Discriminating the ecotoxicity due to metals and to low pH in acid mine drainage

Several techniques have been developed to assess the ecotoxicity of contaminated watercourses. Most of these techniques involve chemical alterations of water samples, by diluting it or by adding chelating agents. These changes become particularly severe when assessing the toxicity of samples with very low pH and with high quantities of contaminants. Trying to overcome this problem, a novel toxicity test, specific for acid waters, was previously developed and field validated. The toxicity of acid samples is assessed using the survival time of Ceriodaphnia dubia. During this study, the novel test was applied to a field situation, where an aquatic system is seriously impacted with acid mine drainage. Its efficiency was tested and compared with two classical toxicity tests: the Microtox and the median lethal dilution with C. dubia. The survival time test was performed without adjusting pH and after adjusting pH to a fixed value (pH 2, 3, and 4). At pH 2 and 4 no acceptable results were obtained; at pH 3 it was possible to distinguish the toxicity due to pH from the toxicity due to other toxicants. The test conducted at local pH was able to discriminate toxicity sources only for highly contaminated samples. The toxicity evaluation of acid mine drainage samples was possible neither with the median lethal dilution test nor with Microtox.     

Novel bioassay based on acetylcholinesterase and lactate dehydrogenase activities to evaluate the toxicity of chemicals to soil isopods

This study developed a bioassay with the isopod Porcellio dilatatus based on the activity of the enzymes acetylcholinesterase (AChE) and lactate dehydrogenase (LDH). The in vivo effects of the insecticides parathion-ethyl and endosulfan-sulfate on AChE and LDH activities of P. dilatatus under laboratory conditions were investigated. The route of uptake of the pesticides was through the food (alder leaves). Isopods were exposed to a wide range of concentrations of parathion or endosulfan (0.1, 1, 10, 25, 50, 100, 250, and 500 microg/g of food) for 21 days. After this period, the activity of AChE and LDH was determined. Parathion induced significant depression of both AChE and LDH activities. Animals fed with endosulfan-contaminated food exhibited lower LDH activities than control animals, while AChE activity was similar in all treatments. The results of the present investigation suggest that the isopod. P. dilatatus is a suitable species for use in toxicity tests and indicate that the enzymes AChE and LDH could be used as effect criteria both in laboratory and in field studies with this species.     

Exercise-induced signs of muscle overuse in children

Signs of overuse after intense muscular exertion are well described in adults, while little research has been conducted in children. The aim of the study was to investigate some indirect markers of muscle damage in 13 years old boys following two different protocols of one-leg stepping exercise to exhaustion. This stepping exercise was performed by two experimental groups with different contributions of concentric and eccentric contractions in a 1:1 vs 1:2 ratio of timing. Subjective soreness perception and maximum voluntary isometric force of the knee extensor muscles were measured immediately prior to and immediately following the exercise, and at 1, 3, 24, 48, 72, 96 hours post exercise. Metabolic markers of exercise stress were taken at similar time intervals and included plasma glutathione concentrations as a marker for oxidative stress, circulating leukocyte numbers, and plasma creatine kinase (CK) activity. All parameters studied demonstrated a higher level of muscular exertion, with more evident signs of overuse in the group with the more eccentric contribution. Complete recovery was achieved between 72 and 96 hours after exertion. However, in this group of boys, the CK activity did not show the typical adult-like increase. Therefore the wide use of CK as an indicator of intense muscle exertion was not supported in this group of children. It can be concluded that children, like adults, experience similar degrees of muscle disturbances following intense exercise and that they may recover more quickly from such exercise.     

Dizziness predicts initial worsening in panic disorder: an otoneurological investigation

Dizziness is a frequent complaint during the initial worsening of panic patients treated with clomipramine. In order to investigate the relationship between dizziness and initial worsening mechanisms, otoneurological tests were administered to 32 consecutive patients with panic disorder, with or without agoraphobia, before treatment, 36 h after the first dose of 25 mg clomipramine and after treatment and full remission of the panic and agoraphobic symptoms. A pretreatment complaint of 'dizziness during panic attacks' but not the occurrence of otoneurological abnormalities, predicted the occurrence of clinical worsening at the start of treatment. A specific pattern of otoneurological abnormalities was not found, but only three patients had normal results in all three sessions. The inconsistent test results suggest that functional vestibular pathology is frequently associated with panic disorder.     

The pharmacist's role in risk management

The role of risk management is vitally important in the hospital. As institutions grow and the field of health care advances into the future, the number of patient-associated risks will continue to multiply. In response, the Joint Commission has changed its policies to reflect the importance of patient outcomes. This new Joint Commission focus, coupled with the increasing number of patient risks, will create the need for health care professionals to recognize their role in risk management. In anticipation of the future, pharmacy has been guiding itself toward that role for some time. With a large portion of the profession participating in activities such as DUE and QA programs, pharmacists can be a useful resource to the risk manager. Participation in retrospective analysis such as ADRs and peer review committees also aids the pharmacy profession in establishing guidelines that will decrease future patient risks. Future trends in drug development will increase the pharmacist's role in drug selection, in an effort to ensure both safety and cost containment. The profession's continuing development and implementation of practice standards will ensure that pharmacy remains dedicated to improving patient outcomes and decreasing patient risks. In addition, by learning to use the risk manager as both a source of information and a partner in identifying pharmacy-related areas of risk, the pharmacy profession will be able to continue its pursuit of improved quality of patient care.     

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants

Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.      

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.