Numerical and Experimental Extraction of Dynamic Parameters for Pyramidal Truss Core Sandwich Beams with Laminated Face Sheets

Sandwich beams that are composed of laminated face sheets and aluminum pyramidal truss cores are considered to be essential elements of building and aerospace structures. In this paper, a methodology for the experimental and numerical analysis of such structures is presented in order to support their industrial application. The scope of the present research covers both the experimental and numerical extraction of the dynamic parameters of the sandwich beams. Vibration tests are performed while using an optical system for three-dimensional vibrations sensing. The in-plane and out-of-plane vibration modes can thus be examined. A detailed numerical model of the sandwich beam is developed, including an adhesive joint (an additional layer of material) between the parent components of the beam. The numerically predicted modal parameters (eigenfrequencies, mode shapes, modal loss factors) are comported with their corresponding experimentally-obtained values. The modal loss factors are predicted based on the strain energy method, for which a brief theoretical introduction is provided. The obtained experimental and numerical results coincide with good accuracy. The circumstances for possible model simplifications are provided depending on the solution objectives.     

Carnitine and γ‐Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2‐mediated Transport

Meldonium (3‐(2,2,2‐trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization‐related cardioprotective effects. The recent inclusion of meldonium in the World Anti‐Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, γ‐butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice. Here, we show that carnitine and GBB administration during the washout period effectively stimulated the elimination of meldonium. GBB induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of GBB for OCTN2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and GBB. In conclusion, the competition of meldonium, carnitine and GBB for OCTN2‐mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for OCTN2, GBB and carnitine but not furosemide stimulated meldonium elimination. During long‐term treatment, OCTN2‐mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.     

The resuscitative fluid you choose may potentiate bleeding

BACKGROUND: Trauma is the leading cause of death in the younger population in the United States, frequently from the development of hemorrhagic shock. Controversy exists over the type of volume resuscitation for restoring hemodynamic stability that should be used in hemorrhagic shock. Little is known about how various resuscitative paradigms affect the coagulation cascade, which is essential to controlling hemorrhagic shock. METHODS: We studied the effect of various resuscitative formulas on blood coagulation using a new model of whole blood in a controlled setting with corn trypsin inhibitor and a 5-pM stimulus of tissue factor. We investigated thrombin generation, fibrin formation, and platelet activation with four diluents: 0.9% NaCl (NS), lactated Ringer's solution (LR), 6% hydroxyethyl starch (HES), and 3% NaCl (HS), each from 0% to 75% blood dilution. Thrombin generation was measured periodically during a time course of 20 minutes in its complex with antithrombin III. Platelet activation and fibrinopeptide A (FPA) release were monitored in serum at a 20-minute time point. Fibrin clots were collected and weighed. RESULTS: The coagulation markers (thrombin generation, platelet activation, and FPA release) were significantly different by dilution (p < 0.001 in all) and diluent by dilution (p < 0.001 in all). Thrombin generation, platelet activation, and FPA release decreased the least with the diluents NS and LR. LR caused the least amount of variation in thrombin generation over the dilution course. HS produced the most dramatic change in all of the markers; no coagulation was seen between 30% to 75% dilution (p < 0.05). HES produced greater decreases in thrombin generation and FPA release than NS and LR. Fibrin clot mass decreased with a 10% to 20% dilution for NS and LR, whereas stable fibrin mass did not decrease with the diluents HES and HS at 10% to 20% dilutions. At >30% dilutions, HS produced no stable clots and HES dramatically decreased clot formation by 61% and maintained this level. CONCLUSIONS: LR and NS had the least effect on thrombin generation, clot formation, and platelet activation at various concentrations compared with HES and HS. This observational data suggests that volume expanders such as HES and HS may be detrimental in treatment of hemorrhagic shock.     

Basophil allergen threshold sensitivity,CD‐sens,is a measure of allergen sensitivity in asthma

Background Allergic asthma is IgE‐mediated and the IgE‐sensitisation is usually demonstrated by skin prick tests (SPT) and IgE antibody determinations in serum. The SPT and IgE‐antibody values do not directly predict if the allergy clinically contributes to the asthma. There is therefore a need for new objective tests that may indicate the clinical importance of an IgE‐sensitisation. Objective To evaluate basophil allergen threshold sensitivity (CD‐sens) as a measure of allergen sensitivity in allergic asthma. Methods Twenty‐six subjects with stable, intermittent allergic asthma were tested with SPT and spirometry, and methacholine and allergen inhalation challenges to determine methacholine PD₂₀ (provocative dose causing a 20% drop in forced expiratory volume in 1 s) and allergen PD₂₀. The results were compared with CD‐sens and serological parameters, i.e. IgE‐ and IgG4 antibodies to the relevant allergens. Results A significant correlation was found between CD‐sens and allergen PD₂₀ (P=0.01; r=0.49; n=26) as well as between CD‐sens and the ratio of allergen PD₂₀ to methacholine PD₂₀ (P=0.007; r=0.52; n=26). In patients with a moderate to low degree of bronchial hyperresponsiveness there was an excellent correlation (P=0.0001; r=0.88, n=13) between CD‐sens and allergen sensitivity. No relation to either allergen PD₂₀ or the ratio was found for basophil allergen reactivity measured as CD63 up‐regulation at high concentrations of the respective allergen. Conclusions and Clinical Relevance CD‐sens was found to be an objective marker of airway allergen sensitivity in stable allergic asthmatics, that may be used to predict airway responsiveness when bronchial challenge tests cannot be performed. Cite this as: B. Dahlén, A. Nopp, S. G. O. Johansson, M. Eduards, M. Skedinger and J. Adédoyin, Clinical & Experimental Allergy, 2011 (41) 1091–1097.     

