Abstract. Matrix metalloproteinases (MMPs) occupy a central role in embryogenesis and in normal physiological conditions, such as proliferation, cell motility, remodeling, wound healing, angiogenesis, and key reproductive events. MMPs form a multigenic family of proteolytic, zinc-dependent enzymes, with 26 members described until present, displaying multidomain structures and substrate specificities. MMPs are involved in both the turnover and degradation of extracellular matrix (ECM) proteins and in the processing, activation, or deactivation of a variety of soluble factors. They are regulated at the level of transcription, activation of the precursor zymogens, and inhibition mainly by tissue inhibitors of metalloproteinases (TIMPs). Any loss in activity control may result in various diseases. This review provides an update of biological functions of MMPs, facilitating the understanding of the complex pathogenic mechanisms of medical conditions characterized by imbalance between MMP and TIMP expression. The design of potent specific inhibitors for MMPs represents a scientific challenge for the development of new therapies.
Keywords: matrix metalloproteinases (MMPs), protease, tissue inhibitors of metalloproteinases (TIMPs), extracellular matrix (ECM), domain.
Abstract. The aim of the study was to analyze the association between chronic cholecystitis, premalignant lesions and gallbladder cancer. The group consisted in 3901 cases of cholecystectomies, diagnosed as acute cholecystitis (250 cases - 6.4%), chronic cholecystitis (3619 cases - 92.8%) and gallbladder carcinoma (32 cases - 0.8%). Chronic cholecystitis associated premalignant lesions as follows: hyperplasia in 124 cases (7.8%), metaplasia in 86 cases (5%) and dysplasia in 10 cases (0.4%). Only in nine cases, the diagnosis of gallbladder carcinoma was formulated presumptively, before surgery; for the other 23 cases this diagnosis was established after the pathologic exam on the cholecystectomy piece. In the areas adjacent to the neoplastic proliferation, premalignant lesions (hyperplasia, metaplasia, dysplasia) were identified in 34.4% cases. The identification of premalignant modifications in the morphologic background of chronic cholecystitis is an argument in favor of the metaplasia-dysplasia-neoplasia sequence and justifies recent recommendations for the performing of colecystectomy.
Keywords: chronic cholecystitis, hyperplasia, metaplasia, dysplasia, gallbladder carcinoma.
Abstract. Cutaneous melanomas has become one of the most discussed and studied tumor because its particular immunologic development but also its increasing rate worldwide in the last decades. Even thought many patients are diagnosed at an early stage, the death rate continues to rise due to the increasing incidence of more advanced lesions. The aim of this study is to detect apoptosis in 30 cases of cutaneous melanomas using the in situ end-labeling technique (TUNEL) who quantify apoptotic cell death at single cell level and tissues.
Keywords: apoptotic index (AI), cutaneous melanomas.
Abstract. Aim. To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CRC). Methods. A number of 507 CRC, surgical specimens, were analyzed, 12 cases (1.97%) being ACC. In 20 cases from left and right colon (CRC) and in the 12 ACC we analyzed the immunohistochemical parameters related to angiogenesis, utilizing the following LabVision antibodies: CD31, CD105 (endoglin) and VEGF1. Morphometrical analysis and positive cell counting were performed in the tumoral and peritumoral tissue. Immunoperoxidase method was used. Results. The average age was 63.17 +/- 10.87 years in CRC, respectively 57.9 +/- 10.05 years in the ACC (p<0.0001). Compared with CRC the ACC occur more frequently at the females (58%). Angiogenesis was expressed in the majority of cases. In CRC, the microvascular density (MVD) was higher than that from ACC. The ratio CD31/CD105 was 1 in ACC and 3 in CRC. VEGF was positive in 25% of ACC and 80% of CRC. In CRC were more mature vessels, marked only with CD31 than immature vessels or endothelial isolated cells marked with both CD31 and CD105. In ACC prevailed the neoformed vessels marked with both CD31 and CD105. Conclusions. The performed assessments have showed a higher incidence of ACC at females and at younger ages. The angiogenesis in ACC was not so high like in CRC and the immature neoformed vessels was more frequently. In ACC, the antiangiogenic treatment that regards the VEGF inhibition seems to be not as efficient as in CRC. The radiotherapy could stop the angiogenesis and could inhibit the vessels' maturation.
Keywords: angiogenesis, anal canal carcinoma, immunohistochemistry.
