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Background: Invasive cardiac procedures, such as arrhythmia ablation, cardiac resynchronisation therapy, percutaneous mitral annuloplasty and retrograde cardioplegia delivery require cannulation of the coronary sinus (CS). Detailed knowledge of the CS ostium region, including recognition of the presence of the Thebesian valve which sometimes covers the sinus, is a key to successfully carry out such procedures. Materials and methods: In the present study, 160 autopsied human hearts from both sexes were examined for the presence of the Thebesian valve. If identified, the histological structure of the valve was studied. Results: Five types of the CS valve were distinguished; all of them presented with a typical histological structure with the exception of the cord-like type, in which cells were similar to those of the conduction system of the heart. Conclusions: Proper identification of the CS valve and analysis of its size and histological features could have important implications for electrophysiologists. (Folia Morphol 2014; 73, 3: 298–301)
Background: The aim of this study was to determine the fundamental relationships between cervical intervertebral disc (IVD) degeneration, endplate calcification, and the patency of endplate marrow contact channels (MCC). Materials and methods: Sixty cervical IVDs were excised from 30 human cadavers. After sectioning the specimens underwent micro computed tomography (microCT) — from all images the number, calibre, diameter and distribution of endplate openings were measured using ImageJ. Next, the specimens were scored for macroscopic degeneration (Thompson’s classification), and subsequently underwent histological analysis for both IVD and endplate degeneration (Boos’s classification) and calcification. Results. The study group comprised 30 female and 30 male IVDs (mean age ± SD: 51.4 ± 19.5). Specimen’s age, macroscopic and microscopic degeneration correlated negatively with the number of MCCs (r = –0.33–(–0.95); p < 0.0001), apart from the MCCs > 300 µm in diameter (r = 0.66–0.79; p < 0.0001). The negative relationship was strongest for the MCCs 10–50 µm in diameter. Conclusions. There is a strong negative correlation between the number of endplate MCCs, and both macroscopic and microscopic cervical IVD and endplate degeneration. This could further support the thesis that endplate calcification, through the occlusion of MCCs, leads to a fall in nutrient transport to the IVD, and subsequently causes its degeneration. (Folia Morphol 2015; 74, 1: 84–92)
Background: The aim of the current study was to analyse the extra- and intracerebral course of the recurrent artery of Heubner (RAH) to provide detailed information for neurosurgeons operating in this area. Materials and methods: The material for this study was obtained from cadavers (ages 31–75 years) during routine autopsies. A total of 70 human brains (39 male and 31 female) were examined. The material was collected not later than 48 h post-mortem. People who died due to neurological disorders were not included into the study. Right after dissection the arteries were perfused with either acrylic paint emulsion, polyvinyl chloride or Mercox CL-2R resin, through the Circle of Willis or electively through the RAH. The obtained material was analysed using a stereoscopic light microscope, magnification 2–40 x. Results: The RAH was present in 138 hemispheres with a mean of 1.99 RAH per hemisphere (275 RAH in total). The mean RAH length was 25.2 mm and the mean RAH diameter, in its place of origin, was 1 mm. In 168 (61%) cases the RAH ran superiorly, in 88 (32%) cases anteriorly, in 11 (4%) cases inferiorly and in 8 (3%) cases posteriorly to the A1 segment. In 70.2% of the cases the course of the RAH was parallel to the anterior communicating artery A1 segment, and in 29.8% of the cases the RAH arched towards the olfactory tract. As the extracerebral course of the RAH was always tortuous, its length was 1 to 5 times the distance between its place of origin and the most lateral point of anterior perforated substance (APS) penetration. The intracerebral course of the RAH was almost always univectorial — towards the head of the caudate nucleus. The course of RAH branches depended on their number. When the number of RAHs and their branches was low, they separated immediately after penetrating the APS and formed multiple small branches. When the number of RAHs and branches was high, post-APS branching was less frequent and occurred in distal segments. Conclusions: The origin and course of the RAH is highly variable. The RAH, in its extra- and intracerebral course, may join with the middle group of the lenticulostriate arteries or directly with the middle cerebral artery. This artery should be routinely identified during anterior communicating artery aneurysm clipping to prevent postoperative neurological deficits. (Folia Morphol 2013; 72, 2: 94–99)
