The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter

Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats

Although it is well established that long-term heparin therapy causes osteoporosis, it is unknown whether heparin-induced bone loss is reversible when heparin treatment is stopped. To address this question, we randomized rats to once daily subcutaneous injections of either unfractionated heparin (1.0 U/g or 0.5 U/g) or saline for 28 days and then followed the rats for an additional 28 days off treatment. Based on histomorphometric analysis of the distal third of the right femur proximal to the epiphyseal growth plate, 1.0 U/g heparin caused a 30% loss in cancellous bone volume over the first 28 days. This was accompanied by a 137% increase in osteoclast surface and a 60% decrease in both osteoblast and osteoid surface. One month after cessation of heparin treatment, no recovery in these parameters was observed. Similarly, serum levels of alkaline phosphatase, a biochemical marker of bone formation, which continued to decrease over the course of heparin treatment, showed no signs of recovery in the subsequent 28 days off treatment. To explore the mechanism responsible for the prolonged effect of heparin on bone, we repeated the experiment giving 125I-labeled heparin in place of unlabeled heparin. 125I-labeled heparin was found to accumulate in bone during the course of its administration, and be retained in bone for at least 56 days after stopping heparin treatment. These findings suggest that heparin-induced osteoporosis is not rapidly reversible because heparin is sequestered in bone for an extended period.     

Two Pheromones of Coniferophagous Bark Beetles Found in the Bark of Nonhost Angiosperms

Volatiles from fresh bark of black cottonwood, Populus trichocarpa; trembling aspen, P. tremuloides; paper birch, Betula papyrifera; bigleaf maple, Acer macrophyllum; red alder, Alnus rubra; and Sitka alder, Alnus viridis, were collected on Porapak Q and subjected to coupled gas chromatographic–electroantennographic detection analyses by utilizing the antennae of several scolytid beetles (Dendroctonus pseudotsugae, D. rufipennis, D. ponderosae, Ips pini, and Dryocoetes confusus). Among the antennally active volatiles identified by coupled gas chromatographic-mass spectroscopic analysis were frontalin, 1,5-dimethyl-6,8-dioxabicyclo[3.2.1]-octane, in the two Alnus species and conophthorin, (E)-7-methyl-1,6-diox-aspiro[4.5]decane, in the other four species. Field trapping experiments demonstrated that conophthorin had a significant disruptant effect on the response to a pheromone-host kairomone blend by both Dendroctonus pseudotsugae and D. ponderosae. Our results, and the recent identification of other scolytid pheromones in various tree species, pose major questions regarding the evolution and ecological roles of these semiochemicals, including the possibility of Batesian mimicry by the beetles. They also suggest a need for comparative studies on the biosynthetic pathways for these compounds.     

Ability of lymphokine-activated killer cells to lyse mycobacteria-infected cells

In cats and monkeys, we examined the parasympathetic component of the oculomotor complex, which directly innervates the ciliary muscle, using horseradish peroxidase (HRP). Labeled neurons of varying form and size were found in the Edinger-Westphal(EW) and the Perlia nuclei of the cat and in the anteromedian, EW, and Perlia nuclei of the monkey. Our study confirmed that a direct parasympathetic pathway exists from the midbrain to the ciliary muscles, and that accommodation is controlled in part by this direct link from the midsagittal region via a parasympathetic neuron of the oculomotor nuclear complex.     

Structural characterization of the molecular dimer of the peptide antibiotic vancomycin by distance geometry in four spatial dimensions

OBJECTIVE: The objectives of this study were to know the prevalence of hepatitis C virus (HCV) in a population of pregnant women, to evaluate the vertical transmission rates of HCV in a prospective study and to determine the repercussions and consequences in children born to infected mothers. PATIENTS AND METHODS: A total of 6556 pregnant women were tested for HCV antibodies from January 1993 to August 1995. We followed 50 babies born to infected mothers for at least 12 months (mean 15 months). Serological assays employed included a screening ELISA II confirmed with immunoblot. Viral detection was performed by qualitative and quantitative PCR for HCV-RNA. RESULTS: Fifty-nine pregnant women were AcHCV(+). This represents a seroprevalence of 0.9%. Of the 50 babies followed, 6 were PCR(+) and 44 were PCR(-). The risk of transmission is correlated with the titer of HCV-RNA in the mother. All mothers of infected babies were HIV (-). CONCLUSIONS: The rate of prevalence in our pregnant women population is 0.9%. We found a vertical transmission rate of 12%. The high serum HCV-RNA titers in the mothers are a risk factor of transmission of HCV. The viremia in the children does not predict the apparition of the clinical disease, although they can exhibit intermittent increases of transaminases.