Comparison of Pure Nicotine- and Smokeless Tobacco Extract-Induced Toxicities and Oxidative Stress

The toxicities and oxidative stress-inducing actions of (−)-nicotine and smokeless tobacco extract (STE), containing equivalent amounts of nicotine, were studied. Toxicities were determined by colony formation assays using Chinese hamster ovary (CHO) cells. Results indicated that nicotine is less toxic than smokeless tobacco extract that contained the same amount of nicotine. The generation of reactive oxygen species, following treatment with smokeless tobacco extract and nicotine, was assessed by measurement of changes in glutathione (GSH) and malondialdehyde (MDA) levels. CHO cells (5 × 10⁵ cells/5 ml media) were incubated with 4, 0.8, and 0.08 mg of nicotine and STE containing the same amounts of nicotine. All preparations of smokeless tobacco extract significantly decreased GSH levels and increased MDA generation. However, 0.08 mg of nicotine treatment did not result in a significant change in GSH level, and only 4 mg of nicotine were sufficient to increase MDA generation. Addition of free radical scavenging enzymes, superoxide dismutase (SOD) and catalase (CAT), and an intracellular GSH precursor, N-acetyl-L-cysteine (NAC), replenished the GSH levels in nicotine-treated cells. GSH levels in cells exposed to smokeless tobacco extract containing 4 and 0.8 mg nicotine remained significantly lower than the control with the addition of SOD and CAT. However, co-addition of NAC with smokeless tobacco extract preparations returned the GSH levels to the control level. Lactate dehydrogenase (LDH) activities were measured in the media to establish the membrane damage following exposure to smokeless tobacco extract and nicotine. Treatment of cells with 4 mg nicotine caused a significant increase in LDH activity, which was returned to control level in the presence of the antioxidant enzymes and NAC. Smokeless tobacco extract did not change the LDH activity. Received: 14 September 1998/Accepted: 24 February 1999     

Distribution along a Stages-of-Behavioral-Change Continuum for Condom and Contraceptive Use among Women Accessed in Different Settings

The numbers of women of childbearing age in the US with HIV and AIDS from heterosexual transmission continues to rise. Behavioral interventions remain the best means of preventing transmission of HIV. Program planners often implement interventions to promote behavioral change in a wide range of settings such as family planning or sexually transmitted disease clinics, drug treatment facilities, or medical facilities that serve high risk and HIV positive women. Women recruited in different types of settings, however, may differ with respect to their experience with, attitudes toward, and willingness to use condoms and contraception. Such differences should be considered when tailoring interventions to the populations being served. We examined the readiness to use condoms and contraception among 3784 women in four cities recruited in three different types of settings: community, facilities not targeted to HIV positive women and medical facilities for HIV positive populations. Readiness to use condoms or contraception was measured using The Transtheoretical Model of Change. Women reported being in different stages along the continuum of condom and contraceptive use in the three settings. A greater proportion of women in the HIV-facility, 45%, had used condoms consistently for the previous 6 months compared to women in the other two settings (12% and 11%). Similarly, variation across settings was seen for contemplation of consistent contraceptive use to prevent unintended pregnancies. The variability in the distribution of condom and contraceptive use across settings underscores the importance of assessing the readiness for the behavior change and designing interventions that meet the specific needs of the populations being served.     

Do beta-amyloid (Abeta) deposits in patients with Alzheimer's disease and Down's syndrome grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and classic beta-amyloid (Abeta) deposits were studied in single sections of cortical tissue from patients with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those predicted by the log-normal model. In a sample of brain regions, these size distributions were compared with those obtained by serial reconstruction through the tissue and the data used to adjust the size distributions obtained in single sections. The adjusted size distributions of the diffuse, primitive and classic deposits deviated significantly from a log-normal model in AD and DS, the greatest deviations from the model being observed in AD. More Abeta deposits were observed close to the mean and fewer in the larger size classes than predicted by the model. Hence, the growth of Abeta deposits in AD and DS does not strictly follow the log-normal model, deposits growing to within a more restricted size range than predicted. However, Abeta deposits grow to a larger size in DS compared with AD which may reflect differences in the mechanism of Abeta formation.     

The role of the clinical nurse specialist

Despite the prevalence of clinical nurse specialists, research suggests that their role remains poorly understood (O'Hanlan and Gibbon 1996). In practice, they fulfil a number of important roles linked to developing practice. Here, the author critically examines the range of roles the clinical nurse specialist may undertake and how they influence patient care.     

Measurement tools used in the study of eccentric contraction-induced injury

The objective of this review is to evaluate the measurement tools currently used in the study of eccentric contraction-induced muscle injury, with emphasis on their usefulness for quantifying the magnitude and duration of the injury and as indicators of muscle functional deficits. In studies in humans, it was concluded that measurements of maximal voluntary contraction torque and range of motion provide the best methods for quantifying muscle injury. Similarly, in animal studies, the in vitro measurement of electrically elicited force under isometric conditions was considered to be the best of the measurement tools currently in use. For future studies, more effort should be put into measuring other contractile parameters (e.g. force/torque-velocity and force/torque-length relationships maximal shortening velocity and fatigue susceptibility) that may reflect injury-induced functional impairments. The use of histology, ratings of soreness and the measurement of blood or bath levels of myofibre proteins should be discouraged for purposes of quantifying muscle injury and/or functional impairment.     

