Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells.

Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating the metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed increased levels of genome-wide histone H3K18 lactylation, a recently described marker for active chromatin in macrophages, in lactate-treated Th17 cells. In addition, we show that high lactate concentrations suppress Th17 pathogenicity during intestinal inflammation in mice. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotypes into regulatory T cells.

Clostridium sporogenes-derived metabolites protect mice against colonic inflammation.

Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).

T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms.

Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.

[Influence of gelatin-alginian matrixes on morphological and functional changes of blood leukocytes]. / Wplyw matryc zelatynowo-alginianowych na zmiany morfologiczne i czynnosciowe leukocytów krwi.

BACKGROUND: Knowledge of the relation of biomaterials and living tissues constitutes necessary information which should be used when composing a set of optimal carriers, e.g. for drugs or preparations supporting blood clotting. OBJECTIVES: This paper presents an assessment of the influence of contact of gelatin-alginian matrixes with blood on leukocyte reactivity: the ability of mononuclear cells (lymphocytes and monocytes) to create a radial segmentation of nuclei--RS (the morphological change), and the ability of leukocytes to phagocytosis of yeast Saccharomyces cerevisiae cells and to produce active oxygen derivatives (functional changes). MATERIAL AND METHODS: After having contact with the matrixes, the test of induced and spontaneous RS, the phagocytic test and nitroblue tetrazolium reduction test for blood leukocytes were performed. RESULTS: The obtained results showed a decrease in the ability of mononuclear cells to form RS and in the ability of granulocytes to reduce nitroblue tetrazolium--NBT, but an increase in their phagocytic activity. CONCLUSIONS: Temporary contact of gelatin-alginian matrixes with blood did not cause any morphological changes in the leukocytes. However, changes of their reactivity were observed.

Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development.

It is well known that neurodegenerative diseases' development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of mitochondrial function, cellular damage, and dysfunction of DNA repair systems. The increased consumption of antioxidants can postpone the development of these disorders and improve the quality of patients' lives who have already been diagnosed with neurodegenerative diseases. Prolonging life span in developed countries contributes to an increase in the incidence ratio of chronic age-related neurodegenerative disorders, such as PD (Parkinson's disease), AD (Alzheimer's disease), or numerous forms of age-related dementias. Dietary supplementation with neuroprotective plant-derived polyphenols might be considered an important element of healthy aging. Some polyphenols improve cognition, mood, visual functions, language, and verbal memory functions. Polyphenols bioavailability differs greatly from one compound to another and is determined by solubility, degree of polymerization, conjugation, or glycosylation resulting from chemical structure. It is still unclear which polyphenols are beneficial because their potential depends on efficient transport across the BBB (blood-brain barrier), bioavailability, and stability in the CNS (central nervous system). Polyphenols improve brain functions by having a direct impact on cells and processes in the CNS. For a direct effect, polyphenolic compounds must be able to overcome the BBB and accumulate in brain tissue. In this review, the latest achievements in studies (animal models and clinical trials) on the effect of polyphenols on brain activity and function are described. The beneficial impact of plant polyphenols on the brain may be summarized by their role in increasing brain plasticity and related cognition improvement. As reversible MAO (monoamine oxidase) inhibitors, polyphenols are mood modulators and improve neuronal self-being through an increase in dopamine, serotonin, and noradrenaline amounts in the brain tissue. After analyzing the prohealth effects of various eating patterns, it was postulated that their beneficial effects result from synergistic interactions between individual dietary components. Polyphenols act on the brain endothelial cells and improve the BBB's integrity and reduce inflammation, thus protecting the brain from additional injury during stroke or autoimmune diseases. Polyphenolic compounds are capable of lowering blood pressure and improving cerebral blood flow. Many studies have revealed that a nutritional model based on increased consumption of antioxidants has the potential to ameliorate the cognitive impairment associated with neurodegenerative disorders. Randomized clinical trials have also shown that the improvement of cognitive functions resulting from the consumption of foods rich in flavonoids is independent of age and health conditions. For therapeutic use, sufficient quantities of polyphenols must cross the BBB and reach the brain tissue in active form. An important issue in the direct action of polyphenols on the CNS is not only their penetration through the BBB, but also their brain metabolism and localization. The bioavailability of polyphenols is low. The most usual oral administration also conflicts with bioavailability. The main factors that limit this process and have an effect on therapeutic efficacy are: selective permeability across BBB, gastrointestinal transformations, poor absorption, rapid hepatic and colonic metabolism, and systemic elimination. Thus, phenolic compounds have inadequate bioavailability for human applications to have any beneficial effects. In recent years, new strategies have been attempted in order to exert cognitive benefits and neuroprotective effects. Converting polyphenols into nanostructures is one of the theories proposed to enhance their bioavailability. The following nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as neuroprotectors. Perhaps some modification of the chemical structure of a given polyphenol may increase its neuroprotective activity and transportation through the BBB. However, numerous questions should be answered before developing neuroprotective medications based on plant polyphenols.

