Abstract. Dental stem niches (DSNs) reside in different dental tissues, being of particular importance in tissue engineering and dental regeneration procedures. The present paper aims to review the DSNs from the view of niche inhabitants, either extrinsic, such as cells of the myeloid lineage, or intrinsic, such as endothelial cells, perivascular cells and spindle-shaped stromal cells, e.g., telocytes. DSNs harbor different dental stem/progenitor cell morphologies, in different stages of differentiation and with various potentialities, the angiogenic potential with respect to regenerative endodontic procedures being emphasized here. It seems therefore important to consider the DSNs as being heterogeneous, for a better understanding of an accurate identification of niche team players in regenerative medicine.
Keywords: dental pulp, apical papilla, Stro-1, CD117, endothelial progenitor cells, endothelial-mesenchymal transformation
Abstract. Ventricular septal defects (VSDs) are the most common congenital heart diseases. Sometimes they can be complex because of anatomy, age of the patients or associated diseases. Surgery has been performed for many years and is considered as the gold standard for the treatment of VSD. However, it is associated with morbidity and mortality. Less invasive techniques have been developed in last 15 years. Two types of devices from the Amplatzer family are currently used to close percutaneously muscular and perimembranous VSD. Methods: Comparative data and technical aspects of percutaneous closure in complex congenital defects (muscular and perimembranous VSDs) and in acquired defects (residual post-surgery, traumatic and postinfarction) are presented and discussed in this review. Hybrid approach to VSD closure is another complex situation and it is presented, too. Results: Successful closure is obtained in around 95% with a rate of major complication of 5.3% for muscular VSD. For the perimembranous VSD, the complete and successful closure is reported in 97.5% of patients, while major acute complications occur in 1.2%. Occurrence of complete atrioventricular block is reported in 1.6% of subjects. Acquired VSD can occur as post-surgical residual leak, traumatic or postinfarction VSD. Procedures are usually complex and different techniques should be used. Conclusions: Percutaneous closure of complex VSDs is possible, safe and effective procedure in highly specialized centers. Appropriate patient selection is of paramount importance to the success of the procedure.
Keywords: congenital heart defects, transcatheter, treatment
Abstract. The aim of this study is to make a foray in the world of constitutive elements of the architectural and functional organizing of the cardiomyocytes involved in cardiomyopathies and of the genetic molecules that they express. Primary cardiomyopathies represent a group of diseases characterized by primary structural and functional changes of the myocardium, without myocardial ischemic disease, hypertension, valvulopathies or congenital cardiac diseases being involved. In the pathogenesis of the cardiomyopathies proteins, especially from the sarcomere, Z-disc, cellular cytoskeleton, sarcolemma, intercalated discs, nuclear envelope and other constitutive proteins of the cardiomyocytes are involved. Deciphering of these pathophysiological mechanisms is part of the new model of personalized medicine, and it is useful in developing and in the optimization of new strategies for the management of the patients diagnosed with this type of disease.
Keywords: cardiomyopathy, cellular cytoskeleton, genetic diseases, structural and functional changes
Abstract. Fracture healing is a complex process that involves presence of osteoprogenitor cells and growth factors. Therefore, the integrity of the fracture site surrounding tissues including periosteum is necessary in order to provide the resources for bone regeneration. The purpose of this review is to organize and synthesize the relevant information regarding periosteum and fracture repair. Periosteum cells are involved in endochondral or intramembranous ossification according to the presence of a new formed cartilage. The periosteal osteoprogenitor mesenchymal cells differentiation is guided by a multitude of signaling molecules, especially bone morphogenetic protein 2 (BMP2), but also as a response to mechanical stimuli. If the periosteum is traumatized or removed, there are other osteoprogenitor cell sources as the ones located in the medullar cavity of the bones, the pericytes from the blood vessel walls as well as the undifferentiated cells from the adjacent soft tissue, muscles and fascia. However, total absence of the periosteum and lesions of the intramedullary vascular network is associated with fracture non-union. In these cases, muscular tissue surrounding the site could take over some of the cambium functions. In conclusion, there are other factors that can influence significantly fracture healing, besides periosteum.
Keywords: periosteum, bone morphogenetic protein, osteoprogenitor, fracture healing, periosteal substitutes
Abstract. Primary lung cancer is an increasing health issue worldwide, with an ever-growing incidence due to various risk factors dispersed in all settings of modern society. Late discovery and poor survival rates for patients that do not qualify for surgical treatments greatly decrease overall mortality. Imaging methods remain powerful tools for early detection; however, molecular profiling is currently required for better understanding treatment options and for developing novel agents. Most procedures that are associated with tissue collection are invasive and, if performed in suboptimal conditions, may lead to morbidity and mortality. The need for better optical biopsy tools has thus arisen, directing further tissue collection and minimizing the chance of misdiagnosis. A series of methods have been proposed, including optical coherence tomography, narrow band imaging or autofluorescence. Lately, a novel in vivo tool for rapid and non-invasive microscopy gained traction - probe based confocal laser endomicroscopy became available in an increased number of referral centers worldwide. Miniaturization and the use of optical fibers allowed for the development of a dedicated device for pulmonary applications; lung cancer diagnosis and characterization are key issues targeted by this novel technology. We present here recent advancements in the field of optical biopsy of lung tissue, with a focus on emerging technologies and their involvement in cancer diagnostics and future therapeutic options.
