Vol. 49 No. 1, January-March 2008

1. Diversity of Aβ deposits in the aged brain: a window on molecular heterogeneity?

L. C. Walker, Rebecca F. Rosen, H. LeVine

The Aβ peptide forms a morphologically heterogeneous assortment of aggregates in the brains of patients with Alzheimer's disease. The reasons for the diversity of the histopathologically identified lesions (Aβ-plaques and cerebral Aβ-amyloid angiopathy) are uncertain. However, there is growing evidence for the existence of higher order structural heterogeneity in protein molecules with the same amino acid sequence and differential involvement in disease. Focused analysis of plaque morphotypes could yield novel insights into the organization and function of putative protein variants in the diseased brain. In addition to classical amyloid-selective dyes, new techniques are emerging to undertake such analyses, including selective, small molecule binding agents, specific antibodies, and conformationally sensitive optical probes. By illuminating the relationships between specific lesions and their molecular components, these agents can help to clarify the complex pathology of Alzheimer's disease.

Corresponding author: Lary C. Walker, PhD, e-mail:

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2. Nonalcoholic fatty liver disease and metabolic syndrome: a concise review

Letiția Adela Maria Streba, Doina Cârstea, P. Mitruț, C. C. Vere, Nicoleta Dragomir, C. T. Streba

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological entity increasingly recognized as a major health burden in developed countries. In the last decade, several studies have independently provided evidence for a strong association between NAFLD and each component of the metabolic syndrome, including central obesity, hyperglycemia, dyslipidemia, and hypertension. This article focuses on epidemiological, clinical, pathogenic and therapeutic aspects, which link these two syndromes.

Corresponding author: Letiția Adela Maria Streba, MD, PhD, e-mail:

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3. Molecular bases of hepatic fibrogenesis - genetic and therapeutical implications in chronic viral C hepatitis

I. Rogoveanu, Daniela Larisa Săndulescu, D. I. Gheonea, T. Ciurea, Violeta Comănescu

Hepatitis C virus represents one of the major health problems of actual world, as almost 170 million of world population and 1 million persons in Romania are infected with HCV. Considering the increasing importance of HCV, it is imposed that we elucidate the molecular mechanisms, which are the base of hepatic fibrogenesis and potential targets for therapy, for diminishing progression to cirrhosis and avoid the appearance of complications. Activation of stellate cells is the main event in hepatic fibrosis. They also express almost all key components needed for the pathological degradation of matrix and that is why they play an important role not only in the production, but also in the degradation of the matrix. Recently, the worldwide research has also been oriented towards another type of cells with possible function in fibrogenesis and response to antiviral therapy: hepatic progenitor cells. The presence of hepatic progenitor cells in chronic C viral hepatitis is associated with severity of the disease, grade of fibrosis and the risk of hepatocarcinoma. Traditionally perceived as irreversible, reversibility of advanced fibrosis has been described recently in antiviral therapy trials for chronic C viral hepatitis. The favorable effect of interferon therapy on hepatic histology, including fibrosis, has been shown even in patients without sustained virusological response. During the last years, the advantages of the so-called support therapy using interferon have been demonstrated in patients with an increased rate in progression of fibrosis. Further research of the factors associated with progression of fibrosis will allow optimization of criteria for patient's antiviral therapy.

Corresponding author: Ion Rogoveanu, MD, PhD, e�?�­mail:

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4. The article has been retracted

The article has been retracted

The article has been retracted

Corresponding author: The article has been retracted

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5. Immunohistochemical expression of vascular endothelial growth factor (VEGF) in intestinal type gastric carcinoma

