A Systems Approach to Remediating Human Exposure to Arsenic and Fluoride From Overexploited Aquifers.

In semiarid agricultural regions, aquifers have watered widespread economic development. Falling water tables, however, drive up energy costs and can make the water toxic for human consumption. The study area is located in central Mexico, where arsenic and fluoride are widely present at toxic concentrations in well water. We simulated the holistic outcomes from three pumping scenarios over 100 years (2020-2120); (S1) pumping rates increase at a similar rate to the past 40 years, (S2) remain constant, or (S3) decrease. Under scenario S1, by 2120, the depth to water table increased to 426 m and energy consumption for irrigation increased to 4 × 109 kWh/yr. Arsenic and fluoride concentrations increased from 14 to 46 µg/L and 1.0 to 3.6 mg/L, respectively. The combined estimated IQ point decrements from drinking untreated well water lowered expected incomes in 2120 by 27% compared to what they would be with negligible exposure levels. We calculated the 100-year Net Present Value (NPV) of each scenario assuming the 2020 average crop value to water footprint ratio of 0.12 USD/m3. Without drinking water mitigation, S1 and S3 yielded relative NPVs of -5.96 × 109 and 1.51 × 109 USD, respectively, compared to the base case (S2). The relative NPV of providing blanket reverse osmosis treatment, while keeping pumping constant (S2), was 11.55 × 109 USD and this gain increased when combined with decreased pumping (S3). If a high value, low water footprint crop was substituted (broccoli, 1.51 USD/m3), the net gains from increasing pumping were similar in size to those of implementing blanket drinking water treatment.

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity.

Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl2). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction.

Changes in the expression of calcitonin gene-related peptide after exposure to injurious stretch-shortening contractions.

UNLABELLED: One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344×BN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia.

Stereological analysis of muscle morphology following exposure to repetitive stretch-shortening cycles in a rat model.

Repetitive motion is one risk factor associated with contraction-induced muscle injury, which leads to skeletal muscle degeneration, inflammation, and dysfunction. Since current methods are unable to quantify the acute degenerative and inflammatory responses of muscle tissue concurrently, the purpose of this study was to quantify the temporal myofiber response after exposure to injurious stretch-shortening cycles (SSCs) using a standardized stereological technique. Functional testing was performed on the ankle dorsiflexor muscles of Sprague-Dawley rats in vivo. Rats were anesthetized and exposed to 15 sets of 10 SSCs. Control rats were exposed to 15 sets of single isometric contractions of the same stimulation duration. Changes in muscle morphometry were assessed at 0.5, 24, 48, 72, and 240 h post-exposure to quantify the degree of myofiber degeneration and inflammation in the tibialis anterior muscle from each group. There was an increase in the volume density and average thickness of degenerating myofibers over time in the muscle collected from rats exposed to SSCs (p < 0.0001) that was significantly greater than in muscle exposed to isometric contractions at 24, 48, and 72 h post-exposure (p = 0.003). The volume density of degenerative myofibers was associated with functional deficits at 48 h. Stereological quantification of degenerative myofibers and interstitial space changes were associated with functional defects 48-72 h after SSC-induced injury, thus demonstrating stereology is an accurate measure of SSC-induced skeletal muscle injury.

Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin G.

Investigators frequently face the quandary of how to interpret the often times disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta-analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis. Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two-Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach.

Impact of muscle length during stretch-shortening contractions on real-time and temporal muscle performance measures in rats in vivo.

