A combined molecular dynamics simulation and DFT study on mercapto-benzamide inhibitors for the HIV NCp7 protein.

Molecular dynamics and quantum simulations are performed to elucidate some aspects of the action mechanism of mercapto-benzamides, a proposed class of antivirals against HIV-1. These molecules act as prodrugs that, after modifications in the biological environment, are able to denature the HIV nucleocapsid protein 7, a metal binder protein, with two zinc finger motifs, vital for RNA maturation and viral replication. Despite their attractive features, these molecules and their biological target are not well understood. Simulations were performed to support a proposed action mechanism, based on the activation of mercapto-benzamides by acetylation, targeting a relatively rare protein hydrolyzed state, followed by trans-molecular acetylation from the molecule to the protein and finally the direct interaction of the molecular sulphur atom of mercapto-benzamides with the zinc atom coordinated by the protein. Our simulation results are in agreement with the NMR data about the zinc finger binding protein equilibrium configurations.

Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation. CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast. CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.

Effects of TIPS-functionalization and perhalogenation on the electronic, optical, and transport properties of angular and compact dibenzochrysene.

We report a systematic comparative study on dibenzo[b,def]chrysene (angular) and dibenzo[def,mno] chrysene (compact) polyaromatic hydrocarbons and their bis-triisopropylsilylethynyl (TIPS)-functionalized and perhalogenated (F, Cl) counterparts. We used density functional theory (DFT) and time-dependent DFT to quantify the effects of morphology and chemical modifications on the electronic, optical, and transport properties. In particular, we compared electron affinity, ionization energy, fundamental gap, optical absorption, exciton binding energy, and reorganization energies for holes and electrons. For both TIPS-functionalization and halogen substitutions, we found larger electron affinities (nearly tripled with perchlorination). Ionization energies are found to be reduced for TIPS-functionalization (by ∼5%) and enhanced following halogen substitution (up to 17%). In both compact and angular dibenzochrysenes, the above trends reflect in a general reduction of the fundamental gap (up to 22%) following chemical modification. The effect of perhalogenation and TIPS-functionalization is always to increase molecular reorganization energies for both holes and electrons. Concerning the optical properties, we observe a redshift of the optical onset in all cases; for TIPS-functionalized molecules, in particular, we additionally found a remarkable enhancement of the absorption in the visible region.

Extracao e purificacao do hormonio de crescimento de hipofises humanas congeladas (hGH-HC). / Extration and purification of growth hormone from frozen human pituitaries (hGH-HC)

Os autores relatam a aplicacao de um metodo de extracao e purificacao de hormonio de crescimento obtido de hipofises humanas congeladas. O processo consiste em hemogeneizacao e extracao em buffer salino e precipitacao com alcool. O extrato e concentrado em Millipore e a purificacao realizada em duas colunas, Sephadex G-100 e DEAE celulose. Especial atencao foi dada a obtencao de um produto isento de pirogenio O controle de qualidade mostrou que se obteve um produto ativo, esteril, apirogenico e isento de antigeno Au que esta sendo aplicado no Hosptial das Clinicas da Universidade de Sao Paulo