In-vitro antiplatelet effect of melatonin in healthy individuals and patients with type 2 diabetes mellitus.

PURPOSE: The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in patients with diabetes mellitus (DM). The night's decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM. METHODS: Platelet aggregation was measured in blood samples from healthy individuals (n = 15) and type 2 DM patients (n = 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations. RESULTS: In healthy individuals, melatonin inhibited platelet aggregation in both higher (10-5 M) and lower concentrations (10-9 M) induced by ADP, ASPI, and TRAP (p < 0.001, p = 0.002, p = 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (p = 0.005, p = 0.045 and p = 0.048, respectively). CONCLUSION: Platelet aggregation was inhibited by melatonin in healthy individuals. In-vitro antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.

The Overview of Anatomical Variations and Congenital Anomalies of the Uterine Tubes and Their Impact on Fertility.

Anatomical variations and congenital anomalies of the uterine tubes (UTAVsCAs) are rare conditions, which are often undiagnosed, or accidentally diagnosed upon imaging, laparotomy, laparoscopy for unrelated condition, or during the Cesarean section. UTAVsCAs are often asymptomatic, but their clinical relevance lies in their possibly adverse impact on fertility. Since their rare occurrence, they are usually published as case reports. The most typically described are: agenesis of the uterine tubes (UTs), accessory UT (UT duplication), accessory UT ostium, and paratubal cysts (e.g. the hydatid cyst of Morgagni). UTAVsCAs are classified into an umbrella category of Müllerian duct anomalies (MDAs) which comprises anomalous development of all the organs developing from the paramesonephric (Müllerian) ducts, i.e., UTs, uterus and upper portion of the vagina. Interestingly, most of the classification systems of MDAs discuss solely the uterine and vaginal anomalies, while the UTs are often utterly ignored. This probably originates from the fact that UTs are no longer interesting for many clinicians as they think of UTs as superfluous organs whose function can be easily replaced in the in vitro fertilization (IVF) laboratory. Indeed, the modern reproductive medicine has been helping enormously with the conception of infertile couples. In many instances, the UTs are in fact successfully bypassed and a "test-tube" baby is born. Nevertheless, the UTs are still absolutely unique in providing suitable environment for fertilization and early embryo development - processes that hasn´t been still completely understood. This fact could partially explain why the success rate of IVF is "only" around 30-50 % depending on age. Therefore, the research of the UTAVsCAs is still clinically relevant in the context of reproductive medicine and should not be omitted from research endeavors.

Acellular Dermal Matrix in Plastic and Reconstructive Surgery.

Despite significant advances in medical research, plastic surgeons still face a shortage of suitable patient tissues, and soft tissue reconstruction is no exception. In recent years, there has been a rapid boom in the use of acellular dermal matrix (ADM) in reconstructive and aesthetic surgery. ADM is incorporated into the surrounding tissue and gradually replaced by the host's collagen, thus promoting and supporting the healing process and reducing the formation of scar tissue. The main goal of this article is to provide a brief review of the current literature assessing the clinical applications of ADM across a broad spectrum of applications in plastic and reconstructive surgery.

When Less Is More - Pipelle Endometrial Sampling for Quantification of Uterine Natural Killer Cells in Patients With Recurrent Implantation Failure or Habitual Abortion.

Despite recent advancements in reproductive medicine, recurrent implantation failure and habitual abortion remain ongoing issues. One of the most important aspects of successful implantation is the intricate immune response and regulation necessary for the acceptance of the hemiallogenic embryo. The most numerous immune cells in the decidua are uterine natural killer cells (uNK). Studies suggest that changes in the uNK count and physiology may be responsible for the aforementioned pathological conditions. Thus, testing for uNK may provide valuable insights into their pathogenesis. The study compared Pipelle endometrial sampling with conventional curettage to find out whether the less invasive Pipelle method is a viable alternative of tissue collection. Tissue samples from 14 patients obtained by both methods were examined. The average size of tissue samples obtained with Pipelle was 17 mm2, samples obtained with curettage had on average 34 mm2. Using immunohistochemical visualization of CD56 (NK cells) and granzyme B antigens (serine protease-expressing activation state of NK cells), it was found that the average total count of CD56 / mm2 was for Pipelle 115 and 120 for curettage, respectively. The study also proved a correlation between granzyme B positivity and identification of NK cells clusters. The results indicated that Pipelle endometrial sampling seems a suitable method of tissue harvesting for the purpose of uNK cells examination. Pipelle endometrial sampling is safe, cost-effective and can be performed on an outpatient basis without the need of anesthesia or analgesia. Several issues remain yet to be solved: how to standardize the subsequent uNK testing, how to interpret the results and finally yet importantly, how to use this knowledge in personalized treatment protocols.

