Abstract: The migrating motility complex (MMC), a cyclical phenomenon, represents rudimentary motility pattern in the gastrointestinal tract. The MMC is observed mostly in the stomach and gut of man and numerous animal species. It contains three or four phases, while its phase III is the most characteristic. The mechanisms controlling the pattern are unclear in part, although the neural control of the MMCseems crucial. The main goal of this article was to discuss the importance of intrinsic innervation of the gastrointestinal tract in MMC initiation, migration, and cessation to emphasize that various MMC-controlling mechanisms act through the enteric nervous system. Two main neural regions, central and peripheral, are able to initiate the MMC. However, central regulation of the MMC may require cooperation with the enteric nervous system. When central mechanisms are not active, the MMC can be initiated peripherally in any region of the small bowel. The enteric nervous system affects the MMC in response to the luminal stimuli which can contribute to the initiation and cessation of the cycle, and it may evoke irregular phasic contractions within the pattern. The hormonal regulators released from the endocrine cells may exert a modulatory effect upon the MMC mostly through the enteric nervous system. Their central action could also be considered. It can be concluded that the enteric nervous system is involved in the great majority of the MMC-controlling mechanisms.
Keywords: migrating motor complex, man, animals, intrinsic control, enteric nervous system
Abstract: Background: Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods: To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique. Results: WT cav-3 significantly decreased HCN4 current density and shifted midpoint of activation into negative direction. HCN4 current properties were differentially modulated by LQTS-associated cav-3 mutations. When compared with WT cav-3, A85T, F97C, and T78M did not alter the specific effect of cav-3, but S141R significantly increased HCN4 current density. Compared with WT cav-3, no significant modifications of voltage dependence of steady-state activation curves were observed. However, while WT cav-3 alone had no significant effect on HCN4 current activation, all LQTS-associated cav-3 mutations significantly accelerated HCN4 activation kinetics. Conclusions: Our results indicate that HCN4 channel function is modulated by cav-3. LQTS-associated mutations of cav-3 differentially influence pacemaker current properties indicating a pathophysiological role in clinical manifestations.
Keywords: long-QT syndrome, caveolin-3, hyperpolarization-activated cyclic nucleotide gated channel 4, If, whole-cell current
Abstract: Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or withoutMTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.
Keywords: methotrexate, vitamin C, kidney, liver, oxidative stress
Abstract: Alzheimer’s disease (AD) has been reported to be linked with diabetes mellitus and insulin resistance. Adiponectin (ADN), an adipocytokine secreted from adipose tissue, is involved in the regulation of insulin sensitivity, energy homeostasis, and mitochondrial dysfunction. In this study, we examined the effect of ADN on passive avoidance memory in animal model of sporadic AD (sAD). On days 1 and 3 after cannulation, rats received intracerebroventricular (icv) injection of streptozotocin (STZ) (3 mg/kg). Thirty minutes before the learning process, animals received saline or ADN in different doses (6, 60, and 600 μg). The step-through latency (STL) and total time spent in the dark compartment (TDC) were recorded and analyzed. In STZ-treated rats, STL was significantly decreased, whereas TDC showed a dramatic increase. In ADN-treated rats, STL was significantly increased (P < 0.01) in all treatment doses. The number of entries was decreased in all applied doses; however, TDC was reduced only by the application of 6 ng of ADN (P < 0.05). It can be concluded that ADN is useful to improve the STZ-induced memory impairment. This study showed, for the first time, that icv administration of ADN could improve the memory acquisition in animal model of sAD.
Keywords: adiponectin, alzheimer’s disease, dementia, memory, streptozotocin
Abstract: It has been reported that changes in cytokine levels affect mitochondrial functions, levels of hypoxia-inducible factor α (HIF-1α), and tissue damage during sepsis. We aimed to investigate the effects of simvastatin pretreatment on mitochondrial enzyme activities, and on levels of ghrelin, HIF-1α, and thiobarbituric acid reactive substances (TBARS) in kidney tissue during sepsis. Rats were separated into four groups, namely, control, lipopolysaccharides (LPS) (20 mg/kg), simvastatin (20 mg/kg), and simvastatin + LPS. We measured the levels of mitochondrial enzyme activities and TBARS in the kidney using spectrophotometry. The histological structure of the kidney sections was examined after staining with hematoxylin and eosin. Tumor necrosis factor α (TNF-α), IL-10, HIF-1α, and ghrelin immunoreactivity were examined using proper antibodies. In tissue, TNF-α (p < 0.01) and HIF-1α (p < 0.05). Ghrelin immunoreactivity was lower in the LPS group (p < 0.05). We observed that pretreatment of simvastatin caused favorable changes on ghrelin and TBARS levels in rats with sepsis.
