[Lysosomal glycosidases and glycoproteinoses].
The development of chemicall, physical and enzymatic methods lead to the determination of numerous structures of glycoprotein glycans and allowed to classify them into "structural families". On the basis of this knowledge, it has been possible, 1) to demonstrate that the oligosaccharides and glycoasparagines accumulating in tissues and urines of patients with diseases characterized by a lack in lysosomal glycosidases originate from glycoprotein glycans incompletely catabolized; 2) to propose a scheme for the normal and pathological catabolism of glycoproteins and 3) to elucidate the problem of the origin of lysosomal glycosidases. These latter are internalized into the lysosomes either through a mechanism of secretion-reuptake, or by following an intracellular traffic, or via the cell plasma membrane. In al cases, membrane receptors intervene which specifically recognize phosphorylated oligomannosidic structures carried by the acidic hydrolases.


A model-based method for computation of correlation dimension, Lyapunov exponents and synchronization from depth-EEG signals.
In order to predict epileptic seizures many precursory features, extracted from the EEG signals, have been introduced. Before checking out the performance of features in detection of pre-seizure state, it is required to see whether these features are accurately extracted. Evaluation of feature estimation methods has been less considered, mainly due to the lack of a ground truth for the real EEG signals' features. In this paper, some simulated long-term depth-EEG signals, with known state spaces, are generated via a realistic neural mass model with physiological parameters. Thanks to the known ground truth of these synthetic signals, they are suitable for evaluating different algorithms used to extract the features. It is shown that conventional methods of estimating correlation dimension, the largest Lyapunov exponent, and phase coherence have non-negligible errors. Then, a parameter identification-based method is introduced for estimating the features, which leads to better estimation results for synthetic signals. It is shown that the neural mass model is able to reproduce real depth-EEG signals accurately; thus, assuming this model underlying real depth-EEG signals, can improve the accuracy of features' estimation.


Nanoparticles affect bacterial colonies' optical diffraction patterns.
It is increasingly being accepted that bacteria are able to alter their shape/colony pattern in response to adverse environmental conditions. Morphological adaptation of bacteria is known as one of their defence mechanisms against environmental stress/variations. As nanoparticles (NPs) have a unique capacity to induce a wide range of stresses to bacteria, we hypothesized that such NPs can affect the bacterial colony pattern. To test this hypothesis, we incubated a series of superparamagnetic iron oxide nanoparticles (SPIONs) with different physicochemical properties with bacterial colonies and probed the colonies' diffraction patterns by laser. The diffraction patterns of Escherichia coli, Lactobacillus rhamnosus, and Staphylococcus aureus colonies were recorded using a laser. Our results revealed the formation of distinct bacterial diffraction patterns in response to SPIONs with various concentrations and surface chemistries. Our results may pave the way toward the development of new optical approaches for the high-throughput screening of bacterial-NPs/drugs interactions.


Insulin adsorbance to polyvinylchloride surfaces with implications for constant-infusion therapy.
Because of the current interest in constant intravenous infusions of insulin for hyperglycemic conditions, we have re-examined the problem of insulin adsorption to the solid surfaces of commonly used infusion sets. Using both labeled and unlabeled insulin, we have compared solutions with and without albumin through various methods of delivery. An infusion system incorporating a 50-ml. wash-out with a solution of 25 U. regular insulin in 500 ml. normal saline permits delivery of at least 75 per cent of expected insulin for the first 50 ml. of the infusion and 100 per cent thereafter. After the first 20 ml. of the infusion, the per cent insulin recovered from the system is identical to that observed when albumin was added to the infusion solution at a concentration of 1.25 gm. per cent. From these date, we conclude that if an insulin concentration of at least 25 U./500 ml. is used, and if 50 cc. is washed through the infusion apparatus before treatment of a hyperglycemic patient is instituted, no extra protein additives are necessary.


Quantitative assessment of the biological effects of follicle regulatory protein on dihydrotestosterone-maintained spermatogenesis in hypophysectomized rat.
Follicle regulatory protein (FRP) isolated from porcine ovarian follicles influences folliculogenesis through a paracrine mechanism. A similar protein has been found in the testes and seems to have some inhibitory effects on spermatogenesis when administered to intact male experimental animals. On the basis of female and male studies, it has been ascertained that the effects of FRP are at the level of gonads and not the pituitary or the hypothalamus. In the studies with intact males it was not possible to determine the exact site of FRP action on the testes. Dihydrotestosterone (DHT) has been shown to maintain spermatogenesis in hypophysectomized rats. In order to determine if the inhibitory effects of FRP are at steps prior to the formation of DHT, FRP was administered to hypophysectomized rats that were injected with DHT. Groups of adult rats were hypophysectomized and treated daily with FRP, DHT, FRP + DHT, or vehicle alone for 30 days. At necropsy, body, testes, prostate glands, and seminal vesicle weights were recorded. One testis and sexual accessory glands were fixed for histological evaluation. The contralateral testis was decapsulated, six 2 mm segments of seminiferous tubules, representing defined stages of spermatogenesis, were isolated by transillumination-assisted microdissection, and spermatogenic cells were quantified by DNA flow cytometry. Histologically, the seminiferous tubules of vehicle-treated hypophysectomized controls showed advanced regression. Rats treated with FRP alone showed similar degeneration. On the other hand, rats treated with DHT showed maintenance of spermatogenesis comparable to normal controls. The testes of rats treated with FRP + DHT were indistinguishable from those treated with DHT only. Flow cytometric quantification of germinal cells from all groups confirmed the histological findings. In this study FRP did not exert deleterious effects on DHT-maintained spermatogenesis. This finding suggests that the inhibitory effects of FRP on spermatogenesis in intact animals may not be a direct effect on spermatogenic cells but may impair androgen action or production or DHT formation.


Holoprosencephaly in hungary: birth prevalence and clinical spectrum.
A retrospective population based survey of patients born with holoprosencephaly in South-Eastern Hungary between July 1, 1992 and June 30, 2006 was performed. All live birth cases with craniofacial and non-craniofacial abnormalities were included in the study. A total of 9 patients (5 boys and 4 girls) were found with holoprosencephaly among 185 486 live births, which correspond to a birth prevalence of 0.49 per 10,000 live births (95% confidence interval [CI]: 0.17-0.80). These figures were similar to those ones found in New York State and several European regions. In our series one newborn had trisomy 13. Eight patients did not have chromosomal abnormalities on routine testing, 4 of them had craniofacial abnormalities only and another 4 showed non-craniofacial anomalies as well. Three patients died in the neonatal period and another one in childhood. Patients surviving the neonatal period had intellectual and motor handicap, and epilepsy.


Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine.
Mesenchymal stem cells (MSCs) are self-renewing precursor cells that can differentiate into bone, fat, cartilage, and stromal cells of the bone marrow. Recent studies suggest that MSCs themselves are critical for forming a niche that maintains hematopoietic stem cells (HSCs). The ease by which human MSC-like and stromal progenitor cells can be isolated from the bone marrow and other tissues has led to the rapid development of clinical investigations exploring their anti-inflammatory properties, tissue preservation capabilities, and regenerative potential. However, the identity of genuine MSCs and their specific contributions to these various beneficial effects have remained enigmatic. In this article, we examine the definition of MSCs and discuss the importance of rigorously characterizing their stem cell activity. We review their role and that of other putative niche constituents in the regulation of bone marrow HSCs. Additionally, how MSCs and their stromal progeny alter immune function is discussed, as well as potential therapeutic implications.


A delta-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles.
We have isolated delta-conotoxin EVIA (delta-EVIA), a conopeptide in Conus ermineus venom that contains 32 amino acid residues and a six-cysteine/four-loop framework similar to that of previously described omega-, delta-, microO-, and kappa-conotoxins. However, it displays low sequence homology with the latter conotoxins. delta-EVIA inhibits Na+ channel inactivation with unique tissue specificity upon binding to receptor site 6 of neuronal Na+ channels. Using amphibian myelinated axons and spinal neurons, we showed that delta-EVIA increases the duration of action potentials by inhibiting Na+ channel inactivation. delta-EVIA considerably enhanced nerve terminal excitability and synaptic efficacy at the frog neuromuscular junction but did not affect directly elicited muscle action potentials. The neuronally selective property of delta-EVIA was confirmed by showing that a fluorescent derivative of delta-EVIA labeled motor nerve endings but not skeletal muscle fibers. In a heterologous expression system, delta-EVIA inhibited inactivation of rat neuronal Na+ channel subtypes (rNaV1.2a, rNaV1.3, and rNaV1.6) but did not affect rat skeletal (rNaV1.4) and human cardiac muscle (hNaV1.5) Na+ channel subtypes. delta-EVIA, in the range of concentrations used, is the first conotoxin found to affect neuronal Na+ channels without acting on Na+ channels of skeletal and cardiac muscle. Therefore, it is a unique tool for discriminating voltage-sensitive Na+ channel subtypes and for studying the distribution and modulation mechanisms of neuronal Na+ channels, and it may serve as a lead to design new drugs adapted to treat diseases characterized by defective nerve conduction.


