Is it possible that menopause is associated with telomere length? Findings of an integrative review.

OBJECTIVE: Knowing the important repercussions of menopause for women's health and that female longevity can be better understood through studies based on aging biomarkers, studies on the relationship between menopause and telomere shortening may help to better understand this stage of life. This study aimed to analyze what research has been produced regarding the relationship between menopause and telomere length. METHODS: This integrative literature review included searches in PubMed, CINAHL, LILACS, Web of Science and Scopus databases. Four studies were selected for the final sample. RESULTS: The findings of these studies indicate that older age for menopause and longer reproductive life (difference between age at menopause and menarche) are associated with longer telomeres, that is, with longevity. CONCLUSION: The relationship between menopause and telomere length is uncertain. The small number of studies included in this review, and the fact that the results indicate that the relationship between menopause and telomere length may be dependent on the stage of the menopause and race/ethnicity, suggest that additional research focusing on these variables should be carried out.

A long-period radio transient active for three decades.

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds1,2. In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated3. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10-13 s s-1, which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

Analysis of Signaling Pathways of Necroptotic and Pyroptotic Cell Death in the Hearts of Rats With Type 2 Diabetes Mellitus.

Diabetes mellitus is known to produce various cell-damaging events and thereby underlie heart dysfunction and remodeling. However, very little is known about its inflammation-associated pathomechanisms due to necrosis-like cell death. For this purpose, we aimed to investigate signaling pathways of necroptosis and pyroptosis, known to produce plasma membrane rupture with the resultant promotion of inflammation. One-year old Zucker diabetic fatty (ZDF) rats did not exhibit significant heart dysfunction as revealed by echocardiographic measurement. On the other hand, there was a decrease in heart rate due to diabetes. Immunoblotting analysis showed that the left ventricles of ZDF rats overexpress neither the main necroptotic proteins including receptor-interacting protein kinase 3 (RIP3) and mixed lineage domain kinase-like pseudokinase (MLKL), nor the pyroptotic regulators including NLR family pyrin domain containing 3 protein (NLRP3), caspase-1, interleukin-1 beta (IL-1beta and the N-terminal gasdermin D (GSDMD-N). On the other hand, the increased activation of the RIP3 kinase due to phosphorylation was found in such hearts. In summary, we showed for the first time that the activation of cardiac RIP3 is upregulated due to disturbances in glucose metabolism which, however, did not proceed to necrosis-like cell death. These data can indicate that the activated RIP3 might also underlie other pleiotropic, non-necroptotic signaling pathways under basal conditions.

Pleiotropic, non-cell death-associated effects of inhibitors of receptor-interacting protein kinase 1 in the heart.

Inhibition of receptor-interacting protein kinase 1 (RIP1) has been recognized as a compelling tool for limiting necroptosis. Recent findings have indicated that RIP1 inhibitor, necrostatin-1 (Nec-1), is also able to modify heart function under non-cell death conditions. In this study, we investigated its underlying molecular mechanisms and compared with those of novel pharmacologically improved agents (Nec-1s and GSK'772) and its inactive analog (Nec-1i). Heart function was examined in Langendorff-perfused rat hearts. Certain proteins regulating myocardial contraction-relaxation cycle and oxidative stress (OS) were evaluated by immunoblotting and as the extent of lipid peroxidation, protein carbonylation and nitration, respectively. In spite of the increase of left ventricular developed pressure (LVDP) due to treatment by both Nec-1 and Nec-1i, only the former agent increased the phosphorylation of Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) at threonine 287 and cardiac myosin-binding protein-C (cMyBPc) at serine 282. In contrast, Nec-1s did not elicit such changes, while it also increased LVDP. GSK'772 activated CaMKIIδ-phospholamban (PLN) axis. Neither protein kinase A (PKA) nor its selected molecular targets, such as serine 16 phosphorylated PLN and sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), were affected by either RIP1 inhibitor. Nec-1, like other necrostatins (Nec-1i, Nec-1s), but not GSK'772, elevated protein tyrosine nitration without affecting other markers of OS. In conclusion, this study indicated for the first time that Nec-1 may affect basal heart function by the modulation of OS and activation of some proteins of contraction-relaxation cycle.