The function of primary sensory neurons is to receive and transmit information from external environment and these neurons are able to release neuromediators from the activated peripheral endings. The aim of this study was to determine the influence of sensory nerves and administration of their mediator — calcitonin gene related peptide (CGRP) on the course of acute pancreatitis (AP). Ablation of sensory nerves was performed by neurotoxic dose of capsaicin (100 mg/kg). Single or repeated episodes of AP were induced by caerulein infusion (10 µg/kg/h for 5 h). Five repeated AP were performed once a week. Capsaicin at the dose which stimulates sensory nerves (0.5 mg/kg/dose) or CGRP (10 µg/kg/dose) was administrated before and during or after single induction of AP, as well as, after each induction of repeated AP. Rats were killed at the time 0, 3 or 9 h after single induction of AP or two weeks after last induction of repeated AP. Ablation of sensory nerves aggravated pancreatic damage in caerulein-induced AP. Treatment with stimulatory doses of capsaicin or CGRP before and during single induction of AP attenuated the pancreatic damage in morphological examination. This effect was also manifested by partial reversion of AP evoked drop in DNA synthesis and pancreatic blood flow (PBF). Administration of CGRP after single AP induction aggravated histologically manifested pancreatic damage. The further decrease in PBF and DNA synthesis was also observed. Animals with five episodes of AP showed almost full pancreatic recovery two weeks after last induction of AP concerning all parameters tested. In stimulatory doses of capsaicin treated rats, we observed the decrease in pancreatic amylase and fecal chymotrypsin activity, as well as, the drop in DNA synthesis. Similar but less pronounced effects were observed after treatment with CGRP. We conclude that effect of sensory nerves and CGRP on AP is two-phase and time dependent. Stimulation of sensory nerves or the administration of CGRP during development of AP exhibits protective effects against pancreatic damage induced by caerulein overstimulation. After induction of AP, persistent activity of sensory nerves and presence of CGRP aggravate pancreatic damage and lead to functional insufficiency typical for chronic pancreatitis.
Acute pancreatitis is accompanied by the enhanced expression of EGF in the pancreas and the administration of EGF was found to exhibit the beneficial effect on edematous cerulein-induced pancreatitis. Therefore, we decided to determine the influence of EGF on necro-hemorrhagic pancreatitis induced by ischemia and reperfusion (I/R). Acute pancreatitis was induced in rats by restricting the pancreatic blood flow (PBF) in the inferior splenic artery for 30 min using microvascular clips. EGF was administered three times daily (10µg/kg per dose s.c.) starting immediately after the clips removal. Rats were sacrificed on day 1, 3, 5, 10 and 21 following ischemia. PBF was measured using a laser Doppler flowmeter. Morphological signs of pancreatitis, as well as the levels of plasma amylase, lipase, interleukin-1ß and interleukin-10 concentration and pancreatic cell proliferation were examined. Results: Ischemia with reperfusion caused acute necro-hemorrhagic pancreatitis with a histological and biochemical manifestation of pancreatic damage, followed by a spontaneous regeneration. The administration of EGF caused the reduction in the histological signs of pancreatic damage, such as necrosis, edema and leukocyte infiltration, and accelerated the pancreatic repair. Also, EGF treatment significantly attenuated the reduction in pancreatic blood flow and DNA synthesis. The activity of plasma amylase and lipase, as well as plasma interleukin-1ß and interleukin-10 concentrations were decreased in EGF treated animals. Conclusions: EGF exerts beneficial influence on the course of I/R induced pancreatitis and this effect seems to be related to the reduction in the activation of pro-inflammatory interleukin cascade, the improvement of PBF, and the increase in pancreatic cell growth.
