Expression of stromal elements of prostatic adenocarcinoma in different gleason scores

Abstract Purpose: To quantify and compare the expression of stromal elements in prostate adenocarcinoma of different Gleason scores with non-tumor area (control). Methods: We obtained 132 specimens from samples of prostate peripheral and transition zone. We analyzed the following elements of the extracellular matrix: collagen fibers, elastic system, smooth muscle fibers and blood vessels. The tumor area and non-tumor area (control) of the TMA (tissue microarray) were photographed and analyzed using the ImageJ software. Results: The comparison between the tumor area and the non-tumor area showed significant differences between stromal prostate elements. There was an increase of collagen fibers in the tumor area, mainly in Gleason 7. Elastic system fibers showed similar result, also from the Gleason 7. Blood vessels showed a significant increase occurred in all analyzed groups. The muscle fibers exhibited a different behavior, with a decrease in relation to the tumor area. Conclusions: There is a significant difference between the extracellular matrix in prostate cancer compared to the non-tumor area (control) especially in Gleason 7. Important modifications of the prostatic stromal elements strongly correlate with different Gleason scores and can contribute to predict the pathological staging of prostate cancer.

The effect of different flushing methods in a short peripheral catheter

Abstract Purpose To develop a rabbit model of a short peripheral catheter (SPC) and to observe the effects of different flushing methods on blood vessels. Methods Thirty rabbits were randomly divided into three groups (A, B, and C), with ten rabbits per group. In group A, we used pulsed flush; in group B, we used uniform flush; and no treatment was used in group C. Results We observed that a uniform flush reduced blockage, phlebitis, and exudation compared to a pulsed flush by visual observation. The histopathological examination found that the morphological changes in group A were more severe than in group B and C related to loss of venous endothelial cells, inflammatory cell infiltration, edema, epidermal and chondrocyte degeneration, except for the thrombosis on group B that was more serious than in group A, especially in the distal side of puncture points. The distal region of groups A and B had more inflammatory cell infiltration than the proximal region. Thrombosis was more severe in the distal region than in the proximal region in group B. Conclusions The uniform flush produced less damage to the vascular endothelium and surrounding tissues and was superior to the pulsed flush. However, the uniform flush is prone to thrombosis.

Comparison of two soft tissue substitutes for the treatment of gingival recession defects: an animal histological study

Abstract Objectives: This study aimed to compare two different soft tissue replacement grafts in their ability to treat gingival recession defects and successfully integrate with the surrounding tissues. Methodology: Nine beagle dogs were included and followed up to 10 weeks. Sites for intervention were allocated to one of the grafting materials investigated. Treatment consisted of coronally advanced flap combined with one of the two soft tissue substitutes on a previous surgically created defect. Materials employed were porcine-derived acellular dermal matrix (ADM) [Novomatrix™ (Test)] and collagen-based matrix (CBM) [Mucograft® (Control)]. Animals were sacrificed at 2, 6, and 10 weeks postoperatively and compared using descriptive histology and histomorphometric outcomes. Results: Macroscopic findings were similar between test and control groups at all intervals. After 10 weeks, both groups demonstrated successful incorporation of the grafting materials without signs of rejection and with comparable tissue integration. The histomorphometric data were similar between groups at 2 weeks; however, the test group provided greater root coverage and increase in tissue thickness than the control at 6- and 10-weeks post surgically. Conclusions: Both porcine-derived ADM and CBM revealed similar histological outcomes with successful integration and absence of adverse events. Test group provided superior outcomes regarding root coverage and increase in tissue thickness.

Intravascular large B-cell lymphoma: The Great Imitator

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma with an estimated incidence of less than one per million. Unlike other hematopoietic malignancies, lymphadenopathy and hepatosplenomegaly are uncommon, and patients typically present with nonspecific symptoms. IVLBCL presents a diagnostic challenge and patients are usually diagnosed late in the disease course, if at all, and the prognosis is poor. The differential diagnosis is broad, and physicians often pursue multiple diagnostic possibilities during patient workup. We present a case of IVLBCL discovered at autopsy in an 80-year-old male who presented with history and symptoms pointing to the tick-borne illness ehrlichiosis.

