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Objective: While Cyclosporine A (CsA) is an effective therapy for nephrotic syndrome, it has nephrotoxic side effects. We comparatively tested Mycophenolate mofetil (MMF), as to its antiproteinuric effects and nephrotoxicity in rats with passive Heymann nephritis (PHN). Methods: PHN was induced in female Wistar rats. Two treatment groups consisting of eight rats each received either 25 mg of CsA or 25 mg of MMF/kg body weight/day and were compared with untreated controls. Kidney function and proteinuria were monitored over four weeks. Western blots were used for densitometrical analysis of renal cycloxygenase-2 (COX-2) protein expression. Thromboxane B2 (TxB2) and 6-keto-PGF1a were determined by radioimmunoassays (RIA) in renal tissue and urine. Results: Rats with PHN exhibited a marked proteinuria of 12.76mg ± 4.42/24 h vs. 0.73 ± 0.28 mg/24 h (p < 0.01) and showed increased glomerular concentrations of TxB2 and 6-keto-PGF1a ± (992.6 ± 216.9 rsp. 1,187.0 ± 54.2 pg/mg/protein) as compared to healthy controls (595 ± 196.17 rsp. 729 ± 297.84) and a strongly induced COX-2 protein expression. CsA and MMF treatment comparatively reduced PHN-related proteinuria to 2.10 ± 1.47 mg/24 h rsp. 1.47 ± 7.2 mg/24 h. In rats with PHN, CsA induced a significant deterioration of renal function and enhanced urine excretion of thromboxane A2, paralleled by a significant, 2-fold increase in COX-2 protein expression and renal prostaglandins. In contrast, MMF treatment in rats with PHN was not nephrotoxic and had no effect on prostaglandin production. COX-2 protein expression under MMF was suppressed. Conclusions: While the antiproteinuric efficacy of MMF and CsA in PHN was comparable, the absence of nephrotoxicity might favor MMF in the treatment of nephrotic syndrome. The CsA-induced increase of COX-2 expression and COX-2 dependent prostacyclin may indicate a mechanism compensatory to nephrotoxicity in the diseased and CsA-exposed kidney. [ABSTRACT FROM AUTHOR]

Laser scribing with nanosecond (ns) diode pumped solid-state laser sources is the industry standard in the fabrication of silicon-based thin-film photovoltaic (TFPV) modules. Reducing the interconnection area is one of the on-going challenges for the next generation of TFPV modules. In this regard, replacing ns laser sources by picosecond (ps) laser sources is one of the logical steps. Ps-laser pulses reduce the heat-affected zones compared to ns pulses, and thus enable a reduction of the interconnection zone. This work describes the substrate-side ablation of fluorine-doped tin oxide, amorphous silicon (a-Si:H) and a-Si:H with an aluminum layer on top, using a 10-ps laser with a wavelength of 1064 nm. The investigation of single-pulse ablation and trench scribing demonstrates that the complete monolithic interconnection can be achieved at the fundamental wavelength. In addition, the evaluation of the ablation efficiency shows that the best trench quality is achieved at the efficiency maximum. [ABSTRACT FROM AUTHOR]

Background: Normothermic ex vivo liver perfusion (NEVLP) is an exciting strategy to preserve livers prior to transplant, however, the effects of NEVLP on the phenotype of tissue-resident immune cells is largely unknown. The presence of tissue-resident memory T cells (TRM) in the liver may protect against acute rejection and decrease allograft dysfunction. Therefore, we investigated the effects of NEVLP on liver TRMs and assessed the ability of anti-inflammatory cytokines to reduce TRM activation during NEVLP., Methods: Rat livers underwent NEVLP with or without the addition of IL-10 and TGF-β. Naïve and cold storage livers served as controls. Following preservation, TRM T cell gene expression profiles were assessed through single cell RNA sequencing (scRNA-seq). Differential gene expression analysis was performed with Wilcoxon rank sum test to identify differentially expressed genes (DEGs) associated with a specific treatment group. Using the online Database for Annotation, Visualization and Integrated Discovery (DAVID), gene set enrichment was then conducted with Fisher's exact test on DEGs to highlight differentially regulated pathways and functional terms associated with treatment groups., Results: Through scRNA-seq analysis, an atlas of liver-resident memory T cell subsets was created for all livers. TRM T cells could be identified in all livers, and through scRNA-seq, DEG was identified with Wilcoxon rank sum test at FDR < 0.05. Based on the gene set enrichment analysis of DEGs using Fisher's exact test, NEVLP is associated with downregulation of multiple gene enrichment pathways associated with surface proteins. Furthermore, NEVLP with anti-inflammatory cytokines was associated with down regulation of 52 genes in TRM T cells when compared to NEVLP alone (FDR <0.05), most of which are pro-inflammatory., Conclusion: This is the first study to create an atlas of liver TRM T cells in the rat liver undergoing NEVLP and demonstrate the effects of NEVLP on liver TRM T cells at the single cell gene expression level., Competing Interests: Declaration of competing interest Nothing to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are major contributors to immunological responses following solid organ transplantation. Donor derived EVs are best known for their role in transplant rejection through transferring donor major histocompatibility complex proteins to recipient antigen presenting cells, a phenomenon known as ‛cross-decoration'. In contrast, donor liver-derived EVs are associated with organ tolerance in small animal models. Therefore, the cellular source of EVs and their cargo could influence their downstream immunological effects. To investigate the immunological effects of EVs released by the liver in a physiological and transplant-relevant model, we isolated EVs being produced during normothermic ex vivo liver perfusion (NEVLP), a novel method of liver storage prior to transplantation. We found EVs were produced by the liver during NEVLP, and these EVs contained multiple anti-inflammatory miRNA species. In terms of function, liver-derived EVs were able to cross-decorate allogeneic cells and suppress the immune response in allogeneic mixed lymphocyte reactions in a concentration-dependent fashion. In terms of cytokine response, the addition of 1 × 10 9 EVs to the mixed lymphocyte reactions significantly decreased the production of the inflammatory cytokines TNF-α, IL-10 and IFN-γ. In conclusion, we determined physiologically produced liver-derived EVs are immunologically regulatory, which has implications for their role and potential modification in solid organ transplantation., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Aims: This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys., Methods: Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment., Results: On stainless steel, both nonactivated and activated cell groups were shown to have a significant increase in metal ion release for Cr, Fe, and Ni (p < 0.001, p = 0.002, and p = 0.020 respectively) compared with medium only and showed macrophage-sized corrosive pits on the stainless steel surface. On titanium alloy discs there was a significant increase in aluminum (p < 0.001) among all groups compared with medium only., Conclusion: These results indicated that macrophages were able to attach to and affect the oxide surface of stainless steel and titanium alloy discs. Cite this article: Bone Joint J 2020;102-B(7 Supple B):116-121.