Keywords: hypoxia-inducible factor, ghrelin, kidney, lipopolysaccharides, sepsis, simvastatin
Abstract: We hypothesized that cochlear frequency discrimination occurs through medial olivocochlear efferent (MOCE)- induced alterations in outer hair cell (OHC) electromotility, which is independent from basilar membrane traveling waves. After obtaining informed consent, volunteers with normal hearing (n = 10; mean age: 20.6 ± 1.2 years) and patients with unilateral deafness (n = 10; mean age: 30.2 ± 17.9 years) or bilateral deafness (n = 8; mean age: 30.7 ± 13.8 years) underwent a complete physical and audiological examination, and audiological tests including transient evoked otoacoustic emission and spontaneous otoacoustic emission (TEOAE and SOAE, respectively). SOAE recordings were performed during contralateral pure-tone stimuli at 1 and 3 kHz. SOAE recordings in the presence of contralateral puretone stimuli showed frequency-specific activation out of the initial frequency range of SOAE responses. Basilar membrane motion during pure-tone stimulation results from OHC activation by means of MOCE neurons rather than from a traveling wave. Eventually, frequency-specific responses obtained from SOAEs suggested that OHC electromotility may be responsible for frequency discrimination of the cochlea independently from basilar membrane motion.
Keywords: otoacoustic emissions, spontaneous, hair cells, auditory, outer, cochlea, audiometry, pure-tone, medial olivocochlear efferents
Abstract: Atherosclerosis is a disease caused by a build-up of fatty plaques and cholesterol in the arteries. The lumen of the vessels is obliterated resulting in restricted blood supply to tissues. In ischemic conditions, the cytosolic Ca2+ level of skeletal muscle may increase, indicating the alteration of Ca2+ removal mechanisms. Ca2+ is transported from cytosol into the sarcoplasmic reticulum by Ca2+ ATPase (SERCA), with its 1a isoform expressed in adult, while its 1b isoformin neonatal and regenerating fast-twitch skeletalmuscle. To investigate the role of these isoforms in ischemic skeletal muscle, biopsies from musculus biceps femoris of patients who underwent amputation due to atherosclerosis were examined. Samples were removed from the visibly healthy and hypoxia-affected tissue. Significantly increased SERCA1a expression was detected under the ischemic conditions (246 ± 69%; p < 0.05) compared with the healthy tissue. Furthermore, the ratio of SERCA1a-positive fibers was slightly increased (46 ± 4% in healthy tissue and 60 ± 5% in ischemic tissue; p > 0.05), whereas SERCA2a did not change. In addition, in primary cultures derived from hypoxia-affected tissue, the diameter and fusion index of myotubes were significantly increased (30 ± 1.6 μm vs. 41 ± 2.4 μm and 31 ± 4% vs. 45 ± 3%; p < 0.05). We propose that the increased SERCA1a expression indicates the existence and location of compensating mechanisms in ischemic muscle.
Keywords: atherosclerosis, amputation, Ca2+, skeletal muscle, SERCA1
Abstract: Recent studies suggest that proinsulin-connecting peptide (C-peptide) may exhibit characteristics of a hormone and show physiological functions in various tissues. This study was aimed to determine whether C-peptide could be involved in the regulation of lipolysis, adiponectin release, and function of mesenchymal stem cells (MSCs) in adipose tissue. Human subcutaneous adipose tissue was cultured in the presence of C-peptide. The level of lipolysis was determined by glycerol measurement in the conditioned media. Effect of C-peptide on adiponectin secretion was evaluated in differentiated adipocytes. The adipogenic and osteogenic abilities of adipose MSCs were evaluated using oil red and alizarin red staining, respectively. The tetrazolium bromide test was conducted for evaluating the effect of C-peptide on MSCs proliferation. C-peptide induced a significant decrease in basal lipolysis at concentrations of 8 and 16 nM (p < 0.05). It had no significant effects on isoproterenol-stimulated lipolysis, adiponectin secretion, and adipogenic or osteogenic differentiation of MSCs. At a concentration of 4 nM, this peptide significantly increased the proliferative capability of MSCs (p < 0.05). These results suggest that C-peptide has some physiological effects in human subcutaneous adipose tissue and contributes to the regulation of basal lipolysis and pool of MSCs.
Keywords: adipose tissue, adiponectin, C-peptide, stem cells, differentiation
Abstract: Introduction: Myocardial contractility of the left ventricle (LV) is related to arterial distensibility. Sport activity is frequently associated with changes in both LV and arterial functions. This study aimed to find correlations between three-dimensional speckle-tracking echocardiography-derived segmental LV deformation parameters and echocardiographically assessed aortic stiffness index (ASI) in athletes. This study comprised 26 young elite athletes (mean age: 26.7 ± 8.4 years, nine men). Results: Among segmental circumferential strains (CSs), only that of apical anterior (r = 0.40, p = 0.05), septal (r = 0.47, p = 0.01), inferior (r = 0.59, p = 0.001), lateral (r = 0.44, p < 0.05), and midventricular anteroseptal (r = 0.44, p < 0.05) segments correlated with ASI, whereas LV-CS of the midventricular anterior segment showed a correlation tendency. Only longitudinal strain of basal anteroseptal (r = −0.46, p < 0.05) and inferoseptal (r = −0.57, p < 0.01) segments showed correlations with ASI, whereas that of the basal anterior segment had only a tendency to correlate. Some segmental multidirectional strains also correlated with ASI. Conclusions: Correlations could be demonstrated between increased aortic stiffness and circular function of the apical and midventricular LV fibers and longitudinal motion of the basal septum and LV anterior wall (part of LV outflow tract) in maintaining circulation in the elite athletes.
Keywords: aortic, echocardiography, function, left ventricle, speckle-tracking, stiffness, strain, three-dimensional