Association analysis of urotensin II gene (UTS2) and flanking regions with biochemical parameters related to insulin resistance.

Background. Urotensin II (UII) is a potent vasoconstrictor peptide, which signals through a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR). UII exerts a broad spectrum of actions in several systems such as vascular cell, heart muscle or pancreas, where it inhibits insulin release. Objective. Given the reported role of UII in insulin secretion, we have performed a genetic association analysis of the UTS2 gene and flanking regions with biochemical parameters related to insulin resistance (fasting glucose, glucose 2 hours after a glucose overload, fasting insulin and insulin resistance estimated as HOMA). Results and Conclusions. We have identified several polymorphisms associated with the analysed clinical traits, not only at the UTS2 gene, but also in thePER3 gene, located upstream from UTS2. Our results are compatible with a role for UII in glucose homeostasis and diabetes although we cannot rule out the possibility that PER3 gene may underlie the reported associations.

Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010.

Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. METHODS: Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. RESULTS: From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. CONCLUSIONS: The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.

Mutant prevention concentrations of fluoroquinolones for Enterobacteriaceae expressing the plasmid-carried quinolone resistance determinant qnrA1.

The influence of qnrA1 on the development of quinolone resistance in Enterobacteriaceae was evaluated by using the mutant prevention concentration parameter. The expression of qnrA1 considerably increased the mutant prevention concentration compared to strains without this gene. In the presence of qnrA1, mutations in gyrA and parC genes were easily selected to produce high levels of quinolone resistance.

In Vivo Selection of Fluoroquinolone-Resistant Escherichia coli Isolates Expressing Plasmid-Mediated Quinolone Resistance and Expanded-Spectrum β-Lactamase

A ciprofloxacin-resistant Escherichia coli isolate, isolate 1B, was obtained from a urinary specimen of a Canadian patient treated with norfloxacin for infection due to a ciprofloxacin-susceptible isolate, isolate 1A. Both isolates harbored a plasmid-encoded sul1-type integron with qnrA1 and blaVEB-1 genes. Isolate 1B had amino acid substitutions in gyrase and topoisomerase.

Plasmid-mediated quinolone resistance in Australia

The aim of this study was to search for plasmid-encoded quinolone resistance determinants QnrA and QnrS in fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing enterobacterial isolates recovered in Sydney, Australia, in 2002. Twenty-three fluoroquinolone-resistant, of which 16 were also ESBL-positive, enterobacterial and nonrelated isolates were studied. PCR with primers specific for qnrA and qnrS genes and primers specific for a series of ESBL genes were used. A qnrA gene was identified in two ESBL-positive isolates, whereas no qnrS-positive strain was found. The QnrA1 determinant was identified in an Enterobacter cloacae isolate and in a carbapenem-resistant Klebsiella pneumoniae isolate, both of which expressed the same ESBL SHV- 12. Whereas no plasmid was identified in the E. cloacae isolate, K. pneumoniae K149 possessed two conjugative plasmids, one that harbored the qnrA and bla (SHV)-12 genes whereas the other expressed the carbapenemase gene bla (IMP-4). The qnrA gene, was located in both cases downstream of the orf513 recombinase gene and upstream of the qnrA1 gene, a structure identical to that found in sul1-type integron In36 and qnrA-positive strains from Shanghai, China. However, the gene cassettes of the sul1-type integrons were different. This study identified the first plasmid-mediated quinolone resistance determinant in Enterobacteriaceae in Australia.