Morphofunctional Alterations Research Articles

Olive leaf extract counteracts epithelial to mesenchymal transition process induced by peritoneal dialysis, through the inhibition of TGFβ1 signaling.

The mesothelial cells (MCs) play an important role in the morpho-functional alterations of the peritoneal membrane (PM) undergoing peritoneal dialysis (PD). MCs, through the epithelial-mesenchymal transition process (EMT), progressively acquire a myofibroblast-like phenotype, promoting peritoneal fibrosis (PF) and failure of peritoneal membrane function. Transforming growth factor β1 (TGFβ1), through canonical and non-canonical pathways, promotes the epithelial-mesenchymal transition (EMT) process leading to PF. To investigate the therapeutic potential of an olive leaf extract (OLE) on preserving peritoneal membrane function, we evaluated the effect of OLE on the TGFβ1-induced EMT in mesothelial cells, Met5A, and elucidated the underlying molecular mechanisms. As assessed by changes in the expression of epithelial, mesenchymal, and fibrotic cell markers (such as E-cadherin, N-cadherin, α-SMA, fibronectin, vimentin), levels of matrix metalloproteinases (MMP2 and MMP9), and cell migration, OLE inhibited the TGFβ1-induced EMT. Importantly, the beneficial effect of OLE was mediated by reduction of the TGFβ1-induced activation of Smad2/3 signaling and the mitigation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Smad/non-Smad signaling pathways, activated by TGFβ1, both reduce expression of epithelial marker E-cadherin which has a crucial role in EMT initiation. Interestingly, we observed that in presence of OLE activity of the E-cadherin, promoter was increased and concomitantly OLE reduced the nuclear content of its co-repressor SNAIL. Our results suggest the potential therapeutic of OLE to counteract fibrotic process in peritoneal dialysis patients.

Anisometropia and Anisometropic Amblyopia (Literature Review)

To study the world literature (monographs and periodicals) regarding the frequency of anisometropia, its role in amblyopia development and prevalence of anisometropic amblyopia, its clinical and morphofunctional features, to reveal new aspects of etiology and pathogenesis.We have performed a literature review of Russian and foreign monographs and periodicals, internet resources. The paper presents statistical data regarding the wide prevalence of anisometropia (which manifests by asymmetry in the fellow eye and doesn’t reduce it, and anisometropia that leads to amblyopia), its classification and describes the alterations in the human organism that accompany anisometropia. It is shown that along with the sensory disorders which are peculiar to the other types of amblyopia, in anisometropic amblyopia we observe morphofunctional alterations that are special enough and differentiate anisometropic amblyopia from its other types. The paper describes the peculiarities of the retina and choroid in anisometropic amblyopia, revealed by means of optical coherence tomography and determining its specificity. Anisometropia is widely spread among children and adults. As a possible reason for visual acuity reduction, it is found in 1.0–2.3% of cases according to the different investigation data (the difference in refraction of both eyes of more than 1.5 D may become the reason for amblyopia). Anisometropia of less than 1.5 D, i.e. one that does not lead to visual acuity reduction, is found almost in 50% of cases among unselected population. Therefore, further investigation of anisometropic amblyopia pathogenesis as well as of accompanying sensory, morphological and functional alterations is of great importance

Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases.

Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervous system lead to intestinal secretory and motor dysfunctions. The factors at the basis of these conditions are still to be totally identified and current therapeutic strategies are aimed only at achieving and maintaining remission states, by using therapeutic tools like aminosalicylates, corticosteroids, immunomodulators, biological drugs (i.e., monoclonal antibodies), and eventually surgery. Recent reports described a key role of purinergic mediators (i.e., adenosine and its nucleotides ATP and ADP) in the regulation of the activity of immune cells and enteric nervous system, showing also that alterations of the purinergic signaling are linked to pathological conditions of the intestinal tract. These data prompted to a series of investigations to test the therapeutic potential for inflammation-related intestinal conditions of compounds able to restore or modulate an altered purinergic signaling within the gut. This review provides an overview on these investigations, describing the results of preclinical and/or clinical evaluation of compounds able to stimulate or inhibit specific P2 (i.e., P2X7) or P1 (i.e., A2A or A3) receptor signaling and to modify the adenosine levels through the modulation of enzymes activity (i.e., Adenosine Deaminase) or nucleoside transporters. Recent developments in the field are also reported and the most promising purine-based therapeutic strategies for the treatment of inflammation-related gastrointestinal disorders are schematically summarized.

