Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.

We purified poly(A)+ mRNA from the spleen and lymph nodes at designated times after infection with Leishmania major in genetically susceptible BALB/c and resistant C57BL/6 mice. The steady-state levels of IL-2, IFN-gamma, IL-4, and IL-1 beta mRNA were determined using Northern hybridizations. IL-2 mRNA levels in the infected organs of BALB/c and C57BL/6 mice were comparable after infection, but IFN-gamma and IL-4 mRNA levels were reciprocally expressed. Levels of IFN-gamma mRNA in C57BL/6 draining nodes and spleen were significantly greater than in BALB/c mice except at 4 and 6 wk of infection, when splenic IFN-gamma mRNA levels were transiently comparable. In contrast, IL-4 mRNA was apparent only in BALB/c and not in C57BL/6 nodes and spleen. Tissue levels of IL-1 beta mRNA were 10-20-fold greater in BALB/c mice. BALB/c mice were pretreated with GK1.5 mAb, a manipulation that promotes healing of subsequent infection by transiently depleting L3T4+ cells. At 8 wk of infection, by which time lymphoid organs were repopulated with L3T4+ cells, GK1.5-pretreated BALB/c mice produced IFN-gamma, but not IL-4 message. Serum levels of IgE were markedly elevated in infected BALB/c, but not in infected C57BL/6 or GK1.5-pretreated BALB/c mice, consistent with in vivo biologic activity of IL-4 in nonhealing mice. Treatment of infected BALB/c mice with neutralizing anti-IL-4 antibody abolished the elevation of serum IgE and significantly attenuated the progression of disease as assessed by size and ulceration of the lesion, and by reduction in the number of tissue parasites. Both protective and deleterious responses to Leishmania infection have previously been shown to be L3T4+ cell dependent. Our findings are consistent with the differential expansion of protective, IFN-gamma-producing Th1 cells in healing mice, and the expansion of deleterious, IL-4-producing Th2 cells in nonhealing mice. The inverse relationship of IFN-gamma and IL-4 gene expression during leishmaniasis may underlie the divergence of cellular and humoral immunity that occurs during chronic infection with Leishmania and possibly other intracellular parasites

Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism.

BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatment with anti-IFN-gamma. These data suggest a novel mechanism of cellular immunity established by interference with the development of Th2 cells during infection

Tegumentary leishmaniasis and coinfections other than HIV

<div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div

Treatment for cellulite

Cellulite is a multifactorial condition that is present in 80% to 90% of postpubertal women and is one of the most intolerable esthetic imperfections. There are several theories on the pathophysiology of cellulite, and a number of different therapeutic regimens have been developed, from topical treatments to mechanical or energy-based devices. In this brief review, we summarize the scientific landscape to determine the clinical evidence with regard to the safety and efficacy of cellulite treatment options. Clinical protocols and the author’s experience using a combination of internal and external procedures are also discussed. Studies using laser and light modalities along with radiofrequency have shown improvements in cellulite and a good safety profile, but acoustic wave therapy, subcision, and the 1440-nm Nd:YAG minimally invasive laser have demonstrated the most beneficial results in cellulite reduction. Although there is paucity of scientific evidence for treatments that improve cellulite, future emerging options and their combination may pave the way to eradicate this primarily cosmetic esthetic concern. Keywords: Cellulite, pathophysiology, adipocytes, radiofrequency, laser

Vaginal rejuvenation: From scalpel to wands

Vaginal rejuvenation procedures are increasing in popularity in terms of types of treatment offered, number of patients undergoing them, clinical studies, and in the controversy surrounding them. Both non-invasive and invasive solutions are being developed by pharmaceutical and technological companies. Radiofrequency devices and lasers are spearheading the energy-based device space, and fillers and platelet-rich plasma are used to address several concerns surrounding vaginal health. In this review, an overview of the growing field of vaginal rejuvenation is presented, as well as the authors’ personal view and analysis of this clinical space

Low dose time-resolved CT-angiography in pediatric patients with venous malformations using 3rd generation dual-source CT: Initial experience

Objectives: To prospectively evaluate the diagnostic value and radiation dose of time-resolved CT-Angiography (4D-CTA) in pediatric patients with venous malformations using 3rd generation dual-source CT (DSCT) at 70 kVp tube voltage. Methods: Between November 2014 and August 2015, seven children (2 male, 5 female; median age, 9 years; range 3–12 years) with suspected peripheral, non-cerebral, venous malformations were included in this feasibility study and underwent US, MRI and 4D-CTA. All three imaging modalities were analyzed and compared individually by an experienced interventional radiologist and a pediatric surgeon using a 5-point Likert scale, with regard to diagnosis of the vascular anomaly, additional information like presence of thrombophlebitis and lesion extension, flow dynamics, localization, volume and significance for treatment planning. For quantitative statistical analysis, an unifactorial analysis of variance was performed for every parameter and all three imaging modalities. Radiation dose values as expressed by the volume CT dose index (CTDIvol) and dose-length product (DLP) were recorded for of all patients. Results: Three out of six patients had isolated type I venous malformations without peripheral venous drainage which could be demonstrated on MRI and CT. In two out of six patients a type II venous malformation with drainage into normal veins was diagnosed. In one case, 4D-CT was the only imaging modality that revealed a slow-flow venous malformation with shunting supply by a hypodynamic arterial feeder. Treatment planning: 4D-CTA was rated as the best imaging modality for treatment planning with agreement between radiologist and surgeon, especially with respect to the hemodynamics of the venous malformation. Conclusions: 4D-CTA at 70 kVp is a fast imaging modality that provides comprehensive diagnostic information of venous malformations in pediatric patients and is very valuable for therapy planning. Radiation dose of 4D-CTA must be weighted against the diagnostic information as well as the potential risk for sedation and contrast administration during MRI. Keywords: 4D-CTAngiography, Venous malformation, Low dose dual-score CT, Pediatri