M. Raica, L. Mogoantă, Anca Maria Cîmpean, Aurora Alexa, S. Ioanovici, Cl. Mărgăritescu, Daniela Lazăr, D. Izvernariu

Background. Gastric cancer still represents a difficult problem in the field of oncology, in terms of morbidity and mortality. The local progression and systemic spread is significantly influenced by tumor angiogenesis and lymphangiogenesis. In spite of many studies on the topic, data about the significance of growth factors in gastric cancer is controversial. Aim: to investigate the immunohistochemical expression of VEGF and to evaluate the relationships with the tumors stage and grade. Material and methods. The immunohistochemical expression of VEGF was investigated on 80 patients with intestinal type gastric carcinoma. Specimens were fixed in buffer formalin, embedded in paraffin, and sections were stained with Hematoxylin-Eosin and immunohistochemistry was performed for VEGF (clone VG-1). Evaluation was performed using the VEGF score, based on the intensity of reaction and percent of positive cells. Results. The reaction for VEGF was positive in 52 from 80 cases (70%). The final product of reaction was found in the cytoplasm of tumor cells, with granular pattern. Positive reaction was also found in eight from 28 cases with associated intestinal metaplasia, and in six from nine cases with gastric dysplasia. In the adjacent apparently normal mucosa, the reaction was positive in hyperplastic gastric pits and parietal cells. A strong correlation was found between VEGF expression and lymph node status and grade of the primary, but not with the stage of the tumor. Conclusions. The investigation of the immunohistochemical expression of VEGF in the intestinal type of gastric carcinoma showed positive reaction in 70% of the cases. It was demonstrated the expression of VEGF in intestinal metaplasia and gastric dysplasia, which could signify an early angiogenic switch during tumorigenesis.

Corresponding author: Marius Raica, MD, PhD, e-mail:

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6. Morphometry of posterior cerebral artery: embryological and clinical significance

A. Krishnamurthy, S. R. Nayak, C. Ganesh Kumar, Raghu Jetti, Latha V. Prabhu, Anu V. Ranade, Rajalakshmi Rai

Posterior cerebral artery, terminal branch of basilar artery joins the posterior communicating artery to help complete the circulus arteriosus cerebri in human beings. A study of 89 formalin-fixed brain specimen of either sex and of Indian origin has showed that the mean length and diameter of the posterior cerebral artery was 6.75+/-1.482 mm and 1.7+/-0.7 mm respectively. Anomalous origin of the posterior cerebral artery was the only variation found during the present study. The incidence of occurrence of the particular variant was 2.2%. The variation did not have any sex or side predilection.

Corresponding author: Ashwin Krishnamurthy, MD, PhD, e-mail:

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7. Morphopathological changes induced by the Obstetrical Antiphospholipid Antibody Syndrome in fetal adnexa and uterus

Sabina Berceanu, Anca Pătraşcu, C. Berceanu, A. A. Tica, Adriana Bădulescu, M. B. Brăila, Cristiana Simionescu

The Obstetrical Antiphospholipid Antibody Syndrome (OAAS) is representing a separate entity of the global Antiphospholipid Antibody Syndrome (APS), focusing the pregnancy morbidity. OAAS is generating morphopathological changes in almost all components of the gestational biologic transitory system (GBTS): placenta, umbilical cord or uterine wall. The most important, serious and lengthened anomalies are occurring in placenta. Our research has been developed on a group of 68 patients diagnosed with OAAS, initially using the Sapporo criteria and later using the 'Sydney' ones. There have been morphopathologically examined: placenta, umbilical cord and myometrium. Histological examination revealed on one hand macroscopic modifications: fibrinoid deposits, white or red placental infarctions, intervillous thrombosis, marginal or basal decidual hematoma, calcareous deposits, umbilical cord thrombosis, and on the other hand microscopic findings: placental infarction, fibrinoid necrosis, myometrial thrombosis, degenerative myometrial disorders, focal myometrial necrosis, villous stasis and necrosis, umbilical cord thrombosis. Because of the increased prothrombotic background, in APS, any vessel or organ could be involved, with no exception for GBTS elements. The basis of the pregnancy morbidity from the obstetrical APS is represented by the morphopathological changes occurring in fetal adnexa and uterine structures.

Corresponding author: Sabina Berceanu, MD, PhD, e-mail:

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8. Particularities of vascular reactivity of the conjunctiva and iris in rats

Oana Andreia Coman, Brânduşa Tăranu, Isabel Ghiță Cristescu, I. Fulga

Considering that the conjunctiva and iris are developed from different embryological origins, an analysis of any possible differences in the density and type of adrenoceptors between these two areas was tried. An experimental study on male adult Wistar rats was performed. Six groups (six rats per group) were used by recording the iris and conjunctival vessels after eye instillations with solutions of adrenaline 0.1%, isoprenaline chlorhydrate 0.00002% and distilled water. The image analyze were carried out using VirtualDub 1.5.1 and Adobe PhotoShop 6.0, measuring the variations of the vessels diameters before and after the solutions instillations at fixed time intervals. The means of each eye values were compared with the control value using a statistical significance T test. The analysis of the two groups treated with adrenaline 0.1% showed a different reactivity of the vessels from the conjunctiva and iris, respectively. The iris vessels performed a gradual vasoconstriction. On the contrary, the conjunctival vessels showed initially mild, but significant vasodilatation, while vasoconstriction started later and was not as intense as for the iris vessels. The iris vessels treated with isoprenaline 0.00002% showed no significant changes in the vascular diameters. On the contrary, the conjunctival vessels showed a significant vasodilatation. The differences in the vascular reactivity of the two ocular areas (conjunctiva and iris) to vasoactive amines (epinephrine, isoprenaline) support the idea that beta 2 adrenergic receptors are present only in conjunctiva vessels but not in iris vessels, while alpha adrenoceptors are present in both vascular territories.