[Vaginal repair of a vesico-uterine fistula type I (Jozwik) after caesarean section].
The development of a vesico-uterine fistula is a problem which occurs with an increasing number of caesarean sections. The main symptoms are permanent urinary incontinence, cyclic hematuria ("menouria") and amenorrhoea. In only 5 % of cases, spontaneous closure with bladder catheterization over weeks and hormonal management is possible, most of the time a surgical procedure is the definitive treatment. Until now, the resection of this kind of fistula was performed using a transabdominal approach most of the time. Our procedure describes a surgical repair using a transvaginal approach by exciding the fistula out of the bladder and uterus with primary closure. In this way, a recurrent laparotomy with all known associated risks could be avoided. However, after definitive treatment of the fistula, a new pregnancy should be delivered by performing a caesarean section. In this way, a rupture of the uterus during delivery could be prevented.


[Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods].
The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.


Efficacy of antidepressant medications in children and adolescents with obsessive-compulsive disorder: a systematic appraisal.
The aim of this article was to analyze systematically literature information published in English (between 1966 and January 2011) on the efficacy of antidepressants in pediatric obsessive-compulsive disorder. Data were identified through different databases by using variously combined patterns of search terms. Searches provided 85 articles, excluding duplicates, but only articles reporting primary data on use of antidepressants in this specific disorder were reviewed. Fifty-nine articles were excluded because they did not report primary efficacy data or investigated patients with different psychiatric diagnosis. Twenty-five electronically recognized articles met the inclusion criteria. Two additional studies, available as congress communication, were identified by manually checking the references' list of electronically identified articles. Reviewed studies show several methodological biases (the lack/limited number of long-term trials and head-to-head comparisons and the inclusion of patients who continued different forms of psychotherapy), which make it difficult to individuate the best pharmacological strategy. Despite these limitations, evidence-based information suggests that clomipramine and sertraline, especially for long-term treatments, should be considered as first-choice agents for treating obsessive-compulsive disorder at onset during childhood or adolescence.


Possible immortalization of Hodgkin and Reed-Sternberg cells: telomerase expression, lengthening of telomere, and inhibition of apoptosis by NF-kappaB expression.
Telomerase, an enzyme associated with cellular immortality, is expressed on malignant tumor cells. Deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells with unlimited proliferation capacity. Hodgkin and Reed-Sternberg (H&RS) cells are generally considered as neoplastic cells in Hodgkin's disease (HD), however, such cells are only found in a minority of HD lesions. In addition, H&RS cells with mitotic features are rare and mummified forms are occasionally encountered. There are no available data on the relationship between telomerase activity and apoptosis in HD. We studied 14 cases with Hodgkin's disease (mixed cellularity type, nine cases; nodular sclerosis type, five cases) to clarify the relationship between telomerase activity and apoptosis using in situ hybridization of human telomerase reverse transcriptase (hTERT), reverse transcriptase-polymerase chain reaction (RT-PCR) of hTERT, using extracted RNA and immunohistochemistry of nuclear factor-?B (NF-?B), and TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for apoptosis. We also analyzed the telomere length, using sorted H&RS cells. TUNEL showed a few apoptotic H&RS cells, but the cells frequently expressed hTERT, as confirmed by ISH and RT-PCR. Lengthening of the telomere of H&RS cells was noted in ten cases. In addition, H&RS cells frequently expressed NF-?B, which is known as an inducible transcription factor and inhibitor of apoptosis. Our findings of telomerase activity in H&RS cells indicate that these cells are neoplastic and are potentially immortal. In addition, NF-?B expression on H&RS cells suggests its possibility in inhibition of apoptosis of these cells.


The abdominoperineal resection itself is associated with an adverse outcome: the European experience based on a pooled analysis of five European randomised clinical trials on rectal cancer.
The aim of this study is to identify factors associated with the decision to perform an abdominoperineal resection (APR) and to assess if these factors or the surgical procedure itself is associated with circumferential resection margin (CRM) involvement, local recurrence (LR), overall survival (OS) and cancer-specific survival (CSS). The Swedish Rectal Cancer Trial (SRCT), TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial (PRCT) were pooled. A propensity score was calculated, which indicated the predicted probability of undergoing an APR given gender, age and distance, and used in the multivariate analyses. An APR procedure was associated with an increased risk of CRM involvement [odd ratio (OR) 2.52, p<0.001], increased LR rate [hazard ratio (HR) 1.53, p=0.001] and decreased CSS rate (HR 1.31, p=0.002), whereas the propensity score was not. The results suggest that the APR procedure itself is a significant predictor for non-radical resections and increased risk of LR and death due to cancer for patients with advanced rectal cancer.


[Contra: Is Postoperative Epidural Analgesia the Gold Standard?]
As strategy for postoperative pain therapy, epidural analgesia (EDA) is superior to systemic opiate analgesia after abdominal and thoracic surgery. In addition, EDA may significantly reduce the incidence of complications in some large operations, such as, e.g. cardiac (myocardial infarction, atrial fibrillation) and pulmonary complications (pneumonia, atelectasis), and even reduce mortality. Intestinal motility can also be improved. However, these positive effects do not appear in all interventions and not to the same degree. Therefore, for benefit-risk assessment, it is important to know both the operation-specific benefits and disadvantages of EDA. In the meantime, the distinctly different complication rates of epidural bleeding and abscesses after EDA are also known for different surgical interventions. In large open abdominal interventions, open thorax operations, and especially open abdominal aortic surgeries, EDA reduces pain and complications. It should be noted that the positive effects of EDA have so far hardly been directly compared with those of intraoperative lidocaine administration.


[Is therapeutic drug monitoring (TDM) in paediatric patients necessary?].
There is increasing discussion about the clinical usefulness of routine TDM of selected drugs in paediatrics. Routine TDM is performed as a way to individualize dosing requirements so as to achieve "therapeutic" concentrations in all patients, independently of age and individual drug response. The therapeutic ranges established for most drugs are based upon studies performed in adults. Extrapolation of these ranges to paediatric patients, especially to neonates, is questionable because drugs disposition and pharmacodynamics differ in this population compared to adults. The scepticism of the value of routine TDM in paediatric patients concerns antiepileptic drugs and digoxin. Recently also the value of vancomycin TDM in neonates has been the subject of discussion, resulting in new recommendation for dosing schedule in this age group. Therapeutic monitoring of methotrexate, especially administered in high doses in anticancer therapy is not questioned. Aminoglycosides have an extremely important role in paediatric antimicrobial therapy. They are still frequently used in the neonatal period. The rationale for monitoring of aminoglycosides is a narrow therapeutic range resulting in risk of oto- and nephrotoxicity, and large inter- and intra-subject variation in pharmacokinetics. Routine TDM is not recommended for paediatric patients (other than neonates) with normal renal function and without chronic illnesses associated with changes in pharmacokinetics of aminoglycosides. In these patients the peak and trough concentrations are within the therapeutic range using standard dosing regimes. Therapeutic monitoring of aminoglycosides is still obligatory in neonates, especially in premature and low birthweight neonates because of particularly wide inter-patient and intra-patient pharmacokinetic variability and risk of oto- and nephrotoxicity.


Efficacy of ceftazidime/avibactam in monotherapy or combination therapy against carbapenem-resistant Gram-negative bacteria: A meta-analysis.
Clinicians may use ceftazidime/avibactam in combination with other active agents to treat infections due to carbapenem-resistant organisms, although no conclusive data support this practice. This meta-analysis compared the efficacy of ceftazidime/avibactam as monotherapy or combination therapy against infections due to carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPa). An online literature search was conducted to identify observational studies published as full papers and indexed up to February 2019 comparing the efficacy, in terms of mortality and microbiological cure rates, of ceftazidime/avibactam monotherapy or combination therapy with other active agents for infections due to CRE or CRPa. The relative risk (RR) of mortality and microbiological eradication was estimated based on pooled data from all eligible studies. Eleven studies were included in the meta-analysis accounting for 396 subjects, of whom 202 received combination therapy. The mortality rate was 38.1% for combination therapy and 30.9% for monotherapy (RR = 1.18, 95% CI 0.88-1.58; P = 0.259). Similarly, no difference was found between the two groups when analysing the rate of microbiological cure (64.9% for combination therapy vs. 63.4% for monotherapy; RR = 1.04, 95% CI 0.85-1.28, P = 0.705). Moreover, no difference was observed for both outcomes when patients infected with P. aeruginosa were excluded from the analysis. This meta-analysis suggests that use of ceftazidime/avibactam in monotherapy or combination therapy for infections due to CRE or CRPa could show a similar effect on mortality and microbiological cure rates. Studies on larger samples are needed to address this important issue.


Three-dimensional fibril-reinforced finite element model of articular cartilage.
Collagen fiber orientations in articular cartilage are tissue depth-dependent and joint site-specific. A realistic three-dimensional (3D) fiber orientation has not been implemented in modeling fluid flow-dependent response of articular cartilage; thus the detailed mechanical role of the collagen network may have not been fully understood. In the present study, a previously developed fibril-reinforced model of articular cartilage was extended to account for the 3D fiber orientation. A numerical procedure for the material model was incorporated into the finite element code ABAQUS using the "user material" option. Unconfined compression and indentation testing was evaluated. For indentation testing, we considered a mechanical contact between a solid indenter and a medial femoral condyle, assuming fiber orientations in the surface layer to follow the split-line pattern. The numerical results from the 3D modeling for unconfined compression seemed reasonably to deviate from that of axisymmetric modeling. Significant fiber orientation dependence was observed in the displacement, fluid pressure and velocity for the cases of moderate strain-rates, or during early relaxation. The influence of fiber orientation diminished at static and instantaneous compressions.


