Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Importance of tissue sampling, laboratory methods, and patient characteristics for detection of Pneumocystis in autopsied lungs of non-immunosuppressed individuals.

To understand the epidemiological significance of Pneumocystis detection in a lung tissue sample of non-immunosuppressed individuals, we examined sampling procedures, laboratory methodology, and patient characteristics of autopsy series reported in the literature. Number of tissue specimens, DNA-extraction procedures, age and underlying diagnosis highly influence yield and are critical to understand yield differences of Pneumocystis among reports of pulmonary colonization in immunocompetent individuals.

Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

Resinas de intercambio iónico para prolongar la liberación de los fármacos / Resins of ionic exchange to prolong the liberation of the fármacos

Se realizó el estudio de las resinas de intercambio iónico como sistemas para liberación prolongada con atención a los factores que afectan la formación de los resinatos o complejos fármacoresina. También se estudió la liberación de los principios activos a partir de los complejos y de las formas terminadas que los contienen, evaluándose los factores que afectan dicho proceso y las cinéticas a las que se ajusta. Se revisaron las combinaciones de procesos tecnológicos (principalmente la formación de complejos iónicos y su recubrimiento) que potencian la utilidad de los resinatos para prolongar la liberación a través de mecanismos combinados de intercambio iónico y difusión a través de membranas, combinaciones dirigidas a reducir las limitaciones inherentes a cada proceso por separado y conseguir un control eficaz de la liberación de fármacos iónicos(AU)

Resinas de intercambio iónico para prolongar la liberación de los fármacos / Ion-exchange resins for prolonged release of drugs

Se realizó el estudio de las resinas de intercambio iónico como sistemas para liberación prolongada con atención a los factores que afectan la formación de los resinatos o complejos fármacoresina. También se estudió la liberación de los principios activos a partir de los complejos y de las formas terminadas que los contienen, evaluándose los factores que afectan dicho proceso y las cinéticas a las que se ajusta. Se revisaron las combinaciones de procesos tecnológicos (principalmente la formación de complejos iónicos y su recubrimiento) que potencian la utilidad de los resinatos para prolongar la liberación a través de mecanismos combinados de intercambio iónico y difusión a través de membranas, combinaciones dirigidas a reducir las limitaciones inherentes a cada proceso por separado y conseguir un control eficaz de la liberación de fármacos iónicos