Abstract. The venous system anatomy of the lower limbs and especially its functionality still presents half-lighted areas, fact easily qualified as incredible for the third millennium. Our dissections on fresh amputation segments, methylene blue injected in superficial veins or in deeper veins pointed out that venous circulation is much more complex than it seemed, that there are subdermal collectors connected to the saphene trunks which permit bidirectional transfer of blood mass to saphene venous roots or to derm. The dermal plexus has also a complex connection with the deep venous system by Delater perforators, by perforators, which drain saphene systems after having previously received dermal affluents, and by Delater equivalences (submillimetric perforators) that provide blood mass transfer from deep to surface under the conditions of a moderate and temporary venous hypertension. High- and long-term venous hypertension determines the valvular device deterioration of classical perforators making possible a pathological bi-directional flow.
Keywords: superficial veins, deep veins, "compartment", perforators, Delater-like.
Abstract. Background. Systemic sclerosis or scleroderma is a rare collagen disease, characterized by insufficient angiogenesis. Few data are available about the morphologic and histochemical peculiarities of the skin in these patients with this condition. The purpose of the present work was to evaluate the histochemical aspects of sclerodermic skin, obtained through biopsy of the typical lesions from the forearm skin. Patients and methods. The study was conducted on 31 patients, from which skin biopsies were obtained, after informed consent. The specimens were fixed in buffer formalin, embedded in paraffin and processed for staining with HE, Masson, Orcein, Gordon-Sweet silver staining, and Alcian blue-Safranin, in order to identify elastic fibers, reticular fibers, glycosaminoglycans and mast cells. Results are partially similar to other studies: the constant depletion of elastic fibers in the papillary dermis and disorders of the network in the reticular dermis, such as their absence in the skin blood vessels walls. The reticular fibers were absent in the papillary dermis, the reaction in the reticular dermis structure was variable from a case to another. The staining with Alcian blue-Safranin proved that there is a gathering of glycosaminoglycans in the superficial papillary dermis, the heterogeneity of collagen fibers and the decrease of mast cells in the dermis.
Keywords: scleroderma, skin biopsy, elastic fibers, reticular fibers, mast cells.
Abstract. Infracranial nonmetric variations have been considered for determining population distance between different regions and continents, in recent times. We studied different infracranial nonmetric traits from the Dakshina Kannada (South India) region to compare with the data available from the Gujarati (North India) region. The mean measure of divergence between the two different geographic regions showed significant variation. In our study, the incidence like i) Allen's fossa of the femur, ii) plaque formation in the upper end of the femur, iii) exostosis in trochanteric fosse of femur, iv) third trochanter of femur, v) os trigonum of talus, vi) medial talar facet, vii) peroneal tubercle of calcaneus, viii) bipartite transverse foramen in the cervical vertebra, too showed significant side difference.
Keywords: infracranial nonmetric variation, population divergence, geographic region, significance.
Abstract. The early gastric cancer is an endoscopic notion in which gastric cancer is strictly placed to mucosis and submucosis without extensive manifestations. It is the form with favorable prognosis and better survival at 5 and 10 years. Our study tries to systematize the debut forms of early gastric cancer and their association with the lesions with malignisation risk. We also try to evaluate the incidence of endoscopic and histopathologic forms of early gastric cancer found in an internal medicine division. Our study included 435 patients with gastric cancer endoscopic and histologic diagnosed. Statistically, 64.36% were men and 35.64% were women, the mean age 48 +/- 7 years. The endoscopic forms of early gastric cancer were type I: protruded in 19 cases, type II: superficially in eight cases, type III: excavated in six cases. Early gastric cancer is diagnosed with difficulty, it represents in 7.58% of the gastric cancer, being most frequently asymptomatic. The endoscopic forms frequently found in early gastric cancer in the population were type I: protruded and type IIa: superficially elevated. The histopathological examination is compulsory at this form of gastric cancer, while in advanced gastric cancer endoscopy is often sufficient for diagnosis. Analyzing the histopathological results of cases diagnosed with early gastric cancer we found: 22 cases with intestinal type and 11 cases diffuse type. Microscopically, 15 were intramucosal and 18 had submucosal invasion. I and IIa lesions were predominantly located at the antrum and are histologically differentiated adenocarcinoma. Differentiated carcinoma frequently produces an elevated lesion and the border is well demarcated. There are frequent opportunities to detect gastric cancer in the early phase and the patient can expect a complete cure by the surgical operation or endoscopical mucosal resection.
Keywords: early gastric cancer, type I: protruded adenocarcinomas, type IIa: superficially elevated adenocarcinomas, type III: excavated adenocarcinomas, malign lymphomas, stomach sarcomas.