Keywords: optical biopsy, probe-based confocal laser endomicroscopy, lung cancer, diagnosis, therapy
Abstract. A tumor represents an abnormal tissue growth that can arise from any ocular structure, such as eyelids, muscles or the optic nerve. At the eyelids, there are two main tumor types: basal cell carcinoma and squamous cell carcinoma. Angiogenesis plays a crucial role in growth, invasion and metastasis processes of any tumor. It is well known the fact that without new vessels formation tumors cannot exceed 1-2 mm diameter. Immunohistochemical analysis has been performed on 43 cases of primary carcinomas of the eyelid, diagnosed between 2010 and 2014 in the Laboratory of Pathological Anatomy of the University Emergency County Hospital of Craiova, Romania. Biological material was represented by surgical resection samples, coming from the Clinic of Ophthalmology the anteriorly named Hospital. Within the immunohistochemical study, we have evaluated epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression in a group of 43 cutaneous carcinomas of the eyelid, depending on the type and differentiation grade of the tumor. Of the 43 samples, 23 came from patients with eyelid basal cell carcinoma and 20 came from patients with eyelid squamous cell carcinoma. In our study, EGFR and VEGF immunoexpression was superior for squamous cell carcinomas, compared to basal cell carcinomas, fact that was statistically significant. Regarding squamous cell carcinomas, the immunoexpression of these two markers was superior in moderate/poor differentiated forms, compared to well differentiated forms, fact that was statistically significant. The markers used in this study were found to be associated with the acquisition of aggression and angiogenic phenotypes by analyzed carcinomas.
Keywords: angiogenesis, basal cell carcinoma, squamous cell carcinoma, VEGF, EGFR
Abstract. E-cadherin and beta-catenin are two molecules implicated in cellular adhesion. The reduced expression of beta-catenin and E-cadherin is associated with the tumoral epithelial-mesenchymal transition process, a key event in the development of endometrial carcinoma. The aim of our study was to investigate the association between the immunoexpression of beta-catenin/E-cadherin and the tumor differentiation degree, presence of lymph nodes, depth of tumor invasion and pTNM stage of endometrioid endometrial carcinomas in order to enhance the potential aggressiveness of these tumors. Our results revealed significant differences in the expression of beta-catenin, when grouping for the tumor stage, invasion in the myometrium and degree of differentiation, as well as significant differences in the expression of E-cadherin for tumor degrees of differentiation. E-cadherin and beta-catenin expression was stronger in well-differentiated tumors, superficial myometrium invasion and early tumor stages I or II, thus was associated with better prognostic forms of endometrioid endometrial carcinoma. Our study indicated that decreased of the E-cadherin and beta-catenin expression is useful for the assessment of tumor aggressiveness.
Keywords: E-cadherin, beta-catenin, endometrioid endometrial carcinoma
Abstract. Aim: The authors assessed the morphological profile of tumor masses belonging to the small bowel discovered in their daily practice. Materials and Methods: 31 tumor masses located in different segments of small intestine operated between 2002 and 2013 in the 1st Surgical Department, Emergency County Hospital of Craiova, Romania, were analyzed. The investigated parameters were: tumor location and number, tumor dimensions, gross assessment, tumor extension and histological assessment. Results: Tumor masses belonging to small intestine were rare. They usually expressed by their complications. In many cases, they were placed at the extremities of the small intestine. They were usually small but sometimes large and developing outwards intestinal wall. Commonly they had a fungating and ulcerated appearance. They were rather of mesenchymal origin than epithelial. However, some of them were inflammatory pseudotumors. Almost all neoplastic proliferations had a malignant phenotype, most often with regional extension. Conclusions: Our series of tumors had a morphological profile somehow similar with the profile described in the literature but with some particularities: the polarization to the extremities of the intestinal segment, a significant number of large tumors, clinical expression through different complications, the balance inclined in favor of mesenchymal origin of tumors and the clear predominance of malignant aggressive phenotype.
Keywords: small bowel, tumor, morphology
Abstract. The main target in rectal cancer management is an individualized therapeutic strategy, based on tumor and patient characteristics. The assessment of clinical and pathological factors is important because they represent powerful predictors of the postoperative outcome and have to be considered in the decision making regarding the appropriate surgical technique. The aim of the study was to analyze how the tumor clinical and pathological features correlate with the chosen type of surgical intervention in influencing survival of rectal cancer patients. We ran a retrospective study on 289 patients (N=289) surgically treated for rectal cancer. We analyzed the individual influence of the studied parameter on survival rate in multivariate analysis and we also grouped them in associations of parameter variations and performed a survival analysis for prognostic univariate analysis. For patients with vascular and lymphatic invasion and without perineural invasion, choosing a sphincter function preserving technique brought a better long-term outcome. The TNM stages showed the strongest statistically significant effect upon survival. Patients in T3 or T4 stage benefited best from a performed sphincter saving technique and the positive effect was even higher for those in N1 stage. Assessment of pathological parameters, in association with the type of the surgical procedure, has a strong predictive value upon survival. Sphincter function preserving techniques are followed by good long-term outcome. Accurate preoperative staging can help in choosing the best individualized therapeutic management improving the life expectancy of patients with rectal cancer.
