Search

That course in nursing ethics may be more useful than you think. [ABSTRACT FROM AUTHOR]

Introduction: The Seraph® 100 Microbind® Affinity blood filter (Seraph® 100) has been in use since 2019 for the treatment of fulminant or difficult to treat blood stream infections as an adjunct to pharmacotherapy. In 2020 the device received emergency use authorization by the US Food and Drug Administration for the treatment of critically ill COVID-19 patients with confirmed or imminent respiratory failure. Results of an international registry showed that the Seraph® 100 was operated under blood flow rates of 100-350 mL/min. As those conditions require a large bore central line, a dialysis catheter is currently considered indispensable to operate the Seraph® 100. The use of smaller catheter lumina has neither been evaluated in vitro nor in vivo., Methods: In vitro pressure data before and after the Seraph® 100 at various blood pump rates (prepump line 16 G, postpump line 18 G) with saline and human plasma were obtained. Further, anecdotal flow and pressure data of two patients treated with the Seraph® 100 for a COVID-19 infection are reported., Results: At a pump speed of 50 mL/min pre-Seraph® pressure using saline was -70 [-70 to -60] mm Hg. In comparison, using plasma pre-Seraph® pressure was lower at -120 [-120 to -105] mm Hg; p  < 0.001 ( t -test). The post-Seraph® pressure at 50 mL/min using saline of 120 [110-130] mm Hg was not different from plasma at 130 [120-140] mm Hg, p  = 0.152 ( t -test). Blood flow rates of 50 mL/min did not lead to preAP levels below -250 mm Hg in the two clinical cases., Conclusion: Seraph® 100 blood flow rate of 50 mL/min may be achieved using low flow vascular access, allowing to treat a blood volume 72 L in 24 h., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MTS, JJS, and JTK received research funding from ExThera Medical. MTS and JTK received travel support from ExThera Medical. All other authors: none to declare.

Objectives: Establishing direct reference intervals for pediatric patients is a costly, challenging, and time-consuming enterprise. Indirectly established reference intervals can help to ameliorate this situation. It was our objective to establish population-specific reference intervals for automated white blood cell differentials via data mining and non-parametric percentile method., Methods: Blood counts and automated white blood cell differentials of patients aged 0 days to 18 years, performed from the 1st of January 2018 until the 30th of June 2022, were identified in our laboratory information system. Reference intervals were established in accordance with IFCC and CLSI recommendations as well as the propositions by Haeckel et al., Results: Initially, 47,173 blood counts on our SYSMEX XN-9000 were identified. 11,707 data sets were excluded, leaving 35,466 sample sets for analysis. Of these, 17,616 contained automated white blood cell differentials. Due to insufficient patient numbers, no reference intervals for automated white blood cell differentials could be established for children aged <7 months. In comparison to the corresponding reference intervals published by Herklotz et al., reference intervals determined by us showed relevant differences throughout all age groups., Conclusions: The combination of non-parametric percentile method and the propositions by Haeckel et al. utilizing conscientious data mining appears to be potent alternative to direct reference interval determination., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

