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Breast surgeons seem to agree on the fact that a same-day surgery (mastectomy and breast reconstruction) protocol provides appropriate cancer treatment during times of unprecedented resource limitations, such as in the COVID era. In this scenario, pre-pectoral implant-based breast reconstruction can be definitively considered a sustainable technique. Nevertheless, the authors focus on the management of patients who had already undergone a same day procedure with two-stage breast reconstruction, implanting a breast tissue expander during the last two-year period and have been progressively delayed according to a surgical care based on priority. We coined the expression "unhappy tissue expander" to define all those symptomatic patients for which surgery should not be delayed even during an epidemic context.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Implantes de Mama , Neoplasias de la Mama , COVID-19 , Mamoplastia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Estudios Retrospectivos , SARS-CoV-2 , Dispositivos de Expansión Tisular , Resultado del TratamientoRESUMEN
Considering the diagnostic capability offered by cone-beam computed tomography (CBCT), nowadays orthodontists often use this exam for treatment planning, especially in cases of impacted teeth, maxillary ipoplasia, orthognathic surgery etc. The aim of this study was to compare the radiation doses related to a conventional CBCT setting and that of a low dose protocol, usable in orthodontic practice. The absorbed organ doses were measured using an anthropomorphic phantom loaded with thermo-luminescent dosimeters related to sensitive organs (brain, bone marrow, salivary glands, thyroid, esophagus, oral mucosa, extrathoracic airways, lymph nodes). The device used was a MyRay Hyperion X9-11x5. The standard setting of the apparatus was 90 Kv, 36 mAs, CTDI/Vol 4.09 mGy, instead the low dose one was 90 Kv, 27 mAs, CTDI/Vol 2.89 mGy. Equivalent and effective doses have been calculated; the measurement of the effective doses was based on the ICRP recommendations. For the assessment of image quality, five readers, independent and experienced orthodontists, were asked to state if the images were sufficient enough to perform an orthodontic diagnosis. The lowest organ dose (5.01 microSv) was received by the esophagus during low dose CBCT acquisition. The highest mean organ dose instead (1227.67 microSv) was received by the salivary glands during conventional setting CBCT acquisition. Image quality has been considered sufficient for orthodontic diagnostic needs for both CBCT protocols. CBCT low dose setting should be preferred over the standard one in orthodontic practice, because it provides a significant lower radiation dose to the patients ensuring a good image quality. However, further studies are necessary to evaluate the opportunity of CBCT exams in orthodontic treatment planning.
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Tomografía Computarizada de Haz Cónico/métodos , Ortodoncia , Humanos , Fantasmas de ImagenRESUMEN
Nipple-areola complex (NAC) loss is one of the most devastating complications of mastopexy or breast reduction, and it requires revisional procedures with poor aesthetic outcome. In high-risk patients, a free nipple graft could be a choice, but it is associated with the same aesthetic concerns for both patients and surgeons. We report our experience with the septum-supero-medial-based mammaplasty to treat 22 patients with severe breast ptosis (nipple-to-sternal-notch distance > 40 cm). No NAC loss was observed. The study highlights surgical technical details and discusses anatomical considerations to justify the successful result. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Mama/anomalías , Hipertrofia/cirugía , Mamoplastia/métodos , Pezones/cirugía , Colgajos Quirúrgicos/trasplante , Cicatrización de Heridas/fisiología , Adulto , Mama/cirugía , Estudios de Cohortes , Estética , Femenino , Estudios de Seguimiento , Humanos , Hipertrofia/diagnóstico , Mamoplastia/efectos adversos , Persona de Mediana Edad , Seguridad del Paciente , Satisfacción del Paciente , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/cirugía , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: To investigate the influence of interrupted rotation on cyclic fatigue of two nickel-titanium rotary instruments. METHODOLOGY: Cyclic fatigue of 300 new ProTaper Next size X1; X2 and Mtwo size 10, .04 taper; size 15, .05 taper; size 20, .06 taper and size 25, .06 taper instruments was tested in continuous or interrupted rotation. Fifty files of the same brand and size were randomly assigned to five groups (n = 10). Group 1 instruments were tested in continuous rotation; groups 2 and 3 in paused rotation for 1 s every 10 or 20 s, respectively; groups 4 and 5 in interrupted rotation for 5 s every 10 or 20 s, respectively. Cyclic fatigue was expressed in time to fracture (TtF) in an artificial canal with 60° angle and 5 mm radius of curvature. The fracture surface was examined with a scanning electron microscope (SEM). Data were evaluated by two-way analysis of variance. RESULTS: Cyclic fatigue of groups 2 and 4 of ProTaper Next X2 and Mtwo size 25, .06 taper was significantly lower than that of group 1 of the same instruments (P < 0.01). ProTaper Next X2 had significantly reduced cyclic fatigue in groups 3 and 5 (P < 0.05). No differences were found by interrupting the rotation for 1 or 5 s in all instruments (P > 0.05). Fatigue of other instruments was not affected by interrupted rotation (P > 0.05). CONCLUSIONS: Interrupted rotation reduced cyclic fatigue resistance of ProTaper Next X2 and Mtwo size 25, .06 taper, especially when a higher number of interruptions was performed.