The objective of the present study was to investigate the impact of muscle length during stretch-shortening cycles on static and dynamic muscle performance. Animals were randomly assigned to an isometric (control, Con, n = 12), a short-muscle-length (S-Inj, 1.22-2.09 rad, n = 12), or a long-muscle-length (L-Inj, 1.57-2.44 rad, n = 12) group. The dorsiflexor muscles were exposed in vivo to 7 sets of 10 stretch-shortening contractions (conducted at 8.72 rad/s) or 7 sets of isometric contractions of the same stimulation duration by using a custom-designed dynamometer. Performance was characterized by multipositional isometric exertions and positive, negative, and net work before exposure, 6 h after exposure, and 48 h after exposure to contractions. Real-time muscle performance during the stretch-shortening cycles was characterized by stretch-shortening parameters and negative, positive, and net work. The S-Inj group recovery (force difference) was similar to the Con group force difference at 48 h, whereas the L-Inj group force difference was statistically greater at 1.39, 1.57, and 1.74 rad than the Con group force difference (P < 0.05). Negative work (P < 0.05) and net work (P < 0.05) were statistically lower in the S-Inj and L-Inj groups than in the Con group 48 h after exposure to contractions. Of the real-time parameters, there was a difference in cyclic force with treatment during the stretch-shortening cycles (P < 0.0001), with the L-Inj group being the most affected. Thus longer ranges of motion result in a more profound isometric force decrement 48 h after exposure to contractions and in real-time changes in eccentric forces.

Dynamic force responses of skeletal muscle during stretch-shortening cycles.

Muscle damage due to stretch-shortening cycles (i.e., cyclic eccentric/concentric muscle actions) is one of the major concerns in sports and occupational related activities. Mechanical responses of whole muscle have been associated with damage in neural motor units, in connective tissues, and the force generation mechanism. The objective of this study was to introduce a new method to quantify the real-time changes in skeletal muscle forces of rats during injurious stretch-shortening cycles. Male Sprague Dawley rats ( n=24) were selected for use in this study. The dorsi flexor muscle group was exposed to either 150 stretch-shortening cycles ( n=12) or 15 isometric contractions ( n=12) in vivo using a dynamometer and electrical stimulation. Muscle damage after exposure to stretch-shortening cycles was verified by the non-recoverable force deficit at 48 h and the presence of myofiber necrosis. Variations of the dynamic forces during stretch-shortening cycles were analyzed by decomposing the dynamic force signature into peak force ( F(peak)), minimum force ( F(min)), average force ( F(mean)), and cyclic force ( F(a)). After the 15th set of stretch-shortening cycles, the decrease in the stretch-shortening parameters, F(peak), F(min), F(mean), and F(a), was 50% ( P<0.0001), 26% ( P=0.0055), 68% ( P<0.0001), and 50% ( P<0.0001), respectively. Our results showed that both isometric contractions and stretch-shortening cycles induce a reduction in the isometric force. However, the force reduction induced by isometric contractions fully recovered after a break of 48 h while that induced by stretch-shortening cycles did not. Histopathologic assessment of the tibialis anterior exposed to stretch-shortening cycles showed significant myofiber degeneration and necrosis with associated inflammation, while muscles exposed to isometric contractions showed no myofiber degeneration and necrosis, and limited inflammation. Our results suggest that muscle damage can be identified by the non-recoverable isometric force decrement and also by the variations in the dynamic force signature during stretch-shortening cycles.

Force deficits after stretches of activated rat muscle-tendon complex with reduced collagen cross-linking.

The forces produced during stretches of passive and activated muscles, and isometric force deficits after stretching of activated muscles were examined in rat plantor flexor muscle-tendon complexes with reduced collagen cross-links (pyridinoline). Female Sprague-Dawley rats (n = 6, age 87 days) were injected twice daily for 43 days with beta-aminopropionitrile (BAPN, 333 mg/kg/day i.p.), an inhibitor of lysyl oxidase, which is responsible for the production of collagen cross-links. The relative weights of the plantar flexor muscles were similar for BAPN and saline-injected (control, C) rats (n = 6). Pyridinoline was lower in the tendon (22.9%), and in the plantaris (17.1%), and soleus (7.4%) muscles (P < 0.05), with no changes observed in collagen content (hydroxyproline), as determined by high-pressure liquid chromatography. At an ankle position of 90 degrees, groups had similar forces at 5, 10, 20, 40, 60 and 80 Hz before stretching. Forces at 40 degrees with stretches of the passive muscles (five times from 90 degrees to 40 degrees) were lower for all stretches in BAPN-injected rats (P < 0.05). Isometric force deficits resulting from stretches of activated muscles (80 Hz, 20 times from 90 degrees to 40 degrees, rest intervals 3 min) followed similar courses for BAPN-injected and C rats, and were 51.1 (2.4)% (C) and 54.7 (4.6)% (BAPN) before the last stretch. After 1 h of rest, isometric force deficits were 26% and 29% larger at 10 Hz and 5 Hz, respectively, in BAPN-treated rats (P < 0.05). The reduction in BAPN-injected collagen cross-linking of the skeletal muscle-tendon complex reduced the forces produced during stretches without muscle stimulation (i.e. passive stretch), and stretching of activated muscles produced larger isometric force deficits only at low stimulation frequencies.

