Bioavailability of phyto-oestrogens

The term phyto-oestrogen encompasses isoflavone compounds, such as genistein and daidzein, found predominantly in soya products and the lignans, such as matairesinol and secoisolariciresinol, found in many fruits, cereals and in flaxseed. There is evidence that they have potential health benefits in man particularly against hormone-dependent diseases such as breast and prostate cancers and osteoporosis. This has led to intense interest in their absorption and biotransformation in man. The metabolism of isoflavones and lignans in animals and man is complex and involves both mammalian and gut microbial processes. Isoflavones are present predominantly as glucosides in most commercially available soya products; there is evidence that they are not absorbed in this form and that their bioavailability requires initial hydrolysis of the sugar moiety by intestinal beta-glucosidases. After absorption, phyto-oestrogens are reconjugated predominantly to glucuronic acid and to a lesser degree to sulphuric acid. Only a small portion of the free aglycone has been detected in blood, demonstrating that the rate of conjugation is high. There is extensive further metabolism of isoflavones (to equol and O-desmethylangolensin) and lignans (to enterodiol and enterolactone) by gut bacteria. In human subjects, even those on controlled diets, there is large interindividual variation in the metabolism of isoflavones and lignans, particularly in the production of the gut bacterial metabolite equol (from daidzein). Factors influencing absorption and metabolism of phyto-oestrogens include diet and gut microflora.     

Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men

Inflammatory and oxidative stresses play a pivotal role in atherogenesis. Vitamin E and vitamin C are the two most important dietary antioxidants; moreover, vitamin E has anti-inflammatory effects. Combined supplementations with vitamin E and vitamin C twice daily for 3 y reduced lipid peroxidation and retarded the progression of common carotid atherosclerosis in healthy men in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. To further elucidate the underlying mechanisms that retarded the progression of atherosclerosis in the ASAP study, we investigated the effect of a combined intake of vitamin E and vitamin C on inflammatory markers in vivo. Circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C reactive protein (CRP) were measured in 45- to 69-y-old men from the ASAP study with cholesterol >5.0 mmol/L before and after treatment with either placebo (n = 52) or a combined supplementation with 91 mg (136 IU) alpha-tocopherol and 250 mg of slow-release vitamin C twice a day (n = 55) for 3 y. Antioxidant treatment for 36 mo had no effect on circulating levels of TNF-alpha, IL-6 or CRP. In conclusion, long-term combined supplementations with alpha-tocopherol and vitamin C in reasonable doses have no detectable systemic anti-inflammatory effects in a healthy population of men with slight hypercholesterolemia and no overt signs of inflammation.     

Cyclodextrins and chitosan derivatives in sublingual delivery of low solubility peptides: A study using cyclosporin A, α-cyclodextrin and quaternary chitosan N-betainate

Systemic drug delivery through intraoral membranes may offer a promising administration route for lipophilic peptide drugs. The aim of the present study was to investigate the effect of α-cyclodextrin (α-CD) and a novel chitosan derivative, chitosan N-betainate (CH), on sublingual absorption of a hydrophobic model peptide cyclosporin A (CsA), and the effect of temperature on the complexation of CsA with α-CD.     

Activity of T-1106 in a hamster model of yellow Fever virus infection

Yellow fever virus (YFV) causes 30,000 deaths worldwide, despite the availability of a vaccine. There are no approved antiviral therapies for the treatment of YFV disease in humans, and, therefore, these studies were designed to investigate the anti-YFV properties of T-1106, a substituted pyrazine, in a hamster model of YFV disease. Intraperitoneal (i.p.) treatment with 100 mg/kg of body weight/day of T-1106 starting 4 h prior to virus inoculation and continuing twice daily through 7 days post-virus inoculation (dpi) resulted in significantly improved survival, alanine aminotransferase levels in the serum, weight gain, and mean day to death. Virus titer in the liver at 4 dpi was significantly reduced in treated animals, as determined by both quantitative real-time PCR and infectious cell culture assay. No toxicity (weight loss or mortality) was observed at a dose of 100 mg/kg/day in sham-infected control animals. The observed minimal effective dose of T-1106 was 32 mg/kg/day administered either by oral or i.p. treatment. Therapeutic treatment was effective in significantly improving survival when T-1106 was administered beginning as late as 4 days after virus challenge with twice-daily treatment for 8 days at a dose of 100 mg/kg/day. With favorable safety, bioavailability, and postviral challenge treatment efficacy, T-1106 was effective in the treatment of disease in hamsters infected with YFV and should be further studied for potential use as a therapy for human YFV disease.     