While a rich literature addresses legislative agenda-setting in multiparty democracies, relatively little is known how members of parliament disseminate the legislative agenda beyond the parliamentary floor. Drawing on content analyses of 110 legislative debates and 5,847 press releases from Austrian MPs (2013-2017), we test whether legislators are more likely to send press releases on issues that are salient to their party ( party agenda-setting ) and to other parties in the party system ( systemic salience ). MPs should also communicate more on issues that fall within their area of expertise ( issue specialization ) and when they have given a speech on that issue during the legislative debate ( intra-party delegation ). While we find empirical support for all these expectations, communication of the legislative agenda largely rests on each parties' issue specialists and their speakers in plenary debates. Importantly, there is no significant discrepancy overall between the actual parliamentary issue agenda and the agenda communicated by party MPs., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Placement of central venous catheters (CVC) into the internal jugular vein represents a routine clinical intervention. The periprocedural complication rate ranges from 5 to 20% and can be reduced by ultrasound guidance, training of residents and other measures. We aimed to proof that the average Seldinger needle is too long, increasing the risk of periprocedural injury, best epitomized in the stellate ganglion injury/irritation. The first part of the study was an online market analysis to investigate the standard needle length currently offered as part of the CVC placement sets. The second part of the study involved 35 hospitalized patients (14 female; median age 74.5 years). In those the distance between the skin and the internal jugular vein as well as the diameter of the internal jugular vein was measured by ultrasound in both, supine position as well as 45° semi-sitting position. In the third part of the study 80 body donors (45 female; median age 83.0 years) preserved by the ethanol/formaldehyde method were studied. In those the distance and angle between the typical landmark for insertion of the Seldinger needle for internal jugular vein catheter placement to the stellate ganglion was measured. The median [interquartile range] Seldinger needle length was 7 [4.0-10.0] cm. In the examined patients the maximum distance between the skin and the internal jugular vein was 1.87 cm. The minimum distance was 0.46 cm and the median distance averaging supine and 45° position was 1.14 [0.94-1.31] cm. Regarding the body donors the median distance from the insertion point of the internal jugular vein to the stellate ganglion was longer in men 5.5 [4.95-6.35] cm than in women 5.2 [4.7-5.9] (p = 0.031 unpaired t-test). With 7 cm average length the Seldinger needle currently sold as part of CVC sets is long enough to physically reach the stellate ganglion, not to mention more proximal structures. A shorter needle length would be sufficient to reach the internal jugular vein even in obese patients and with a small insertion angle while minimizing the possibility to cause severe injury as structures like the pleura and the stellate ganglion could not be reached by shorter needles., (© 2022. The Author(s).)

Objectives: Establishing direct reference intervals (RIs) for pediatric patients is a very challenging endeavor. Indirectly determined RIs can address this problem by utilization of existing clinical laboratory databases. In order to provide better laboratory services to the local pediatric population, we established population-specific hematology RIs via data mining., Methods: Our laboratory information system (LIS) was searched for pediatric blood counts of patients aged from 0 days to 18 years, performed from 1st of January 2018 until 31st of March 2021. In total, 27,554 blood counts on our SYSMEX XN-9000 were initially identified. After application of pre-defined exclusion criteria, 18,531 sample sets remained. Age- and sex-specific RIs were established in accordance with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical & Laboratory Standards Institute (CLSI) recommendations., Results: When compared to pediatric RIs supplied by other authors, the RIs determined specifically for pediatric patients from Berlin and Brandenburg showed several relevant differences, especially with regard to white blood cell counts (WBCs), red blood cell counts (RBCs), red cell distribution widths (RDW) and platelet counts (PLTs) within the distinct age groups. Additionally, alterations to several published age-specific partitions had to be made, while new sex-specific partitions were introduced for WBCs and PLTs., Conclusions: Generic RIs from textbooks, manufacturer information and medical publications - even from nationwide or multicenter studies - commonly used in many laboratories might not reflect the specifics of local patient populations properly. RIs should be tailored to the serviced patient population whenever possible. Careful data mining appears to be suitable for this task., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

Background: Few studies assessing the correlation between patient-reported outcomes and patient-generated health data from wearable devices exist., Objective: The aim of this study was to determine the direction and magnitude of associations between patient-generated health data (from the Fitbit Charge HR) and patient-reported outcomes for sleep patterns and physical activity in patients with type 2 diabetes mellitus (T2DM)., Methods: This was a pilot study conducted with adults diagnosed with T2DM (n=86). All participants wore a Fitbit Charge HR for 14 consecutive days and completed internet-based surveys at 3 time points: day 1, day 7, and day 14. Patient-generated health data included minutes asleep and number of steps taken. Questionnaires assessed the number of days of exercise and nights of sleep problems per week. Means and SDs were calculated for all data, and Pearson correlations were used to examine associations between patient-reported outcomes and patient-generated health data. All respondents provided informed consent before participating., Results: The participants were predominantly middle-aged (mean 54.3, SD 13.3 years), white (80/86, 93%), and female (50/86, 58%). Use of oral T2DM medication correlated with the number of mean steps taken (r=.35, P=.001), whereas being unaware of the glycated hemoglobin level correlated with the number of minutes asleep (r=-.24, P=.04). On the basis of the Fitbit data, participants walked an average of 4955 steps and slept 6.7 hours per day. They self-reported an average of 2.0 days of exercise and 2.3 nights of sleep problems per week. The association between the number of days exercised and steps walked was strong (r=.60, P<.001), whereas the association between the number of troubled sleep nights and minutes asleep was weaker (r=.28, P=.02)., Conclusions: Fitbit and patient-reported data were positively associated for physical activity as well as sleep, with the former more strongly correlated than the latter. As extensive patient monitoring can guide clinical decisions regarding T2DM therapy, passive, objective data collection through wearables could potentially enhance patient care, resulting in better patient-reported outcomes., (©James Weatherall, Yurek Paprocki, Theresa M Meyer, Ian Kudel, Edward A Witt. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 05.06.2018.)

