The reference values in the interpretation of toxicological data

The worldwide gradual expansion of industrialization has led to a dramatic increase in the production and use of chemical substances. This has resulted in a greater dispersion of these elements in the environment and in an increased exposure of the general population and workers. In this scenario, a thorough knowledge of exposure levels is needed in order to assess chemical risks in environmental and occupational settings. Biological monitoring is among the most useful tools for assessing exposure. However, in order to provide really effective guidance in the application/implementation of risk management measures, biomonitoring results need to be compared with appropriate references. Reference values (RVs) are an excellent resource since useful information for a correct interpretation of toxicological data can be obtained by comparing them with biomonitoring results. In the field of public health, this may enable us to identify potential sources of exposure, define the principal and most frequently exploited routes of exposure, and outline chemical absorption. Similarly, in occupational medicine, RVs can be used to give meaning to biomonitoring findings, especially when a biological limit value is not available for the chemical in question. Furthermore, these values are a valid tool for assessing exposure to chemical carcinogens. Therefore, by integrating reference values in an appropriate and complete system of guide values that also includes action levels and biological limit values, we could obtain both an adequate assessment of exposure and a better understanding of toxicological data.Key words: Biological limit values, biological monitoring, chemical risk, exposure assessment, reference values     

Pharmacodynamics of combined estrogen–progestin oral contraceptives: 4. Effects on uterine and cervical epithelia

ABSTRACT

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.

Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 μg), medium- (30 μg), low- (20 μg), ultralow- (15 μg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.

Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.

Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.

In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.     

Fetal Size in a Rural Melanesian Population with Minimal Risk Factors for Growth Restriction: An Observational Ultrasound Study from Papua New Guinea

We conducted a prospective longitudinal study of fetal size in rural Papua New Guinea (PNG) involving 439 ultrasound-dated singleton pregnancies with no obvious risk factors for growth restriction. Sonographically estimated fetal weights (EFWs; N = 788) and birth weights (N = 376) were included in a second-order polynomial regression model (optimal fit) to generate fetal weight centiles. Means for specific fetal biometric measurements were also estimated. Fetal weight centiles from a healthy PNG cohort were consistently lower than those derived from Caucasian and Congolese populations, which overestimated the proportion of fetuses measuring small for gestational age (SGA; < 10th centile). Tanzanian and global reference centiles (Caucasian weight reference adapted to our PNG cohort) were more similar to those observed in our cohort, but the global reference underestimated SGA. Individual biometric measurements did not differ significantly from other cohorts. In rural PNG, a locally derived nomogram may be most appropriate for detection of SGA fetuses.     

Structure and Properties of Cast Ti-Al-Si Alloys

Intermetallic compounds based on Ti-Al- (Si) are attractive materials with good thermal stability and low density. However, the production of these materials is quite complicated. Partially modified conventional methods of melting metallurgy are most often used due to availability, possible high productivity, and relatively low production costs. Therefore, some technologies for the production of intermetallics based on Ti-Al are currently available, but with certain disadvantages, which are caused by poor casting properties or extreme reactivity of the melt with crucibles. Some shortcomings can be eliminated by modifying the melting technology, which contributes to increasing the cost of the process. The work deals with the preparation of Ti-Al-Si intermetallic compounds with different contents of aluminum and silicon, which were produced by centrifugal casting in an induction vacuum furnace Linn Supercast-Titan. This process could contribute to the commercial use of these alloys in the future. For this research, the TiAl15Si15(in wt.%) alloy was selected, which represents a balanced ratio of aluminides and silicides in its structure, and the TiAl35Si5 alloy, which due to the lower silicon content allows better melting conditions, especially with regard to the melting temperature. This alloy was also investigated after HIP (“Hot Isostatic Pressing”) treatment.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Light-curing time reduction with a new high-power halogen lamp

INTRODUCTION: Orthodontic brackets are routinely bonded with light-cured adhesives. Conventional halogen lights used in bonding have the disadvantage of a long curing time, and the available alternatives (laser and plasma lights) are expensive. Our aim was to investigate the minimum time necessary to bond brackets with a new, relatively low-priced, high-power halogen light. METHODS: Five groups of 15 deciduous bovine incisors were bonded with stainless steel brackets (Mini Diamond Twin, Ormco, Orange, Calif) by using different lamps and curing times. Three of the groups were bonded by using a high-power halogen light (Swiss Master Light, Electro Medical Systems, Nyon, Switzerland) for 2, 3, and 6 seconds, respectively. The fourth group, bonded with a fast halogen light (Optilux 501, Sybron Dental Specialties, Danbury, Conn) for 40 seconds, served as the positive control group. The fifth group, the comparison group, was bonded with a plasma light (Remecure, Remedent, Deurle, Belgium) for 4 seconds. After storage for 24 hours in the dark at 37 degrees C in water, shear bond strength was measured with a universal testing machine. RESULTS: A curing time of 2 seconds with the high-power halogen light negatively affected the bond strength and the probability of bond survival. The adhesive remnant index scores were not significantly different among the groups. Most failures (> 60%) occurred at the bracket base/adhesive interface. CONCLUSIONS: The high-power halogen light seems to be a cost-effective solution to reducing curing time. The recommended curing times to bond stainless steel brackets are 6 seconds and, with caution, even 3 seconds.