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Instrumentos Dentales/normas , Níquel , Titanio , RotaciónRESUMEN
The lack of geometrical and hydraulic information about sewer networks often excludes the adoption of in-deep modeling tools to obtain prioritization strategies for funds management. The present paper describes a novel statistical procedure for defining the prioritization scheme for preventive maintenance strategies based on a small sample of failure data collected by the Sewer Office of the Municipality of Naples (IT). Novelty issues involve, among others, considering sewer parameters as continuous statistical variables and accounting for their interdependences. After a statistical analysis of maintenance interventions, the most important available factors affecting the process are selected and their mutual correlations identified. Then, after a Box-Cox transformation of the original variables, a methodology is provided for the evaluation of a vulnerability map of the sewer network by adopting a joint multivariate normal distribution with different parameter sets. The goodness-of-fit is eventually tested for each distribution by means of a multivariate plotting position. The developed methodology is expected to assist municipal engineers in identifying critical sewers, prioritizing sewer inspections in order to fulfill rehabilitation requirements.
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Aguas del Alcantarillado/análisis , Administración de Residuos/estadística & datos numéricos , Ciudades , Análisis Multivariante , Probabilidad , Administración de Residuos/métodosRESUMEN
Furnas volcano, in São Miguel island (Azores), being the surface expression of rising hydrothermal steam, is the site of intense carbon dioxide (CO2) release by diffuse degassing and fumaroles. While the diffusive CO2 output has long (since the early 1990s) been characterized by soil CO2 surveys, no information is presently available on the fumarolic CO2 output. Here, we performed (in August 2014) a study in which soil CO2 degassing survey was combined for the first time with the measurement of the fumarolic CO2 flux. The results were achieved by using a GasFinder 2.0 tunable diode laser. Our measurements were performed in two degassing sites at Furnas volcano (Furnas Lake and Furnas Village), with the aim of quantifying the total (fumarolic + soil diffuse) CO2 output. We show that, within the main degassing (fumarolic) areas, the soil CO2 flux contribution (9.2 t day-1) represents a minor (~15 %) fraction of the total CO2 output (59 t day-1), which is dominated by the fumaroles (~50 t day-1). The same fumaroles contribute to ~0.25 t day-1 of H2S, based on a fumarole CO2/H2S ratio of 150 to 353 (measured with a portable Multi-GAS). However, we also find that the soil CO2 contribution from a more distal wider degassing structure dominates the total Furnas volcano CO2 budget, which we evaluate (summing up the CO2 flux contributions for degassing soils, fumarolic emissions and springs) at ~1030 t day-1.
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Interval nodes (IN) are defined as lymph nodes that lie along the course of lymphatic collecting vessels between a primary tumor site and a draining node field. Sometimes INs contain metastases and a consensus on their surgical management is needed. Therefore, to optimize the surgical management of melanoma patients with metastatic lymphatic involvement, especially when the sentinel lymph node biopsy identifies an unusual drainage field, we identified patients treated at the Department of Plastic and Reconstruction Surgery of Bari between July 1994 and December 2012 identified with a primary-cutaneous melanoma who underwent lymphoscintigraphy and subsequent positive-IN the lymphadenectomy to evaluate the impact of this procedure on overall survival and disease-free-period. 51 patients presented INs, and lymphadenectomy (LA) of the subsequent lymphatic field was performed in 13 subjects with positive-IN. In 4 cases additional lymphatic metastases were detected in the usual basin beyond the IN+. Recurrence-free period and survival rate at 5 years were higher in patients with positive-IN who underwent LA than in subjects who underwent LA due to positive lymph nodes in the usual field. Immediate lymphadenectomy of the subsequent lymphatic field in patients with positive-INs may afford patients earlier stage treatment of their disease and improved prognosis.
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Melanoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Although the number of excised LNs has been associated with patient prognosis in many solid tumors, this association has not been widely investigated in cutaneous melanoma. This study aims to evaluate the association between the number of excised regional lymph nodes (LNs) and melanoma-specific survival. PATIENT AND METHODS: Clinico-pathological data from 2507 patients with LN metastasis treated at nine Italian centers were retrospectively collected. RESULTS: The number of excised LNs correlated with younger age (P < 0.001), male sex (P < 0.001), neck LN field (P < 0.001), LN micrometastasis (P < 0.001) and number of positive LNs (P < 0.001). The number of excised LNs was an independent prognostic factor (HR = 0.85; P = 0.002) after adjustment for other staging features. Upon subgroup analysis, the number of excised LNs had a significant prognostic value in patients bearing 1.01-2.00 mm (HR = 0.79; P = 0.032) and 2.01-4.00 mm (HR = 0.71; P < 0.001) thick melanomas, primary tumors showing ulceration (HR = 0.86; P = 0.033) and Clark level V of invasion (HR = 0.86; P = 0.010), LN micrometastasis (HR = 0.83; P = 0.014) and two to three positive LNs (HR = 0.71; P = 0.001). Finally, this study investigated the influence of the number of excised LNs on patient staging: only when ≥11 nodes were excised the AJCC N stage could stratify prognosis (P < 0.001). Considering the number of excised LNs for each lymphatic field, at least 14, 11, 10 and 12 LNs were needed to stage patients according to the AJCC N stage after a lymphadenectomy of the neck, axilla, inguinal and ilioinguinal LN fields, respectively. CONCLUSIONS: The number of excised LNs can be considered for risk stratification of patients with regional LN metastasis from cutaneous melanoma. We demonstrated that a minimum number of LNs is required for the correct staging of patients. Further research is needed to evaluate the effectiveness of the minimum number of LNs to be dissected.
