In-vitro antidiabetic activity of a Bistorta officinalis Delarbre root extract can not be confirmed in the in-vivo models hen's egg test and Drosophila melanogaster.

The potential of plant bioactives for the prevention and therapy of diabetes is increasingly being recognized. In the present study we investigated the antidiabetic properties of an aqueous Bistorta officinalis Delarbre extract (BODE) by employing both in-vitro assays and in-vivo models. Multiple targets in glucose homeostasis which are involved in the regulation of the blood glucose level were affected by BODE in-vitro. The extract exhibited inhibitory activities towards the intestinal carbohydrate-hydrolysing enzymes α-amylase and α-glucosidase with IC50 values of 81.5 µg/mL and 8.4 µg/mL, respectively. Furthermore, moderate reduction of the dipeptidyl peptidase-4 (DPP4) enzyme activity was evident when tested in the presence of 1.0 mg/mL BODE. A significant inhibition of the intestinal glucose transporter sodium-dependent glucose transporter 1 (SGLT1) in response to 1.0 mg/mL BODE was shown for Caco-2 cells mounted in Ussing chambers. High performance liquid chromatography-mass spectrometry analyses of the BODE revealed several plant bioactives including gallotannins, catechins and chlorogenic acid. Although our in-vitro data were promising, BODE-supplementation in the model organism Drosophila melanogaster lacked to confirm the antidiabetic effect of the extract in-vivo. Moreover, BODE failed to reduce blood glucose levels in chicken embryos (in-ovo). Hence, BODE is probably not a suitable candidate for developing a pharmaceutical against diabetes mellitus.

[Life-threatening subcutaneous emphysema after minor blow to the neck]. / Lebensbedrohliches Hautemphysem nach banalem Stoß gegen den Hals.

After a minor blow to the neck from the handlebars of a bike, a 5-year-old boy developed a massive subcutaneous emphysema with respiratory distress. Orotracheal intubation was performed. A computed tomography (CT) scan of the neck and thorax showed a pneumomediastinum and a bilateral pneumothorax. No injury to the large airways was identified. The patient was stabilized by insertion of chest tubes and controlled ventilation. The endoscopic examination of the trachea revealed a tear of the pars membranacea, which was successfully treated conservatively. The specific features of the injury and the airway management are discussed based on a review of the current literature.

Long term peritoneal dialysis in an anuric preterm infant - a futile treatment?

The primarily anuric very low birth weight infant (VLBWI) is an ethical challenge for the attending doctor as well as for the parents. Long term peritoneal dialysis (PD) might provide an acceptable way in treating a primarily anuric VLBWI prior to kidney transplantation without endangering the child's neurologic development. We report a case of a VLBWI born at 30 weeks gestational age after anhydramnion for 5 weeks. Postnatally the neonate had persisting anuria and was successfully treated with peritonealdialysis for 31 months followed by hemodialysis for 12 months and eventually received a renal transplantion at the age of 43 months.

Continuous S-(+)-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass.

BACKGROUND: Coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) leads to elevated circulating plasma cytokines. In this prospective randomized study, the effect of an S-(+)-ketamine-based anaesthetic protocol on perioperative plasma cytokine levels was compared with standard anaesthesia with propofol and sufentanil during CPB. METHODS: Patients undergoing elective on-pump CABG were randomly allocated to anaesthesia with sufentanil-propofol-midazolam (Sufentanil) or S-(+)-ketamine-propofol-midazolam (Ketamine). Blood samples were obtained before induction of anaesthesia (baseline) and also at 1, 6, and 24 h after aortic unclamping. Plasma levels of the interleukins (IL)-6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha were determined by enzyme-linked immunosorbent assay. RESULTS: One hundred and twenty-eight patients were studied (Ketamine: n=60; Sufentanil: n=68). All measured cytokines increased during and after CPB. However, the increase in the pro-inflammatory cytokines IL-6 and IL-8 6 h after aortic unclamping was significantly lower in the Ketamine group compared with the Sufentanil group [mean (sd): IL-6 56.75 (46.28) pg ml⁻¹ (Ketamine) vs 172.64 (149.93) pg ml⁻¹ (Sufentanil), P<0.01; IL-8 7.74 (14.72) pg ml⁻¹ (Ketamine) vs 26.3 (47.12) pg ml⁻¹ (Sufentanil), P<0.01]. In contrast, the anti-inflammatory cytokine IL-10 showed higher levels 1 h after unclamping in the Ketamine group compared with the Sufentanil group [mean (sd): 69.59 (78.78) vs 24.63 (37.7) pg ml⁻¹, P<0.001]. CONCLUSION: Our data demonstrate that S-(+)-ketamine possesses anti-inflammatory potential. Anaesthesia with S-(+)-ketamine may have beneficial effects in attenuating the CPB-induced systemic inflammatory response.

