High bone density masks architectural deficiencies in an individual with spinal cord injury

Context

Spinal cord injury (SCI) causes a decline of bone mineral density (BMD) in the paralyzed extremities via the gradual degradation and resorption of trabecular elements. Clinical tools that report BMD may not offer insight into trabecular architecture flaws that could affect bone''s ability to withstand loading. We present a case of a woman with a 30-year history of SCI and abnormally high distal femur BMD.

Findings

Peripheral quantitative-computed tomography-based BMD for this subject was ∼20% higher than previously published non-SCI values. Computed tomography (CT) revealed evidence of sclerotic bone deposition in the trabecular envelope, most likely due to glucocorticoid-induced osteonecrosis. Volumetric topologic analysis of trabecular architecture indicated that the majority of the bone mineral was organized into thick, plate-like structures rather than a multi-branched trabecular network. Visual analysis of the CT stack confirmed that the sclerotic bone regions were continuous with the cortex at only a handful of points.

Conclusions

Conventional clinical BMD analysis could have led to erroneous assumptions about this subject''s bone quality. CT-based analysis revealed that this subject''s high BMD masked underlying architectural flaws. For patients who received prolonged glucocorticoid therapy, excessively high BMD should be viewed with caution. The ability of this subject''s bone to resist fracture is, in our view, extremely suspect. A better understanding of the mechanical competency of this very dense, but architecturally flawed bone would be desirable before this subject engaged in activities that load the limbs.     

Activation of natriuretic peptide receptor-C attenuates the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats: implication of Gialpha protein

We have recently shown that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins, which was attributed to the enhanced oxidative stress. Since C-ANP_4-23 that specifically interacts with natriuretic peptide C (NPR-C) receptor has been shown to decrease the expression of Giα protein in VSMC, the present study was undertaken to examine if C-ANP_4-23 can also decrease the enhanced expression of Giα protein in VSMC from SHR and whether it is attributed to its ability to attenuate the enhanced oxidative stress. Aortic VSMC from 12-week-old SHR and their age-matched Wistar-Kyoto (WKY) rats were used for the present studies. VSMC from SHR exhibited enhanced expression of Giα-2 and Giα-3 proteins, different subunits of NADPH oxidase such as Nox⁴ and p^47phox proteins but not of p^22phox, enhanced production of superoxide anion as well as NADPH oxidase activity as compared to age-matched WKY rats. Treatment of VSMC from SHR with C-ANP_4-23 decreased towards control levels the enhanced expression of Giα proteins, enhanced superoxide anion production and enhanced NADPH oxidase activity as well as the enhanced expression of Nox⁴ and p^47phox. However, C-ANP_4-23-induced attenuation of the enhanced level of O₂⁻ and NADPH oxidase activity occurs at 4 h before the decrease in the enhanced expression of p^47phox that occurs at 16 h of C-ANP_4-23 treatment. The decreased expression of NADPH oxidase in SHR was also associated with further decrease in O₂⁻ and NADPH oxidase activity. Furthermore, treatment of VSMC from SHR with pertussis toxin (PT) decreased the enhanced levels of superoxide anion as well as NADPH oxidase activity; however, the enhanced levels of different subunits of NADPH oxidase were not attenuated by PT treatment. These results suggest that C-ANP_4-23 decreases the enhanced oxidative stress in SHR by attenuating the enhanced expression of Giα proteins and also the enhanced levels of NADPH oxidase.     

Gender and willingness to undergo invasive cardiac procedures

To explore the role of patient preferences in explaining gender differences in the use of invasive cardiac procedures, we surveyed 174 patients presenting for cardiac stress testing at a university hospital. Controlling for sociodemographic factors, health status, symptom severity, and history of prior procedures, women expressed greater willingness than men to accept a physician's recommendation of cardiac catheterization (odds ratio 7.1; 95% confidence interval 1.1, 45.3) and similar willingness to accept a recommendation for coronary angioplasty or coronary artery bypass graft surgery. We conclude that patient preferences are unlikely to explain gender disparities in the use of invasive cardiac procedures.     

Activation of prophage P4 by the P2 Cox protein and the sites of action of the Cox protein on the two phage genomes.