A histological and ultrastructural investigation of the female reproductive system of the water snake (Erythrolamprus miliaris): Oviductal cycle and sperm storage

AbstractWe studied the structural and cellular organisation of the oviduct of Erythrolamprus miliaris including its morphological variation during the reproductive cycle using light microscopy, scanning electron microscopy and transmission electron microscopy. Four anatomically distinct regions compose the oviduct of E. miliaris including the anterior and posterior infundibulum, glandular uterus, non‐glandular uterus and pouch. The cells of the oviductal epithelium secrete material by apocrine and merocrine processes, which vary between the anatomical regions and according to each phase of the reproductive cycle. The infundibular epithelium secretes electron dense vacuoles, which suggests the production of lipids, whereas the epithelial secretion of the glandular uterus, non‐glandular uterus and pouch creates lucent and slightly electron dense vacuoles, indicating the production of glycoproteins. The timing of mating, vitellogenesis and sperm storage directly influences the morphofunctional alterations in the oviducts of E. miliaris. Sperm storage occurs only in the infundibular receptacles with increased production of the neutral carbohydrates in the presence of male gametes. Sperm storage happens in vitellogenic, non‐vitellogenic and pregnant females of E. miliaris. Thus, females may be able to produce multiple clutches at different seasons of the year regardless of mating during autumn.

IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney.

IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36α+ DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36α receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36α stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36α-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36α-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36α overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36α may be a novel kidney injury marker useful for evaluating DT damages.

Metabolic alterations in generalised anxiety disorder: a review of proton magnetic resonance spectroscopic studies.

Generalised anxiety disorder (GAD) is a common psychiatric illness characterised by selective morpho-functional brain alterations. The breath of neuroimaging studies investigating the neural basis of GAD is extensive; however, its pathophysiology is still largely unknown. Specifically for proton Magnetic Resonance Spectroscopy (¹H MRS) investigations, which have the aim of identifying differences in metabolite levels between conditions in key brain areas, often showed contrasting results. Indeed, there are selected ¹H MRS studies reporting deficits of key metabolites in GAD patients; however, collectively the literature remains mixed with respect to consistency of major findings. In this review, we evaluate published ¹H MRS studies on GAD with the final aim of providing a comprehensive overview of the extent of neurometabolic dysfunctions associated with GAD. Interestingly, the majority of the studies reviewed showed altered metabolite levels in the dorsolateral prefrontal cortex and hippocampus suggesting regional specificity. These results also provide evidence of the utility of ¹H MRS not only for elucidating the pathophysiology of neuropsychiatric diseases, but also for the identification of more beneficial and targeted pharmacological interventions. Additionally, future studies are warranted to overcome methodological differences observed across the studies.

The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

We investigated the quantitative and morphofunctional alterations of neuron-astrocyte-microglia triads in CA3 hippocampus, in comparison to CA1, after 2 Vessel Occlusion (2VO) and the protective effect of dipyridamole. We evaluated 3 experimental groups: sham-operated rats (sham, n=15), 2VO-operated rats treated with vehicle (2VO-vehicle, n=15), and 2VO-operated rats treated with dipyridamole from day 0 to day 7 (2VO-dipyridamole, n=15), 90days after 2VO. We analyzed Stratum Pyramidalis (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of CA3. 1) ectopic neurons increased in SL and SR of 2VO-vehicle, and 2VO-dipyridamole rats; 2) apoptotic neurons increased in SP of 2VO-vehicle rats and dipyridamole reverted this effect; 3) astrocytes increased in SP, SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 4) TNF-α expression increased in astrocytes, blocked by dipyridamole, and in dendrites in SR of 2VO-vehicle rats; 5) total microglia increased in SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 6) triads increased in SR of 2VO-vehicle rats and dipyridamole reverted this effect. Microglia cooperated with astrocytes to phagocytosis of apoptotic neurons and debris, and engulfed ectopic non-fragmented neurons in SL of 2VO-vehicle and 2VO-dipyridamole rats, through a new mechanism called phagoptosis. CA3 showed a better adaptive capacity than CA1 to the ischemic insult, possibly due to the different behaviour of astrocytes and microglial cells. Dipyridamole had neuroprotective effects.