Genetic diversity of Pasteurella dagmatis as assessed by analysis of the 16S rRNA and rpoB gene sequences.

A total of 16 Pasteurella dagmatis strains, including 11 feline and 4 canine isolates as well as one strain isolated from a tiger, were analyzed using partial 16S rRNA and rpoB gene sequence comparison. Phylogenetic studies based on both genes revealed that the population of P. dagmatis recovered from cats in Poland differs markedly from canine strains, constituting a well-separated cluster within Pasteurella sensu stricto species group. The isolate from a tiger seems to represent yet another evolutionary lineage within P. dagmatis.

Definitive treatment of Graves' disease in children and adolescents.

Graves' disease (GD) is the most common cause of paediatric hyperthyroidism. In children and adolescents, the clinical GD course is different from that seen in adults, due to low remission rate and high prevalence of adverse events related to treatment with antithyroid drugs (ATDs). Most patients in this group require definitive therapy. As in adults, there are 2 treatment options- thyroid ablation with radioactive iodine (RAI) or surgery with preferred procedure of total thyroidectomy (TT). The choice of definitive therapy depends on many important factors such as the child's age, effectiveness of the first-line ATD treatment, presence of ATD side effects, presence of large goitre or thyroid nodules, and concomitant diseases. The following paper provides the current guidelines on GD management in children and compares the efficacy of both definitive treatment methods as well as the acute and long-term complication rates, which must be taken into account when choosing the optimal therapeutic option.

Pro- and Antitumorigenic Capacity of Immunoproteasomes in Shaping the Tumor Microenvironment.

Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1, and LMP7 is expressed in most immune cells. In this study, we describe opposing roles for immunoproteasomes in regulating the tumor microenvironment (TME). During chronic inflammation, immunoproteasomes modulated the expression of protumorigenic cytokines and chemokines and enhanced infiltration of innate immune cells, thus triggering the onset of colitis-associated carcinogenesis (CAC) in wild-type mice. Consequently, immunoproteasome-deficient animals (LMP2/MECL-1/LMP7-null mice) were almost completely resistant to CAC development. In patients with ulcerative colitis with high risk for CAC, immunoproteasome-induced protumorigenic mediators were upregulated. In melanoma tumors, the role of immunoproteasomes is relatively unknown. We found that high expression of immunoproteasomes in human melanoma was associated with better prognosis. Similarly, our data revealed that the immunoproteasome has antitumorigenic activity in a mouse model of melanoma. The antitumor immunity against melanoma was compromised in immunoproteasome-deficient mice because of the impaired activity of CD8+ CTLs, CD4+ Th1 cells, and antigen-presenting cells. These findings show that immunoproteasomes may exert opposing roles with either pro- or antitumoral properties in a context-dependent manner.

Parameters of Hemostasis in Sheep Implanted with Composite Scaffold Settled by Stimulated Mesenchymal Stem Cells-Evaluation of the Animal Model.

Implantation of composite scaffolds could be potentially associated with the risk of hemostatic disturbances in a recipient. However, there is a lack of information on possible alterations in clotting mechanisms resulting from such a procedure. The aim of the present work was to investigate changes in hemostatic parameters in sheep implanted with a scaffold composed of poly(ε-caprolactone) and hydroxyapatite and tricalcium phosphate (9:4.5:4.5), settled previously with mesenchymal stem cells stimulated by fibroblast growth factor-2 and bone morphogenetic protein-2. Nine Merino sheep were examined for 7 days, and measurements of clotting times (PT, aPTT), activities of antithrombin, protein C and clotting factors II-XII, and concentrations of fibrinogen and D-dimer were carried out before and 1 h, 24 h, 3 days and 7 days after scaffold implantation. The introduction of scaffold initially resulted in a slowdown of the clotting processes (most evident 24 h after surgery); PT and aPTT increased to 14.8 s and 33.9 s, respectively. From the third day onwards, most of these alterations began to return to normal values. The concentration of fibrinogen rose throughout the observation period (up to 8.4 g/L), mirroring the ongoing inflammatory reaction. However, no signals of significant disturbances in hemostatic processes were detected in the sheep tested.

