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The role of compound III in reversible and irreversible inactivation of lactoperoxidase.

In the presence of iodide (I-, 10 mM) and hydrogen peroxide in a large excess (H2O2, 0.1-10 mM) catalytic amounts of lactoperoxidase (2 nM) are very rapidly irreversibly inactivated without forming compound III (cpd III). In contrast, in the absence of I- cpd III is formed and inactivation proceeds very slowly. Increasing the enzyme concentration up to the micromolar range significantly accelerates the rate of inactivation. The present data reveal that irreversible inactivation of the enzyme involves cleavage of the prosthetic group and liberation of heme iron. The rate of enzyme destruction is well correlated with the production of molecular oxygen (O2), which originates from the oxidation of excess H2O2. Since H2O2 and O2 per se do not affect the heme moiety of the peroxidase, we suggest that the damaging species may be a primary intermediate of the H2O2 oxidation, such as oxygen in its excited singlet state (1 delta gO2), superoxide radicals (O-.2), or consequently formed hydroxyl radicals (OH.).

Free Radicals↗

Enhanced sensitivity for peripherally-presented collinearly-aligned stimulus elements: contour detection or spatial summation?

BACKGROUND: It has been shown that the detection threshold for a foveally presented Gabor stimulus (Gaussian-windowed sinusoidal grating) is reduced in the presence of two suprathreshold flanking Gabors and that such facilitation is orientation and configuration dependent, with maximal threshold reductions occurring with collinear flanking elements. METHODS: We assessed the effect of varying relative orientation on detection thresholds for chains of three Gabors, with 0.96(o) centre-to-centre spacing, presented at 4.8(o) in the periphery. The central Gabor element in each chain was either collinear with its flanking elements or oriented orthogonally to them. RESULTS: Thresholds for the configuration as a whole were found to be lower using the collinear configuration compared with the orthogonal configuration, consistent with the proposal that orientation-specific long-range intracortical interactions are involved. However, this configuration-dependent threshold difference disappeared when the spatial frequency of the Gabors was doubled from 3.33 cpd to 6.66 cpd. CONCLUSIONS: Configurational dependencies may disappear at higher spatial frequencies because, despite increased spatial summation at detection threshold contrast levels, the intrinsically smaller receptive field sizes of neurons tuned to high spatial frequencies render them incapable of encapsulating more than one of the spatially separated Gabors within their individual receptive fields.

Journal Article↗

Vaginal birth after one previous caesarean section: a Jordanian experience.

In this prospective study, 119 women out of 135 (88%) of cases delivered previously by one lower segment caesarean section at Princess Basma Teaching Hospital in North Jordan, had a trial of labour, 103 out of 119 women (86.6%) delivered vaginally. A high incidence of vaginal delivery occurred in women originally delivered by caesarean section for cephalopelvic disproportion (CPD) (69%). Repeat caesarean section was necessary only in 13.4% of women mainly because of CPD and foetal distress. Labour was induced for obstetric reason only. The incidence of scar rupture was very low 1 of 119 cases (0.8%), with no maternal deaths. The duration of labour doesn't differ significantly for those who had from those who never had vaginal delivery before. So it is relatively safe to have a trial of labour in patients delivered previously by one caesarean section.

Cesarean Section, Repeat↗

Atherosclerosis as a risk factor for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the relationship between clinical benign prostatic hyperplasia (BPH) and atherosclerosis, using colour Doppler ultrasonography (CDUS) and symptom scores. PATIENTS, SUBJECTS AND METHODS: CDUS was used to evaluate prostatic vascularity in four groups of men, comprising young healthy subjects, patients presenting with coronary artery disease (CAD), diabetes mellitus, or peripheral arterial occlusive disease (PAOD). Resistive index (RI) measurements and computer-assisted quantification of colour pixel density (CPD) were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function were used to quantify symptoms. RESULTS: In diabetic patients and men with PAOD, perfusion of the transition zone (TZ) of the prostate was significantly lower (P < 0.001) and the RI of the TZ was significantly higher (P < 0.001) than in healthy controls and men with CAD. In diabetics and men with PAOD, the mean prostate volume was greater than in healthy controls and men with CAD. The IPSS in patients with vascular damage (diabetes, PAOD) was significantly worse than in the control group. CONCLUSIONS: The significantly lower CPD and higher RI values of the TZ in patients with vascular disease than in healthy subjects support the hypothesis that an age-related impairment of blood supply to the prostate has a key role in the development of BPH.