Corresponding author: Oana Andreia Coman, MD, PhD, e-mail:

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9. Enteric nervous system development in cavitary viscera allocated to the celiac plexus

Alina Maria Sişu, Codruța Ileana Petrescu, C. C. Cebzan, M. C. Niculescu, V. Niculescu, P. L. Matusz, M. C. Rusu

Enteric nervous system (ENS) is a network made of neuronal cells and nervous fibers. There are two plexuses: myenteric of Auerbach and sub mucous of Meissner and Henle. Many substances are involved in neurotransmission at ENS level. ENS assures all gastrointestinal system functions: digestion, absorption, etc. Our study is made on 23 human fetal specimens at different ages of evolution with crown-rump lengths from 9 to 28 cm, and three new born human specimens. We used the Trichrome Masson stain technique and the argental impregnation Bielschowsky on block technique for microscopic evidence. Our study concerned the cavitary viscera allocated to the celiac plexus, involving all layers of each studied viscera.

Corresponding author: Alina Maria şişu, MD, PhD, e-mail:

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10. Management of second branchial cleft anomalies

Mihaela Mitroi, Daniela Dumitrescu, Cristiana Simionescu, Camelia Popescu, Carmen Mogoantă, Luminiț a Cioroianu, C. Surlin, Alina Căpitănescu, Monica Georgescu

Branchial cleft anomalies are developmental disorders of the neck. The aim of this study was to evaluate the data of our patients, who have been diagnosed and treated for second branchial abnormalities in the last six years. We report our clinical experience in second branchial anomalies with a review of the literature. Our study is a retrospective one on a number of 23 patients hospitalized within 2001-2007 in ENT Clinic of Craiova for second branchial abnormalities in relation with age, gender, origin environment, clinical and paraclinical context in which the therapeutic decision was made, surgical procedures, post-surgical evolution. Among the anomalies of the second branchial arch, we encountered 10 (43.47%) patients with branchial cyst and 13 (56.52%) patients with branchial sinus. Twelve (52.17%) of the 23 patients were women and 11 (47.83%) were men; 9 (39.13%) patients were diagnosed and treated within the first age decade, seven (30.43%) within the second age decade, five (39.13%) within the third age decade and two (8.71%) in the fourth age decade. Histological examination of the lesions after excision established the diagnosis in all the cases. Second branchial arches anomalies are the most common branchial anomalies. Sinuses are more frequently than cysts and branchial fistulae are extremely rare. There is no gender predilection. The majority of patients (approximately 70%) were diagnosed and treated during their childhood. Treatment for these lesions is complete surgical excision for prevent recurrences.

Corresponding author: Mihaela Mitroi, MD, PhD, e-mail:

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11. Glomerulopathies in locked-up persons. Histopathologic and clinic study

D. Gh. Mălăescu, M. Motocu, Letiția Adela Maria Streba, Adriana Bold, C. C. Vere

The diseases of the urinary apparatus are frequently-enough inside the locked-up spaces of the penitentiaries. Among them, glomerulonephritis and pyelonephritis take a special place, by their late diagnosis and their lasting evolution. The authors clinically and paraclinically investigated a number of 214 locked-up male persons aged between 18-57 years, presenting various clinical forms of glomerulonephritis. Histopathological exams performed in 51 patients confirmed the diagnosis.

Corresponding author: Dan Gheorghe Mălăescu, MD, e-mail:

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12. Dendritic cell component in fetal dermatitis

A. Fernandez-Flores

Fetal dermatitis (FD) has been proposed as the cutaneous counterpart of chorioamnionitis. One of its main characteristics is the expression by the inflammatory cells of Toll-like receptors (TLR). Antigen-presenter cells, such as histiocytes, neutrophils and dendritic cells usually express the latter. Histiocytes as well as neutrophils have been demonstrated in the inflammatory infiltrate of FD, but no studies have been performed about dendritic cells. Our objective is to study the population of dendritic cells in cases of FD. We have studied three cases of FD by immunohistochemistry with CD1a antibody. Dendritic cells were present in the dermis as well as in the epidermis of all the cases of FD. Nevertheless, they did not seem to be greater in number from what is considered as normal in a dermis without inflammation. Although our results are not incompatible with a main role of dendritic cells in FD, at least such a role would be plaid without an increase in the number of dendritic cells.

