Dorothea Kapoukranidou

Concealment of Information in Clinical Practice: Is Lying Less Stressful Than Telling the Truth?

From the Lab of Hygiene; Lab of Physi-ology, Medical School, Aristotle Univer-sity, Thessaloniki, Greece.Submitted May 31, 2007; acceptedJune 21, 2007.The first and second author haveconducted the same amount of workand share first authorship.Authors’ disclosures of potential con-flicts of interest and author contribu-tions are found at the end of thisarticle.Corresponding author: E. Panagopoulou,Lab of Hygiene, 54124, Medical School,Aristotle University, Thessaloniki, Greece;e-mail: efharis@the.forthnet.gr.© 2008 by American Society of ClinicalOncology0732-183X/08/2607-1175/

Ropivacaine myotoxicity after single intramuscular injection in rats

20.00DOI: 10.1200/JCO.2007.12.8751

Alcohol Affects the Brain's Resting-State Network in Social Drinkers

Background and objective: We conducted this study in order to evaluate the potential myotoxic effects of ropivacaine after single injection in rats and the time‐course of the possible damage. Methods: One hundred and twenty‐eight male Wistar rats were allocated to four different groups. The first three groups received intramuscular injections with ropivacaine 0.75%, ropivacaine 0.5% and normal saline, respectively, into the right tibialis anterior muscle. The fourth group received needle puncture without injection. Eight rats from each group were sacrificed 2, 4, 7 and 30 days after injection. Samples were blindly examined under light microscope for evidence of myotoxicity, scored as 0 = no damage to 3 = myonecrosis and statistically analysed. Samples obtained 7 days after injection were also examined under transmission electron microscope. Results: Ropivacaine 0.75% and ropivacaine 0.5% caused extensive destruction to muscles fibres, compared to saline or needle on days 2, 4 and 7. Statistically significant differences were found in muscle damage by drug injections among all groups except for saline vs. needle groups. Thirty days after injections all sample appearances had returned to normal. Conclusions: Ropivacaine after single intramuscular injection caused reversible muscle damage in a dose‐dependent manner.

Magnesium administration provokes motor unit survival, after sciatic nerve injury in neonatal rats

Acute alcohol intake is known to enhance inhibition through facilitation of GABAA receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC) on standardized Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta bands (eyes-closed) following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo). Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as expected, to increased GABA transmission and functional connectivity, while long-term alcohol consumption may be linked to exactly the opposite effect.

Multitarget Molecular Hybrids of Cinnamic Acids

BackgroundWe examined the time course of the functional alterations in two types of muscles following sciatic nerve crush in neonatal rats and the neuroprotective effect of Mg2+.MethodsThe nerve crush was performed on the 2nd postnatal day. MgSO4*7H2O was administered daily for two weeks. Animals were examined for the contractile properties and for the number of motor units of extensor digitorum longus and soleus muscles at three postnatal stages and adulthood. Four experimental groups were included in this study: i) controls, ii) axotomized rats, iii) magnesium treated controls and iv) axotomized and Mg2+-treated rats.ResultsAxotomy resulted in 20% MU survival in EDL and 50% in soleus. In contrast, magnesium treatment resulted in a significant motor unit survival (40% survival in EDL and 80% in soleus). The neuroprotective effects of Mg2+ were evident immediately after the Mg2+-treatment. Immature EDL and soleus muscles were slow and fatigueable. Soleus gradually became fatigue resistant, whereas, after axotomy, soleus remained fatigueable up to adulthood. EDL gradually became fastcontracting. Tetanic contraction in axotomized EDL was just 3,3% of the control side, compared to 15,2% in Mg2+-treated adult rats. The same parameter for axotomized soleus was 12% compared to 97% in Mg2+-treated adult rats.ConclusionsThese results demonstrate that motoneuron death occurs mostly within two weeks of axotomy. Magnesium administration rescues motoneurons and increases the number of motor units surviving into adulthood. Fast and slow muscles respond differently to axotomy and to subsequent Mg2+ treatment in vivo.

Baroreceptors discharge due to bilateral aortic denervation evokes acute neuronal damage in rat brain

In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC50 = 0.34 μM and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μM) and the highest anti-proteolytic activity (IC50= 5 μM). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.

Efficiency of different decalcification protocols for nasal osseous structures in a rat experimental model of allergic rhinitis, and their effects on epithelial histology: an attempt at standardization.