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Ghrelin attenuates the development of acute pancreatitis in rats

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Ghrelin, a circulating growth hormone-releasing peptide isolated from human and rat stomach, stimulates growth hormone secretion, food intake and exhibits gastroprotective properties. Ghrelin is predominantly produced by a population of endocrine cells in the gastric mucosa, but its presence in bowel, pancreas, pituitary and hypothalamus has been reported. In human fetal pancreas, ghrelin is expressed in a prominent endocrine cell population. In adult pancreatic islets the population of these cell is reduced. The aim of present study was to investigate the influence of ghrelin administration on the development of acute pancreatitis. Methods: Acute pancreatitis was induced in rat by caerulein injection. Ghrelin was administrated twice (30 min prior to the first caerulein or saline injection and 3 h later) at the doses: 2, 10 or 20 nmol/kg. Immediately after cessation of caerulein or saline injections the following parameters were measured: pancreatic blood flow, plasma lipase activity, plasma interleukin-1ß (IL-1ß) and interleukin 10 (IL-10) concentration, pancreatic DNA synthesis, and morphological signs of pancreatitis. Results: Administration of ghrelin without induction of pancreatitis did not affect significantly any parameter tested. Caerulein led to the development of acute edematous pancreatitis. Treatment with ghrelin at the dose 2 nmol/kg, during induction of pancreatitis, was without effect on pancreatic histology or biochemical and functional parameters. Treatment with ghrelin at the dose 10 and 20 nmol/kg attenuated the development of pancreatitis and the effects of both doses were similar. Administration of ghrelin (10 or 20 nmol/kg) reduced inflammatory infiltration of pancreatic tissue and vacuolization of acinar cells. Also, plasma lipase activity and plasma IL-1ß concentration were reduced, and caerulein-induced fall in pancreatic DNA synthesis was reversed. Administration of ghrelin at the dose 10 and 20 nmol/kg was without effect on caerulein-induced pancreatic edema and pancreatitis-related fall in pancreatic blood flow. Conclusions: (1) Administration of ghrelin attenuates pancreatic damage in caerulein-induced pancreatitis; (2) Protective effect of ghrelin administration seems to be related the inhibition in inflammatory process and the reduction in liberation of pro-inflammatory IL-1ß.
Caerulein-induced acute pancreatitis was studied in rats. Consistent with this type of acute pancreatitis morphological (edema, leukocytic infiltration and acinar cell vaculization) and biochemical (increase in pancreatic protein content, PAF release and serum amylase) changes developed 5 hours after caerulein administration. In addition increase in pancreatic weight and decrease in pancreatic blood flow were noticed. PAF administration caused pancreatic damage similar in some parameters to caerulein-induced pancreatitis, along with reduction of pancreatic blood flow, increase in pancreatic protein content, and serum amylase. TCV-309, a selective PAF antagonist, administered prior to caerulein and/or PAF, reduced caerulein-induced pancreatitis and prevented PAF-induced pancreatitis. Results of our present studies indicate the crucial role of PAF in pathogenesis of experimental acute pancreatitis.
Insulin-like growth factor-1 (IGF-1) and other growth factors overexpression was reported in acute pancreatitis. Previous studies have shown the protective effect of epidermal growth factor (EGF), Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor (FGF) in the course of experimental acute pancreatitis. The aim of our studies was to determine the effect of IGF-1 administration on the development of caerulein-induced pancreatitis. Methods: Acute pancreatitis was induced by infusion of caerulein (10 µg/kg/h) for 5 h. IGF-1 was administrated twice at the doses: 2, 10, 50, or 100 µg/kg s.c. Results: Administration of IGF-1 without induction of pancreatitis increased plasma interleukin-10 (IL-10). Infusion of caerulein led to development of acute edematous pancreatitis. Histological examination showed pancreatic edema, leukocyte infiltration and vacuolization of acinar cells. Also, acute pancreatitis led to an increase in plasma lipase and interleukin 1ß (IL-1ß) level, whereas pancreatic DNA synthesis and pancreatic blood flow were decreased. Treatment with IGF-1, during induction of pancreatitis, increased plasma IL-10 and attenuated the pancreatic damage, what was manifested by histological improvement of pancreatic integrity, the partial reversion of the drop in pancreatic DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis-evoked increase in plasma amylase, lipase and IL-1ß level. Protective effect of IGF-1 administration was dose-dependent. Similar strong protective effect was observed after IGF-1 at the dose 2 x 50 and 2 x 100 µg/kg. Conclusions: (1) Administration of IGF-1 attenuates pancreatic damage in caerulein-induced pancreatitis; (2) This effect is related, at least in part, to the increase in IL-10 production, the reduction in liberation of IL-1ß and the improvement of pancreatic blood flow.
