Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

BACKGROUND: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. OBJECTIVE: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. RESULTS: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

Melatonin metabolite, N(1)-acetyl-N(1)-formyl-5-methoxykynuramine (AFMK), attenuates acute pancreatitis in the rat: in vivo and in vitro studies.

Melatonin protects the pancreas from inflammation and free radical damage but the effect of the melatonin metabolite: N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on acute pancreatitis is unknown. This study assessed the effects of AFMK on acute pancreatitis (AP) in the rats in vivo and on pancreatic cell line AR42J in vitro. AFMK (5, 10 or 20 mg/kg) was given intraperitoneally to the rats 30 min prior to the induction of AP by subcutaneous caerulein infusion (25 µg/kg). Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue. Blood samples were taken for evaluation of amylase activity and TNF-α concentration. GPx, TNF-α, proapoptotic Bax protein, antiapoptotic Bcl-2 protein and the executor of apoptosis, caspase-3, were determined by Western blot in AR42J cells subjected to AFMK or to melatonin (both used at 10(-12), 10(-10), or 10(-8)M), without or with addition of caerulein (10(-8)M). AP was confirmed by histological examination and by serum increases of amylase and TNF-α (by 800% and 300%, respectively). In AP rats, pancreatic MDA + 4-HNE levels were increased by 300%, whereas GPx was reduced by 50%. AFMK significantly diminished histological manifestations of AP, decreased serum amylase activity and TNF-α concentrations, reduced MDA + 4-HNE levels and augmented GPx in the pancreas of AP rats. In AR42J cells, AFMK combined with caerulein markedly increased protein signals for GPx, Bax, caspase-3 and reduced these for TNF-α and Bcl-2. In conclusion, AFMK significantly attenuated acute pancreatitis in the rat. This may relate to the antioxidative and anti-inflammatory effects of this molecule and possibly to the stimulation of proapoptotic signal transduction pathway.

Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study.

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.

Pretreatment with low doses of acenocoumarol inhibits the development of acute ischemia/reperfusion-induced pancreatitis.

Coagulative disorders are known to occur in acute pancreatitis and are related to the severity of this disease. Various experimental and clinical studies have shown protective and therapeutic effect of heparin in acute pancreatitis. Aim of the present study was to determine the influence of acenocoumarol, a vitamin K antagonist, on the development of acute pancreatitis. Studies were performed on male Wistar rats weighing 250 - 270 g. Acenocoumarol at the dose of 50, 100 or 150 µg/kg/dose or vehicle were administered once a day for 7 days before induction of acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. The severity of acute pancreatitis was assessed after 5-h reperfusion. Pretreatment with acenocoumarol given at the dose of 50 or 100 µg/kg/dose reduced morphological signs of acute pancreatitis. These effects were accompanied with a decrease in the pancreatitis-evoked increase in serum activity of lipase and serum concentration of pro-inflammatory interleukin-1ß. Moreover, the pancreatitis-evoked reductions in pancreatic DNA synthesis and pancreatic blood flow were partially reversed by pretreatment with acenocoumarol given at the dose of 50 and 100 µg/kg/dose. Administration of acenocoumarol at the dose of 150 µg/kg/dose did not exhibit any protective effect against ischemia/reperfusion-induced pancreatitis. We concluded that pretreatment with low doses of acenocoumarol reduces the severity of ischemia/reperfusion-induced acute pancreatitis.

Analysis of the intensity of immune cell infiltration and immunoreactivity of RCAS1 in diffuse large B-cell lymphoma of the palatine tonsil and its microenvironment.

Non-Hodgkin lymphoma of Waldeyer's ring constitutes a small percentage of cases of palatine tonsil malignancies and its precise etiology remains unknown. RCAS1 (receptor cancer-binding antigen expressed on SiSo cells) has been demonstrated to be associated with poor prognosis, the development of lymph node metastases and participation in tumor microenvironment remodeling. Our aim is to analyze the potential role of RCAS1 expression in the tumor and tumor microenvironment in the development of early-stage palatine tonsil B-cell lymphomas. We selected 20 patients and analyzed tissue samples from the lymphoma and tumor microenvironment of each patient and from a reference group of 20 patients with chronic tonsillitis. The presence of RCAS1 protein immunoreactivity was demonstrated in 65% of the examined tissue samples of diffuse large B-cell lymphoma and in 25% of the analyzed stromata in which it was exhibited by CD68-positive cells identified as macrophages and dispersed throughout the stroma. RCAS1 immunoreactivity in the lymphoma tissue samples remained at a level comparable with that of the reference and was significantly higher in these samples than in those from the stroma. Chronic inflammation of the palatine tonsils thus results in intensive infiltration by various types of immune system cells and in excessive RCAS1 immunoreactivity, both of which confirm the important regulatory role of RCAS1 in the immune response in the mucosa-associated lymphatic tissue of Waldeyer's ring. RCAS1 seems to be involved in creating tumor-induced inflammation in the tumor and its microenvironment.