[Life-threatening macroglossia following cleft palate palatoplasty]. / Lebensbedrohliche Makroglossie nach Gaumenspaltenverschluss.

The case of a 13-month-old child who developed a life-threatening macroglossia with airway obstruction following palatoplasty for a cleft palate is reported. As direct laryngoscopy was not feasible a laryngeal mask (LM) was inserted to secure the airway. Under fiber optic guidance an endotracheal tube was then introduced via the LM. In this article the incidence, pathophysiology, clinical dynamics, options for emergency anesthesia management and organizational implications of this rare but typical complication in the field of oral and craniomaxillofacial surgery are reported.

Comparison of S-(+)-ketamine- with sufentanil-based anaesthesia for elective coronary artery bypass graft surgery: effect on troponin T levels.

BACKGROUND: S-(+)-ketamine anaesthesia carries potential benefits for the cardiovascularly compromised patient. However, the use of S-(+)-ketamine in ischaemic coronary artery disease is controversial. In a prospective, randomized, clinical trial, we have investigated whether an S-(+)-ketamine-based anaesthetic protocol leads to increased cardiac troponin T levels (cTnT) after coronary artery bypass grafting (CABG). METHODS: Two hundred and nine patients undergoing elective CABG were randomized to receive either i.v. anaesthesia with sufentanil-midazolam-propofol (SMP; n=108) or S-(+)-ketamine-midazolam-propofol (KMP; n=101). Haemodynamic variables were maintained within the normal range. Invasive haemodynamic monitoring was performed using a pulmonary artery catheter. Plasma cTnT levels were sampled before induction and 1, 6, and 24 h after aortic unclamping. Cardiovascular adverse events, such as electrocardiographic signs of ischaemia, perioperative myocardial infarction, and death, were recorded. RESULTS: Patient characteristics, cardiac profile, intraoperative management, and the incidence of cardiovascular adverse events were comparable between the groups. Plasma cTnT levels increased after operation in both groups. cTnT levels were significantly lower in the KMP group 6 h after aortic unclamping compared with the SMP group (P=0.004), but did not differ 24 h after aortic unclamping [median (range): SMP 0.4 (0.01-3.9) vs KMP 0.4 (0.07-6.6) microg litre(-1), P=0.338]. CONCLUSIONS: S-(+)-ketamine does not accentuate postoperative cTNT rises in haemodynamically stable elective CABG patients.

Electron density controlled carbamate ligand binding mode: towards a better understanding of metalloenzyme activity.

The first structurally characterized mononuclear biscarbamate complex of Zn with eta1-coordinated carbamate ligands can be prepared by reaction between [EtZn(O2CN(iBu)2)]4 and a guanidine base. Usage of a weaker base leads to eta2-coordinated complexes.

[Partial CO(2) rebreathing technique versus thermodilution: measurement of cardiac output before and after operations with extracorporeal circulation]. / "Partielle CO(2)-Rückatmungstechnik" versus Thermodilution Bestimmung des Herzzeitvolumens vor und nach Eingriffen mit extrakorporaler Zirkulation.

BACKGROUND: The NICO(2) monitor determines "pulmonary capillary blood flow" (Qpc) and cardiac output (Qt) using the "partial CO(2) rebreathing technique". The agreement between NICO(2) and thermodilution (TD) cardiac output was compared before and after cardiac surgery with cardiopulmonary bypass (CBP). In addition, the possibility of calculating the intrapulmonary shunt fraction (Qs/Qt) by combining data from the NICO(2) monitor and the TD was investigated. METHODS: In 32 patients measurements were made following induction of anesthesia ("pre-CBP"), 30 min after weaning from CBP ("post-CBP"), and 6-8 h after surgery ("post-OP"). Qt was determined by the NICO(2) monitor and TD, Qpc by the NICO(2) monitor, and Qs/Qt(O(2)) from the standard formula. An intrapulmonary shunt was calculated using Qpc(NICO(2)) and Qt(TD) according to the equation Qs/Qt=1-Qpc/Qt. Bland-Altman and regression analysis techniques were used for statistical evaluation. RESULTS: "Pre-CBP" there was a good agreement between Qt(NICO(2)) and Qt(TD) with both a bias and precision of -0.13+/-0.46 l/min and a correlation of r=0.88+/-0.47 ( p<0.001). In contrast, "post-CBP" and "post-OP" there was a lack of agreement for Qt (bias and precision: 0.97+/-1.05 l/min and -0.33+/-0.8 l/min, respectively). Regarding the shunt calculations no significant correlations between methods could be found. CONCLUSION: Cardiac output measurement by the NICO(2) monitor agree well with TD under steady-state conditions but after CBP the agreement was too small. Combining Qpc(NICO(2)) and Qt(TD) does not offer a reliable possibility for calculating intrapulmonary shunt.