Arterial Blood Supply of the Mesosalpinx Appears Segmentally Organized in Absence of Uterine Tubes Arteries.

Arterial branches to the uterus and ovaries that pass through the mesosalpinx contribute significantly to the maintenance of the ovarian reserve. Especially arterial supply of the uterine tube is provided by a number of anastomoses between both the uterine and ovarian vessels. Knowledge on the morphologic peculiarities will allow to identify main contributors especially blood flow ultrasound examination for the purpose of ovary preserving surgery. This study aimed at identifying landmarks especially for so-called low-flow tubal vessels. Arteries of 17 female Thiel-embalmed bodies were studied along three preselected paramedian segments and measurements taken. A section was made through the center of the ovary perpendicular to uterine tube, then the mesosalpinx tissue distance was divided into 3 equivalent zones: upper, middle and lower thirds. The surface area of the mesosalpinx averaged 1088 ± 62 mm2. 47.7 ± 7.1 % of the mesosalpinx zones included macroscopically visible vessels. The lower third segment of mesosalpinx was the thickest averaging 2.4 ± 1.5 mm. One to three tubal branches were identified in the middle third of the mesosalpinx. Arterial anastomoses were found in the upper segment of the mesosalpinx, but no presence of a marginal vessel supplying the fallopian tube could be found. Statistically significant moderate positive correlations were established between the diameters of the mesosalpingeal arteries between the three zones. The mesosalpinx, uterine tube and the ovary form areas of segmental blood supply. Variants of tubal vessels appear to be a sparse source of blood supply.

Scanning electron microscopic study of the human uterine tube epithelial lining: surgical biopsy samples and epithelial cell culture.

This article summarizes the importance of the exact morphology of human uterine/fallopian tube epithelium at the scanning electron microscopy (SEM) level for the clinical outcome even nowadays. Visual referential micrographs from SEM reflect two ways to view human epithelial cell lining surfaces: the surface epithelial uterine tube from surgical tissue biopsy and human fallopian tube epithelial cells (HFTEC) culture monolayer surface. One colorized image visualizes ciliated cells, distinguishes them from non-ciliated cells, and provides an educational benefit. A detailed description of the ultrastructure in referential and pathologic human uterine tube epithelium is important in defining the morphological basis of high-grade carcinomas, in the mechanism of pathophysiology, and in discussing options for its prevention. Cell cultures of human fallopian tube epithelial cells offer new approaches in simulating the mechanisms of cancer genesis or may help to elucidate the genetic basis of several diagnoses. New technical approaches in SEM provide higher resolution and detailed surface images. The SEM modality is still one of the current options in diagnostics and may be useful for advancing human reproductive organ cancer research.

Functional Morphology of the Human Uterine Tubes in the 21st Century: Anatomical Novelties and Their Possible Clinical Applications.