Aged↗

Effects of capsaicin and 5-HT3 antagonists on 5-hydroxytryptamine-evoked release of calcitonin gene-related peptide in the guinea-pig heart.

1. The effect of 5-hydroxytryptamine (5-HT) on the release of calcitonin gene-related peptide (CGRP) was studied directly in the isolated perfused heart and indirectly in the isolated left atria of guinea-pig. 2. 5-HT injection into the guinea-pig isolated and perfused heart evoked a dose-dependent (1-100 microM) release of CGRP-like immunoreactivity (LI) that was abolished by in vitro pretreatment with capsaicin and was not affected by indomethacin. 3. Chlorophenyldiguanide (CPD, 100 microM), but not 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 100 microM), sumatriptan (100 microM) or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 100 microM) evoked a release of CGRP-LI. Ondansetron (10 microM) or ICS205-930 (20 microM) completely abolished the 5-HT (100 microM)-evoked CGRP-LI release. 4. In the isolated electrically driven left atria of the guinea-pig 5-HT (1-10 microM) and CPD (3-100 microM) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8-OH-DPAT (10 microM) and DOI (10 microM) were inactive. Ondansetron inhibited the response to 5-HT with a pA2 of 6.50 (CL 6.08-6.91). 5. It is concluded that 5-HT causes a release of CGRP in the whole heart and a positive inotropic response in the isolated atria of guinea-pig. Both these effects are sensitive to capsaicin pretreatment and to 5-HT3 antagonists.

Animals↗

Diagnostic yield of prothrombotic state studies in cryptogenic stroke.

OBJECTIVES: Around 30% of ischemic strokes are considered cryptogenic. We analyzed the diagnostic yield of prothrombotic state (PS) studies in patients with an initial cryptogenic stroke (CS). MATERIAL AND METHODS: We prospectively included consecutive CS patients according to the TOAST criteria. PS included plasmatic determinations of antiphospholipid (APL) antibodies and lupus anticoagulant (LA), S (SPd) and C (CPd) protein deficiencies, and genetic analysis of the prothrombin gene mutation (PT G20210A) and the factor V Leiden mutation (FV G1691A). We recorded age, sex and vascular risk factors. RESULTS: From a total of 89 patients (mean age 56.9 +/- 14.3 years, 53% men), we identified 16 PS in 15 patients (16.85%): APL-6, LA-2, SPd-2, CPd-1, PT G20210A -3 and FV G1691A -2. One patient presented an association (APL and PT G20210A). CONCLUSIONS: One of every six patients with initial CS present a PS. Age or sex and conventional cardiovascular risk factors were not related to PS study findings, supporting the relevance of such studies in all patients with an initial CS.

Adult↗

Improved periodontal conditions following therapy.

The aim of the present clinical trial was to evaluate the effect of different modes of periodontal therapy on patients with moderately advanced periodontal disease and to express the findings in terms of probing pocket depth and attachment level alterations at periodontal sites with different initial probing depths. The material consisted of 16 patients, 35-65 years of age. Following a Baseline examination including assessments of oral hygiene status, gingival conditions, probing pocket depths and probing attachment levels, the patients were subjected to periodontal treatment. A "split-mouth" design approach of therapy was used and the jaw quadrants were randomly selected for the following different treatment procedures: (1) scaling and root planning, (2) scaling and root planing in conjunction with a gingivectomy procedure, (3) scaling and root planing in conjunction with an apically repositioned flap procedure without bone recontouring, (4) scaling and root planing in conjunction with an apically repositioned flap procedure including bone recontouring, (5) scaling and root planing in conjunction with a modified Widman flap procedure without bone recontouring and (6) scaling and root planing in conjunction with a modified Widman flap procedure including bone recontouring. The patients were following active treatment enrolled in a supervised maintenance care program including "professional tooth cleaning" once every 2 weeks during a 6-month period of healing, after which a final examination was performed. The investigation demonstrated that active therapy including meticulous subgingival debridement resulted in a low frequency of gingival sites which bled on probing, a high frequency of sites with shallow pockets (less than 4 mm) and the disappearance of pockets with a probing depth of greater than 6 mm. Between the Baseline examination and the 6-month re-examination, the probing attachment level for initially shallow pockets remained basically unaltered, but with a tendency of a minor apical shift. This occurred in all 6 treatment groups. For sites with initial probing depths of 4-6 mm and greater than 6 mm, there was in all groups some gain of probing attachment. This gain was most pronounced in the initially deeper (greater than 6 mm) pockets. With the use of regression analysis, the "critical probing depth" (CPD) value (i.e. the initial probing depth value below which loss of attachment occurred as a result of treatment and above which gain of probing attachment level resulted) was calculated for each of the 6 methods of treatment used. A comparison of the CPD-values between the 6 treatment groups did not reveal any major differences.