Recovery from 6 weeks of repeated strain injury to rat soleus muscles.

Recovery from chronic strain injury (50 strains daily, five times weekly for 6 weeks to hyperactive soleus muscles) was followed for 3 months in female rats after cessation of chronic hyperactivity induced by pretreatment of the plantar flexor muscles with tetanus toxin. After 6 weeks of repeated strains, muscle mass decreased by 62%, myofiber areas were reduced by 87%, and noncontractile tissue expanded dramatically by 222%. Collagen content increased by almost ninefold (control 40 +/- 3 microg/mg, chronic injury 392 +/- 53 microg/mg), whereas the molar ratio of collagen (pyridinoline) crosslinks to collagen remained the same (control 0.20 +/- 0.01, chronic injury 0.16 +/- 0.01). After 3 months of ambulation, muscle mass returned to normal but myofiber areas remained smaller by 21%, noncontractile tissue was still markedly elevated by 18% with increased collagen content (107 +/- 15 microg/mg), and the molar ratio of crosslinks to collagen increased by 75% during recovery. Thus, rat soleus muscles recovered very slowly and incompletely from chronic strain injuries that produced muscle fibrosis, highlighting the necessity of devising preventative strategies for repeated strain injuries.

Isotonic dynamometry for the assessment of power and fatigue in the knee extensor muscles of females.

Impairments in muscle power production and recovery following short-duration intense activity could lead to decreased performance and risk of injury. We developed a power test for the knee extensor muscles using torque-velocity testing and moderate isotonic loads. Twenty-eight female volunteers performed three maximal efforts at each of four isotonic loads (27.1, 40.6, 54.2 and 67.8 N. m). If the calculated regression line for the torque-velocity data had an r2 >/= 0.95 (i.e. an acceptable test), maximal power (408 +/- 56 W) was computed from the data. Immediately after torque-velocity testing, the subjects repeated maximal effort knee extensions with 33.9 N. m for three bouts of 15 repetitions with 15 s of rest to produce muscle fatigue, defined as a decrease in power output during isotonic exercise. After a 4 min rest, the torque-velocity test was repeated and power calculated (345 +/- 48 W). For the group, the recovery of maximal power after the fatigue protocol was 85%. The extremes were represented by one subject who recovered only 70% of her maximal power and another who recovered completely (>98%). Physiological differences in muscle power following repeated exercise could have an impact on the outcome of therapeutic interventions for sports injuries, fatigue syndromes and occupational over-use conditions.

Determination of fibrosis from cryostat sections using high performance liquid chromatography: skeletal muscle.

Analysis of hydroxyproline (collagen) and pyridinoline (collagen cross-links) in biopsies prepared for routine histological evaluation with OCT compound was performed. Frozen sections (250 microm-thick) were cut from cardiac muscle, diaphragm, liver, and soleus muscle from the rat. After removal of OCT compound by rinsing, the samples were dried, weighed and hydrolyzed in 6 N HCl. A portion of the hydrolysate was analyzed for hydroxyproline using high performance liquid chromatography with collagen type I as the standard. Collagen concentrations ranged from 6.6 microg/mg dry weight (liver) to 74.7 microg/mg dry weight (diaphragm). From the remainder of the hydrolyzate, pyridinoline cross-links of collagen were separated and analyzed similarly by high performance liquid chromatography. The concentration of pyridinoline ranged from 2.6 ng/mg dry weight (liver) to 35.6 ng/mg dry weight (diaphragm). These techniques were adequate to analyze both collagen and pyridinoline (i.e. collagen cross-links) in small biopsy samples (< 1 mg dry weight) routinely used in clinical pathology. The method proved useful in the quantitation of focal fibrosis in a partially denervated rat soleus. Denervation was confirmed using fast myosin immunohistochemistry which revealed large areas of small myofibres containing fast myosin. Collagen concentration increased by five-fold and collagen cross-links by more than 7-fold consistent with fibrotic changes known to occur with denervation.