Epidemiological profile and findings found intra operatively of glioblastoma at the neurosurgery service of Santa Casa of Ribeirão Preto Hospital - SP - Brazil / Perfil epidemiológico y hallazgos intraoperatorios de los glioblastomas en el servicio de neurocirurgia del Hospital Santa Casa de Ribeirão Preto - SP - Brasil

Introducción: El Glioblastoma (GB) o Astrocitoma grado IV (OMS), representan 15-20 por ciento de los tumores del SNC y aproximadamente 50 por ciento de los gliomas en adultos. Objetivo: Revelar el perfil epidemiológico del HSCMRP, correlacionar los hallazgos macroscópicos y microscópicos durante la cirugía de enero de 2011 a noviembre de 2015. Método: Estudio epimedeológico observacional, descriptivo, retrospectivo, 429 casos de tumores intracraneales a partir de los datos obtenidos de los archivos de La institución y los registros patológicos de los pacientes tratados quirúrgicamente. Resultados: Tumores encontrados 429 y 96 (22,37 por ciento) GB, edad media de 59 años, predominante séptima década 33 por ciento. Una relación entre mujeres y hombres fue de 1:1.12, respectivamente. Las quejas más frecuentes: dolor de cabeza (58 por ciento), confusión (41 por ciento), hemiparesia 37 por ciento. Comorbilidades frecuentes: hipertensión (64 por ciento), diabetes (22 por ciento) y fumadores (24 por ciento). La topografía más común fue la frente izquierdo. El tiempo medio de inicio de los síntomas a la cirugía fue de 39 días. Resección completa en 76 por ciento de los casos. La duración media de la recurrencia fue de 96 días, en 68% de los pacientes se observó una exuberancia de los vasos trombosados durante la cirugía Hallazgos patológicos: necrosis 98 por ciento, mitosis atípica 96 por ciento, proliferación microvascular 73 por ciento y polimorfismo nuclear 57 por ciento. Discusión: GB estado del arte. Conclusión: Nuestros resultados son similares con la literatura. Observación intraoperatoria de vasos trombosados y agresividad tumoral en pacientes con peor pronóstico y menor tiempo de recaída sugiere que es real, sin embargo. El pequeño número de casos, necesita más investigación, incluyendo otros hallazgos y resultados inmunohistoquímicos.

Introduction: Glioblastoma (GB) or Astrocytoma grade IV (WHO), represent 15-20 percent of CNS tumors and approximately 50 percent of gliomas in adults. Objective: Reveal the epidemiological profile of HSCMRP, correlate macroscopic and microscopic findings during surgery treated from January 2011 to November 2015. Method: Observational epidemiological study, descriptive, retrospective, of medical records of 429 cases of intracranial tumors from data obtained from the files of the institution and pathological records of patients treated surgically. Results: Total tumors found 429 and 96 (22.37 percent) GB with a mean age of 59 years, predominant seventh decade of life 33 percent. A relationship between women and men was with little difference 1:1.12, respectively. The most common complaints were headache (58 percent), confusion (41 percent), hemiparesis 37 percent. Most prevalent comorbidities: hypertension (64 percent) and diabetes (22 percent) and smokers (24 percent). Most common topography were followed by left front lesions. The average time of onset of symptoms to surgery was 39 days. Complete resection in 76 percent of cases. The mean length of postoperative recurrence was 96 days, in 68 percent patients were noticed an exuberance of thrombosed vessels during surgery. Pathological findings: necrosis 98%, atypical mitosis 96%, microvascular proliferation 73 percent and nuclear polymorphism 57 percent. Discussion: GB state of art. Conclusion: Our results are very slightly with the literature. The association of intraoperative observation thrombosed vessels, and tumor aggressiveness in patients with worse prognosis and shorter time to relapse, suggests that it is real, however, the small number of cases, needs further investigation, including other findings and immunohistochemical results.

