Simulated herbicide drift alters native plant flowering phenology.

Data for herbicide effects on plant flowering are needed to determine potential impacts on plant reproduction. Thus, flowering phenology was determined for up to 12 weeks after herbicide treatment for native Willamette Valley plants growing in small plots on two Oregon State University experimental farms. Six perennial species were evaluated: Camassia leichtlinii (CALE), Elymus glaucus (ELGL), Eriophyllum lanatum (ERLA), Festuca idahoensis subsp. roemeri (FEID), Iris tenax (IRTE), and Prunella vulgaris var. lanceolata (PRVU). Effects of glyphosate and dicamba, alone and in combination, were determined using simulated drift rates of 0.1 or 0.2 x field application rates (FAR) of 1119 g ha-1 active ingredient (a.i.) (830 g ha-1 acid glyphosate) for glyphosate and 560 g ha-1 a.i. for dicamba. Flowering phenology was evaluated as stage of development on a scale from no buds (converted to 0), buds (1), pre-flowering (2), flowering (3), post-flowering (4), to mature seeds (5) before herbicide treatment and for 12 weeks after treatment. Flowering response to herbicides varied by species and farm; but, in general, dicamba and glyphosate resulted in earlier flowering stages (delayed or not full flowering) for the dicot ERLA, and to a lesser extent, PRVU; and glyphosate resulted in earlier flowering stages for the monocot IRTE. Based on these data, the concentration of herbicide affecting flowering stage was 0.1 x FAR. Once flowering stage was inhibited by dicamba and glyphosate, plants generally did not recover to full flowering. This study provided evidence that common herbicides can affect flowering phenology of native plants with implications for seed production.

Modeling Anthropogenic and Environmental Influences on Freshwater Harmful Algal Bloom Development Detected by MERIS Over the Central United States.

Human and ecological health have been threatened by the increase of cyanobacteria harmful algal blooms (cyanoHABs) in freshwater systems. Successful mitigation of this risk requires understanding the factors driving cyanoHABs at a broad scale. To inform management priorities and decisions, we employed random forest modeling to identify major cyanoHAB drivers in 369 freshwater lakes distributed across 15 upper Midwest states during the 2011 bloom season (July-October). We used Cyanobacteria Index (CI_cyano)-A remotely sensed product derived from the MEdium Resolution Imaging Spectrometer (MERIS) aboard the European Space Agency's Envisat satellite-as the response variable to obtain variable importance metrics for 75 landscape and lake physiographic predictor variables. Lakes were stratified into high and low elevation categories to further focus CI_cyano variable importance identification by anthropogenic and natural influences. "High elevation" watershed land cover (LC) was primarily forest or natural vegetation, compared with "low elevation" watersheds LC dominated by anthropogenic landscapes (e.g., agriculture and municipalities). We used the top ranked 25 Random Forest variables to create a classification and regression tree (CART) for both low and high elevation lake designations to identify variable thresholds for possible management mitigation. Mean CI_cyano was 3 times larger for "low elevation" lakes than for "high elevation" lakes, with both mean values exceeding the "High" World Health Organization recreational guidance/action level threshold for cyanobacteria (100,000 cells/mL). Agrarian-related variables were prominent across all 369 lakes and low elevation lakes. High elevation lakes showed more influence of lakeside LC than for the low elevation lakes.

Effects of circuit resistance training and timely protein supplementation on exercise-induced fat oxidation in tetraplegic adults.