Endplate calcification and cervical intervertebral disc degeneration: the role of endplate marrow contact channel occlusion.

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.

Therapeutic effect of ghrelin in the course of ischemia/reperfusion-induced acute pancreatitis.

BACKGROUND: Protective effect of pretreatment with ghrelin against different forms of acute pancreatitis (AP) has been recently reported. Moreover, the healing properties of this peptide have been proved in AP evoked by cerulein. However, no studies have investigated whether the administration of ghrelin affects the course of ischemia/reperfusion-induced AP. AIM: The aim of this study was to evaluate the impact of ghrelin therapy on the course of necrotizing inflammation of the pancreas and to test its impact on peroxidation of lipids and antioxidant defense system in the acutely inflamed pancreas. METHODS: Acute inflammation of the pancreas was triggered by pancreatic ischemia which was then followed by reperfusion of the gland. Ghrelin (8 nmol/kg/dose) was administered to intraperitoneally twice daily, 24h after the initiation of AP. The impact of ghrelin on the course of necrotizing pancreatitis was evaluated between 1 and 21 days, and involved histological, functional, and biochemical analyses. RESULTS: Treatment with ghrelin ameliorated morphological signs of pancreatic damage including edema, acinar cells vacuolization, hemorrhages, acinar necrosis, leukocytic infiltration of the gland, and led to its earlier regeneration. These effects were accompanied by an improvement in pancreatic blood flow, enhanced DNA synthesis, reduced serum level of pro- inflammatory interleukin-1ß, decreased levels of malondialdehyde and an enhanced superoxide dismutase activity in pancreatic tissue. CONCLUSIONS: Ghrelin exerts a pronounced therapeutic effect against ischemia-reperfusion-induced pancreatitis. The mechanisms involved are likely multifactorial and are mediated by its anti-inflammatory, as well as anti-oxidative properties.

The Thebesian valve and its significance for electrophysiologists.

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 carryout 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.

Proliferative index activity in oral squamous cell carcinoma: indication for postoperative radiotherapy?

The predictive value of the Ki-67 labelling index and its relationship with radiosensitivity in oral squamous cell carcinoma (SCC) remains controversial. We sought to evaluate whether the expression of Ki-67 antigen found in SCC of the tongue and the floor of the mouth is an indication for postoperative radiotherapy (PORT). The first study group included 34 patients who were treated only with primary surgery, while the second group included 26 patients who underwent primary surgery combined with PORT. The correlation between Ki-67 expression and loco-regional recurrence, as well as the 5-year disease-specific survival, was assessed in the two groups. Cases of high-proliferative tumours showed a significantly higher risk of loco-regional recurrence (P=0.018) and a poorer prognosis (P=0.001) only in the 34 patients treated with surgery alone. In multivariate Cox regression analysis, high Ki-67 expression was an independent predictor of loco-regional recurrence (HR 5.42, P=0.029) and disease-specific survival (HR 9.02, P=0.004). The correlation between Ki-67 expression and the risk of loco-regional recurrence in SCC of the tongue and the floor of the mouth may be useful in the selection of patients at a higher risk of recurrence who would benefit from PORT, despite adequate margins of resection and early stage of the disease.

Morphological characteristics of potentially malignant pulmonary nodules in high-risk male smokers detected in lung cancer screening trial in Cracow, Poland.

The purpose of this paper was to present morphological characteristics of potentially malignant nodules revealed in a group of male smokers aged 50-74 with a very high risk for developing lung cancer estimated in the study for lung cancer screening in Cracow (Poland). Nine hundred male smokers aged 50 to 74 years were invited to the study and were asked in questionnaires about e.g. smoking exposure history. Exclusion criteria included e.g. positive cancer history and chest computed tomography (CT) examination in the previous year. Based on CT results and characteristics of pulmonary nodules subjects were classified to group A (low risk), group B (indeterminate) and group C (high-risk individuals - required work-up). Final diagnosis was based on pathological results of postoperative material. Thirty-nine males of mean age 63.4 (standard deviation (SD): 6.69 years) revealed 41 potentially malignant pulmonary nodules in baseline screening. In 14 subjects 16 type C pulmonary nodules were histologically proved. Nine nodules were found to be benign lesions, while 7 nodules revealed malignant lung cancer: 5 cases of adenocarcinoma and 2 cases of adenosquamous carcinoma. We determined morphological characteristics of potentially malignant pulmonary nodules in 39 high-risk male smokers and proved lung cancer in 7 subjects.

Extra- and intracerebral course of the recurrent artery of Heubner.

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 acrylicpaint 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´. 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 RAH sand 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.

Heparin inhibits protective effect of ischemic preconditioning in ischemia/reperfusion-induced acute pancreatitis.

UNLABELLED: Previous studies have shown that pancreatic ischemic preconditioning or heparin, applied before induction of acute pancreatitis inhibit the development of this disease and accelerate pancreatic recovery. The aim of the study was to determine the influence of treatment with heparin on protective effect of ischemic preconditioning (IP) in ischemia/reperfusion-induced acute pancreatitis. Heparin was administered twice, before and during induction of acute pancreatitis. IP was performed by short-term clamping of celiac artery, 30 min before induction of acute pancreatitis. Acute pancreatitis was induced in rats by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed after 6-h and 24-h reperfusion. RESULTS: IP applied alone caused a mild pancreatic damage associated with a limited increase in plasma amylase activity, concentration of pro-inflammatory interleukin-1ß and plasma level of D-dimer. Pretreatment with heparin or IP applied alone reduced the severity of acute pancreatitis. Both these procedures caused a similar reduction in plasma lipase, amylase and interleukin-1ß, as well as in histological signs of pancreatic damage. These changes were associated with partial reversion of the pancreatitis-evoked fall of pancreatic blood flow and DNA synthesis. Combination of heparin plus IP reduced the protective effect of heparin or IP applied alone. It was manifested by an increase in pancreatic damage and plasma level of lipase, amylase and interleukin-1ß, as well as by reduction in pancreatic DNA synthesis and plasma concentration of D-dimer and interleukin-10. CONCLUSIONS: heparin abolishes the protective effect of ischemic preconditioning in ischemia reperfusion-induced pancreatitis. This observation suggests that initial clot formation is necessary to induce pancreatic protection by IP.

The adipose tissue gene expression in mice with different nitric oxide availability.

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.

Role of hormonal axis, growth hormone - IGF-1, in the therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis.

Ghrelin is a ligand for growth hormone secretagogue receptor and stimulates release of growth hormone (GH). Recent studies have shown that treatment with ghrelin exhibits protective and therapeutic effect in the course of experimental pancreatitis. The aim of present study was to examine the role of GH and insulin-like growth factor-1 (IGF-1) in these effects. Acute pancreatitis was induced by cerulein. Study was performed on pituitary-intact hypophysectomized rats. Ghrelin was administered twice a day at the dose of 8 nmol/kg/dose. IGF-1 was given twice a day at the dose of 20 nmol/kg/dose. The severity of acute pancreatitis was assessed 0 h or 1, 2, 3, 5 and 10 days after the last dose of cerulein. Administration of cerulein led to the development of acute edematous pancreatitis. In pituitary-intact rats, treatment with ghrelin reduced biochemical indexes of the severity of acute pancreatitis and morphological signs of pancreatic damage, leading to faster regeneration of the pancreas reduction in serum concentration of pro-inflammatory interleukin-1ß and decrease in serum activity of amylase and lipase. These effects were accompanied with an improvement of pancreatic blood flow and an increase in pancreatic DNA synthesis. Hypophysectomy delayed the healing of the pancreas and abolished the therapeutic effect of ghrelin. In hypophysectomized rats with pancreatitis, treatment with IGF-1 exhibits therapeutic effect similar to that observed in ghrelin-treated rats with the intact pituitary. We conclude that therapeutic effect of ghrelin in cerulein-induced pancreatitis is indirect and depends on the release of GH and IGF-1.

Therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis in rats.