The reliability of the "absent cistern sign" in assessing LP shunt function

OBJECTIVE: One of the difficulties with lumboperitoneal (LP) shunts has been non-invasively ascertaining shunt function. It has been previously reported that in the presence of a functioning LP shunt the perimesencephalic cisterns become obliterated--the "absent cistern sign". In order to more rigorously test this association we performed a retrospective analysis of LP shunt patients at the Hospital for Sick Children, Toronto. METHODS: The CT scans of all patients undergoing LP shunting over a 17 year period were reviewed. The "absent cistern sign" and ventricular size were compared against the results of either an isotope shunt study or surgical findings performed within 2 days of the CT. RESULTS: There were 38 CT scans (27 patients) performed within 2 days of an isotope shunt study and 15 CT scans (14 patients) performed within 2 days of a surgical intervention. These results give the absent cistern sign a sensitivity of 75% and a specificity of 57% when compared to the shunt isotope findings and a sensitivity of 100% and a specificity of 50% when compared to the surgical findings. Over 30% of the CT scans showed ventriculomegaly in the presence of a functioning shunt and, conversely, nearly 45% of the CT scans had normal or small lateral ventricles in the presence of a malfunctioning shunt. CONCLUSIONS: The "absent cistern sign" appears to reliably rule out a completely blocked shunt, but is less reliable in detecting a normal or partially obstructed shunt. Ventricular size correlates poorly with LP shunt function.     

Intracellular signals and cytoskeletal elements involved in oligodendrocyte progenitor migration

We have examined the potential roles of intracellular Ca2+ regulation and of multiple cytoskeletal elements in control of the directed migration of cultured oligodendrocyte progenitor cells (OPs). OPs were found to migrate in response to platelet-derived growth factor (PDGF) or to a lesser extent to basic fibroblast growth factor (FGF) in a non-additive manner. This response was inhibited by chelation of intracellular Ca2+ by using BAPTA-AM. OP migration was not evoked by the neurotransmitter agonists phenylephrine or methacholine, which elevate OP Ca2+ levels. Inhibition of the MAP kinase pathway with PD 098059 did not affect OP migration to PDGF. Within growth cone-like leading edges of migratory OP processes, monomeric and filamentous actin were found to be colocalized with myosin and filamentous actin was prominent in filopodia extending beyond the leading edge. Tubulin was distributed throughout OP processes and cell bodies. Inhibition of actin or tubulin polymerization, by using cytochalasin B or nocodazole, respectively, altered OP morphology and markedly impaired migration. Inhibition of the myosin ATPase by BDM, which prevents force-generating actin/myosin interactions, greatly inhibited the chemotaxic response at concentrations that did not disrupt cell morphology. These results indicate that growth factors stimulate OP migration by activating pathways which include intracellular Ca2+ regulation, and characterize the distribution of multiple cytoskeletal elements involved in the generation of directed OP movement.     

Effect of four computer keyboards in computer users with upper extremity musculoskeletal disorders.

Eighty computer users with musculoskeletal disorders participated in a 6-month, randomized, placebo-controlled trial evaluating the effects of four computer keyboards on clinical findings, pain severity, functional hand status, and comfort. The alternative geometry keyboards tested were: the Apple Adjustable Keyboard [kb1], Comfort Keyboard System [kb2], Microsoft Natural Keyboard [kb3], and placebo. Compared to placebo, kb3 and to a lesser extent kb1 groups demonstrated an improving trend in pain severity and hand function following 6 months of keyboard use. However, there was no corresponding consistent improvement in clinical findings in the alternative geometry keyboard groups compared to the placebo group. Overall, there was a significant correlation between improvement of pain severity and greater satisfaction with the keyboards. These results provide evidence that keyboard users may experience a reduction in hand pain after several months of use of some alternative geometry keyboards.     

Study on the reduction of chemotherapy induced neutropenia in mice using glucosaminylmuramyl dipeptide.

Neutropenia is a common and often dose limiting side effect of some chemotherapy regimens. The aim of this study was to investigate the ability of an immunomodulator, glycosaminylmuramyl dipeptide (GMDP, CAS 78113-36-7, romurtide) to reduce chemotherapy induced neutropenia. BALB/c mice were treated with 200 mg kg-1 cyclophosphamide (CY) to induce a reversible neutropenia lasting approximately 6-7 days. There was no change in the duration or depth of neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection. In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response. However, a marked neutrophilia compared to controls was consistently observed in all cases. Neutrophil counts of up to 14 times the baseline value were measured 6-7 days after the induction of neutropenia. GMDP had no effect in the absence of CY. Less variation was seen in white cell counts of older non-SPF mice treated with CY. When the activity of GMDP (5 mg kg-1) was compared with G-CSF (granulocyte colony stimulating factor, 100 micrograms kg-1) in these animals, GMDP showed a consistent trend to reduce the length of neutropenia, however, under the conditions tested only G-CSF treatment resulted in a significant reduction in the duration of neutropenia. In the 12-week-old mice, the neutrophilia seen with both G-CSF and GMDP was much smaller than in the 8-week-old mice, and was not significantly different from that in control mice treated with CY alone.