Deep hypothermic circulatory arrest in cardiothoracic surgery evokes severe brain damages. On the other hand, blood pressure stimuli discontinuation to the brain has been found to induce alterations in neurotransmitter release, including glutamate, in numerous brain regions. Furthermore, it is well established that excessive glutamate release can induce neuronal injury, a process called excitotoxicity. Aim of the present study was the evaluation of possible acute neuronal damage after bilateral aortic denervation (bAD), imitating the baroreceptors discharge during circulatory arrest. Male, Wistar rats underwent either bAD or Sham operation under continuous hemodynamic monitoring. Two hours after completion of the procedure, rats were sacrificed and the brains were dissected and cut in specific levels corresponding to selective brain regions, based on either their participation in neuronal circuits, regulating blood pressure, or their vulnerability, after deep hypothermic circulatory arrest. Slices were stained and examined under light microscope using morphometric techniques. Increased number of necrotic neurons were found among bAD rats in amygdaloid complex (p=0.005), motor cortex (p=0.001), CA1 and CA3 (p=0.02 and 0.015) but not in posterior hypothalamic nucleus and Purkinje cell. Higher ratios of necrotic neurons were found in amygdaloid complex (p=0.002), motor layer (p=0.003 and p=0.000) and the hippocampal CA1 region (p=0.027) of bAD rats. The present study shows that baroreceptors discharge due to bAD may induce acute neuronal loss in brain regions involved in blood pressure regulation. Neuronal loss might be attributed to excitotoxic phenomena and it is following the same topographic distribution seen in deep hypothermic circulatory arrest, revealing a concurrent to hypoxia/ischemia mechanism of brain damage.

Contractile properties and movement behaviour in neonatal rats with axotomy, treated with the NMDA antagonist DAP5

INTRODUCTION Decalcification of osseous specimens is required for histological analysis; this however may cause tissue damage. In rodent models of allergic rhinitis (AR), epithelial histologic assessment necessitates prior decalcification of the nasal osseous structures. However, respiratory epithelium is highly susceptible to damage, and rat nasal architecture is elaborate and its sectioning is challenging. Nevertheless, decalcification is not standardized in experimental AR. We therefore undertook this task, in order to reduce experimental bias. METHODS Six-to-eight week-old Wistar rats underwent an AR protocol. Subsequently, nasal structures were decalcified in the following mediums: (i) formic acid 10% for 5 and 20 days; (ii) formic acid 15% for 5 and 15 days; (iii) Morse Solution for 5 and 20 days and (iv) EDTA for 20 and 40 days. Decalcification efficiency/speed was evaluated via radiographic analysis. Furthermore, specimens were stained with hematoxylin and eosin and assessed for preservation of epithelial features. RESULTS Specimens were appropriately decalcified in 5 days in the formic acid-based mediums and in 20 days in EDTA with minimal epithelial damage. EDTA for 40 days had no unacceptable adverse effects; conversely, 15 and/or 20 days in acid-based agents provided no extra benefit for decalcification and were detrimental to the epithelium. CONCLUSIONS EDTA treatment for 20 days is appropriate for decalcification of nasal structures in rat models of allergic rhinitis; further incubation preserves epithelial integrity but is not required. When urgency is a factor, formic-acid-based decalcification for 5 days yields acceptable results.

Osmotic nephrosis due to the use of anti-adhesive membrane intraperitoneally

BackgroundIt is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury.MethodsWistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (injection of 0.9% NaCl solution) b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months).Results1. Administration of DAP5 alone provoked no apparent adverse effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p<0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their locomotor behaviour were significantly improved compared to axotomized ones (p<0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p<0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p<0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles.ConclusionsOur results confirm that contractile properties and locomotor behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.

The effect of porcine orexin A on glucose dependent insulinotropic polypeptide plasma concentrations in pigs

BACKGROUND A common strategy for the prevention of intra-abdominal adhesions post-operatively has been the application of adhesion barriers into the peritoneal cavity. Side effects of these barriers are infection, abscesses and inadequate wound healing. There is no information about such a side effect of these materials on renal function. The aim of this study was to evaluate the effect of two different, commercially available polysaccharide-based anti-adhesive materials on renal function. METHODS In 24 adult Wistar rats, an abdominal midline incision was performed, and an anti-adhesion membrane was placed in the peritoneal cavity so as to cover its whole surface. Four rats were used as the control group. In 12 rats, a membrane of macromolecular polysaccharides, weighing 40 mg/cm2, was placed intra-abdominally and in 8 rats, a hyaluronic acid-hydroacidmethylcellulose membrane weighing 0.4 mg/cm2 was placed. At 24 or 70 h, the rats were sacrificed, and we evaluated changes in serum creatinine, urea, uric acid, K and Na, and histologic examination of the kidney was performed. RESULTS The use of the thicker macromolecular membrane was associated with a rise in serum creatinine and urea levels, vacuolization of all the tubular epithelial cells and mild interstitial infiltration. Rats in which the hyaluronic acid-hydroacidmethylcellulose membrane was used did not show any creatinine elevation, and they presented milder histologic lesions. CONCLUSION Polysaccharide and cellulose anti-adhesive membrane cause renal damage with tubular cell vacuolization. The severity of kidney damage is relative to the quantity of the membrane material used.