Keywords: rectal cancer, sphincter function preserving technique, survival, pathological parameters
Abstract. Background and Aims: Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-beta1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-gamma (PPARgamma) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis. Materials and Methods: In this research, we used two groups of Wistar rats, which received intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) 40% dissolved in olive oil, twice weekly for four consecutive weeks (initial dose of 5 mL/kg, and other doses 3 mL/kg). After one week, one group was received by gavage telmisartan (TS) dissolved in saline 0.9%, daily in dose of 8 mg/kg, for 28 days. One group of Wistar rats was used for control. The antifibrotic action of telmisartan was investigated on the pathological changes of the liver and immunohistochemical analysis for hepatic stellate (Ito) cells (HSCs) reaction using anti-alpha-smooth muscle actin (anti alpha-SMA) antibody and macrophages cells (Kupffer cells) reaction using anti-CD68 antibody. Results and Conclusions: In group treated with telmisartan, hepatic fibrogenesis process was significantly reduced, in comparison with CCl4 group.
Keywords: hepatic fibrosis, antifibrotic action, telmisartan, myofibroblasts, hepatic stellate cells
Abstract. As one of the fundamental requirements for an optimal function of the locomotive system is the integrity of the skeleton, the morphology of proximal humerus is crucial for upper limb performance. Not only that the bone is the support for muscle insertion, but its particular form is responsible especially for the complex movement of the shoulder joint, so that any pathological features of this morphology results in different degrees of dysfunction. Since trauma is the most frequent cause for morphological changes of this area, this paper studies the anatomical landmarks, which are affected by proximal humeral fractures and must be targeted when treating these injuries, for they influence the functional outcome. Evaluating the results from a Level 1 Trauma Centre, the authors underline the importance of these anatomical landmarks in approaching proximal humeral fractures and aim to establish a morphology-based therapeutic algorithm, crucial for optimal functional restoration.
Keywords: proximal humerus morphology, proximal humerus fractures, functional restoration, therapeutic algorithm
Abstract. Taking account of increasing world population life expectancy, health services will face with a large number of elderly people with chronic age-related diseases. It has been established that chronic diseases are usually accompanied by oxidative stress induced by the overproduction of reactive oxygen species damaging cellular constituents, under conditions of weakening antioxidant defense systems. The balance between free radicals and antioxidant endogenous systems has a defining role in preventing the damage of macromolecules. In addition to the enzymatic (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase) and non-enzymatic (vitamins A, C, E) endogenous systems, a good source of natural antioxidants are medicinal herbs products or phytochemical compounds. The aim of this study is to evaluate the hepatoprotective effect of Syringae vulgaris flos ethanolic extracts in a rat model of streptozotocin-induced diabetes.
Keywords: Syringa vulgaris, hepatoprotective effect, diabetes mellitus, streptozotocin
Abstract. The skin burns are an issue of great interest and seriousness in the public health domain, by their destructive features. Natural medicinal products are extensively used from ancient times, in ethnopharmacology, for the treatment of skin injuries (burns, wounds, ulcerations) due to the local modulation of the cellular response, in terms of emollient, demulcent, astringent, anti-inflammatory, antimicrobial, epithelizing, wound-healing, immunomodulatory and antioxidant effects. Aim: Histological and immunohistochemical assessment of antiseptic, anti-inflammatory, astringent and cicatrizing effects of Scutellariae (altissimae, galericulatae, hastifoliae) herba extracts administered in the form of 20% topical preparations (cold-creams), in experimental model of third degree skin burns, at Wistar rats. Caffeic acid and chlorogenic acid derivatives were identified in all herbal samples. The most active was the cold-cream with 20% Scutellariae hastifoliae herba soft extract, promoting the neoangiogenesis vessels and granulation tissue. Flavonoids, tannins and polyphenol carboxylic acids are the main active principles responsible for antiseptic, anti-inflammatory, astringent and cicatrizing effects of herbal extracts. Beeswax, from the formulation of cold-creams, acts as emollient, epithelizing, cicatrizing and biostimulator.
Keywords: Scutellariae herba, extracts, experimental model, rats, skin burns
Abstract. Introduction: We conducted a retrospective study on patients who were hospitalized in the Emergency County Hospital of Craiova, Romania, between 2009-2014. We selected 75 patients out of 248 cases of fatty liver disease who underwent liver biopsies performed during surgical procedures for various diagnoses. Patients and Methods: We analyzed the patients data recorded in examination charts: anthropometric parameters [height, weight, body mass index (BMI), abdominal circumference], metabolic lab tests (blood glucose, lipid profile), liver destruction enzymes, imaging examinations (abdominal ultrasound). The pathological study was performed on specimens directly after sampling as well as after staining. Results: After analyzing the results of the histological examination, we grouped our studied patients according to the degree of the liver steatosis: 21 (28%) cases with mild steatosis, 46 (61.33%) cases with moderate disease and eight (10.66%) cases with severe steatosis. The necrotic-inflammatory activity was mild in 28 (37.33%) cases, moderate in 36 (48%) cases and severe in 11 (14.66%) cases. Most of the studied patients exhibited septal fibrosis (45 cases - 60%) and porto-portal and porto-central bridging fibrosis (21 cases - 28%). Septal fibrosis and cirrhosis were recorded in four (5.33%) and five (6.66%) cases, respectively. There was a significant correlation between the degree of the hepatic steatosis, the degree of obesity (as expressed by BMI) and the waist circumference (as a measure of central obesity) - p<0.001. Conclusions: The non-alcoholic fatty liver disease (NAFLD) was found to be significantly associated with waist circumference, BMI, triglycerides. The liver enzymes are not considered to be sensitive or specific for diagnosing NAFLD. Concerning the association between the steatosis and fibrosis, in our study the septal fibrosis was associate with mild steatosis in most of the cases. Moderate steatosis was mostly associated with septal fibrosis as well as porto-portal and porto-central fibrosis. Severe steatosis was correlated with both porto-portal and porto-central fibrosis and cirrhosis in the majority of cases.
