Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucleus test

Ten halogenated aliphatic hydrocarbons (carbon tetrachloride, 1-chlorohexane, 2,3-dichlorobutane, 1,2-dichloroethane, 1,2-dichloroethylene, 1,3-dichloropropane, hexachloroethane, 1,1,2-trichloroethane, 1,2,3-trichloropropane and 1,1,3-trichloropropene), previously assayed in genetic assays in fungi, were evaluated in the mouse bone marrow micronucleus test in order to assess their genotoxicity in vivo. All chemicals were administered once i.p. at 40 and 70-80% of their respective LD50 to male and female CD-1 mice, 24 and 48 h before killing. All treatments produced evident clinical symptoms, but no marked depression of bone marrow proliferation. No statistically significant increases in the incidence of micronucleated polychromatic erythrocytes over the control values were observed at any sampling time with any of the 10 halogenated hydrocarbons assayed. The comparison of the results obtained in this study with the findings provided by in vitro micronucleus assays on the same chemicals, reported by other authors, indicate that mouse bone marrow is weakly sensitive to the genotoxic effects induced by halogenated hydrocarbons in other test systems. This suggests that the role of such an assay in carcinogen screening may be questionable for this chemical class. An examination of mouse bone marrow micronucleus test results with the halogenated aliphatic hydrocarbons classified as carcinogens by IARC supports this conclusion.     

Stroke-prone rats exhibit prolonged behavioral deficits without increased brain injury: an indication of disrupted post-stroke brain recovery of function

Stroke-prone rat strains exhibit an increased stroke risk and sensitivity, and reduced endogenous mechanisms of ischemic brain tolerance. This experiment provides a comparative, serial evaluation of neurological deficits and brain injury following middle cerebral artery occlusion/permanent focal stroke in this high-risk strain. Stroke-prone spontaneously hypertensive (SHR-SP), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated over 28 days using magnetic resonance imaging (MRI), histopathology, and neurobehavioral testing. T2- and diffusion weighted-MRI was performed after 1, 10 and 28 days to measure the degree of stroke-induced brain injury. Normotensive WKY rats receiving the same stroke and other SHR-SP rats receiving sham surgery were used for control comparisons. Functional deficits were scored after 1, 4, 11, 18 and 28 days. The degree of brain infarction/injury was practically identical in hypertensive and stroke-prone rats. WKY rats exhibited significantly smaller infarcts (P<0.05), with neurological function recovering quickly to normal by day 11 in this strain. Functional deficits persisted longer in hypertensive rats, with function recovering to normal by day 18 (P<0.05). Functional deficits in SHR-SP rats persisted the longest, and were observed even after 28 days (P<0.05). This increased and prolonged neurologic dysfunction exhibited by SHR-SP compared to SHR rats, while exhibiting practically identical degrees of brain injury/infarction, reflects the increased stroke risk and sensitivity of this strain and suggests a reduced SHR-SP brain plasticity following injury. Therefore, the stroke-prone rat provides an enhanced and prolonged functional deficit model that can be used to elucidate those mechanisms/novel targets critical to longitudinal neurobehavioral recovery post-stroke.     

Associations of Sleep With Sedentary Behavior and Physical Activity Patterns Across Pregnancy Trimesters