Obstacles facing translational research in academic medical centers.

Over the last quarter of the 20th century, there has been a boom in biomedical research discoveries that, for the most part, has not been successfully exploited for improving medical therapy or diagnosis. This lack of success is surprising because there is a broad consensus within academic medical centers (AMCs) that a primary mission is to move scientific discoveries into meaningful clinical outcomes, and there are numerous opportunities for doing so. We illustrate the latter point with 10 clinical opportunities for translating scientific discoveries from our field of vascular biology and transplantation. We attribute the limited success of translation to various factors, chief of which is that translation is rarely straightforward and requires continuing research in both the clinic and the laboratory. Translational research is hindered by insufficient targeted resources, a shortage of qualified investigators, an academic culture that hinders collaboration between clinical and laboratory-based investigators, a traditional structure of the AMC that favors departmental efforts over interdisciplinary programs, an increasing regulatory burden, and a lack of specific mechanisms within the AMC for facilitating solutions to these problems. We offer several suggestions to reduce these impediments.

Gene function analysis by amber stop codon suppression: CMBF is a nuclear protein that supports growth and development of Dictyostelium amoebae.

The C-module-binding factor, CMBF, is a nuclear DNA-binding protein which was originally identified through its specific binding to a promoter element within the retrotransposable element TRE5-A of Dictyostelium discoideum AX2 cells. In order to analyse putative physiological functions of CMBF for the TRE5-A-hosting D. discoideum cells, we used a novel strategy to create mutant cell lines which stably underexpressed functional CMBF. An amber (UAG) translation stop codon was introduced into the chromosomal copy of the CMBF-encoding gene (cbfA), and an amber suppressor tRNA gene was expressed in the same mutant cells. Due to the low efficiency of translation stop codon suppression in this system all recovered cell lines expressed <20 % of wild-type CMBF levels. The mutant cell lines displayed strong growth phenotypes when plated on their natural food source, bacteria. We show evidence that growth reduction was due to impaired phagocytosis of bacteria in the mutants. All obtained mutants showed a strong developmental defect which was defined by the formation of very small fruiting bodies. The strength of the developmental phenotype appeared to depend upon the residual CMBF levels maintained in the mutants. We propose that CMBF is a general transcription regulator which supports the normal expression of several genes required for the maintenance of high proliferation rates of D. discoideum amoebae as well as proper aggregation and development. Our results demonstrate that amber stop codon suppression may be a useful strategy to stably underexpress proteins whose coding genes cannot be successfully disrupted by homologous recombination.

The ancestral graph and gene genealogy under frequency-dependent selection.

Minority-advantage frequency-dependent selection has been proposed as the cause for the high level of observed polymorphism in some self/nonself-recognition systems. We present a mathematically rigorous derivation of the ancestral graph for a sample of genes that evolved according to a haploid infinite-alleles model of minority-advantage frequency-dependent selection. In the case of sufficiently weak selection, the gene genealogy can be extracted from the ancestral graph. We demonstrate that the gene genealogy under this model is identical to that obtained for a diploid model with heterozygote advantage. The case of strong selection is exemplified by a one-locus haploid self-incompatibility system; in this context, we investigate the number of alleles that can be maintained in a spatial versus a non-spatial habitat. Finally, we compare gametophytic self-incompatibility to the haploid self-incompatibility model.

Habitat Destruction and Competitive Coexistence in Spatially Explicit Models with Local Interactions.

