Frequency and antimicrobial susceptibility of Shigella species isolated in Children Medical Center Hospital, Tehran, Iran, 2001-2006

AbstractAppropriate antimicrobial treatment of shigellosis depends on identifying its changing resistance pattern over time. We evaluated 15,255 stool culture submitted from July 2001 to June 2006 to the Laboratory of Children Medical Center Hospital. Specimen culture, bacterial identification, and disk diffusion susceptibility testing were performed according to National Committee for Clinical Laboratory Standards guidelines. From 15,255 stool samples, 682 (4.5%) were positive for Shigella species. The most common species of Shigella were S. flexneri (48%) and S. sonnei (45%); other results were S. dysenteriae (5%) and S. boydii (2%). The rate of Sensitivity to ceftriaxone (95%), ceftizoxime (94%), and nalidixic acid (84%) were among our isolates. Resistance to co-trimoxazole and ampicillin was 87% and 86%, respectively. S. flexneri was more multiresistant than other species (47.9%). Our isolates are overall most sensitive to ceftriaxone, ceftazidime, and nalidixic acid (> 84%). They were most resistant to co-trimoxazole and ampicillin (> 86%). Because resistance varies according to specific location, continuous local monitoring of resistance patterns is necessary for the appropriate selection of empirical antimicrobial therapy

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed

Molecular characterization of occult hepatitis B virus infection in patients with end-stage liver disease in Colombia.

ABSTARCT: Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease. METHODS: Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia). Samples obtained from patients who were negative for the surface antigen of HBV (n = 50) were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to determine the genotype and mutations; additionally, viral genome integration events were examined by the Alu-PCR technique. RESULTS: In five cases out of 50 patients (10%) the criteria for OBI was confirmed. HBV genotype F (subgenotypes F1 and F3), genotype A and genotype D were characterized in liver samples. Three integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing Factor 2, and the zinc finger 263 genes were identified in two OBI cases. Sequence analysis of the viral genome of the 5 OBI cases showed several punctual missense and nonsense mutations affecting ORFs S, P, Core and X. CONCLUSIONS: This is the first characterization of OBI in patients with end-stage liver disease in Colombia. The OBI cases were identified in patients with HCV infection or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12) described in this study have not been previously reported. Further studies are required to validate the role of mutations and integration events in OBI pathogenesis

Virtue and Happiness in Socratesâ Moral Thought

The question of âwhat is happiness?â is among the most important questions of Greek philosophy. In those early works of Plato that very likely represent the views of Socrates, Socrates mainly focuses on moral issues and tries to get close to an explanation of the nature of virtue (or virtues), the happy life and the relation between virtue (or virtues) and the realization of happiness (Eudemonia). Given the Principle of Eudemonism, in this paper it is tried to examine Socratesâ views on the relation between virtue and happiness and defend what is known as the âPrinciple of the Sovereignty of Virtueâ

The Doctrine of Prime Matter in Aristotle’s Science of Nature

Aristotle presents his doctrine of prime matter in order to give an explanation for change and especially for generation and corruption. Hence, no surprise, the place to look for the origin of this doctrine is nowhere but Aristotle’s science of nature. The first three sections of this article examine the Aristotle’s explanation of this doctrine according to his teachings in the works concerning the science of nature (Physics and On Generation and Corruption) and show that why Aristotle introduces such a thing as prime matter into his science of nature and what he does mean by that. Then, in the last section, I will show that Aristotle’s explanation of prime matter as the ultimate substratum of all things, at least as far as these works are concerned, is not plausible and without difficulties

Virtue and Happiness in Socrates’ Moral Thought

The question of “what is happiness?” is among the most important questions of Greek philosophy. In those early works of Plato that very likely represent the views of Socrates, Socrates mainly focuses on moral issues and tries to get close to an explanation of the nature of virtue (or virtues), the happy life and the relation between virtue (or virtues) and the realization of happiness (Eudemonia). Given the Principle of Eudemonism, in this paper it is tried to examine Socrates’ views on the relation between virtue and happiness and defend what is known as the “Principle of the Sovereignty of Virtue”