Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO- binding mode.

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+ complexes, the NO- binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]- complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO- binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.

The Management of Stroke Rehabilitation: A Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Description: In June 2019, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved an update of the joint clinical practice guideline for rehabilitation after stroke. This synopsis summarizes the key recommendations from this guideline. Methods: In February 2018, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and stroke survivors and conformed to the National Academy of Medicine (formerly the Institute of Medicine) tenets for trustworthy clinical practice guidelines. The guideline panel identified key questions, systematically searched and evaluated the literature, and developed 2 algorithms and 42 key recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Stroke survivors and their family members were invited to share their perspectives to further inform guideline development. Recommendations: The guideline recommendations provide evidence-based guidance for the rehabilitation care of patients after stroke. The recommendations are applicable to health care providers in both primary care and rehabilitation. Key features of the guideline are recommendations in 6 areas: timing and approach; motor therapy; dysphagia; cognitive, speech, and sensory therapy; mental health therapy; and other functions, such as returning to work and driving.

The use of laboratory sand, soil and crushed-glass filter columns for polishing domestic-strength synthetic wastewater that has undergone secondary treatment.

The aim of this study was to examine the performance of intermittently loaded, 150 mm-diameter stratified filter columns of 2 depths (0.65 and 0.375 m) comprising different media--sand, crushed glass and soil--in polishing the effluent from a laboratory horizontal flow biofilm reactor (HFBR) treating synthetic domestic-strength wastewater. The HFBR has been successfully used to remove organic carbon and ammonium-nitrogen (NH4-N) from domestic wastewater. In this treatment method, wastewater is allowed to flow over and back along a stack of polyvinyl chloride (PVC) sheets. Biofilms on the sheets reduce organic carbon, suspended matter, and nutrients in the wastewater, but to achieve the quality of a septic tank system, additional treatment is required. In all filters, at a hydraulic loading rate of 100 L m(-2) d(-1), 40-65% of chemical oxygen demand (COD) and practically 100% of total suspended solids (TSS) were removed, nitrification was complete, and bacterial numbers were reduced by over 80%, with best removals achieved in the soil filters (93%). Soil polishing filters with the depth of 0.65 m performed best in terms of organic carbon, total nitrogen (Tot-N) and bacterial removal. Data from this preliminary study are useful in the design of treatment systems to polish secondary wastewaters with similar water quality characteristics.

Alitretinoin for the treatment of severe chronic hand eczema.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer's model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Determining phosphorus and sediment release rates from five Irish tillage soils.

The aim of this study was to compare the nutrient and sediment releases from five Irish tillage soils, inclined at 10- and 15-degree slopes, under a simulated rainfall intensity of 30 mm h(-1) in a controlled laboratory study. Using the relationship between soil test phosphorus (STP) in the five soils and the dissolved reactive phosphorus (DRP) released in surface runoff, a runoff dissolved phosphorus risk indicator (RDPRI) was developed to identify the STP level for Irish tillage soils above which there may be a potential threat to surface water quality. The results of this study indicated that tillage soils may produce surface runoff P concentrations in excess of 30 microg L(-1) (the value above which eutrophication of rivers is likely to occur and the maximum allowable concentration of DRP in rivers under the EU Water Framework Directive, WFD) if their Morgan's phosphorus (P(m)), Mehlich 3 phosphorus (M3-P), and water extractable phosphorus (WEP) concentrations exceed 9.5 mg L(-1), 67.2 mg kg(-1), and 4.4 mg kg(-1), respectively. This work reinforces the statutory agronomic based requirements of the European Communities (Good Agricultural Practice for Protection of Waters) Regulations 2009 (S.I. no. 101 of 2009). A statistical analysis showed that WEP gave the best prediction for runoff DRP.

Use of ochre from an abandoned metal mine in the south east of Ireland for phosphorus sequestration from dairy dirty water.