The influence of traumatic occlusion on the repair process for teeth following subluxation.

Traumatic occlusion (TO) can cause morphofunctional alterations that interfere in the homeostasis of the periodontium. The aim of this study was to assess the influence of TO on the periodontal repair process for teeth following subluxation. Ninety Wistar rats aged 12weeks were divided into three groups: control (C), subluxation (S) and subluxation with traumatic occlusion (S+TO). Subluxation was created with an impact force of 900cN applied by a tensiometer and TO was created with a direct composite resin filling. Healing after two experimental periods of 7 and 21days was assessed histologically. The Kruskal-Wallis and Dunn post hoc tests were used for group comparison. At 7days, there was a significant increase in periodontal ligament (PDL) width and amorphous fundamental substance, as well as a significant bone area reduction in groups S and S+TO. After 21days, there was a significant PDL width increase in group S+TO, and in the percentage of collagen fibres in group S, whereas group S+TO showed a 52% bone area reduction compared to the same group at 7days. Subluxation with or without TO caused only superficial root resorption. However, only group S+TO showed damage to the repair process of resorbed root areas after 21days. TO can increase damage to the PDL after subluxation and it can also delay the repair process after PDL damage.

Seasonal reproductive cycle and variability in plasma testosterone levels in the domestic duck (Anas platyrhynchos)

Morphofunctional gonadal alterations constitute an annual cycle in birds during which four phases can be distinguished in the testes based on histological modifications in the seminiferous epithelium, called quiescence, recrudescence, reproduction and regression. The aim of the present investigation was to conduct a morphometric and morphological study of the seminiferous epithelium on the testis of domestic duck and to evaluate the plasma testosterone levels in order to determine the possible presence of a reproductive cycle in the tropical region. The study was conducted on 60 adult domestic ducks ( Anas platyrhynchos ), where five animals were sacrificed per month and the testes were removed and histologically and morphometrically studied. Blood samples of the five animals were collected monthly in the morning period and the testosterone levels were analyzed. Annual reproductive cycle of the domestic duck presented by four distinct phases, starting with the reproductive phase at the beginning of winter (July) and peak of reproduction in spring (October), accompanied by an increase in tubule seminiferous diameter, epithelium height, weight and testicular volume, followed by a regressive phase at the end of spring (November) and the beginning of summer (December). Testicular quiescence was observed during summer (January and February) and was followed by a phase of spermatogenic recrudescence, which lasted throughout autumn (March to June), corresponding to the longest phase of the cycle. Complete spermiogenesis in terms of spermatozoa maturation and spermiation was observed during the reproductive phase, coinciding with the plasma testosterone peak. At regressive phase an exfoliation of the seminiferous epithelium was observed, accompanied by a great amount of fibrillar collagen. A decrease in tubular seminiferous diameter and epithelium height was observed during testicular quiescence, with predominance of spermatogonia and Sertoli cells and a second plasma testosterone peak was also observed during this phase (January), probably representing the preparation for a gradual return to the spermatogenic process during recrudescence. The latter phase was characterized by gradual recovery of the seminiferous epithelium, accompanied by the increase of spermatogonia, onset of meiosis, and the presence of primary spermatocytes and maturing spermatids. In conclusion the domestic duck presented the testicular cycle divided in four distinct phases in the tropical region with testosterone peaks in the testicular quiescence and reproductive phases.