The activity of the Drosophila Vestigial protein is modified by Scalloped-dependent phosphorylation.
The Drosophila vestigial gene is required for proliferation and differentiation of the adult wing and for differentiation of larval and adult muscle identity. Vestigial is part of a multi-protein transcription factor complex, which includes Scalloped, a TEAD-class DNA binding protein. Binding Scalloped is necessary for translocation of Vestigial into the nucleus. We show that Vestigial is extensively post-translationally modified and at least one of these modifications is required for proper function during development. We have shown that there is p38-dependent phosphorylation of Serine 215 in the carboxyl-terminal region of Vestigial. Phosphorylation of Serine 215 occurs in the nucleus and requires the presence of Scalloped. Comparison of a phosphomimetic and non-phosphorylatable mutant forms of Vestigial shows differences in the ability to rescue the wing and muscle phenotypes associated with a null vestigial allele.


Optimal protocol for preparation of leukocyte-poor red cells with a blood cell processor.
The optimal red cell override (RCO) protocol for preparation of leukocyte-poor red cells (LPRCs) with a blood cell processor (IBM 2991) was studied. By a four-step process, including determining leukocyte (WBC) and red cell (RBC) distributions in the processing bag after centrifugation, the optimal RCO sequence was determined. The "effectiveness index" of WBC removal also was used for comparison of the efficiencies of various RCO protocols. In this way, a four-cycle RCO sequence of 1.5/1.5/1.5/1.5 was found to be optimal for washing 130-ml units of concentrated red cells (CRCs). This protocol yielded LPRCs with means of 5.4 percent of WBCs remaining and an 84.2 percent recovery of RBCs. The optimal RCO sequence of 2.0/2.0/2.0/2.0 for washing 260-ml units of CRC gave LPRCs with means of 6.2 percent of WBCs remaining and an 87.8 percent recovery of RBCs.


Microneurographic evidence of excessive sympathetic outflow in the Guillain-Barré syndrome.
We investigated 3 patients with moderate to severe Guillain-Barré syndrome (GBS) who had transient hypertension and tachycardia during the illness. Microelectrode recordings of muscle nerve sympathetic activity were made in the peroneal nerve once during the acute phase when hypertension and tachycardia were present and twice after recovery from these symptoms. During the acute recording the level of sympathetic activity was considerably higher than after recovery, when the two recordings showed reproducible levels. The normal cardiac rhythmicity was preserved except during brief periods in one patient. Control recordings were made during the acute phase and after recovery in 4 GBS patients without clinical signs of autonomic involvement and twice in 15 healthy subjects. In each control subject the level of sympathetic activity was reproducible, although recordings were made with intervals of two days to four years. The findings show that in the GBS with transient elevations of blood pressure and heart rate there is sympathetic hyperactivity. It is suggested that the increased activity is due to reduced inhibition of the vasomotor centres caused by lesions of the afferent limbs of arterial and perhaps mainly intrathoracic baroreflexes.


Decreasing frequency of iatrogenic neonatal respiratory distress syndrome.
A retrospective study was undertaken to evaluate the obstetric events preceding delivery of infants who developed respiratory distress syndrome (RDS) at one New York City hospital between January 1970 and July 1973, and January 1980 and July 1983. Elective delivery without adequate documentation of fetal maturity occurred in 7 (11.1%) of 63 pregnancies resulting in RDS during 1970-1973 as compared to only 1 (1.4%) of 71 pregnancies resulting in RDS during 1980-1983 (P less than 0.05). This decline in "iatrogenic" RDS presumably reflects improved physician diligence in the prevention of unnecessary RDS, increased availability of ultrasound and fetal lung maturity studies, and advances in the application and interpretation of these diagnostic procedures.


[Acquired fibrotic atresia of the external auditory canal].
There are very few communications on this pathologic entity, which is also called "postinflammatory medial meatal fibrosis" (PIMMF), its etiology and the adequate therapy. Apparently the cause is a chronic inflammation (or chronic ekzema) of the medial part of the external meatus or also a long-lasting otorrhea in chronic otitis media. The stratified epithelium of the eardrum and of the adjacent bony meatus is destroyed and replaced by fibrotic tissue. The lateral part of the auditory canal remains open and has the form of the finger of a glove, it may contain granulations, but often it is lined with a smooth stratified epithelium. A severe conductive hearing loss is the result of this anomaly. During the last 10 years we operated on 46 patients (52 ears) for this pathology: after retroauricular opening, which allows the best control of the anterior tympanomeatal angle, the fibrotic tissue was removed keeping the lamina propria intact. The bony canal was widened, if necessary. The eardrum and the bony canal were covered with split skin graft from the retroauricular region, then the canal filled with an antibiotic package for 3 weeks. Underneath the fibrotic tissue we detected 3 cholesteatomata of the annular region, so it is important to remember, that the atresia may also cover a dangerous pathology. 6 times a second operation was necessary, besides that, we observed 14 recurrencies. All other patients had a wide epithelialized ear canal, their conductive hearing loss disappeared, and the results were stable over several years. Bacteriological and histological examinations were not helpful to clear up the etiology of this disease. Surgery is the treatment of choice of the acquired atresia of the external meatus. We suppose that in these patients a individual disposition causes the formation of this excessive fibrosis, which has some similarity with keloid formation.


Changes of intraocular pressure during experimental vitrectomy.
To compare the infusion pressure shown by a vitrectomy device with the actual intraocular pressure (IOP) observed during pars plana vitrectomy. Furthermore, we evaluated the effects of variable parameters on the actual IOP during vitrectomy surgery. Porcine eyes were obtained within 24 h of slaughter. Actual IOP was measured by a digital manometer during vitrectomy using the vented gas forced infusion (VGFI) system, as well as the gravity system. We analyzed the actual IOP according to the groups divided by remnant volume of infusion fluid: (500 ml; control group, 250, 125, and 50 ml). Finally, actual IOP was determined after changing variable parameters such as cutting rate, vacuum pressure, and the VGFI setting. Settings for a VGFI system and pressure supplied by a gravity system significantly correlated with actual IOP (r = 0.99, p = 0.0001; r = 0.99, and p = 0.0001). Actual IOP declined with decreasing volume of infusion fluid. If the volume of infusion fluid was <125 ml, actual IOP decreased significantly compared with the control group and the difference in actual IOP reflected a significant difference in the VGFI setting of 30 mmHg. Cutting rate as well as VGFI setting and vacuum pressure affected actual IOP. Infusion pressure shown by the vitrectomy device was similar to actual IOP in porcine eyes. However, volume of infusion fluid and variable parameters could change the actual IOP during pars plana vitrectomy. Our results may help to optimize the ideal parameters such as infusion pressure, vacuum pressure, and cutting rate of vitrectomy systems used to treat vitreoretinal diseases.


Spectral analysis of cytochromes in rat heart myocytes: transient and steady-state photodiode array spectrophotometry measurements.
Myocytes prepared from rat heart have been studied by optical spectroscopy using a photodiode array spectrophotometer adapted to a stopped flow apparatus (PASF). The isolated cells were viable for 3-4 h (i.e., over the total time of the experiments), as tested employing morphological parameters of cell damage, reactivity toward trypan blue, and the ability to use succinate in the absence and presence of digitonin. Respiration was activated by addition of sodium ascorbate and tetramethyl-para-phenylenediamine (TMPD) as exogenous reductants, in order to single out the contributions of cytochrome c and cytochrome c oxidase among the complexes of the mitochondrial respiratory chain. TMPD was shown to be freely permeable across cytoplasmic and mitochondrial membranes, with a measured KD = 0.9 mM. The use of singular value decomposition analysis coupled to PASF acquisition proved very powerful in resolving statically and kinetically, in the millisecond time region, the spectral contributions of the cytochromes. Spectral analysis was improved by adding carbon monoxide at concentrations which did not affect cytochrome c oxidase activity, but kept myoglobin fully saturated (and thus uninfluential to absorbance changes).


The 'thrifty' hypotheses: clinical and epidemiological significance for non-insulin-dependent diabetes mellitus and cardiovascular disease risk factors.
In recent decades incidence of non-insulin-dependent diabetes mellitus has increased to epidemic proportions in several traditional populations due to changes in their lifestyles from those of hunters, gatherers and subsistence agriculturists to a contemporary pattern whose central features are sedentary occupations and high-energy fuel resources. As a result, non-infectious perturbations such as non-insulin-dependent diabetes mellitus, hypertension and cardiovascular diseases emerge as the major causes of morbidity and mortality both in developing and in developed nations. Currently, the highest non-insulin-dependent diabetes mellitus prevalences are found in populations that have undergone rapid alterations in lifestyle, such as Australian Aborigines, native Americans, Pacific islanders and some migrant populations like the Asian Indians. This review focuses on non-insulin-dependent diabetes mellitus as a prime instance of the 'thrifty genotype' and its interrelationship with glucose intolerance as a prime risk factor for cardiovascular diseases including hypertension, dyslipidaemia and hyperinsulinaemia. An alternative hypothesis, namely the 'thrifty phenotype' hypothesis, challenging the genotype hypothesis is hereby presented. The review is presented to provide insight for clinical application of these hypotheses in future studies concerning the prevention and intervention strategy of non-communicable disorders. A comprehensive application of these strategies would be beneficial to researchers, clinicians and patients.