Adaptation of rat gastrocnemius muscles to 2 weeks of centrifugation: myofibers and extracellular matrix.

BACKGROUND: The effect of 2 wk of exposure to centrifugation (2G) on gastrocnemius muscles of rats was investigated by morphometric and computer-assisted image analysis of muscle fiber areas and non-contractile tissue components (extracellular matrix). RESULTS: Muscle atrophy was seen in the myofibers from 2G rats which had decreased in cross-sectional area by 26%. In contrast, the non-contractile tissue component actually increased by 13%. These results were compared with soleus muscle atrophy seen following 2 wk of unloading by tail-suspension. In all cases, the extracellular matrix increased in proportion to the decrease in fiber area. A theoretical model was developed to assess the effect of changes in myofiber cross-sectional area on the relative content of the extracellular matrix. The experimental results from both rat gastrocnemius and soleus muscles were consistent with the model with slight variations due to the known differences in connective tissue content of different muscles in the rat. CONCLUSION: Thus, the gastrocnemius muscle atrophy seen after 2 wk of centrifugation results from loss of contractile and other myofiber specific proteins while the extracellular matrix remains relatively constant. The loss in myofiber content was greater than expected from changes in muscle wet weight and more than required to adapt to a decrease in body weight.

An ophthalmic drape with a built-in breathing outlet.

An ophthalmic surgical drape with an ancillary breathing outlet is described and illustrated. It is believed that this drape will supply a needed emergency feature in current ophthalmic surgical drapes that will contribute to greater safety among elderly patients and give greater assurance to the surgeon who may experience a sudden interruption in surgery caused by an unexpected respiratory problem.

Fibrosis and intercellular collagen connections from four weeks of muscle strains.

The effect of repeated cycles of muscle strain was studied in the soleus muscle of female rats. Muscle strains were repeated 3X/week for 1 month using two different strain protocols. Striking changes, including marked variability in fiber size, evidence of degradation and regeneration, and an expanded extracellular matrix were pronounced in the fast-stretched muscles but not in the slow-stretched muscles. However, the slow-stretched muscles did contain struts of connective tissue joining adjacent myofibers. Therefore, repeated muscle strains at high strain rates produced morphological changes similar to many myopathies, including fibrosis, whereas adaptation occurred in response to the same number of strains at slow strain rates. Such diverse tissue responses have relevance to the understanding of the mechanisms of skeletal muscle dysfunction in cumulative trauma disorders and in the design of preventive actions and treatments.

Use of double labeling and photo CD for morphometric analysis of injured skeletal muscle.

We used computer-assisted analysis of myofiber cross-sectional areas to measure skeletal muscle responses to injury and disease. We developed a simple, inexpensive method for measuring myofiber size in human muscle samples using Kodak photo compact discs (CDs) as the image source. The photo CD serves as a permanent image storage medium and provides a high-resolution image that can be used to detect small myofibers. The use of double labeling for dystrophin and desmin allowed positive identification of both degenerating and regenerating fibers in a single biopsy specimen.

Regulation of monocyte chemoattractant protein-1 gene expression and secretion in rat pulmonary alveolar macrophages by lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1 beta.

