Impact of Cesium Concentration on Optoelectronic Properties of Metal Halide Perovskites

Performance of a perovskite solar cell is largely influenced by the optoelectronic properties of metal halide perovskite films. Here we study the influence of cesium concentration on morphology, crystal structure, photoluminescence and optical properties of the triple cation perovskite film. Incorporation of small amount (x = 0.1) of cesium cations into Cs_x(MA_0.17FA_0.83)_1−x Pb(I_0.83Br_0.17)₃ leads to enhanced power conversion efficiency (PCE) of the solar cell resulting mainly from significant rise of the short-current density and the fill factor value. Further increase of Cs concentration (x > 0.1) decreases the film’s phase purity, carrier lifetime and correspondingly reduces PCE of the solar cell. Higher concentration of Cs (x ≥ 0.2) causes phase segregation of the perovskite alongside with formation of Cs-rich regions impeding light absorption.     

A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer

PURPOSE: To determine the safety, gene transfer, host immune response, and pharmacokinetics of a replication-deficient adenovirus encoding human, recombinant, wild-type p53 (SCH 58500) delivered into the peritoneal cavity (i.p.) alone and sequentially in combination with platinum-based chemotherapy, of patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer containing aberrant or mutant p53. METHODS: SCH 58500 was administered i.p. to three groups of patients with heavily pretreated recurrent disease. Group 1 (n=17) received a single dose of SCH 58500 escalated from 7.5 x 10(10) to 7.5 x 10(12) particles. Group 2 (n=9) received two or three doses of SCH 58500 given alone for one cycle, and then with chemotherapy for two cycles. The SCH 58500 dose was further escalated to 2.5 x 10(13) particles/dose in group 2. A third group (n=15) received a 5-day regimen of SCH 58500 given at 7.5 x 10(13) particles/dose per day i.p. alone for cycle 1 and then with intravenous carboplatin/paclitaxel chemotherapy for cycles 2 and 3. RESULTS: No dose-limiting toxicity resulted from the delivery of 236/287 (82.2%) planned doses of SCH 58500. Fever, hypotension abdominal complaints, nausea, and vomiting were the most common adverse events. Vector-specific transgene expression in tumor was documented by RT-PCR in cells from both ascitic fluid and tissue biopsies. Despite marked increases in serum adenoviral antibody titers, transgene expression was measurable in 17 of 20 samples obtained after two or three cycles of SCH 58500. Vector was detectable in peritoneal fluid by 24 hours and persisted for as long as 7 days whereas none was detected in urine or stool. There was poor correlation between CT scans and CA125 responses. CA125 responses, defined as a greater than 50% decrement in serum CA125 from baseline, were documented in 8 of 16 women who completed three cycles of the multidose regimen. CONCLUSION: CT scans are not a valid measure of response to i.p. SCH 58500 due to extensive adenoviral-induced inflammatory changes. Intraperitoneal SCH 58500 is safe, well tolerated, and combined with platinum-based chemotherapy can be associated with a significant reduction of serum CA125 in heavily pretreated patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.     