BACKGROUND: Substrate utilization during exercise in persons with spinal cord injury (SCI) remains poorly defined. PURPOSE: To investigate effects of circuit resistance training (CRT) and timing of protein supplementation (PS) on fuel utilization in persons with tetraplegia. METHODS: Eleven individuals with chronic tetraplegia underwent 6 months of CRT 3 times weekly. Five randomly assigned participants received immediate PS (iPS) administered in split doses prior to and following all exercise sessions. Other participants consumed a matched dose of PS that was delayed until 24 hours post-exercise (dPS). Participants underwent a maximal graded exercise test (GXT) to volitional exhaustion at 4 conditioning time points: 3 months before (-3mo), at the beginning of (0mo), 3 months into (3mo), and 6 months following (6mo) the CRT conditioning program. Respiratory measures were continuously obtained throughout the GXT via open-circuit spirometry. Fuel utilization and energy expenditure were computed from the respiratory data. RESULTS: The differences in changes in substrate utilization between the PS groups were not significant as determined by the interaction of PS group and conditioning time point, F (3, 27) = 2.32, P = .098, η(2) P = .205. Maximal absolute fat oxidation did not change significantly from 0 to 6mo (mean difference, 0.014 ± 0.031 g/min; P = .170), and fat oxidation remained low never exceeding an average of 0.10 ± 0.09 g/min for any given exercise intensity. CONCLUSION: Maximum fat utilization during exercise and fat utilization at matched exercise intensities were not increased in persons with tetraplegia, independent of PS, and levels of fat oxidation remained low after training.

The Impact of Caregiver/Care-Receiver Co-Treatment in a Therapeutic Lifestyle Intervention for Chronic Spinal Cord Injury: A Comparative Case Series.

Introduction: This study is a prospective comparative case series analysing the differential impacts of a therapeutic lifestyle intervention (TLI) on individuals with spinal cord injury (SCI) and their caregivers. The primary objective was to assess changes across several health metrics predictive of cardio metabolic disease (CMD), fitness, and quality of life, in dyadic partners and between 2 separate cases. Case Presentation: SCI participants and their respective caregivers, forming 10 dyads, were included in the study. Dyads were randomly assigned to two distinct case scenarios: Case 1, where both dyadic partners received TLI; and Case 2, where only the SCI partner received the intervention. Each case series comprised five dyads. TLI constituted a rigorous 6-month program consisting of exercise, adherence to a Mediterranean diet, and behavioural support. Across cases, notable improvements were observed in body mass, and strength among SCI partners; and reductions in body mass and fasting glucose, and improved mental well-being was observed in caregiver partners. Dyadic interaction analysis found that insulin, HOMA, HDL, and mental health improvements in SCI were strongly linked to improvements in caregiver when both dyadic partners received TLI. Conclusion: We conclude that TLI co-treatment for dyadic partners, including exercise, nutrition, and behaviour modification, improves health outcomes related to CMD risks and quality of life in both populations. Trial Registration: ClinicalTrials.gov, ID: NCT02853149 Registered August 2, 2016.

Exercise participation barrier prevalence and association with exercise participation status in individuals with spinal cord injury.

STUDY DESIGN: Pass-code protected web survey. OBJECTIVES: Defining exercise participation barrier prevalence and association with exercise participation status in adults with spinal cord injury (SCI). SETTING: World-wide web. METHODS: Individuals ≥18 years with ShCI in the United States completed a pass-code protected website survey (N=180). Odds ratios (OR) and OR 95% confidence interval (95% CI) assessed association between barrier presence and exercise participation. RESULTS: No differences existed between exercisers and non-exercisers with respect to age, gender, injury level, injury duration, education level, or employment status. A larger percentage of non-exercisers reported household annual incomes <$7,500. The five most prevalent barriers were not associated with participation status (all OR 95% CI included 1). Low prevalence (≤13%) characterized four of the five barriers most strongly related to being a non-exerciser. Identifying too lazy, too difficult, or no interest as a barrier decreased odds of being an exerciser by 86%, 83%, and 71%, respectively. Not liking exercise decreased the odds of being an exerciser by 90%. CONCLUSION: Highly prevalent barriers were not associated with exercise participation status, whereas low prevalence barriers were strongly related to being a non-exerciser. Internal barriers had the strongest association with exercise participation status. The possible association between socioeconomic factors and exercise participation may be underappreciated. The most effective interventions to increase exercise participation may be multifocal approaches to enhance internal perceptions about and motivation to exercise, increase knowledge of how and where to exercise, while also reducing program and transportation financial costs.

Transformation and release of micronized Cu used as a wood preservative in treated wood in wetland soil.