We investigated the quality of smoothness during human unipedal quiet stance. Smoothness is quantified by the time rate of change of the accelerations, or jerks, associated with the motion of the foot and can be seen as an indicative of how controlled the balance process is. To become more acquainted with this as a quantity, we wanted to establish whether or not it can be modeled as a (stationary) stochastic process and, if so, explore its temporal scaling behavior. Specifically, our study focused on the jerk concerning the center-of-pressure (COP) for each foot. Data were collected via a force plate for individuals attempting to maintain upright posture using one leg (with eyes open). Positive tests for stochasticity allowed us to treat the time series as a stochastic process and, given this, we took the jerk to be proportional to the increment of the force realizations. Detrended fluctuation analysis was the primary tool used to explore the scaling behavior. Results suggest that both the medial-lateral and anterior-posterior components of the jerk display persistent and antipersistent correlations which can be modeled by fractional Gaussian noise over three different temporal scaling regions. Finally, we discussed certain possible implications of these features such as a jerk-based control over the force on the foot's COP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Matthew R. Semak et al.)

Recently, inflammatory cell-induced corrosion (ICIC), a unique type of damage, has been reported in cobalt-chromium (CoCr) implants, but the mechanism remains poorly understood and controversial because electrocautery damage has also been shown to produce similar findings. This study aimed to distinguish between these two damage mechanisms. Forty-one CoCr primary total knee arthroplasty specimens were collected at time of necropsy. After removal and cleaning, light microscopy was used to identify areas of ICIC-like damage scars. A CoCr knee implant was intentionally damaged by electrocautery from both Bovie and Aquamantys sources using a 3-second hover method with 3 different energy settings for comparison to necropsy findings. Average roughness (Ra), max peak-to-valley height (Rmax), kurtosis (Rk), and skewness (Rsk) measurements were collected to represent the topography on the damaged areas for the CoCr implants. Necropsy implants showed signs of ICIC in 7 of 41 implants (17%) examined. Fe/C ratios of the Bovie electrocautery-damaged knee implant were shown to be statistically higher than those of necropsy-retrieved implants. Median Ra measurements were statistically less (P = 0.008) for Bovie-damaged areas compared to ICIC-dam-aged areas on CoCr. Median Rmax and Ra measurements were statistically less (P = 0.012, P < 0.001, respectively) for Aquamantys-damaged areas compared to ICIC-damaged areas on CoCr. While the visual patterns seen in necropsy-retrieved implants appeared similar to those with the intentionally damaged CoCrMo implant, the contents of the corroded regions are unique. The difference in roughness found on ICIC-damaged and electrocautery-damaged regions also indicates examination of surface topography as another distinguishing feature between the two mechanisms.

