Compartmentalization of Human Thymic Medulla: Facts and Hypotheses

The thymus function was discovered in the middle of the last century. The role of the thymus in the adaptive immune system facilitated its histological and experimental studies. Before the role of the thymus was discovered, the thymus was called as a gland on the basis of lobulation; even some histological textbook listed it up among the endocrine glands. In addition to the cortex and medulla, the immunohistochemical studies revealed a further compartmentalization in the thymic medulla, which is related to the epithelium-free areas (EFA) and keratin-positive network (KPN). The two medullary compartments have different cellularity that determines their role. This chapter would concentrate on the medullary compartmentalization and their cellularity. Furthermore, this chapter discusses the relationship of thymic septae with the perivascular space, the vascular embedding and thymic dendritic cells

A perioperatív vérgazdálkodási program alapelvei [Principles of the perioperative Patient Blood Management]

The perioperative Patient Blood Management (in Hungary National Blood Donation and Blood Saving Program) is an individualized clinical practice based on a multidisciplinary consensus with a comprehensive and complex approach. It supports the rational and judicious utilization of blood products and abolishes irrational transfusion policy. Its practical implementation is based upon three pillars: 1. anemia management without transfusion, if possible; restrictive transfusion strategy; 2. minimization of blood loss; 3. enhancement of anemia tolerance. Early detection, clarification of etiology and appropriate treatment are the most important tools for the management of preoperative anemia before surgeries with a high risk of bleeding. Minimization of blood loss can be achieved by identifying patients with congenital or acquired bleeding disorders, preparing them appropriately for surgery, discontinuing anticoagulants and antiplatelet drugs for a sufficient time in the preoperative phase of surgery and reversing their effects to comply with current guidelines. Minimal-invasive approaches are preferable. Intraoperatively, atraumatic technique and accurate topical haemostasis should be provided by surgeons. Autologous blood salvage techniques and controlled hypotension in lack of contraindications can also reduce the amount of blood loss. In cases of perioperative bleeding, protocols based on international guidelines but adapted to local circumstances must be used. Ideally, it should be managed by viscoelastic test-guided, goal-directed, individualized and factor concentrate-based algorithm. Perioperatively, an ideal oxygen demand/supply ratio must be ensured to avoid oxygen debt. Restoration and maintenance of homeostasis are essential for both the effectively functioning haemostatic system and the avoidance of oxygen deficit. Implementation of the Patient Blood Management improves patient safety, reduces the cost of medical care and facilitates the national blood product supply. Its successful introduction is our common interest

Interdependence of productive effort and in vitro vegetal extract treatment on specific cell-mediated immunity in horses

The research aimed at identifying and rendering alcoholic extracts of various plants based on their in vitro potential in stimulating cell mediated immunity and in alleviating stress effects subsequent to workout type in horses. Experimental horses were selected from different working environments: (a) draft, agricultural works-n = 16, average age 8 years, (b) inconstant effort, leisure, n = 15, average age 7.5 years and (c) constant training, endurance, average age 3.5 years. Blood samples were collected in heparinized vials (50 UI/ml) before and after the workout. Alcoholic extracts (2 mu l/well, duplicate) of Taraxacum officinale (L) Weber, Symphytum officinale L., Equisetum palustre L., Viola tricolor L., Avena sativa L., Capsella bursa pastoris (L) Medik., Hypericum perforatum L., Chelidonium majus L. were investigated by blast transformation test and statistically interpreted (Students t test). In vitro responses were the highest to all tested extracts in endurance horses and the lowest in draft horses (p<0.01-0.001). C. bursa pastoris. was the most efficient in draft and endurance categories before the workout (draft 45.13 +/- 8.05, in leisure 48.09 +/- 24.13 and 53.44 +/- 9.32 in endurance horses), but not after the workout, where C. majus performed better (41.86 +/- 22.47 in leisure and 48.1 +/- 6.82 in endurance horses), probably due to its complex, protein-rich latex structure. The effects of plant extracts depended on the type of effort and the level of constant training rather than on the taxonomy of the plant