Adult↗

Genomic heterogeneity of DNA repair. Role in aging?

The introduction and repair of DNA lesions are generally heterogeneous with respect to different genomic domains. In particular, the repair of helix-distorting damage, such as the cyclobutane pyrimidine dimers (CPD) induced by ultraviolet light occurs selectively in expressed genes. This is due in large part to the preferential repair of transcribed DNA strands, which is then reflected in a bias toward mutagenesis from persisting lesions in nontranscribed strands. Consequently, determination of overall genomic repair efficiencies may not be a good indicator of cellular sensitivity to agents that damage DNA. Although some studies suggest an age-related accumulation of altered nucleotides in DNA, we do not know the intragenomic distribution of those changes and whether they are relevant to the physiological aspects of aging. Subtle changes in the pattern of preferential repair during maturation could have profound effects on cell and tissue function. DNA repair has been analyzed in differentiating cell systems as possible models for aging. We have observed attenuated overall repair of CPD in differentiated rat myoblasts or PC12 neuron-like cells. In both model systems, several expressed genes have been shown to be repaired relatively efficiently but without strand specificity. In another model system of human HT1080 fibroblasts differentiating in the presence of dexamethasone, we demonstrated enhanced repair in the gene for plasminogen activator inhibitor I whose transcription is induced and, correspondingly, a reduced repair rate in the urokinase plasminogen activator gene whose transcription is suppressed. We conclude that any attempted correlation of the phenomena of aging with DNA repair should focus on the relevant genes in the tissue of interest.

Aging↗

Preferential inhibition of nucleosome assembly by ultraviolet-induced (6-4)photoproducts.

We reconstituted nucleosomes in vitro using two kinds of damaged pBR322 plasmid DNA carrying cyclobutane pyrimidine dimers (CPD) or (6-4)photoproducts. The results indicate that nucleosome assembly is inhibited preferentially by (6-4)photoproducts compared with CPD, suggesting that the regions carrying (6-4)photoproducts retain their nucleosome-free form, i.e. linker-like conformation until completion of the repair processes.

Animals↗

Psychophysical visual function, retinopathy, and glycemic control in insulin-dependent diabetics with normal visual acuity.

We studied relations between psychophysical visual function and grade of retinopathy, glycemic control and clinical background data in 51 insulin-dependent diabetic patients, aged 17-47 years. Three separate qualities of visual function were examined, macular recovery time (nyctometry; 2 min adaptation), contrast sensitivity (Vistech 6000 chart; between 1.5 and 18 cycles per degree (cpd)) and colour vision (Fletcher DS8; protan/deutan and tritan). Only contrast sensitivity of 6 cpd was associated with the grade of retinopathy; reduced function was found in patients with retinopathy compared to those without. No correlations between macular recovery, contrast sensitivity and colour vision were found. None of the visual functions was significantly related to glycemic control, age, duration of diabetes, blood pressure, intraocular pressure, or urinary albumin excretion. Our data suggests that the neurosensory function of contrast sensitivity correlates more sensitively to the grade of diabetic retinopathy than macular recovery and colour vision. Cross-sectional assessments of different psychophysical visual functions seem to be of restricted clinical value as indicators of preceding glycemic control in diabetic patients with no or mild nonproliferative retinopathy.

Adolescent↗

Impaired contrast sensitivity in adolescents and young type 1 (insulin-dependent) diabetic patients with microalbuminuria.

