Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials.

INTRODUCTION: Botulinum toxin A (BTA) injection into the glabellar region is currently being studied as a treatment for major depressive disorder (MDD). Here we explore efficacy data of this novel approach in a pooled analysis. METHODS: A literature search revealed 3 RCTs on this topic. Individual patient data and clinical end points shared by these 3 trials were pooled and analyzed as one study (n=134) using multiple regression models with random effects. RESULTS: In the pooled sample, the BTA (n=59) and the placebo group (n=75) did not differ in the baseline variables. Efficacy outcomes revealed BTA superiority over placebo: Improvement in the Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale 6 weeks after baseline was 45.7% for BTA vs. 14.6% for placebo (p<0.0001), corresponding to a BTA response rate of 54.2% (vs. 10.7%) and a BTA remission rate of 30.5% (vs. 6.7%). DISCUSSION: Equalling the status of a meta-analysis, this study increases evidence that a single treatment of BTA into the glabellar region can reduce symptoms of MDD. Further studies are needed to better understand how BTA exerts its mood-lifting effect.

Characterization of DCTN1 genetic variability in neurodegeneration.

OBJECTIVE: Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration. METHODS: In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with Parkinson disease (PD), frontotemporal lobar degeneration (FTLD), or ALS. RESULTS: This analysis revealed 36 novel variants (9 missense, 5 silent, and 22 noncoding). Segregation analysis in families and association studies in PD, FTLD, and ALS case-control series did not identify any variants segregating with disease or associated with increased disease risk. CONCLUSIONS: This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis.

First Report of False Smut of Corn (Zea mays) in the Mississippi Delta.

False smut, caused by Ustilaginoidea virens, occurs on rice, corn, and other Gramineae, but is of little economic importance. False or green smut of corn resembles most closely false smut of rice (1). During surveys in 2000 at Mississippi State University, Delta Experiment Station, Stoneville, 32 (2.5%) of 1,280 commercial and inbred corn hybrids had false smut on the tassel. The percentage of plants infected with false smut ranged from 5 to 15% based on a sample of 20 corn plants from a single 4.9-m row plot. Galls (sclerotia), which are similar to ergot, replaced flowers on tassels of infected plants. Disease severity ranged from 2 to 50% infected flowers per inbred. Mature sclerotia were spherical, 6 to 17 mm in diameter, olive green to black, and velvety with white interiors. The fungus could not be isolated on potato dextrose agar. Only the tassels were infected, which resulted in little damage to the plant, except for a decrease in pollen production. Although the disease has been reported to infect other parts of the corn plant, the injury will likely be less on corn than rice. In 2001 and 2002, the disease was not observed. Disease incidence was more prevalent in 2000 because of hot, wet weather immediately after the crop was planted. The observation of the disease in one growing season suggests the pathogen may be common in the Mississippi Delta and the disease may occur under favorable environmental conditions and susceptible corn hybrids. Reference: (1) J. K. Pataky. False smut. Page 35 in: Compendium of Corn Diseases, 3rd ed. D. G. White, ed. American Phytopathological Society, St. Paul, MN, 1999.

How to establish a position and hours budget.

Learn how to convert your full-time equivalent (FTE) allocation into a position and hours budget.

How to allocate the right staff mix across shifts, Part 1.

Read about how to calculate, balance, and adjust your staffing needs to fit your unit's specific shifts, conditions, and positions.

How to allocate the right staff mix across shifts, Part 2.

In Part 1, the author explained how to calculate, balance, and adjust your direct caregiver staffing needs. This month, read about how to include fixed staff in your budget for your unit's specific conditions.

Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture.

We have previously shown that the basal uptake of mineral particles by tracheobronchial epithelial cells in organ culture is mediated in part by active oxygen species (AOS) and can be greatly augmented by exposure to cigarette smoke, a concentrated source of AOS, and other radicals. We hypothesized that ozone, another generator of AOS in tissues, might have the same effect. To test this hypothesis, tracheal explants were exposed to room air (control) or ozone in varying concentrations from 0.01 to 1.0 ppm for 10 min, and subsequently to a suspension of either amosite asbestos or titanium dioxide (rutile) for 1 h. Explants were then transferred to an air/CO2 incubator for 1 wk to allow particle uptake to occur, and uptake was determined by morphometry. We found that ozone exposure increased the uptake of both asbestos and titanium dioxide in a dose-response fashion; this effect appeared at lower exposure levels and was more marked with titanium dioxide than with amosite. The ozone effect could be prevented by addition of catalase but not superoxide dismutase to the particle suspension, or by preincubation of the particles with deferoxamine. These observations indicate that ozone can directly increase uptake of mineral particles by tracheobronchial epithelial cells; this effect occurs with brief exposures at very low ozone levels and appears to be mediated by hydrogen peroxide and possibly by hydroxyl radical. These findings support the general hypothesis that AOS are important mediators of epithelial particle uptake in many different settings. Enhanced uptake may be one of the mechanisms by which ozone impairs particle clearance from the lung and may play a role in the increased morbidity seen in populations with exposure to high levels of both ozone and atmospheric particulates.

Mineral dusts cause elastin and collagen breakdown in the rat lung: a potential mechanism of dust-induced emphysema.