Micronized Cu (µ-Cu) is used as a wood preservative, replacing toxic chromated copper arsenate (CCA). Micronized Cu is malachite [Cu2CO3(OH)2] that has been milled to micron/submicron particles, with many particle diameters less than 100 nm, mixed with biocides and then used to treat wood. In addition to concerns about the fate of the Cu from µ-Cu, there is interest in the fate of the nano-Cu (n-Cu) constituents. We examined movement of Cu from µ-Cu-treated wood after placing treated-wood stakes into model wetland ecosystems. Release of Cu into surface and subsurface water was monitored. Surface water Cu reached maximum levels 3 days after stake installation and remained elevated if the systems remained inundated. Subsurface water Cu levels were 10% of surface water levels at day 3 and increased gradually thereafter. Sequential filtering indicated that a large portion of the Cu in solution was associating with soluble organics, but there was no evidence for n-Cu in solution. After 4 months, Cu in thin-sections of treated wood and adjacent soil were characterized with micro X-ray absorption fine structure spectroscopy (µ-XAFS). Localization and speciation of Cu in the wood and adjacent soil using µ-XAFS clearly indicated that Cu concentrations decreased over time in the treated wood and increased in the adjacent soil. However, n-Cu from the treated wood was not found in the adjacent soil or plant roots. The results of this study indicate that Cu in the µ-Cu-treated wood dissolves and migrates into adjacent soil and waters primarily in ionic form (i.e., Cu2+) and not as nano-sized Cu particles. A reduced form of Cu (Cu2S) was identified in deep soil proximal to the treated wood, indicating strong reducing conditions. The formation of the insoluble Cu2S effectively removes some portion of dissolved Cu from solution, reducing movement of Cu2+ to the water column and diminishing exposure.

The role of fetal inflammatory response syndrome and fetal anemia in nonpreventable term neonatal encephalopathy.

OBJECTIVE: To evaluate asphyxial patterns in term encephalopathic newborns caused by chorioamnionitis or intrapartum blood loss that resulted in cerebral palsy and allegations of obstetrical professional liability. STUDY DESIGN: As an expert witness, JKM identified term newborns with profound neurologic impairment: 18 born in the presence of chorioamnionitis and 14 with significant anemia. RESULT: In both study groups, profound depression with low 10-min Apgars was associated with early-onset seizures (88%), multiorgan failure (94%) and a partial prolonged injury to the cortex and subcortical white matter (94%). A cord arterial pH>7.00 was noted in 68% and deep gray matter injury involving the basal ganglia and thalamus occurred in only 19% of the newborns studied. CONCLUSION: The cord arterial pH and pCO2 values, early-onset seizures and paucity of isolated deep gray matter injury support that significant injury occurred postnatally despite appropriate resuscitation. This unique pattern may refute allegations of obstetrical mismanagement in the intrapartum period.

Pertussis toxin-sensitive melatonin receptors negatively coupled to adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells.

PURPOSE: Studies were conducted to investigate the influence of melatonin on adenylate cyclase activity in cultured human and rat retinal pigment epithelial (RPE) cells. METHODS: Adenylate cyclase activity was assessed by measurement of cAMP levels in cultured RPE cells using a specific cAMP-binding protein isolated from bovine adrenal cortex to detect cellular cAMP by competition with a standard amount of tritiated cAMP. The effects of melatonin on basal cAMP levels and those induced by the direct activator of adenylate cyclase, forskolin, were studied. RESULTS: Exposure of human RPE cells to 100 microM of melatonin had no effect on basal cAMP levels, but it caused a 41% reduction in the forskolin (5 microM) stimulation of cAMP. This melatonin-induced reduction in forskolin-stimulated adenylate cyclase activity was dose dependent, with half-maximal (EC50) reduction at 4.2 x 10(-10) M. 2-iodomelatonin, 6-chloromelatonin, and 6-hydroxymelatonin mimicked the melatonin effect with EC50 values of 3.5 x 10(-10) M, 4.3 x 10(-9)M, and 1.9 x 10(-7)M, respectively. Preexposure of cells to pertussis toxin (100 ng/ml) for 18 hours completely attenuated the ability of melatonin to influence the forskolin stimulation of cAMP levels. Propranolol did not influence the action of melatonin but did antagonize the ability of serotonin to reduce the forskolin-elevated cAMP levels. Thus, melatonin receptors are distinct from serotonin receptors. Melatonin receptors negatively linked to cAMP metabolism are also associated with cultured hooded rat RPE cells. Melatonin and iodomelatonin caused dose-dependent reductions in forskolin-stimulated cAMP production with half-maximal values of 2.4 x 10(-9)M and 3.28 x 10(-9)M, respectively. CONCLUSIONS: The results show that human and rat RPE cells possess melatonin receptors negatively coupled to adenylate cyclase and sensitive to pertussis toxin.