Mechanism Of Cytomegalovirus Penetration Through Erythrocyte Membrane

Objective: To study the effect of cytomegalovirus infection on histidine concentration in erythrocytes of peripheral blood in pregnant women at 27-28th week of gestation and virus penetration through the erythrocyte membrane and to demonstrate the morphofunctional alterations of the latter. The objective of this study is to demonstrate the mechanism of cytomegalovirus penetration through the erythrocyte membrane as well as to describe the process of its structure damage which leads to the accumulation in the peripheral blood of degenerative forms of erythrocytes that lose their ability to deformability. This creates the conditions for the formation of hemic anaemia in a pregnant woman. The research has been conducted on the basis of current data and our own studies. Materials and methods: 75 pregnant women at 27-28th weeks of gestation were examined, including 55 CMV-seropositive ones with CMV-infection exacerbation at 27th week of gestation. All the studies were carried out at the Federal State Budget Scientific Institution “Far Eastern Scientific Centre of Physiology and Pathology of Respiration” during one year time. Histidine activity in peripheral blood erythrocytes was found according to the method suggested by Lucenko Michael T and Andrievskaya Irina A.; fatty acid peroxides in erythrocyte membrane-by Winkler-Schultze method; erythrocyte membrane microviscosity was found by spectrofluorimetric method of lateral diffusion of pyrene. Erythrocyte deformability was also found in accordance with the method of Lucenko Michael T and Andrievskaya Irina A. The calculation of deformed erythrocytes was done using automated cytophotometric device “Mekos” (Russia). Erythrocyte membrane condensation was measured in pixels by means of cytophotometric camera “Pixera” (USA). Results: During the exacerbation of CMV infection at 27-28th weeks of gestation the amount of distal histidine was lower 2.13 times per one erythrocyte. The level of unsaturated fatty acids increased 2.9 times, of fatty acid peroxides in erythrocyte membranes increased 3.3 times, which resulted in 1.7 times increase in erythrocyte membrane microviscosity in the lipid bilayer and in 6.8 times increase in erythrocyte deformability. Conclusion: The exacerbation of chronic CMV infection at 27-28th weeks of gestation causes the virus intrusion into erythrocyte membrane damaging the distal histidine content, which promotes further penetration of proteins of viral envelope and tegument into the erythrocyte. That results in the disturbance of phospholipids bond with erythrocyte membrane proteins, increase in fatty acid peroxides in erythrocytes and decrease in the membrane microviscosity. This promotes the accumulation of deformable erythrocytes in peripheral blood thus causing the threat of anemia formation in pregnant woman at late gestation.

Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis.

Dysregulation of Autonomic Nervous System (ANS) and central pain pathways in temporomandibular disorders (TMD) is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS), a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI) is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s) affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS) is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD) are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a) TMD with Central Sensitization ULFTENS Responders; (b) TMD with Central Sensitization ULFTENS Nonresponders; (c) TMD without Central Sensitization ULFTENS Responders; (d) TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology.

Protective Role of Postbiotic Mediators Secreted by Lactobacillus rhamnosus GG Versus Lipopolysaccharide-induced Damage in Human Colonic Smooth Muscle Cells.

Some beneficial effects of probiotics may be due to secreted probiotic-derived factors, identified as "postbiotic" mediators. The aim of this study was to evaluate whether supernatants harvested from Lactobacillus rhamnosus GG (LGG) cultures (ATCC53103 strain) protect colonic human smooth muscle cells (HSMCs) from lipopolysaccharide (LPS)-induced myogenic damage. LGG was grown in de Man, Rogosa, Share medium at 37°C and samples were collected in middle and late exponential, stationary, and overnight phases. Supernatants were recovered by centrifugation, filtered, and stored at -20°C. The primary HSMCs culture was exposed for 24 hours to purified LPS of a pathogen strain of Escherichia coli (O111:B4) (1 μg/mL) with and without supernatants. Postbiotic effects were evaluated on the basis of HSMCs morphofunctional alterations and interleukin-6 (IL-6) production. Data are expressed as mean±SE (P<0.05 significant). LPS induced persistent, significant, 20.5%±0.7% cell shortening and 34.5%±2.2% decrease in acetylcholine-induced contraction of human HSMCs. These morphofunctional alterations were paralleled to a 365.65%±203.13% increase in IL-6 production. All these effects were dose-dependently reduced by LGG supernatants. Supernatants of the middle exponential phase already partially restored LPS-induced cell shortening by 57.34%±12.7% and IL-6 increase by 145.8%±4.3% but had no effect on LPS-induced inhibition of contraction. Maximal protective effects were obtained with supernatants of the late stationary phase with LPS-induced cell shortening restored by 84.1%±4.7%, inhibition of contraction by 85.5%±6.4%, and IL-6 basal production by 92.7%±1.2%. LGG-derived products are able to protect human SMCs from LPS-induced myogenic damage. Novel insights have been provided for the possibility that LGG-derived products could reduce the risk of progression to postinfective motor disorders.

