Evaluating the hazard of dodecyl alkyl sulphate to natural ecosystems using indigenous protistan communities

The effect of the surfactant dodecyl alkyl sulphate (C12AS) on the structure and function of lotic protistan assemblages was examined using the Experimental Stream Facility (ESF) operated by the Procter and Gamble Company. Population- and community-level responses to C12AS were monitored on introduced substrates placed in the channels 28 days prior to dosing (mature communities) as well as those placed in the channels on day 0 of dosing (immature communities), to allow for a broad assessment of the effect of the chemical on processes contributing both to community development and maintenance. C12AS appeared to elicit a subsidy response from the native protistan assemblage which may have resulted from both positive and negative responses at trophic levels above and below the assemblage. Protistan responses to the surfactant tended to occur more rapidly and be more sensitive than those documented for invertebrates and fish. C12AS elicited a modest response (i.e. a 20% change) from several reliable parameters including community respiration (reduced dissolved oxygen at 289 g per L), protozoan species richness (increased at 63 g per L) and protozoan community composition (increased dissimilarity at 1254 g per L). Responses to C12AS exceeded expected exposures in the real world by a factor of six or greater thereby indicating that the hazard of exposure to C12AS to stream communities is low. The results of this study support the use of mesocosms as decisive tools for evaluating the hazard posed by consumer product chemicals to natural communities and ecosystems     

The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo

1. In order to accumulate at sites of inflammation, leukocytes initially roll on endothelial cells of post-capillary venules before becoming firmly attached. This process of rolling is mediated by selectins which bind to carbohydrate counter-ligands present on the surface of both leukocytes and endothelial cells. The polysaccharide fucoidin has been previously shown to inhibit leukocyte rolling in the mesenteric circulation and to reduce neutrophil accumulation in the skin and meninges in experimental inflammation.
2. In the present study we have assessed the effects of fucoidin on eosinophil function in vitro and eosinophil accumulation at sites of inflammation in guinea-pig skin.
3. At concentrations of up to 1200 μg ml⁻¹, fucoidin inhibited phorbol myristate acetate (PMA)-induced eosinophil homotypic aggregation by up to 60% but had no inhibitory effect on PMA-induced eosinophil adhesion to serum-coated plates.
4. Fucoidin effectively reduced the binding of the anti-L-selectin mAb MEL-14 to guinea-pig eosinophils. Binding of a P-selectin-IgG chimera to eosinophils was also partially inhibited by fucoidin, but binding of an anti-CD18 or an anti-VLA-4 mAb were unaffected.
5. When given systemically to guinea-pigs, fucoidin suppressed ¹¹¹In-labelled eosinophil recruitment to sites of allergic inflammation. ¹¹¹In-labelled eosinophil accumulation induced by platelet-activating factor (PAF) and zymosan-activated plasma (as a source of C5a des Arg) was also inhibited.
6. These results demonstrate a role for fucoidin-sensitive selectins in mediating eosinophil recruitment in vivo.

     

The Relationship Between Protein Aggregation and Molecular Mobility Below the Glass Transition Temperature of Lyophilized Formulations Containing a Monoclonal Antibody

Purpose. To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. Methods. The temperature dependence of relaxation time constant, , was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, , in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. Results. For both sucrose and trehalose formulations, the variation in with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited <2% aggregation at t values <10, where t is the time of storage. Conclusions. Since the relaxation times for sucrose and trehalose formulations at 5°C are on the order of 10⁸ and 10⁶ hrs, it is likely that both formulations would undergo very little (<2%) aggregation in a practical time scale under refrigerated conditions.     

Waste not--want not

The waste budget rarely gets the attention it requires. After all, c'mon it's garbage. We produce it and it costs money to get rid of it. There's nothing we can do about it. Sound familiar? We feel as if we have a handle on it when we negotiate to receive the lowest bid, but our efforts can not stop there. Do we really know what we-re getting for our money? Do we really need everything that is being suggested by the hauler? Are we investigating every avenue that involves waste or are we wasting valuable dollars? With the ever increasing need to find savings, let's look for in in our waste. The following overview of current waste issues is Part One of a guide for the review of practices and potential opportunities. The second part will appear next month.     

Waste abatement: recycling, disposal practices can cut costs

On average, most healthcare facilities are doing less than they should in the areas of source reduction and recycling, and will likely do so until mandated by law. The main reasons for this are ever-tightening healthcare budgets, limited staffing, and the cost of operating recycling programs compared to the cost of general solid waste disposal. Poor record keeping also may also be hampering the final decision to recycle. This article, Part II on waste abatement practices in healthcare organizations, examines what factors facilities should consider in establishing a recycling program, and analyzes cost-effective collection and disposal practices.     

