Manifestações urinárias e sexuais em pacientes infectados pelo HTLV-I

HTLV-I is considered to be a virus of low morbidity, since the principal diseases associated with this viral infection, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are observed in less than 5% of infected individuals. Urinary symptoms are frequent in patients with myelopathy and consist principally of nocturia, frequency, urgency, and urinary incontinence; however, the importance of these dysfunctions and their correlation with myelopathy is still to be fully clarified. This review gives particular emphasis to the high frequency of urinary and sexual complaints not only in patients with myelopathy but also in individuals considered to be HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the most common urodynamic findings. The fact that urinary complaints and urodynamic parameters reported in individuals considered to be carriers are similar to those detected in patients with myelopathy supports the hypothesis that urinary disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction is frequently observed in HTLV-I-infected patients with or without myelopathy. Urinary tract infections are also highly prevalent in these patients. Despite the lack of an effective treatment for myelopathy, the use of anticholinergic drugs and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and erectile dysfunction in these patients.O HTLV-1 é considerado um vírus de baixa morbidade sendo a mielopatia associada ao HTLV-1 (HAM/TSP) e a leucemia / linfoma de células T do adulto (ATL) as principais doenças associadas à infecção viral, observados em menos de 5% dos indivíduos infectados. Manifestações urinárias são freqüentes em pacientes com mielopatia, e representadas principalmente por noctúria, polaciúria, urgência e incontinência urinária, embora a importância destas alterações, e a correlação com a patologia medular não tem sido devidamente estudada. Nesta revisão enfatizamos a elevada freqüência de queixas urinárias e sexuais em pacientes, não apenas os portadores de mielopatias, mas também em indivíduos considerados como portadores assintomáticos do HTLV-I. Hiperatividade detrusora e dissinergia vesico-esfincteriana são as manifestações urodinâmicas mais freqüentes. A documentação de queixas urinárias e os achados urodinâmicos observados em indivíduos considerados portadores assintomáticos são semelhantes aos detectados em pacientes com mielopatia dão suporte à hipótese que alterações urinárias possam representar uma forma oligossintomática da HAM/TSP. Disfunção eréctil é freqüentemente observada em pacientes infectados pelo HTLV-1, com ou sem mielopatia. Infecção do trato urinário também tem elevada prevalência nestes pacientes. A despeito da ausência de um tratamento efetivo da mielopatia, o uso de anticolinérgicos e de inibidores da fosfodiesterase tipo 5 podem melhorar as queixas urinárias e a disfunção eréctil destes pacientes

Urinary and sexual manifestations of patients infected by HTLV-I

HTLV-I is considered to be a virus of low morbidity, since the principal diseases associated with this viral infection, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are observed in less than 5% of infected individuals. Urinary symptoms are frequent in patients with myelopathy and consist principally of nocturia, frequency, urgency, and urinary incontinence; however, the importance of these dysfunctions and their correlation with myelopathy is still to be fully clarified. This review gives particular emphasis to the high frequency of urinary and sexual complaints not only in patients with myelopathy but also in individuals considered to be HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the most common urodynamic findings. The fact that urinary complaints and urodynamic parameters reported in individuals considered to be carriers are similar to those detected in patients with myelopathy supports the hypothesis that urinary disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction is frequently observed in HTLV-I-infected patients with or without myelopathy. Urinary tract infections are also highly prevalent in these patients. Despite the lack of an effective treatment for myelopathy, the use of anticholinergic drugs and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and erectile dysfunction in these patients.O HTLV-1 é considerado um vírus de baixa morbidade sendo a mielopatia associada ao HTLV-1 (HAM/TSP) e a leucemia / linfoma de células T do adulto (ATL) as principais doenças associadas à infecção viral, observados em menos de 5% dos indivíduos infectados. Manifestações urinárias são freqüentes em pacientes com mielopatia, e representadas principalmente por noctúria, polaciúria, urgência e incontinência urinária, embora a importância destas alterações, e a correlação com a patologia medular não tem sido devidamente estudada. Nesta revisão enfatizamos a elevada freqüência de queixas urinárias e sexuais em pacientes, não apenas os portadores de mielopatias, mas também em indivíduos considerados como portadores assintomáticos do HTLV-I. Hiperatividade detrusora e dissinergia vesico-esfincteriana são as manifestações urodinâmicas mais freqüentes. A documentação de queixas urinárias e os achados urodinâmicos observados em indivíduos considerados portadores assintomáticos são semelhantes aos detectados em pacientes com mielopatia dão suporte à hipótese que alterações urinárias possam representar uma forma oligossintomática da HAM/TSP. Disfunção eréctil é freqüentemente observada em pacientes infectados pelo HTLV-1, com ou sem mielopatia. Infecção do trato urinário também tem elevada prevalência nestes pacientes. A despeito da ausência de um tratamento efetivo da mielopatia, o uso de anticolinérgicos e de inibidores da fosfodiesterase tipo 5 podem melhorar as queixas urinárias e a disfunção eréctil destes pacientes