Pharmacologic evidence for 5-HT1A receptors associated with human retinal pigment epithelial cells in culture.

PURPOSE: The authors investigate the possible presence of 5-hydroxytryptamine (5-HT1) type serotonin receptors negatively coupled to adenylate cyclase activity in cultured human retinal pigment epithelial (RPE) cells. METHODS: Adenylate cyclase activity was assessed by the determination of cellular adenosine 3':5' cyclic monophosphate (cAMP) levels and the effects of serotonin on both basal and forskolin-stimulated cAMP levels studied. RESULTS: Serotonin at 100 microM had no effect on the basal levels of cAMP in cultured human RPE cells, but attenuated by 43.6% the stimulation in cAMP production induced by forskolin (5 microM). This effect was dose dependent for serotonin with half-maximal inhibition (EC50) occurring at approximately 1.5 x 10(-9) M. The 5-HT1 receptor agonist 8-hydroxy [2-di-n-propylamino] tetralin (8-OH DPAT), buspirone, 5-carboxyamidotryptamine, and RU24969 mimicked the inhibitory effect of serotonin in a dose-dependent manner. The actions of serotonin and 8-OH DPAT (10 microM) were dose-dependently attenuated by the serotonergic antagonists spiroxatrine, propranolol, and spiperone. Pretreatment of RPE cell cultures with pertussis toxin abolished the serotonin-induced reduction of forskolin-elevated cAMP levels. Stimulation of cAMP production by the beta-adrenoceptor agonist isoproterenol at 0.1 microM, but not at 10 microM or 100 microM, also was attenuated by serotonin (100 microM), whereas cAMP production induced by the adenosine receptor agonist 5'-[N-ethyl]-carboxamidoadenosine (NECA) at 1 microM, 10 microM, and 100 microM was unaffected. Serotonin and 8-OH DPAT dose-dependently inhibited isoproterenol-stimulated (0.1 microM) cAMP production with EC50 values of approximately 10 microM, and pertussis toxin pretreatment partially blocked these effects. CONCLUSIONS: Cultured human RPE cells possess 5-HT1A receptors negatively coupled to cAMP production through a pertussis toxin-sensitive G protein. These receptors show differential effects on forskolin-, isoproterenol-, and NECA-stimulated cAMP production, which may reflect a unique spatial distribution of receptor proteins or the phenotypic heterogeneity of RPE cells that is the result of or that is preserved in culture.

Assessment of Thy-1 mRNA levels as an index of retinal ganglion cell damage.

PURPOSE: Thy-1 is primarily, if not entirely, expressed by the ganglion cells within the retina. This knowledge was used to index ganglion cell death after ischemia and excitotoxicity by studying changes in Thy-1 mRNA levels. METHODS: Insults to the rat retina were delivered either by elevation of intraocular pressure for 60 minutes or by intravitreal injection of N-methyl-D-aspartate (NMDA). After a defined period, changes in Thy-1 immunoreactivity and mRNA levels of Thy-1 and NR1 (NMDA receptor subunit) were used to index ganglion cell sensitivity to damage. Opsin mRNA levels were used as an internal control because photoreceptors lack NMDA receptors. RESULTS: Retinal Thy-1 immunoreactivity, associated with the ganglion cell and inner plexiform layers, is reduced by ischemia or intravitreal injections of NMDA in a dose-dependent manner. Using a semi-quantitative polymerase chain reaction (reverse transcription-polymerase chain reaction) methodology, the levels of total retinal Thy-1 and NR1 mRNAs were shown to be dramatically reduced after both transient ischemia and intravitreal injection of NMDA. The effect of NMDA was found to be both time- and dose-dependent. In contrast, no change occurred in the levels of opsin mRNA unless high levels of NMDA (200 nmoles) were administered. CONCLUSIONS: Ischemia and NMDA-induced excitotoxicity caused retinal ganglion cell destruction, but the photoreceptors were unaffected. Measurement of total retinal Thy-1 mRNA levels provides a useful way of following ganglion cell death especially when combined with immunohistochemical localization of Thy-1. Additionally, the effect on other retinal cell types such as the photoreceptors can be followed in concert using this technique.