Ochre found at coal mine drainage sites in the United Kingdom shows a high phosphorus (P) retention capacity with little mobilization of metals. This indicates that ochre has the potential to adsorb P from agricultural wastewaters for possible use as a fertilizer. Little research has focused on the ability of metal mine ochre to sequester P in an environmentally sustainable way. Untreated acid mine drainage from an abandoned copper-sulfur mine in the Avoca-Avonmore catchment in the south east of Ireland results in extensive low-value ochre deposition. In this study, P-amended water (50 mL) was mixed with this ochre (2.5 g) in batch experiments, and a maximum P adsorption capacity, calculated from the Langmuir equation, of between 16 and 21 g P kg(-1) was calculated. However, mobilization of heavy metals from Avoca ochre in distilled, surface, and dirty water batch experiments was observed. This mobilization may inhibit ochre's use in P removal from wastewaters.

Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

OBJECTIVES: To determine the safety, clinical effectiveness and cost-effectiveness of radio frequency catheter ablation (RCFA) for the curative treatment of atrial fibrillation (AF) and typical atrial flutter. DATA SOURCES: For the systematic reviews of clinical studies 25 bibliographic databases and internet sources were searched in July 2006, with subsequent update searches for controlled trials conducted in April 2007. For the review of cost-effectiveness a broad range of studies was considered, including economic evaluations conducted alongside trials, modelling studies and analyses of administrative databases. REVIEW METHODS: Systematic reviews of clinical studies and economic evaluations of catheter ablation for AF and typical atrial flutter were conducted. The quality of the included studies was assessed using standard methods. A decision model was developed to evaluate a strategy of RFCA compared with long-term antiarrhythmic drug (AAD) treatment alone in adults with paroxysmal AF. This was used to estimate the cost-effectiveness of RFCA in terms of cost per quality-adjusted life-year (QALY) under a range of assumptions. Decision uncertainty associated with this analysis was presented and used to inform future research priorities using the value of information analysis. RESULTS: A total of 4858 studies were retrieved for the review of clinical effectiveness. Of these, eight controlled studies and 53 case series of AF were included. Two controlled studies and 23 case series of typical atrial flutter were included. For atrial fibrillation, freedom from arrhythmia at 12 months in case series ranged from 28% to 85.3% with a weighted mean of 76%. Three RCTs suggested that RFCA is more effective than long-term AAD therapy in patients with drug-refractory paroxysmal AF. Single RCTs also suggested superiority of RFCA over electrical cardioversion followed by long-term AAD therapy and of RFCA plus AAD therapy over AAD maintenance therapy alone in drug-refractory patients. The available RCTs provided insufficient evidence to determine the effectiveness of RFCA beyond 12 months or in patients with persistent or permanent AF. Adverse events and complications were generally rare. Mortality rates were low in both RCTs and case series. Cardiac tamponade and pulmonary vein stenosis were the most frequently recorded complications. For atrial flutter, freedom from arrhythmia at 12 months in case series ranged from 85% to 92% with a weighted mean of 88%. Neither of the atrial flutter RCTs reported freedom from arrhythmia at 12 months. One RCT found a statistically significant benefit favouring ablation over AADs in terms of freedom from arrhythmia at a mean follow-up of 22 months. A second RCT reported a more modest effect favouring ablation in terms of freedom from atrial flutter at follow-up in older patients (mean age 78 years) after their first episode of flutter. In the atrial flutter case series, mortality was rare and the most frequent complications were atrioventricular block and haematomas. Complications in the RCTs were similar, except for those events likely to have been caused by AAD therapy (e.g. thyroid dysfunction). The review of cost-effectiveness evidence found one relevant study, which from a UK NHS perspective had a number of important limitations. The base-case analysis in the decision model demonstrated that if the quality of life benefits of RFCA are maintained over the remaining lifetime of the patient then the cost-effectiveness of RFCA appears clear. These findings were robust over a wide range of alternative assumptions, being between 7763 and 7910 pounds per additional QALY with very little uncertainty. If the quality of life benefits of RFCA are assumed to be maintained for no more than 5 years, cost-effectiveness of RFCA is dependent on a number of factors. Estimates of cost-effectiveness that explored the influence of these factors ranged from 23,000 to 38,000 pounds per QALY. CONCLUSIONS: RFCA is a relatively safe and efficacious procedure for the therapeutic treatment of AF and typical atrial flutter. There is some randomised evidence to suggest that RFCA is superior to AADs in patients with drug-refractory paroxysmal AF in terms of freedom from arrhythmia at 12 months. RFCA appears to be cost-effective if the observed quality of life benefits are assumed to continue over a patient's lifetime. However, there remain uncertainties around longer-term effects of the intervention and the extent to which published effectiveness findings can be generalised to 'typical' UK practice. All catheter ablation procedures for the treatment of AF or atrial flutter undertaken in the UK should be recorded prospectively and centrally and measures to increase compliance in recording RFCA procedures may be needed. This would be of particular value in establishing the long-term benefits of RFCA and the true incidence and impact of any complications. Collection of appropriate quality of life data within any such registry would also be of value to future clinical and cost-effectiveness research in this area. Any planned multicentre RCTs comparing RFCA against best medical therapy for the treatment of AF and/or atrial flutter should be conducted among 'non-pioneering' centres using the techniques and equipment typically employed in UK practice and should measure relevant outcomes.

