Cost considerations of the new fixed combinations for glaucoma medical therapy

OBJECTIVE: To compare the costs of the new fixed combinations for glaucoma medical therapy. METHODS: The studied drugs were: Cosopt (5-mL bottle), Combigan (5-mL bottle) and Xalacom (2.5-mL bottle). Five bottles of each drug were obtained from pharmacies, and the medications lot numbers were recorded. To calculate the drop volume, 10 drops and 1 mL of each bottle were weighed with a digital precision scale. Drop volume was calculated by the relation between volume and weight. The cost of each bottle of medication was determined from the average retail price in Canada. The prices were obtained in Canadian dollars (dollars). RESULTS: The drops of Cosopt (39.60 +/- 0.45 microL) were considerably larger than the drops of Combigan (33.75 +/- 0.60 microL) and Xalacom (30.87 +/- 0.37 microL). The average number of drops per millilitre varied from 25.25 +/- 0.29 (Cosopt) to 32.40 +/- 0.39 microL (Xalacom). Combigan presented the lowest daily cost (dollars 0.87 +/- 0.02) followed by Xalacom (dollars 1.09 +/- 0.01) and Cosopt (dollars 1.22 +/- 0.01). The average cost by year varied from dollars 316.75 +/- 5.59 (Combigan) to dollars 445.96 +/- 5.16 (Cosopt), with a total difference of dollars 129.21 per year of treatment. CONCLUSIONS: There was a statistically significant difference in average drop size and cost among the three studied drugs. Combigan presented the lowest daily cost followed by Xalacom and Cosopt.     

Synapsis, recombination, and chromatin remodeling in the XY body of armadillos

Three xenarthrans species Chaetophractus villosus, Chaetophractus vellerosus, and Zaedyus pichiy have been used for the analysis of the structure, behavior, and immunochemical features of the XY body during pachytene. In all these species, the sex chromosomes form an XY body easily identifiable in thin sections by the special and regular packing of the chromatin fibers of the internal region of the XY body (“differential” regions) and those of the peripheral region (synaptic region). Spermatocyte spreads show a complete synapsis between the X- and the Y-axis, which lasts up to the end of pachytene. From the early pachytene substages to the late ones, the X-axis develops prominent branches, which in late pachytene span the synaptic region. Synapsis is regular as shown by SYCP1 labeling. Axial development is followed by SYCP3 labeling and in the asynaptic region of the X-axis by BRCA1. Gamma-H2AX labels exclusively the differential (asynaptic) region of the X chromosome. A single focus is labeled by MLH1 in the synaptic region. The location of this MLH1 focus spans from 0.3 to 1.6 μm from the telomere in the analyzed xenarthrans, covering approximately half of the Y-axis length. It is concluded that xenarthrans, as basal placental mammals, harbor the largest pseudoautosomal regions of presently analyzed mammals, and shows the typical features of meiotic sex chromosome inactivation (MSCI).     

Immunotherapy for patients with persistent allergic rhinitis unsatisfied with free chronic pharmacotherapy

BackgroundChronic pharmacotherapy is recommended to patients with persistent moderate-severe (PM-S) allergic rhinitis (AR). The cost of pharmacotherapy is the main barrier to achieve symptoms control.Aims of the studyTo determine the benefits of mite subcutaneous immunotherapy (SIT) in patients with PM-S AR not satisfied with chronic pharmacotherapy received free of charge.MethodsOpen study with seven (7) patients with PM-S AR not satisfied with chronic pharmacotherapy. Prior to enrollment patients had received monthly for more than five months and free of charge, optimal pharmacotherapy. We compared, off pharmacotherapy, symptoms and quality of life (QOL) before and during SIT.ResultsMite SIT improved nasal symptoms, non nasal symptoms and QOL. Off pharmacotherapy patients reported adequate control of symptoms and were satisfied.ConclusionsNot all patients with PM-S AR are satisfied with chronic pharmacotherapy, even if medication is received free of charge. SIT control symptoms and satisfies patients with PM-S AR unsatisfied with free chronic pharmacotherapy.     

移植胚鼠神经干细胞对大鼠脊髓损伤后红核神经元损伤的影响

目的研究神经干细胞(NSCs)移植对大鼠脊髓损伤(SCI)后红核神经元的作用。方法5-溴脱氧尿嘧啶核苷(BrdU)法标记处于对数生长期的NSCs,采用电控脊髓损伤打击装置制作大鼠脊髓损伤模型。实验分为3组:NSCs组、SCI组和假手术组(Sham组)。SCI后3 d进行NSCs移植,用免疫组化法观察移植细胞的存活及迁移情况,用辣根过氧化物酶(HRP)逆行示踪技术标记红核神经元,并用四甲基联苯胺(TMB)呈色反应显示红核脊髓束神经元的存活情况,用行为学(BBB)评分法观察大鼠瘫痪肢体的恢复情况。结果在损伤脊髓区域可检测到BrdU标记的阳性NSCs,中脑HRP标记红核神经元数目明显多于SCI组(P<0.01),BBB评分亦明显高于SCI组(P<0.01)。结论体外培养的胚胎大鼠NSCs在移植到脊髓损伤区域后可存活和迁移,对SCI后中脑红核神经元具有保护作用,从而促进了大鼠肢体功能的恢复。     

Predominance of Trypanosoma cruzi genotypes in two reservoirs infected by sylvatic Triatoma infestans of an endemic area of Chile

We report results of Trypanosoma cruzi infection and parasite genotypes in the wild Octodon degus and synantropic reservoir Rattus rattus from an endemic area with sylvatic Triatoma infestans as the only detected vector. The infection status was determined by hemi-nested PCR directed to minicircles DNA and genotyping by hybridization tests with a panel of five specific probes, including two probes for TcI subgroups (clones 19 and 20). O. degus was found infected with 13.3% and mainly with sublineage TcIId, and less with TcIIb and TcI. Meantime the synantropic R. rattus was found infected with 27.7% and mainly with TcI and much less with TcIId, TcIIb and TcIIe.The results are discussed to explain the distribution of T. cruzi genotypes between these two reservoirs and the importance of sylvatic foci of T. infestans allowing the permanence of the wild and peridomestic cycle of Chagas disease.     

The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4

BACKGROUND AND PURPOSE

Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data.

EXPERIMENTAL APPROACH

The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data.

KEY RESULTS

The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9–39) over Ex4(9–30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp.

CONCLUSIONS AND IMPLICATIONS

GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor.