Standardized extracts from Chinese herbs induce IL-10 production in human monocyte-derived dendritic cells and alter their differentiation in vitro

BACKGROUND: The efficacy of traditional Chinese medicine (TCM) as a treatment for atopic dermatitis has been evaluated in clinical trials. Until now, the underlying mechanism of this treatment has remained completely elusive; this is particularly true of its putative effects on dendritic cells (DCs), which might play a pivotal role in the disease. OBJECTIVE: We investigated the influence of a standardized extract from 10 Chinese herbs that was successfully used in clinical trials on the generation of monocyte-derived DCs from atopic donors. METHODS: Detailed phenotypic and functional exploration of DCs generated in the presence of IL-4 and GM-CSF and treated with different concentrations of TCM or a placebo control was performed. RESULTS: TCM profoundly affected the morphology and phenotype of the developing DCs. They lost their typical dendritic morphology and decreased their expression of CD1a as well as the low-affinity IgE receptor CD23. Most importantly, TCM-exposed DCs exhibited a diminished stimulatory activity toward autologous antigen-specific and allogeneic T cells while secreting high amounts of IL-10. CONCLUSION: TCM induces immunopharmacologic alterations on DCs from atopic donors in vitro. These alterations might account, at least in part, for the therapeutic effect of this treatment in AD in vivo.     

Effects of glucose in protected ischemic kidneys

Summary Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified Euro-Collins-solution, containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mol/g_dw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25°C, pH decreased to 6.7 with the modified, mannitol containing Euro-Collins-solution. In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural detoriation. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.Supported by the Deutsche Forschungsgemeinschaft, SFB 89 —Kardiologie Göttingen     

Konservative Therapie mit einem Brace bei periprothetischer Humerusfraktur

Background

Due to the increasing number of implanted shoulder prostheses following trauma or omarthritis in the recent past, an increase in the occurrence of periprosthetic humeral fractures is to be expected in the future.

Problem

For type B fractures according to Worland the current literature clearly recommends operative treatment with fixed angle plate osteosynthesis or a long-stemmed cement-free revision endoprosthesis. This article presents a case study on the clinical and radiological results of a conservatively treated periprosthetic humeral fracture (Wright type B or type B2 according to Worland) and a discussion of the current literature.

Material and methods

A 70-year-old woman was diagnosed with a periprosthetic humeral fracture with an enclosed fracture endoprosthesis (Wright type B). The operative treatment with fixed angle plate osteosynthesis and the alternative conservative therapy with a brace construct were discussed with the patient. The patient decided on the conservative therapy with regular radiological course control.

Results

The conservative therapy of periprosthetic type B2 humeral fractures according to Worland using retention in an upper arm brace can lead to excellent radiological and functional results     

Effect of glacial acetic acid and ethiodized oil concentration on embolization with N-butyl 2-cyanoacrylate: an in vivo investigation

BACKGROUND AND PURPOSE: Precise control of the polymerization dynamics of cyanoacrylate mixtures used in the embolization of cerebral arteriovenous malformations is required to achieve a safe and permanent obliteration of the lesion. In this study, in vivo embolization using mixtures of Histoacryl, Lipiodol Ultra-Fluid, and glacial acetic acid (GAA) was investigated. The present study investigated whether increased ethiodized oil concentration or the addition of GAA increased rate of embolization. METHODS: Using embolic mixtures containing Histoacryl (N-butyl 2-cyanoacrylate [NBCA]), the embolization process in the femoral and subclavian arteries of the rabbit was examined. Various embolic agents composed of ethiodized oil and N-BCA mixtures, either with or without the addition of minute quantities of GAA, were injected. Blood flow through the aforementioned arteries was measured during embolization. The transient decay of blood flow to zero was modeled, and an optimized model parameter, termed the time elapsed to flow arrest (TEFA) factor, was compared with the experimental data related to the embolization process. RESULTS: The TEFA factor was independent of the variation of the ethiodized oil concentration in the mixture (P >.05). In contradistinction, the addition of GAA significantly increased the TEFA factor (P <.05). Moreover, a linear relation between the TEFA factor and the quantity of GAA in the mixture was discerned. CONCLUSION: Predictable control of the embolization process with N-BCA in vivo is attained by varying the amount of GAA in the embolic mixture.     

Hyperbaric oxygen therapy (HBO): current standing

For more than thirty years hyperbaric oxygen therapy (HBO) has been an important and ultimate therapeutic tool in special indications. Hyperbaric oxygen improves tissue oxygenation, stimulates important mechanisms in wound healing and exerts beneficial effects on other biochemical and cellular processes. The properties of hyperbaric oxygen have built the rationale for its use as therapy of choice in patients with severe carbon monoxide poisoning, decompression sickness and arterial gas embolism, and as adjunctive therapy for the treatment of osteoradionecrosis, necrotizing fasciitis and compromised skin grafts and flaps. The efficacy of adjunctive hyperbaric oxygen in the treatment of lower extremity problem wounds in diabetic patients seems to be proven. There is little scientific support for other uses of hyperbaric oxygen and its therapeutical benefit should be further investigated. When used according to standard protocols hyperbaric oxygen treatment is a safe therapy with little adverse effects.     