IntroductionSleep, sedentary behavior, and moderate-to-vigorous physical activity (MVPA) are altered in pregnancy and may affect pregnancy health; however, how these behaviors are associated with each other is unclear.MethodsPregnant women (N = 120) completed the Pittsburgh Sleep Quality Index and wore an activPAL3 micro and ActiGraph GT3X for 7 days in each trimester to assess sleep, sedentary behavior, and MVPA, respectively. Latent trajectories described patterns of sleep duration, efficiency, and quality as well as sedentary behavior and MVPA. Multinomial logistic regression examined associations of sleep patterns with sedentary behavior and MVPA patterns and, in exploratory analyses, with adverse pregnancy outcomes.ResultsTrajectories were identified for sleep duration (consistently short, 20.7% of sample; consistently adequate, 79.3%), efficiency (consistently low, 17.5%; consistently high, 82.5%), and quality (consistently poor, 15.1%; worsening, 23.5%; and consistently good, 61.5%). Compared with those in more optimal sleep groups, women in the short duration, low efficiency, and worsening quality groups had lower odds of being in the moderate and/or high sedentary behavior group (odds ratio range, 0.21–0.31; 95% confidence interval range, 0.09–0.65). Women in the worsening quality group had greater odds of being in the low MVPA group (odds ratio, 2.51; 95% confidence interval, 1.18–5.38). Trends were observed with women in less optimal sleep groups having greater odds of adverse pregnancy outcomes and lower odds of excessive gestational weight gain.ConclusionsLess optimal sleep patterns in pregnancy are associated with less sedentary behavior and MVPA; additional research is needed to confirm associations between sleep and pregnancy outcomes.     

Calcium channel blockers in cerebral ischaemia

Ischaemic stroke usually results from the obstruction of a major cerebral vessel which leads to a decrease in cerebral blood flow, and a subsequent reduction in ATP. This energy loss leads to impaired cellular function due to reduced ATP-dependent processes and a disruption in ionic gradients across membranes. Under these conditions, there is a significant efflux of K+ from cells producing cellular depolarisation and the movement of extracellular calcium into cells through calcium channels. It is this increase in intracellular calcium that leads to the 'calcium toxicity' that has been associated with cerebral ischaemia. Increased intracellular calcium triggers the break-down of phospholipids, proteins and nucleic acids. This is activated by calcium-dependent phospholipases, proteases and endonucleases, and contributes to structural and functional damage of the cell membrane, which compromises cell function and facilitates cell death. Calcium channel blockers are used routinely to treat cardiovascular disease and hypertension. Although some experimental studies over the last decade suggest efficacy/benefit in the treatment of experimental ischaemic stroke, clinical data do not bear this out. This article discusses the role of voltage-operated calcium channel blockers in stroke, and reviews much of the available experimental and clinical data.     

Wound healing in forefoot amputations: The predictive value of toe pressure

A retrospective study of 136 men undergoing forefoot amputation was done to test the hypothesis that preoperative toe pressure (TP) could predict the likelihood of wound healing. Demographic data included age, smoking history, diabetes mellitus (DM), hypertension, hyperlipidemia, and coronary artery disease. Clinical data included infection, preoperative arterial Doppler data, TP, wound disposition, concomitant revascularization (REV), and healing outcome. Among diabetics, no primary amputation healed with a preoperative TP <38 mm Hg. Among REV diabetics, no healing occurred with a TP <40 mm Hg after bypass, but no failures occurred either with a TP >68 mm Hg or an increase in TP >30 mm Hg after bypass. Nondiabetic patients exhibited no threshold TP values. Univariate analysis revealed that DM and REV were significantly different in the healed (N=83) vs. nonhealed (N=53) populations ( p =0.027 and 0.034). In healed patients, mean TP (71.8 ± 3.5 mm Hg SEM) was significantly higher than in nonhealed patients (45.1 ± 4.3 mm Hg SEM,p =0.000). Logistic regression analysis identified age >60 years (p =0.03), DM (p =0.003), preoperative TP ( p <0.001), and REV ( p <0.001) as significant independent predictors of forefoot amputation healing. Healing probability was calculated and plotted vs. TP for subpopulations based on age, DM, and REV status for both primary forefoot amputation and amputation concomitant with bypass. In this study population, therefore, preoperative TP appeared to be a useful clinical tool for predicting the healing potential of both primary forefoot amputations and amputations plus concomitant bypass for any given patient.     

A “flipped” kidney in utero in an infant with a double collecting system and a Gartner's duct cyst with a vaginal ectopic ureter

We report an infant with two unique anatomic abnormalities. A flipped kidney in utero is described with the association of a Gartner's duct cyst and a vaginal ectopic ureter with a duplicated collecting system.