Pain mechanisms in chronic pancreatitis

The purpose of the present study is the bibliographic review of chronic pancreatitis (CP) and its underlying pain-induction mechanisms. Chronic pancreatitis is defined as a progressive inflammatory process characterized by destruc­tion or total eradication of the parenchyma and fibrosis. One of its prevailing symptoms is pain. It is severe, dull, epigastric, often radiating to the back, recurrent or permanent. Pain stands for an unpleasant, frustrating sensation evoked by stimuli like harmful agents and inflammation, as a reaction of the human body alerting it for the presence of an intrinsic or extrinsic hazard. In the case of CP pain a great number of causative mechanisms has been proposed. Formerly, it was perceived as originating from the inflammatory and fibrotic process. Pancreatic ischemia related to ductal and parenchymal tissue hyper­tension and extrapancreatic causes like bile duct and duodenal stenosis have also been proposed. Most recently, emphasis has been placed on the neuropathic component of CP as pain is provoked by peripheral nociceptive mechanisms. Pancreatic neuropathy in terms of neural damage, increased neural density and hypertrophy along with central sensitization (spinal and cerebral hyperexcitability) are also involved in this theory. The various hypotheses highlight its multifactory nature and the need for further exploration

Biological factors of inflammation and methods of their detection

Inflammation is a complicated process occurring after a harmful stimuli or infection. During inflammation a large number of biochemical reactions and pathophysiological changes take place. These procedures are all induced by active biological compounds called mediators or chemokines. These molecules are derived from plasma and cells and are capable of performing the appropriate changes both on the endothelium and cells during the inflammatory process. Moreover, some of them have the ability to interact with each other. Today there are different methods to detect and quantitate these compounds. These techniques keep on evolving and improving. Which one is the most suitable depends on the researcher’s scientific aim. A standardized protocol was created in order to make MRU feasible in everyday use, based on protocols suggested by other researchers. Both T1 and T2 weighted images were obtained using the following sequences: 2D Τ2-weighted fat saturation, 3D single shot fast spin-echo (SSFSE/RARE), 2D Radial SSFSE and T1-weighted gradient LAVA (3D SPGR). In 16 out of the 21 cases the MRU images and data agreed with the previous diagnosis based on radionuclide and ultrasound studies. In 5 cases MRU provided additional information, altering or even overruling the previous diagnosis. These 5 cases are presented in this article

Glutamate receptors in blood elements and bone marrow megakaryocytes

Glutamate is one of the primary endogenous amino acids of the Central Nervous System (CNS). Οver the last years research has proven the existance of glutamate subunit receptors in additional non-neuronal tissues outside CNS. In this review, we indicate the distribution of glutamate subunit receptors in peripheral blood elements, as well as in bone marrow cells, as presented in up to date literature. Although the exact significance of glutamate subunit receptors presence in peripheral tissues is not quite clear, it is of no doudt that more research is needed in order to define its purpose and its possible therapeutical role outside CNS

Molecular mechanisms of memory and learning

The aim of the present review is to discuss the molecular mechanisms of learning and memory. The first part of the review investigates implicit memory in Aplysia, a marine snail, studied by Eric Kandel, the Nobel Prize winner. This form of learning can be broadly divided into two temporal phases, an early and a late phase. The molecular mechanisms of each phase will be analyzed in separate sections.The second part of the review investigates hippocampal-dependent explicit memory in ammals and the mechanism that underlies it, known as long-term potentiation (LTP). Similar to the molecular mechanisms in Aplysia, LTP is divided into an early and a late phase. However, LTP in mammals is a very complicated phenomenon that depends on the regulation of many molecular pathways. Moreover, the scientific community cannot always reach a consensus on the role of some of these molecular mechanisms in LTP. Nevertheless, it will be demonstrated that both explicit and implicit memory occur at a synaptic level, result from/in synaptic strengthening, and share common molecular mechanisms in a variety of species far apart on the phylogenetic scale

Behavioral study of rats with spinal cord hemisection in the midthoracic level

Introduction: Various experimental models exist in order to induce a spinal cord lesion and to monitor the potential recovery of the animals, with or without any therapeutic means. From the behavioral point of view, the Basso-Beattie-Bresnahan (BBB) score is the most popular scale, used consistently to evaluate the effect of the traumatism onto the motor behavior of the animals. Although it is well established and it is regarded as the “gold standard” in the literature, in case of partial lesions, with high rate of spontaneous recovery, more elaborate tests may be indicated. Materials-methods: In this study we performed spinal cord hemisection at the midthoracic level in adult Wistar rats, which were evaluated postoperatively with BBB, as well as with a more extended behavioral protocol, comprising grid walking and footprint analysis. Results: Although BBB score improved, grid walking, stride length, step length and limb rotation did not reach statistical significance. Conclusion: More sensitive motor behavior protocols are needed to corroborate the results of the BBB test and to detect subtle defects in sensorimotor coordination. This is especially true in cases of partial lesions, due to a high rate of spontaneous gross motor recovery

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

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

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 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ) and the highest anti-proteolytic activity (IC50= 5 μΜ). 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