It is now accepted that workers with exposure to mineral dusts can develop airflow obstruction. The basis of this process is uncertain, but carefully performed morphologic studies suggest that coal, silica, and perhaps other dusts may produce emphysema in humans. To investigate the mechanisms involved in this process, we administered crystalline silica (quartz) or titanium dioxide (rutile) to rats in a single intratracheal instillation. At varying times after instillation, the animals' lungs were lavaged, the lavageate from one lung was dried and hydrolyzed, and the amounts of desmosine (DES),as a measure of elastin breakdown, and hydroxyproline (HP), as a measure of collagen breakdown, were determined. The lavageate from the other lung was counted for inflammatory cells. Both silica and titanium dioxide caused a dose-dependent increase in DES and HP 24 h after instillation. When an equivalent dose (30 mg) of silica or rutile was administered and animals were sacrificed at various times up to 21 d, a sustained increase in lavage DES and HP was seen in the silica-treated animals, and this was accompanied by a sustained increase in polymorphonuclear leukocytes (PMN); in contrast, both lavage PMN and lavage DES/HP rapidly peaked and then declined in the titanium dioxide-treated animals. Numbers of macrophages remained elevated over the 21-d period of sacrifice with both types of treatment. These data show for the first time that mineral dusts can cause connective-tissue breakdown in the lung, with the release of matrix components into the alveolar spaces. The amount of connective-tissue breakdown appears to parallel the number of PMN but not the number of macrophages in the alveolar spaces, suggesting that PMN-derived proteolytic enzymes are responsible for the breakdown. This process probably plays a role in dust-induced emphysema.

Rat mesothelial and tracheal epithelial cells show equal DNA sensitivity to hydrogen peroxide-induced oxidant injury.

To study the relative sensitivity of rat tracheal epithelial and mesothelial cell DNA to oxidant damage, we used the comet assay, a gel microelectrophoresis method that allows visual determination of DNA strand breaks on a cell-by-cell basis, to evaluate damage after hydrogen peroxide exposure. By both a qualitative and a quantitative assay, tracheal epithelial mesothelial cells demonstrated a similar dose-response increase in the number of cells showing strand breaks and the number of breaks per cell after exposure to increasing concentrations of hydrogen peroxide; but even at the highest concentration, some cells failed to show damage. By contrast, 100% of cultured V79 lung fibroblasts showed evidence of damage. Catalase and deferoxamine largely prevented the formation of strand breaks, while superoxide dismutase was not protective. To evaluate DNA repair, cells were exposed to 10 microM hydrogen peroxide for 10 min, washed, and maintained in culture medium; by 2 h the proportion of mesothelial and epithelial cells showing comets had returned to control levels for both cell types. Both cell types also showed a similar pattern of increasing damage after continuous exposure to 10 microM hydrogen peroxide for periods up to 2 h. We conclude that, in this system, 1) mesothelial and tracheobronchial epithelial cells show a similar pattern of DNA injury and repair after hydrogen peroxide exposure; 2) hydrogen peroxide damages DNA of both cell types via a mechanism probably related to the iron-catalyzed formation of hydroxyl radical; and 3) both types of cells appear to be heterogeneous in their sensitivity to oxidant damage, with some cells showing extreme resistance to such damage.

Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells.

The factors that determine whether an exogenous mineral particle will be taken up by tracheobronchial epithelial cells are unclear. We have previously proposed that active oxygen species play a role in this process, most likely through iron-catalyzed formation of hydroxyl radical and subsequent lipid peroxidation of cell membranes. To further examine this hypothesis, we prepared rat tracheal explant cultures and exposed them for 1 h to suspensions of amosite asbestos or titanium dioxide (rutile) that had been preincubated with varying concentrations of a mixture of ferrous and ferric chloride. Explants were then maintained in organ culture in air/CO2 for 1 wk to allow particle or fiber uptake to occur. Particles or fibers in the tracheal epithelium were determined by light microscopic morphometry. Similarly treated explants were assayed for malondialdehyde as a measure of lipid peroxidation in the epithelial cells. Asbestos fibers without added iron caused lipid peroxidation, but this was not true of titanium dioxide particles. For both types of dust, increasing adsorbed iron concentrations were associated with increasing particle uptake and increasing lipid peroxidation. These observations suggest that cationic iron may play a major role in particle uptake by tracheobronchial epithelia, and that particle uptake is also related to iron-mediated lipid peroxidation.

Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke.

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cigarette smoke on epithelial uptake of non-asbestos mineral particles in tracheal organ culture.

Cigarette smoke is believed to increase the pulmonary retention of many different types of mineral dusts, but the mechanisms of this process are unclear. We have previously shown, using a tracheal organ culture system, that exposure to cigarette smoke directly increases the uptake of asbestos fibers by tracheal epithelial cells, and that this process is mediated by active oxygen species. To determine whether the same effects are seen with other types of mineral dust, we exposed rat tracheal explants to cigarette smoke or air (control) and then to a variety of dusts generally considered "inert" or of low pathogenicity. Explants were maintained in organ culture to allow dust uptake, and segments fixed and prepared for light microscopy at various times up to 1 wk; particle uptake was determined morphometrically. We observed that cigarette smoke significantly increased the epithelial uptake of nonfibrous titanium dioxide and talc, and of fibrous silicon carbide, but not of fibrous or nonfibrous iron oxide, nonfibrous silicon carbide, or fibrous wollastonite. Scavengers of active oxygen species (catalase) or agents that prevent the formation of active oxygen species (deferoxamine) blocked the effects of smoke in enhancing titanium dioxide uptake but did not block the effects of smoke on talc uptake. These observations indicate that cigarette smoke may potentiate the effects of many types of dust, including relatively inert dusts, by directly increasing the numbers of particles entering the tracheobronchial epithelium and eventually reaching the interstitium. However, smoke does not directly enhance the uptake of every dust.(ABSTRACT TRUNCATED AT 250 WORDS)