The uterine tube (UT) pathologies account for 25-35% of female factor infertility. Although these peculiar organs were first studied several hundred years ago, they have become overlooked and neglected mainly due to the successes of reproductive medicine. Nevertheless, the reproductive medicine still faces many challenges regarding the fertility outcomes of in vitro fertilization (IVF). Many obstacles and problems can be resolved by a more detailed understanding of the UT morphology and function during normal reproduction. Over the course of the 21st century, many new insights have been obtained: the presence of a population of telocytes in the tubal wall responsible for normal motility and hormone sensory function, the demonstration of lymphatic lacunae of the mucosal folds necessary for oocyte capture and tubal fluid recirculation, or a thorough profiling of the immune makeup of the UT epithelial lining with the discovery of regulatory T cells presumably important for maternal tolerance towards the semi-allogenic embryo. New discoveries also include the notion that the UT epithelium is male sex hormone-sensitive, and that the UT is not sterile, but harbors a complex microbiome. The UT epithelial cells were also shown to be the cells-of-origin of high-grade serous ovarian carcinomas. Finally, yet importantly, several modern morphological directions have been emerging recently, including cell culture, development of tubal organoids, in silico modelling, tissue engineering and regenerative medicine. All these novel insights and new approaches can contribute to better clinical practice and successful pregnancy outcomes.

A plea for extension of the official nomenclature of the microscopic structure of human tissues and organs, the Terminologia Histologica.

BACKGROUND: At first sight, the issue of terminology in morphological sciences may seem as "closed and changeless chapter", as many of the structures within the human body have been known for centuries. However, the exact opposite is true. Terminologia Histologica: International Terms for Human Cytology and Histology published under the Federative International Programme on Anatomical Terminology in 2008 is a new standard in human cell and tissue terminology. The list of items in the first and still valid official nomenclature of cellular and tissue structures, the Terminologia Histologica (TH), is the best and most extensive of all the histological nomenclatures ever issued. MATERIALS AND METHODS: The aim of this article is a systematic and in-depth analysis of the current internationally accepted nomenclature TH, with focus on important histological structures which are missing in this first edition. Some should be incorporated just for the sake of completeness and consistence, others are purely absent terms for individual structures or some are recently described new tissue structures. RESULTS: We also discuss about a question, how to deal with the issue of eponyms. Eponyms reflect medicine's rich and colourful history. Although they have not been considered official terms in the anatomical nomenclature since 1955, they are still widely used in clinical practice. CONCLUSIONS: We hope that this opinion article will develop a wide scientific discussion before the publication of the second edition, so perhaps the mentioned minor flaws will be corrected, so the new edition of the TH will become truly an internationally accepted communication tool for all histologists, histopathologists and anatomists.

Fertility maintenance in male oncological patients: current state and future perspectives.

Growing cancer incidence in reproductive age goes hand in hand with a rising survival rate of patients who underwent anticancer therapy. This trend points to the necessity of discussion regarding the fertility maintenance. The patient´s future with respect to his reproductive ability has to be addressed properly to achieve a complex approach to cancer management. The germinal epithelium of the testes is highly susceptible to deleterious effects of chemotherapy. After the administration of gonadotoxic chemotherapeutic agents, a patient can develop oligospermia, or even azoospermia. Similarly, radiation exposure can damage spermatogenesis, while higher doses lead to azoospermia. This review brings an overview of the methods of assisted reproduction, which are currently in use for fertility maintenance in oncological patients, but also in those with non-malignant indications. Also, novel, yet still experimental, methods are discussed, which represent promising technologies applicable to prepubertal oncological patients. We also discuss historical milestones in the development of assisted reproduction, summarize the options of semen analysis, and we present a practical guide through the process of sperm cryopreservation and subsequent in vivo or in vitro fertilisation. We deem that fertility maintenance should be an integral part of the health care in oncological patients in reproductive age (Tab. 1, Ref. 85). Keywords: assisted reproduction technique, sperm cryopreservation, testicular tissue cryopreservation, spermatogenesis, sperm quality in oncological patients.

Sentinel lymph node - historical background and current views on its significance in complex management of breast cancer patients.