Psychological interventions can improve Quality of Life (QoL). Object of interest was if different psychological interventions influence short-term QoL after colonic resection for carcinoma. Furthermore, we wanted to see if there is a correlation between patients` preoperative affect and postoperative QoL. Sixty patients that underwent colorectal surgery were divided into three groups. Group one (n = 20) received Guided Imagery and group 2 (n = 22) Progressive Muscle Relaxation. The third group (Control, n = 18) had no intervention. Quality of Life (QoL) was measured using the EORTC QLQ-C30 and the Gastrointestinal Quality of life Index (GIQLI). Patients' affect was measured by the PANAS questionnaire. The higher the preoperative Negative Affect was, the lower were the scores for QoL on the 30th postoperative day. Patients' QoL was highest preoperatively and lowest on the third postoperative day. On the 30th postoperative day scores for QoL were almost as high as preoperative without difference between the three groups. Neither Guided Imagery nor Progressive Relaxation was influencing short-term QoL measured by the EORTC QLQ-C30 and the GIQLI questionnaire after colorectal surgery for cancer. Screening patients' with the PANAS questionnaire might help to identify individuals that are more likely to have a worse QoL postoperatively., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: The purpose of this research study was to determine whether specific local public health agency (LPHA) characteristics were associated with favorable county health status. Specifically, financial and administrative comparisons were made to determine whether variables such as budget size or number of employees, among others, were associated with community health status among the 120 counties in Kentucky. Other financial and administrative variables collected from LPHA data were also investigated in this study., Methods: Administrative and financial data were collected for each local public health agency in Kentucky. This was matched with data on the health status of Kentucky counties from the 2010 University of Wisconsin MATCH (Mobilizing Action Towards Community Health Assessment) counties in select measures of health. MATCH data used included measures of health outcomes, specifically socioeconomic status (SES), mortality, and morbidity. Logistic regressions were used to determine the relationship, if any, between variations in the health agency data variables, SES, and health status., Results: Analysis suggests that SES is the strongest link to county health status. Several other variables that appear to have statistically significant association with health status include the education level of the director, whether the LPHA employees received a raise, whether the LPHA had an associated Home Health agency, and the amount of money used from their reserve account to balance the LPHA budget., Conclusions: For many years, public health in Kentucky has measured the number of clinical visits and other LPHA services but failed to determine specific characteristics and variables that influence community health status. This study suggests that LPHAs in Kentucky can advance public health practice by having well-educated directors, giving annual incremental raises, and utilizing the agency reserve funds to meet budget shortfalls in the short run. Furthermore, LPHAs with an associated home health agency may need to reassess their impact and need in their community, considering the negative effect it may have on county health status.

Aims: We investigated whether a correlation exists between biomarkers of the neurohumoral system and clinical markers in grown-up patients with congenital heart disease (GUCH) and right ventricular function., Methods and Results: Prospective, cross-sectional, multicenter study of 104 GUCH patients (median) 16 years (range 6-43 years) after corrective surgery with RV pressure and/or volume overload and 54 healthy controls. Clinical, functional, and laboratory parameters were assessed. Natriuretic peptide levels were significantly increased in GUCH patients (NTproBNP 101 vs. 25 pg/ml, p < 0.001), but we observed no differences in norepinephrine, aldosterone, angiotensin II and Endothelin-1 levels. NTproBNP correlated significantly with clinical markers such as NYHA classification, prolonged QRS duration and reduced exercise capacity (VO(2) peak) (all p < 0.001), as well as self-reported quality of life (p < 0.001). MRI and echocardiography derived RV volumes were elevated and ejection fraction reduced in the patients (both p < 0.001). Tissue Doppler parameter showed significantly restricted ventricular longitudinal systolic function (longitudinal tricuspid valve movement, 1.7 vs. 2.3 cm, p < 0.001), suggesting stiffness and reduced RV compliance., Conclusion: In conclusion, grown-up patients with congenital right heart disease NTproBNP correlates well with various clinical markers of RV failure, such as prolongation of QRS duration, exercise capacity, echocardiography and MRI parameters, and quality of life.

Background: The purpose of this study was to determine the effect of mid-term mechanical circulatory support on the natriuretic hormone system in children and to assess whether such changes are associated with myocardial recovery., Methods: Serial blood samples were collected from 19 children (median age 10.8 years, range 0.2 to 17.5 years), all supported with a pulsatile ventricular assist device (Berlin Heart EXCOR; median support time 55 days). Levels of NT-proBNP were analyzed before and 7 and 30 days after device implantation. In addition, we determined levels of mid-region proANP (MR-proANP) and BNP in 13 of the 19 children., Results: The actuarial survival rate to discharge home was 84%. Two children could be weaned from the system, 14 reached heart transplantation, and 3 died during mechanical circulatory support. Serial measurements of NT-proBNP, BNP and MR-proANP showed a significant down-regulation of all three natriuretic peptides within the first week of support and a further decrease between Days 7 and 30. The lowest NT-proBNP level while on the device (250 pg/ml) was found in the child later weaned, who reached normal levels (71 pg/ml) within 12 weeks after weaning., Conclusions: Extremely high levels of natriuretic peptides reflect the severity of myocardial failure before device implantation. During mechanical support, the decline of natriuretic peptides appears to be a helpful additional tool in the pre-selection of potential weaning candidates.

Objective: Diaphragmatic palsy (DP) is a rare but severe complication after surgery for congenital heart disease. Transthoracic diaphragmatic plication is an effective means of treatment for those with respiratory impairment due to DP, but little is known about the mid-term effects of diaphragmatic plication., Design: We performed a study in 24 patients with history of DP. Diaphragm movement was assessed using ultrasound. Patients with DP who were old enough were additionally followed-up with lung function and exercise testing. A group of patients with similar age, diagnoses and operations served as controls., Results: Ultrasound showed that in the majority of cases with history of DP the paralysed diaphragm was static, independently of whether it was plicated or not. Patients with DP had a more restrictive lung function pattern (VC: 54.3 vs. 76.4% predicted, p<0.001; FEV(1): 58.4 vs. 86.2% predicted, p<0.001) and a lower exercise capacity compared with the control group (peak VO2: 24.5 vs. 31.3 ml/kg/min, p=0.03). Comparing patients with and without plication for DP, only a tendency towards lower lung function values in patients after diaphragmatic plication, but no differences regarding exercise capacity, could be found., Conclusions: Our results provide evidence that DP is a serious surgical complication with a reduction in lung function and exercise capacity, even at mid-term follow-up; however, diaphragmatic plication, a useful tool in treating post-surgical DP in children with respiratory impairment, seems to be without mid-term risk in terms of recovery of phrenic nerve function, lung function values, and exercise capacity.