Keywords: non-alcoholic fatty liver disease, obesity, steatosis, fibrosis
Abstract. Helicobacter pylori (H. pylori) is the etiological factor for gastritis in more than half of the worldwide population. H. pylori infection increases the risk for gastric pathology, but could also have consequences on cardio-metabolic status. Obesity has as epidemic growth, and the only efficient long-term treatment for morbidly obese patients is currently surgery. Although of vital importance, the preoperative assessment is not standardized, including the aspects related to H. pylori infection. The aim of this prospective study was to evaluate the prevalence of H. pylori (Hp) infection in a group of patients referred to bariatric surgery and the agreement of two commonly used methods for its diagnosis. We included 70 asymptomatic obese patients consecutively for 14 months, who were evaluated by serology (anti-Hp IgG antibodies) and by histology (gastroscopy with gastric mucosa biopsy). If diagnosed, H. pylori infection was standard treated and afterwards, all patients underwent laparoscopic sleeve gastrectomy; the resected stomach was morphologically evaluated. 58.6% of patients were H. pylori positive on serology and 51.4% were H. pylori positive on histology, agreement coefficient factor kappa between the two methods being 0.686, p<0.001. The serological diagnosis had a sensibility of 90.3% and a specificity of 77.8%. The prevalence of H. pylori infection in the resected stomach was 11.4%, and was associated with more severe degrees of chronic gastritis. In conclusion, as gastroscopy should anyhow be performed in all patients referred to surgery, our data favor the histological evaluation in all patients and the eradication treatment according to its results.
Keywords: Helicobacter pylori, chronic gastritis, laparoscopic sleeve gastrectomy, anti-Hp IgG antibodies
Abstract. In this study, we performed microscopic qualitative analyses of the oral epithelium cytological smears in potential early phase of diabetes and in type 1 and 2 diabetic patients versus a healthy control group. The cytological assessment of the oral changes was realized on superficial and profound smears, from jugal and ventral tongue mucosa and it was based on the comparison between three staining methods [Papanicolaou, APT (polychrome tannin blue)-Dragan and Hematoxylin-Eosin (HE)]. Cytological changes of oral cells population were correlated with the type, duration and complications of diabetes. Oral flora was also evaluated. Irrespective the staining used, we found a clear dividing line between the control group and the real diabetic patients. In all diabetes cases (independently of the type of smear, harvest site, clinical form of disorder and present complications), cells presented alterations both at the level of cytoplasm and nucleus. Dyschromasia, cytolysis, different degrees of fatty degenerescence, binucleated cells, hyperchromasia, nuclear enlargement with modified nuclear/cytoplasmic ratio, were the most frequent findings. There were no discrepancies in the cellular aspects of type 1 or 2 diabetic patients smears or between the control group and the potential prediabetic status patients. Findings were interpreted as oral epithelium reactive changes induced by the disease. We concluded that exfoliative cytology alone is of low value as a diagnostic and prognostic tool in the diagnosis of diabetes mellitus (DM); it detects the reactive changes induced by the disease, but it makes no differences between DM types or degree of severity and does not allow by qualitative analysis alone to detect abnormalities in early diabetes.
Keywords: diabetes mellitus, oral exfoliative cytology, cytological staining, squamous cell alterations
Abstract. Periodontal disease is one of the most frequent diseases affecting people all over the world. The relation between periodontal disease and diabetes mellitus raised the interest both of dentists and doctors treating metabolic diseases, as the two conditions influence one another. In our study, we analyzed a number of 75 patients with diabetes mellitus and periodontal disease that presented to the medical consultory for conditions of the dental maxillary system. The clinical study showed that periodontal disease and diabetes may affect young adults as well, still this pathological association more frequently appears after the age of 50. The disease was identified especially in the women living in urban area. The clinical examination of the dental maxillary system identified the presence of gingival ulcerations, dental calculus, gingival bleeding, radicular leftovers with anfractuous margins, fixed prostheses with an inappropriate cervical adjustment. Of the systemic diseases associated to periodontal disease and diabetes mellitus, there was observed that 66.66% of the patients also suffered from cardiovascular diseases (high blood pressure, ischemic cardiopathy, heart failure), and 37.33% suffered from obesity. The histopathological and immunohistochemical tests highlighted the presence of an inflammatory chronic, intense reaction, mainly formed of lymphocytes, plasmocytes, macrophages and granulocytes, heterogeneously disseminated and alteration of the structure of marginal and superficial periodontium. The inflammatory reaction in the patients with periodontal disease and diabetes was more intense than in the patients with periodontal disease without diabetes.