Vasculopatia livedóide: a propósito de um caso clínico / Livedoid vasculopathy: a clinical case proposition

A vasculopatia livedóide é uma dermatose crônica oclusiva dos vasos sanguíneos da derme, de caráter pauci-inflamatório ou não inflamatório, extremamente dolorosa. A etiologia não é totalmente esclarecida; estando associada a eventos pró-trombóticos. Caracterizada pela presença de lesões maculopapulares, eritêmato-purpúricas, nos membros inferiores, especialmente nos tornozelos e pés que ulceram gerando cicatrizes atróficas, denominadas atrofia branca. A histopatologia evidencia oclusão dos vasos da derme, devido à deposição de fibrina intravascular e presença de trombo intraluminal, além de hialinização segmentar e proliferação endotelial, há também, um infiltrado inflamatório perivascular discreto. Descrevemos um caso de vasculopatia livedóide evidenciando os achados histopatológicos encontrados na biópsia. (AU)

Livedoid vasculopathy is a chronic occlusive vasculopathy dermatosis, with a pauciinflammatory or noninflammatory characteristic, and is extremely painful. Its ethiology is not entirely known, being associated with pro-thrombotic events. Characterized by erythematous purpuric maculopapular lesions on the legs, especially on the ankles and feet, that ulcerates and heals with white atrophic scars, named atrophie blanche. Histopathology shows occlusion of dermal vases, segmental hyalinization and endothelial proliferation; there is also a discreet perivascular inflammatory infiltrate. We describe a case of livedoid vasculopathy showing the histopathological findings on the biopsy. (AU)

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

Inflammatory response of human dental pulp to at-home and in-office tooth bleaching

ABSTRACT Tooth bleaching is a technique of choice to obtain a harmonious smile, but bleaching agents may damage the dental pulp. Objective: This study evaluated the inflammatory responses of human dental pulp after the use of two bleaching techniques. Material and Methods: Pulp samples were collected from human third molars extracted for orthodontic reasons and divided into three groups: control - no tooth bleaching (CG) (n=7); at-home bleaching with 15% carbamide peroxide (AH) (n = 10), and in-office bleaching with 38% hydrogen peroxide (IO) (n=12). Pulps were removed and stained with hematoxylin-eosin for microscopic analysis of inflammation intensity, collagen degradation, and pulp tissue organization. Immunohistochemistry was used to detect mast cells (tryptase+), blood vessels (CD31+), and macrophages (CD68+). Chi-square, Kruskal-Wallis, and Mann Whitney tests were used for statistical analysis. The level of significance was set at p<.05. Results: The inflammation intensity and the number of macrophages were significantly greater in IO than in AH and CG (p<0.05). The results of CD31+ (blood vessels per mm2) were similar in CG (61.39±20.03), AH (52.29±27.62), and IO (57.43±8.69) groups (p>0.05). No mast cells were found in the pulp samples analyzed. Conclusion: In-office bleaching with 38% hydrogen peroxide resulted in more intense inflammation, higher macrophages migration, and greater pulp damage then at-home bleaching with 15% carbamide peroxide, however, these bleaching techniques did not induce migration of mast cells and increased the number of blood vessels.

Vascular structures in dermoscopy

AbstractDermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature.

Heart rate turbulence analysis in female patients with fibromyalgia

OBJECTIVE: Fibromyalgia is characterized by diffuse musculoskeletal pain and discomfort. There are several reports regarding autonomic nervous system dysfunction in patients with fibromyalgia. Heart rate turbulence is expressed as ventriculophasic sinus arrhythmia and has been considered to reflect cardiac autonomic activity. Heart rate turbulence has been shown to be an independent and powerful predictor of sudden cardiac death in various cardiac abnormalities. The aim of this study is to determine whether heart rate turbulence is changed in female patients with fibromyalgia compared with healthy controls. METHODS: Thirty-seven female patients (mean age, 40±11 years) with fibromyalgia, and 35 age- and sex-matched healthy female control subjects (mean age, 42±9 years) were included. Twenty-four hours of ambulatory electrocardiography recordings were collected for all subjects, and turbulence onset and turbulence slope values were automatically calculated. RESULTS: The baseline clinical characteristics of the two groups were similar. There were no significant differences in turbulence onset and turbulence slope measures between patients and control subjects (turbulence onset: −1.648±1.568% vs. −1.582±1.436%, p ϝ 0.853; turbulence slope: 12.933±5.693 ms/RR vs. 13.639±2.505 ms/RR, p ϝ 0.508). Although body mass index was negatively correlated with turbulence slope (r ϝ −0.258, p ϝ 0.046), no significant correlation was found between body mass index and turbulence onset (r ϝ 0.228, p ϝ 0.054). CONCLUSION: To the best of our knowledge, this is the first study to evaluate heart rate turbulence in patients with fibromyalgia. It appears that heart rate turbulence parameters reflecting cardiac autonomic activity are not changed in female patients with fibromyalgia. .