Objective: We examined the clinical impact of diaphragmatic palsy (DP) as a result of phrenic nerve injury following cardiothoracic surgery, specifically its effects on morbidity and mortality, early regeneration capacity of the phrenic nerve, and role of surgical diaphragmatic plication., Methods: A retrospective case control study was performed in 74 children with DP and 74 matched controls after cardiothoracic surgery within the past 14 years., Results: Following 5,128 surgical procedures in children (aged under 18 years) we found an incidence of DP of 1.4%. There were no differences in mortality between the groups, and the cause of death was not related to DP or plication in any of the patients. However, patients with diaphragm impairment had significantly longer duration of mechanical ventilation (median 3 days vs. 1), ICU stay (7 days vs. 3.5), duration of hospital stay (16 days vs. 12), and for antibiotic treatment (16 days vs. 7). Because of prolonged respiratory problems 40 children (54%) underwent surgical diaphragmatic plication to flatten the diaphragm in its inspiratory position. In children with DP younger age was a strong predictor for plication (median 3.8 months vs. 12.1)., Conclusions: Especially in newborns and young infants with DP the length of mechanical ventilation, ICU stay, and hospital stay are prolonged. Early spontaneous recovery of the phrenic nerve is rare. In cases of respiratory impairment early transthoracic diaphragmatic plication is an effective means of treatment.

Background: While cyclosporine A (CsA) is an effective therapy for nephrotic syndrome, it has nephrotoxic side effects. We compared the anti-proteinuric effects and nephrotoxicity in rats with passive Heymann nephritis (PHN) of CsA and mycophenolate mofetil (MMF)., Methods: PHN was induced in female Wistar rats. Two treatment groups consisting of 8 rats each received either 25 mg of CsA or 25 mg of MMF/kg body weight/day and were compared with untreated controls. Kidney function and proteinuria were monitored over 4 weeks. Western blots were used for densitometric analysis of renal cyclooxygenase-2 (COX-2) protein expression. Thromboxane B2 (TxB2) and 6-keto-PGF(1alpha) were determined by radioimmunoassays (RIAs) in renal tissue and urine., Results: Rats with PHN exhibited a marked proteinuria of 12.76 +/- 4.42 vs. 0.73 +/- 0.28 mg/24 h (p < 0.01) and showed increased glomerular concentrations of TxB2 and 6-keto-PGF(1alpha) (992.6 +/- 216.9 and 1,187.0 +/- 54.2 pg/mg protein, respectively) compared with healthy controls (595 +/- 196.17 and 729 +/- 297.84, respectively) and a strongly induced COX-2 protein expression. CsA and MMF treatment reduced PHN-related proteinuria to 2.10 +/- 1.47 and 1.47 +/- 7.2 mg/24 h, respectively. In rats with PHN, CsA induced a significant deterioration of renal function and enhanced urine excretion of thromboxane A2, paralleled by a significant, twofold increase in COX-2 protein expression and renal prostaglandins. By contrast, MMF treatment in rats with PHN was not nephrotoxic and had no effect on prostaglandin production. COX-2 protein expression under MMF was suppressed., Conclusion: While the antiproteinuric efficacy of MMF and CsA in PHN was comparable, the absence of nephrotoxicity might favor MMF in the treatment of nephrotic syndrome. The CsA-induced increase in COX-2 expression and COX-2-dependent prostacyclin may indicate a mechanism that compensates nephrotoxicity in the diseased and CsA-exposed kidney.

Background: Cyclooxygenase-2 (COX-2), the inducible isoform of the cyclooxygenases, is upregulated in various inflammatory renal diseases and responsible for prostaglandin formation. As prostaglandins are known to influence cell adhesion processes, we investigated the effect of COX-2 inhibition on the expression of alpha(v) integrins, which are also enhanced in renal diseases and control the adherence between the endothelium and the extracellular matrix (ECM) in the glomerulus., Methods: Healthy female Wistar rats and animals with previously induced passive Heymann nephritis (PHN) received either 5 mg/kg body weight/day celecoxib or a placebo. After 28 days, renal cortical mRNA expression of COX-2 and alpha(v) integrin subunits was determined., Results: Rats with PHN showed a significant 1.7-fold increase in renal cortical mRNA expression of alpha(v) integrin subunits. Treatment with celecoxib increased cortical alpha(v) integrin mRNA expression 2.2-fold (p < 0.05) in healthy animals and 4.0-fold (p < 0.05) in rats with PHN, but lowered COX-2 mRNA expression in rats with PHN to 0.8-fold (p < 0.05). An inverse correlation between the expression of COX-2 and alpha(v) integrins in rats with PHN was demonstrated., Conclusions: It is suggested that COX-2-derived prostaglandins suppress the expression of alpha(v) integrins. This implies a previously unknown role for COX-2 in chronic inflammation in the kidney., (Copyright 2003 S. Karger AG, Basel)