Understanding and addressing adherence issues in schizophrenia: from theory to practice.
If an easy answer to the problem of medication nonadherence in schizophrenia existed, it would have already been found. Despite the magnitude of the problem, in the past decade, significant advances have been made in understanding the nature of the adherence problem in schizophrenia. Just as there is no single adherence intervention but a range of interventions that can be matched to the specific challenges of the individual patient, there is not a single theory that explains adherence and non-adherence. Rather, there are a range of theories and concepts, with their own strengths and limitations. The goal of this article is to help provide a crosswalk from some of the emerging theories and concepts to practical clinical management approaches. To enhance understanding of this complex issue and help practitioners implement practical therapeutic interventions that encourage adherence, the following 5 theories regarding medication adherence are presented and suggestions made for applying them in clinical practice: (1) Adherence is not a clinical outcome and only matters as it interferes with outcome. (2) In schizophrenia, adherence problems are often entangled with efficacy limitations of antipsychotics. (3) Adherence can be viewed as a behavior (taking/not taking) or an attitude (prefers taking/prefers stopping). (4) When considering adherence attitudes, patient belief is always reality. (5) Adherence behavior changes and fluctuates over time and should be considered as part of the illness in the context of the long-term trajectory of desired clinical outcomes such as recovery.


Expression of the IIIc Variant of FGF Receptor-1 Confers Mitogenic Responsiveness to Heparin and FGF-5 in TAKA-1 Pancreatic Ductal Cells.
Human pancreatic cancer is a devastating diseasewith a poor prognosis (1). Although the exact reasonsfor the aggressive nature of this disorder are unknown, certain observations have pointed to theimportant role of growth factors in its pathobiology(2). Many of these cancers frequently overexpressfibroblast growth factors (FGFs) (3). FGF signalingis mediated through four high-affinity tyrosine kinasereceptors, termed fibroblast growth-factor receptors(FGFRs) (3,4). The extracellular domain of FGFRsis usually composed of three immunoglobulin (Ig)-like domains (I-III), a transmembrane region followedby a juxtamembrane domain, and a splittyrosine kinase catalytic domain. Several isoformsof FGFR-1, -2, and -3 have been identified, some of which exhibit different ligand-binding properties(3,5). Alternative splicing of the second half of Igdomain III of FGFR-1 results in three receptor variants,termed IIIa, IIIb, and IIIc. The IIIa splice variantyields a secreted receptor that is devoid of anysignaling capacity (5). The expression of the IIIbvariant is generally restricted to epithelial cell types,whereas the expression of the IIIc variant is restrictedto mesenchymal cell types (6-11).


Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part II: in vivo evaluation.
Albumin-coated Amberlite XAD-7 has been previously shown to be blood compatible in in vitro hemoperfusion experiments whith human blood. In this study, the preliminary results are reported on single hemoperfusions with albumin-coated XAD-7 resin in four patients with acute liver failure. The mean platelet count was 116+/-SE 16.3% of the initial arterial value and the mean white cell count was 96+/-SE 6.5% of initial at the end of four hours of hemoperfusion. Removal of bilirubin, phenols and substances in the middle molecular weight range by the resin was demonstrated. These preliminary results suggest albumin-coated Amberlite XAD-7 resin to be blood compatible and capable of removing protein-bound and middle molecular weight substances from patients with acute liver failure. Further clinical evaluation of repeated resin hemoperfusion is required to determine whether this treatment will be beneficial to patient survival.


A novel approach to condom lubricant analysis: in-situ analysis of swabs by FT-Raman spectroscopy and its effects on DNA analysis.
Current methods for the analysis of swabs for condom lubricants require a portion of the swab to be extracted. This requirement causes issues for those who require the swab for DNA extraction. A novel method is presented that facilitates analysis of the swab without the need for extraction. The method was shown to be equivalent to the traditional methods in terms of its sensitivity and discriminating power. The impact of the method on subsequent DNA extraction of swabs was assessed and no detrimental effects were observed. The method was used to conduct a survey of the current market for the supply of condoms in the U.K. 90% of the U.K. condom market consists of condoms lubricated with PDMS.


ATP and G proteins affect the runup of the Ca2+ current in bovine chromaffin cells.
The Ca2+ current recorded by the whole-cell technique in chromaffin cells shows, before the often described rundown, a transient facilitation or runup. Initial current amplitude was 570 +/- 165 pA and then it increased by 49 +/- 23% (n = 19, SD) over 2 +/- 1 min in the absence of adenosine 5'-triphosphate (ATP). In the presence of ATP, this process occurred with the same magnitude but it was slowed in a dose-dependent manner, lasting 17 +/- 2 min with 2 mM ATP (n = 8). Since adenosine 5'-diphosphate (ADP) does not reproduce this ATP effect, a complex series of phosphorylations is likely to intervene and we show that, at least, a cAMP-dependent i.e., cyclic adenosine monophosphate) phosphorylation occurs. Pertussis toxin (PTX) pretreatment yielded an already maximal Ca2+ current (around 1000 pA) at the time of the patch rupture, which only slightly increased thereafter (10%, n = 11). Also, guanosine 5'-diphosphate (GDP) and guanosine 5'-O-(2-thiodiphosphate) (GDP[ beta s]), induced a fast runup, which was absent in the presence of GTP. Furthermore, we show that facilitation does not occur in the presence of dihydrophyridine (DHP) antagonists. Globally, our data suggest that an ATP-dependent phosphorylation stabilizes the inhibitory control exerted by a PTX-sensitive G protein and, as a result, slows down the facilitation of L-type Ca2+ channels. The recruitment of L-type channels can also be facilitated by the application of a DHP agonist or a depolarizing prepulse protocol.l We show that these processes are only effective over a period which parallels the runup and are not additive to it.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic structure of landraces in foxtail millet (Setaria italica (L.) P. Beauv.) revealed with transposon display and interpretation to crop evolution of foxtail millet.
Although the origin and domestication process of foxtail millet (Setaria italica subsp. italica (L.) P. Beauv.) has been studied by several groups, the issue is still ambiguous. It is essential to resolve this issue by studying a large number of accessions with sufficient markers covering the entire genome. Genetic structures were analyzed by transposon display (TD) using 425 accessions of foxtail millet and 12 of the wild ancestor green foxtail (Setaria italica subsp. viridis (L.) P. Beauv.). We used three recently active transposons (TSI-1, TSI-7, and TSI-10) as genome-wide markers and succeeded in demonstrating geographical structures of the foxtail millet. A neighbor-joining dendrogram based on TD grouped the foxtail millet accessions into eight major clusters, each of which consisted of accessions collected from adjacent geographical areas. Eleven out of 12 green foxtail accessions were grouped separately from the clusters of foxtail millet. These results indicated strong regional differentiations and a long history of cultivation in each region. Furthermore, we discuss the relationship between foxtail millet and green foxtail and suggest a monophyletic origin of foxtail millet domestication.


[Imaging of primary muscular diseases : What do neurologists expect from radiologists?]
Imaging, in particular magnetic resonance imaging (MRI), has in recent years increasingly become a crucial tool for the diagnostics of inherited and acquired muscular diseases. The aim of imaging in neuromuscular disorders goes beyond the detection and quantification of degenerative muscular changes, such as fatty degeneration and includes recognition of very early signs of muscular pathologies presenting as muscular edema. Therefore, imaging is a valuable diagnostic method to support the clinical diagnosis and to narrow down the differential diagnoses, leading to specific additional diagnostic tests in order to establish the correct diagnosis. Although advances in MRI hardware and technology have led to a faster, more accurate and advanced image acquisition allowing whole body examination in a feasible fashion, the standardization of image acquisition and interpretation remains a challenge. The aim of this review article is to address the important and clinically relevant issues concerning the role of imaging of neuromuscular diseases in order to facilitate a good interdisciplinary management for the diagnostics and monitoring of neuromuscular diseases.


Implementation and evaluation of an undergraduate research practicum.
Although collegiate faculty once believed that lecture and discussion were the best strategies for teaching research to undergraduate students, educators now question using these strategies exclusively. At present, more active involvement is recommended for learning the research process and for changing students' attitudes. The development of a practicum, designed to involve students in a meaningful research experience within a limited time frame, is discussed. An evaluation of the practicum shows its contribution to increasing knowledge in selected areas and changing attitudes in undergraduate students.


[Comparative in vitro tests of silver sulphadiazine and zinc sulfadiazine swabs on burn patients].
The antibacterial effect of silver sulphadiazine is compared with that of zinc sulphadiazine in three in vitro tests with 14 different bacterial colonies. Our results demonstrate that silver sulphadiazine is more efficient than zinc sulphadiazine as an antibacterial agent. As the local application of zinc promotes and accelerates wound healing, we suggest to apply first silver sulphadiazine and then zinc sulphadiazine in combined local therapy of burn wounds.


