnancies. Progesterone, hCG, hPL, estradiol, estrone, estriol and testosterone levels were measured by different assays in culture media of cells maintained in monolayer culture after incubation for 12, 24, 48 or 72 h with leptin or placebo. Incubation with leptin did not modify hCG, hPL, progesterone, estriol and estrone secretion for any of the doses and times assayed. However, leptin led to a dose-dependent decrease in estradiol release. This effect was observed when treatment with recombinant human leptin spanned from 12 to 72 h. At this time an increase in testosterone levels was observed in leptin-treated cells versus placebo. These results indicate that leptin can be considered a gestational hormone implied in the endocrine function of the placenta, with an important role in control of the production of steroid reproductive hormones in placental cells in vitro.     

Female pelvic floor. Descriptive anatomy and clinical exploration by transvaginal ultrasound

In order to assess the state and pathology of the woman's pelvis minor, a number of methods are commonly used among practitioners, encompassing clinical exploration, radiology, MRN, urodynamics, endoscopy and echography.

Echography has been poorly used in clinical pelvic exploration and its reliability is actually a matter of controversy 1. However, echographic surveys can provide us with valuable gynecological data on the state and pathologies of the soft pelvis, within the genital regions or even going beyond them, i.e. the rectal channel, bladder, urethra, anus, vascular plexuses, and all of their supporting tissues.

At our research unit, we have been employing Transvaginal Ultrasound echography (TVU) for a long time in conjunction with other pelvis-focused methods in order to study different kinds of pelvic alterations. TVU has proven to be friendly to use, fast, harmless and inexpensive, allowing serial explorations and producing high-quality dynamic images (loop-cinema, video-tape). Furthermore, this method is fairly aseptic in that the occurrence of faeces in the rectal ampolla is not a nuisance but a bonus in tracking the contours of the rectum walls and other topographical features which would be otherwise difficult to survey.

A complete pelvic floor TVU may add no longer than 5-8 minutes to a routine gynecological examination, can be implemented by the general gynecologist and generates data that can be further studied by the appropriate specialist for a more insightful evaluation 2.     

Hormone replacement therapy and bleeding disorders.

Bleeding disorders encountered during administration of hormone replacement therapy (HRT) are reviewed. The incidence of bleeding disorders is dependent on the phase of HRT and the age of the patient. In the diagnosis of these bleedings transvaginal sonography and minihysteroscopy are very important methods. Endometrial thickness can be monitored exactly by transvaginal sonography. Outpatient minihysteroscopy without anesthesia results in higher compliance to HRT after the procedure. In hormonal treatment of bleeding disorders during HRT, the sonographically supported progestogen test is very useful and can reduce endometrium thickness. Operative treatments include myoma and polyp resection as well as endometrial ablation. By these methods a high rate of bleeding-free HRT can be reached. The problem of endometrial cancer during HRT is discussed on the basis of new literature and critical statements. The review shows the importance of individual diagnostic and treatment schedules for bleeding disorders during HRT.