Updated clinical recommendations for the use of tibolone in Asian women

Tibolone, which is indicated for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women, has a tissue-specific mode of action different to that of conventional hormone replacement therapy (HRT). A large proportion of Asian postmenopausal women experience symptoms that most frequently include musculoskeletal pain, insomnia, forgetfulness, hot flushes and sexual dysfunction, and there is a need to address their specific requirements. Recent studies show that, in comparison to HRT, tibolone is as effective in alleviating menopausal symptoms and preventing bone loss, has a greater positive effect on sexual dysfunction and is associated with less vaginal bleeding, but it is rarely mentioned in guidelines for menopausal treatment. Levels of awareness amongst women about treatments for menopausal symptoms vary between Asian countries but, even in countries where awareness is high, HRT usage is much lower than in the West. To provide a practical approach to the use of tibolone in Asian postmenopausal women, a panel of experts in the management of menopause from 11 Asia Pacific countries has developed recommendations for its use, based on the evidence from clinical studies published since 2005. However, as much of the clinical data reviewed are from international studies, the recommendations and the treatment algorithm presented here are widely applicable

Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women; A 2 year, placebo-controlled study

Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise-healthy postmenopausal women aged 54.8±3.5 (mean±SD) years who entered this double- blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (n = 15) or 150 mg/d (n= 13), placebo (n= 13), or CEEs 0.625 mg/d (n = 15). At baseline and after 6, 12, and 24 months of treatment, we assessed serum lipids, blood pressure, glucose metabolism, C-reactive protein, and various hemostatic parameters. Compared with placebo, both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L (all P<0.04) and lowered, at 24 months, the level of fibrinogen by 0.71 to 0.86 g/L (all P<0.05). The effects of raloxifene and CEEs did not differ significantly. In contrast to raloxifene, from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL (all P<0.02 versus both placebo and raloxifene). CEEs transiently increased C- reactive protein by 1.0 mg/L at 6 months (P<0.05 versus placebo) and- prothrombin-derived fragment F1 +2 by 0.79 nmol/L at 12 months (P<0.001 versus placebo). Finally, from 12 months on, CEEs increased triglycerides by 0.33 to 0.56 mmol/L (all P<0.05 versus both placebo and raloxifene). Our findings suggest that in healthy postmenopausal women, raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels. These treatments differ, however, in their effects on high density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1+2 and C-reactive protein

Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma.

The goal of this study was to investigate the efficacy of photodynamic therapy (PDT) of a single tumour growing intraperitoneally. For this purpose the CC531 colon carcinoma, implanted in an intraperitoneal fat pad of Wag/RijA rats, was treated with intraperitoneal photodynamic therapy (IPPDT) using Photofrin as the photosensitiser. Two illumination techniques have been compared. An invasive illumination technique using Perspex blocks to illuminate 30 cm2 of the lower abdomen gave a significant delay in tumour growth with 25 J cm-2 applied 1 day after Photofrin. A minimally invasive illumination technique using a balloon catheter to illuminate 14 cm2 resulted in an equivalent growth delay with 75 J cm-2. The route of administration of the photosensitiser did not influence regrowth times of the tumour. Mitomycin C (MMC), a bioreductive agent, was used to exploit the known PDT-induced hypoxia. The combination of IPPDT with MMC resulted in an increased tumoricidal effect. In conclusion, IPPDT led to a significant growth delay for a single tumour implanted intraperitoneally and repetition of the PDT treatment was possible using a minimally invasive illumination technique. Repeated treatments resulted in increased tumour response

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions.

Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes. MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer- and type-specific primer mediated PCR (GP/TS PCR). Both techniques were performed on paraffin embedded tissue sections. Results show disturbed MHC class I heavy chain expression in CIN I to CIN III, as well as in cervical carcinomas. Upregulated MHC class II expression on dysplastic epithelial cells was also found in the different CIN groups and carcinomas. Prevalence of HPV genotypes increased with the severity of the lesion, mainly due to the contribution of the HPV types 16 and 18. No correlation could be established between the presence of specific HPV genotypes and any MHC expression pattern in the different CIN groups or cervical carcinomas. In some cases these data were confirmed by RNA in situ hybridisation showing HPV 16 E7 transcripts in the same dysplastic/neoplastic cells from which MHC status was determined. The results indicate that local differences may exist in the type of cellular immune response to HPV induced lesions

Catecholaminergic and cholinergic neuromodulation in autism spectrum disorder: A comparison to attention-deficit hyperactivity disorder

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems [dopamine (DA), norepinephrine (NE)] in ADHD are obvious targets for stimulant treatment. Recent findings suggest that dysfunction in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that (1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; (2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point toward NE- or ACh-directed intervention; (3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD

Стилі керівництва як моделі вербальної поведінки у корпоративному дискурсі

Статья посвящена анализу лингвистических особенностей директивного и демократического стилей руководства как распространенных моделей вербального поведения в корпоративном дискурсе. Внимание уделяется также гендерному фактору, который учитывается при авторитарном коммуникативном поведении.Стаття присвячена аналізові лінгвістичних особливостей директивного та демократичного стилів керівництва як поширених моделей вербальної поведінки у корпоративному дискурсі. Увага приділяється також гендерному фактору, який враховується в авторитарній комунікативній поведінці.The article is dedicated to the analysis of linguistic peculiarities of the directive and democratic management styles as models of the verbal behaviour in the corporate discourse. Attention is also paid to the gender factor, which is considered in the authoritarian communicative behaviour