Chemotactic cytokines coordinate the recruitment of leukocytes into the lung during pulmonary inflammation. In a previous study, we determined that rat pulmonary alveolar macrophages (PAMs) facilitate monocyte recruitment and activation in the lung during acute inflammatory lung injury, in part, through the inducible expression of monocyte chemoattractant protein-1 (MCP-1). MCP-1 is an 11 to 15 kD basic peptide that specifically mediates monocyte chemotaxis and activation. Inflammatory mediators that regulate the expression and secretion of MCP-1 by rat PAMs have not been identified. We determined that stimulation of resident rat PAMs with bacterial lipopolysaccharide (LPS), murine tumor necrosis factor-alpha, or human interleukin-1 beta resulted in the inducible expression of MCP-1 mRNA and the secretion of biologically active MCP-1. In contrast, phorbol myristate acetate, a nonphysiologic leukocyte activator, was significantly less effective in stimulating either enhanced MCP-1 mRNA expression or secretion of MCP-1. These results indicate that the expression of MCP-1 mRNA and the secretion of MCP-1 by rat PAMs are regulated by bacterial products (LPS) and inflammatory cytokines. Further, these results suggest PAMs are regulated by bacterial products (LPS) and inflammatory cytokines. Further, these results suggest that resident PAMs, through elaboration of MCP-1, may play a pivotal role in regulating recruitment and activation of monocytes in the lung during acute inflammatory lung injury.

Adaptation of rat soleus muscles to 4 wk of intermittent strain.

The effect of repeated strains on rat soleus muscles was investigated by stretching active muscles 3 times/wk for 4 wk with two different methods of stretching. The adaptation of myofibers and noncontractile tissue was followed by histochemical techniques and computer-assisted image analysis. Muscle hypertrophy was seen in the slow-stretched muscles, which increased in mass by 13% and increased in myofiber cross-sectional area by 30%. In the fast-stretched muscle, mass increased by 10% but myofiber cross-sectional area actually decreased. This decrease in mean fiber area was the result of a population of very small fibers (population A) that coexisted with slightly smaller normal-sized fibers (population B). Fibers in population A did not have the distribution expected from atrophy compared with atrophic fibers from unloaded muscles; they were much smaller. In addition, there was a 44% increase in noncontractile tissue in the fast-stretched muscles. Thus, soleus muscles subjected to repeated strains respond differently to slow and fast stretching. Slow stretching results in typical muscle hypertrophy, whereas fast stretching produces somewhat larger muscles but with a mixture of small and normal-sized myofibers accompanied by a marked proliferation of noncontractile tissue.

Use of computer-assisted analysis for myofiber size measurements of rat soleus muscles from photographed images.

Since myofiber cross-sectional area measurements are important in describing myofiber adaptations to physiological and pathological changes, we developed a reproducible method for measuring myofiber size using fluorescent stains. Several 35-mm slides of dystrophin-, laminin-, and concanavalin A (ConA)-stained muscle sections were used to calculate myofiber cross-sectional areas and to compare different techniques and settings of an image capture system. Although variation in equipment settings did result in variation in myofiber area, the overall effect was of little practical significance (< 6%). Using midrange values for the settings of illumination, black level, and gain, reproducible quantitative data were collected and analyzed from 35-mm slides of FITC-labeled conA taken from atrophic, normal, and hypertrophic muscle samples. As expected, the atrophic muscle fibers were smaller. However, in hypertrophic muscle from compensatory overload, the fibers were composed of both large and small fibers. We found it important that the myofiber cross-sectional area measurements be expressed both in terms of average fiber areas and as frequency distribution histograms. In addition, detailed methodology of fiber area measurement must be provided.

Expression of monocyte chemoattractant protein-1 (MCP-1) by rat alveolar macrophages during chronic lung injury.

Using a well-characterized model of bleomycin-induced pulmonary fibrosis in the rat, we determined that there was a time-dependent elaboration of monocyte chemotactic activity in bronchoalveolar lavage fluid. Northern hybridization analysis revealed markedly increased expression of rat monocyte chemoattractant protein-1 (MCP-1) mRNA in alveolar macrophages (AMs) from rats following induction of pulmonary fibrosis. Monocyte chemotactic activity was also significantly increased in conditioned media from AMs retrieved from injured rat lungs. These data suggest that one important role of AMs in the pathogenesis of chronic inflammatory lung injury and pulmonary fibrosis is the regulation of monocyte recruitment and activation within the lung secondary to secretion of monocyte chemoattractants including MCP-1.