Exuberant Vasculoconnective Component in Mediastinal Mixed Germ Cell Tumors

We aimed to evaluate the histologic components of primary mediastinal mixed germ cell tumors. A total of 221 patients diagnosed with a mediastinal germ cell tumor (GCT) were retrospectively reviewed. Among them, 14 patients underwent surgical resection after chemotherapy and 8 patients were diagnosed with mixed GCT, who were then selected for further evaluation. Clinical chart review and histologic review of biopsy and surgical specimens of 8 patients were performed. All 8 patients were young males and showed a mature teratoma or a mature teratoma with a focal immature teratoma in the resected specimens. Serum alpha-feto protein was variably elevated. Seven patients experienced an increase in tumor size after the chemotherapy. In 5 patients, a variable amount of vasculoconnective tissue was found along with the mature teratoma occupying average 66.3% of resected mass, and 3 of them showed an identical vasculoconnective component on biopsy before chemotherapy. We suggest that vasculoconnective tissue might be the intrinsic component of primary mediastinal mixed GCT. When vasculoconnective tissue is obtained on small biopsy of an anterior mediastinal mass of a young male, the possibility of underlying mixed GCT should be considered and further clinical work up should be performed.

Structural alterations of foreskin caused by chronic smoking may explain high levels of urethral reconstruction failure using foreskin flaps

OBJECTIVES: The aim of the present study was to perform a stereological and biochemical analysis of the foreskin of smoker subjects. MATERIALS AND METHODS: Foreskin samples were obtained from 20 young adults (mean = 27.2 years old) submitted to circumcision. Of the patients analyzed, one group (n = 10) had previous history of chronic smoking (a half pack to 3 packs per day for 3 to 13 years (mean = 5.8 ± 3.2). The control group included 10 nonsmoking patients. Masson's trichrome stain was used to quantify the foreskin vascular density. Weigert’s resorcin-fucsin stain was used to assess the elastic system fibers and Picrosirius red stain was applied to study the collagen. Stereological analysis was performed using the Image J software to determine the volumetric densities. For biochemical analysis, the total collagen was determined as µg of hydroxyproline per mg of dry tissue. Means were compared using the unpaired t-test (p < 0.05). RESULTS: Elastic system fibers of smokers was 42.5% higher than in the control group (p = 0.002). In contrast, smooth muscle fibers (p = 0.42) and vascular density (p = 0.16) did not show any significant variation. Qualitative analysis using Picrosirius red stain with polarized light evidenced the presence of type I and III collagen in the foreskin tissue, without significant difference between the groups. Total collagen concentration also did not differ significantly between smokers and non-smokers (73.1µg/mg ± 8.0 vs. 69.2µg/mg ± 5.9, respectively, p = 0.23). CONCLUSIONS: The foreskin tissue of smoking patients had a significant increase of elastic system fibers. Elastic fibers play an important role in this tissue’s turnover and this high concentration in smokers possibly causes high extensibility of the foreskin. The structural alterations in smokers’ foreskins could possibly explain the poor results in smoking patients submitted to foreskin fasciocutaneous flaps in urethral reconstruction surgery.

An aetiological & clinicopathological study on cutaneous vasculitis.