Classification analysis of P-glycoprotein substrate specificity

Prediction of P-glycoprotein substrate specificity (S(PGP)) can be viewed as a constituent part of a compound's "pharmaceutical profiling" in drug design. This task is difficult to achieve due to several factors that raised many contradictory opinions: (i) the disparity between the S(PGP) values obtained in different assays, (ii) the confusion between Pgp substrates and inhibitors, (iii) the confusion between lipophilicity and amphiphilicity of Pgp substrates, and (iv) the dilemma of describing class-specific relationships when Pgp has no binding sites of high ligand specificity. In this work, we compiled S(PGP) data for 1000 compounds. All data were represented in a binary format, assigning S(PGP) = 1 for substrates and S(PGP) = 0 for non-substrates. Each value was ranked according to the reliability of experimental assay. Two data sets were considered. Set 1 included 220 compounds with S(PGP) from polarized transport across MDR1 transfected cell monolayers. Set 2 included the entire list of 1000 compounds, with S(PGP) values of generally lower reliability. Both sets were analysed using a stepwise classification structure-activity relationship (C-SAR) method, leading to derivation of simple rules for crude estimation of S(PGP) values. The obtained rules are based on the following factors: (i) compound's size expressed through molar weight or volume, (ii) H-accepting given by the Abraham's beta (that can be crudely approximated by the sum of O and N atoms), and (iii) ionization given by the acid and base pKa values. Very roughly, S(PGP) can be estimated by the "rule of fours". Compounds with (N + O) > or = 8, MW > 400 and acid pKa > 4 are likely to be Pgp substrates, whereas compounds with (N + O) < or = 4, MW < 400 and base pKa < 8 are likely to be non-substrates. The obtained results support the view that Pgp functioning can be compared to a complex "mini-pharmacokinetic" system with fuzzy specificity. This system can be described by a probabilistic version of Abraham's solvation equation, suggesting a certain similarity between Pgp transport and chromatographic retention. The chromatographic model does not work in the case of "marginal" compounds with properties close to the "global" physicochemical cut-offs. In the latter case various class-specific rules must be considered. These can be associated with the "amphiphilicity" and "biological similarity" of compounds. The definition of class-specific effects entails construction of the knowledge base that can be very useful in ADME profiling of new drugs.     

ACD/Log P method description

This study describes the development of the ACD/Log P calculation method. Analysis of 14 calculation methods revealed that the most accurate calculations are obtained when correction factors are used. We evaluated the correction factors used by Hansch and Leo in CLOGP in order to simplify their method. Most of the CLOGP structural factors are included in our fragmental increments. Aliphatic and aromatic factors are replaced with additive interfragmental increments. Missing increments are estimated by two empirical equations with simple physical interpretation. The final method uses three simple equations with several types of parameters. The training set included 3601 compounds and the correlation between experimental and calculated Log P values gave R = 0.992, S = 0.21. The method was validated by comparing it with 17 other methods on various data sets of independently selected drugs and other compounds. In all cases, our method produced the best results. The weakness of this method is that it uses a large number of individual increments for aromatic interactions. Each increment represents a combination of several effects which presently cannot be separated. This revised version was published online in August 2006 with corrections to the Cover Date.     

Ionization-specific analysis of human intestinal absorption

This study presents a mechanistic QSAR analysis of human intestinal absorption of drugs and drug-like compounds using a data set of 567 %HIA values. Experimental data represent passive diffusion across intestinal membranes, and are considered to be reasonably free of carrier-mediated transport or other unwanted effects. A nonlinear model was developed relating %HIA to physicochemical properties of drugs (lipophilicity, ionization, hydrogen bonding, and molecular size). The model describes ion-specific intestinal permeability of drugs by both transcellular and paracellular routes, and also accounts for unstirred water layer effects. The obtained model was validated on two external data sets consisting of in vivo human jejunal permeability coefficients (P_eff) and absorption rate constants (K_a). Validation results demonstrate good predictive power of the model (RMSE = 0.35–0.45 log units for log K_a and log P_eff). High prediction accuracy together with clear physicochemical interpretation (log P, pK_a) makes this model particularly suitable for use in property-based drug design. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4039–4054, 2009     

Prevalence of hepatitis B virus chronic carriers and risk factors for hepatitis B virus infection among Lithuanian army soldiers

The aim of this study was to evaluate the prevalence of hepatitis B serological markers (hepatitis B virus (HBV) superficial antigen (HBsAg)) and risk factors for HBV infection among Lithuanian Army soldiers. The study was carried out in Lithuanian military subunits in 2003. Serum samples were draw from 1,830 soldiers (average age, 21.6 (0.707) years) and tested for hepatitis B infection markers (HBsAg). Questionnaires were used to obtain information about risk factors associated with HBV infection. A total of 1.97% of soldiers was seropositive for HBsAg. The prevalence rate of HBV infection was related to military subunit (p > 0.05). Most of the HBsAg-positive soldiers (53.8%) served 4 to 6 months. Among soldiers who were offered to use drugs, the prevalence of HBsAg was 4.3%; in the remaining group, the prevalence was 1.9%. No association was found between other risk factors for HBV infection and the prevalence rate of the hepatitis B marker. Study data proved the need for health promotion, prophylactic vaccination, and monitoring programs at the Lithuanian Armed Forces.