Parties try to shape media coverage in ways that are favorable to them, but what determines whether media outlets pick up and report on party messages? Based on content analyses of 1,496 party press releases and 6,512 media reports from the 2013 Austrian parliamentary election campaign, we show that media coverage of individual party messages is influenced not just by news factors, but also by partisan bias. The media are therefore more likely to report on messages from parties their readers favor. Importantly, this effect is greater rather than weaker when these messages have high news value. These findings have important implications for understanding the media's role in elections and representative democracies in general.

Multiparty government in parliamentary democracies entails bargaining over the payoffs of government participation, in particular the allocation of cabinet positions. While most of the literature deals with the numerical distribution of cabinet seats among government parties, this article explores the distribution of individual portfolios. It argues that coalition negotiations are sequential choice processes that begin with the allocation of those portfolios most important to the bargaining parties. This induces conditionality in the bargaining process as choices of individual cabinet positions are not independent of each other. Linking this sequential logic with party preferences for individual cabinet positions, the authors of the article study the allocation of individual portfolios for 146 coalition governments in Western and Central Eastern Europe. The results suggest that a sequential logic in the bargaining process results in better predictions than assuming mutual independence in the distribution of individual portfolios.

The concept of the niche party has become increasingly popular in analyses of party competition. Yet, existing approaches vary in their definitions and their measurement approaches. We propose using a minimal definition that allows us to compare political parties in terms of their 'nicheness'. We argue that the conceptual core of the niche party concept is based on issue emphasis and that a niche party emphasizes policy areas neglected by its rivals. Based on this definition, we propose a continuous measure that allows for more fine-grained measurement of a party's 'nicheness' than the dominant, dichotomous approaches and thereby limits the risk of measurement error. Drawing on data collected by the Comparative Manifesto Project, we show that (1) our measure has high face validity and (2) exposes differences among parties that are not captured by alternative, static or dichotomous measures.

Purpose: Peyronie 's disease is an acquired connective tissue disorder of the penile tunica albuginea with fibrosis and inflammation. The disease produces palpable plaques, penile curvature and pain during erections. Usually it results in impairment of the quality of life. Our objective is to review the long-term results of the albugineal grafting harvested from the penile crura for the treatment of severe penile curvature., Materials and Methods: Thirty-three patients with Peyronie 's disease were submitted to a grafting with tunica albuginea from the penile crura for the correction of penile curvature. The results were evaluated after 6 months of the procedure. Variables studied were overall satisfaction with the procedure, correction of the penile curvature, erectile capacity, penile shortening and the presence of surgical complications., Results: Mean follow-up after surgery was 41 months. Complete correction of the curvature was achieved in 30 patients (90%). The mean preoperative curvature was 91.8 degrees and median plaque length was 2 cm (ranged from 1 to 5 cm). Three patients (9%) experienced recurrence of the penile curvature and required a new procedure. In 30 men (90%) the procedure fulfilled their expectations and in 31 patients (93.9%) their opinions were that sexual partners were satisfied with the penile correction. Penile shortening or augmentation was referred in 6 (18.1%) and 1 (3%) patient, respectively., Conclusion: Our series demonstrated that grafting the albugineal defect after incision of the tunica albuginea with tunica from the crus for the correction of penile curvature is safe and results in satisfactory straight erections during along-term follow-up.