Comparison of peripheral quantitative computed tomography forearm bone density versus DXA in rheumatoid arthritis patients and controls.

Rheumatoid arthritis (RA) has been associated with osteoporosis. Quantitative computed tomography (QCT) is capable of assessing bone density and composition. We found lower bone density in RA compared to controls. Age and RA duration influenced bone density. QCT may be useful to assess bone metabolism in RA. INTRODUCTION: RA is associated with generalized and periarticular osteoporosis. In addition to DXA that determines areal bone mineral density (BMD), peripheral QCT also detects volumetric BMD. QCT differentiates between total, trabecular, and cortical BMD. Here, we compared DXA and QCT in RA patients and healthy controls. METHODS: BMD of 57 female RA patients and 32 age-matched healthy female controls were assessed by DXA. QCT of the forearm ultradistal region was also performed. Densitometry data were correlated with age, disease duration, disease activity, serum CRP, and anti-CCP levels. RESULTS: Total bone density (310.4 ± 79.7 versus 354.0 ± 54.1 mg/cm3; p = 0.007) and attenuation (0.37 ± 0.05 versus 0.40 ± 0.03 1/cm; p = 0.001), trabecular density (157.6 ± 57.0 versus 193.8 ± 48.7 mg/cm3; p = 0.005) and attenuation (0.28 ± 0.03 versus 0.32 ± 0.04 1/cm; p < 0.0001), and cortical density (434.3 ± 115.8 versus 492.5 ± 64.0 mg/cm3; p = 0.006) and attenuation (0.44 ± 0.07 versus 0.47 ± 0.04 1/cm; p = 0.004) were significantly lower in RA. Both lumbar and femoral neck BMD, as well as T-scores, were significantly lower in RA versus controls (p < 0.001 in all cases). In RA, total and cortical QCT attenuation and density were associated with age, the presence of RA, and their combination. In contrast, trabecular density and attenuation were only affected by the presence of the disease but not by age. Also in RA, total trabecular and cortical density as determined by QCT significantly correlated with lumbar and/or femoral neck BMD as measured by DXA. Finally, anti-CCP seropositivity was associated with lower trabecular density and attenuation. CONCLUSIONS: Both DXA and QCT may be suitable to study bone metabolism in RA. Areal BMD determined by DXA may correlate with volumetric bone density measured by QCT. Moreover, trabecular osteoporosis may be associated by the underlying autoimmune-inflammatory disease, while cortical osteoporosis may rather be age-related.

Survivorship and clinical outcome of the minimally invasive Uniglide medial fixed bearing, all-polyethylene tibia, unicompartmental knee arthroplasty at a mean follow-up of 7.3years.

BACKGROUND: Medial UKA performed in England and Wales represents seven to 11% of all knee arthroplasty procedures, and is most commonly performed using mobile-bearing designs. Fixed bearing eliminates the risk of bearing dislocation, however some studies have shown higher revision rates for all-polyethylene tibial components compared to those that utilize metal-backed implants. The aim of the study is to analyse survivorship and maximum eight-year clinical outcome of medial fixed bearing, Uniglide unicompartmental knee arthroplasty performed using an all-polyethylene tibial component with a minimal invasive approach. METHODS: Between 2002 and 2009, 270 medial fixed UKAs were performed in our unit. Patients were reviewed pre-operatively, five and eight years post-operatively. Clinical and radiographic reviews were carried out. Patients' outcome scores (Oxford, WOMAC and American Knee Score) were documented in our database and analysed. RESULTS: Survival and clinical outcome data of 236 knees with a mean of 7.3years follow-up are reported. Every patient with less than 4.93years of follow-up underwent a revision. The patients' average age at the time of surgery was 69.5years. The American Knee Society Pain and Function scores, the Oxford Knee Score and the WOMAC score all improved significantly. The five-year survival rate was 94.1% with implant revision surgery as an end point. The estimated 10years of survival rate is 91.3%. Fourteen patients were revised before the five-year follow-up. CONCLUSION: Fixed bearing Uniglide UKA with an all-polyethylene tibial component is a valuable tool in the management of a medial compartment osteoarthritis, affording good short-term survivorship. Level of evidence IV.