Data warehouse approach to nursing management

AIM: This article describes a data warehouse approach when designing an information system to meet nursing management needs in acute hospital setting. BACKGROUND: The rapidly changing health care environment has created new challenges for nursing leaders and requires appropriate, accurate and timely data for decision-making. METHOD: Key aspects of current information needs were identified by a nursing expert group. A data warehouse-based Nursing Management Information System was produced and piloted in nine wards. A survey and interviews were conducted to evaluate the piloting. RESULTS: Data from the patient administrative system together with nursing rostering data and measures for nursing care intensity brought new opportunities for nursing management. CONCLUSIONS: A Nursing Management Information System is suggested to be built using data warehouse model. Successful implementation of a Nursing Management Information System requires systematic data quality checks. An information analyst is essential for interpreting and communicating nursing data to multi-professional management groups.     

A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure

Inactivating mutations of the FSH receptor (FSHR) are known to cause ovarian failure with amenorrhea and infertility in women. The first mutation identified in the FSHR gene was a missense mutation (566C-->T, predicting Ala189Val transition) found in several Finnish patients with primary amenorrhea due to ovarian failure. Only five additional, partially or totally inactivating, mutations of the FSHR have been reported. Here, we report a novel FSHR mutation, 1255G-->A, in a Finnish female with primary amenorrhea. The patient was a compound heterozygote for two mutations in the FSHR gene: 566C-->T, the Finnish founder mutation, and 1255G-->A, a previously unidentified mutation. The new mutation is located in exon 10 in the second transmembrane stretch of the FSHR, and it predicts an Ala419Thr change in the protein structure. In functional testing, the mutation was shown to have minimal effect on ligand binding capacity and affinity, but it almost totally abolished the cAMP second messenger response. Neither of the two FSHR mutations (566C-->T or1255G-->A) was identified in 40 other Finnish patients with premature ovarian failure. Based on this and previous studies, FSHR mutations remain a rare cause of ovarian failure.     

RAF1–MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation

Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF–MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS–MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1–MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1–ARL4C and BRAFV600E–MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1–MEK/ERK–ARL4C axis, which may function in cooperation with the BRAFV600E–MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Relationship between unemployment and health among health care professionals: health selection or health effect?

OBJECTIVE: The aim of this longitudinal study was to examine (a) the causal effect of unemployment 1990-1997 on health 1998-2001 (in-patient periods) and (b) the selection effect of health 1996-1999 on unemployment 2000-2002. We examined the effects of different diagnoses, namely, all causes, circulatory diseases, diseases of the digestive system, musculoskeletal diseases, and mental disorders. METHODS: The data from the Central Register of Health Care Professionals of persons born 1945-1970 were linked to data from employment statistics and Finnish Hospital Discharge Register including 78,195 women and 12,455 men aged 31 to 56 in 2001. The associations were analyzed with logistic regression analyses and expressed as odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: After adjustments, existence of unemployment periods was associated with lower odds for in-patient periods due to musculoskeletal diseases for both women (OR=0.82, 95% CI=0.76-0.89) and men (OR=0.74, 95% CI=0.60-0.89). Unemployment periods were more likely among women (OR=1.65, 95% CI=1.33-2.04) and men (OR=2.54, 95% CI=1.44-4.48) having had in-patient periods due to mental diseases and among women also due to diseases of the digestive system (OR=1.17, 95% CI=1.04-1.31). CONCLUSION: The present study found evidence for selection to unemployment according to mental diseases and diseases of the digestive system among health care professionals. In addition, our results show that unemployment periods may protect health care workers from musculoskeletal diseases.