Intermittent hypobaric hypoxia combined with aerobic exercise improves muscle morphofunctional recovery after eccentric exercise to exhaustion in trained rats.

Unaccustomed eccentric exercise leads to muscle morphological and functional alterations, including microvasculature damage, the repair of which is modulated by hypoxia. We present the effects of intermittent hypobaric hypoxia and exercise on recovery from eccentric exercise-induced muscle damage (EEIMD). Soleus muscles from trained rats were excised before (CTRL) and 1, 3, 7, and 14 days after a double session of EEIMD protocol. A recovery treatment consisting of one of the following protocols was applied 1 day after the EEIMD: passive normobaric recovery (PNR), a 4-h daily exposure to passive hypobaric hypoxia at 4,000 m (PHR), or hypobaric hypoxia exposure followed by aerobic exercise (AHR). EEIMD produced an increase in the percentage of abnormal fibers compared with CTRL, and it affected the microvasculature by decreasing capillary density (CD, capillaries per mm2) and the capillary-to-fiber ratio (CF). After 14 days, AHR exhibited CD and CF values similar to those of CTRL animals (789 and 3.30 vs. 746 and 3.06) and significantly higher than PNR (575 and 2.62) and PHR (630 and 2.92). Furthermore, VEGF expression showed a significant 43% increase in AHR when compared with PNR. Moreover, after 14 days, the muscle fibers in AHR had a more oxidative phenotype than the other groups, with significantly smaller cross-sectional areas (AHR, 3,745; PNR, 4,502; and PHR, 4,790 µm2), higher citrate synthase activity (AHR, 14.8; PNR, 13.1; and PHR, 12 µmol·min-1·mg-1) and a significant 27% increment in PGC-1α levels compared with PNR. Our data show that hypoxia combined with exercise attenuates or reverses the morphofunctional alterations induced by EEIMD.NEW & NOTEWORTHY Our study provides new insights into the use of intermittent hypobaric hypoxia combined with exercise as a strategy to recover muscle damage induced by eccentric exercise. We analyzed the effects of hypobaric exposure combined with aerobic exercise on histopathological features of muscle damage, fiber morphofunctionality, capillarization, angiogenesis, and the oxidative capacity of damaged soleus muscle. Most of these parameters were improved after a 2-wk protocol of intermittent hypobaric hypoxia combined with aerobic exercise.

Reduced neuronal density in the CA1 anterodorsal hippocampus of the mdx mouse

Duchenne muscular dystrophy (DMD) is associated with non-progressive cognitive dysfunction including hippocampal-dependent memory deficits. Loss of the cytoskeleton-associated dystrophin protein in central inhibitory synapses, associated with consequent alterations in GABAergic function and synaptic plasticity, has been proposed as a primary mechanism responsible for cognitive impairments. However, several lines of evidence suggest a multifactorial etiology involving alternative signaling pathways, some of which could affect neuronal survival. To determine whether changes in neuronal density in the hippocampus could contribute to the emergence of memory deficits, we undertook an unbiased stereological estimation of neuron number in the anterodorsal CA1 region of the hippocampus of the dystrophin-deficient mdx mouse model of DMD. We found a significant reduction (~34%) in the number of pyramidal neurons, with a heterogeneous magnitude of genotype differences along the hippocampal antero-posterior axis. This extends previous knowledge of brain morphofunctional alterations induced by dystrophin loss and suggests that putative mechanisms involved in neurogenesis and/or neuron survival might contribute to the emergence of hippocampal-dependent learning and memory deficits in DMD.

