Fast Heck-Cassar-Sonogashira (HCS) Reactions in Green Solvents.

The replacement of toxic solvents with greener alternatives in Heck-Cassar-Sonogashira (HCS) cross-couplings was investigated. The fine-tuning of the HCS protocol allowed to achieve complete conversions and high speed under mild conditions. N-Hydroxyethylpyrrolidone (HEP) gave the best results. Moreover, the methodology was successfully applied to the synthesis of an intermediate of the anticancer drug Erlotinib, demonstrating the versatility of the new green protocol.

Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers.

OATP1B1 is an influx transporter known to mediate the uptake of various endogenous compounds and xenobiotics. Several sequence variations have been discovered in the SLCO1B1 gene encoding OATP1B1. The aim of this study was to investigate the effects of SLCO1B1 polymorphisms on the pharmacokinetics of atorvastatin in healthy volunteers of Macedonian origin. Twenty three participants, genotyped for SLCO1B1 c.388A > G, c.521T > C, c.571T > C, c.597C > T, c.1086C > T, c.1463G > C and c.*439T > G polymorphisms using TaqMan allelic discrimination assay, ingested a single 80 mg dose of atorvastatin. The plasma concentrations of atorvastatin were measured for 48 h using Tandem Liquid Chromatography-Mass Spectrometry, LC-MS-MS, and the peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t1/2), constant rate of elimination (k(el)), mean residence time (MRT, expo), volume of distribution (Vd/kg), clearance (CL/kg), area under curve AUC(0.48h) and AUC(0-∞), were determined. Our data confirmed that the SLCO1B1 gene is highly polymorphic, with a frequency of the c.521T > C single-nucleotide polymorphism (SNP) being the lowest (app. 15%) and of all other SNPs alleles above 40%. Exceptions were c.1463G > C and c.1086C > T SNPs for which variant alleles were not identified. The strongest correlation was observed between the c.521T > C and c.571T > C SNPs pair. The haplotype analysis revealed 10 different haplotypes, with *1J/*1K/*1L being the dominant, with a frequency of app. 40%. The haplotype *15/*16/*17, containing both variant alleles of the functionally most distinguished SNPs, c.388A > G and c.521T > C, occurred with a frequency of 13%. However, *15/*16/*17 homozygotes were not identified in the study group. In this study, no significant differences in the k(el), t1/2, C(max), T(max), AUC(0-48h), AUC(0-∞), MRT expo, Vd and CL between the carriers of different c.388A > G, c.597C > T and c.*439T > G genotypes were observed. Subject with a variant allele C in the c.521T > C SNP, c.521CC genotype, had markedly higher values for C(max) and AUC(0.48h), 140% and 67%, respectively, in comparison with the carriers of the c.521TT genotype. Also, the carriers of the variant allele C at c.571T > C SNP, c.571 CC genotype, had 55% and 43% lower mean C(max) and AUC(0-48h) in comparison with the carrier of c.571TT. These differences lacked statistical significance due to the size of the sample. In addition, no significant differences in the pharmacokinetic parameters of atorvastatin between the *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers were observed. In conclusion, this extensive analysis of the effect of SLCO1B1 polymorphisms on the pharmacokinetic profile of atorvastatin showed that c.521T > C and c.571T > C SNPs may affect the inter-individual response to atorvastatin. Additional studies, with a large sample size, are needed to confirm this finding.

The impact of blood use on patients undergoing coronary artery bypass surgery: a prospective study.

OBJECTIVES: This survey aimed at assessing the incidence of blood use and the impact of cardiopulmonary bypass (CBP), sex, age, number of grafts, combined cardiac interventions, and hematocrit level in patients who undergo coronary artery bypass graft (CABG) surgery. PATIENTS AND METHODS: A prospective study included patients in the department of cardiac surgery at the American Hospital, in Tirana, Albania. We studied 164 consecutive patients who underwent CABG surgery over a 2-year period (2011-2013). RESULTS: We analyzed 164 patients: 138 men and 26 women. The average age was 61.8 years (range, 34-82 years). Of these, 116 patients (101 men/15 women) and 48 patients (37 men/11 women) were operated on-pump and off-pump, respectively. Packed red blood cells (PRBC) were administered to 79.87% of patients (131/164). In total, 334 units were transfused. The average number of PRBC units per patient was 2.03 ± 1.5 (range, 0-8 units). Blood transfusion was administered to 87.06% and 62.5% of on-pump and off-pump patients, respectively. On-pump and off-pump patients received 2.4 and 1 unit of PRBC, respectively (p < 0.001). Female and male patients received 2.2 and 2 units, respectively (p = 0.1). Patients aged ≥ 62.5 years received 2.3 units on average versus the average of 1.7 units received by patients aged < 62.5 years (p < 0.001). Interventions with 4-6 grafts (79/164) received an average 2.5 units, while those with 1-3 grafts (85/164) received 1.5 units (p < 0.001). Patients requiring other cardiac surgical interventions (35/164) received an average of 2.6 units, while those without other cardiac surgical interventions (129/164) received an average of 1.8 units (p < 0.001). Patients with preoperative hematocrit < 35% received an average 1.2 units of PRBC intraoperatively, and 2.8 units throughout the hospital stay, while patients with preoperative hematocrit ≥ 35% received an average of 0.75 units intraoperatively (p < 0.001) and 1.9 units throughout the hospital stay (p < 0.001). CONCLUSION: Blood transfusion was required for 79.87% of patients. Five variables were important factors in the use of blood in patients undergoing CABG: using CBP, a higher number of grafts, age ≥ 62.5 years, combined heart interventions and preoperative hematocrit< 35%. Female patients required more PRBC than male patients, although it was not statistically significant. Knowledge of these risk factors enables better prediction of the probability of patients who might require more blood, better distribution of blood in CABG procedures, use by the blood bank, and evaluation of cost-effectiveness in the use of blood products.

Clinical role of Cefixime in community-acquired infections.

UNLABELLED: Cefixime is an oral third generation cephalosporin, frequently used in respiratory tract infections (RTI) in the pediatric population. However, in some publications cefixime has demonstrated poor efficacy against staphylococci and streptococci. THE AIM: of this study was to evaluate the efficacy of cefixime in the treatment of community-acquired infections in a country where parenteral third generation cephalosporins have been used for a long time. The present study was designed to assess the clinical efficacy, bacteriological eradication rates and tolerability of cefixime in children with community-acquired upper RTI (URTI), lower RTI (LRTI) and uncomplicated urinary tract infections (UTI). MATERIALS AND METHODS: The study was prospective, open, and included 89 patients, from 6 months to 28 years, of both sexes, with the diagnosis of community-acquired URTI, LRTI and UTI. RESULTS: The treatment with cefixime was successful in 30/30 (100%) patients suffering from acute otitis media (AOM), in 10/12 (83.3%) with acute sinusitis, in 12/12 patients (100%) with pneumonia, in 31/35 (88.57) with uncomplicated UTI. The antibiotic was well tolerated. In 10 days treatment we recorded one case (1.3%) with acute gastroenteritis and two cases (2.6%) of maculopapular rash. Side-effects were transient and disappeared after finishing therapy in all three of the cases. CONCLUSIONS: Community-acquired infections, such as AOM, LRTI and UTI, caused by susceptible pathogens, can be treated with cefixime, as a good choice for a successful clinical response.

The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.

Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)