Dynamic spin labeling angiography in extracranial carotid artery stenosis

BACKGROUND AND PURPOSE: Similar to digital subtraction angiography, dynamic spin labeling angiography (DSLA) provides time-resolved measurements of the influx of blood into the cerebral vascular tree. We determined whether DSLA may help in assessing the degree of stenosis and whether it provides information about intracerebral collateralization and allows us to monitor the hemodynamic effects of vascular interventions. METHODS: We developed a segmented DSLA sequence that allowed the formation of images representing inflow delays in 41-ms increments. Thirty patients with unilateral carotid artery stenosis and 10 control subjects underwent DSLA. Arrival times of the labeled arterial blood bolus were measured in the carotid siphon (CS) and the middle cerebral artery (MCA) on both sides, and the corresponding side-to-side arrival time differences (ATDs) were calculated. ATDs before and after carotid endarterectomy or percutaneous angioplasty were studied in 10 patients. RESULTS: The degree of stenosis was significantly correlated with ATD in the cerebral vessels. Receiver operating characteristic analysis yielded a cutoff CS ATD of 110 ms to separate stenoses <70% from those > or =70%, with a sensitivity of 90% and a specificity of 67%. In one third of patients, ATD was higher in the MCA than in the CS; this finding suggested an absence of collateralization. Most patients had reduced ATD in the MCA. The degree of ATD reduction was regarded as a quantitative measure of collateralization. Successful intervention resulted in normalized ATDs. CONCLUSION: DSLA is a promising method that allowed us to noninvasively quantify the hemodynamic effect of extracranial carotid stenosis and the resulting intracranial collateralization.     

Acute and chronic swine rete arteriovenous malformation models: hemodynamics and vascular remodeling

BACKGROUND AND PURPOSE: An acute and a chronic arteriovenous malformation (AVM) model were developed by using the swine rete to study hemodynamics and vascular remodeling. The models were also used to study in vivo polymerization kinetics and the distribution of various N-butyl 2-cyanoacrylate (NBCA) and Lipiodol mixtures. METHODS: In the acute swine AVM model, retrograde flow through the left side of the rete was created by the placement of an endovascular shunt through the ipsilateral ascending pharyngeal artery. In the chronic model, flow was redirected retrograde through the left side of rete and ascending pharyngeal artery by creating an arteriovenous fistula between the ipsilateral jugular vein and the common carotid artery. After a period of at least 6 months, the entire head with the rete was connected to a perfusion loop driven by a peristaltic pump. A total of 30 swine were used for both the acute (n = 23) and chronic groups (n = 7). Hemodynamic parameters, including the flow and pressure drop across the rete, were recorded before NBCA embolization. Image processing was used on high-resolution radiographs of the explanted retia to measure the total rete length. Measurements of rete vessel calibers were based on histology. RESULTS: The pressure gradients across retia were higher in the chronic model than in the acute model, but they did not reach the level of statistical significance (23.7 +/- 12.0 mm Hg vs 15.4 +/- 1.4 mm Hg). The rete blood outflow was significantly higher in the chronic model compared with the acute one (139.9 +/- 100.3 mL/min vs 32.5 +/- 17.6; P = .03). The rete length in the chronic model was significantly higher than in the acute model (593.1 +/- 39.9 vs 401.3 +/- 65.2 pixel; P < .001). The average vessel diameter of the rete in the chronic group was 520 microm and 320 microm in the control animals. CONCLUSION: Increased pressure gradients and flow in the chronic swine rete AVM model may be related to increased size and decreased impedance. The resulting hemodynamic changes reflect a true flow-induced vascular remodeling rather than a simple change related to aging and size of the animal.     