CXCR1 and SLC11A1 polymorphisms affect susceptibility to cutaneous leishmaniasis in Brazil: a case-control and family-based study.

BACKGROUND: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice. To look at the interplay between PMN and macrophages in disease progression in humans we asked whether polymorphisms at genes that regulate their infiltration or function are associated with different clinical phenotypes. Specifically, CXCR1 (IL8RA) and CXCR2 (IL8RB) are receptors for chemokines that attract PMN to inflammatory sites. They lie 30-260 kb upstream of SLC11A1, a gene known primarily for its role in regulating macrophage activation, resistance to leishmaniasis, and wound healing responses in mice, but also known to be expressed in PMN, macrophages and dendritic cells. METHODS: Polymorphic variants at CXCR1, CXCR2 and SLC11A1 were analysed using Taqman or ABI fragment separation technologies in cases (60 CL; 60 ML), unrelated controls (n = 120), and multicase families (104 nuclear families; 88 ML, 250 CL cases) from Brazil. Logistic regression analysis, family-based association testing (FBAT) and haplotype analysis (TRANSMIT) were performed. RESULTS: Case-control analysis showed association between the common C allele (OR 2.38; 95% CI 1.23-4.57; P = 0.009) of CXCR1_rs2854386 and CL, supported by family-based (FBAT; Z score 2.002; P = 0.045) analysis (104 nuclear families; 88 ML, 250 CL cases). ML associated with the rarer G allele (Z score 1.999; P = 0.046). CL associated with a 3' insertion/deletion polymorphism at SLC11A1 (Z score 2.549; P = 0.011). CONCLUSIONS: The study supports roles for CXCR1 and SLC11A1 in the outcome of L. braziliensis infection in humans. Slc11a1 does not influence cutaneous lesion development following needle injection of Leishmania in mice, suggesting that its role here might relate to the action of PMN, macrophage and/or dendritic cells in the wound healing response to the sand fly bite. Together with the CXCR1 association, the data are consistent with hypotheses relating to the possible role of PMN in initiation of a lesion following the delivery of parasites via the sand fly bite. Association of ML with the rare derived G allele suggests that PMN also have an important positive role to play in preventing this form of the disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice

Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatmentinfo:eu-repo/semantics/publishedVersio

Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production

BACKGROUND: Disseminated leishmaniasis is an emerging infectious disease, mostly due to L. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis. METHODS: In the current study we evaluated the in vitro production of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates. RESULTS: Regardless of the source of L. braziliensis antigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the two L. braziliensis antigens was assessed in a paired analysis in which we showed that L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients. CONCLUSION: This study provides evidence that antigens prepared from genotypically distinct strains of L. braziliensis induce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome of L. braziliensis infection

Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study

BACKGROUND: The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite. METHODS: Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry. RESULTS: A significant decrease in plasma Zn was observed in all three patient groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r = 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with deficient cellular (VL<<LCL<ML) and exacerbated humoral (VL>LCL>ML) immune response. Ex vivo production of parasite-induced IFN-γ was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). In vitro, increased Cu levels inhibited IFN-γ production. CONCLUSIONS: 1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-γ production