We investigate the competition-colonization trade-off in a two-species competition model in various heterogeneous environments. The competitiveness of species is hierarchically ordered and the dynamics of the model are described by spatially local interactions of individuals. The size of the local neighborhood may depend on the species. The habitat consists of inhabitable and permanently destroyed sites. It was previously observed (Nee & May, 1992; Tilman et al., 1994, 1997) that destruction of habitat may aid the inferior species and cause the superior species to go extinct. These conclusions were based on an n-species model in which the spatial arrangement of destroyed sites was ignored. We examine the effects of different spatial arrangements of destroyed sites on survival and coexistence of the two species. We conclude that the spatial arrangement plays an important role and can influence the outcome qualitatively. The key quantity for predicting the outcome of habitat destruction on species survival is the relationship between the mean dispersal distance and the mean distance between inhabitable and destroyed sites. We contrast the hierarchical model with a version of the Lotka-Volterra model of interspecific competition and show that habitat destruction can alter the dominance relationship between species by reducing intraspecific competition.Copyright 1998 Academic Press

Ancestral Processes with Selection

In this paper, we show how to construct the genealogy of a sample of genes for a large class of models with selection and mutation. Each gene corresponds to a single locus at which there is no recombination. The genealogy of the sample is embedded in a graph which we call the ancestral selection graph. This graph contains all the information about the ancestry; it is the analogue of Kingman's coalescent process which arises in the case with no selection. The ancestral selection graph can be easily simulated and we outline an algorithm for simulating samples. The main goal is to analyze the ancestral selection graph and to compare it to Kingman's coalescent process. In the case of no mutation, we find that the distribution of the time to the most recent common ancestor does not depend on the selection coefficient and hence is the same as in the neutral case. When the mutation rate is positive, we give a procedure for computing the probability that two individuals in a sample are identical by descent and the Laplace transform of the time to the most recent common ancestor of a sample of two individuals; we evaluate the first two terms of their respective power series in terms of the selection coefficient. The probability of identity by descent depends on both the selection coefficient and the mutation rate and is different from the analogous expression in the neutral case. The Laplace transform does not have a linear correction term in the selection coefficient. We also provide a recursion formula that can be used to approximate the probability of a given sample by simulating backwards along the sample paths of the ancestral selection graph, a technique developed by Griffiths and Tavare (1994).

[Effects of various feeding regimens in multiple trauma patients on septic complications and immune parameters]. / Auswirkungen verschiedener Ernährungsregime bei polytraumatisierten Patienten auf septische Komplikationen und Immunparameter.

OBJECTIVE: The aim of this study was to investigate the incidence of septic complications, the immunological changes by the course of lymphocyte subsets and metabolic parameters on polytraumatised patients when given nutritional support in form of early enteral and total parenteral nutrition. Furthermore, we looked for differences between a standard enteral diet and a diet supplemented with arginine, omega-3-fatty acids, nucleotide, and selenium. METHODS: 30 polytraumatised patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II)-Score > 10 points, who received nutritional support for a minimum of 7 days, were randomised to a "supplemented enteral group" (group 1), an "enteral standard group" (group 2), or a "parenteral group" (group 3). In the first both groups there were early enteral feeding. The patients of group 3 were fed isonitrogenous and isocaloric to group 2. Leucocytes, lymphocytes, CD3(+)-, CD4(+)-, CD3+HLA-DR(+)-, CD8(+)-, CD19(+)-subsets, natural killer-cells (CD56+) and metabolic parameters were measured on days 1, 3, 5, 7. RESULTS: Septic complications occurred in 2 patients in group 1, in 1 patient in group 2 and in 4 patients in group 3. The total number of lymphocytes had an increase on day 7 in group 1 (1420/microliter) and group 2 (1620/microliter) and were higher compared with group 3 (1044/microliter). On day 7 T-cells (CD3+) were 1107/microliter in group 1, 1014/microliter in group 2 and 770/microliter in group 3, T-helper-cells (CD4+) rose on day 7 higher in the enteral fed groups (group 1:746/microliter, group 2:719/microliter) than in group 3 (570/microliter). No significant differences between the groups were seen by CD3+HLA-DR(+)-cells, T-suppressor-cells (CD8+), B-cells (CD19+) and natural killer-cells (CD56). CONCLUSION: Early enteral nutrition seems to stabilise the immunosuppression of polytraumatised patients in an earlier phase. There is a consolidation of the lymphocyte counts, and of T(CD3+)- and T-helper-cells (CD4+). This could be the immunological correlate for the number of septic complications in the enteral fed groups. Therefore polytraumatised patients should be fed rather early enteral than parenteral when possible. In the initial phase after the trauma the way of nutritional support has more importance on the immune system as nutritional contents. So, in this form of studying, there is no advantage of immunonutrition.

The genealogy of samples in models with selection.

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

Children's concepts of healing: cognitive development and locus of control factors.

This study of young children's understanding of the process of healing indicates that both level of cognitive development and locus of control are relevant factors. The importance of the children's locus of control orienation to their understanding was found to depend upon the interaction of the cognitive level and the complexity of the concept considered.