The Role of Vitamin C in Two Distinct Physiological States: Physical Activity and Sleep.

This paper is a literature overview of the complex relationship between vitamin C and two opposing physiological states, physical activity and sleep. The evidence suggests a clinically important bidirectional association between these two phenomena mediated by different physiological mechanisms. With this in mind, and knowing that both states share a connection with oxidative stress, we discuss the existing body of evidence to answer the question of whether vitamin C supplementation can be beneficial in the context of sleep health and key aspects of physical activity, such as performance, metabolic changes, and antioxidant function. We analyze the effect of ascorbic acid on the main sleep components, sleep duration and quality, focusing on the most common disorders: insomnia, obstructive sleep apnea, and restless legs syndrome. Deeper understanding of those interactions has implications for both public health and clinical practice.

Involvement of hemostasis in pathophysiology of RAO in horses.

Recurrent Airway Obstruction (RAO), also called severe asthma or heaves, is a chronic disease in adult horses caused by aeroallergens from straw or hay. Disturbances in hemostasis (intensified coagulation and depressed fibrinolysis) are considered one of the prominent reasons of inflammatory process, injury and dysfunction of the lungs. The aim of the study was to evaluate chosen parameters of hemostasis in horses with active form of RAO. Ten RAO-horses (group R) and ten healthy horses (group C) were exposed to straw and hay allergen challenge. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen concentration (Fb), stabilized fibrin degradation product (d-dimer), antithrombin (AT), protein C and coagulation factors II through XII were assessed in plasma obtained from blood of all the horses. Exposure to aeroallergens resulted in prolongation of aPTT in both groups of animals; it was evident in the group R and moderate in the group C. There were no differences in PT and TT. Concentrations of fibrinogen and d-dimer and activity of protein C in both groups were increased but lay within or near to reference values. The activity of AT was depressed in RAO-horses. All exposed horses showed increased activity of coagulation factors II, VIII and X but they had no changes in activity of factor V. Factors VII and XII displayed a reduction in activity. The decrease in factor IX activity was noted in the group C only. Various changes were observed in activity of factor XI; in horses with RAO it was elevated but in healthy horses it was declined. The changes of the parameters tested in RAO-horses indicate the involvement of coagulation and fibrinolysis which apparently remained under control of efficient and active mechanisms of general hemostasis.

Laparoscopic cortical-sparing adrenal surgery in pheochromocytomas associated with hereditary neoplasia syndromes.

INTRODUCTION: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas. MATERIAL AND METHODS: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3-1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5-4 years). RESULTS: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved. CONCLUSIONS: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.

Postoperative Radioiodine Treatment within 9 Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma.

PURPOSE: Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC. MATERIAL: The analyzed group involved 701 DTC patients staged pT1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5-15.2). RESULTS: Based on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant. CONCLUSION: If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.

Publisher Correction: Low-level light therapy reduces platelet destruction during extracorporeal circulation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Endocrine complications of cancer immunotherapy.

Immunotherapy using monoclonal antibodies - checkpoint inhibitors - is a dynamically evolving discipline of clinical oncology and a new hope for patients with advanced and disseminated cancer. However, the activation of T-lymphocytes can at the same time lead to autoimmune response and destruction of healthy organs, which is a serious adverse effect that can also affect the endocrine system. Here we present possible endocrine complications of immunotherapy with contemporary inhibitors of immune checkpoints (CTLA-4, PD-1, PD-L1/L2), their frequency, symptoms, and proposed grade-dependent treatment.Failure to diagnose endocrine pathology can in adverse circumstances lead to treatment failure and condemn the patient's fate. Due to tremendous progress in cancer immunotherapy during the last few years and an increase in the number of treated patients, endocrinologists should become acquainted with the specificity of this mode of oncological treatment.

Effect of antigen challenge on dynamics of CD62P and CD41/61 expression on platelets in horses with recurrent airway obstruction (RAO).

