Rifampin pharmacokinetics in tuberculosis-diabetes mellitus patients: a pilot study from Baja California, Mexico.

BACKGROUND: Worldwide, there has been an increase in type 2 diabetes mellitus (DM2) as a comorbidity of tuberculosis (TB), which is characterized by alterations in the pharmacokinetics of drugs used for TB treatment.OBJECTIVE: To characterize the pharmacokinetics of rifampin in patients with TB and TB-DM2.METHODS: Blood samples were collected in two hospitals in Baja California, Mexico from March through December 2017. Sampling was not random and included 14 patients with TB and 16 with TB-DM2. High-performance liquid chromatographic (HPLC) was carried out to determine the concentration of rifampin in human serum.RESULTS: On average, the highest concentration of rifampin for both groups was registered at 2.5 h after ingestion (3.5 ± 2.64 µg/ml). The maximum difference in concentration (Cmax) of rifampin between TB and TB-DM2 group was not significant (P > 0.05). Importantly however, the analysis showed suboptimal levels of Cmax in a high proportion of both groups of patients studied.CONCLUSION: The study suggests that under the currently recommended rifampin dose, suboptimal Cmax levels are reached in a high proportion of patients, regardless of whether they have diabetes or not. It may therefore be necessary to use higher doses of rifampin and perform routine monitoring of serum levels. However, further work is needed to confirm these findings.

Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico.

The most frequent mutations associated with rifampin and isoniazid resistance in Mycobacterium are the substitutions at codons 531 and 315 in the rpoB and katG genes, respectively. Hence, the aim of this study was to characterize these mutations in Mycobacterium isolates from patients suspected to be infected with drug-resistant (DR) pulmonary tuberculosis (TB) in Veracruz, Mexico. Drug susceptibility testing of 25 clinical isolates revealed that five were susceptible while 20 (80%) were DR (15% of the annual prevalence for Veracruz). Of the DR isolates, 15 (75%) were resistant to rifampin, 17 (85%) to isoniazid and 15 (75%) were resistant to both drugs (MDR). Sequencing analysis performed in the isolates showed that 14 (93%) had mutations in the rpoB gene; seven of these (47%) exhibited a mutation at 531 (S-->L). Ten (58%) of the 20 resistant isolates showed mutations in katG; nine (52%) of these 10 exhibited a mutation at 315 (S-->T). In conclusion, the DR profile of the isolates suggests a significant number of different DR-TB strains with a low frequency of mutation at codons 531 and 315 in rpoB and katG, respectively. This result leads us to consider different regions of the same genes, as well as other genes for further analysis, which is important if a genetic-based diagnosis of DR-TB is to be developed for this region.

Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico

The most frequent mutations associated with rifampin and isoniazid resistance in Mycobacterium are the substitutions at codons 531 and 315 in the rpoB and katG genes, respectively. Hence, the aim of this study was to characterize these mutations in Mycobacterium isolates from patients suspected to be infected with drug-resistant (DR) pulmonary tuberculosis (TB) in Veracruz, Mexico. Drug susceptibility testing of 25 clinical isolates revealed that five were susceptible while 20 (80 percent) were DR (15 percent of the annual prevalence for Veracruz). Of the DR isolates, 15 (75 percent) were resistant to rifampin, 17 (85 percent) to isoniazid and 15 (75 percent) were resistant to both drugs (MDR). Sequencing analysis performed in the isolates showed that 14 (93 percent) had mutations in the rpoB gene; seven of these (47 percent) exhibited a mutation at 531 (S[L). Ten (58 percent) of the 20 resistant isolates showed mutations in katG; nine (52 percent) of these 10 exhibited a mutation at 315 (S[T). In conclusion, the DR profile of the isolates suggests a significant number of different DR-TB strains with a low frequency of mutation at codons 531 and 315 in rpoB and katG, respectively. This result leads us to consider different regions of the same genes, as well as other genes for further analysis, which is important if a genetic-based diagnosis of DR-TB is to be developed for this region.

Secondary structure prediction of the hemagglutinin-neuraminidase from a porcine rubulavirus.

The Hemagglutinin-Neuraminidase (HN) from 'La Piedad, Michoacan' porcine rubulavirus (LPMV) interacts specifically with NeuAc alpha 2,3 lactose residues on the target cell. In this work we report the secondary structure of this protein, determined with five different theoretical algorithms. Results indicate that the HN protein is organized in: an intracellular region (from amino acid 1 to 25); in a beta-strand transmembrane region (residue 26 to 47), typically hydrophobic, rigid and solvent inaccessible; and extracellular region (48 to 576), which possesses hemagglutinating and neuraminidase activity. The secondary structure in this region is organized in a beta-loop-beta alternated with few alpha-helices. Regions with structural and functional implications were determined by pattern search and multiple alignment of the HN from LPM with 12 rubulaviruses and paramyxoviruses HN sequences. The low diversity observed among the HN sequences evaluated indicates that in general the structural organization of the protein, and in particular its sugar binding domain, is closely related among both genera, thus suggesting that the sugar binding domain is well preserved through evolution.

VIR: a computational tool for analysis of immunoglobulin sequences.

In this paper a microcomputer software named VIR (Variable domains of the Immune Receptors) is reported. This package can be used in sequence studies of immunoglobulin variable domains. The main features of the VIR software in the sequences management are: (1) ease of information recovery/extraction from amino acid sequences; and (2) its capability to obtain multiple sequence alignments with predefined characteristics (i.e. specie and/or specificity). As an analytical tool, the VIR package employs such multiple sequence alignments to compute: (1) tables showing amino acid frequencies; (2) three variability indexes; (3) identity matrices; (4) random samples; and (5) sequences with possible canonical structures. Thus the software reported here is proposed as a useful tool to carry out detailed studies of immunoglobulin variable domains.