Medicare: past, present and future

The history of the Medicare program, including changes that have been enacted over the years in an effort to control spiraling costs, is reviewed. Medigap insurance and preventive medical care for the elderly are examined, as is the impact of Medicare coverage for the terminally ill. Trends indicate that the Medicare system as presently structured is not financially viable. The question is: what will replace it?     

Cerebrovascular effects of nitric oxide manipulation in spontaneously hypertensive rats

1. Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension is conflicting, possibly as a result of heterogeneity in both the nature of the dysfunction and in the disease process itself. The brain is particularly vulnerable to the vascular complications of chronic hypertension, and the aim of this study was to assess whether differences in the cerebrovascular responsiveness to the NO synthase (NOS) inhibitors, N^G-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3-morpholinosydnonimine (SIN-1) might indicate one possible source of these complications.
2. Conscious spontaneously hypertensive (SHR) and WKY rats, were treated with L-NAME (30 mg kg⁻¹, i.v.), 7-NI (25 mg kg⁻¹, i.p.), SIN-1 (0.54 or 1.8 mg kg⁻¹ h⁻¹, continuous i.v. infusion) or saline (i.v.), 20 min before the measurement of local cerebral blood flow (LCBF) by the fully quantitative [¹⁴C]-iodoantipyrine autoradiographic technique.
3. With the exception of mean arterial blood pressure (MABP), there were no significant differences in physiological parameters between SHR and WKY rats within any of the treatment groups, or between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18% in SHR groups, whilst 7-NI had no significant effect in either group. Following the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both groups (around −20%). There was no significant difference in MABP between groups following the higher dose of SIN-1, but this represented a decrease of −41% in SHR and −21% in WKY rats.
4. With the exception of one brain region (nucleus accumbens), there were no significant differences in basal LCBF between WKY and SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between −10 and −40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging from −34 to −57%) compared with the WKY (ranging from −14 to −43%), and in seven out of the thirteen brain areas examined there were significant differences in LCBF.
5. Following the lower dose of SIN-1, in the WKY 8 out of the 13 brain areas examined showed significant increases in blood flow compared to the saline treated animals. In contrast, only 2 brain areas showed significant increases in flow in the SHR. In the rest of the brain areas examined the effects of SIN-1 upon LCBF were less marked than in the WKY.
6. Infusion of the higher dose of SIN-1 resulted in further significant increases in LCBF in the WKY group (ranging between +30% and +74% compared to saline-treated animals), but no significant effects upon LCBF were found in the SHR. As a result, there were significant differences in LCBF between SIN-1-treated WKY and SHR in six brain areas. In most brain areas examined, cerebral blood flow in SHR following the higher dose of SIN-1 was less than that measured with the lower dose of SIN-1.
7. Despite comparable reductions in MABP (∼20%) in both groups, calculated cerebrovascular resistance (CVR) confirmed that the vasodilator effects of the lower dose of SIN-1 were significantly more pronounced throughout the brain in the WKY (ranging between −3% and −50%; median=−38%) when compared to the SHR (ranging between −10% and −36%; median=−26%). In the animals treated with the higher dose of SIN-1, CVR changes were broadly similar in both groups (median=−45% in WKY and −42% in SHR), but with the reduction in MABP in SHR being twice that found in WKY, this is in keeping with an attenuated blood flow response to SIN-1 in the SHR.
8. The results of this study indicate that NO-dependent vasodilator capacity is reduced in the cerebrovasculature of SHR. In addition, the equal responsiveness to a non-specific NOS inhibitor but an enhanced effectiveness of a specific neuronal NO inhibitor upon LCBF in the SHR could be consistent with an upregulation of the neuronal NO system.

     

Smoking, Lung Function, and Atherosclerosis in the 5,000 Elderly Participants of the Cardiovascular Health Study

The Cardiovascular Health Study (CHS) is an observational study of heart disease and stroke designed to evaluate risk factors and noninvasive measures and to describe and predict atherosclerotic events in older adults. Five thousand two hundred one individuals ages 65 or older were recruited from a stratified random sample of Medicare recipients from 4 US communities. This review of cross-sectional data from the CHS baseline examination describes the cigarette smoking habits of elderly persons and the relationships of smoking to lung function (spirometry) and atherosclerosis, as noninvasively measured by the ankle-arm index (AAI) and carotid ultrasonography. Only 10% of the men and 13% of the women were current smokers, and about half were former smokers. Forced expiratory flow (FEV1) was about 20% lower in current smokers when compared with never smokers. Current and former smoking were strongly associated with an increased risk for an abnormal AAI. Common and internal carotid artery walls were thicker and stenosis more common in current smokers and former smokers, when compared with never smokers. Analysis of long-term follow-up morbidity and mortality data from the CHS cohort should provide even stronger evidence of the effects of smoking in the elderly. Vigorous efforts should be made to persuade elderly smokers to quit.