Background & objectives: Cutaneous vasculitis has protean clinical manifestations. It may be idiopathic or associated with a spectrum of conditions such as infections, drugs, etc. Skin is involved in both small vessel vasculitis (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between SVV and MVV. The histopathological features may not always relate with the clinical lesions. The aim of the present study was to evaluate the aetiological factors and clinicopathological association in patients with cutaneous vasculitis. Methods: In this cross-sectional study, detailed history and clinical examination were done on patients with biopsy proven cutaneous vasculitis. Two skin biopsies were taken from each patient for routine histopathology and direct immunofluorescence. Results: Of the 61 patients studied, hypersensitivity vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)] were the two most common forms. Systemic involvement was seen in 32 (52.45%) patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most common pattern, seen in all the clinically diagnosed patients with SVV (47), and in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence showed positivity for at least one immunoreactant in 62 per cent of the patients and the most common deposit was C3 followed by IgG, IgA and IgM. Interpretation & conclusions: Majority of our patients with cutaneous vasculitis were idiopathic. Histologically, SVV was seen in most of our patients. No association was seen between history of drug intake and tissue eosinophilia and also between histologically severe vasculitis and clinical severity. The presence of immunoreactant IgA was not specific for HSP.

Exploring anorganic bovine bone granules as osteoblast carriers for bone bioengineering: a study in rat critical-size calvarial defects

It is known that current trends on bone bioengineering seek ideal scaffolds and explore innovative methods to restore tissue function. In this way, the objective of this study was to evaluate the behavior of anorganic bovine bone as osteoblast carrier in critical-size calvarial defects. MC3T3-E1 osteoblast cells (1x10(5) cells/well) were cultured on granules of anorganic bovine bone in 24-well plates and after 24 h these granules were implanted into rat critical-size calvarial defects (group Biomaterial + Cells). In addition, other groups were established with different fillings of the defect: Blood Clot (negative control); Autogenous Bone (positive control); Biomaterial (only granules) and Cells (only MC3T3-E1 cells). After 30 days, the animals were euthanized and the calvaria were technically processed in order to allow histological and morphometric analysis. It was possible to detect blood vessels, connective tissue and newly formed bone in all groups. Particularly in the Biomaterial + Cells group, it was possible to observe a profile of biological events between the positive control group (autogenous bone) and the group in which only anorganic bovine granules were implanted. Altogether, the results of the present study showed that granules of anorganic bovine bone can be used as carrier to osteoblasts and that adding growth factors at the moment of implantation should maximize these results.

Sabe-se que uma das atuais tendências na bioengenharia óssea é procurar um carreador ideal e explorar métodos inovadores para restaurar a função do tecido. Desta forma, nosso objetivo foi avaliar o comportamento do osso bovino inorgânico como carreador de osteoblastos em defeitos ósseos de tamanho crítico em calvária de ratos. Osteoblastos da linhagem MC3T3-E1 (1x10(5) células/poço) foram cultivadas em grânulos de osso bovino inorgânico sob placas de 24 poços e após 24 h esses grânulos foram implantados em defeitos ósseos de tamanho crítico em calvária de ratos. Além deste grupo experimental (Biomaterial + Células), foram estabelecidos outros grupos com diferentes preenchimentos do defeito crítico: coágulo sanguíneo (controle negativo); osso autógeno (controle positivo); Biomaterial (apenas grânulos) e Células (apenas células MC3T3-E1). Após 30 dias, os animais foram eutanasiados e as calvárias foram processadas histotecnicamente, a fim de permitir a análise histológica e morfometria. Nossos resultados mostraram que em todos os grupos avaliados foi possível detectar vasos sanguíneos, tecido conjuntivo e osso neoformado. Em especial para o grupo tratado com Biomaterial + Células, foi possível observar um perfil de eventos biológicos intermediário ao grupo controle positivo (osso autógeno) e o grupo de biomaterial (apenas grânulos inorgânico bovino). Ao todo, nossos resultados mostraram que os grânulos de osso bovino inorgânico podem ser usados como carreador de osteoblastos e que a adição de fatores de crescimento no momento em que ocorre o implante deve maximizar os resultados.