LuxS (S-ribosylhomocysteinase) catalyzes the cleavage of the thioether linkage of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a small signaling molecule that mediates interspecies bacterial communication called autoinducer 2 (AI-2). Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. In this work, SRH analogues containing substitution of a nitrogen atom for the endocyclic oxygen as well as various deoxyriboses were synthesized and evaluated for LuxS inhibition. Two of the [4-aza]SRH analogues showed modest competitive inhibition (K(I) ∼40 μM), while most of the others were inactive. One compound that contains a hemiaminal moiety exhibited time-dependent inhibition, consistent with enzyme-catalyzed ring opening and conversion into a more potent species (K(I)(∗)=3.5 μM). The structure-activity relationship of the designed inhibitors highlights the importance of both the homocysteine and ribose moieties for high-affinity binding to LuxS active site., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Studies of the effects of disclosing stressful experiences among patients with rheumatoid arthritis (RA) have yielded inconsistent findings, perhaps due to different disclosure methods--writing or speaking--and various methodological limitations. We randomized adults with RA to a writing (n=88) or speaking (to a recorder) sample (n=93), and within each sample, to either disclosure or 1 of 2 control groups (positive or neutral events), which conducted four 20-minute, at-home sessions. Follow-up evaluations at 1, 3, and 6 months included self-reported, behavioral, physiological, and blinded physician-assessed outcomes. In both writing and speaking samples, the disclosure and control groups were comparably credible, and the linguistic content differed as expected. Covariance analyses at each follow-up point indicated that written disclosure had minimal effects compared with combined controls--only pain was reduced at 1 and 6 months, but no other outcomes improved. Spoken disclosure led to faster walking speed at 3 months, and reduced pain, swollen joints, and physician-rated disease activity at 6 months, but there were no effects on other outcomes. Latent growth curve modeling examined differences in the trajectory of change over follow-up. Written disclosure improved affective pain and walking speed; spoken disclosure showed only a marginal benefit on sensory pain. In both analyses, the few benefits of disclosure occurred relative to both positive and neutral control groups. We conclude that both written and spoken disclosure have modest benefits for patients with RA, particularly at 6 months, but these effects are limited in scope and consistency., (Copyright © 2011 International Association for the Study of Pain. All rights reserved.)

We determined the substrate specificities of the protein tyrosine phosphatases (PTPs) PTP1B, RPTPα, SHP-1, and SHP-2 by on-bead screening of combinatorial peptide libraries and solution-phase kinetic analysis of individually synthesized phosphotyrosyl (pY) peptides. These PTPs exhibit different levels of sequence specificity and catalytic efficiency. The catalytic domain of RPTPα has very weak sequence specificity and is approximately 2 orders of magnitude less active than the other three PTPs. The PTP1B catalytic domain has modest preference for acidic residues on both sides of pY, is highly active toward multiply phosphorylated peptides, but disfavors basic residues at any position, a Gly at the pY-1 position, or a Pro at the pY+1 position. By contrast, SHP-1 and SHP-2 share similar but much narrower substrate specificities, with a strong preference for acidic and aromatic hydrophobic amino acids on both sides of the pY residue. An efficient SHP-1/2 substrate generally contains two or more acidic residues on the N-terminal side and one or more acidic residues on the C-terminal side of pY but no basic residues. Subtle differences exist between SHP-1 and SHP-2 in that SHP-1 has a stronger preference for acidic residues at the pY-1 and pY+1 positions and the two SHPs prefer acidic residues at different positions N-terminal to pY. A survey of the known protein substrates of PTP1B, SHP-1, and SHP-2 shows an excellent agreement between the in vivo dephosphorylation pattern and the in vitro specificity profiles derived from library screening. These results suggest that different PTPs have distinct sequence specificity profiles and the intrinsic activity/specificity of the PTP domain is an important determinant of the enzyme's in vivo substrate specificity.