Nutrient removal from slaughterhouse wastewater in an intermittently aerated sequencing batch reactor.

The performance of a 10 L sequencing batch reactor (SBR) treating slaughterhouse wastewater was examined at ambient temperature. The influent wastewater comprised 4672+/-952 mg chemical oxygen demand (COD)/L, 356+/-46 mg total nitrogen (TN)/L and 29+/-10 mg total phosphorus (TP)/L. The duration of a complete cycle was 8 h and comprised four phases: fill (7 min), react (393 min), settle (30 min) and draw/idle (50 min). During the react phase, the reactor was intermittently aerated with an air supply of 0.8L/min four times at 50-min intervals, 50 min each time. At an influent organic loading rate of 1.2g COD/(Ld), average effluent concentrations of COD, TN and TP were 150 mg/L, 15 mg/L and 0.8 mg/L, respectively. This represented COD, TN and TP removals of 96%, 96% and 99%, respectively. Phase studies show that biological phosphorus uptake occurred in the first aeration period and nitrogen removal took place in the following reaction time by means of partial nitrification and denitrification. The nitrogen balance analysis indicates that denitrification and biomass synthesis contributed to 66% and 34% of TN removed, respectively.

The performance of fibrous peat biofilters in treating domestic strength wastewater.

Peat is an abundant resource in Ireland and has the capacity to be used in low-cost, low-maintenance wastewater treatment systems for single houses. In this study four fibrous peat columns, of varying depths were constructed and tested in the laboratory for their capacity to remove contaminants from domestic-strength synthetic wastewater. The four filters had peat depths of 0.3 m, 0.6 m, 0.9 m and 1.2 m. During the 360 day study the filters were intermittently loaded with domestic strength synthetic wastewater at a hydraulic loading rate of 180 l/m2cd. Hydrographs and residence times for each filter were examined as was their ability to remove impurities from the wastewater. Removal of 5-day biochemical oxygen demand (BOD5) and total chemical oxygen demand (CODt) were > or =96% and 84%, respectively, in all filters with almost complete nitrification (> or =99%) being recorded for each filter. The removal of total suspended solids (TSS) was excellent at > or =94% and no clogging was recorded on any filter during the study. For the 0.6 m, 0.9 m and 1.2 m deep filters, total viable counts (TVC) were less than EU surface water directive limits for Class A2 potable water sources. The systems were cheap to construct and very easy to maintain.

The efficiency of a sequencing batch biofilm reactor in organic carbon and phosphorus removal.

A laboratory sequencing batch biofilm reactor (SBBR), operated for a period of 158 days, was used to treat domestic-strength synthetic effluent. The biofilm reactor comprised a bulk fluid reactor, a biofilm plastic module, a synthetic wastewater feed tank, and pneumatic devices with pneumatic controls. The reactor cycle time was 8 h, and its operation consisted of five phases: feeding (59 min), mixing (1 min), anoxic/anaerobic (3 h), aerobic (3 h), and settling (1 h). At total chemical oxygen demand (CODT) loading rates of 8.8 g CODT m(-2) d(-1) and 1.2 kg CODT m(-3) d(-1), expressed in terms of the plastic module surface area and reactor volume, respectively, the SBBR had average removal rates of 8.3 g CODT m(-2) d(-1) and 1.1 kg CODT m(-3) d(-1), or 94%. Total orthophosphorus (PO4-PT) and filtered orthophosphorus (PO4-PF) removals were 44% and 50%, respectively.