A fluorescence-based method to assess plasma protein extravasation in rat dura mater using confocal laser scanning microscopy

We describe a nonradioactive, fluorescence-based method to assess plasma protein extravasation (PPE) in rat dura mater using confocal laser scanning microscopy (CLSM). Unilateral PPE can be induced by electrical stimulation of the ipsilateral trigeminal ganglion (TG) and is widely used as an experimental migraine model. The gold standard to determine PPE in the meninges is based on the detection of radiolabeled albumin ([125]I-BSA). The aim of this study was to develop a nonradioactive, histological method to quantify PPE in the meninges. The fluorescent dye Evans Blue (50 mg/kg) was injected intravenously to the rat 7 min prior to TG stimulation. PPE in dura mater was detected by a CLSM. The amount of extravasated Evans Blue in the dura mater was measured at six to eight regions of interest (ROIs) in the vicinity of large meningeal vessels. The ratio of the average fluorescence intensity within dura mater of the "stimulus side", compared to the contralateral "control side", was calculated for each animal. By using this method, The PPE ratio was 1.67+/-0.12 (n=5). Intravenous injection of three different dosages of the 5HT(1B/1D)-receptor agonist sumatriptan (25, 50, and 100 microg/kg) 15 min prior to stimulation attenuated PPE by 42+/-12%, 49+/-9%, and 86+/-15%, respectively (p<0.01). The approximated ED(50) value was 48 microg/kg. Our results are in accordance with previous reports in the literature using the radioactive approach. We conclude that CLSM is a safe, sensitive, and reliable method to assess PPE in rat meninges in an experimental migaine model.     

Lidocaine pharmacokinetics during hyperbaric hyperoxia in humans.

METHODS: The disposition of drugs may be influenced by hyperbaric conditions, in particular by changes of liver perfusion. The effect of hyperbaric hyperoxia on the pharmacokinetics of lidocaine, a drug eliminated in the liver with a perfusion-limited clearance, was investigated in human volunteers in a crossover trial. METHODS: A single dose lidocaine i.v. bolus (0.69 or 0.75 mg x kg(-1)) was administered to two volunteers under normobaric conditions (NB: 1 bar or 0.1 MPa, air) and under hyperbaric/hyperoxic conditions (HBO: 2.5 bar or 0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). Blood samples were serially collected for 5 h (NB) or 75 min (HBO), and lidocaine concentration in serum was measured by immunoassay. Data were analyzed assuming linear kinetics and an open two-compartment model. RESULTS: At 1 bar or 0.1 MPa, lidocaine injection caused only slight dizziness and buzzing in the ear. Heart rate and blood pressure were not influenced. Under HBO, lidocaine injection caused marked dizziness and buzzing in the ears, sweating, tremor and coordination-disturbances, even though maximal lidocaine concentrations (0.63 mg x L(-1) and 0.70 mg x L(-1)) were far below therapeutic serum concentrations (1.5-5.0 mg x L(-1)). Pharmacokinetic parameters of lidocaine were similar to those published earlier (T1/2beta: 110+/-16 min; CI: 12.6+/-2.9 ml x min(-1) x kg(-1); Vss: 1.73+/-0.18 L x kg(-1)). There was no indication for effects of HBO on the disposition of lidocaine (p > 0.05). CONCLUSION: The pharmacokinetics of lidocaine do not seem to be influenced in a clinically relevant way in humans by a single HBO-exposure under usual therapeutic conditions. Side effects of lidocaine at 2.5 bar or 0.25 MPa may be caused by pharmacodynamic interactions between lidocaine and hyperbaric/hyperoxic conditions.     

Development, validation, and certification by isotope dilution gas chromatography-mass spectrometry of lyophilized human serum reference materials for cortisol (CRM 192 and 193) and progesterone (CRM 347 and 348)

The Community Bureau of Reference of the European Communities has produced four batches of lyophilized serum Certified Reference Materials, two for cortisol (CRM 192 and 193) and two for progesterone (CRM 347 and 348). For cortisol, one of the pools consisted of serum from healthy blood donors, whereas the second batch was supplemented with pure cortisol. The progesterone Reference Materials contained only endogenous hormone concentrations. Assessment of vial-to-vial variability in the cortisol and progesterone concentrations showed no between-sample inhomogeneity, and the materials were stable. The quality of the materials was therefore considered sufficient for certification of the values for the cortisol and progesterone concentrations by a collaborative study involving several laboratories from the European Communities, using isotope dilution gas chromatography-mass spectrometry. Inaccuracy in reconstitution of the lyophilized materials was less than 0.3%; imprecision of sampling was less than 0.2%. For determinations of cortisol and progesterone concentrations, the mean within-laboratory coefficients of variation (CVs) were 1.76% (CRM 192), 1.19% (CRM 193), 1.64% (CRM 347), and 1.75% (CRM 348). The between-laboratory CVs were greater: CRM 192, 1.79%; CRM 193, 1.48%; CRM 347, 2.08%; and CRM 348, 2.16%. The concentrations in the reconstituted Reference Materials were certified to be 273 nmol/L in CRM 192 and 763 nmol/L in CRM 193 for cortisol and 10.13 nmol/L in CRM 347 and 40.3 nmol/L in CRM 348 for progesterone. Uncertainties at the 0.95 confidence level--6 (CRM 192), 14 (CRM 193), 0.21 (CRM 347), and 1.0 nmol/L (CRM 348)--were considered compatible with the intended use of the materials.