Purpose: The biologic relevance of human connective tissue growth factor (hCTGF) for primary human tenon fibroblasts (HTFs) was investigated by RNA expression profiling using affymetrix(TM) oligonucleotide array technology to identify genes that are regulated by hCTGF., Methods: Recombinant hCTGF was expressed in HEK293T cells and purified by affinity and gel chromatography. Specificity and biologic activity of hCTGF was confirmed by biosensor interaction analysis and proliferation assays. For RNA expression profiling HTFs were stimulated with hCTGF for 48h and analyzed using affymetrix(TM) oligonucleotide array technology. Results were validated by real time RT-PCR., Results: hCTGF induces various groups of genes responsible for a wound healing and inflammatory response in HTFs. A new subset of CTGF inducible inflammatory genes was discovered (e.g., chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-X-C motif] ligand 6 [CXCL6], interleukin 6 [IL6], and interleukin 8 [IL8]). We also identified genes that can transmit the known biologic functions initiated by CTGF such as proliferation and extracellular matrix remodelling. Of special interest is a group of genes, e.g., osteoglycin (OGN) and osteomodulin (OMD), which are known to play a key role in osteoblast biology., Conclusions: This study specifies the important role of hCTGF for primary tenon fibroblast function. The RNA expression profile yields new insights into the relevance of hCTGF in influencing biologic processes like wound healing, inflammation, proliferation, and extracellular matrix remodelling in vitro via transcriptional regulation of specific genes. The results suggest that CTGF potentially acts as a modulating factor in inflammatory and wound healing response in fibroblasts of the human eye.

Purpose: The Authors present their results using laparoscopic prostatectomy in the treatment of large benign prostatic hyperplasia (BPH)., Materials and Methods: Between March 1999 and March 2005, 60 patients were submitted to laparoscopic prostatectomy with vascular control for large BPH. The demographic, operative period and outcome data were recorded., Results: The average prostate weight was 144.50+/-41.74 gm. Mean operative time was 138.48+/-23.38 minutes and estimated blood loss of 330.98+/-149.52 ml. No patient required transfusions or conversion to open surgery. Post operative complications included one case of septicemia and three cases of prolonged ileum. The most frequent long-term complication was retrograde ejaculation, presented in all patients after 6 months of follow-up. The erectile function was preserved in all those patients who were potent before surgery. No urinary incontinence was reported by patients., Conclusions: The results demonstrate that resection of large prostatic adenomas can be performed with a laparoscopic approach. The patients had a shorter hospital stay and early return to normal activity.

Purpose: It has been reported that more aggressive prostate cancer (PC) can be associated with low serum testosterone levels. The relationship between serum androgens and PC is still not completely understood. In this study we examined the association of prognostic factors in men who underwent radical retropubic (RRP) prostatectomy with low or normal total testosterone., Materials and Methods: We retrospectively evaluated 64 consecutive patients with localized PC treated with RRP between July 2002 and November 2003. PC was diagnosed by transrectal ultrasonography guided biopsy performed for either a suspicious digital rectal examination or serum prostate specific antigen greater than 4.0 ng/ml. Gleason score was determined in prostatic biopsies. Pathological TNM staging (1997), capsular perforation, seminal vesicle involvement and surgical margin status were determined in all surgical specimens. The threshold for serum total testosterone was 270 ng/dl. In all analyses p <0.05 was considered statistically significant., Results: There were no statistically significant differences among prostate specific antigen, Gleason score (biopsy or specimen), pathological stage, capsular perforation and seminal vesicle involvement. However, patients with low total testosterone had increased positive surgical margins (p = 0.026)., Conclusions: Patients with low total testosterone more frequently present with positive surgical margins in RRP specimens. The true association between low testosterone and poor clinical outcome in the long term needs validation in large prospective studies.

Objective: African Americans often report greater pain than do Caucasians, but the factors responsible for this discrepancy are not known. We examined whether alexithymia-the trait of difficulty identifying and describing one's feelings and lacking introspection-may contribute to this ethnic group difference. We tested whether the mean level of alexithymia is higher, and whether alexithymia and pain are more highly correlated, among African Americans than among Caucasians in patients with chronic pain disorders., Design: Three cross-sectional, correlational studies were conducted on three separate samples of patients with chronic pain. Analyses examined the full sample and then Caucasians and African Americans separately., Setting and Patients: Patients were recruited primarily from treatment settings. Samples were patients with rheumatoid arthritis (N = 155), migraine headaches (N = 160), or systemic lupus erythematosus (N = 123), and each sample included only Caucasians or African Americans., Measures: The Toronto Alexithymia Scale-20 assessed global alexithymia and three alexithymia facets. Pain severity, functional disability, or symptoms were also measured on each sample., Results: Similar findings occurred across all three samples. African Americans had only slightly higher mean alexithymia levels than did Caucasians, and this was partly accounted for by socioeconomic differences between groups. More importantly, alexithymia correlated only weakly with pain or symptom severity for each full sample, but the two ethnic groups showed different patterns. Alexithymia correlated positively with pain severity among African Americans, but was uncorrelated with pain among Caucasians, even after covarying for various socioeconomic variables., Conclusions: Alexithymia is more correlated with pain severity among African Americans with chronic pain disorders than among Caucasians, potentially contributing to the higher pain reports among African Americans.