Health-related quality of life in children and young adults with post-thrombotic syndrome: results from a cross-sectional study.
While post-thrombotic syndrome (PTS) is increasingly recognized in children with a history of deep vein thrombosis (DVT), its impact on the health-related quality of life (HRQoL) is unknown. Our objective was to evaluate the association between the PTS and HRQoL by surveying a cohort of patients treated at our institution for DVT. All unique pediatric patients (0-18 years) treated for a DVT at the Mayo Clinic during the 15-year period, 1995-2009 were identified. A previously validated PTS survey instrument and age appropriate Pediatric Quality of Life inventory, version 4 (PedsQL 4.0) were mailed to eligible patients. Linear regression models were fit to compare the HRQoL scores between PTS groups (none, mild, moderate/severe), after adjusting for the presence of potential covariates. Of the 90 respondents, 65 (72%) reported signs and/or symptoms of PTS. Mean age (± SD) at DVT diagnosis and survey completion were 12.8 (± 6.1) and 19.3 (± 7.7) years, respectively. Self-report PedsQL 4.0 module was completed by 79 patients, and 34 guardians completed the parent-proxy module. Patients with moderate to severe PTS reported significantly worse total HRQoL score (mean ± SD, 71.3 ± 13.4) as compared to patients with mild PTS (84.8 ± 14.2) and no PTS (83.4 ± 14) (P = 0.001). Moderate to severe PTS has a significant impact on self-reported HRQoL as measured using the generic PedsQL 4.0. Further research is warranted to develop a venous disease-specific quality of life measure for children with a history of DVT.


Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitis: report of the overlapping of these two autoimmune diseases.
Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC. In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen. We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.


[Ectopic parathyroid adenoma].
Ectopic parathyroid adenoma is a rare cause of primary hyperparathyroidism and can become a diagnostic challenge. We present a case report of an ectopic mediastinal parathyroid adenoma leading to primary hyperparathyroidism and responsible for a persistent asymptomatic hypercalcemia. The preoperative location of the tumor assessed by imaging studies contribute to the choice of the surgical cervical approach. Tumor resection was successful and the calcemia levels promptly returned to normal levels.


Phyllosphere Colonization by a Soil Streptomyces sp. Promotes Plant Defense Responses Against Fungal Infection.
Streptomycetes are soil-dwelling, filamentous actinobacteria and represent a prominent bacterial clade inside the plant root microbiota. The ability of streptomycetes to produce a broad spectrum of antifungal metabolites suggests that these bacteria could be used to manage plant diseases. Here, we describe the identification of a soil Streptomyces strain named AgN23 which strongly activates a large array of defense responses when applied on Arabidopsis thaliana leaves. AgN23 increased the biosynthesis of salicylic acid, leading to the development of salicylic acid induction deficient 2 (SID2)-dependent necrotic lesions. Size exclusion fractionation of plant elicitors secreted by AgN23 showed that these signals are tethered into high molecular weight complexes. AgN23 mycelium was able to colonize the leaf surface, leading to plant resistance against Alternaria brassicicola infection in wild-type Arabidopsis plants. AgN23-induced resistance was found partially compromised in salicylate, jasmonate, and ethylene mutants. Our data show that Streptomyces soil bacteria can develop at the surface of plant leaves to induce defense responses and protection against foliar fungal pathogens, extending their potential use to manage plant diseases.


Metabolic agents in the management of diabetic coronary patients: a new era.
Modulation of myocardial free fatty acid metabolism is the key target for metabolic interventions in patients with coronary artery disease (CAD) with diabetes mellitus (DM). Because of its beneficial effects on heart metabolism at rest and on myocardial ischemia and left ventricular function, trimetazidine should be always combined with classical anti-ischemic treatment in patients with DM with CAD. We believe that, the new metabolic agents including L-carnitine, dichloroacetate, perhexiline and etomoxir will be added into our arsenal for the battle against CAD especially in patients with DM in the near future.


Loss of autoreceptor functions in mice lacking the dopamine transporter.
Autoreceptors provide an important inhibitory feedback mechanism for dopamine neurons by altering neuronal functions in response to changes in extracellular levels of dopamine. Elevated dopamine may be a component of several neuropsychiatric disorders. However, evidence concerning the state of autoreceptors in such conditions has remained elusive. The function of dopamine autoreceptors was assessed in mice lacking the dopamine transporter (DAT). Genetic deletion of the DAT gene in mice results in a persistent elevation in levels of extracellular dopamine. Direct assessment of impulse-, synthesis- and release-regulating autoreceptors in these mice reveals a nearly complete loss of function. These findings may provide insight into the neurochemical consequences of hyperdopaminergia.


A first principle study of graphene functionalized with hydroxyl, nitrile, or methyl groups.
By means of ab initio calculations, we study the functionalization of graphene by different chemical groups such as hydroxyl, nitrile, or methyl. Two extreme cases of functionalization are considered: a single group on a supercell of graphene and a sheet of graphene fully functionalized. Once the equilibrium geometry is obtained by density functional theory, we found that the systems are metallic when a single group is attached to the sheet of graphene. With the exception of the nitrile functionalized boat configuration, a large bandgap is obtained at full coverage. Specifically, by using the GW approximation, our calculated bandgaps are direct and range between 5.0 and 5.5 eV for different configurations of hydroxyl functionalized graphene. An indirect GW bandgap of 6.50 eV was found in nitrile functionalized graphene while the methyl group functionalization leads to a direct bandgap with a value of 4.50 eV. Since in the two limiting cases of minimal and full coverage, the electronic structure changes drastically from a metal to a wide bandgap semiconductor, a series of intermediate states might be expected by tuning the amount of functionalization with these different groups.


Hb E and alpha-thalassemia; variability in the assembly of beta E chain containing tetramers.
The level of Hb E (including Hb A2) was quantitated in 30 adult Hb E heterozygotes by cation exchange high performance liquid chromatography; in 20 subjects the alpha-globin gene status was determined by gene mapping and polymerase chain reaction methodology. A decrease in Hb E level was observed which was directly related to the type of alpha-thalassemia that was present; the lowest percentage of Hb E (and Hb A2) was 10.2%, seen in two persons with Hb Constant Spring (CS)-Hb H disease (alpha CS alpha/--). Similar analyses were made for several newborn babies with a Hb E heterozygosity, the Hb E level was determined as beta E by a reversed phase high performance liquid chromatographic procedure. One baby with Hb E trait and Hb H disease (-alpha/--) had a beta E level of 17.7% (as % of beta A + beta E) comparable to that seen for adults with an identical genotype. One fetus with hydrops fetalis (--/--) and Hb E trait had low beta E and beta A levels which, however, were nearly identical (1.5 and 1.3% of the total hemoglobin). These beta chains apparently combine with the embryonic zeta chain to form Hb Portland-II (zeta 2 beta 2A) and a variant of this hemoglobin (zeta 2 beta 2 E). The affinity of the two beta chains for the zeta chain must be the same and quite different from that for the alpha chain. Moreover, this single observation suggests an equal synthesis of beta A and beta E chains, the low level of Hb E in adult heterozygotes being primarily the result of a greatly decreased rate of assembly of alpha beta E dimers.


Standard resection for cancer of the esophagus and cardia.
Standard techniques of esophagectomy are the most common operations currently performed for cancer of the esophagus and cardia. A review of the recent literature discloses a wide difference in findings and postoperative results. A review of the findings and results in 505 operations for cancer of the esophagus on one surgical service from January 1, 1970 to January 1, 1997 reveals a resectability rate of 90%, a hospital mortality rate of 3.3%, a postoperative complication rate of 33.9%, and an adjusted actuarial 5-year survival rate of 24. 7%. As yet, neither the use of neoadjuvant therapy nor extended techniques or resection, even when applied only in patients with low-grade lesions, have provided convincing evidence of their superiority over standard resection techniques.


[Treatment of obesity with low-carbohydrate diets (author's transl)].
Therapeutic problems with low-carbohydrate diets in the weight reduction of the obese are summarized presenting results of the literature and results of the own group. The small number of patients and the short periods of treatment do account to the controverse results observed by other authors with low-carbohydrate diets. Also studies performed under ambulant conditions should be interpreted carefully. The therapeutic effect of the low-carbohydrate formula diet tested, satisfied even in comparison with a diet discribed in other studies. Concentrations of plasma triglycerides and cholesterol elevated in part turned to normal during therapy. There were no side effects of the gastro-intestinal tract. Hypocaloric diets with reduction of carbohydrates are discussed to have a good therapeutic effect for the following reasons: High value of satiety and increase of the metabolic rate.


Minilaparoscopic versus laparoscopic cholecystectomy: a randomised controlled trial.
Since its introduction in 1987, the technique of cholecystectomy has continued to undergo evolution. Surgeons have reduced the port size and number or both to achieve improvement in postoperative pain control, rapid return to activity and better cosmetic results. Therefore, this study was done to compare the standard 4 port laparoscopic cholecystectomy (LC) with the 3 port laparoscopic cholecystectomy using a 5 mm telescope instead of 10 mm telescope (mini laparoscopic cholecystectomy - MLC). Forty patients were randomised to each group. Mean operating time, intraoperative and postoperative complications, mean period to resume walking, eating and return to normal activities and mean hospital stay were similar in the two groups. The level of postoperative pain was significantly lower in the MLC group. Patients who underwent MLC required a significantly lower dose of analgesics. In conclusion mini laparoscopic cholecystectomy is a feasible and safe procedure with less postoperative pain and better cosmesis and without increased complications.


Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury.
Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It's also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained.


Fibrin Gels Entrapment of a Poly-Cyclodextrin Nanocarrier as a Doxorubicin Delivery System in an Orthotopic Model of Neuroblastoma: Evaluation of In Vitro Activity and In Vivo Toxicity.
Fibrin gels (FBGs) are potential delivery vehicles for many drugs, and can be easily prepared from purified components. We previously demonstrated their applicability for the release of different doxorubicin (Dox) nanoparticles used clinically or in an experimental stage, such as its inclusion complex with the amino β-cyclodextrin polymer (oCD-NH2/Dox). Here we extend these studies by in vitro and in vivo evaluations. An in vitro cytotoxicity model consisting of an overlay of a neuroblastoma (NB) cell-containing agar layer above a drug-loaded FBG layer was used. Local toxicity in vivo (histology and blood analysis) was studied in a mouse orthotopic NB model (SHSY5YLuc+ cells implanted into the left adrenal gland). In vitro data show that FBGs loaded with oCD-NH2/Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH2/Dox than those loaded with Dox. Our results suggest a possible increase of the therapeutic index of Dox when locally administered through FBGs loaded with oCD-NH2/Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.


Dynamic properties of proteins from NMR spectroscopy.
Two-dimensional proton-detected heteronuclear nuclear magnetic resonance spectroscopy has been used to measure 13C and 15N spin-relaxation rate constants for several proteins. Generalized order parameters and effective internal correlation times have been calculated from the relaxation data to characterize intramolecular motions that are more rapid than overall rotational diffusion. These studies provide detailed descriptions of the magnitudes and timescales of fluctuations in protein molecules.


Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat.
Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.


Indium(III) Triflate-Catalyzed Reactions of Aza-Michael Adducts of Chalcones with Aromatic Amines: Retro-Michael Addition versus Quinoline Formation.
The indium(III) triflate-catalyzed reaction of aza-Michael adducts of chalcones with aromatic amines has been investigated. The Michael adducts derived from substituted anilines and chalcones underwent retro-Michael addition to give the original starting materials, whereas the adducts derived from 1-naphthylamines and chalcones afforded quinolines. A six-membered cyclic transition state has been proposed to explain the retro-Michael addition, while a Povarov mechanism has been put forward to explain the quinoline formation.


Simultaneous determination of water and enediols or thiols in chemical products and drugs not amenable to direct Karl Fischer titration.
A method proposed for determining water and enediols or thiols is based on consecutive titration of the enediols or thiols by a novel reagent and of water by the conventional Karl Fischer reagent in the same cell. The time for both titrations is 8-20 min. The novel reagent consists of iodine, sodium acetate as a base, and potassium iodide in a nonaqueous solvent system. The method is applicable for quality control of chemical products and drugs during their production and trade.


Relative hypophosphatemia early after transplantation is a predictor of good kidney graft function.
Phosphate level is a potent independent risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. The association between hypophosphatemia and kidney function in kidney transplant patients is uncertain. In total, 90 kidney transplant recipients were divided into two groups: one group of patients with hypophosphatemia and the other group without hypophosphatemia. The recipients with hypophosphatemia were identified as having less than or equal to the lowest quartile of serum phosphate levels at 1-, 3-, and 12-month post-transplant. The cumulative kidney survival rates were calculated for each group using the Kaplan-Meier method, and the adjusted hazard ratio (HR) was calculated using the Cox regression model. The mean age of patients was 47 years and the median follow-up period was 58 months. During the follow-up period, the following results were demonstrated in 90 transplant patients: graft loss (n = 6), mortality (n = 3). According to the Kaplan-Meier analysis results, the patients with hypophosphatemia demonstrated a significantly lower risk of 30% decline in eGFR compared to those without hypophosphatemia at 1- and 3-month post-transplant, but not at 12-month post-transplant. After adjusting for confounding factors, hypophosphatemia at 1- and 3-month post-transplant was an independent predictor of good kidney survival (HR 0.31, 95% CI 0.10-0.82 and HR 0.31, 95% CI 0.07-0.92, respectively). Our findings suggest that hypophosphatemia during the first 3 months after kidney transplantation was associated with better kidney survival.


Highly coherent supercontinuum in the mid-infrared region with cascaded tellurite and chalcogenide fibers.
We numerically investigate two-step supercontinuum (SC) generation using cascaded tellurite and chalcogenide fibers with all-normal group velocity dispersion pumped by a femtosecond laser at 2 μm. The optimized tellurite fiber is a hybrid microstructured optical fiber with a core surrounded by 12 rods. It has flat normal chromatic dispersion from 2 to 5 μm. The chalcogenide fiber is a double-core fiber with flat normal chromatic dispersion from 4 to 10 μm. The output SC spectrum from the best candidate fibers spans from 0.78 to 8.3 μm with coherence of unity all over the spectrum. Such high coherence pulse with broad spectrum will be valuable for many applications in tomography, ultrafast transient absorption spectroscopy, etc. The proposed fiber structures are all-solid and are feasible for fabrication with the common rod-in-tube method. This implies that two-step SC is a potential way to obtain broad, highly coherent SC in the mid-infrared.


A quantitative method for determination of aflatoxin B in roasted corn.
Roasting aflatoxin-contaminated corn will reduce toxin levels. A quantitative analysis for aflatoxin in roasted corn has been developed by modifying a cleanup technique for green coffee extracts approved as official first action by the AOAC. A chloroform extract is partially purified on a Florisil column, and thin layer chromatographic (TLC) plates are developed with methylene chloride-chloroform-isoamyl alcohol-formic acid (81+15+3+1). Recoveries average 101% and the sensitivity limit is 5 ppb aflatoxin B1. A 2-dimensional TLC procedure can also be used to separate the aflatoxins from background interferences.


The influence of weather on community gastroenteritis in Australia.
Infectious gastroenteritis is a common illness in Australia as elsewhere. Data from a year-long national gastroenteritis survey in 2001-2002 showed that gastroenteritis was more common in the northern and hotter part of Australia. These data were used to quantify associations between local weather variables and gastroenteritis in people aged >5 years while controlling for socioeconomic status. A distributed lag model was used to examine the influence of weather over a period of days prior to an event and the maximal effect was found at a lag of 2-5 days. The total effect over the preceding week indicated a relative increase from baseline in the probability of gastroenteritis of 2·48% (95% CI 1·01-3·97) for each degree rise (°C) over that period. Given the very high burden of gastroenteritis, this represents a substantial effect at the population level and has relevance for health predictions due to climate change.


Emerging water-borne pathogens.
Emerging water-borne pathogens constitute a major health hazard in both developed and developing nations. A new dimension to the global epidemiology of cholera-an ancient scourge-was provided by the emergence of Vibrio cholerae O139. Also, water-borne enterohaemorrhagic Escherichia coli ( E. coli O157:H7), although regarded as a problem of the industrialized west, has recently caused outbreaks in Africa. Outbreaks of chlorine-resistant Cryptosporidium have motivated water authorities to reassess the adequacy of current water-quality regulations. Of late, a host of other organisms, such as hepatitis viruses (including hepatitis E virus), Campylobacter jejuni, microsporidia, cyclospora, Yersinia enterocolitica, calciviruses and environmental bacteria like Mycobacterium spp, aeromonads, Legionella pneumophila and multidrug-resistant Pseudomonas aeruginosa have been associated with water-borne illnesses. This review critically examines the potential of these as emerging water-borne pathogens. It also examines the possible reasons, such as an increase in the number of immunocompromised individuals, urbanization and horizontal gene transfer, that may underlie their emergence. Further, measures required to face the challenge posed by these pathogens are also discussed.


Comparison of four staging systems of lymph node metastasis in gastric cancer.
The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis. In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate). In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system. Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.


Binding of bovine follicular fluid glycosaminoglycans to fibronectin, laminin and low-density lipoproteins.
Interactions of bovine follicular fluid glycosaminoglycans (GAGs) with extracellular matrix (ECM) components fibronectin and laminin and with low-density lipoproteins (LDL) were examined using affinity chromatography. Glycosaminoglycans from small (diameter less than 5 mm) and large (diameter 11-20 mm) follicles were isolated from follicular fluid. The dermatan sulphate or heparan sulphate from small or large follicles was applied to Fn-, Lm- or LDL-Sepharose columns. Portions of each fraction of the bound or unbound GAG were then subjected to gel filtration h.p.l.c. for quantification. The binding interaction between dermatan sulphate and fibronectin was significantly greater than between heparan sulphate and fibronectin (P less than 0.05); the binding interaction between GAGs from small follicles and fibronectin was significantly greater than between GAGs from large follicles (P less than 0.05). The binding interaction between GAGs from small follicles and laminin was significantly greater than for GAGs from large follicles (P less than 0.05). Dermatan sulphate from small follicles bound to fibronectin (42%), laminin (36%) and LDL (14%) and that from large follicles bound to fibronectin (14%), laminin (23%) and LDL (14%). Heparan sulphate from small follicles bound to fibronectin (17%), laminin (15%) and that from large follicles bound to fibronectin (13%), laminin (10%) and LDL (6%). These results suggest that dermatan sulphate, but not heparan sulphate, from follicles at different stages of development exhibit a varied ability to interact with components of the ECM. Both substances bound to LDL comparably in small amounts.