[ARDS after Incidental Aspiration of Petroleum in an Adult]. / ARDS nach akzidentieller Aspiration von Petroleum bei einem Erwachsenen.

Petroleum aspiration as a reason for lipid pneumonia is a rare complication. Mostly children are affected and mortality rates are low. In most case series, virtually every subject survived.We describe here the case of a patient who developed ARDS and pneumatoceles with a fatal outcome. Due to the undulant nature of the disease, multipe thoracic CT were performed, enabling us to describe the precise radiologic course of the disease.

Wintertime surgery increases the risk of conversion to hip arthroplasty after internal fixation of femoral neck fracture.

UNLABELLED: The study demonstrates that wintertime surgeries are associated with impaired fracture healing and increases the risk of conversion to hip arthroplasty after osteosynthesis of femoral neck fracture. Furthermore, the results raise the possibility of association between seasonal changes in vitamin D levels and impaired fracture healing of femoral neck fracture. INTRODUCTION: Although the changes of vitamin D level and calcitropic hormones influencing bone metabolism are seasonal, the effect of seasons on hip fracture healing is unknown. We assessed the effects of seasonal periodicity on conversion to hip arthroplasty after primary osteosynthesis of femoral neck fracture. METHODS: This nationwide retrospective observational cohort study involved 2779 patients aged ≥ 60 years who underwent internal screw fixation for primary femoral neck fracture and were discharged in 2000. Cases requiring conversion to arthroplasty during the 8-year follow-up derived from the Hungarian health insurance database were registered. Risk factors assessed included sex, age, fracture type, season of primary surgery and surgical delay. Competing-risks regression analysis was used for data analyses. RESULTS: During the observation period, 190 conversions to hip arthroplasty (6.8%) were identified, yielding an overall incidence of 19.5 per 1000 person-years. The crude incidence rates of conversions after osteosynthesis in winter, spring, summer and fall were 28.6, 17.8, 16.9 and 14.7 per 1000 person-years, respectively. Besides younger age, female sex and intracapsular fracture displacement, wintertime primary osteosynthesis significantly increased the risk of conversion (fall vs. winter, hazard ratio (HR): 0.50, 95% confidence interval [95% CI 0.33-0.76]; spring vs. winter, HR: 0.63, [95% CI 0.44-0.92]; summer vs. winter, HR: 0.62, [95% CI 0.42-0.91]). CONCLUSIONS: Our study demonstrate that wintertime primary osteosynthesis increases the risk of conversion surgeries. The results may help improving the outcome of primary fixation of femoral neck fractures.

Pulmonary M. tuberculosis infection delays Th1 immunity via immunoadaptor DAP12-regulated IRAK-M and IL-10 expression in antigen-presenting cells.

Interaction of mycobacteria with the host leads to retarded expression of T helper cell type 1 (Th1) immunity in the lung. However, the immune mechanisms remain poorly understood. Using in vivo and in vitro models of Mycobacterium tuberculosis (M. tb) infection, we find the immunoadaptor DAP12 (DNAX-activating protein of 12 kDa) in antigen-presenting cells (APCs) to be critically involved in this process. Upon infection of APCs, DAP12 is required for IRAK-M (interleukin-1 receptor-associated kinase M) expression, which in turn induces interleukin-10 (IL-10) and an immune-suppressed phenotype of APCs, thus leading to suppressed Th1 cell activation. Lack of DAP12 reduces APC IL-10 production and increases their Th1 cell-activating capability, resulting in expedited Th1 responses and enhanced protection. On the other hand, adoptively transferred DAP12-competent APCs suppress Th1 cell activation within DAP12-deficient hosts, and blockade of IL-10 aborts the ability of DAP12-competent APCs to suppress Th1 activation. Our study identifies the DAP12/IRAK-M/IL-10 to be a novel molecular pathway in APCs exploited by mycobacterial pathogens, allowing infection a foothold in the lung.

Bone mineral density (BMD) and computer tomographic measurements of the equine proximal phalanx in correlation with breaking strength.