Keywords: diabetes mellitus, chronic periodontitis, risk factors, metabolic disease, glycemic control
Abstract. Introduction: The neuropathogenesis of multiple sclerosis (MS) lesions has been explained by several mechanisms, which emphasize the unpredictable nature of these lesions. The aim of this study is to present the neuromuscular changes in MS at the patients without gait or motor disorders using a noninvasive method named tensiomyography (TMG). Patients and Methods: The studied group included a number of seven MS patients without clinically detected gait disorders, with mean age of 33.28 years (min. 22 years-max. 60 years), diagnosed with progressive multiple sclerosis with relapses - three patients and with relapsing-remitting multiple sclerosis (RRMS). They have been evaluated using clinical, functional scales for evaluation and neuromuscular assessment using TMG parameters (displacement Dm, contraction time - Tc, delay time - Td, supporting time - Ts, relaxation time - Tr), for rectus femoris (mRF). Results: The group with MS patients recorded functional asymmetries with higher values in the left lower limb. We determined Tc values lower than the minimum normally required, which meant that in the group with MS there was an increase in the percentage of type II fibers. Other TMG parameters show important difference between left and right side even if they do not have gait disorders. Discussion and Conclusions: These patients with MS underwent modifications in their muscle tone, muscle strength and other changes related to the presence or absence of muscle atrophy. The muscle tone could be affected by the muscle atrophy or hypertrophy. In conclusion, this type of assessment performs the non-invasive assessment of contractile properties of the muscles, without the integration of the tendon properties, joint mechanics or connective tissue in the mechanical response to muscle deformation produced by electrical stimulation.
Keywords: tensiomyography, multiple sclerosis, assessment, muscle tone
Abstract. Introduction: An adnexal mass (mass of the ovary, Fallopian tube, or surrounding connective tissues) is a common gynecological problem. Ovarian pathology can occur at any time from fetal life to menopause. Sonography is a clinically important imaging modality for assessing whether an adnexal mass is likely benign or possibly malignant. Most ovarian surgeries are for benign disease and can be performed laparoscopically. Patients, Materials and Methods: We retrospectively evaluated all the patients from our Clinic who underwent laparoscopy for adnexal tumors in the last three year. We were studying the correlation of the preoperative ultrasound examination and the pathological result for each case. Results: In this study, there were included 71 patients who underwent a laparoscopic intervention for adnexal tumors. The average age was 33 years old. The ultrasound findings were ovarian endometriosis in 23.9% of cases, left ovarian cysts and right ovarian tumors, and the lowest percentage was of left ovarian tumors. Regarding the histopathological examination, we found the following results: ovarian endometriosis, ovarian functional cysts, serous ovarian cysts, salpingitis, ovarian myoma, papillary serous ovarian cysts, ovarian teratoma cysts, one caseof ovarian carcinoma and one case of borderline serous tumor. In this study, we observed that it was a strong correlation between the ultrasound finding and the pathological result for adnexal tumors. Conclusions: The laparoscopy was performed in our Clinic for adnexal masses with benign characters in ultrasound examination. The histopathological examination confirmed the diagnosis, being only one case of ovarian carcinoma in this study.
Keywords: adnexal mass, Fallopian tube, ovarian tumor, malignancy, borderline tumor
Abstract. We aim to investigate whether the -759C/T polymorphism in 5-HTR2C gene was associated with weight change and hyperinsulinemia in Romanian pediatric patients with schizophrenia and bipolar disorders. The patients under investigation were enrolled between 2009 and 2014. A total of 81 schizophrenic and bipolar-disorder patients, aged between nine to 20 years (median age 15.74+/-4 years), who were following an atypical antipsychotic treatment (Risperidone, Aripiprazole, Olanzapine), were enrolled from University Hospital for Child and Adolescent Psychiatry and Neurology from Timisoara, Romania. The outcomes that we measured were the changes in Body Mass Index (BMI) from baseline to different time points: three months, six months, 12 months and 18 months, and the change in insulinemia over time, after atypical antipsychotic treatment. After carrying out the 5-HTR2C 759C/T polymorphism identification, we found that 22 patients presented the -759C/T polymorphism in 5-HTR2C gene. Between the patients exhibiting the 5-HTR2C -759C/T polymorphism and the patients having the wild type alleles, there was no significant statistical difference in changes of BMI from baseline to endpoints that indicates the lack of the protective effect of the T allele against atypical antipsychotics-induced weight gain. Interestingly, we found a statistically significant association between insulinemia and T alleles carriers, after 18 months of treatment with the above-mentioned antipsychotics. Taking into consideration that atypical antipsychotics have been associated with elevated insulin levels and insulin resistance, maybe in the future the -759C/T polymorphism would find a role in the development of a more complex algorithm for prediction of diabetes mellitus risk, in patients taking atypical antipsychotics.
Keywords: pharmacogenetics, polymorphisms, antipsychotics, schizophrenia, bipolar disorder
Abstract. Myocardial fibrosis is one of the most common histopathological lesions found in chronic heart diseases. Progressive development of myocardial fibrosis will cause heart failure, an extremely debilitating and life threatening condition. The correlation between the severity of fibrosis and myocardial microcirculation is an important prognostic factor in this disease entity. In our study, myocardial microvascular density evaluation of the patients with high blood pressure (hypertension), atrial fibrillation (AF), coronary heart disease, and heart failure showed a significant decrease of the values of this parameter, which means that myocardial fibrosis is the direct result of stimulation of myocardial fibroblasts induced by local hypoxia.