Effect of high-glucose conditions on human periodontal ligament endothelial cells: in vitro analysis.
Endothelial cells participate in key aspects of vascular biology, such as maintenance of capillary permeability and regulation of inflammation. According to previous reports, endothelial cells have revealed highly specific characteristics depending on the organs and tissues. In particular, periodontal endothelial cells have a higher permeability than vascular endothelial cells of other types of tissue. Periodontal disease is not only a chronic disease in oral, but also affect the entire body. Diabetes and periodontal disease are closely related, with periodontal disease even been referred to as the sixth complication of disease. However, no reports have investigated the pathophysiology of microvascular in periodontal tissue once diabetes has developed. Therefore, the aim of the present study is to investigate changes in the properties of human periodontal endothelial cells (HPDLECs) that were cultured under high-glucose conditions. We isolated HPDLECs from human periodontal ligament cells. HPDLECs were cultured under high-glucose (5.5, 11.0, 22.0 mM) and investigated proliferation, apoptosis, tube formation and the expression of cell adhesion molecules. A 5.5 mM (100 mg/dl) control was used in this study. HPDLECs stimulated with high glucose concentration exhibited suppression of cell proliferation and an increased percentage of apoptosis-positive cells. This results suggested that apoptosis was caused by TNF-α expression. The expression levels cell adhesion molecules increased. These results suggest that when HPDLECs are stimulated with a high glucose concentrations, PKC in the intracellular cell substrate is activated, increasing the expression of intercellular and vascular adhesion molecules. Thus, the results of this study demonstrate that diabetes exacerbates periodontal disease.


Isotype-like suppression of T cell-mediated immunity in vivo. II. Suppression of the early component of contact sensitivity by a Ly-2+ T cell-derived suppressor factor that binds to contact sensitivity-initiating, antigen-specific, Ly-1+ T cell-derived factors that are of different antigen specificities.
Recognition that delayed-type hypersensitivity (DTH) reactions, such as contact sensitivity (CS) in mice, are initiated by Ly-1+ T cell-derived, antigen-specific factors has led to identification of a new kind of suppressor T cell that regulates this initiation phase of CS. Regulation by these suppressor T cells is T cell isotype-like in that initiation of DTH of various antigenic specificities is suppressed, whereas, Ly-1+ T cells mediating the antigen/major histocompatibility complex-restricted, classic delayed phase of CS responses are not affected, nor are other T cell activities. This study shows that these isotype-specific suppressor T cells probably act by release of soluble, isotype-specific, suppressor factors. These isotype-specific T cell factors bind to and can be eluted from columns linked with antigen-specific Ly-1+ T cell factors that initiate CS, and are of different antigen specificities. These T cell regulating, anti-isotypic suppressor factors are derived from Lyt-2+ I-J- T cells and suppress CS-initiating T cells, but do not affect the delayed-acting T cells of CS. This is in contrast with antigen-specific T cell suppressor factors that affect the late-acting and not the early-acting T cells of CS. It is suggested that the antigen-binding, CS-initiating, T cell factors, and their regulatory, anti-isotypic T cell factors are, respectively, T cell analogues of immunoglobulin(Ig)E antibody, and IgE-binding factors, that regulate IgE antibody production by IgE+ B cells.


Pharmacokinetics of aclarubicin and its metabolites in humans and their disposition in blood cells.
The pharmacokinetics of aclarubicin, a new anthracycline antibiotic, was studied in five patients with acute leukemia or in L1210 cell suspension. Aclarubicin disappeared very rapidly from plasma and whole blood after administration at a dose of 20 mg per patient by iv bolus injection. The concentration of active metabolite M1, on the other hand, increased for up to 2 or 4 hrs after administration and exceeded that of aclarubicin, and then remained at much higher concentrations than aclarubicin for up to 24 hrs after administration. In addition, the levels of aclarubicin and its metabolites in whole blood were much higher than the corresponding plasma levels in four of the patients. The drug concentrations in blood cells of 11 patients determined 4 hrs after administration showed a significant positive correlation with leukocyte counts. Moreover, the concentration of aclarubicin and its metabolites was found to be much higher in the leukocyte fraction than in the erythrocyte fraction in vivo and in vitro. These findings indicate that aclarubicin and its metabolites in blood cells were mainly accumulated in leukocytes. In the study of intracellular drug distribution in L1210 cells, the largest amount of aclarubicin was incorporated into the nuclear fraction. This suggests a close relationship between the pronounced drug accumulation in leukocytes and the high affinity of aclarubicin for DNA.


Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells.
Monoamine oxidases (MAOs) are mitochondrial enzymes which control the levels of neurotransmitters in the brain and dietary amines in peripheral tissues via oxidative deamination. MAO has also been implicated in cell signalling. In this study, we describe the MAO-A isoform as functional in apoptosis induced by staurosporine (STS) in human dopaminergic neuroblastoma cells (SH-SY5Y). Increased levels of MAO-A activity were induced by STS, accompanied by increased MAO-A protein and activation of the initiator of the intrinsic pathway, caspase 9, and the executioner caspase 3. MAO-A mRNA levels were unaffected by STS, suggesting that changes in MAO-A protein are due to post-transcriptional events. Two unrelated MAO-A inhibitors reduced caspase activation. STS treatment resulted in sustained activation of the mitogen-activated protein kinase pathway enzymes extracellular regulated kinase, c-jun terminal kinase and p38, and depletion of the anti-apoptotic protein Bcl-2. These changes were significantly reversed by MAO inhibition. Production of reactive oxygen species was increased following STS exposure, which was blocked by both MAO inhibition and the antioxidant N-acetylcysteine. Therefore our data provide evidence that MAO-A, through its production of reactive oxygen species as a by-product of its catalytic activity on the mitochondrial surface, is recruited by the cell to enhance apoptotic signalling.


High content screening: seeing is believing.
High content screening (HCS) combines the efficiency of high-throughput techniques with the ability of cellular imaging to collect quantitative data from complex biological systems. HCS technology is integrated into all aspects of contemporary drug discovery, including primary compound screening, post-primary screening capable of supporting structure-activity relationships, and early evaluation of ADME (absorption, distribution, metabolism and excretion)/toxicity properties and complex multivariate drug profiling. Recently, high content approaches have been used extensively to interrogate stem cell biology. Despite these dramatic advances, a number of significant challenges remain related to the use of more biology- and disease-relevant cell systems, the development of informative reagents to measure and manipulate cellular events, and the integration of data management and informatics.


[Laparoscopic appendectomy and laparotomy appendectomy: comparison of methods].
The study compares the real advantages of laparoscopic appendicectomy using only a transumbilical trocar, with laparotomic appendicectomy in the management of acute and/or chronic pain in the lower right abdominal quadrant. From May 1997 to April 2000, 88 patients were treated: 27 (group I) with the laparoscopic approach, and 61 (group II) with laparotomy. We compared operating times, incidence of complications, hospital stay and cosmetic result. We also reviewed the literature on this subject over the past ten years. Average operating time was 45 minutes in group I and 30 minutes in group II; complications consisted in 2 cases of omphalitis in the laparoscopic group and 3 infections of the wound and 2 cases of lipolysis of the abdominal wall in the laparotomic group. The average hospital stay was 3.2 days in the laparoscopic group against 4.7 days in the laparotomic group. Resumption of work and sport occurred after 10 to 20 days and 15 to 45 days in groups I and II, respectively. The total cost was lower in the laparoscopic group. The laparoscopic approach appears to be an effective technique for the management of acute and chronic appendicitis, as it allows both treatment of the pathology and diagnosis and treatment of other unknown pathologies, with exploration of the abdominal cavity. In addition, it guarantees a good cosmetic result, a short hospital stay with a low incidence of complications and an advantageous cost/benefit ratio.


Shoulder impingement syndrome. Results of operative release.
For the release of mechanical impingement occurring during the movement of the humeral head and its overlying rotator cuff beneath the coracoacromial arch, 21 patients who had a painful arc resistant to conservative treatment, were treated by subacromial recession operations. The procedure consisted of resection of the coracroacromial ligament, anterior acromioplasty, excision of the acromioclavicular joint and shaving of the greater tuberosity. Resection of the coracoacromial ligament was carried out in all patients. The other procedures were added when required for complete release of the impingement. Nineteen patients obtained satisfactory results with a minimum follow-up of one year. A satisfactory result was obtained only when the operative procedure relieved the specific mechanical impingement, i.e., coracoacromial ligament, acromial spur, osteoarthritic acromioclavicular joint or exuberant greater tuberosity.


Psychotherapy of the otolaryngology patient.
Psychotherapy is an essential skill in the treatment of the medically ill patient. It represents to a significant extent the manner in which we understand and intervene in the patient's efforts to cope with overwhelming loss and grief. Psychotherapy of the Otolaryngology patient is especially challenging because of the substantial impediments to communication in this population. This paper will review some of the special issues that apply to many medically or surgically ill individuals but which are almost universal to the Otolaryngology patients. In particular the special topics of "Body Image" including disfigurement and cosmetic surgery, and "The Role of Verbalization" will be discussed. Consideration is also given to the special topic of countertransference which is also encountered in psychotherapy in reaction to these patients.


