The synthesis, antibacterial, and beta-lactamase inhibitory activity of a novel asparenomycin analog.

An analog, 6-(2'-hydroxyethylidene)-4 beta-methyl-1-azabicyclo[3.2.0]hept-2-ene-2- carboxylate (11), of the carbapenem beta-lactamase inhibitor, asparenomycin A, was synthesized. It possessed a spectrum of antibacterial activity that was comparable to that of asparenomycin A but was less effective as a beta-lactamase inhibitor. With ampicillin, it only exhibited a moderate level of synergy against a variety of beta-lactamase-producing organisms. Although the presence of a 4 beta-methyl group in the analog brought about a significant increase in chemical stability relative to that of asparenomycin A, it did not result in an increase in stability to kidney dehydropeptidase enzyme.     

Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease

BACKGROUND: Growing evidence supports a role for peroxidation in the pathogenesis of Crohn disease (CD). The activation of inflammatory cells, the release of their mediators, and the excessive production of free radicals may affect circulating lipids. OBJECTIVE: We examined the lipid profile, lipoprotein composition, and oxidant-antioxidant status of children with CD. DESIGN: We studied 22 pediatric CD patients and 10 healthy control subjects. RESULTS: The proportion of saturated and monounsaturated fatty acids in plasma of CD patients was higher but that of polyunsaturated fatty acids was lower than in control subjects. This resulted in higher ratios in CD patients of palmitoleic acid to linoleic acid (P < 0. 05) and of eicosatrienoic acid to arachidonic acid (P < 0.04), 2 established indexes of essential fatty acid deficiency. Hypocholesterolemia was noted in CD patients as a result of lower LDL-cholesterol concentrations than in control subjects (P < 0.02). Plasma apolipoproteins B (P < 0.02) and A-I (P < 0.02) were also lower in CD patients, whereas plasma triacylglycerols were higher (P < 0.005). Lipoprotein composition was altered in CD patients, with relative triacylglycerol depletion and protein enrichment in VLDL. In contrast, intermediate-density lipoprotein of CD patients was characterized by an increased percentage of triacylglycerol and protein (P < 0.005) and a reduced proportion of phospholipids (P < 0. 01). Additional abnormalities were observed in the chemical distribution of HDL(2) and HDL(3) moieties. Lipid peroxidation was documented by higher plasma malondialdehyde concentrations in CD patients (P < 0.05), accompanied by lower retinol concentrations (P < 0.02). CONCLUSION: Disturbances in the lipid profile, in lipoprotein concentrations and composition, and in oxidant-antioxidant status occur in CD patients.     

Development of a vibration haptic simulator for shoulder arthroplasty

Purpose

Glenoid reaming is a technically challenging step during shoulder arthroplasty that could possibly be learned during simulation training. Creation of a realistic simulation using vibration feedback in this context is innovative. Our study focused on the development and internal validation of a novel glenoid reaming simulator for potential use as a training tool.

Methods

Vibration and force profiles associated with glenoid reaming were quantified during a cadaveric experiment. Subsequently, a simulator was fabricated utilizing a haptic vibration transducer with high- and low-fidelity amplifiers; system calibration was performed matching vibration peak–peak values for both amplifiers. Eight experts performed simulated reaming trials. The experts were asked to identify isolated layer profiles produced by the simulator. Additionally, experts’ efficiency to successfully perform a simulated glenoid ream based solely on vibration feedback was recorded.

Results

Cadaveric experimental cartilage reaming produced lower vibrations compared to subchondral and cancellous bones (\(p\le 0.03\)). Gain calibration of a lower-fidelity (3.5 \({g}_{\mathrm{pk-pk}}, 0.36\,{g}_{\mathrm{rms}})\) and higher-fidelity (3.4 \({g}_{\mathrm{pk-pk}}, 0.33\,{g}_{\mathrm{rms}})\) amplifier resulted in values similar to the cadaveric experimental benchmark (3.5 \({g}_{\mathrm{pk-pk}}, 0.30\,{g}_{\mathrm{rms}})\). When identifying random tissue layer samples, experts were correct \(52\pm 9\%\) of the time and success rate varied with tissue type (\(p=0.003\)). During simulated reaming, the experts stopped at the targeted subchondral bone with a success rate of \(78\pm 24\%\). The fidelity of the simulation did not have an effect on accuracy, applied force, or reaming time (\(p>0.05\)). However, the applied force tended to increase with trial number (\(p=0.047\)).