Recent studies have shown that pretreatment with ghrelin exhibits protective effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as well as inhibits the development of experimental pancreatitis. However, this protective effect requires administration of ghrelin before gastric or pancreatic damage and thus has a limited clinical value. The aim of present study was to assess the influence of ghrelin administered after development of acute pancreatitis on the course of this disease. Acute pancreatitis was induced by cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours after last injection of cerulein. The severity of acute pancreatitis was assessed between 0 h and 10 days after cessation of cerulein administration. Administration of caerulein led to the development of acute edematous pancreatitis and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with ghrelin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Also biochemical indexes of the severity of acute pancreatitis, serum activity of lipase and amylase were significantly reduced in animals treated with ghrelin. These effects were accompanied by an increase in the pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1b. Administration of ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We conclude that: (1) treatment with ghrelin exhibits therapeutic effect in caerulein-induced experimental acute pancreatitis; (2) this effect is related, at least in part, to the improvement of pancreatic blood flow, reduction in proinflammatory interleukin-1beta and stimulation of pancreatic cell proliferation.

The presence of B7-H4+ macrophages and CD25+CD4+ and FOXP3+ regulatory T cells in the microenvironment of nasal polyps - a preliminary report.

The nasal polyp (NP) seems to represent the end-stage of longstanding inflammation in patients with chronic rhinosinusitis. The aim of our study has been to evaluate the presence of two regulatory cell populations in the microenvironment of NP: CD4+CD25high Foxp3+ (Treg) cells and B7-H4-expressing macrophages. Treg cells are actively able to inhibit T lymphocytes, while the population of B7-H4-expressing macrophages has recently been described as characterized by a regulatory function similar to that of Treg cells. For our study, we evaluated 14 NP tissue samples. The samples were divided into two main groups, eosinophilic (NP) and lymphocytic (NP), according to the predominant type of immune cell infiltration. The presence of Treg cells and B7-H4 positive macrophages in the samples was analyzed by FACS. Treg cells and B7-H4-expressing macrophages were identified in all the examined nasal polyps. The percentages of both Treg cells and of B7H4 positive cells found in the eosinophilic nasal polyps were higher than those found in the lymphocytic nasal polyps. Treg cells and B7H4+ macrophage subpopulations were present in the NP microenvironment and the alterations in their percentages were related to a distinct pattern of immune cell infiltration.

Pretreatment with obestatin inhibits the development of cerulein-induced pancreatitis.

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 beta-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 microg/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-1beta 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-1beta 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 proinflammatory interleukin-1beta release.

Effect of neonatal endotoxemia on the pancreas of adult rats.

UNLABELLED: Bacterial endotoxin (lipopolysaccharide, LPS), is the component of the cellular wall of Gram negative bacteria. Endotoxemia (sepsis) could produce multiorgan failure and could be particularly danger in the early period of life. The effects of endotoxemia induced in the neonatal period of life on the pancreatic secretory function and on pancreatic defense of adult organism have not been investigated yet. To induce endotoxemia suckling rats (30 g) have been injected intraperitoneally with LPS from E. coli (5, 10 or 15 mg/kg-day) during 5 consecutive days. Three months later in these animals (300 g) the studies on pancreatic secretion and acute pancreatitis were carried out. In the adult rats, which have been subjected in infancy to endotoxemia, basal pancreatic secretion was unaffected, whereas amylase secretions stimulated by caerulein or by diversion of pancreatic-biliary juice to the exterior were significantly, and dose-dependently reduced as compared to the untreated control. In the rats pretreated with LPS in the suckling period of life caerulein-induced amylase release from isolated pancreatic acini was significantly decreased, and dose-dependent reduction of mRNA signal for CCK1 receptor on pancreatic acini have been observed. Caerulein infusion (25 microg/kg) produced caerulein induced pancreatitis (AP) in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS (10 or 15 mg/kg-day x 5 days) all manifestations of AP have been reduced. In these animals acute inflammatory changes of pancreatic tissue have been significantly diminished. Pancreatic weight and plasma lipase activity, have been markedly decreased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in an antioxidative enzyme; SOD concentration was reversed and accompanied by significant reduction of lipid peroxidation products; MDA+ 4 HNE in the pancreatic tissue. CONCLUSIONS: 1/ neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age; 2/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age and this effect could be related to the increased concentration of antioxidative enzyme SOD in the pancreatic tissue.