Regulation of bone cell function by acid-base balance

Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In this region pH shifts of < 0.05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive 'fail-safe' that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.     

Assessment of bioavailability limitations during slurry biodegradation of petroleum hydrocarbons in aged soils

In an effort to determine whether bioavailability limitations are responsible for the slow or incomplete hydrocarbon biodegradation in aged soils, both the rate of desorption (rdes) and biodegradation (rbio) was measured for n-alkanes and polynuclear aromatic hydrocarbons (PAHs) at different times during the slurry biotreatment of six different soils. While all n-alkanes were biodegraded to various degrees depending on their respective carbon number and the soil organic matter content, none of them were desorbed to a significant extent, indicating that these saturated hydrocarbons do not need to be transferred from the soil particles into the aqueous phase in order to be metabolized by microorganisms. Most two- and three-ring PAHs biodegraded as fast as they were desorbed (rbio = rdes); that is, desorption rates controlled biodegradation rates. By contrast, the biodegradation kinetics of four-, five-, and six-ring PAHs was limited by microbial factors during the initial phase (rbio < rdes) while becoming mass-transfer rate limited during the final phase of bioremediation treatment (rbio = rdes). Whenever PAH biodegradation stalled or did not occur at all (rbio = 0), it was never due to bioavailability limitations (rdes > 0) but was more likely caused by microbial factors. such as the absence of specific PAH degraders or cometabolic substrates. Consequently, PAHs that are found to be microbially recalcitrant in aged soils may not be so because of limited bioavailability and thus could pose a greater risk to the environment than previously thought.     

Predicting sediment toxicity using logistic regression: a concentration-addition approach

The question posed in this article is how useful the chemical concentration measurements for predicting the outcome of sediment toxicity tests are. Using matched data on sediment toxicity and sediment chemical concentrations from a number of studies, we investigated several approaches for predicting toxicity based on multiple logistic regression with concentration-addition models. Three models were found to meet criteria for acceptability. The first model uses individual chemicals selected using stepwise selection. The second uses derived variables to reflect combined metal contamination, polycyclic aromatic hydrocarbon (PAH) contamination, and the interaction between metals and PAHs. The third and final model is a separate species model with derived variables. Overall, these models suggest that toxicity may be correctly predicted approximately 77% of the time, although prediction is better for samples identified as nontoxic than for those known to be toxic.     

Exposure assessment of particulate matter for susceptible populations in Seattle

In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 microm (PM2.5) were similar to the average outdoor PM2.5 concentrations but significantly higher than the average indoor concentrations. Personal PM2.5 exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM2.5, PM10 (PM with aerodynamic diameters < 10 microm), and the ratio of PM2.5 to PM10 were significantly higher during the heating season. The increase in outdoor PM10 in winter was primarily due to an increase in the PM2.5 fraction. A similar seasonal variation was found for personal PM2.5. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM2.5 and PM10 concentrations. Personal PM2.5 exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM2.5 exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM2.5 measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM2.5 exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children.     

Effects of 17 alpha-ethinylestradiol on sexual development of the amphipod Hyalella azteca

The effects of the synthetic estrogen 17alpha-ethinylestradiol (EE) on sexual development of the freshwater amphipod Hyalella azteca was investigated. Organisms were exposed in a multigeneration experiment to EE concentrations ranging from 0.1 to 10 microg/L and the development of both external and internal sexual characteristics were studied. Second-generation male H. azteca exposed from gametogenesis until adulthood to 0.1 and 0.32 microg EE/L developed significantly smaller second gnathopods. The sex ratio of the populations exposed to EE for more than two generations tended, although not statistically significantly, to be in favor of females. Histological aberrations of the reproductive tract, i.e., indications of hermaphroditism, disturbed maturation of the germ cells, and disturbed spermatogenesis, of post-F1-generation males were observed in all EE exposures. These findings provide evidence that sexual development of H. azteca is affected by exposure to sublethal concentrations of EE.     

Projecting the cost of essential services in Bangladesh

Utilizing a study of the costs of providing essential services in rural areas in Bangladesh projections of the cost of expanding services to the entire rural population are derived. These estimates are based on the current system of primary care, the demographic structure of the population and normatives for desired utilization. Scenarios make use of known demographic characteristics of average rural areas together with information on disease prevalence. The estimates highlight a number of difficulties involved in deriving costs and in comparing the cost-effectiveness of service provision. The integrated nature of much primary care, both in terms of the technical exploitation of joint costs and clinical diagnostic and treatment protocols, means that treating services in isolation is likely to lead to inexact estimates of service cost. The context of any costs derived is required in order to make comparisons.     