We compared neurosensorial visual function by psychophysical tests (macular recovery time and contrast sensitivity) in two well matched groups of young Type 1 (insulin-dependent) diabetic patients with micro- and normoalbuminuria, respectively. The patients had normal visual acuity (> or = 1.0) and either no retinopathy or non-proliferative retinopathy. Thirty patients with microalbuminuria (albumin excretion > or = 15 micrograms/min in a least two out of three timed overnight urine samples) were matched (age, diabetes duration, mean one-year HbA1c, gender) with normoalbuminuric (n = 27) patients. Retinopathy (50 degree colour fundus photography) was assessed by counting microaneurysms and hemorrhages as 'red spots'. Contrast sensitivity was examined for the spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree (cpd). Macular recovery time (nyctometry) refers to the time-related (2 min) ability of the retina to regain visual acuity following exposure to bright light (photostress). Contrast sensitivity score was reduced in patients with microalbuminuria compared to those without; 18 cpd (mean and 95% confidence intervals): [4.2 (3.8-4.7) vs 5.0 (4.6-5.4), p = 0.03]. Macular recovery performance was not significantly reduced: [21.0 arbitrary units (17.5-24.6) vs 26.0 (22.6-30.7), p = 0.12]. We conclude that impaired contrast sensitivity independent of background retinopathy is shown in a group of young Type 1 (insulin-dependent) diabetic patients with low-grade microalbuminuria compared to a group of patients with normoalbuminuria.

Adolescent↗

A university accredited renal nursing course delivered by distance learning.

Continuous professional development (CPD) is limited in some regions of the UK and within Europe generally. This is compounded for all by limited resources for course fees and the lack of study leave granted away from the clinical area for full-time courses. This is set against recommendations from national and European governments and renal clinical guidelines concerning expectations of CPD and competency levels of renal nurses. In the past renal nurses have been trained in all areas of the speciality by local Schools of Nursing linked to renal units. However, since the formation of Trusts in 1990 education delivery has been ring-fenced and separated from the control of local hospitals by Schools of Nursing being incorporated into Institutes of Higher Education. That has led in some instances to a rationalising of post registration education delivery for some geographical areas. This paper will discuss the development and implementation of a distance learning renal care course taking into consideration the clinical, academic and educational requirements necessary for effective education and training at the post basic level.

Accreditation↗

Evaluating staff and student experiences of multidisciplinary continuous professional development via distance-learning.

Continuous professional development (CPD) in caring for people with kidney disease is limited in some regions of the UK and within Europe generally. This is compounded for all by limited resources for course fees and the lack of study leave granted away from the clinical area for full-time courses. This is set against recommendations from National and European governments, and renal clinical guidelines concerning expectations of CPD and clinical competency levels of renal nurses (1-4). In the past renal practitioners have been trained in all areas of the renal speciality by Schools of Nursing linked to renal units based in large teaching hospitals. However, more recent changes in the structure of Health Care provision have led in some instances to a rationalising of post registration education delivery.

Education, Distance↗

Biomechanical analysis of the three-dimensional foot structure during gait: a basic tool for clinical applications.

A novel three-dimensional numerical model of the foot, incorporating, for the first time in the literature, realistic geometric and material properties of both skeletal and soft tissue components of the foot, was developed for biomechanical analysis of its structural behavior during gait. A system of experimental methods, integrating the optical Contact Pressure Display (CPD) method for plantar pressure measurements and a Digital Radiographic Fluoroscopy (DRF) instrument for acquisition of skeletal motion during gait, was also developed in this study and subsequently used to build the foot model and validate its predictions. Using a Finite Element solver, the stress distribution within the foot structure was obtained and regions of elevated stresses for six subphases of the stance (initial-contact, heel-strike, midstance, forefoot-contact, push-off, and toe-off) were located. For each of these subphases, the model was adapted according to the corresponding fluoroscopic data, skeletal dynamics, and active muscle force loading. Validation of the stress state was achieved by comparing model predictions of contact stress distribution with respective CPD measurements. The presently developed measurement and numerical analysis tools open new approaches for clinical applications, from simulation of the development mechanisms of common foot disorders to pre- and post-interventional evaluation of their treatment.