Padrões dermatoscópicos do molusco contagioso: estudo de 211 lesões confirmadas por exame histopatológico / Dermoscopic patterns of molluscum contagiosum: a study of 211 lesions confirmed by histopathology

FUNDAMENTOS: Embora de fácil diagnóstico, o molusco contagioso pode apresentar-se como lesões inflamadas, únicas ou pequenas de difícil diagnóstico. OBJETIVO: Descrever características dermatoscópicas do molusco contagioso e comparar achados do exame clínico e dermatoscópico. MÉTODOS: Avaliou-se clínica e dermatoscopicamente lesões confirmadas pela histopatologia em 57 pacientes. RESULTADOS: Nos exames clínico e dermatoscópico de 211 lesões, foram visualizados orifícios em 50,24 por cento e 96,68 por cento das lesões e vasos em 6,16 por cento e 89,10 por cento delas, respectivamente. Os padrões vasculares encontrados em 188 lesões que apresentaram vasos à dermatoscopia foram coroa (72,34 por cento), radial (54,25 por cento) e puntiforme (20,21 por cento). Metade das 188 lesões apresentou padrão vascular combinado, sendo o padrão em flor (novo padrão vascular) responsável por 19,68 por cento. Foram identificados mais orifícios e vasos no exame dermatoscópico que no clínico, inclusive naquelas com inflamação, eczema perilesional e de tamanho pequeno. Vasos puntiformes relacionaram-se com inflamação, escoriação e eczema perilesional. CONCLUSÕES: A dermatoscopia das lesões de molusco mostrou-se superior ao exame dermatológico mesmo quando seu diagnóstico clínico torna-se difícil. A presença de orifícios, vasos e padrões vasculares específicos auxilia no seu diagnóstico e na diferenciação de outras lesões de pele.

BACKGROUNDS: Although easily diagnosed, molluscum contagiosum may present as a single lesion or as several small, inflamed lesions of difficult diagnosis. OBJECTIVE: To describe the dermoscopic characteristics of molluscum contagiosum and to compare the findings from clinical examination and dermoscopy. METHODS: Histopathologically confirmed lesions were evaluated clinically and dermoscopically in 57 patients. RESULTS: At clinical examination and dermoscopy of 211 lesions, orifices were visualized in 50.24 percent and 96.68 percent of the lesions, and vessels in 6.16 percent and 89.10 percent, respectively. The vascular patterns found in the 188 lesions in which vessels were found at dermoscopy were the crown (72.34 percent), radial (54.25 percent) and punctiform patterns (20.21 percent). Half of the 188 lesions had a combination of vascular patterns, with the flower pattern (a new vascular pattern) being found in 19.68 percent of cases. More orifices and vessels were identified at dermoscopy than at clinical examination, including cases with inflammation or perilesional eczema and small lesions. Punctiform vessels were associated with inflammation, excoriation and perilesional eczema. CONCLUSIONS: Dermoscopy performed on molluscum contagiosum lesions proved superior to dermatological examination even in cases in which clinical diagnosis was difficult. The presence of orifices, vessels and specific vascular patterns aids diagnosis, including differential diagnosis with other types of skin lesion.

[Angiogenesis and tumor]

Angiogenesis, the process of new blood vessel formation from existing ones, plays an important role in the physiologic circumstances such as embryonic development, placenta formation, and wound healing. It is also crucial to progress of pathogenic processes of a variety of disorders, including tumor growth and metastasis. In general, angiogenesis process is a multi-factorial and highly structured sequence of cellular events comprising migration, proliferation and differentiation of endothelial cells and finally vascular formation, maturation and remodeling.Thereby, angiogenesis inhibition as a helping agent to conventional therapies such as chemotherapy and radiation has attracted the scientists' attentions studying in this field

Evaluation of vascular endothelial growth factor (VEGF) in interradicular bone marrow in olpadronate treated animals