Abstract. Congenital anomalies of the kidney and urinary tract are frequent. They can be detected once every 500 ultrasonography fetal examinations. Causes that determine a dilated ureter compared to the rest of the urinary tract are still partly unknown. If concerning the exploration and the clinical diagnosis of these anomalies important progresses have been made, the morphological research is still able to bring forth data that, together with genetic researches, may help reveal the pathogeny of the disease and may ease the planning of the screening genetic tests for early diagnosis. Material and methods. During the surgical operations realized in order to recalibrate the ureter, ureter fragments have been harvested, colored with 1% tionin, in sections thinner then 1 micron and examinated through immersion, ob. 100x. Other fragments have been prepared and examinated through electronic microscope. We have followed the structural modifications of the muscular tissue, nervous tissue, connective tissue and the rapports between these components. Results. Congenital megaureter presents qualitative and quantitative anomalies of the connective tissue and muscular tissue, and also structural modifications of the nervous tissue. Connective tissue. We have noticed the abundance of the connective tissue in congenital megaureter. Connective tissue, with an important representation of typical elements, such as fibroblasts, mastocytes and plasmocytes is partly hyalinated, dissociating muscular fiber bundles and nervous fiber bundles. Connective tissue/muscular tissue report is evidently increased. Muscular tissue. Muscular fibers are hypoplasic, smooth endoplasmic reticulum is present in the tubular form, rare mitochondria are vacuolized. Dense corps are increased in number, plasmatic membranes are folded. Sarcoplasm contains vacuolized organites. The nuclei are rigged with visible nucleoli. Nervous structures. We have noticed varied alterations of the axons and myelin. In some axons, there are multiple cavities that may produce the opacifiation of the entire axonal structure. The proliferation of the myelin sheath under the nodular form or vortex form produces the destruction of the axonal structure. Mitochondria are condensed, partially vacuolized. The modifications in the axonal structure and those of the myelin sheath determine modifications of the nervous excitability and conductibility. All the lesions we have pointed out in congenital megaureter participate in compromising of the peristaltic. Nervous and muscular structures lesions indicate a process of incomplete development of the ureter. They are structures that do not achieve functional maturation. We may consider congenital megaureter as a digenesis with hypoplasia.
Keywords: congenital megaureter, electronic microscopy, disgenesis, hypoplasia.
Abstract. Bronchial supply plays an important role in both the protecting mechanisms and the pathogenic ones of many chronic inflammatory, infections or ischemic diseases of the lung. However, little is known regarding the bronchial supply development; the appearance of the connections to the functional pulmonary supply; the territory supplied by the bronchial veins. In this study, we follow the distribution of the pulmonary veins branches at the level of the subcarinal airways and their relationship to the bronchial veins in the human lungs. For studying the venous supply of the airways, we used the corrosion and colored gelatin injection methods followed by microdissection by means of an operator microscope. Venous circulation of the intrapulmonary airways is mainly tributary to the pulmonary vein branches. Venous circulation of the extrapulmonary airways is tributary to both the pulmonary and the bronchial veins. Taking into account the difference of sizes, we consider that, under physiologic conditions, the main venous collector is represented by the pulmonary veins.
Keywords: bronchial circulation, pulmonary veins, vascular casting, dissection.
Abstract. Introduction. Mast cells are normal connective tissue residents. Their densities vary from an organ to other, but are constantly well represented in respiratory tract. Mast cell hyperplasia was found in many malignant tumors, but the significance of this phenomenon is still unknown. In the literature, there are few data about mast cell reaction in malignant laryngeal neoplasm. Material and methods. We studied archive blocks from 127 laryngeal carcinomas. For histological diagnosis two sections were prepared for Hematoxylin-Eosin staining and Alcian blue-Safranin histochemistry at pH 0.2 for identifying mast cells. Examination has been performed with Nikon Eclipse 600 microscope. Microscopic images were analyzed with Lucia G program. Microvessel density was calculated using the hot spot method. Results. Most of the cases were squamous cell carcinoma G1 - 24.4%, G2 - 56.69%, G3 - 18.11%, and 0.78% adenoid cystic carcinoma. Invasive squamous cell carcinoma mast cell microdensity was 2.19 and 4.66 in microinvasive squamous cell carcinoma. Mast cell microdensity in malignant laryngeal papillomatosis was 9.33 and 46.66 in adenoid cystic carcinoma. In carcinoma-associated mast cell hyperplasia, the large majority of mast cells were Alcian blue positive. Conclusions. In early stages, the mast cells are numerous (microinvasive squamous cell carcinoma mast cell microdensity 4.66) and rare or even absent in late stages (invasive squamous cell carcinoma mast cell microdensity 2.19). Mast cell microdensity in malignant laryngeal papillomatosis was 9.33 and 46.66 in cystic carcinoma. Alcianophil mast cells are present in tumor area, and safraninophil mast cells are residents of connective and muscular tissue, at a distance from the tumor.