Melatonin counteracts ischemia-induced apoptosis in human retinal pigment epithelial cells.

PURPOSE: To investigate whether the neurohormone melatonin can prevent apoptosis caused by deprivation of oxygen, glucose, and serum (experimental ischemia) in cultured human retinal pigment (RPE) cells. METHODS: Cultures of human RPE cells established from a variety of donors were grown to passage four and then subjected to experimental ischemia, with or without various substances, for up to 72 hours. Cells were examined for morphologic changes and breakdown of DNA, assessed by TdT-dTUP terminal nick-end labeling (TUNEL) and agarose gel electrophoresis. Changes in transcription and translation of various proto-oncogenes (bcl-2, TIAR, ICH-1S/1) were assessed by analysis of mRNA and protein levels, respectively. The effect of various substances on the iron-ascorbate-induced formation of reactive oxygen species (ROS) in chick retinal dissociates was also investigated. RESULTS: Cultured human RPE cells on coverslips that were incubated in serum-free medium, glucose, and oxygen remained viable for up to 40 hours. Thereafter, there was a steady decrease in cell numbers and an increase in the number of cells labeled by the TUNEL method. By 72 hours 65% of cells remained attached to the coverslips, of which approximately 65% were TUNEL positive. Furthermore, most of the experimental ischemia-treated cells exhibited a shrunken appearance typical of apoptosis. Fragmentation of the DNA from cells in which ischemia was induced for 72 hours was also confirmed by agarose gel electrophoresis. Inclusion of 100 microM melatonin significantly decreased the amount of apoptotic cell nuclei after ischemia, but the effect was mild compared with that of fetal calf serum, which almost completely counteracted cell death. The action of melatonin was not prevented by 0.01 mM to 1 mM luzindole, a melatonin receptor antagonist. In addition, 100 microM ascorbate did not counteract ischemia-induced apoptosis. Treatment of RPE cells with 100 microM flupirtine gluconate for 72 hours caused an upregulation of the proto-oncogene protein Bcl-2 and a decrease in TIAR and ICH-1L proteins compared with that in control cells. Melatonin at 100 microM had no such effect. The levels of the mRNA transcripts for ICH-1L relative to those for ICH-1S were significantly decreased in cultures treated with 100 microM flupirtine or 100 microM melatonin when compared with levels in control cells. However, the effect of flupirtine was greater than that of melatonin. Ten micromolar ascorbate and 5 microM iron stimulated the formation of ROS in chick retinal cell dissociates. Ascorbate, melatonin, and flupirtine (all at 100 microM) blunted this response in the order flupirtine > melatonin >> ascorbate. Luzindole had no effect, alone or in the presence of melatonin. CONCLUSIONS: The presented data show that melatonin counteracted ischemia-induced apoptosis in human RPE cells by a process that seemed to be independent of melatonin receptors. Moreover, melatonin and flupirtine counteracted iron-ascorbate-induced ROS formation and decreased the ratio of mRNA for ICH-1L and ICH-1S. However, melatonin was less potent than flupirtine in its action in each case, which suggests that either the two compounds act on different signaling pathways or that they act on the same pathway with differing potency. The failure to detect an effect of melatonin on the levels of Bcl-2, ICH-1L, and TIAR proteins when compared with the effect of flupirtine was probably caused by the sensitivity of the procedures. It is suggested that substances that can prevent ROS formation can potentially nullify apoptotic cell death, but this is difficult to detect experimentally when the substance has only a mild effect, such as in the case of ascorbate.