Biofilm formation initiating rotifer-specific biopolymer and its predicted components

The rotifer-specific biopolymer, namely Rotimer, is a recently discovered group of the biomolecule family. Rotimer has an active role in the biofilm formation initiated by rotifers (e.g., Euchlanis dilatata or Adineta vaga) or in the female-male sexual interaction of monogononts. To understand the Ca2+- and polarity-dependent formation of this multifunctional viscoelastic material, it is essential to explore its molecular composition. The investigation of the rotifer-enhanced biofilm and Rotimer-inductor conglomerate (RIC) formation yielded several protein candidates to predict the Rotimer-specific main components. The exudate of E. dilatata males was primarily applied from different biopolimer-containing samples (biofilm or RIC). The advantage of males over females lies in their degenerated digestive system and simple anatomy. Thus, their exudate is less contaminated with food and endosymbiont elements. The sequenced and annotated genome and transcriptome of this species opened the way for identifying Rotimer proteins by mass spectrometry. The predicted rotifer-biopolymer forming components are SCO-spondins and 14-3-3 protein. The characteristics of Rotimer are similar to Reissner's fiber, which is found in the central nervous system of vertebrates and is mainly formed from SCO-spondins. This molecular information serves as a starting point for its interdisciplinary investigation and application in biotechnology, biomedicine, or neurodegeneration-related drug development

Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer

Background: During the last decade, one of the most important treatment options for locally advanced, potencially resectable rectal tumours was neoadjuvant chemoradiotherapy (CRT) followed by surgery.Methods: Effects of the neoadjuvant treatment on surgical outcomes were retrospectively analysed in 185 patients with stage T2–T4 and N0–2, resectable rectal tumour among two patient groups defined by radiosensitizer agents. Group 1 (n = 94) involved radiotherapy (RT) with 50.4 Gy total dose (25 × 1.8 Gy + 3 × 1.8 Gy tumour bed boost), and intravenous 5-fluorouracil (5-FU) (350 mg/m2) with leucovorin (20 mg/m2) on the 1–5 and 21–25 days, while Group 2 (n = 91) RT and orally administrated capecitabine (daily 2 × 825 mg/m2) on RT days. Surgery was carried out after 8–10 weeks. Side effects, perioperative complications, type of surgery, number of removed regional lymph nodes, resection margins and tumour regression grade (TRG) were analysed.Results: More favourable side effects were observed in Group 2. Despite the same rate of diarrhoea (Group 1 vs. Group 2: 54.3% vs. 56.0%), Grade 2–3 diarrhoea ratio was lower (p = 0.0352) after capecitabine (Group 2). Weight loss occurred in 17.0% and 2.2% (p = 0.00067), while nausea and vomiting was described in 38.3% and 15.4% (p = 0.00045) with 5-FU treatment and capecitabine respectively. Anaemia was observed in 33.0% and 22.0% (p = 0.0941). Complete tumour regression occurred in 25.3% after oral- and 13.8% after intravenous treatment (p = 0.049). Ratio of sphincter preservation was higher with laparoscopy than open surgery (72.3% vs. 39.7%) (p = 0.00001).Conclusion: The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and overall clinical outcome, with increased rate of complete tumour regression

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P &lt; 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP

The Reactivity of Human and Equine Estrogen Quinones towards Purine Nucleosides

Conjugated estrogen medicines, which are produced from the urine of pregnant mares for the purpose of menopausal hormone replacement therapy (HRT), contain the sulfate conjugates of estrone, equilin, and equilenin in varying proportions. The latter three steroid sex hormones are highly similar in molecular structure as they only differ in the degree of unsaturation of the sterane ring “B”: the cyclohexene ring in estrone (which is naturally present in both humans and horses) is replaced by more symmetrical cyclohexadiene and benzene rings in the horse-specific (“equine”) hormones equilin and equilenin, respectively. Though the structure of ring “B” has only moderate influence on the estrogenic activity desired in HRT, it might still significantly affect the reactivity in potential carcinogenic pathways. In the present theoretical study, we focus on the interaction of estrogen orthoquinones, formed upon metabolic oxidation of estrogens in breast cells with purine nucleosides. This multistep process results in a purine base loss in the DNA chain (depurination) and the formation of a “depurinating adduct” from the quinone and the base. The point mutations induced in this manner are suggested to manifest in breast cancer development in the long run. We examine six reactions between deoxyadenosine and deoxyguanosine as nucleosides and estrone-3,4-quinone, equilin-3,4-quinone, and equilenin-3,4-quinone as mutagens. We performed DFT calculations to determine the reaction mechanisms and establish a structure–reactivity relationship between the degree of unsaturation of ring “B” and the expected rate of DNA depurination. As quinones might be present in the cytosol in various protonated forms, we introduce the concept of “effective barriers” to account for the different reactivity and different concentrations of quinone derivatives. According to our results, both equine estrogens have the potential to facilitate depurination as the activation barrier of one of the elementary steps (the initial Michael addition in the case of equilenin and the rearomatization step in the case of equilin) significantly decreases compared to that of estrone. We conclude that the appearance of exogenous equine estrogen quinones due to HRT might increase the risk of depurination-induced breast cancer development compared to the exposure to endogenous estrone metabolites. Still, further studies are required to identify the rate-limiting step of depurination under intracellular conditions to reveal whether the decrease in the barriers affects the overall rate of carcinogenesis

Policy support and impact on third births in post-socialist Hungary

<b>Abstract: </b>Since the early 1990s fertility fall steeply in Central-East European countries including Hungary where substantial governmental efforts sought to stop or at least reduce the decline. Specific policy measures have benefited parents with three or more children: i) the flat-rate child-raising support paid from the 3rd until the 8th birthday of the youngest child in large families (signalling recognition of ‘motherhood as profession’) and ii) a comprehensive tax-relief system. The success of these measures, if any, is however difficult to detect in aggregate statistics. Here we rely on event-history methods analyzing data from the Hungarian Generation and Gender Survey to examine the effect of these policies and to reveal differences in higher-order childbearing behaviour among socio-economic groups related to the measures in question. The results indicate a significant and differentiated effect on third-birth risks. While the child-raising support increased third-birth risks among the least educated, the generous tax relief seems to have similar effect on parents with tertiary education

The interacting rotifer-biopolymers are anti- and disaggregating agents for human-type beta-amyloid in vitro

Neurodegeneration-related human-type beta-amyloid 1-42 aggregates (H-Aβ) are one of the biochemical markers and executive molecules in Alzheimer's disease. The exogenic rotifer-specific biopolymer, namely Rotimer, has a protective effect against H-Aβ toxicity on Euchlanis dilatata and Lecane bulla monogonant rotifers. Due to the external particle-dependent secreting activity of these animals, this natural exudate exists in a bound form on the surface of epoxy-metal beads, named as Rotimer Inductor Conglomerate (RIC). In this current work the experiential in vitro molecular interactions between Rotimer and Aβs are presented. The RIC form was uniformly used against H-Aβ aggregation processes in stagogram- and fluorescent-based experiments. These well-known cell-toxic aggregates stably and quickly (only taking a few minutes) bind to RIC. The epoxy beads (as carriers) alone or the scrambled version of H-Aβ (with random amino acid sequence) were the ineffective and inactive negative controls of this experimental system. The RIC has significant interacting, anti-aggregating and disaggregating effects on H-Aβ. To detect these experiments, Bis-ANS and Thioflavin T were applied during amyloid binding, two aggregation-specific functional fluorescent dyes with different molecular characteristics. This newly described empirical interaction of Rotimer with H-Aβ is a potential starting point and source of innovation concerning targeted human- and pharmaceutical applications. Keywords: Aggregation; Biopolymer; Euchlanis dilatata; Monogonant; Rotifer; beta-amyloi