Vascular endothelial growth factor (VEGF) is a protein that increases vascular permeability and induces the proliferation, migration and survival of endothelial cells. Bisphosphonates (BPs) are antiresorptive drugs that are widely used in the treatment of bone metabolism diseases and bone metastases. Since 2003, cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been reported. Few papers explain the mechanisms that induce BRONJ; some authors mention alterations in bone remodelling and a certain antiangiogenic effect of BPs. The aim of this study is to evaluate the expression of VEGF in bone marrow cells and the number of blood vessels and area occupied by them in animals treated with the BP sodium olpadronate (OPD). We used 16 Wistar rats, 60 days old, divided into two groups, experimental (OPD) and control. The OPD group received 0.3 mg/kg/week intraperitoneal OPD for 5 weeks. The control group received an equivalent intraperitoneal volume of physiological saline solution. After euthanasia, hemimandibles were processed and mesio-distal histological sections of the first molar were prepared. Sections were stained with hematoxylin-eosin (HE), immunohistochemical detection of VEGF was performed (sc- 7269) and the following histomorphometric parameters were evaluated: In HE-stained sections - number of blood vessels per sq. mm. and percentage (%) of area occupied by blood vessels in relation to total area evaluated; in sections with immunohistochemical detection of VEGF – number of VEGF+ bone marrow cells per sq. mm. Data underwent statistical analysis. Number of blood vessels/mm2 was significantly lower in the OPD group (OPD: 92 ± 16; Control: 140 ± 31; p<0.05) and % vascular area/ total area evaluated showed no significant difference (OPD: 15.6 ± 6.1; Control: 10.2 ± 4.2). Number of VEGF+ cells/mm2 was lower in the OPD group than in the control group, with statistically significant differences (OPD: 7804.8 ± 597; Control: 13187.6 ± 894; p<0.001). The results of this study suggest that monosodium olpadronate has an antiangiogenic effect. Further studies are needed to reveal its potential as an antitumor agent and its connection with the onset of BRONJ.

El factor de crecimiento vascular (VEGF) es una proteina que incrementa la permeabilidad vascular, induce la proliferacion, migracion y supervivencia de las celulas endoteliales. Los bifosfonatos (BFs) son drogas antirresortivas ampliamente utilizadas en el tratamiento de enfermedades que alteran el metabolismo oseo y de metastasis oseas. Desde el 2003 se han reportado casos de osteonecrosis de maxilar asociada al uso de BFs (ONAB). Escasas publicaciones explican los mecanismos que inducen la ONAB, algunos autores mencionan las alteraciones en la remodelacion osea y un cierto efecto antiangiogenico de los BFs. El objetivo del presente trabajo es evaluar la expresion de VEGF en celulas de la medula osea y el numero y el area ocupada por vasos sanguineos en animales tratados con el BF olpadronato monosodico (OPD). Se utilizaron 16 ratas Wistar de 60 dias divididas en dos grupos, experimental (OPD) y control. El grupo OPD, recibio 0,3 mg/kg/sem de OPD via IP, durante 5 semanas. El grupo control, recibio un volumen equivalente via IP de solucion fisiologica. Luego de practicada la eutanasia se obtuvieron las hemimandibulas y se procesaron para obtener cortes histologicos mesio-distales del primer molar. Se realizo la coloracion hematoxilina-eosina (HE) y la deteccion inmunohistoquimica de VEGF (sc-7269) y se evaluaron los siguientes parametros histomorfometricos: En cortes con H&E: Numero de vasos sanguineos por mm2 y porcentaje (%) de area ocupada por los vasos sanguineos en relacion al area total evaluada; en cortes con la deteccion inmunohistoquimica de VEGF: Numero de celulas medulares VEGF+ por mm2. Los datos fueron estadisticamente analizados. El N° vasos sanguineos/mm2 fue significativamente menor en el grupo OPD (OPD: 92 ± 16; control: 140 ± 31; p<0,05) y el % area vascular/area total evaluada no mostro diferencias significativas (OPD: 15,6 ± 6.1; Control: 10.2 ± 4.2). El N° de celulas VEGF+/mm2 en el grupo OPD fue menor que en el grupo control con diferencias estadisticamente significativas (OPD: 7804,8 ± 597; Control: 13187,6 ± 894; p<0,001). Los resultados de este estudio sugieren que el olpadronato monosodico tiene un efecto antiangiogenico. Futuros estudios revelaran su potencial como agente antitumoral asi como tambien su relacion con la aparicion de ONAB.