The immediate and long-term outcome of a mutilating hand injury can be positively influenced by health care professionals adopting a biopsychosocial perspective toward treatment and management. Such an injury produces a psychological and social impact that should be openly and candidly addressed with the injured individual and with the family. The earlier and the more skillfully these issues are addressed, the more likely it is that psychological factors will not impede functional outcome.

A method has been developed for the trace analysis of two classes of antimicrobials consisting of six sulfonamides (SAs) and five tetracyclines (TCs), which commonly are used for veterinary purposes and agricultural feed additives and are suspected to leach into ground and surface water. The method used solid-phase extraction and liquid chromatography/mass spectrometry (LC/MS) with positive ion electrospray. The unique combination of a metal chelation agent (Na2EDTA) with a macroporous copolymer resulted in quantitative recoveries by solid-phase extraction (mean recovery, 98 +/- 12%) at submicrogramper-liter concentrations. An ammonium formate/formic acid buffer with a methanol/water gradient was used to separate the antimicrobials and to optimize the signal intensity. Mass spectral fragmentation and ionization characteristics were determined for each class of compounds for unequivocal identification. For all SAs, a characteristic m/z 156 ion representing the sulfanilyl fragment was identified. TCs exhibited neutral losses of 17 amu resulting from the loss of ammonia and 35 amu from the subsequent loss of water. Unusual matrix effects were seen only for TCs in this first survey of groundwater and surface water samples from sites around the United States, requiring that TCs be quantitated using the method of standard additions.

Activity-related shifts in intracellular pH (pHi) can exert potent neuromodulatory actions. Different states of neuronal activity of thalamocortical neurons were found to differentially modulate pHi. Tonic activity evoked by injection of depolarizing current led to a reversible rise in [H+]i which was nearly abolished in the presence of TTX. Block of voltage-gated calcium channels with I mM Ni2+ reduced the [H+]i transients related to tonic activity. Rhythmic activation of burst discharges caused changes of [H+]i which were decreased by TTX, whereas I mM Ni2+ almost abolished the [H+]i transients. The present results show that different forms of neuronal activity can lead to intracellular acidification caused by different mechanisms, i.e. Na+ and Ca2+ influx through sodium and Ca2+ channels, respectively, and the subsequent activation of a Ca2+/H+ pump. The resulting acidosis is suggested to reduce further Ca2+ influx and prevent excessive neuronal excitation.

The recent discovery of glycine transporters in both the central nervous system and the periphery suggests that glycine transport may be critical to N-methyl-D-aspartate receptor (NMDAR) function by controlling glycine concentration at the NMDAR modulatory glycine site. Data obtained from whole-cell patch-clamp recordings of hippocampal pyramidal neurons, in vitro, demonstrated that exogenous glycine and glycine transporter type 1 (GLYT1) antagonist selectively enhanced the amplitude of the NMDA component of a glutamatergic excitatory postsynaptic current. The effect was blocked by 2-amino-5-phosphonovaleric acid and 7-chloro-kynurenic acid but not by strychnine. Thus, the glycine-binding site was not saturated under the control conditions. Furthermore, GLYT1 antagonist enhanced NMDAR function during perfusion with medium containing 10 microM glycine, a concentration similar to that in the cerebrospinal fluid in vivo, thereby supporting the hypothesis that the GLYT1 maintains subsaturating concentration of glycine at synaptically activated NMDAR. The enhancement of NMDAR function by specific GLYT1 antagonism may be a feasible target for therapeutic agents directed toward diseases related to hypofunction of NMDAR.