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Transforming growth factor-[beta]1 (TGF-[beta]1) is abundantly expressed in pulmonary hypertension, but its effect on the pulmonary circulation remains unsettled. We studied the consequences of TGF-[beta]1 stimulation on freshly isolated human pulmonary artery smooth muscle cells (HPASMC). TGF-[beta]1 initially promoted differentiation, with upregulated expression of smooth muscle contractile proteins. TGF-[beta]1 also induced expression of Nox4, the only NAD(P)H oxidase membrane homolog found in HPASMC, through a signaling pathway involving Smad 2/3 but not mitogen-activated protein (MAP) kinases. TGF-[beta]1 likewise increased production of reactive oxygen species (ROS), an effect significantly reduced by the NAD(P)H oxidase flavoprotein inhibitor diphenylene iodonium (DPI) and by Nox4 siRNAs. In the absence of TGF-[beta]1, Nox4 was present in freshly cultured cells but progressively lost with each passage in culture, paralleling a decrease in ROS production by HPASMC over time. At a later time point (72 h), TGF-[beta]1 promoted HPASMC proliferation in a manner partially inhibited by Nox4 small interfering RNA and dominant negative Smad 2/3, indicating that TGF-[beta]1 stimulates HPASMC growth in part by a redox-dependent mechanism mediated through induction of Nox4. HPASMC activation of the MAP kinases ERK1/2 was reduced by the NAD(P)H oxidase inhibitors DPI and 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that TGF-[beta]1 may facilitate proliferation by upregulating Nox4 and ROS production, with transient oxidative inactivation of phosphatases and augmentation of growth signaling cascades. These findings suggest that Nox4 is the relevant Nox homolog in HPASMC. This is the first observation that TGF-[beta]1 regulates Nox4, with important implications for mechanisms of pulmonary vascular remodeling. Smad 2/3; pulmonary arterial hypertension; hypertrophy; superoxide anion; rac 1; ERK 1/2; phosphatases

Summary: A case presentation of syncope during forced exhalation and cough paroxyms due to an endobronchial neoplasm in the left mainstem bronchus; clinical findings and mechanism of syncope are reviewed. [Copyright &y& Elsevier]

Orbital floor fractures can result in herniation of orbital tissues and impairment of ocular function. In this experimental study, orbital defects were created surgically in cats. The gross and histologic healing of these defects was compared among animals implanted with silicone rubber sheeting or absorbable gelatin film and animals that received no implants. Both implanted animal groups demonstrated enhancement of healing. The absorbable gelatin film showed less migration, less inflammatory response, and improved healing. This animal study supports the use of absorbable gelatin film in the surgical management of orbital fractures. [ABSTRACT FROM AUTHOR]

Background: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS. Methods: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups. Results: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score ≥3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001). Conclusion: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required. [Copyright &y& Elsevier]

Background. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. We hypothesized that a combination of recombinant angiogenic proteins might induce myocardial VEGF production and cause a shift in the mRNA signal produced.Materials and methods. The left ventricles of New Zealand white rabbits were injected with 500 μL of saline, basic fibroblast growth factor (bFGF), platelet-derived growth factor-AB (PDGFAB), platelet-derived growth factor-BB (PDGFBB), bFGF + PDGFAB, or bFGF + PDGFBB. Myocardial VEGF production was analyzed by ELISA while mRNA splice variants were analyzed by RT-PCR 3 and 7 days after injection.Results. PDGFBB alone caused the most pronounced induction of VEGF. Three days after injection the induction of VEGF by PDGFBB was significant compared to all treatment groups, except the bFGF + PDGFBB group. Induction of VEGF by PDGFBB was associated with a decrease in mRNA production of VEGF121 within the myocardium.Conclusions. Injection of PDGFBB induces significant production of VEGF within the myocardium. This induction of VEGF production is associated with a shift toward other, less soluble forms of VEGF. These findings may allow more precise regulation of the myocardial response to therapeutic angiogenesis. [Copyright &y& Elsevier]