The relationship between National Heart,Lung, and Blood Institute Weight Guidelines and concurrent medical costs in a manufacturing population

PURPOSE: To explore the relationship between the 1998 National Heart, Lung, and Blood Institute (NHLBI) weight guidelines and concurrent medical costs. DESIGN: Cross-sectional study. SETTING: In a nationwide manufacturing corporation (General Motors Corporation). SUBJECTS: A total of 177,971 employees, retirees, and their adult dependents who were enrolled in Indemnity/PPO health insurance plan during the years 1996 and 1997 and completed one health risk appraisal (HRA) in the same period. MEASURES: The participants were categorized into six weight groups according to the NHLBI 1998 guidelines (body mass index [BMI] < 18.5, 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, > or = 40 kg/m2). The height and weight data were collected by self-reported values on an HRA or biometric screening completed during 1996 to 1997. To represent the typical medical costs in a given group, the median, instead of mean, medical charges were used in this article. The annual median medical charges (including drug charges) for years 1996 and 1997 were compared among the six weight groups by using Wilcoxon rank sum tests. The differences in median charges were also tested between the normal weight group and the other five groups for each of the 10 gender-age subgroups (five age groups: 19-44, 45-54, 55-64, 65-74, 75+). RESULTS: Overall median medical costs were consistent with the NHLBI weight guidelines. The normal-weight group costs the least and both underweight and overweight-obesity groups cost more. The median medical costs of the six weight groups were $3184, $2225, $2388, $2801, $3182, and $3753, respectively, with statistical differences existing between any two groups of the last five categories. The underweight groups, especially in females, were not consistent with the guidelines in the two young groups (ages 19-44 and 45-54). An inconsistent relationship between medical costs and BMI groups was seen in the oldest males (age 75+). CONCLUSIONS: The six weight groups defined by the 1998 NHLBI guidelines are consistent with concurrent medical costs. Except for the underweight group (BMI < 18.5 kg/m2), medical costs gradually increased with BMI. Given that the prevalence of obesity continues to increase in western countries, effective weight control programs would help avoid a substantial amount of medical costs associated with overweight/obesity and related diseases.     

The toxicity of metal mixtures to the estuarine mysid Neomysis integer (Crustacea: Mysidacea) under changing salinity

Water quality criteria are mainly based on data obtained in toxicity tests with single toxicants. Several authors have demonstrated that this approach may be inadequate as the joint action of the chemicals is not taken into account. In this study, the combined effects of six metals on the European estuarine mysid Neomysis integer (Leach, 1814) were examined. Acute 96-h toxicity tests were performed with mercury, copper, cadmium, nickel, zinc and lead, and this as single compounds and as a mixture of all six. The concentrations of the individual metals of the equitoxic mixtures were calculated using the concentration-addition model. The 96-h LC50's for the single metals, at a salinity of 5 per thousand, ranged from 6.9 to 1140 microg/l, with the following toxicity ranking: Hg>Cd>Cu>Zn>Ni>Pb. Increasing the salinity from 5 to 25 per thousand resulted in lower toxicity and lower concentrations of the free ion (as derived from speciation calculations) for all metals. This salinity effect was strongest for cadmium and lead and could be attributed to complexation with chloride ions. The toxicity of nickel, copper and zinc was affected to a smaller extent by salinity. The 96-h LC50 for mercury was the same for both salinities. In order to evaluate the influence of changing salinity conditions on the acute toxicity of metal mixtures, tests were performed at different salinities (5, 10, 15 and 25 per thousand ). The 96-h LC50 value (1.49 T.U.) of the metal mixture, at a salinity of 5 per thousand, was clearly lower than the expected value (6 T.U.) based on the non-additive hypothesis, thus confirming the additive effect of these metals in the marine/estuarine environment. Changing salinity had a profound effect on the toxicity of the mixture. The toxicity clearly decreased with increasing salinity until 15 per thousand. Higher salinities (25 per thousand ) had no further influence on the 96-h LC50 of the mixture which is situated at a value between 4.4 and 4.6. Finally, the relative sensitivity to the selected metals was compared with the relative sensitivity of the commonly used mysid Americamysis (=Mysidopsis) bahia.