Despite the fact that bone mineral density (BMD) is an important fracture risk predictor in human medicine, studies in equine orthopedic research are still lacking. We hypothesized that BMD correlates with bone failure and fatigue fractures of this bone. Thus, the objectives of this study were to measure the structural and mechanical properties of the proximal phalanx with dual energy X-ray absorptiometry (DXA), to correlate the data obtained from DXA and computer tomography (CT) measurements to those obtained by loading pressure examination and to establish representative region of interest (ROI) for in vitro BMD measurements of the equine proximal phalanx for predicting bone failure force. DXA was used to measure the whole bone BMD and additional three ROI sites in 14 equine proximal phalanges. Following evaluation of the bone density, whole bone, cortical width and area in the mid-diaphyseal plane were measured on CT images. Bones were broken using a manually controlled universal bone crusher to measure bone failure force and reevaluated for the site of fractures on follow-up CT images. Compressive load was applied at a constant displacement rate of 2 mm/min until failure, defined as the first clear drop in the load measurement. The lowest BMD was measured at the trabecular region (mean +/- SD: 1.52 +/- 0.12 g/cm2; median: 1.48 g/cm2; range: 1.38-1.83 g/cm2). There was a significant positive linear correlation between trabelcular BMD and the breaking strength (P = 0.023, r = 0.62). The trabecular region of the proximal phalanx appears to be the only significant indicator of failure of strength in vitro. This finding should be reassessed to further reveal the prognostic value of trabecular BMD in an in vivo fracture risk model.

Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: a critical role of airway luminal T cells.

The immune mechanisms underlying unsatisfactory pulmonary mucosal protection by parenteral Bacillus Calmette-Guérin (BCG) immunization remain poorly understood. We found that parenteral BCG immunization failed to elicit airway luminal T cells (ALT) whereas it induced significant T cells in the lung interstitium. After Mycobacterium tuberculosis (M.tb) challenge, ALT remained missing for 10 days. The lack of ALT correlated with lack of lung protection for 14 days post-M.tb challenge. To further investigate the role of ALT, ALT were elicited in BCG-immunized animals by intranasal inoculation of M.tb culture-filtrate (CF) proteins. Installment of ALT by CF restored protection in the early phases of M.tb infection, which was linked to rapid increases in ALT, but not in lung interstitial T cells. Also, adoptive transfer of T cells to the airway lumen of BCG-immunized animals also accelerated protection. This study thus provides novel evidence that unsatisfactory lung protection by parenteral BCG immunization is due to delayed ALT recruitment after pulmonary M.tb exposure.

The beliefs which motivate young male and female drivers to speed: a comparison of low and high intenders.

In Australia, young drivers aged 17-24 years, and particularly males, have the highest risk of being involved in a fatal crash. Investigation of young drivers' beliefs allows for a greater understanding of their involvement in risky behaviours, such as speeding, as beliefs are associated with intentions, the antecedent to behaviour. The theory of planned behaviour (TPB) was used to conceptualise beliefs using a scenario based questionnaire distributed to licenced drivers (N=398). The questionnaire measured individual's beliefs and intentions to speed in a particular situation. Consistent with a TPB-based approach, the beliefs of those with low intentions to speed ('low intenders') were compared with the beliefs of those with high intentions ('high intenders') with such comparisons conducted separately for males and females. Overall, significant differences in the beliefs held by low and high intenders and for both females and males were found. Specifically, for females, it was found that high intenders were significantly more likely to perceive advantages of speeding, less likely to perceive disadvantages, and more likely to be encouraged to speed on familiar and inappropriately signed roads than female low intenders. Females, however, did not differ in their perceptions of support from friends, with all females reporting some level of disapproval from most friends and all females (i.e., low and high intenders) reporting approval to speed from their male friends. The results for males revealed that high intenders were significantly more likely to speed on familiar and inappropriately signed roads as well as having greater perceptions of support from all friends, except from those friends with whom they worked. Low and high intending males did not differ in their perceptions of the advantages and disadvantages of speeding, with the exception of feelings of excitement whereby high intenders reported speeding to be more exciting than low intenders. The findings are discussed in terms of how they may directly inform the content of mass media and public education campaigns aimed at encouraging young drivers to slow down.

Cervical cytology biobanking: quality of DNA from archival cervical Pap-stained smears.