It was hypothesized that certain ground reaction force (GRF) variables are positively correlated with running economy (RE; the aerobic demand at a single speed of running). Excessive momentum changes, quantified by linear impulse measures, as well the free moment applied to the running surface could be considered potentially wasteful efforts in terms of metabolic energy requirements. Recreational runners (n = 16) ran on a treadmill at 3.35 m.s-1 for physiological measurements and overground for biomechanical measurements. Correlation coefficients were calculated between RE and total vertical impulse (TVI), net impulses in three orthogonal directions, and descriptors of the free moment. The TVI and the net vertical impulse were the only GRF characteristics significantly correlated to RE (r = 0.62, r = 0.60, respectively). Greater overall muscle support requirements during ground contact, as represented by TVI, may have been responsible for greater aerobic demand.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce an inhibition of cyclooxygenase (COX), an enzyme that makes prostaglandins. Two isoforms of COX exist: COX-1 represents the constitutively expressed enzyme, whereas COX-2 is the inducible isoform. This study investigated the role of COX-2 in the inflammatory processes of the kidneys of rats with passive Heymann nephritis (PHN), and focused of the effect of a selective COX-2 inhibitor, flosulide. COX-2-selective inhibitors are thought to represent potent anti-inflammatory agents without major renal side effects., Methods: PHN was induced by injecting heterologous Fx1A antiserum into female Wistar rats. Two treatment groups, each consisting of 12 rats with PHN, received either 3 or 9 mg of flosulide/kg body wt/day and were compared with untreated controls. After four weeks, the generation of thromboxane B2 (TxB2) and 6-keto-PGF1alpha were determined in renal tissue and in urine. COX-2 protein expression was investigated by Western blotting using a selective antibody., Results: Rats with PHN exhibited a marked proteinuria of 71 +/- 8 mg/24 hr as compared with 2.0 +/- 0.3 mg/24 hr in healthy controls (P < 0.01). Treatment with flosulide reduced the proteinuria to 26.1 +/- 9 mg/24 hr at 3 mg flosulide/kg body wt/day and 35.5 +/- 6 mg/24 hr at 9 mg/kg body wt/day, which was equivalent to a reduction of proteinuria by a maximum of 65% (P < 0.05). This was accompanied by an increase in glomerular TxB2 from 3073 +/- 355 to 5255 +/- 1041 pg/mg glomerular protein and 6-keto-PGF1alpha from 1702 +/- 161 to 2724 +/- 770 pg/mg glomerular protein in rats with PHN. COX-2 protein expression was also highly elevated in comparison to healthy controls. Low-dose flosulide treatment had no effect on COX protein expression and renal prostaglandin formation. High-dose flosulide treatment reduced renal prostaglandin production and caused a marked decline in COX-1 and COX-2 protein expression. Urine prostanoid excretion remained unchanged in all therapeutic groups. There was a small though significant reduction in renal creatinine clearance from 0.86 ml +/- 0.2/min in untreated controls to 0.6 ml +/- 0.1/min in flosulide-treated rats with PHN (P < 0.01) after four weeks., Conclusions: Under the influence of flosulide, a highly COX-2-selective inhibitor, we observed an antiproteinuric drug effect. The inflammation in PHN induced COX-2 protein expression that was not affected by low-dose flosulide. COX-1 and COX-2 protein expression was affected by high-dose flosulide, which therefore might lose its selectivity. High-dose flosulide induced a decrease in glomerular prostanoid production possibly because of COX-1 inhibition. Our results suggest that the therapeutic use of flosulide in proteinuria seems advantageous and deserves further studies because the basal prostaglandin levels remain unchanged in the low-dose-treated group, indicating that the compensatory capacity of prostaglandin production, which is essential for the regulation of renal hemodynamics, is maintained.

The prostaglandin cyclooxygenase (Cox) exists in two isoforms with different genetic representation. The isoform, which is constitutively expressed (Cox 1), and mediates physiological functions of prostaglandins, and the inducible isoform (Cox 2) which is upregulated by inflammatory stimuli. This study attempts to determine whether a Cox 2 selective inhibitor, flosulide, differs from the mixed type Cox 1 and Cox 2 inhibitor aspirin in respect of renal function and eicosanoid excretion in experimental nephritis. The effects of flosulide and aspirin were studied during the autologous phase of passive Heymann nephritis (PHN) in rats. Female Wistar rats were injected i.v. with 1 ml of Fx1A antiserum at day 1. From day 7 to day 14 they received either aspirin (aspirin, 50 mg/day), flosulide, (0.75 mg/day) or vehicle p.o. The kidney function was evaluated and the animals sacrificed. The kidneys were removed and glomeruli isolated. The glomeruli were incubated in physiological buffer solution. Basal prostaglandin generation was determined in the supernatant. Treatment with flosulide significantly reduced proteinuria as compared to aspirin treatment (64+/-15 vs. 109+/-14 mg/24 h, p < 0.05). Plasma protein and albumin levels were significantly lower in the aspirin-treated group than in flosulide-treated animals (4.7+/-0.26 vs. 5.48+/-0.08 mg/dl, p < 0. 05 and 0.96+/-0.04 vs. 1.25+/-0.10 mg/dl, p < 0.05). Glomerular prostaglandin production (6-keto-PGF1alpha, TxB2, Bicyclo-PGE2) was significantly reduced in aspirin-, but not in flosulide-treated animals. This was mainly due to a reduction of glomerular TxB2 production by aspirin. Our data demonstrate that a Cox 2 selective inhibitor of prostaglandin formation, flosulide, has beneficial effects on preservation of kidney function in rats with PHN, whereas aspirin has not. These beneficial effects of flosulide possibly result from preservation of the physiological glomerular prostaglandin production. Thus, selective Cox 2 inhibitors might be interesting substances for treatment of nephrotic syndrome.

