Angiogenesis in pre-malignant conditions

Evidence from human studies suggests that angiogenesis commences during the pre-malignant stages of cancer. Inhibiting angiogenesis may, therefore, be of potential value in preventing progression to invasive cancer. Understanding the mechanisms inducing angiogenesis in these lesions and identification of those important in human tumourigenesis are necessary to develop translational strategies that will help realise the goal of angioprevention

Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease

BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P<0.005), and between in situ and invasive carcinomas (P<0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (P<0.05) cancers and in invasive compared with in situ cancers (P<0.005). Hypoxia-inducible factor-1alpha, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (P<0.05). Moreover, HIF-1alpha was expressed by 60-75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (P<0.005) and invasive tumour cells (P<0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1alpha, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion

Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling

The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight) effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavonolignans inhibit tumor angiogenesis biomarkers (CD31 and nestin) and signaling molecules regulating angiogenesis (VEGF, VEGFR1, VEGFR2, phospho-Akt and HIF-1α) without adversely affecting the vessel-count in normal tissues (liver, lung, and kidney) of tumor bearing mice. These flavonolignans also inhibited the microvessel sprouting from mouse dorsal aortas ex vivo, and the VEGF-induced cell proliferation, capillary-like tube formation and invasiveness of human umbilical vein endothelial cells (HUVEC) in vitro. Further studies in HUVEC showed that these diastereoisomers target cell cycle, apoptosis and VEGF-induced signaling cascade. Three dimensional growth assay as well as co-culture invasion and in vitro angiogenesis studies (with HUVEC and DU145 cells) suggested the differential effectiveness of the diastereoisomers toward PCA and endothelial cells. Overall, these studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention

2013 WSES guidelines for management of intra-abdominal infections

Peer reviewe

Testosterone Usage Leading to Pulmonary Embolisms and Deep Vein Thrombosis: A Case Report and Review of the Literature

Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented to the hospital after the usage of testosterone for one month, leading to the development of multiple pulmonary emboli and deep vein thrombosis. The authors hope to elucidate the relationship between testosterone usage and thrombosis formation

Phenazopyridine-Induced Methemoglobinemia in a Jehovah’s Witness Treated with High-Dose Ascorbic Acid Due to Methylene Blue Contradictions: A Case Report and Review of the Literature

Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that present with hypoxemia that does not resolve with supplemental oxygenation, and they should confirm this suspicion with a positive methemoglobin concentration on arterial blood gas. There are multiple medications that can induce methemoglobinemia, such as local anesthetics, antimalarials, and dapsone. Phenazopyridine is an azo dye used over-the-counter as a urinary analgesic for women with urinary tract infections, and it has also been implicated in causing methemoglobinemia. The preferred treatment of methemoglobinemia is methylene blue, but its use is contraindicated for patients with glucose-6-phosphatase deficiency or those who take serotonergic drugs. Alternative treatments include high-dose ascorbic acid, exchange transfusion therapy, and hyperbaric oxygenation. The authors report a case of a 39-year-old female who took phenazopyridine for 2 weeks to treat dysuria from a urinary tract infection and subsequently developed methemoglobinemia. The patient had contraindications for the use of methylene blue and was therefore treated with high-dose ascorbic acid. The authors hope that this interesting case promotes further research into the utilization of high-dose ascorbic acid for managing methemoglobinemia in patients who are unable to receive methylene blue

Acquired Factor X Deficiency without Amyloidosis Presenting with Massive Hematuria: A Case Report and Review of the Literature

Acquired factor X deficiency is a rare diagnosis, especially without the association of other co-existing conditions such as amyloidosis. The authors report the case of a 34-year-old male with severe frank hematuria found to have markedly prolonged prothrombin time and activated partial thromboplastin time. A mixing study showed correction utilizing normal plasma and a coagulation panel testing revealed decreased factor X activity. The patient was treated with multiple blood transfusions, fresh frozen plasma, high-dose pulse steroids, and rituximab. The patient’s condition improved during his 21-day hospital stay and was followed up every 2 weeks for 3 months. The patient’s factor X level recovered after two weeks of discharge with no other hemorrhagic episodes

Vascular injuries of the upper extremity Lesões vasculares de membros superiores

OBJECTIVE: This study analyzes the causes of injuries, presentations, surgical approaches, outcome and complications of vascular trauma of the upper limbs, in spite of limited hospital resources. METHODS: A 5-year retrospective analysis. From 01/01/2001 to 31/12/2005, 165 patients were operated for vascular injuries at King Fahd Hospital, Medina, Saudi Arabia. Of all peripheral vascular trauma patients (115), upper limb trauma was present in 58. Diagnosis was made by physical examination and hand-held Doppler alone or in combination with Doppler scan/angiography. Primary vascular repair was performed whenever possible; otherwise, the interposition vein graft was used. Fasciotomy was considered when required. Patients with unsalvageable lower extremity injury requiring primary amputation were excluded from the study. RESULTS: Fifty patients were male (86%) and eight were female (14%), aged between 2.5-55 years (mean 23 years). Mean duration of presentation was 8 h after the injury. The most common etiological factor was road traffic accidents, accounting for 50.5% in the blunt trauma group and 33% among all penetrating and stab wound injuries. Incidence of concomitant orthopedic injuries was very high in our study (51%). The brachial artery was the most affected (51%). Interposition vein grafts were used in 53% of the cases. Limb salvage rate was 100%. CONCLUSION: Patients who suffer vascular injuries of the upper extremities should be transferred to vascular surgery centers as soon as possible. Decisive management of peripheral vascular trauma will maximize patient survival and limb salvage. Priorities must be established in the management of associated injuries, and delay must be avoided when ischemic changes are present.<br>OBJETIVO: Este estudo analisa as causas de lesões, apresentação, abordagens cirúrgicas, desfechos e complicações do trauma vascular de membros superiores, apesar de recursos hospitalares limitados. MÉTODOS: Análise retrospectiva de 5 anos. De 01/01/2001 a 31/12/2005, 165 pacientes foram operados devido a lesões vasculares no King Fahd Hospital, Medina, Arábia Saudita. De todos os pacientes com trauma vascular periférico (115), trauma de membros superiores esteve presente em 58. O diagnóstico foi realizado por exame físico e Doppler manual isoladamente ou associado com ultra-som Doppler/angiografia. A restauração vascular primária foi realizada sempre que possível; do contrário, utilizou-se a interposição de veia. A fasciotomia foi considerada quando necessário. Pacientes com lesão de membro inferior não resgatável necessitando de amputação foram excluídos do estudo. RESULTADOS: Cinqüenta pacientes eram homens (86%) e oito eram mulheres (14%), com idade entre 2,5 e 55 anos (média de 23 anos). A duração média de apresentação foi 8 h pós-lesão. O fator etiológico mais comum foi acidente em estradas, sendo responsável por 50,5% no grupo de trauma contuso e 33% entre as lesões penetrantes e por arma branca. A incidência de lesões ortopédicas concomitantes foi muito alta em nosso estudo (51%). A artéria braquial foi a mais afetada (51%). A interposição de veias foi utilizada em 53% dos casos. A taxa de preservação de membros foi de 100%. CONCLUSÃO: Pacientes que sofrem lesões vasculares de membros superiores devem ser transferidos para centros de cirurgia vascular o mais rápido possível. O tratamento imediato do trauma vascular periférico aumentará a sobrevida dos pacientes e a preservação dos membros. Devem-se estabelecer prioridades no tratamento de lesões associadas e evitar o atraso quando alterações isquêmicas estiverem presentes