AIMS: Cervical cytology biobanking is a feasible concept in cervical pathology and could be an indispensable tool for fundamental and applied molecular biological research. PCR is a powerful molecular technique that can be performed on a variety of cervical sample types including Pap-stained cervical smears. However, since the quality of DNA from such specimens is inferior to that from fresh tissue, the correct processing methods are required. This study evaluates three commercial isolation methods and one digestion procedure for their ability to obtain DNA suitable for PCR from fixed and stained Pap smears. METHODS: The High Pure PCR Template Preparation kit, the NucliSENS easyMAG system, the QIAamp DNA Mini Kit and crude proteinase K digestion were used to obtain DNA for subsequent PCR applications. Amplification of beta-globin was performed to verify the presence and integrity of target DNA. The influence of PCR inhibitors and extent of DNA fragmentation were analysed. RESULTS: All commercial DNA isolation techniques provided DNA suitable for PCR amplification, and DNA isolated from 10-year-old archival smears yielded amplicons up to 400 base pairs. Conversely, crude proteinase K digestion limited the amplicon size to 300 bp and did not consistently yield amplifiable digests, as these were contaminated with PCR-inhibiting factors and debris. CONCLUSION: The study indicates that commercial DNA isolation techniques are suitable for PCR amplification of DNA isolated from archival smears, yielding amplicons up to 400 base pairs. Proteinase K digestion is not suitable to obtain amplifiable DNA from fixed and stained Pap-stained smears.

Epidemiology of osteoporosis related fractures in Hungary from the nationwide health insurance database, 1999-2003.

UNLABELLED: The Hungarian national health insurance database was screened for fractures of patients aged 50-100, 1999-2003. On average, there were 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year. INTRODUCTION: The incidence of fractures differs among populations. Our aim was to study the incidence of fractures in Hungary, focusing on classical osteoporotic sites and to compare the results with those of other European countries. METHODS: The Hungarian National Health Insurance Fund database, covering 100% of the population, was screened for fractures of patients aged 50-100, 1999-2003. The search of vertebral fractures was restricted to those admitted to hospital. A gender and age-matched comparison was performed with available data from Europe. RESULTS: There were mean 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year; the female/male ratio was between 1.2-2.4. Multiple fractures occurred in 23.1% of the cases. Hip fracture incidence in Hungary lies between the rates of northern and southern countries of Europe. CONCLUSIONS: Our study offers nationwide epidemiological data on fractures in Hungary. The incidence of fractures increased by age, regardless of the type of fracture. Incidence of hip fractures in Hungary fits in the previously established geographic trends in Europe. Our results fulfil a need for fracture data from Central Europe.

Effects of fixation on RNA integrity in a liquid-based cervical cytology setting.

AIMS: Despite many improvements, cervical cancer screening is still subject to shortcomings. Diagnostic accuracy may improve by using molecular biological techniques, requiring RNA of superior quality. This study determined the effect of SurePath fixation on RNA integrity to assess the suitability of clinical samples collected in this medium for RNA-based molecular assays. METHODS: RNA isolation was performed on fresh and fixed HeLa cells and exfoliated cervical cells fixed in SurePath. The RNA integrity was evaluated by analysis of ribosomal RNA as an indicator of quality. The effect of SurePath preservation on PCR amplification was evaluated by real-time reverse transcriptase (RT)-PCR. RESULTS: In contrast to unfixed cells, SurePath-fixed cells yielded less and severely degraded RNA, as shown by the absence of ribosomal RNA bands. RNA derived from SurePath-fixed cells showed poor real-time RT-PCR amplification characteristics, as evidenced by the absent correlation between threshold values and log cDNA concentration. CONCLUSIONS: Implementation of molecular biology in a clinical context is on the rise and may alleviate shortcomings in current screening and diagnostics. This study shows that SurePath fixation gives rise to highly fragmented RNA with insufficient quality for further reliable analysis by standard real-time RT-PCR applications. The increasing prominence of molecular screening stresses the importance of this finding, which must be considered in relation to choice of an appropriate liquid-based cytology system.

Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types.

