Treatment of intracellular Mycobacterium avium complex infection by free and liposome-encapsulated sparfloxacin

Mycobacterium avium-M. intracellulare complex (MAC) is the most frequent cause of opportunistic bacterial infection in patients with AIDS. Previous studies have indicated that liposome-encapsulated aminoglycosides are highly effective in treating MAC infections in mice. We investigated whether the fluoroquinolone sparfloxacin is effective in treating MAC infection in the murine macrophage-like cell line J774. Sparfloxacin was encapsulated in the membrane phase of multilamellar liposomes composed of phosphatidylglycerol-phosphatidylcholine-cholesterol (1:1:1 molar ratio). MAC-infected macrophages were treated for either 24 h or 4 days with free or liposome-encapsulated sparfloxacin. Treatment with free or liposome- encapsulated sparfloxacin (6 μg/ml) for 24 h resulted in the reduction of the growth index to 25 and 30% of that of untreated controls, respectively. When cultures were treated for 4 days, free sparfloxacin reduced the growth index to 6% of that of the untreated control, while liposome-encapsulated sparfloxacin reduced it to 8% of that of the control

Antiprotozoal and antimycobacterial activities of Persea americana seeds

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC(50) <0.634 μg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 μg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 μg/ml). CONCLUSIONS: The CHCl(3) and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl(3) extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 μg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 μg/ml

Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes

We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 μg mL−1; the pure compounds eupomatenoid-1, fargesin, and (8R,8′R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 μg mL−1), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 μg mL−1). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC50 < 0.624 μg mL−1); in contrast, fargesin and (8R,8′R,9R)-cubebin were moderately active (IC50 < 275 μg mL−1). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity

B Lymphocyte as a Target of Bacterial Infections

B lymphocytes are central players in the immune response; canonically, they have been recognized as precursors of antibody-producing cells: plasma cells. Recent findings have shown that the role of B lymphocytes goes far beyond the production of antibodies. There are different subtypes of B lymphocytes with different participations in innate and adaptive responses that include the recognition of the antigen, its processing, and its presentation to T lymphocytes, as well as the production of cytokines that impact and modulate the response toward the pathogen. Traditionally, it has been considered that B lymphocytes do not have phagocytic abilities that allow them to internalize, to process, or even to be infected by bacterial pathogens. The new information has shown that B lymphocytes can be readily infected by bacterial pathogens like Salmonella, Francisella, Moraxella, and Mycobacterium, among others, and respond to those infections. Some of the recent advances on these topics will be presented in this chapter

Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

BACKGROUND: New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). METHODS: The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. RESULTS: The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. CONCLUSION: UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB

A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer:International Journal of Molecular Sciences

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9–12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9–12 and identifying which of them has developed cancer