RESUMEN
Bacterial infections caused by intracellular pathogens are difficult to control. Conventional antibiotic therapies are often ineffective, as high doses are needed to increase the number of antibiotics that will cross the host cell membrane to act on the intracellular bacterium. Moreover, higher doses of antibiotics may lead to elevated severe toxic effects against host cells. In this context, antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) have shown great potential to treat such infections by acting directly on the intracellular pathogenic bacterium or performing the delivery of cargos with antibacterial activities. Therefore, in this mini-review, we cover the main AMPs and CPPs described to date, aiming at intracellular bacterial infection treatment. Moreover, we discuss some of the proposed mechanisms of action for these peptide classes and their conjugation with other antimicrobials.
Asunto(s)
Infecciones Bacterianas , Péptidos de Penetración Celular , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Humanos , Proteínas Citotóxicas Formadoras de PorosRESUMEN
BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete FreundÌs adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. RESULTS: Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. CONCLUSIONS: Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration and secretion of inflammatory mediators. Our results corroborate and support the notion that mice with different genetic background have different susceptibility to EAP induction. Prostate 77:94-104, 2017. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/patología , Dolor Pélvico/genética , Dolor Pélvico/patología , Prostatitis/genética , Prostatitis/patología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedad Crónica , Susceptibilidad a Enfermedades , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Dolor Pélvico/inmunología , Prostatitis/inmunología , Especificidad de la EspecieRESUMEN
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has significant variability in its presentation. In this study, we present 2 novel cases of prostatitis in which "buzz" is described as the primary pain symptom. These cases describe patients with the primary complaint of "cell phone-like buzzing" within the perineum, with accompanying urinary symptoms consistent with prostatitis. CP/CPPS is a multifactorial disease within which psychological, inflammatory, neurologic, and neuromuscular etiologies are at play. As in other disease descriptions, a buzzing sensation represents the interaction of multiple pathways that have significant overlay with CP/CPPS. As such, we believe buzzing might represent a new symptom of CP/CPPS.