Nowadays, breast cancer is the leading oncological diagnosis in women worldwide. On the other hand, breast cancer treatment can be considered one of the most progressive therapeutic approach in the medical field of oncology. The invasive types of breast cancer have a tendency to spread via lymphatic route, what brings in the issue of sentinel lymph node - the first node into which the lymph drains from a given anatomical location. This review paper discusses the historical background of the concept of sentinel lymph node and focuses on clinical significance of the positivity of sentinel lymph node(s) as well. Modern-day conservative therapeutic surgery of breast cancer should be in accordance with diagnostic and preventive interventions in the axilla, whose rate of invasiveness and morbidity must be also attenuated without worsening the patient´s prognosis and survival rate. Formerly, a complete axillary lymph node dissection was routinely performed for prophylactic and cancer staging purposes. The indiscriminate application of this approach was replaced by sentinel lymph node biopsy. Along with common histopathological examination, immunohistochemistry, as well as modern techniques of molecular biology are often employed. These state-of-the-art methods enabled the identification of micrometastases, or even nanometastases, though their real prognostic value is yet to be concluded (Ref. 52). Keywords: sentinel node, breast cancer, biopsy, historical background.

Significance of MRI in rectal carcinoma therapy optimization - correlation of preoperative T- and N-staging with definitive histopathological findings.

In past decades, both prognosis and therapy of rectal cancer patients showed significant improvement, on the other hand, the incidence of rectal carcinoma continues to have a rising tendency. According to current UICC classification, patients in stage II rectal cancer or higher are indicated for neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) is currently the most common diagnostic method used for preoperative staging of rectal cancer. Several studies already pointed out the inaccuracy of preoperative lymph node staging in patients with rectal cancer. The present study analyzed overall accuracy of MRI staging of rectal cancer and thus its accuracy in neoadjuvant therapy indication, by comparing preoperative MRI staging with definitive histopathologic results from resected tumors. This study evaluated cases of 92 patients with rectal tumor that underwent MRI examination followed by surgical resection. Tumors included in the analysis were ranging from T1 to T3b according to TNM staging, with free circumferential resection margin (CRM), distance form mesorectal fascia more than 5 mm, negative intersphincteric plane and also negative extramural venous invasion (EMVI), while the N stage was not decisive. In all cases both N-staging and T-staging were evaluated histologically and compared with preoperative MRI results. Significant difference in preoperative and postoperative N-staging was shown in 51 patients (61.45%). In majority of cases MRI lead to overstaging, which was observed in 44 cases (53.1 %), with complete negativity of lymph nodes proven by histological examination in 34 cases. On the other hand, understaging of lymph nodes was observed only in 7 cases (7.4 %). The T-staging did not show significant differences. Results from this study confirm that MRI plays an important role in T-staging of rectal tumors, however, there are admittedly issues in N-staging of tumors, which should lead to reevaluation of neoadjuvant therapy indication in patients with positive lymph nodes according to MRI examination. Based on the results of this study, we see the future of preoperative staging of rectal tumors in precise T-staging together with accurate assessment of CRM and distance of tumor from mesorectal fascia as well as evaluation of intersphinteric plane and EMVI.

Effect of long-term culture on the biological and morphological characteristics of human adipose tissue-derived stem Cells.

Mesenchymal stem cells (MSCs) are multipotent cells that can be obtained from different tissues, including bone marrow, adipose tissue, umbilical blood, Wharton's jelly, and dental pulp. Due to their differentiation potential, regenerative and immunosuppressive properties, as well as ability to expand under in vitro conditions, these cells represent a promising therapeutic tool for regenerative medicine. However, the basic prerequisite for the therapeutic utilization of MSCs is obtaining a sufficient amount. While this may be achieved by prolonged cultivation, long-term culture of MSCs is associated with accumulation of morphological and functional changes. In our study, we focused on analyzing morphological and biological changes of cultured adipose tissue-derived stem cells over 30 passages. We performed morphological analysis using light and electron microscopy, as well as analysis of selected biological properties (expression of surface antigens and selected genes involved in cell regulation and apoptosis, cell cycle, and cell senescence) every 5 passages. Our results showed that long-term expansion leads to significant changes in morphology and affects proliferation kinetics and the cell cycle. On the other hand, the MSCs maintained a prototypical immunophenotype, normal cell cycle and apoptosis regulator function, and maintained a low level of telomerase activity during later passages.

Cardiac telocytes as principal interstitial cells for myocardial reparation and regeneration after infarction - our hope.