Conclusions

Development of the glenoid reaming simulator, coupled with expert evaluation furthered our understanding of the role of haptic vibration feedback during glenoid reaming. This study was the first to (1) propose, develop and examine simulated glenoid reaming, and (2) explore the use of haptic vibration feedback in the realm of shoulder arthroplasty.

     

High-velocity low-amplitude thrust manipulation of the lumbar spine immediately modifies soleus T reflex in asymptomatic adults

BackgroundHigh-velocity low-amplitude thrust manipulations (HVLAM) are routinely used in osteopathic treatment. Despite the large number of studies that have been realized till now, the effects of spinal HVLAM on the physiological properties of muscles and nerves are not fully characterized.ObjectiveThe present study was designed to investigate the effects of a spinal lumbar L4/L5 HVLAM on the functional properties of the soleus T reflex in asymptomatic young adults.DesignControlled pre/post measures experimental design.MethodsRight and left soleus T reflexes were elicited by striking right and left Achilles tendons with an instrumented reflex hammer and the electromyographic (EMG) signals were monitored in right and left soleus muscles. The amplitude and latency of EMG responses were measured before and after the delivery of a HVLAM targeting the L4/L5 segment. The conduction velocity was calculated from the latency value.Subjects50 asymptomatic adults met all inclusion criteria. They were randomly allocated to either group a) receiving a sham manipulation (SM), or b) a HVLAM. Because of subject loss, the final size of SM and HVLAM groups was 24 and 18, respectively.ResultsOur data show that the conduction velocity, but not the amplitude of the T reflex, is significantly increased by HVLAM in both soleus muscles with small to medium effect size. SM neither changes the amplitude nor modifies the conduction velocity.ConclusionOur data show that a lumbar L4/L5 HVLAM modifies the electrophysiological properties of the soleus T reflex.     

Effect of erythropoietin on blood pressure and on the vascular endothelial ET-1/ETB receptor system

BACKGROUND: Recombinant human erythropoietin (rhEPO) increases blood pressure (BP) and the vascular production of endothelin-1 in renal failure rats. This study was designed to investigate the effect of rhEPO on BP and on the ET-1/ET(B)R system in rats with normal renal function. To further characterize the effect of rhEPO on the ET-1/ET(B)R system, we also studied heterozygous (+/-) ET(B)R knockout (KO) mice. METHODS: The animals received either the vehicle or rhEPO (100 U/kg subcutaneously three times per week). ET(B)R(+/-) mice were compared with ET(A)R(+/-) and wild-type (WT) mice. In rats, the ET(B)R mRNA expression was assessed in blood vessels as well as the vascular ET(B)R density using immunohistochemistry. In mice, ET-1 concentration was measured in the thoracic aorta. RESULTS: RhEPO administration increased hematocrit levels in all treated animals. This therapy had no effect on BP in normal rats, but it did increase vascular and renal cortex ET(B)R mRNA expression. Immunohistochemistry confirmed that the ET(B)R density was increased in blood vessel endothelium in these normal rats. In contrast, rhEPO increased BP in ET(B)R(+/-) mice and this pressor effect was associated with higher ET-1 concentrations in the thoracic aorta. CONCLUSIONS: RhEPO exerts a pleotropic effect on the endothelial ET-1/ET(B)R system. The increase in endothelial ET(B)R expression may contribute to maintaining normal BP during rhEPO administration in normal animals. Conversely, conditions with deficient ET(B)R expression, such as in ET(B)R(+/-) mice, may lead to hypertension while receiving the same therapy.     

Possible courses of caregiver's support in Alzheimer's disease

The Legos (a laboratory specialized on health economics at Dauphine University, Paris) conducted a detailed survey at three daycare centres for persons suffering from Alzheimer's disease in France, Germany and Spain, to examine in depth their objectives, organization, practices and relations to patients' families. Though it proved difficult to establish a true typology, the analysis showed that the support provided to caregivers by the daycare centres were responding to three main approaches: one aimed at stimulating or keeping the cognitive abilities of the patients; a second one based on the remaining autonomy of the patients and striving to improve the provided home cares and services, in order to avoid or postpone a departure to a nursing home; the last one dealing with the socialization of the patients through an action on the strong relationship with their family. The survey, as well as the study of the available literature published in English and French on the day care centres, also stressed that some delicate questions were not getting the thorough attention they deserve; e.g. the interaction between what is going on in the day care centre and the life outside the centre, the management of the transition between the day care centre and home when the patient returns, the information and professional training of the carers (formal and informal), the various financial aspects of caregivers' support and of attendance at a daycare centre and, last but not least, the different ways of taking into consideration the opinion and the quality of life of the patients.