Nordihydroguaiaretic acid (NDGA) inhibits ritonavir-induced endothelial dysfunction in porcine pulmonary arteries.

BACKGROUND: HIV infection and treatment with highly active antiretroviral therapy (HAART) including HIV protease inhibitor ritonavir (RTV) have been associated with endothelial dysfunction and cardiovascular disease including pulmonary arterial hypertension. The objective of this study was to determine if nordihydroguaiaretic acid (NDGA), a natural herbal antioxidant found in the creosote bush Larrea tridentate, can protect vascular tissues against RTV-induced vascular injury. MATERIAL/METHODS: Fresh porcine pulmonary artery (PA) rings were treated with a clinically relevant concentration of RTV (15 µmol/L) with or without NDGA for 24 hours, and then subjected to myograph analysis for vasomotor reactivity. Expression of endothelial nitric oxide synthase (eNOS) in both treated PA rings and human pulmonary artery endothelial cells (HPAECs) was analyzed by real-time PCR and immunohistochemistry. Oxidative stress levels were analyzed with the lucigenin-enhanced chemiluminescence and glutathione assay. RESULTS: In response to bradykinin at 10-10 mol/L, RTV-treated PA rings showed a 39% reduction in endothelium-dependent vasorelaxation compared with the control vessels (P<0.05); when co-cultured with NDGA (1.75 or 3.50 µmol/L), the relaxation increased by 25% and 48%, respectively. RTV also decreased the maximal contraction and endothelium-independent vasorelaxation in RTV-treated vessels, while NDGA improved these vasomotor responses. In addition, treatment of RTV significantly decreased eNOS mRNA levels in both porcine PAs and HPAECs, and reduced eNOS immunoreactivity in porcine PAs, while NDGA significantly inhibited this effect of RTV. Furthermore, NDGA significantly blocked RTV-induced increase of superoxide anion in the PA rings and inhibited RTV-induced decrease of glutathione in HPAECs. CONCLUSIONS: NDGA effectively inhibits the detrimental effects of HIV protease inhibitor RTV on vasomotor functions in porcine PAs. NDGA also blocks RTV-induced decrease of eNOS expression and increase of oxidative stress in both porcine PAs and HPAECs. This study may provide valuable information for the development of effective strategies for the prevention and treatment of HAART-associated cardiovascular complications.

Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update.

Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Nordihydroguaiaretic acid (NDGA), the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders and cancers. Creosote bush is a promising agent of North American herbal medicine, and it has extensive pharmacological effects and specific mechanisms of actions. This review provides an update of recent in vitro and in vivo research about NDGA and describes experimental studies using NDGA as antioxidant. Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed.

Surgical benefits conveyed by biopsy site marking system using ultrasound localization.

BACKGROUND: With vacuum-assisted biopsy technology all, or most, of a breast lesion may be removed during the initial biopsy; in such cases a metallic marker is often inserted at the site of the biopsy for future localization. The aim of this study was to evaluate the efficacy and impact of the Gel Mark Ultra biopsy site marking system (SenoRx, Aliso Viejo, CA) on the practice of needle localization breast biopsy. METHODS: We retrospectively analyzed the experience of 45 general surgeons across the United States in a variety of practice settings using the Gel Mark Ultra clip. Imaging-guided biopsy technique, localization quality, surgeon confidence, and margin status were assessed and compared against the broad data reported in the literature. RESULTS: A total of 432 records of patients who underwent imaging-guided breast biopsy with placement of Gel Mark Ultra clip were reviewed. Of these, 63 (15%) patients required definitive surgical intervention, for which 41 cases were localized with ultrasound and assessed for margin clearance. Clear margins were achieved in 37 (90%) of the 41 cases. These results are statistically superior (P < .01) to positive margins rates reported in the literature. CONCLUSIONS: The Gel Mark Ultra biopsy site marking system is a new localization device that provides a safe and effective alternative to traditional localization methods with a significant reduction in the percentage of positive margins, as well as advantages in terms of surgical approach, time, and patient comfort.

Interim results from the FibroAdenoma Cryoablation Treatment Registry.

OBJECTIVE: The aim of this prospective study was to assess the intermediate- (6 months) and longer-term (12 months) follow-up of patients with breast fibroadenomas treated by cryoablation in community-based practice settings. METHODS: The FibroAdenoma Cryoablation Treatment (FACT) registry was created to systematically collect procedural and follow-up data for patients with fibroadenomas treated by cryoablation without subsequent excision. This report summarizes the experience from 55 different practice settings across the United States. Baseline and follow-up clinical data at 6 months and 12 months were tabulated for all patients. RESULTS: Data from 444 treated fibroadenomas were analyzed. The mean tumor diameter was 1.8 cm. Before cryoablation, 75% of fibroadenomas were palpable by the patient. Follow-up at 6- and 12-month intervals revealed palpability of the treated site in 46% and 35%, respectively. When fibroadenomas were grouped by size, for lesions 2 cm, residual cryoablation induce changes were visible by ultrasound in 39% of the patients at 6 months. The treatment area was palpable in 78% of the cases at the same time. Visibility by ultrasound was 32%, and palpability was 59% at 12 months follow-up. Patient satisfaction with the procedure was rated as high at 91% and 88% at 6 and 12 months follow-up, respectively. CONCLUSIONS: Before implementing this technique, patients should be apprised of the likely persistence of a palpable mass of the treated site for a prolonged period that will reabsorb over time. Palpability of the treated site persists for a substantially longer period of time for lesions greater than 2 cm in diameter. For patients with a fibroadenoma smaller than 2 cm, complete resolution can be expected in two thirds and three quarters of the patients at 6 and 12 months, respectively. We will continue to follow these patients to better define the length of time and factors influencing the resolution of the treatment induced physical and radiographic findings.

Image-guided breast surgery.

With recent advances in technology and increased use of ultrasound, breast surgery has dramatically changed its approach towards nonpalpable lesions. Several image-guided diagnostic and therapeutic procedures have been implemented for the treatment of breast disease. Some of these modalities, including percutaneous image-guided biopsy techniques, were developed for the management of nonpalpable lesions, and they have been incorporated as the current standard of practice. Other innovating image-guided technologies, such as radiofrequency ablation and cryoablation therapy, are being explored in clinical protocols as promising new treatment modalities. In this article, the authors review the indications, advantages, and application techniques of the most common and current image-guided procedures performed today for the approach of breast pathology.

El simulador ®Harvey¼ de paciente cardiológico: la utilización de simuladores, computadoras y equipo multimedia en el aprendizaje de la cardiología / Cardiologic Harvey simulator: utilizing simulators, computers and multimedia equipment in the learning of cardiology

A través de un maniquí y un programa multimedia es posible adquirir conocimientos y destrezas necesarios para la evaluación y tratamiento de múltiples situaciones clínicas en el área de cardiología. Desde 1968, en la Escuela de Medicina de la Universidad de Miami, se viene utilizando un simulador de paciente cardiológico conocido como Harvey con una gran aceptación por parte de paramédicos, estudiantes de medicina, residentes, adscritos y enfermeras. El maniquí está programado para simular 27 situaciones cardiológicas que representan el mínimo necesario que debe de conocer y manejar un estudiante de medicina en el cuarto año, durante su periodo de aprendizaje en la materia clínica de cardiología.