Keywords: myocardial fibrosis, endothelial cells, fibroblasts, myofibroblasts, cardiomyocyte, extracellular matrix
Abstract. The inconsistency of efficiency in murine embryonic stem cell (ESC) production might be associated with the differences in preparation and cryopreservation of the feeder cell layer. As the cryopreservation of mouse embryonic fibroblast (MEF) declined the quality of MEF as feeder cell layer, an effective protocol should be determined to produce murine ESC on frozen-thawed feeder cell layer as efficient on fresh feeder cell layer. Under appropriate culture conditions, isolated inner cell mass (ICM) of murine blastocyst will form ESC and be maintained in undifferentiated state. Therefore, the aims of this study were to determine the most optimum freezing density and equilibration duration for cryopreserving MEF feeder cell layer and to determine the effect of fresh and frozen-thawed feeder cell layer on murine ESC production. Freezing density of 5x106 cells/mL gave a significantly higher viability rate than 0.5x106 cells/mL (68.08% vs. 59.78%, p<0.05) and comparable with 2x106 cells/mL. The viability rates of frozen-thawed MEF derived from 15 minutes equilibration was significantly higher than 20 hours equilibration (79.4% vs. 68.08, p<0.05). There were no significant differences between fresh and frozen-thawed MEF feeder cell layer for percent successful attachment of blastocysts, consecutive passages of murine ESC up to passage 3. In conclusion, freezing density of 5x106 cells/mL and 15 minutes equilibration duration are optimizing the cryopreservation of MEF feeder cell layer to subsequently improve the production of murine ESC.
Keywords: murine embryonic stem cell, mouse embryonic fibroblast, cryopreservation, freezing cell density, equilibration duration
Abstract. Epithelioid trophoblastic tumor (ETT) is a very rare case of malignant trophoblastic tumor, which can occur particularly during the fertile age of women with a long history of abortion and delivery. ETT originates from the intermediate trophoblastic cells of chorion laeve. The main features of this tumor include lack of vessels within the tumor, nuclear hyperchromasia and pleomorphism and a large zone of necrosis and hyalinization. The clinical features of ETT are specific to each case and often consist of vaginal bleeding or amenorrhea in the absence of other complains. The beta-human chorionic gonadotropin (beta-hCG) serum level cannot be an absolute criterion useful in defining diagnosis. The right diagnosis can only be established by a histopathological examination of the tissue picked-up via intrauterine curettage. This paper describes the case of a 35-year-old woman who required gynecological investigation for amenorrhea. The diagnosis established by biopsic curettage and the clinical evolution have influenced the physician s decision to perform hysterectomy. The only method to differentiate between the microscopic diagnosis of ETT and choriocarcinoma was the immunohistochemical staining of trophoblastic cells for cytokeratin AE1/AE3, p63, Ki67. Despite the diagnosis of malignity, this tumor does not usually require a recommendation for chemotherapy and does not seem to have a bad prognostic. However, these data do not rule out that clinical behavior is sometimes difficult to predict. We analyzed the clinical and histology criteria in line with the data published in literature.
Keywords: epithelioid trophoblastic tumor, choriocarcinoma, gestational trophoblastic disease
Abstract. The clinical spectrum of perinatal infection varies from asymptomatic infection or mild disease to severe systemic involvement. The aim of this paper is to present a severe intrauterine infection, which led to difficulties in diagnosis and unfavorable evolution. Case presentation: M.E., 6-weeks-old, born small for gestational age, was admitted in our Hospital for gastrointestinal signs: diarrhea, abdominal distension, observed three days earlier. Clinical and biological exams revealed hepatic disease related with hepatic cytolysis and cholestasis. Abdominal ultrasound showed large amounts of ascitic fluid, cirrhotic liver, enlarged portal vessel with hepatopetal flow, normal gallbladder and biliary tract. Computed tomography (CT) angiography revealed a wide hepatic artery, the presence of portal vein and absence of splenic vein. Serology detected IgM anti-cytomegalovirus antibodies. Postmortem histological exam confirmed the liver cirrhosis; cell free cytomegalovirus (CMV) antigens were found among alveoli with atelectasis. Discussion: The onset of hepatic disease was acute or chronic? Anamnesis offered reliable diagnostic criteria for intrauterine infection (flu during first trimester of pregnancy, intrauterine growth restriction, prolonged jaundice). The mother had been tested for all TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex) infections other than CMV. The strict liver cell tropism raised questions regarding virulence, host immunology or the existence of other disease (vascular?) Conclusions: Liver cirrhosis at this age is very rare; the most frequent etiology is viral. The late diagnosis of this case led to the impossibility of etiological treatment.
Keywords: congenital cirrhosis, cytomegalovirus, intrauterine infection, absence of splenic vein
Abstract. Vulvar malignant melanomas are extremely rare neoplasms, representing less than 3% of all cancers in women, 9% of all external genital tract malignancies and 9% of all primary vulvar malignancies. We present the case of a 60-year-old Caucasian patient, who has been admitted in the Clinic of Obstetrics and Gynecology with polymorphic, vulvar local, pelvic-abdominal, genitourinary and general symptoms, being diagnosed with nodular and superficial spreading vulvar melanoma and multiple voluminous uterine leiomyoma with various degenerations. Our study presents the approach of this case in terms of surgical pathology, management, prognosis and outcome. Surgical treatment is the central element of therapeutic management. Vulva melanomas are in general a relatively unpredictable unfavorable prognosis. The sizes of the tumor, the thickness and micro-staging are essential factors for prognosis.