Keywords: carcinoma, larynx, mast cell, Alcian blue-Safranin histochemistry.
Abstract. The eye is a target organ for the action of several topical or systemic drugs. The aim of the present study is to analyze the differences in reactivity between the iris and conjunctiva vessels after the topical administration of histamine and histamine receptor blockers respectively. Using a novel non-invasive technique for the quantification of the vascular diameters in the eye vessels, the response of these vessels to histamine, to H1 receptor blocker promethazine, and to H2 receptor blocker ranitidine versus vehicle (control) was analyzed. The results show differences in reactivity between iris and conjunctiva vascular territories. This data suggest that the population of histamine receptors differs between these two vascular areas.
Keywords: histamine, iris, conjunctiva, H1 receptor blockade, H2 receptor blockade, vascular diameter.
Abstract. Hibernating myocardium represent a prolonged but potentially reversible myocardial contractile dysfunction, an incomplete adaptation caused by chronic myocardial ischemia and persisting at least until blood flow restored. The purpose of this study was to investigate the morphological changes and weather relations exist among function, metabolism and structure in left ventricular hibernating myocardium. Material and methods. Experimental study is making on 12 dogs incomplete coronary obstruction during six weeks for morphologic studies of ischemic zones. On 48 patients with coronary stenosis myocardial biopsies was effectuated during aorto-coronarian bypass graft. On 60 patients with valvular disease associated with segmental coronary atherosclerotic obstructions during surgical interventions on an effectuated repeatedly biopsies from ischemic zones. Dyskinetic ischemic areas was identified by angiography, scintigraphy, low dose dobutamine echography to identify the cells viability. On myocardial biopsies various histological, histoenzymological, immunohistochemical and ultrastructural methods were performed. Results. The morphological cardiomyocytic changes can summarized: loss of myofilaments, accumulation of glycogen, small mitochondria with reversible lesions, decrease of smooth reticulum, absence of T tubules, depression of titin in puncted pattern, loss of cardiotonin, disorganization of cytoskeleton, dispersed nuclear heterochromatin, embryofetal dedifferentiation, and persistence of viability. Extracellular matrix is enlarged with early matrix protein such fibronectin, tenascin, fibroblasts. In experimental material the morphological changes present similarities with the human biopsies, but intermixed with postinfarction scar tissue. Redifferentiation of hibernanting cells end remodeling of extracellular matrix is possible after quigle revascularization through aorto-coronary bypass grafts.
Keywords: hibernating myocardial biopsy, experiment, embryo-fetal dedifferentiation.
Abstract. The authors present the results of optical microscopic studies of some lesions of cartilage and subchondral bone of the knee, the arthroscopy allowing this structure's biopsy during the endoscopic procedures. These histological criteria are very important estimation factors of long term results of these "repair" techniques, the microstructure showing the real biological status of these specific tissues.
Keywords: arthroscopy, biopsy, cartilage, microstructure.
Abstract. Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous tumor with a high rate of recurrence. Nevertheless, it responds to the drug Imatinib. The pathogenic mechanism why this drug works seems to be different to the inhibition of the Kit receptor of tyrosine kinase, since DFSP has repeatedly failed to express CD117 when immunohistochemically tested. Due to previous reports that claimed the presence of CD117 in DFSP, we designed a model of antigen retrieval under extreme conditions with two cases of DFSO from our archives. The slides were kept in the pressure cooker during 15 minutes (pH 9). Moreover, the tissue was incubated with the primary antibody for 60 minutes. Three negative controls were also used. Even after the "over-retrieval" process, no convincing positivity was shown, although high background staining notably increased. We also discuss several alternatives that have been given in literature to explain the mechanism of how Imatinib works in DFSP.
Keywords: CD117, Imatinib, dermatofibrosarcoma protuberans, c-kit, antigen retrieval.
Abstract. Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited genodermatosis, caused by mutations in ATP2A2 gene and ATP2C1 respectively. We investigated clinical and laboratory two patients - a men with Darier disease and a woman with Hailey-Hailey disease. The patient with Darier disease has mucosal lesions and dental modifications associated with mild mental retardation. At Hailey-Hailey case, the skin lesions are associated with neuropsychiatric and endocrinologic disorders. In both cases, the mutation is inherited from parents. Even if this diseases have similar features, clinical, genetical and histopathological they are distinct entities.
