The synergetic effect of ambient PM2.5 exposure and rhinovirus infection in airway dysfunction in asthma: a pilot observational study from the Central Valley of California.

BACKGROUND: Elevated levels of particulate matter PM2.5 and rhinovirus infection have been known to exacerbate asthma. However, the combined effect of rhinovirus infection and high PM2.5 has not been investigated. PURPOSE: To investigate the effect of PM2.5 and concomitant rhinovirus infection on airway function in asthma in an area with high PM2.5 concentration. METHODS: Asthmatics and their matched controls were monitored for lung function, exhaled nitric oxide (eNO) and respiratory symptoms on days with varying levels of PM2.5. As the study was a repeated measure design, repeated clinical findings, and laboratory data were used in the mixed model analysis. RESULTS: Wheezing and dyspnea in asthmatics were worsened with increasing ambient PM2.5. Increasing PM2.5 decreased FEV1% predicted (-0.51, -0.79 to -0.23) and FEF25-75% predicted (-0.66, -1.07 to -0.24) in subjects with asthma (all P < .01). Rhino viral infection reduced FEF25-75% predicted in subjects with asthma (-11.7, -20 to -2.9). The reductions in FEV25-75 and FEV1 per 10 µg/m(3) increase in ambient PM2.5 were 6% and 5% respectively. A significant interaction was observed between presence of rhinovirus infection and elevated PM2.5 in asthmatics causing a 4-fold decrease in FEF25-75 (P = .01) and a 2-fold decrease in FEV1% predicted values (P = .01) compared with asthmatics with no rhino viral infection. CONCLUSIONS: Increasing ambient PM2.5 and low temperature independently worsened airway function in asthma. The interaction between rhinovirus and PM2.5 significantly impairs airway function in asthma. A larger sample size study is suggested to investigate these observations.

Method development for the measurement of quinone levels in urine.

A method was developed for the quantification of 1-4 ring quinones in urine samples using liquid-liquid extraction followed by analysis with gas chromatography-mass spectrometry. Detection limits for the ten quinones analyzed are in the range 1-2 nmol dm(-3). The potential use of this approach to monitor urinary quinone levels was then evaluated in urine samples from both Sprague-Dawley rats and human subjects. Rats were exposed to 9,10-phenanthraquinone (PQ) by both injection and ingestion (mixed with solid food and dissolved in drinking water). Urinary levels of PQ were found to increase by up to a factor of ten compared to control samples, and the levels were found to depend on both the dose and duration of exposure. Samples were also collected and analyzed periodically from human subjects over the course of six months. Eight quinones were detected in the samples, with levels varying from below the detection limit up to 3 µmol dm(-3).

Effects of collagen nerve guide on neuroma formation and neuropathic pain in a rat model.

BACKGROUND: Posttraumatic neuroma formation is a major cause of neuropathic pain that can occur after elective surgery, amputation, or trauma. This study examined the use of biosynthetic collagen nerve guides to prevent the development of posttraumatic neuromas. METHODS: Collagen nerve guides were applied after neurectomy in a rat sciatic nerve model in an effort to stimulate linear neuronal outgrowth and reduce random axon sprouting. Animals were monitored for evidence of neuropathic pain--autotomy scores were recorded for 8 weeks posttransection--after which proximal stumps were excised and processed for histologic analyses. RESULTS: Moderate to severe autotomy was observed in 88% (7 of 8) of the control (neurectomy) animals. In contrast, 13% (1 of 8) of animals receiving collagen nerve guides developed autotomy, which was significantly less than controls (P < .01). Qualitative analyses of neurofilament and Schwann cell-labeled nerve sections showed a significant enhancement in Schwann cell migration away from the proximal stump and advanced linear axonal regrowth in the collagen nerve guide-treated animals. CONCLUSIONS: Collagen nerve guides alter the regrowth of transected nerves and reduce the severity of symptoms associated with neuropathic pain.

Dichloroacetate reduces tissue necrosis in a rat transverse rectus abdominis musculocutaneous flap model.

OBJECTIVE: Ischemia-related complications may occur during postmastectomy transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction. The aim of our study was to investigate whether necrosis of susceptible flap regions could be reduced by dichloroacetate (DCA)-induced stimulation of oxidative metabolism in hypoxic tissue. METHODS: The study was a randomized control trial using male Sprague-Dawley rats. A pedicled TRAM flap based upon the right inferior epigastric artery was elevated and reapproximated. Animals were randomly assigned to 1 of 5 treatment groups (n = 6). Group I received no DCA; groups II through V were administered 75 mg/kg DCA orally 24 hours preoperative; in addition, groups II through IV received 75 mg/kg/d DCA orally postoperative for 4 days; group III also received 75 mg/kg DCA (IP) intraoperatively; groups IV and V were given 15 mg/kg/d DCA orally for 6 days before the 24-hour preoperative treatment. Four days postsurgery, skin paddles were photographed and assessed for viability. Underlying TRAM muscle was biopsied for histologic analysis. Blood lactate levels were measured at pre- and postoperative time points. The mean percentages of viable skin paddle were as follows: 32.0%+/- 4.0% (group I), 68.1% +/- 6.2% (group II), 84.3% +/- 5.9% (group III), 92.8% +/- 2.0% (group IV), 82.6% +/- 5.8% (group V). RESULTS: Statistically significant differences were found in all experimental (DCA) groups relative to the controls (P < 0.01). Group IV (6-day DCA preconditioning, plus 24-hour preoperative and 4-day postoperative treatment) displayed the greatest improvement in flap viability, significantly better than other DCA groups (P < 0.01). Group IV also had significantly lower serum lactate levels than controls (P < 0.05). Histologic examination of muscle biopsies revealed reductions in inflammation and necrosis correlating with DCA treatment and skin paddle survival. CONCLUSIONS: This study indicates that DCA may provide a useful pharmacologic tool for reducing ischemia-related necrosis in TRAM flaps.

Propofol improves skin flap survival in a rat model: correlating reduction in flap-induced neutrophil activity.

Accumulation of neutrophils in a random pattern skin flap has been demonstrated to contribute to the necrosis of distal flap tissue. This study proposes that administration of propofol anesthesia can effectively reduce neutrophil activity and enhance skin flap survival. The study was a randomized controlled trial using male Sprague-Dawley rats as subjects. For flap survival studies, a 3- by 12-cm, dorsal, cranial-based, random pattern skin flap was elevated and reapproximated. Flaps were examined for viability 10 days postsurgery. To assess neutrophil activity, flap biopsies were taken 12, 24, or 48 hours postsurgery from distal, middle, and proximal flap regions, and myeloperoxidase enzyme content was analyzed. Animals were randomly assigned to 1 of 4 groups: group 1, ketamine anesthesia (controls); group 2, propofol anesthesia; group 3, ketamine anesthesia plus 10% lipid emulsion (propofol vehicle); group 4, ketamine anesthesia without flap elevation (nonoperated controls for myeloperoxidase study). Flap survival was significantly improved in the propofol group compared with both the ketamine and vehicle control groups (P <0.01). Increased flap viability was correlated with a reduction in myeloperoxidase content in the propofol group compared with control operated animals, with minor variations observed in the different flap regions and time points tested. This study indicates that the use of propofol can potentially improve skin flap survival. The beneficial effects may be attributed to a reduction in neutrophil activity within the flap.