Morphofunctional alterations in the olivocochlear efferent system of the genetic audiogenic seizure-prone hamster GASH:Sal.

The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Does acute exposure to aldehydes impair pulmonary function and structure?

Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations.For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups.In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

CHOROIDAL THICKNESS IN BEST VITELLIFORM MACULAR DYSTROPHY.

To assess the changes in choroidal thickness in different stages of Best vitelliform macular dystrophy (VMD). Thirty-four patients affected by VMD were prospectively enrolled and underwent a complete ophthalmologic examination, including best-corrected visual acuity measurement, biomicroscopic examination, and spectral domain optical coherence tomography. The Gass classification was used in defining the stages of VMD. Twenty healthy subjects served as the control group. Main outcome measures were the identification of choroidal changes in different stages of VMD and detection of a correlation between choroidal thickness and best-corrected visual acuity. No significant difference was found in the subfoveal choroidal thickness (SFCT) between eyes displaying Stage 1 and the control group (P = 0.181). Stages 2 and 3 showed an increased SFCT (320.4 and 319.1 μm, respectively) compared with that of control patients (P < 0.001 and P = 0.004, respectively). Stage 4 had a significantly inferior SFCT compared with Stages 2 and 3 (P = 0.007 and P = 0.025, respectively) but no significant difference was found between Stage 4 and control patients (P = 0.733). The Stage 5 group displayed a significant decrease in SFCT compared with that of the control group (181.3 μm and 238.4 μm, respectively, P = 0.002). Analyzing the association between SFCT and best-corrected visual acuity in patients affected by clinical VMD (Stages 2-5), the authors found that the best-corrected visual acuity decreased as the choroid thinned (P = 0.004). Choroidal thickness varies according to the stage of VMD, being higher in the vitelliform stage and thinner in the atrophic/cicatricial stage. Long-term studies are warranted to provide a more precise evaluation of the morphofunctional alterations in the different stages of VMD.

Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective

Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood.Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders.Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern.The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal.

BACKGROUND CHANGES OF THE DIGESTIVE SYSTEM MUCOSA IN PATIENTS WITH ACROMEGALY

Background: Gastrointestinal tract lesions due to the growth hormone impact on mucosa of both the stomach and colon contribute to the complications of acromegaly. In this case, there is a deficiency of the objective assessment data concerning the gastrointestinal tract condition in the acromegaly patients. Aim: To reveal the character of changes in the mucosa of both stomach and colon in the acromegaly patients. Materials and methods: The study is based on the results of analysis of 107 in-patients (32 men and 75 women) with suspected acromegaly who were observed during the period of 2006 to 2012 in the MONIKI Department of Therapeutic Endocrinology. Diagnosis of acromegaly was confirmed. Distribution of patients by gender showed that women suffer from acromegaly in the majority of cases. The ratio men/women equal to 1:2.2 correlates with the literature data. All acromegaly patients underwent the fibroesophago-gastroduodenoscopy, morphological investigation of the stomach mucosa, cytological analysis in search for Helicobacter pylori as well as fibrocolonoscopy plus biopsy in case of the pathological neoplasm identification. Results: Comparative study of changes in the gastrointestinal tract mucosa demonstrated that endoscopic investigation more often showed pathological changes in the upper areas of the digestion tract. It may be explained by the Helicobacter pylori contamination or a side effect of somatostatin analogues in the given group of patients which impairs the stomach epithelium vital activity and enables development of neoplasms in the acromegaly patients. Analysis of the morphofunctional alterations of the stomach-and-colon mucosa in the acromegaly patients revealed concomitant diseases in these patients which were as follows: foveolar hyperplasia of the tegumental-foveolar epithelium, hyperplastic polyps, and tubular adenomas which are an indication for obligatory morphologic investigation of the stomach-and-colon mucosa in this group of patients. Our study proved a high degree of the stomach mucosa contamination with Helicobacter pylori in the acromegaly patients: in 81% of our patients. Conclusion: Our results showed that endoscopy with obligatory targeted biopsy and a search for Helicobacter pylori are extremely necessary for this group of patients. The results obtained are indicative of the necessity of annual gastroenterological examination of patients suffering from acromegaly.

Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.