Purpose: By applying a simple, linear mass-spring model to running, the normalized leg spring stiffness (Kleg), the normalized effective vertical stiffness (Kvert), and the mass-specific mechanical power output of the spring (Psp) were determined and correlated with aerobic demand. The purpose of the study was to determine whether leg spring characteristics explain any of the interindividual variability observed in aerobic demand at a given submaximal running speed., Methods: Recreational runners (N = 16) ran on a treadmill at 3.35 m x s(-1) for physiological measures and overground for biomechanical measures. The latter included a sagittal plane video record of the running motion and ground reaction data., Results: We found no relationship between the aerobic demand of running and Kleg (r = -0.18), an inverse relationship between aerobic demand and Kvert (r = -0.48), and a positive correlation between aerobic demand and Psp (r = 0.45)., Conclusions: The inverse relationship between Kvert and aerobic demand indicates that less economical runners possess a more compliant running style during ground contact. This running style may place greater force demands on extensor musculature.

The purpose of this investigation was to determine, for a planar, multijoint throwing skill, if the relative contributions of the components of the net joint moment (NJM) at the elbow and shoulder change after practice. Each participant (N = 7) performed 200 throwing trials equally distributed across 5 consecutive days. Each participant threw a 0.15-kg ball as far as possible using the nondominant arm while the motion of the throwing arm was restrained to a horizontal plans. From video data and body segment inertial estimations, NJMs and NJM components (i.e., generalized muscle moments and motion-dependent moments) were calculated for selected early and late practice trials. Performance (throwing distance) showed an expected improvement from early to late practice. The dynamics analysis indicated that participants increased average NJMs and NJM components at both joints. However, the relative contribution of NJM components, expressed as ratios of those components to the NJM at each joint, did not change after extended practice. Restraining the throwing arm to a horizontal plane may partly explain why no changes were found in the relative contributions of NJM components. The lack of change in moment ratios support a motor strategy of scaling joint moments for faster movements.

Relationships between running economy (RE; submaximal VO(2) for a given running speed) and the temporal EMG characteristics of bi-articular leg muscles were quantified in a group of well-trained runners. Nine subjects completed three test sessions: a determination of maximal aerobic demand (VO(2)max); an accommodation session at the experimental speed of 4.13 m.s(-1) and a session during which EMG and RE data were collected simultaneously at the experimental speed of 4.13 m.s(-1) Measures of muscle onset, on-time durations, and on-time coactivation durations were calculated from the following muscles: rectus femoris, medial hamstrings, lateral hamstrings, and gastrocnemius. Nonparametric correlations between RE and EMG characteristics displayed both positive and negative relationships and exhibited a wide range of values. Two EMG measures were significantly correlated (r > 0.67) with RE. Earlier onset of rectus femoris during swing phase and a shorter duration of hamstring - gastrocnemius coactivation during swing were associated with more economical runners. Although not statistically significant, correlation coefficients calculated for measures of coactivation during stance and RE ranged from -0.42 to -0.65. This trend indicates that individuals who exhibited a greater amount of coactivation between bi-articular muscles during the stance phase of the running cycle tended to be more economical. These relationships suggest different activation patterns in bi-articular muscles between economical and uneconomical runners.

The purpose of this investigation was to determine, for a planar multijoint throwing skill, if electromyographic (EMG) amplitudes of eccentric and concentric muscle activity for two agonist muscles (i.e. agonists for the concentric phase) changed over the course of practice. Eighteen men threw a weighted ball with their dominant arm at a target while the motion was restrained to a horizontal plane. EMG and kinematic data were collected for selected practice trials. EMG signals of the triceps brachii (lateral head) and posterior deltoid were full-wave rectified and integrated (IEMG) over two portions of the movement: the countermovement and the throw. Performance showed an expected improvement over trial blocks. IEMG activities of both muscles did not change across trial blocks for the countermovement (eccentric phase) or for the throw (concentric phase) even though several kinematic and kinetic descriptors changed significantly (e.g. during the throw, peak elbow angular velocity and mechanical work by the elbow extensor moment increased during practice). Results suggest that EMG amplitudes of assistive or auxiliary muscles may change rather than primary agonists or that limitations inherent in skill acquisition research and EMG signal processing may be the reasons why no changes were observed in EMG amplitudes.

The near-end cross talk of InGaAsP-InP waveguide directional couplers is investigated. It is shown that the cross-talk level is strongly dependent on the optical path difference between the two link-end arms of the coupler. By locally heating one of these arms with an argon laser beam this path difference, and hence the couplers' near-end cross talk, can be tuned. The ultimate limit for the near-end cross talk is determined by stray light and has therefore approximately the same level as the far-end cross talk.