Nutrient removal in a sequencing batch biofilm reactor (SBBR) using a vertically moving biofilm system.

In this paper, the performance of a sequencing batch biofilm reactor (SBBR) using an anoxic/anaerobic phase followed by an aerobic phase for nutrient removal from wastewater was investigated. In the laboratory SBBR unit, biofilm was grown on a plastic biofilm media module, which was vertically moved up into the air and down into the bulk fluid during the aerobic phase. The vertical movement of the biofilm module supplied oxygen to the microorganisms. The module was submerged in the wastewater during the anoxic/anaerobic phase. The percentage removals of total chemical oxygen demand (COD), total nitrogen (TN) and soluble orthophosphate (PO4-P) were 95.4%, 68.3% and 89.5% respectively at influent concentrations of COD 773 mg l(-1), TN 49.9 mg l(-1) and PO4-P 16.5 mg l(-1). The effluent COD was 35 mg l(-1), NH4-N 10.2 mg l(-1), NO3-N 5.5 mg l(-1), soluble PO4-P 1.7 mg l(-1) and suspended solids (SS) 19 mg l(-1).

Pharmacokinetic and phototherapeutic properties of axially substituted Si(IV)-tetradibenzobarreleno-octabutoxyphthalocyanines.

Three Si(IV)-tetradibenzobarreleno-octabutoxyphthalocyanines (TDiBOPcs) bearing different axial ligands on the metal ion were studied for their tumour-localizing and-photosensitizing properties after i.v. injection via a Cremophor emulsion (0.35 mumol kg-1 b.w.) to Balb/c mice bearing an intramuscularly implanted MS-2 fibrosarcoma. In all cases, the maximum tumour accumulation of the photosensitizer (0.8-1.9 nmol g-1 of tissue) was found at 24 h after injection. The efficiency and selectivity of tumour targeting appeared to be dependent on the nature of the axial ligands; optimal values of these parameters were obtained in the case of the bis(trihexyl-siloxy)-substituted Si(IV)-TDiBOPc, which gave a 7-9 tumour/muscle ratio of phthalocyanine concentration at 24-48 h after injection. The extent of tumour response to PDT treatment was correlated with the concentration of the photosensitizer in the tumour tissue: upon 740 nm irradiation (180 mW cm-2, 200 J cm-2) at 48 h after injection of 0.35 mumol kg-1 of Si(IV)-TDiBOPc-C6H13, the tumour growth exhibited a delay of about 7 days.

Tibial bone density loss in spinal cord injured patients: effects of FES exercise.

A group of 37 spinal cord injured (SCI) patients underwent bone density measurements at the distal and proximal end of the tibia by a special computed tomography scanner, the OsteoQuant. Fifteen of these patients had follow-up measurements while enrolled in a lower-limb exercise training program with functional electrical stimulation (FES). The pre-exercise measurements revealed a strong correlation (0.88 < or = r < or = 0.90) of trabecular, subcortical, and cortical bone density between the distal and proximal ends of the tibia. The expected bone density loss during the first two years post injury (as calculated from the regression lines of bone density vs. time post injury) amounted to 51.5% for trabecular, 44.2% for subcortical, and 32.7% for cortical bone. No major bone density loss was calculated after 7 years post injury. Analysis of the bone density data during the FES exercise program revealed various degrees of loss. However, the rate of bone loss for this FES exercise group was less than expected from the regression lines. The reduction of bone loss was between 0.2 and 3.3% per year, and was significant (p < 0.05) for all bone parameters at the distal end and for trabecular bone density at the proximal end of the tibia. These bone density measurements revealed a potentially positive effect of FES exercise intervention for the rehabilitation of SCI patients.

