Synthesis and molluscicidal activity of new chromene and pyrano[2,3-c]pyrazole derivatives

The chromene derivative 4 reacts with acetic anhydride, phenylisothiocyanate and ethyl orthoformate to afford the N-acetyl derivative 6, the chromenopyrimidine 8 and the formimidate 9, respectively. 2-(1H-Indol-3-ylmethylene)-malononitrile 10b reacts with 1,3-cyclohexanedione and dimedone 11a, b to afford the 4(3-indolyl)-chromene derivatives 12a, b respectively, and with the pyrazolone derivatives 13a-d to afford the arylidene exchange derivatives 14a-c and the pyranopyrazole derivative 15, respectively. The arylidene derivatives 10a, b react also with indane-1,3-dione 16 to afford the arylidene exchange derivatives 18a, b. The molluscicidal activity of the synthesized compounds towards Biomphalaria alexandrina snails, the intermediate host of Schistosoma mansoni, was investigated and most of them showed weak to moderate activity.     

Treatment of muscle-invasive bladder cancer

In the USA, the incidence of bladder cancer is three-times higher in men than in women and it is the fourth most common cancer in men after prostate, lung and colorectal cancer. Muscle-invasive urothelial urinary bladder cancer has a very high mortality rate. This is regardless of intensive therapeutic efforts such as radical surgery in combination with oncological treatment options. The development of treatments with better outcomes regarding disease-specific survival and treatment-inflicted morbidity is likely to occur over the next few years. The significance of meta-analyses on the effect of neoadjuvant chemotherapy, the development of sentinel node dissection and the impact of the introduction of robot-assisted surgery on the possibility of performing minimally invasive surgery in advanced bladder cancer patients is discussed.     

High-dose melphalan versus busulfan, cyclophosphamide, and etoposide as preparative regimens for autologous stem cell transplantation in patients with multiple myeloma

High-dose chemotherapy (HDC) with autologous stem cell transplant (ASCT) has improved response rates and survival for patients with multiple myeloma (MM). We report a single-institution experience using two conditioning regimens, busulfan, cyclophosphamide, and etoposide (BCV) or high-dose melphalan (HDM). Between July 1992 and August 2003, 110 patients with MM (median age=56.1) underwent HDC with ASCT using either BCV (n=62) or HDM (n=48) in sequential cohorts as the preparative regimen. Overall response rates, progression-free survival, and median overall survival were similar. BCV and HDM confer similar long-term outcomes with similar toxicity profiles as conditioning regimens prior to autologous stem cell transplant in patients with MM.     

Effects of mycophenolate mofetil on cisplatin-induced renal dysfunction in rats

Purpose Inflammation and oxidative stress are important events among the plethora of mechanisms involved in cisplatin (CDDP)-induced nephrotoxicity. The aim of this study was to evaluate the effect of mycophenolate mofetil (MMF), an immunosuppressive, in the protection against CDDP-induced renal dysfunction. Methods Rats were divided into four groups; untreated-control group, CDDP-treated group (7 mg/kg, single intraperitoneal dose), MMF-treated group (40 mg/kg/day orally for 5 successive days) and the fourth group was treated with both drugs and MMF treatment was started 1 day prior to CDDP administration. Nephrotoxicity was assessed 7 days after the CDDP treatment by measuring serum indices of nephrotoxicity, kidney weight as a percentage of total body weight, kidney’s tissue peroxidative alterations and total nitrate/nitrite concentration (NOx) and the results were confirmed histopathologically. Results Rats treated with CDDP showed marked nephrotoxicity as evidenced from the significant increase in serum creatinine and urea levels and decrease in serum calcium and albumin levels. Kidneys of CDDP-treated rats showed significant increases in kidney weight and malondialdehyde (MDA) production level and decreases in total NOx concentration, glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content levels. Histopathological assessment of kidneys of CDDP-treated rats revealed extensive tubular necrosis with “sloughing off” of the renal tubular lining cells, intratubular hyaline casts and mononuclear cell infiltration. Treatment with MMF significantly protected the rats against CDDP-induced nephrotoxicity. The rise in serum creatinine and urea levels, kidney weight and kidney tissue MDA production, depletion of “endogenous antioxidant reserve” including GPx activity and reduced GSH content levels and the deleterious histopathological changes induced by CDDP treatment were significantly mitigated by MMF treatment. Conclusions MMF treatment dramatically ameliorates CDDP-induced renal dysfunction.     

Fast calculation of multipath diffusive reflectance in optical coherence tomography

We show how to efficiently calculate the signal in optical coherence tomography (OCT) systems due to the ballistic photons, the quasi-ballistic photons, and the photons that undergo multiple diffusive scattering using Monte Carlo simulations with importance sampling. This method enables the calculation of these three components of the OCT signal with less than one hundredth of the computational time required by the conventional Monte Carlo method. Therefore, it can be used as a design tool to characterize the performance of OCT systems, and can also be used in the development of novel signal processing techniques that can extend the imaging range of OCT systems. We investigate the parameter dependence of our importance sampling method and we validate it by comparison to an existing method.