The interrelationships between aerobic demand, kinematic and kinetic-based estimates of mechanical power output and energy transfer, and total body angular impulse (summation of net joint moments integrated with respect to time over a stride) were quantified for walking at 1.69 m.s-1 and running at 3.35 m.s-1 to assess the ability of these various biomechanical expressions to explain interin-dividual differences in walking and running economy. Fourteen healthy men participated in the walking study and 16 recreational male runners were subjects for the running analysis. Each subject performed treadmill locomotion for determination of aerobic demand and overground locomotion from which biomechanical measures were quantified. It was expected that mechanical power and angular impulse expressions would correlate positively with aerobic demand while energy transfer expressions would correlate negatively. Correlations between aerobic demand and power estimates primarily were positive, but explained no more than 32% of the variability in walking or running VO2 (center of mass model: 0.22 < r < 0.57; segment-based model: -0.02 < r < 0.20; kinetic model: -0.07 < r < 0.22). Total body angular impulse also correlated positively with aerobic demand (0.32 < r < 0.42). Energy transfer expressions from the various analytical models showed no consistent relationship with aerobic demand, either in terms of magnitude or direction (-0.26 < r < 0.48). It was concluded that mechanical power, energy transfer, and angular impulse expressions frequently used in analyses of gait explain only a small proportion of normal interindividual variability in the aerobic demand at a given speed of walking or running.

The following points can be made about liposarcoma of the oral cavity: 1) it is rare and slow growing; 2) it is often mistaken for a benign lesion; 3) there is a direct correlation of microscopic appearance with biological behavior and prognosis; 4) treatment is primarily surgical, with radiation used for selected cases; and 5) the better-differentiated tumors seem to respond more favorably to radiation.

Two experiments examined the effects of physostigmine on acquisition and performance of operant serial reversals by rats. In Experiment 1, four groups of rats (n = 6/group) were injected with either vehicle or 0.03 mg/kg physostigmine five minutes prior to each session, or vehicle or 0.5 mg/kg physostigmine immediately after each session of a three-stimulus (bright, dim or flashing light) repeated discrimination/reversal procedure. Rats treated with physostigmine pre- or postsession learned significantly more reversals over 50 sessions than animals injected with vehicle. Experiment 2 used only two discriminative stimuli, a light and a 2,500 Hz tone. Following establishment of a stable daily reversal baseline, postsession injections of physostigmine significantly increased the number of trials to criterion on the next session compared to each subject's control baseline. Results are attributed to enhanced between-session transfer of previously learned discriminated instrumental responses by physostigmine-treated animals.

A series of related experiments was conducted to examine the effects of scopolamine on discrimination performance in the presence or absence of a stimulus signalling non-reinforcement. In Experiment 1, rats trained to respond on 1 of two levers in the presence of a 1000-Hz tone and on the other lever in the presence of a 3000-Hz tone were not reinforced when white noise was added to 1 of the tones. Pairing white noise with the other tone during an extinction session demonstrated that the white noise had become a conditioned inhibitory stimulus. In Experiment 2, scopolamine decreased responding and discrimination accuracy on the excitatory (reinforced) trials, and increased responding on the inhibitory (non-reinforced) trials. The magnitude of the drug's effect was similar on excitatory and inhibitory trials. Using combination of visual and auditory discriminative stimuli, Experiment 3 confirmed the results of Experiment 2. These experiments show that scopolamine disrupts animals' ability to discriminate, and that scopolamine-induced increases in non-rewarded responses cannot be attributed solely to a disinhibitory effect of the drug as Carlton (1969) and others have claimed.

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and two reference drugs, physostigmine and chlordiazepoxide, were measured on the performance of rats trained on a continuous non-match (CNM) delayed comparison, working memory procedure. These same compounds were also tested in analogous, large and small stimulus difference discrimination (i.e., non working-memory) procedures. The effects of the pesticides and physostigmine on CNM performance were qualitatively similar, and also similar to their effects on discrimination performance. As dosage of these compounds increased, only small effects on accuracy were observed, followed at still larger doses by an abrupt and non-selective decrease in all responding. The pesticides and physostigmine did not selectively affect working memory: the magnitude of their effects did not increase with intertrial interval, and the compounds were equally effective in disrupting discrimination and CNM performance. Effects of chlordiazepoxide on performance in the CNM and discrimination control procedures differed qualitatively from those of the pesticides and physostigmine.

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITI's ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials ('memory'). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.

The effects of scopolamine and methyl scopolamine on working memory processes were investigated in a paired trial, go-no go delayed response procedure in which rats initiated their own trials. Drug effects were examined concurrently on performance at three delays--no, 0, and 2.5 sec. Scopolamine disrupted no-delay (discrimination) performance in a dose-related manner. Scopolamine also progressively reduced performance at 0-delay and 2.5 sec delay more than at no-delay, but only at the highest administered dose (0.5 mg/kg). Scopolamine affected sensitivity, but not response bias. Although both scopolamine and methyl scopolamine reduced the probability of trial initiation, only scopolamine disrupted accuracy of performance on the initiated trials.