According to our knowledge, this is the first research experiment that focuses on the study of the distribution of c-kit positive cells at the sites of myocardial infarction in human hearts (Fig. 3, Ref. 16).

Telocytes (interstitial Cajal-like cells) in human Fallopian tubes.

BACKGROUND: Telocytes represent a relatively newly discovered population of cells found within the various tissues and organs, including Fallopian tubes. It is presumed that telocytes could serve as a sensor of hormone levels or regulate activity of muscle peristaltic movement. METHODS: Tissue sections from anatomically different parts of Fallopian tubes of 48 women (age 48.8±9.1) were stained for the expression of five different antigens: c-kit (CD117), CD34, vimentin, podoplanin (D2-40) and Dog-1. RESULTS: Telocytes form a network associated with the smooth muscle cells. From the mentioned antibodies, only anti-c-kit (CD117) seems to be relatively selective specific to the telocytes, others react also with numerous other cells and tissue structures. Our results when using antibodies against podoplanin and Dog-1 are in dissonance with recent literature - with regards to our results, they are not suitable for detection of telocytes. CONCLUSION: Methods of immunohistochemistry are suitable for identification of telocytes in Fallopian tubes. C-kit (CD117) antigens are useful for routine identification of telocytes in histological sections. This antigen can be combined with CD34 or vimentin in cases of double staining immunohistochemistry.

[Functional morphology of recently discovered telocytes inside the female reproductive system]. / Funkcná morfológia novo objavených telocytov v zenskom pohlavnom systéme.

Discovery of telocytes has become an important and key challenge in past few years. These cells are interstitial cells extending very long cytoplasmic processes named telopodes, by which they create functional networks in the interstitium of different organs. Telocytes are considered to be connective tissue elements that create contacts among each other, but they also function as intercellular structures, functionally connected with cells of the immune system, neurons and smooth muscle cells. Telocytes can be found also in the different parts of female reproductive system with functions and purpose, which is summarized in our overview. Telocytes regulate for example peristaltic movements in fallopian tubes. The decrease of their number (due to inflammatory disease or endometriosis) causes impairment in transport through fallopian tubes which may result in sterility or tubal gravidity. In uterus they regulate contraction of myometrial smooth muscle (blood expulsion in menstrual phase, childbirth) as well as they contribute in immunological care during embryo implantation. Telocytes probably control also the involution of uterus after delivery. Their function in vagina has not been yet clearly defined; they probably take part in slow muscle contraction movement during sexual intercourse. In mammary glands some scientists suppose their function in control of cell proliferation and apoptosis, that is why, they may play a role in carcinogenesis. In placenta they probably monitor and regulate flow of blood in vessels of chorionic villi and they may be responsible also for etiopathogenesis of pre-eclampsy. All these mentioned functions of telocytes are only in the level of hypothesis and have been published recently. New research and studies will try to answer the questions whether telocytes play a key role in these processes. Our review we completed with some original microphotographs of telocytes in different organs of female reproductive system.

Ultrastructural analysis of different human mesenchymal stem cells after in vitro expansion: a technical review.

Transmission electron microscopy reveals ultrastructural details of cells, and it is a valuable method for studying cell organelles. That is why we used this method for detailed morphological description of different adult tissuederived stem cells, focusing on the morphological signs of their functions (proteosynthetic activity, exchange with external environment, etc.) and their comparison. Preparing a specimen from the cell culture suitable for transmission electron microscopy is, however, much more challenging than routine tissue processing for normal histological examination. There are several issues that need to be solved while working with cell pellets instead of solid tissue. Here we describe a simple protocol for the isolation and culture of mesenchymal stem cells from different adult tissues, with applications to stem cell biology and regenerative medicine. Since we are working with population of cells that was obtained after many days of passaging, very efficient and gentle procedures are highly necessary. We demonstrated that our semi-conservative approach regarding to histological techniques and processing of cells for transmission electron microscopy is a well reproducible procedure which results in quality pictures and images of cell populations with minimum distortions and artifacts. We also commented about riskiest steps and histochemical issues (e.g., precise pH, temperature) while preparing the specimen. We bring full and detailed procedures of fixation, post-fixation, infiltration, embedding, polymerization and contrasting of cell obtained from in vitro cell and tissue cultures, with modifications according to our experience. All this steps are essential for us to know more about adult stem cells derived from different sources or about other random cell populations. The knowledge about detailed ultra-structure of adult stem cells cultured in vitro are also essential for their using in regenerative medicine and tissue engineering.