Biomechanical Phenomena↗

Rapid characterization of spores of Bacillus cereus group bacteria by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption-ionization (MALDI) time-of-flight mass spectrometry was used to characterize the spores of 14 microorganisms of the Bacillus cereus group. This group includes the four Bacillus species B. anthracis, B. cereus, B. mycoides, and B. thuringiensis. MALDI mass spectra obtained from whole bacterial spores showed many similarities between the species, except for B. mycoides. At the same time, unique mass spectra could be obtained for the different B. cereus and B. thuringiensis strains, allowing for differentiation at the strain level. To increase the number of detectable biomarkers in the usually peak-poor MALDI spectra of spores, the spores were treated by corona plasma discharge (CPD) or sonicated prior to MALDI analysis. Spectra of sonicated or CPD-treated spores displayed an ensemble of biomarkers common for B. cereus group bacteria. Based on the spectra available, these biomarkers differentiate B. cereus group spores from those of Bacillus subtilis and Bacillus globigii. The effect of growth medium on MALDI spectra of spores was also explored.

Bacillus cereus↗

Evidence against direct involvement of cyclic GMP or cyclic AMP in bacterial chemotactic signaling.

Defects in phosphotransferase chemotaxis in cya and cpd mutants previously cited as evidence of a cyclic GMP or cyclic AMP intermediate in signal transduction were not reproduced in a study of chemotaxis in Escherichia coli and Salmonella typhimurium. In cya mutants, which lack adenylate cyclase, the addition of cyclic AMP was required for synthesis of proteins that were necessary for phosphotransferase transport and chemotaxis. However, the induced cells retained normal phosphotransferase chemotaxis after cyclic AMP was removed. Phosphotransferase chemotaxis was normal in a cpd mutant of S. typhimurium that has elevated levels of cyclic GMP and cyclic AMP. S. typhimurium crr mutants are deficient in enzyme III glucose, which is a component of the glucose transport system, and a regulator of adenylate cyclase. After preincubation with cyclic AMP, the crr mutants were deficient in enzyme II glucose-mediated transport and chemotaxis, but other chemotactic responses were normal. It is concluded that cyclic GMP does not determine the frequency of tumbling and is probably not a component of the transduction pathway. The only known role of cyclic AMP is in the synthesis of some proteins that are subject to catabolite repression.

Adenylyl Cyclases↗

Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.

Acute Disease↗

Child and adolescent injury and death from urban firearm assaults: association with age, race, and poverty.

OBJECTIVE: To describe rates and trends in the incidence of non-fatal and fatal firearm assault among children (16 years old or younger) over an 11 year period in Chicago, Illinois and to identify the socioeconomic characteristics of community areas where assaults are common. METHODS: The Chicago Police Department (CPD) records from 1986 through 1996 were reviewed for children assaulted with a firearm. United States census data for 1990 for Chicago were used to calculate incidence rates; census data were also used for community area (defined by census tract) socioeconomic descriptions. RESULTS: The CPD recorded 11,163 pediatric firearm assaults during the study period: 10,571 non-fatal and 592 (5%) fatal. From 1986 through 1996 non-fatal assaults more than doubled, with the highest rates in 1994; fatal assaults tripled, with rates peaking in 1993-94. Significant increases in non-fatal firearm assaults occurred among black and Hispanic males and females. In 1994, compared with white males, the relative risk of non-fatal assault was 7.0 (95% confidence interval (CI) 5.3 to 9.1) for black males and 3.3 (95% CI 2.5 to 4.4) for Hispanic males; the relative risk was 1.5 (95% CI 1.1 to 2.1) for black females. A handgun was the firearm used in most assaults (88% of non-fatal and 84% of fatal). Within community areas, the correlation between non-fatal and fatal assault incidence was strong (r=0.80, p<0.001). The proportion of families with income below the 1989 poverty level ($12,674) and the per cent black race in the community area together accounted for 70% of the variance in assault rates. CONCLUSIONS: From 1986 to 1994 there were significant increases in both non-fatal and fatal firearm assaults, usually by handguns; thereafter, rates declined. Urban children who were victims of non-fatal firearm assault appear to come from the same population as those who suffer fatal assaults. Black and Hispanic youth living in poverty were at particular risk.

Adolescent↗