Agonist-induced effects on cyclic AMP metabolism are affected in pigment epithelial cells of the Royal College of Surgeons rat.

Recent work has demonstrated that stimulation of cAMP production via A2-adenosine receptors is reduced in cultured retinal pigment epithelial cells from the RCS rat. Cultured rat RPE cells are also shown to possess beta 2-adrenergic receptors positively coupled to cAMP production. Isoproterenol and salbutamol both stimulate cAMP levels with half maximal (EC50) values of 0.5 and 0.2 microM, respectively. Isoproterenol action is attenuated most effectively by the beta 2-antagonist, ICI 118551, while the beta 1-antagonist, CGP 20712A, is only partially effective. Isoproterenol-stimulated cAMP production is markedly reduced in the RCS rat RPE when compared to control cultures. In passaged RCS rat RPE cells cAMP stimulation by 10 microM isoproterenol was 6.4% of that by control cultures and in primary cultures it was around 75% of controls. The observed EC50 values were 0.4 and 1.3 microM for passaged control and RCS rat RPE cells, respectively. Melatonin negatively influences cAMP production in the RPE via Gi-proteins. Melatonin attenuated the action of forskolin by 51.1% in control rat RPE but only by 18.6% in the RCS rat RPE. The dose-response curve for melatonin shows an approximate 1000-fold shift in potency in the RCS rat. bFGF also has an inhibitory effect on rat RPE cells. bFGF (50ng/ml) attenuated forskolin-stimulated cAMP levels by 61.9% in control rat RPE but had not effect on the action of forskolin in RCS rat RPE. Serotonin (100 microM) potentiates the forskolin-induced stimulation of cAMP by 140.1%. However, unlike isoproterenol, melatonin and bFGF, the action of serotonin on adenylate cyclase appears normal in the RCS rat RPE. We conclude that the defect in the RCS rat RPE is likely to be due to impaired coupling of the components of the adenylate cyclase system and that this is most probably an abnormal interaction of adenylate cyclase with G-protein alpha-subunits.

Neuroprotection in relation to retinal ischemia and relevance to glaucoma.

Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP isjust an important risk factor in glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result from a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover, experimental studies show that betaxolol is an efficient neuro protective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally.

NMDA induces BDNF expression in the albino rat retina in vivo.

The effect of an intravitreal injection of NMDA on the expression of brain-derived neurotrophic factor (BDNF) in retinal ganglion cells was investigated in rats. Forty-eight hours after intravitreal injection of NMDA retinal ganglion cell BDNF immunoreactivity was practically obliterated, as was the choline acetyltransferase (ChAT) immunoreactivity associated with a subset of amacrine cells. However, 2h following treatment with NMDA the BDNF immunoreactivity and BDNF mRNA associated with the ganglion cells was enhanced while the amacrine cell ChAT immunoreactivity was clearly reduced and the levels of mRNA coding for rhodopsin and Thy-1 did not change. However, 4h after NMDA injection the increase in BDNF mRNA was now no longer apparent. The results show that synthesis of BDNF is increased in the ganglion cells immediately following an insult by NMDA. It is suggested that this is a natural protective mechanism of rat retinal ganglion cells.

Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx.

The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified.

Photoreceptors are preferentially affected in the rat retina following permanent occlusion of the carotid arteries.

Carotid artery occlusion (two vessel occlusion; 2-VO) for 3 or 9 months causes a suppression of the electroretinogram. However, after 3 months the retinal morphology appears unaffected judging from the localisation of GABA, ChAT, alpha PKC, Thy-1 and GFAP immunoreactivities. Moreover, no difference in NMDA-R1, opsin or Thy-1 mRNA levels were detected. In contrast, after 9 months 2-VO photoreceptor degeneration occurred as indicated by thinning of the outer nuclear layer and reduced Ret-P1 immunoreactivity. All other immunoreactivities appeared normal. These findings were supported by analysis of retinal mRNA levels. We conclude that the major effect of prolonged 2-VO is photoreceptor degeneration.