Phage P2 induces the unrelated prophage P4. In this paper we show that this is due to the activation of the P4 late promoter PII by the P2 Cox protein. This is in contrast to the effects of Cox on P2, for which it is known from previous work that it acts as a repressor of the promoter Pc, which is responsible for expression of the immunity repressor C. The activator role of Cox was revealed by its effect on replication of P4 DNA and on the formation of chloramphenicol acetyltransferase when a promoterless cat gene was inserted downstream of the P4 PII promoter. DNase I protection studies revealed that the Cox protein binds to the repressor promoter Pc of phage P2 and to the promoter PII of phage P4. In the latter case the Cox protein binds upstream of the -35 region, in analogy to several other activators of promoters. A weak binding was found in the promoters Pe of phage P2 and Ple of phage P4. The Cox protein is a case of viral transactivation of the replication genes of one phage by a control protein of the other. However, the effects of the Cox protein are totally different in the two phages, repressive in one case and activating in the other.     

Leishmanial lipid suppresses tumor necrosis factor alpha, interleukin-1beta, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial-mediated pathway

OBJECTIVE: Leishmanial lipid is a strong immunosuppressor of host cells. Inhibition of the inflammatory responses of synovial cells through induction of apoptosis is one of the main targets of therapeutic intervention in rheumatoid arthritis (RA). This study was undertaken to examine the antiinflammatory and apoptosis-inducing effects of leishmanial lipid on adherent synovial fluid mononuclear cells (SFMCs) in patients with RA. METHODS: Lipid was extracted from a Leishmania donovani promastigote (MHO/IN/1978/UR6) by the Bligh and Dyer method. Nitric oxide (NO) was measured using the Griess reaction, and enzyme-linked immunosorbent assays for cytokines, NF-kappaB, and cytochrome c were performed. Levels of cytokines, inducible nitric oxide synthase, caspases, Bcl-2, Bax, t-Bid, and cytochrome c in the cell lysate and of NF-kappaB p65 in the nucleus were determined by Western blotting. Microscopic analysis, nuclear staining, DNA fragmentation assay, fluorescence-activated cell sorting, colorimetric assay for caspases, and fluorescent probe for measurement of mitochondrial membrane potential were used to study the leishmanial lipid-induced apoptotic pathway in SFMCs. RESULTS: Leishmanial lipid inhibited the release of tumor necrosis factor alpha, interleukin-1beta, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-kappaB p65 levels in SFMCs, in a dose-dependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the down-regulation of Bcl-2. CONCLUSION: These results suggest that leishmanial lipid has strong antiinflammatory and apoptosis-inducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.     

Chronic low-level arsenic exposure reduces lung function in male population without skin lesions

Objectives

The respiratory effects of chronic low-level arsenic exposure from groundwater have been investigated in West Bengal, India.

Methods

The participants (834 non-smoking adult males) were subdivided in two groups: an arsenic-exposed group (n = 446, mean age 35.3 years) drinking arsenic-contaminated groundwater (11–50 μg/L) and a control group of 388 age-matched men drinking water containing <10 μg/L of arsenic. Arsenic in water samples was measured by atomic absorption spectroscopy. The prevalence of respiratory symptoms was documented by structured, validated questionnaire. Pulmonary function test (PFT) was assessed by portable spirometer.

Results

Compared with control, the arsenic-exposed subjects had higher prevalence of upper and lower respiratory symptoms, dyspnea, asthma, eye irritation and headache. Besides, 20.6 % of arsenic-exposed subjects had lung function deficits (predominantly restrictive and combined types) compared with 13.6 % of control (p < 0.05). A positive association was observed between arsenic concentration in drinking water and the prevalence of respiratory symptoms, while a negative association existed between arsenic level and spirometric parameters.

Conclusions

The findings suggest that even low-level arsenic exposure has deleterious respiratory effects.     

ADHD and the externalizing spectrum: direct comparison of categorical,continuous, and hybrid models of liability in a nationally representative sample

Purpose

Alcohol use disorders, substance use disorders, and antisocial personality disorder share a common externalizing liability, which may also include attention-deficit hyperactivity disorder (ADHD). However, few studies have compared formal quantitative models of externalizing liability, with the aim of delineating the categorical and/or continuous nature of this liability in the community. This study compares categorical, continuous, and hybrid models of externalizing liability.

Method

Data were derived from the 2004–2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Seven disorders were modeled: childhood ADHD and lifetime diagnoses of antisocial personality disorder (ASPD), nicotine dependence, alcohol dependence, marijuana dependence, cocaine dependence, and other substance dependence.

Results

The continuous latent trait model provided the best fit to the data. Measurement invariance analyses supported the fit of the model across genders, with females displaying a significantly lower probability of experiencing externalizing disorders. Cocaine dependence, marijuana dependence, other substance dependence, alcohol dependence, ASPD, nicotine dependence, and ADHD provided the greatest information, respectively, about the underlying externalizing continuum.

Conclusions

Liability to externalizing disorders is continuous and dimensional in severity. The findings have important implications for the organizational structure of externalizing psychopathology in psychiatric nomenclatures.