The causal relationship between persistent infection with high-risk HPV and cervical cancer has resulted in the development of HPV DNA detection systems. The widely used MY09/11 consensus PCR targets a 450bp conserved sequence in the HPV L1 gene, and can therefore amplify a broad spectrum of HPV types. However, limitations of these consensus primers are evident, particularly in regard to the variability in detection sensitivity among different HPV types. This study compared MY09/11 PCR with type-specific PCRs in the detection of oncogenic HPV types. The study population comprised 15, 774 patients. Consensus PCR failed to detect 522 (10.9%) HPV infections indicated by type-specific PCRs. A significant correlation between failure of consensus PCR and HPV type was found. HPV types 51, 68 and 45 were missed most frequently. The clinical relevance of the HPV infections missed by MY09/11 PCR was reflected in the fraction of cases with cytological abnormalities and in follow-up, showing 104 (25.4%) CIN2+ cases. The MY09/11 false negativity could be the result of poor sensitivity, mismatch of MY09/11 primers or disruption of L1 target by HPV integration or DNA degradation. Furthermore, MY09/11 PCR lacked specificity for oncogenic HPVs. Diagnostic accuracy of the PCR systems, in terms of sensitivity (MY09/11 PCR: 87.9%; type-specific PCRs: 98.3%) and specificity (MY09/11 PCR: 38.7%; type-specific PCRs: 76.14%), and predictive values for histologically confirmed CIN2+, suggest that type-specific PCRs could be used in a clinical setting as a reliable screening tool.

Correlation between laminin-5 immunohistochemistry and human papillomavirus status in squamous cervical carcinoma.

BACKGROUND: Human papillomavirus (HPV) plays a critical role in the carcinogenesis of squamous cervical carcinoma. Integration of viral DNA into the host genome is a major contributing factor to malignant transformation. Viral load may influence integration. AIMS: To compare HPV status (type, viral load, integration status) between normal samples, carcinoma in situ and invasive carcinoma in order to elucidate the role of HPV in progression to invasive lesions. METHODS: The study population comprised 10 biopsy samples from each diagnostic group. Laminin-5 immunohistochemistry was performed to distinguish invasive carcinoma from non-invasive high-grade lesions. Real-time PCR was used to detect specific HPV types, viral load and integrated HPV, with quantification of viral E2 and E6 genes. RESULTS: Invasive carcinomas contained a higher number of laminin-5 immunoreactive cells as compared to non-invasive lesions. Almost all samples contained HPV, with a higher viral load and copy number of HPV16 integrated in E2 in cases of laminin-5 immunoreactivity and cases of invasive carcinoma. High HPV16 viral load was associated with more integrated copies in E2. CONCLUSIONS: HPV is important in progression from carcinoma in situ to invasive carcinoma. Viral load and HPV integration influence the development of cervical cancer towards invasiveness. Overall HPV status may be more predictive of patient outcome and may influence patient management.

CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulfate level, and bone mineral density in postmenopausal women.

The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A7*1C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A7*1C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A7*1C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A7*1C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations.

Blood vitamin concentrations in privately owned dogs fed non-standardized commercial diets and after intake of diets with specified vitamin concentrations.

The objective was to investigate in a survey study the blood vitamin concentrations in healthy dogs fed non-specified commercial complete diets and in an intervention study to determine the effects of defined dietary vitamin intakes on blood vitamin levels and hair and skin condition. Sixty-four privately owned dogs, aged from 1 to 8 years, without history of skin or coat problems were included. All animals were fed commercial complete diets with uncertain vitamin concentrations before enrolment. The animals were assigned, according to weight and gender, to four groups with graded vitamin intakes. The blood vitamin levels and skin and coat quality of the dogs were investigated at days 0 and day 122. Coat and hair condition was not influenced by the experimental diets. The retinol concentrations were reduced at the end of the experiment compared with the baseline levels, retinyl esters were not influenced. 25-Hydroxycholecalciferol decreased in all groups, alpha-tocopherol was constant or tended to decrease. Ascorbic acid, thiamine pyrophosphate and riboflavin concentrations were not affected by treatment, flavin adenine dinucleotide and pyridoxal-5'-phosphate were partially reduced on day 122. Cobalamin, pantothenate and biotin concentrations increased with higher dietary intakes, folate levels in tendency. In conclusion, this study gives a survey of blood vitamin concentrations in healthy dogs and provides a data base for the evaluation of the vitamin status in health and disease.