Exercise and immunology.

The documented effects of physical activity on host defense date to the early 1900s, although the influences of exercise on infectious and neoplastic disease susceptibility in healthy persons have long been subject to widespread disagreement. Even less is known of the effects of exercise in reducing illness predilection for persons already susceptible to, or afflicted by, immune disease or dysfunction. Recently, however, reports suggest that exercise may reduce the incidence and severity of infection. These reports have been bolstered by well-conducted epidemiologic and laboratory studies demonstrating a link between moderate exercise and either heightened immune function or reduced disease incidence, a relationship that is reversed in instances of immoderate exercise. This symposium will present current information addressing beneficial and detrimental influences of exercise on immune function and disease susceptibility. The authors will emphasize direct effects of acute exercise and physical training on immune cells and their neuroendocrine/immune modulators. The relationship among exercise, infection susceptibility, and immune system function will be highlighted, as well as exercise-induced activation of, and illness/disease regulation by, natural killer cells. Consequences of exercise on immune function and disease advancement will be addressed for persons with neoplasia, autonomic dysfunction, aging-related immunosenescence, and AIDS.

Immune responses to nervous system decentralization and exercise in quadriplegia.

Interactions among the nervous, neuroendocrine, and immune systems render host defenses highly sensitive to autonomic over- or understimulation. Persons with quadriplegia experience decentralization of directly innervated immune tissues and neuroendocrine axis dysregulation, immobilization deconditioning, heightened exposure to immune suppressing xerobiologicals, and psychic and nonpsychic stressors differing from those of nondisabled cohorts. When compared with matched nondisabled controls, young survivors of quadriplegia have reduced CD4:CD8 ratios, suppressed proliferative responses to mitogen challenge, reduced number and cytotoxicity of CD3-CD56+ (NK) cells, and elevation of the soluble IL-2 receptor. Deviations from control values are typically observed in persons with injuries higher than sympathetic outflow, suggesting a cause related to autonomic dysfunction. Cycling exercise performed by persons with quadriplegia using computer-sequenced electrically stimulated contraction of the quadriceps, hamstring, and gluteus muscle groups fails to provoke an archetypical leukocytosis, but transitionally elevates NK cell number and cytotoxicity lasting one-half hour after exercise. These findings show that the immune system of persons with quadriplegia is selectively responsive to exercise challenge. As opportunistic infections of the urinary tract, lungs, and skin are major causes of morbidity in survivors of quadriplegia, these observations may identify a treatment through which their host defenses can be fortified.

Circuit training provides cardiorespiratory and strength benefits in persons with paraplegia.

PURPOSE: This study tested the safety and the effects of circuit resistance training (CRT) on peak upper extremity cardiorespiratory endurance and muscle strength in chronic survivors of paraplegia due to spinal cord injury. METHODS: Ten men with chronic neurologically complete paraplegia at the T5-L1 levels participated in the study. Subjects completed 12 wk of CRT, using a series of alternating isoinertial resistance exercises on a multi-station gym and high-speed, low-resistance arm ergometry. Peak arm ergometry tests, upper extremity isoinertial strength testing, and testing of upper extremity isokinetic strength were all performed before and after training. RESULTS: None of the subjects suffered injury from exercise training. Significant increases were observed in peak oxygen consumption (29.7%, P < 0.01), time to fatigue (P < 0.01), and peak power output during arm testing (P < 0.05). Significant increases in isoinertial strength for the training maneuvers ranged from 11.9% to 30% (Ps < 0.01). Significant increases in isokinetic strength were experienced for shoulder joint internal rotation, extension, abduction, adduction, and horizontal adduction (Ps < 0.05). CONCLUSION: Chronic survivors of paraplegia safely improve their upper extremity cardiorespiratory endurance and muscle strength when undergoing a short-term circuit resistance training program. Gains in fitness and strength exceeded those usually reported after either arm endurance exercise conditioning or strength training in this subject population.