The effects of functional electrical stimulation on shoulder subluxation, arm function recovery, and shoulder pain in hemiplegic stroke patients.

The purpose of this study was to evaluate the effectiveness of a functional electrical stimulation (FES) treatment program designed to prevent glenohumeral joint stretching and subsequent subluxation and shoulder pain in stroke patients. Twenty-six recent hemiplegic stroke patients with shoulder muscle flaccidity were randomly assigned to either a control group (n = 13; 5 female, and 8 male) or experimental group (n = 13; 6 female, and 7 male). Both groups received conventional physical therapy. The experimental group received additional FES therapy where two flaccid/paralyzed shoulder muscles (supraspinatus and posterior deltoid) were induced to contract repetitively up to 6 hours a day for 6 weeks. Duration of both the FES session and muscle contraction/relaxation ratio were progressively increased as performance improved. The experimental group showed significant improvements in arm function, electromyographic activity of the posterior deltoid, range of motion, and reduction in subluxation (as indicated by x-ray) compared with the control group. We concluded that the FES program was effective in reducing the severity of shoulder subluxation and pain, and possibly facilitating recovery of arm function.

Microsomally associated heme proteins from French bean: characterization of the cytochrome P450 cinnamate-4-hydroxylase and two peroxidases.

Three heme-containing proteins of M(r) 57,000, 46,000, and 42,000 have been isolated from microsomes of elicitor-treated suspension-cultured cells of French bean. Following purification to homogeneity they were shown to be distinct with respect to amino acid and sugar compositions. The M(r) 57,000 protein proved to be the cytochrome P450 cinnamate-4-hydroxylase (CYP 73), by immunopurification and characterization. The M(r) 46,000 showed peroxidative activity toward guaiacol and all substituted phenylpropanoids tested and also gave a form of binding spectrum with cinnamic acid. The M(r) 42,000 had peroxidative activity toward guaiacol and a similar apparent binding spectrum to the M(r) 46,000 protein but was less active toward hydroxylated and methoxylated phenylpropanoids. The two peroxidases had cationic pIs and were distinct proteins rather than glycosylated or proteolytic variants.

Partial purification of Golgi-bound arabinosyltransferase and two isoforms of xylosyltransferase from French bean (Phaseolus vulgaris L.).

The purification of glycosyltransferases involved in wall matrix polysaccharide synthesis has been attempted. A number of activities readily demonstrated in isolated Golgi membranes are lost following detergent solubilization. However, solubilization releases pyrophosphorylases and phosphatases that hydrolyse the substrate in enzyme assays, whether UDP-glucose, -arabinose or -xylose is used. This hydrolysis, which cannot be completely inhibited, appears to be the major factor in the apparent loss of activity. Separation of this hydrolytic activity during further purification by ion-exchange and gel exclusion leads to recovery of glycosyltransferase activity. Thus two xylosyltransferases and one arabinosyltransferase could be partially purified. These appeared to be differentially expressed. The arabinosyltransferase of apparent M(r) 70,000 on size-exclusion chromatography was isolated from cells undergoing rapid growth and division. A xylosyltransferase of apparent M(r) 38,000 on size-exclusion chromatography was associated with cell expansion and primary wall synthesis. A second xylosyltransferase, which was purified to near homogeneity with M(r) 40,000, showed a peak of activity during the period of maximum secondary wall synthesis.

Physiologic effects of electrical stimulation leg cycle exercise training in spinal cord injured persons.