Cardiovascular Screening and Management Among Kidney Transplant Candidates in Hungary.

INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. METHODS: Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. RESULTS: According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. CONCLUSION: In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes.

The normal human newborns thymus.

The thymic microenvironment constitutes a unique cell environment composed of thymic epithelial cells, myoid cells, and bone marrow-derived accessory cells for the differentiation, maturation and selection of T lymphocytes. The histological feature of thymus is markedly dependent on the age of individual and on various negative stimuli. Our study group consisted of fourteen newborns whose thymuses were removed during surgery performed for various congenital heart defects. We used a palette of seven monoclonal antibodies for exact localization of different cells creating the thymic microenvironment (cytokeratin AE1/AE3, desmin, actin, S100 protein, CD68, CD20, and CD45RO) as well as three monoclonal antibodies against proteins regulating the process of apoptosis (bcl2 oncoprotein, p53 protein, and survivin). We described and microphotographically illustrated the localization of thymic cytokeratin AE1/AE3-positive epithelial cells (subcapsular part of the cortex and medulla, especially Hassall's corpuscles), dendritic cells (medulla, often inside the Hassall's corpuscles), thymic myoid cells (medulla, often in close contact with Hassall's corpuscles), macrophages (mostly cortex, but also medulla and inside the Hassall's corpuscles), B lymphocytes (thymic medulla) and CD45RO-positive T lymphocytes (mostly thymic cortex). We found p53-positive thymic epithelial cell nuclei in subcapsular part of cortex and in outer epithelial cell layer of Hassall's corpuscles (very similar to the basal layer of epidermis). Bcl2 positive lymphocytes were mostly localized in thymic medulla, especially nearby Hassall's corpuscles. The thymuses were mostly survivin-negative with exception of round cells in border between cortex and connective tissue septa (probably migrating progenitor cells) (Tab. 1, Fig. 14, Ref. 66).

The long-term response to treatment with calcium channel blockers in a patient with idiopathic pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disease characterised by a gradual increase in resistance of pulmonary circulation leading to right ventricular failure and death. In only 10 % of cases, there is a response to acute vasoreactivity testing with a significant reduction in mean pulmonary artery pressure (PAP), while in this group of patients, less than one half of cases benefit from long-term treatment with calcium channel blockers (CCB). This paper describes a case report of a young patient with dyspnoea and suspicion of pulmonary hypertension who was referred to a specialised centre. The complex evaluation of her clinical state led to confirmed diagnosis of idiopathic pulmonary arterial hypertension (IPAH). Because there was a positive response to vasoreactivity testing, the treatment for IPAH was initiated with a high dose of CCB. This treatment markedly improved her clinical state as well as echocardiographic and hemodynamic findings.In this study, the authors present a diagnostic algorithm in pulmonary hypertension and emphasise the role of CCB in treatment of PAH in carefully selected patients (Tab. 1, Fig. 5, Ref. 7).

Growth factors and chondrogenic differentiation of mesenchymal stem cells.

The main purpose of the article is to review recent knowledge about growth factors and their effect on the chondrogenic differentiation of mesenchymal stem cells under in vitro conditions. Damaged or lost articular cartilage leads to progressive debilitation, which have major impact on the life quality of the affected individuals of both sexes in all age groups. Mature hyaline cartilage has a very low self-repair potential due to intrinsic properties - lack of innervation and vascular supply. Another limiting factor is low mitotic potential of chondrocytes. Small defects are healed by migration of chondrocytes, while large ones are healed by formation of inferior fibrocartilage. However, in many cases osteoarthritis develops. Recently, cellular therapy combining mesenchymal stem cells and proper differentiation factors seems to be promising tool for hyaline cartilage defects healing.