Complete nucleotide sequence of an Argentinean isolate of sweet potato virus G.
Sweet potato virus G belongs to the largest plant virus genus Potyvirus. This virus was detected for the first time in Argentina and then sequenced using the method of next-generation pyrosequencing. The complete genome was found to be 10,798 nucleotides excluding the poly-A tail with a predicted genome organization typical for a member of the genus Potyvirus. This is the first report of the complete genomic sequence of a SPVG isolated from South America.


The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus.
The purpose of this study was to compare the effects of 3 different modalities of exercise on metabolic control, insulin resistance, inflammatory markers, adipocytokines, and tissue expression of insulin receptor substrate (IRS)-1 after 12 weeks of training among patients with type 2 diabetes mellitus. Forty-eight patients with type 2 diabetes mellitus were randomly assigned to 4 groups of training (3 times a week, 60 minutes per session): aerobic group (n = 12), resistance group (n = 12), combined (aerobic and resistance) group (n = 12), and control group (n = 12). Fasting and postprandial blood glucose, glycated hemoglobin, lipid profile, insulin resistance index (homeostasis model assessment of insulin resistance), adipocytokines (adiponectin, visfatin, and resistin), tumor necrosis factor, interleukin, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at the end of the study. Patients also underwent a muscle microbiopsy before and after training to quantify IRS-1 expression. All 4 groups displayed decreases in blood pressure, fasting plasma glucose, postprandial plasma glucose, lipid profile, and hs-CRP (P < .05); and there was no difference across the groups. After training, the IRS-1 expression increased by 65% in the resistance group (P < .05) and by 90% in the combined group (P < .01). Exercise training favorably affects glycemic parameters, lipid profile, blood pressure, and hs-CRP. In addition, resistance and combined training can increase IRS-1 expression.


A critical review of low-carbohydrate diets in people with Type 2 diabetes.
The efficacy of low-carbohydrate diets (LCD) in people with Type 2 diabetes has divided the nutrition community. This review seeks to re-examine the available data to clarify understanding. A comprehensive search of databases was used to identify meta-analyses of LCD in Type 2 diabetes. To improve the quality of the studies analysed, the following inclusion criteria were applied: randomized control trials ≥ 4 weeks in people aged > 18 years with Type 2 diabetes; a carbohydrate intake ≤ 45% of total energy intake per day; and a dietary intake assessment at the end of the study. The resulting studies were subjected to a thematic analysis. Nine meta-analyses were identified containing 153 studies. Twelve studies met our amended inclusion criteria. There were no significant differences in metabolic markers, including glycaemic control, between the two diets, although weight loss with a LCD was greater in one study. Carbohydrate intake at 1 year in very LCD (< 50 g of carbohydrates) ranged from 132 to 162 g. In some studies, the difference between diets was as little as 8 g/day of carbohydrates. Total energy intake remains the dietary predictor of body weight. A LCD appears no different from a high-carbohydrate diet in terms of metabolic markers and glycaemic control. Very LCDs may not be sustainable over a medium to longer term as carbohydrate intake in diets within studies often converged toward a more moderate level. The variable quality of studies included in earlier meta-analyses likely explains the previous inconsistent findings between meta-analyses.


[Indications-related use of stockings--measuring venous pump function].
In 48 patients (16 healthy persons, 16 patients with venous incompetence and 16 patients with phlebographic proved status after thrombosis) the effect of medical compression stockings of different compression pressure (Sigvaris Thrombo, Sigvaris 503, Sigvaris 504) on venous pumping function was studied by foot volumetry. In patients with varicosis and preexistent reduced pumping function the expelled volume in average ascended from 13.0 to 16.23 (+25%, Sigvaris 503), respectifly to 16.52 (+27%, Sigvaris 504) (p less than 0.05 Wilcox and Wilcoxon test). In patients in status after deep leg vein thrombosis with very reduced pumping function it came to an increase of expelled volume from 8.48 to 11.08 (+31%, Sigvaris 503) and to 12.55 (+48%, Sigvaris 504) (p less than 0.01). The hospital stocking Sigvaris Thrombo did not really improve the venous pumping function. So for the first time the common prescription of medical compression stockings class II in patients with varicosis and in mild cases of chronic venous incompetence and of stockings class III in patients in status after deep leg vein thrombosis is justified by measurement.


Effect of high population density environment on skin barrier function in mice.
Previous reports have demonstrated that stressful stimuli markedly influenced physiological conditions and homeostasis. In this study, we examined the influence of high population density environment on barrier function and water retention property of skin in mice. Overcrowding stress induced dramatic body weight reduction and significant increase in adrenal gland weight. Macroscopic skin appearance showed moderate exfoliation and slight wrinkle formation in the stress group. Moreover epidermis hyperplasia not concomitant with inflammatory reactions such as infiltration of immunocytes and vasodilation was observed in the skin from the stress group. Skin surface conductance in the stress group was significantly lower than in the control group. On the other hand, transepidermal water loss in the stress group increased significantly, compared to the control group. Moreover, transdermal penetration of indomethacin and nicotinic acid amide was enhanced significantly. These results suggest that overcrowding stress induced impairment of barrier function and water retention property. To elucidate the mechanism of overcrowding stress-induce dry skin, contents of ceramide and pyrrolidone carboxylic acid, which are the important compounds contributing to those functions were evaluated. Both of them in stratum corneum declined significantly in the stress group. Taken together, these results demonstrate that overcrowding stress induced dry skin, and that the impairment of barrier function and water retention property correlated with decrease in ceramide and pyrrolidone carboxylic acid.


Simultaneous nitrification, denitrification and phosphorus removal in a sequencing batch reactor (SBR) under low temperature.
Simultaneous nitrogen and phosphorus removal in winter is one of the great challenges in wastewater treatment processes due to the poor bioactivity of microbial communities. In this study, excellent performance of simultaneous nitrification, denitrification and phosphorus removal (SNDPR) was achieved at low temperature of 10 °C and COD/N ratio of 6 in a lab-scale sequencing batch reactor. Total nitrogen (TN) and phosphorus (TP) removal efficiency reached 89.6% and 97.5%, respectively, accompanied with N2O emission of 7.46% TN due to the primary contribution (70%) of nitrifier denitrification. It was further confirmed that polyphosphate accumulating organisms (PAOs) were dominant in microbial communities revealed by fluorescence in situ hybridization and 16S rRNA amplicon sequencing. Moreover, denitrifying phosphorus removal by PAOs through nitrite pathway was found to be the main reason for the high efficiency of this SNDPR process. Denitrifying PAOs, especially the subgroup PAOII capable of utilizing nitrite to take up phosphorus, played a significant role in highly efficient TN and TP removal at low temperature. Furthermore, genus Propionivibrio was enriched (48.9%) in the bacterial community based on the 16S rRNA analysis, which was proposed to be a crucial member involved in the nitrogen and phosphorus removal simultaneously at low temperature in this system.


Different responses of human anti-HLA and anti-alphagal antibody to long-term intravenous immunoglobulin therapy.
Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose alpha1-3 galactose (alphaGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-alphaGal IgG. Levels of PRA, anti-alphaGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-alphaGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alphaGal IgG, catabolism of anti-alphaGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-alphaGal IgG level it would be necessary to use IVIG depleted of this antibody.


Predictors of hospitalized patients' intentions to prevent healthcare harm: a cross sectional survey.
Patients can play an important role in reducing healthcare harm but little is known about the factors that may affect patients' willingness to participate. In order to encourage the 'active' patient it is critical that we gain a deeper understanding of the antecedents of safety-relevant behaviours. Doing this will enable the implementation of effective interventions aimed at supporting patients to work with healthcare professionals in ensuring safe care. To examine predictors of patients' intentions to engage in two safety behaviours: (1) reminding healthcare staff to wash their hands and; (2) notifying healthcare staff if they are not wearing a hospital identification bracelet. Cross-sectional survey study. A purposive sampling method was employed to recruit 80 medical and surgical hospital inpatients aged 18-80 (mean 48) from one inner city London teaching hospital. A 42 item survey that measured the extent that patients' control beliefs, behavioural beliefs, normative beliefs and perceived susceptibility and severity towards a hospital-acquired infection or a misidentification error could predict their intentions to ask doctors/nurses about their hand washing compliance or notify doctors/nurses if they are not wearing a hospital identification bracelet. Data was analysed using multiple regression analysis. Control beliefs, normative beliefs and perceived severity were the strongest predictors of patients' intentions to participate in both behaviours. The regression models accounted for a smaller percentage of the variance in patients' intentions to ask doctors/nurses if they have washed their hands (42%/37%) than notifying staff if they were not wearing an identification bracelet (54%/56%). If patients understand why a behaviour is beneficial, they perceive it as acceptable to participate in and that they have control over the decision to engage in the behaviour, we hypothesise that more patients will intend to participate in that behaviour. When designing interventions aimed at encouraging the participation of patients in promoting their own safety, consideration should be given to the potential influence of patients' control beliefs, normative beliefs and perceived severity of errors on their intentions to participate.