The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery

Middle cerebral artery occlusion (MCAO) is the most commonly used method to study the neurological and histological outcomes and the pathological mechanisms of ischaemic stroke. The current work compares sensorimotor and cognitive deficits and the infarct volume in rats following a transient 90- or 120-min MCAO, which allows the appropriate behavioural tests to be chosen based on the goal and design of the experiment. In the beam-walking test, we found significant differences between the 90- and 120-min MCAO groups in the number of foot faults made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder test, a difference between the 90- and 120-min groups was observed on post-operation day 14. The responses to tactile and proprioceptive stimulation were impaired to a similar extent after 90- and 120-min MCAO in the vibrissae-evoked forelimb-placing and limb-placing tests. Moreover, we found significant memory impairment in the 120-min MCAO group 6 days after the acquisition trial. The brain tissue damage was significantly higher after 120-min occlusion of the MCA compared with 90-min occlusion; the infarct volumes were 13% and 25% of the contralateral hemispheres, respectively. In conclusion, both the 90- and 120-min occlusion models result in a significant impairment of sensorimotor, tactile and proprioceptive function, but memory impairment is only observed in the 120-min MCAO group. The beam-walking and cylinder tests detected neurological dysfunction after the 120-min MCAO, whereas the limb-placing and vibrissae-evoked forelimb-placing tests were able to evaluate the neurological dysfunction in rats after 90- and 120-min MCAO.     

The heart is better protected against myocardial infarction in the fed state compared to the fasted state

Objective

A variety of calorie restriction diets and fasting regimens are popular among overweight people. However, starvation could result in unexpected cardiovascular effects. Therefore, it is necessary to evaluate the short-term effects of diets on cardiovascular function, energy metabolism and potential risk of heart damage in case of myocardial infarction. The objective of the present study was to investigate whether the increased level of glucose oxidation or reduction of fatty acid (FA) load in the fed state provides the basis for protection against myocardial infarction in an experimental rat model of ischemia–reperfusion.

Materials/Methods

We tested the effects of the availability of energy substrates and their metabolites on the heart functionality and energy metabolism under normoxic and ischemia–reperfusion conditions.

Results

In a fasted state, the heart draws energy exclusively from FAs, whereas in a fed state, higher concentration of circulating insulin ensures a partial switch to glucose oxidation, while the load of FA on heart and mitochondria is reduced. Herein, we demonstrate that ischemic damage in hearts isolated from Wistar rats and diabetic Goto–Kakizaki rats is significantly lower in the fed state compared to the fasted state.

Conclusions

Present findings indicate that postprandial or fed-state physiology, which is characterised by insulin-activated glucose and lactate utilisation, is protective against myocardial infarction. Energy metabolism pattern in the heart is determined by insulin signalling and the availability of FAs. Overall, our study suggests that even overnight fasting could provoke and aggravate cardiovascular events and high-risk cardiovascular patients should avoid prolonged fasting periods.     

CntA oxygenase substrate profile comparison and oxygen dependency of TMA production in Providencia rettgeri

CntA oxygenase is a Rieske 2S‐2Fe cluster‐containing protein that has been previously described as able to produce trimethylamine (TMA) from carnitine, gamma‐butyrobetaine, glycine betaine, and in one case, choline. TMA found in humans is exclusively of bacterial origin, and its metabolite, trimethylamine oxide (TMAO), has been associated with atherosclerosis and heart and renal failure. We isolated four different Rieske oxygenases and determined that there are no significant differences in their substrate panels. All three had high activity toward carnitine/gamma‐butyrobetaine, medium activity toward glycine betaine, and very low activity toward choline. We tested the influence of low oxygen concentrations on TMA production in CntA‐containing Providencia rettgeri cell cultures and discovered that this process, although dependent on the amount of oxygen, is still feasible in environments with 1 and 0.2% oxygen, which is comparable to oxygen levels in some parts of the digestive system.