Corresponding author: Angel Fernandez-Flores, MD, PhD, e-mail:

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13. Giant intracranial endolymphatic sac tumor (ELST). Case presentation and histogenetic considerations

D. Arsene, Alina Georgescu, L. Dănăilă, Carmen Ardeleanu

We present a giant tumor of the skull base compressing the brain in a 40-year-old man. The tumor was policystic at imaging. Its histopathology, immunohistochemical profile and long evolution suggest an endolymphatic sac tumor (ELST), a rare case of neoplasia. Since the patient had multiple otolaryngological procedures in his medical history, a possible traumatic pathogenesis could be suspected. On the other way, some immunohistochemical aspects found in our case may imply a histogenesis divergent from that currently accepted. This could be from either the organ of Corti or some local cells that generate a resemblance with a systemic tumor, the so-called benign mesothelioma. Further studies are needed in order to clarify this topic.

Corresponding author: Dorel Arsene, MD, PhD, e-mail:

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14. Metastasized squamous cell carcinoma developed on lupus vulgaris

V. Pătraşcu, Claudia Valentina Georgescu, Loredana Elena Tănase, S. S. Mogoantă

Lupus vulgaris (LV) is the most frequent cutaneous tuberculosis, representing more than 55% of the tuberculoses with this location. Malignization can occur after a long latency (10-30 years), in 1-2% of the cases, and it is mainly in squamous cell carcinoma. The histological exam is highly important in the observation of neoplasic transformations. The authors present a 59-year-old female patient, from the rural environment, working as a farmer, with lupus vulgaris developing since her first childhood years. It started at the age of 2 years, at the right ear lobule, after the empiric perforation for earrings. The evolution was progressive, eccentric, interesting the pinna and the right cheek in the meanwhile. At the first examination, in 2002, a diffuse mass of red-yellowish infiltration was found at the level of the right ear and the right cheek. In the following two years, an ulcero-vegetating tumor developed at the level of the right ear lobule, accompanied by the presence of a right retromandibular adenopathy, of about 1 cm, which was proved by the histopathologic exam to be a squamous cell carcinoma developed from a lupus vulgaris. After scraping out the right retromandibular ganglion, detected by palpation, a histological exam showed ganglion metastasis.

Corresponding author: Virgil Pătraşcu, MD, PhD, e-mail:

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15. Multiple variations of the extensor tendons of the forearm

S. R. Nayak, A. Krishnamurthy, Mangala M. Pai, Latha V. Prabhu, Lakshmi A. Ramanathan, C. Ganesh Kumar, Merin M. Thomas

Anatomic variations of the extensor tendons of the forearm are frequent and its knowledge is important to assess the diseased and traumatized hand. During routine cadaveric dissection in the Department of Anatomy, Kasturba Medical College, Mangalore, India, we came across unusual variations in the left upper limb of a 51-year-old male cadaver. The variants are, the complete absence of the extensor pollicis brevis (EPB), the abductor pollicis longus (APL) having six slips of insertion with additional muscle slip from the brachio-radialis (BR). The extensor digitorum communis (EDC) had five tendon slips, the extra tendon splits close to the metacarpo-phalangeal (MP) joint and contribute to the tendons of the ring and little fingers. The number of accessory tendons of APL has functional significance in the development of de Quervain's stenosing tendovaginitis. The present case is unique in the sense that, all the three variations are present in the ipsilateral upper limb. The occurrence of these anomalies and its clinical and embryological significance are discussed.

Corresponding author: Soubhagya Ranjan Nayak, PhD, e-mail:

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16. Electron microscopic study of the arterial wall in the cerebral aneurysms

F. Drăghia, Alina Cătălina Drăghia, Doina Onicescu

The ultrastructural modifications were observed in electron microscopy of the congenital aneurysm of the internal carotid artery with subarachnoid hemorrhage. The tunica intima very enlarged contains in the endothelial cells numerous microvesicles of pinocytosis, and rare cell organelles. The internal elastic lamina presented ruptured or absence zones. The luminal face of the cells appeared irregular with large evaginations and deep and narrow invaginations. Under the endothelial lining, large masses of extracellular matrix with different degrees of edema, and fragmented collagen fibrils realize a metabolic barrier between the tunica intima and media. The muscle fibers of the tunica media and the myofilaments in each myocyte are in reduced number.