The purpose of this study was to assess the physiologic training effects of functional electrical stimulation leg cycle ergometer (FES-LCE) exercise in persons with spinal cord injury (SCI) who were previously untrained in this activity. Ten persons with quadriplegia (C5 to C7) and eight with paraplegia (T4 to T11) performed FES-LCE training on an ERGYS I ergometer 10 to 30 minutes per day, 2 or 3 days per week for 12 to 16 weeks (36 total sessions). Training session power output (PO) ranged from 0.0W (no external resistance) to 30.6W. Each subject completed discontinuous graded FES-LCE and arm crank ergometer (ACE) tests before and after training for determinations of peak lower and upper extremity metabolic, pulmonary, and hemodynamic responses. Compared with pretraining, this SCI group exhibited significantly (p less than or equal to .05) higher posttraining peak PO (+45%), oxygen uptake ([O2], + 23%), pulmonary ventilation (+27%), heart rate (+11%), cardiac output ([Qt], + 13%) and significantly lower total peripheral resistance ([TPR], - 14%) during FES-LCE posttests. There were no significant changes in peak stroke volume (+6%), mean arterial pressure ([MAP], - 5%), or arteriovenous oxygen difference ([a-vO2diff], + 10%) during posttraining FES-LCE tests. In addition, no significant differences were noted for the peak level of any monitored variable during ACE posttests after FES-LCE training. The rise in total vascular conductance, implied by the significant decrease in posttraining TPR during FES-LCE tests, denotes that a peripheral circulatory adaptation developed in the persons with SCI during FES-LCE exercise training.(ABSTRACT TRUNCATED AT 250 WORDS)

L-phenylalanine ammonia-lyase from French bean (Phaseolus vulgaris L.). Characterization and differential expression of antigenic multiple Mr forms.

L-Phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) purified from suspension-cultured cells of French bean (Phaseolus vulgaris) has been further characterized. A number of techniques, including use of an antiserum and affinity probes, have established that all the antigenic polypeptides represent polymorphic Mr forms of the enzyme. These peptides include an apparently higher-Mr (83,000) form which shows different kinetics of induction from the Mr-77000 forms that have been extensively characterized previously. The larger subunit appeared to be PAL by the following criteria: (a) binding to specific affinity and antibody matrices; (b) peptide mapping; (c) active-site labelling; and (d) amino acid composition. The increased Mr of the larger subunit was not completely attributable to glycosylation, although some sugar residues were detected in this Mr-83000 form but not in the other Mr forms. Mr-83000 subunits were also immunoprecipitated from translations in vitro of mRNA from cells that had been stressed for a long period. They were also detected in leaf tissues that were not yet undergoing an extensive wound response. This form of the enzyme may be constitutive and involved in the low-level accumulation of phenolics in most cell types. By contrast, the Mr-77000 forms of PAL were rapidly induced during elicitor action, wounding or cytokinin-induced xylogenesis as a key regulatory enzyme involved in the synthesis of phenolics under stress conditions or during differentiation.

Physiologic responses to prolonged electrically stimulated leg-cycle exercise in the spinal cord injured.

This study determined the physiologic responses to prolonged functional neuromuscular stimulation (FNS) leg-cycle exercise in seven quadriplegic and seven paraplegic subjects. Each subject completed 30 minutes of continuous FNS leg cycling during which open-circuit spirometry, impedance cardiography, auscultation, and fingertip capillary blood sampling were used to assess metabolic and hemodynamic responses. Compared with resting values, oxygen uptake, carbon dioxide production, respiratory exchange ratio (RER), pulmonary ventilation, heart rate (HR), left ventricular stroke volume (SV), cardiac output (Qt), and blood lactate (La) concentration were significantly (p less than .05) elevated, whereas plasma volume, bicarbonate concentration, and pH were significantly decreased in both groups during prolonged FNS leg-cycle exercise. Mean arterial pressure remained unchanged in quadriplegic and paraplegic subjects during the prolonged FNS leg-cycle exercise bout. Persons with quadriplegia elicited significantly lower MAP and tended to have lower SV and Qt responses than persons with paraplegia, probably due to a higher degree of sympathetic dysfunction and circulatory hypokinesis during FNS leg-cycle exercise. All other physiologic variables responded similarly between groups. We speculate that the relative increases observed for HR (33% to 60%), SV (45% to 69%), and Qt (113% to 142%) during prolonged FNS leg-cycle exercise create a sufficient cardiac-volume load to promote central cardiovascular conditioning in persons with both quadriplegia and paraplegia. The La accumulation (4.7 to 5.2 mmol.L-1) in the spinal cord injured during prolonged FNS leg cycling is unusually high for the power output attained (5.2W and 6.1W for quadriplegia and paraplegia, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)