Keywords: genital cancer, abdominal tumor, immunohistochemistry, diagnosis, prognosis
Abstract. Tuberculosis (TB) is considered a pulmonary disease that can however disseminate to other organs through hematogenous dissemination following primary TB infection. Evolution of the disease can either be precocious, before healing of the primary infection, or late after primary infection, due to reactivation of initial lesions usually because of simultaneous immunosuppressive factors such as diabetes, renal disease, hepatic disease or different type of immunosuppressing treatments. Rare cases when tuberculosis and cancer are diagnosed at the same time create diagnostic difficulties and therapeutic challenges. We present the case of an asymptomatic 52-year-old female that was diagnosed by chance, at the right moment with a form of skin melanoma on the right forearm, for which she received a rather well tolerated cytostatic treatment. At the end of this treatment, she was also investigated for a breast mass that proved to be benign; however, enlarged lymph nodes were discovered in the right armpit were discovered upon further investigation. One of the lymph nodes was surgically removed, as first suspicion was of a metastasis from the skin melanoma. However, it was lymph node tuberculosis therefore anti-tuberculosis treatment was initiated. The patient tolerated the treatment with minor side effects. On few occasions, a patient can be diagnosed with incipient stages of skin melanoma and even more rarely the same patient is diagnosed and treated prematurely for lymph node tuberculosis. Sometimes, a successful outcome needs an organized and well-educated patient and a little luck.
Keywords: lymph node tuberculosis, melanoma, immunosuppression, chemotherapy
Abstract. Introduction: Central nervous system (CNS) germ cell tumors are very rare, accounting for 0.3-3% of primary intracranial neoplasms; of these, the teratomas are even more uncommon. The immature variant of teratomas, defined by the presence of incompletely differentiated components resembling fetal tissues is considered as having a low, almost borderline malignancy state. Case presentation: A 35-year-old male presented with a left fronto-basal tumor. At surgery, a grey white tumor, mostly solid, was excised. The histopathological examination revealed an infiltrating teratoma. The histological spectrum varied from epithelial and mesenchymal mature to immature tissues. These structures were intimately mixed with significant areas of primitive neuroepithelial tubules and/or primitive neuroectodermal tissues. The diagnosis was that of an immature intracranial teratoma, with high histological grade WHO (World Health Organization) (Norris grade III). After surgical resection, a rapid infratentorial contralateral subarachnoid extension followed. The second tumor was largely formed by primitive neuroectodermal tumor (PNET)-like structures and rare mature epithelial tissues, meaning a PNET-like overgrowth or malignant transformation of an immature teratoma. After specific oncological treatment, the patient had a favorable evolution with no signs of relapse (2016). Conclusions: The present case highlights the value of the Norris grading system (mostly used in grading ovarian immature teratomas) in a very rare case of intracerebral immature teratoma with rapid subarachnoid extension caused by an unexpected secondary malignant transformation.
Keywords: teratoma, immature, neuroectodermal, intracranial, overgrowth
Abstract. Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor originating from the Cajal interstitial cells, immunologically characterized by the c-kit gene. The evolution may be asymptomatic, discovered by chance during a necropsy, upper gastrointestinal endoscopy or due to complications of type-algic, occlusive or hemorrhage. We present the case of a voluminous gastric GIST complicated with serious upper gastrointestinal bleeding in a patient with multiple hard associated diseases, undergoing an emergency surgery in hemorrhagic shock. The surgery consisted in the resection of the upper polar esogastric, the pathological and immunohistochemistry tests confirming the diagnosis of GIST. The evolution was unfavorable at discharge after 45 days after surgery by an anastomotic fistula.
Keywords: gastrointestinal stromal tumor, upper gastrointestinal bleeding, immunohistochemistry, Ki67
Abstract. Bardet-Biedl syndrome (BBS) represents a rare ciliopathy recessive autosomal inherited. The main clinical features are retinal dystrophy, postaxial polydactyly, obesity, different degrees of cognitive deficit, renal impairment, hypogonadism and genital malformations. The genetic explanation consists in BBS genes mutations, which encode modified proteins, altering the function of the immotile cilia. As a multitude of BBS genes mutations were described, the phenotypic aspect of these disorders varies according to that. We present the case of a 22 years old female patient, known with BBS since the age of 11 and which was diagnosed and operated for bilateral ovarian dermoid cysts, at the age of 21. We did not find a similar case in literature, regarding the association between the two disorders. We consider that our case points towards the importance of periodic imagistic evaluations [magnetic resonance imaging (MRI), computed tomography (CT) or ultrasound] of these patients, not only clinical and biological. Usually, the moment they are diagnosed with hypogonadism or genital malformations (in childhood or adolescence), the genital evaluation is neglected thereafter. We also consider that our therapeutic approach can be helpful in other similar clinical situations. Another important conclusion is represented by the importance of genetic counseling of the relatives of a BBS patient, unfortunately insufficiently provided in our region.