Rats were trained to press two levers in alternation on discrete trials spaced 10 sec apart. During the final sessions of alternation training, error responses per opportunity on the trials that followed reinforced trials (initial trials) did not differ from error responses per opportunity on repetitive (correction) trials (Experiment 1). Scopolamine did not increase the rats' tendency to perseverate: drug treatment did not cause the error responses per opportunity to increase over runs of consecutive error responses (Experiment 2). Scopolamine did not impair performance when alternation was controlled by visual stimuli present in the external environment at the time of the response (Experiment 3). The disruption in delayed alternation performance produced by scopolamine was attributed to effects on stimulus discrimination, resulting in impairment of control of responding by stimuli not present in the environment at the time of the response.

This review describes methods for measuring effects of drugs on learning and memory in animals, proceeding from relatively simple nonassociative learning (habituation) to classical and instrumental conditioning, and concluding with complex measures for measuring learning and memory repeatedly in the individual animal. Procedures for separating drug effects specific to learning and memory from non-specific effects on activity, motivation, sensory and motor capacity, etc., were emphasized. For each method, selected experimental examples were presented which described the action of drugs on learning and memory, elucidated the behavioral processes involved in the drug effects, or illustrated methodological points. The various procedures used to measure drug effects on learning and memory in animals have yielded a bewildering array of often-contradictory results. Quantitative differences in effectiveness of drugs in the different procedures are common. Drugs (for example, the nootropics) that alter learning or memory in a few procedures may be totally without activity in many others. How are these discrepancies to be interpreted? The apparent inconsistencies in the data can, for the most part, be understood in terms of the nature of learning and memory. "Learning" and "memory" are hypothetical processes presumed to underlie enduring changes in behavior resulting from the organism's interaction with environmental stimuli. Given such a broad definition, the prevalence of inconsistencies in the data is hardly surprising. It is unlikely that the same mechanisms should underlie all of the wide variety of behavioral changes included under the rubrics "learning" or "memory." (For a contrary view, based on consistencies among results obtained in the diverse procedures, see Zornetzer). How, then, should drug effects on learning and memory be identified or measured? The first step, of course, is to rule out those drug effects that do not conform to the definition of learning or memory. This review has described strategies and procedures by which this can be accomplished. However, even when this is done there is no single procedure that can detect drug effects on learning and memory in general, nor, in view of the heterogeneous behaviors involved, is it likely that such a universal procedure will ever be found. Thus, a multi-faceted strategy will be required. Some of the simpler procedures described in this review may be adequate for the initial identification of interesting effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Discrete trial procedures permit exact control or description of the time of occurrence of stimuli, the probability of response occurrence, and the patterning of responses. They also make possible the experimental manipulation of the composition of the stimuli controlling behavior. The use of discrete trial procedures is illustrated here in an examination of the effects of scopolamine, a representative cholinergic blocker, on several aspects of behavior: Memory. Response alternation experiments, in which the spacing of discrete trials varies within the experimental session, show that, whereas accuracy of responding is consistently poorer under drug, the decline of accuracy with time since last trial is similar for drugged and nondrugged animals. Thus the drug does not affect memory "storage". Inhibition. Experiments in which discrete trials are presented in pairs, such that the correct response on Trial 2 of the pair is contingent upon Trial 1 events, show how the "disinhibiting" effect of scopolamine (as indicated by enhanced responding on "no go" trials) is augmented by increasing the time gap between Trial 1 and Trial 2, or by minimizing controlling stimuli on Trial 1. Discrimination. A variety of experiments suggest that scopolamine decreases the "detectability" of stimuli. Detectability effects, along with disinhibition observed under certain specific conditions, constitute the prinicipal behavioral actions of scopolamine observed with discrete trial procedures.

Rats were trained to stable baselines of lever pressing on a variable intertrial interval continuous nonmatching to sample schedule (CNM) or on an analogous discrimination schedule. Scopolamine reduced accuracy of CNM performance to a similar extent over the three intertrial (retention) intervals: 2.5, 5, and 10 s, results indicating that the drug did not affect the time-dependent process of retention in working memory. When baseline levels of performance accuracy were similar in the CNM and discrimination tasks (but stimulus discriminability was greater in the CNM task), scopolamine reduced accuracy equally in the two procedures. Effects of scopolamine on accuracy of noncorrection trial CNM performance were simulated by reducing stimulus discriminability; however, scopolamine disrupted CNM correction trial performance much more than did reductions in stimulus discriminability. It is concluded that scopolamine's effects on working memory are not limited to possible effects on stimulus discrimination: Scopolamine may also affect retrieval of response rules from reference memory.

Effects of four pesticides (carbaryl, propoxur, chlordimeform, and deltamethrin) and four reference drugs (physostigmine, scopolamine, methscopolamine, and chlordiazepoxide) were measured in two delayed response, working memory procedures: go-no go alternation in which rats initiated their own trials, and spatial reversals. Four of these compounds (carbaryl, propoxur, physostigmine, and scopolamine) were also tested in a go-no go alternation procedure in which animals did not initiate their trials. The pesticides and physostigmine did not selectively affect working memory in any of the procedures: low doses only moderately decreased response accuracy, whereas higher doses suppressed responding indiscriminately. The pesticides and physostigmine had similar effects on go-no go alternation (i.e., working memory) and analogous go-no go discrimination performance. Effects on go-no go alternation performance did not depend on whether the animals initiated their own trials. Scopolamine, in contrast, appeared to disrupt working memory. It profoundly disrupted accuracy at doses that only moderately decreased over-all responding and impaired go-no go alternation accuracy much more than discrimination accuracy.