Corresponding author: Florin Drăghia, MD, PhD, e-mail:

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17. Spermatic cord mixed liposarcoma. Case report and review of the literature

I. Domşa, C. D. Olinici, Doinița Crişan

A 75-year-old man presented with a clinical diagnosis of hydrocele. Grossly examination revealed a large (14x8x9 cm) tumor. Histologically, the tumor had a mixed pattern, with major pleomorphic and a minor sclerosing well-differentiated component. The anatomo-clinical features, the prognosis and the principles of treatment of this rare condition are shortly discussed.

Corresponding author: Corneliu Dorin Olinici, MD, PhD, e-mail:

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18. Neural granular cell tumor. A case report

C. Suciu, Anca Maria Cîmpean, M. Raica

It is presented the case of an old female with a solitary tumor at the level of the thorax. The specimen was processed using the routine histological technique and slides were stained with conventional morphologic, histochemical and immunohistochemical methods. On Hematoxylin-Eosin stained slides were noticed large cells with acidophilic cytoplasm, with granular pattern. S100 protein was intensely expressed in all tumor cells and neuron specific enolase was moderate positive. CD68 positive reaction was considered the expression of lysosomes accumulation in the cytoplasm of tumor cells. Histological and immunohistochemical findings are consistent with the diagnosis of neural granular cell tumor.

Corresponding author: Cristian Suciu, MD, e-mail:

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19. Charcot-Marie-Tooth disease

Elena Buteică, Eugenia Roşulescu, B. Stănoiu, F. Burada, Cosmina Stănoiu, Mihaela Zăvăleanu

Charcot-Marie-Tooth (CMT) disease is a group of genetic peripheral neuropathies that is associated with a broad variety of clinical genetic features. Most CMT syndromes are characterized by a progressive muscle weakness and atrophy with a distally pronounced sensory dysfunction. Bone deformities as pes cavus or hammertoes are frequent. The severity of disability varies considerably between different subclasses. Physical examination, electrophysiological testing and family history are current methods to investigate a patient affected by CMT. We used these methods for clinical assessment of two cases. Whenever available molecular genetic testing establishes the certain diagnosis and defines the type of CMT.

Corresponding author: Elena Buteică, PhD, e-mail:

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20. Judah Folkman (February 24, 1933 - January 14, 2008)

M. Raica, Anca Maria Cîmpean


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21. Correlations among the serum levels of some interleukins and the histopathological aspects in chronic viral hepatitis C

Carmen Silvia Avrămescu, Violeta Comănescu, S. N. Popescu, Adriana Turculeanu, Maria Bălăşoiu, Carmen Florina Popescu, Mariana Lungulescu

Premises and objectives. The evolution of the infection with the hepatic virus C depends on the defense of the organism, found under the control of a network of cytokines and chemokines. The mechanisms that are causing both viral persistence as well as hepatic pathology are not entirely elucidated. We have proposed to study the amount in which different categories of cytokines are incriminated in the pathogenesis of the chronic liver disease, as well as the eventual correlations between the serum levels of these cytokines and certain histopathological aspects in the chronic viral hepatitis C. Patients and methods. Thirty-five patients with chronic viral hepatitis C (persistent - nine, active - 15, cirrhosis - 11) have been studied, constituting group P, and 20 healthy subjects constituting the reference group (R). In both groups have been determined the serum concentrations of some proinflammatory interleukins (TNF-alpha, IL-6, IL-8), and antiinflammatory (IL-10) cytokines, through the immunoenzymatic technique ELISA. Results. For the proinflammatory cytokines taken into consideration (TNF-alpha, IL-6, IL-8) increased serum values have been determined to the patients with chronic hepatitis C, the maximal level being observed to the patients active chronic hepatitis and cirrhosis (24/35 patients - 68.57%, 19/35 patients - 54.28% and, namely, 18/35 patients - 51.42%). The serum values of IL-10 are increased in 19/35 patients - 54.28%. The direct relationship among the increased levels of IL-10, the astringency of the inflammation and the hepatic functional insufficiency has been taken into consideration. Conclusions. The immune cellular answer has a fundamental role in the pathogenesis of the liver disease in the patients with chronic viral hepatitis C. The disequilibrium between the pro- and antiinflammatory cytokines participates to the installation of hepatic lesions of cytolysis and/or to the progression of fibrosis. The serum concentrations of the studied cytokines (TNF-alpha, IL-6, IL-8 and IL-10) are correlated to the histopathological spoilages of the liver.

Corresponding author: Carmen Silvia Avrămescu, MD, PhD, e-mail:

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