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Obestatin is a peptide derived from the proghrelin, a common prohormone for ghrelin and obestatin. Obestatin, like the ghrelin has been originally extracted from rat stomach, and the stomach seems to be a major source of circulating obestatin. Previous studies have shown that administration of ghrelin exhibits protective effect in the pancreas, inhibiting the development of acute pancreatitis. Recent study has shown that obestatin promotes survival of ß-cells and pancreatic islets. Aim of the present study was to investigate the influence of obestatin administration on the development of cerulein-induced pancreatitis. Studies were performed on male Wistar rats. Acute pancreatitis was induced by cerulein given intraperitoneally 5 times at a dose of 50 µg/kg/dose with 1-h intervals. Obestatin was injected twice intraperitoneally at the dose of 4, 8 or 16 nmol/kg/dose. In control saline-treated rats, obestatin was without effect on pancreatic morphology, serum activity of pancreatic enzymes, serum level of pro-inflammatory interleukin-1b or pancreatic cells proliferation. In animals with induction of acute pancreatitis, morphological examination showed that administration of obestatin decreased pancreatic leukocyte infiltration and vacuolization of acinar cells. These effects were accompanied by reduction in the pancreatitis-evoked increase in serum level of pancreatic digestive enzymes, lipase amylase and poly-C ribonuclease. Obestatin administered at the highest dose of 16 nmo/kg/dose reduced serum activity of these enzymes by 33, 42 and 44%, respectively. Also serum concentration of pro-inflammatory interleukin-1ß was decreased by obestatin in rats with acute pancreatitis; whereas the pancreatitis-evoked decrease in pancreatic blood flow and pancreatic DNA synthesis was partially reversed. Administration of obestatin reduces the severity of cerulein-induced acute pancreatitis. This effect is related, at least in part, to the improvement of pancreatic blood flow and reduction in pro-inflammatory interleukin-1ß release.
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Mice with the knockout of endothelial nitric oxide synthase (eNOS ko) demonstrate symptoms resembling the human metabolic syndrome. NO has been recently demonstrated to be deeply involved in regulation of not only blood flow and angiogenesis, but also in modulation of mammalian basal energy substrate metabolism. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. The enzyme dimethylarginine dimethylaminohydrolase (DDAH) catabolizes ADMA, what leads to increase of endogenous NO bioavailability. This study was aimed to compare the brown (BAT) and white (WAT) adipose tissue gene expression of age matched mice with decreased (eNOS ko) and increased (overexpressing DDAH) endogenous NO generation. The 19 week old eNOS ko mice demonstrated significantly lower weight, higher circulating glucose, insulin, leptin and cholesterol concentrations. The adiponectin as well as fasting triglyceride concentrations were not significantly altered. Animals with DDAH knock in, presented significantly increased angiogenic activity than eNOS ko mice. The microarray analysis pointed to activation of adipogenesis-related genes in eNOS ko mice in WAT, what was in contrast with the inhibition observed in the DDAH overexpressing mice. The angiogenesis related gene expression was down-regulated in both models in comparison to WT animals. This study support the multipotential role of endogenous NO in maintaining homeostasis of energy substrate catabolism.
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