Keywords: Bardet-Biedl syndrome, retinal dystrophy, hypogonadism, dermoid cysts, ovaries
Abstract. Here we present a report of 61-year-old female patient. Uterus with left appendages was removed together with clinically tagged tumor of right ovary and then extensively sampled and routinely processed with Hematoxylin-Eosin (HE) and some additional staining. There was discernible oviduct adherent to grayish, solid, polycyclic 22 cm in diameter focally necrotic tumor to be diagnosed high-grade conventional leiomyosarcoma FNCLCC (Federation Nationale des Centres de Lutte Contre le Cancer) G3 pT2b, according to 7th edition pTNM, according to World Health Organization (WHO) 2013 International Classification of Diseases for Oncology (ICD-O): 8890/3, in nearby of right oviduct. Grade of differentiation was given according to FNCLCC classification: grade 3 - point score: 6 = 1 [microscopically necrosis comprised 10% of the tumor] + 3 [high mitotic index eight mitoses/one high-power field (HPF) in hot spots in HE slides; Ki67 labeled approximately 60% of tumor cells] + 2 [histopathological type: conventional leiomyosarcoma]. The staging was more appropriate for pT2b (7th edition pTNM) for deeply seated sarcoma of soft tissues, in examined samples, there was no trace of microscopically evident ovarian texture) rather than pT1a for ovarian tumors. The tumor was alpha-smooth muscle actin (alpha-SMA)-positive. Detected epithelial membrane antigen (EMA) immunoreactivity indicates a possible change in mesenchymal origin. Next generation sequencing revealed tumor protein p53 (TP53) mutation C275Y (7577114 C>T). Each soft tissue malignancy should be carefully reported with appropriate choice of staging and precisely graded with internationally acknowledged classification.
Keywords: leiomyosarcoma of broad ligament, EMA immunoreactivity, mesenchymal origin, next generation sequencing, P53 mutation
Abstract. Fetal ultrasonography remains the main diagnostic tool for the assessment of different malformation. Fetal limb anomalies can be either isolated, either associated with other malformations in context of different syndromes. We present two cases of isolated fetal limb anomalies involving the distal part of the upper limb, namely the fetal hand consisting in phalangeal aplasia detected through routine ultrasound fetal examination. We could not identify the etiology in any of the cases, but in one of them, we discovered a bilateral thumb anomaly of the mother s hand. Both fetuses were aborted spontaneously without any relation to the detected anomaly. The upper limb anomaly was confirmed by the clinical, radiological and anatomopathological examinations of the aborted fetuses. The early detection of fetal limb anomalies provides the opportunity of choosing the best therapeutic management. Genetic counseling must also be taken under consideration for further pregnancies.
Keywords: fetal superior hand anomalies, fetal ultrasonography, fingers, phalanges
Abstract. Cystic cervical hygroma or cervical cystic lymphangioma is a congenital benign disease of the lymphatic system that is characterized by the accumulation of lymph in the jugular lymphatic sacs of the nuchal region. The factor that causes this pathology is not clarified yet but the physiopathological mechanism seems to be multifactorial. The incidence and prevalence of cervical hygroma are increased in patients with Turner syndrome, Down syndrome, Klinefelter syndrome, Edwards syndrome, Patau syndrome, Noonan syndrome, pterygium syndrome, Cantrell pentalogy, Fryns syndrome, Apert syndrome, Pena-Shokeir syndrome and achondroplasia. The gold standard method in establishing the antenatal diagnosis is ultrasonography, a non-invasive and low-cost procedure. We report four cases of fetuses who were diagnosed antepartum with cervical hygroma in the Department of Obstetrics and Gynecology of the University Emergency Hospital in Bucharest, Romania. Two products of conception were send to the Department of Anatomy of the Carol Davila University of Medicine and Pharmacy, Bucharest, for an extensive morphological analysis. Cervical cystic hygroma is a congenital condition of variable expression in terms of both morphology and chronology. A complete ultrasound examination, performed by an experimented specialist in maternal-fetal medicine is essential in establishing the diagnosis of cervical hygroma. Screening for aneuploidies, between the 11th and 14th weeks of pregnancy is also mandatory due to the frequent association between cervical hygroma and congenital anomalies.
Keywords: cervical hygroma, ultrasonography, management, congenital disease
Abstract. The association of gastrointestinal stromal tumor (GIST), synchronous or metachronous with other tumors is reported in special literature, the most frequent being associated with other gastrointestinal tumors. GISTs are the most common mesenchymal neoplasm of the gastro-intestinal tract with a malignant potential. We present a case of 68-year-old male patient diagnosed with GIST stage IV, unreachable due to liver metastases, treated with Imatinib, diagnosed at 13 months of prostate adenocarcinoma diagnosis [treated with hormonal therapy (HT) and external beam radiotherapy (EBRT)]; at 45 months from the first neoplasia diagnosis, the patient was diagnosed with the third neoplasia - lung squamous carcinoma - right inferior lobe, for which performed EBRT. The coexistence of GIST with other malignancies with different histology, remain a challenge for the clinician from etiological, and also from therapeutically actions point of view.
Keywords: gastrointestinal stromal tumor, prostate adenocarcinoma, lung squamous carcinoma
Abstract. Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.
Keywords: serous epithelial tumors, borderline epithelial tumors, immunohistochemistry, laparoscopy
Abstract. The Romanian School of Pathology from Cluj has an important prestige, well known in Romania and abroad. It was founded in the same year with the Romanian Faculty of Medicine from the same City. The founder of the School of Pathology was Victor Babes (1854-1926). In 1920, his role was continued by his remarkable pupil Titu Vasiliu (1885-1961). Unfortunately, a personality of this School of Pathology rarely mentioned is Alexandru Serban (1920-1977). He was pupil of T. Vasiliu and he led the Department of Pathology from the Cluj Faculty of Medicine between 1973 and 1977. The purpose of our paper is to put into evidence his contributions in the development of pathology in Cluj and in Romania. We mention some data about his life. Thus, we pay an homage to his memory.
Keywords: Alexandru Serban, underrated personality, the tradition of pathology from Cluj