Keywords: Darier disease, Hailey-Hailey disease, gene, mutation, acantholysis, skin lesion.
Abstract. During routine osteology demonstration of the posterior cranial fossa we noticed a transverse bony canal in the middle third of the clivus of an adult male skull. The canal was situated 1.8 cm in front the anterior border of the foramen magnum. The length of the canal was 0.6 cm long. The possible embryological basis and clinical significance of the variation was discussed.
Keywords: clival canal, cranial fossa, bony canal, clinical significance.
Abstract. The carcinosarcoma is a malignant mixed Mullerian tumor with a highly malignant, biphasic tumor consisting of both epithelial and mesenchymal components. The presented case refers to a patient in climax with a vaginal bleeding. The Doppler echography highlights a polypoid mass, which prolapses in the cervical channel. The histopathological and immunohistochemical analysis of the surgically resected piece allowed the carcinosarcoma diagnosis. The uterine carcinosarcoma's incidence is rare, that is why this case is interesting taking in consideration the biphasic pattern of the tumor.
Keywords: carcinosarcoma, uterus, malignant mixed mesodermal tumor.
Abstract. Renal inflammatory pseudotumor is uncommon, benign tumor that has been classified into separate group but there is a risk that this lesion could be misdiagnosed. The aim of this work is to report a new case of 57-years-old man presented in our hospital with hematuria, minimal grade fever and right flank pain. Magnetic resonance imaging (MRI) and sonography revealed a tumor of the right mediorenal parenchyma, 2.5 cm in diameter. The patient underwent right nephroureterectomy under the diagnosis of renal cell carcinoma. Macroscopically examination carried out on the removed kidney showed a 2/2/1.5 cm yellowish, gelatinous, well circumscribed, mediorenal and pericaliceal mass. Fragments of the tumor were fixed in 10% formaldehyde, included in paraffin, and the sections were stained with HE, VG and immunohistochemically with vimentin (VIM), MNF116, SyN, smooth muscle actin (ACT), desmin, CD68, S100, HMB45, and CD117. The histological examination revealed a compact spindle cell proliferation, a hypocellular fibrous area in an edematous myxoid background infiltrated by small lymphocytes, histiocytes, some plasma cells and small bone area. The spindle cells were diffuse positive for VIM, ACT, CD68 and negative for desmin, MNF116, SyN, S100, HMB45, and CD117. The pathologic diagnosis was renal inflammatory pseudotumor, raising the problem of differential diagnosis, as the clinical and imagistic aspects are similar to those of a renal carcinoma and the problem in establishing a preoperative correct diagnosis.
Keywords: inflammatory pseudotumor, kidney, immunohistochemistry.
Abstract. Erythrokeratodermia represents a group of rare genetic diseases characterized through disorders of keratinization. Clinically, they are presenting themselves with erythematous and hyperkeratosic lesions that can be persistent or variable as to their aspect and localization. They were classified in erythrokeratodermia variabilis (EKV) and erythrokeratodermia symmetric progressive (EKSP). We are presenting the case of a 9-year-old child which presents from birth facial and perioral erythema; erythematous and hyperkeratosic lesions with circinate character, extremely variable, localized especially on the anterior thorax (on the chest and in the axillar and inguinal folds). The neonatal debut, the clinical and histological aspect are suggestive elements for the EKV. In addition, the child has a plan frontal angioma and a congenital horizontal nistagmus. We realized a review of a literature data being different clinical variants of presentation of EKV and the eventual possible associations. It is considered the fact that the clinical presentation in the presented case corresponds to the variant of EKV with variable circinate erythema described by Bazex and Dupré. The case is also particular through the association of a plan frontal angioma, particularly of a congenital horizontal nistagmus, associations that we could not find in the literature.
Keywords: erythrokeratodermia, dermatosis, erythema.
Abstract. Frequency of drug-induced liver diseases is increasingly, more than 200 different drugs being incriminated in hepatic disorders. We performed a retrospective study on 65 cases of deaths due to drug intoxications and an experimental model of subacute hepatitis induced by acetaminophen. In our experimental model, we observed various histological lesions: granular degeneration, vascular congestion, lymphoplasmocyte infiltration, cytonecrosis. Histological criteria are not specifically, but very usefully, because based on these criteria we can suspect a drug etiology in hepatic disorders when any other cause is absent. Ultrastructural study of hepatocytes revealed some modifications, in addition to data provided by optical microscopy.
Keywords: drug-induced hepatitis, acetaminophen, ultrastructural study.