Recurrent airway obstruction (RAO), also known as heaves, is an allergic respiratory condition that develops in horses following an exposure to aeroallergens in hay and straw. This is manifested by airway hyperreactivity, inflammation, bronchoconstriction, as well as a leukocyte and platelet infiltration into the airways. Platelet activation and an increase in circulating platelet-leukocyte aggregates may lead to airway remodeling. The aim of this study was to explore the effect of seven-day antigen challenge on dynamics of platelet indices and CD41/61 and CD62 P expression on platelets in horses with RAO. Ten RAO-affected horses and ten healthy horses were included in this study. All horses were exposed to 7 days hay and straw challenge. Blood samples were collected prior to the challenge (Pre-challenge) and 1, 2, 3, 7 and 14 days after the initiating the antigen challenge. Blood samples were obtained to determine the platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR). Expression of CD62 P and CD41/61 was detected by flow cytometry on activated platelets. Antigen challenge resulted in a significant gradual decrease of PLT in RAO horses, but not in controls. MPV and P-LCR in control and RAO-affected horses remained unchanged after antigen challenge. The expression of CD62 P and CD41/61 in RAO horses was significantly higher compared to control horses. The antigen challenge resulted in an increase expression of CD62 P and CD41/61 on the platelets of RAO-affected horses, while did not lead to significant changes in the control group. An increased expression of CD62 P and CD41/61 indicates platelet activation what may contribute to the formation of platelet aggregates in their respiratory system.

Low-level light therapy reduces platelet destruction during extracorporeal circulation.

Extracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.

Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken's lymphatic system.

BACKGROUND: The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root (SBR) on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens. METHODS: The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups, three SBR supplemented groups (0.5, 1.0, and 1.5% of SBR) and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3rd and 6th wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed. Moreover, the ability of peripheral blood lymphocytes to form radial segmentation (RS) of their nuclei was analyzed. Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded. RESULTS: Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances. CONCLUSION: We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.

Occurrence of phaeochromocytoma tumours in RET mutation carriers - a single-centre study.

INTRODUCTION: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant genetic syndrome caused by germline mutation in RET proto-oncogene. The most common mutations are in a cysteine rich domain. Phaeochromocytoma will develop in approximately 50% of RET proto-oncogene carriers. MATERIAL AND METHODS: The studied population consisted of 228 RET proto-oncogene mutation carriers. Monitoring for the diagnosis of phaeochromocytoma was carried out in all patients with established genetic status. Mean time of follow up was 138 months. Surveillance consisted of periodically performed clinical evaluation, 24-hour urinary determinations of total metanephrines complementary with imaging (CT, MR, MIBG scintigraphy). RESULTS: Phaeochromocytoma developed in 41 patients (18% of all RET proto-oncogene mutations carriers). The mean age of diagnosis for the whole cohort was 43 years. In eight cases phaeochromocytoma was the first manifestation of the MEN 2 syndrome. Only eight (20%) patients were symptomatic at diagnosis of phaeochromocytoma. The mean size of the tumour was 4.3 cm. There was no extra-adrenal localisation. We observed one case of malignant phaeochromocytoma. CONCLUSIONS: In patients with MEN 2 syndrome phaeochromocytomas are usually benign adrenal tumours with high risk of bilateral development. Taking to account the latter risk and non-specific clinical manifestation of the neoplasm it is mandatory to screen all RET proto-oncogene mutations carriers for phaeochromocytoma.

Age-related changes of platelet and plasma coagulation parameters in young pigs.

The literature on hemostatic processes in swine is sparse and often fragmentary; hence, we conducted our study to characterize age-related changes in selected parameters of primary and secondary hemostasis in 50 growing pigs between day 2 and week 24 of age. We measured platelet count (PLT), mean platelet volume, platelet-to-large cell ratio, prothrombin time, activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration. Among primary hemostasis parameters, PLT underwent the largest fluctuation with the animals' age, ranging from 340 to 730 × 10(9)/L. However, statistical significance was only detected for 4-week-old piglets compared to 18-week-old animals. Of the secondary hemostasis parameters measured, TT and aPTT were the most changeable. Activated partial thromboplastin time displayed a characteristic biphasic course, being relatively short before week 5 of age (17.8-19.9 s) and then becoming much longer (28.7-52.5 s). The aPTTs measured in animals 6 weeks of age and older were statistically different (p < 0.01) from those in younger piglets. The 2 main components of hemostasis, platelet hemostasis and plasma coagulation, did not develop at the same time. It took much longer for secondary hemostasis to stabilize, whereas platelet parameters were stable early in life.