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Melanoma/mortalidad , Neoplasias Cutáneas/mortalidad , Adulto , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/secundario , Melanoma/cirugía , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Resultado del Tratamiento , Carga TumoralRESUMEN
AIM: The purpose of this study is to evaluate prognosis and surgical management of head and neck melanoma (HNM) and the accuracy of sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: All patients with a primary cutaneous melanoma treated starting from 01/07/1994 to 31/12/2012 in the department of Plastic and Reconstructive Surgery of Bari are included in a electronic clinical medical registry. Within the 90th day from excision of the primary lesion all patients with adverse prognostic features underwent SLNB. All patients with positive findings underwent lymphadenectomy. RESULTS: out of 680 patients affected by melanoma, 84 (12.35%) had HNM. In the HNM cohort lymphoscintigraphy was performed in 57 patients, 15 of which (26.3%) were positive. The percentage of unfound sentinel lymph node was similar both to the HNM group (5,26%) and to patients with melanoma of different sites (OMS 4,92%). There was a recurrence of disease after negative SLNB (false negatives) only in 4 cases. Recurrence-free period and survival rate at 5 years were worse in HNM cohort. CONCLUSION: SLNB of HNM has been for a long time contested due to its complex lymphatic anatomy, but recent studies agreed with this technique. Our experience showed that identification of sentinel lymph node in HNM cohort was possible in 98.25% of cases. Frequency of interval nodes is significantly higher in HNM group. The prognosis of HNM cohort is significantly shorter than OMS one. Finally, this procedure requires a multidisciplinary team in referral centers.
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Neoplasias de Cabeza y Cuello/cirugía , Melanoma/cirugía , Disección del Cuello , Recurrencia Local de Neoplasia/cirugía , Biopsia del Ganglio Linfático Centinela , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Italia/epidemiología , Masculino , Melanoma/diagnóstico por imagen , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Cintigrafía , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The quantification of soil carbon dioxide (CO2) flux represents an indicator of the agro-ecosystems sustainability. However, the monitoring of these fluxes is quite challenging due to their high spatially-temporally variability and dependence on environmental variables and soil management practices.In this study, soil CO2 fluxes were measured using a low-cost accumulation chamber, that was realized ad hoc for the surveys, in an orange orchard managed under different soil management (SM, bare versus mulched soils) and water regime (WR, full irrigation versus regulated deficit irrigation) strategies. In particular, the soil CO2 flux measurements were acquired in discontinuous and continuous modes, together with ancillary agrometeorological and soil-related information, and then compared to the agrosystem scale CO2 fluxes measured by the eddy covariance (EC) technique.Overall significant differences were obtained for the soil CO2 discontinuous fluxes as function of the WR (0.16 ± 0.01 and 0.14 ± 0.01 mg m-2 s-1 under full irrigation and regulated deficit irrigation, respectively). For the continuous soil CO2 measurements, the response observed for the SM factor varied from year to year, indicating for the overall reference period 2022-23 higher soil CO2 flux under the mulched soils (0.24 ± 0.01 mg m-2 s-1) than under bare soil conditions (0.15 ± 0.00 mg m-2 s-1). Inter-annual variations were also observed as function of the day-of-year (DOY), the SM and their interactions, resulting in higher soil CO2 flux under the mulched soils (0.24 ± 0.02 mg m-2 s-1) than under bare soil (0.15 ± 0.01 mg m-2 s-1) in certain periods of the years, according to the environmental conditions. Results: suggest the importance of integrating soil CO2 flux measurements with ancillary variables that explain the variability of the agrosystem and the need to conduct the measurements using different operational modalities, also providing for night-time monitoring of CO2. In addition, the study underlines that the small-scale chamber measurements can be used to estimate soil CO2 fluxes at orchard scale if fluxes are properly scaled.
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Tartrato de Brimonidina/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Eritema/tratamiento farmacológico , Dermatosis Facial/tratamiento farmacológico , Síndrome de Netherton/complicaciones , Administración Cutánea , Adulto , Femenino , Geles , Humanos , Uso Fuera de lo IndicadoRESUMEN
PURPOSE: The purpose of the study is to show the excellent anatomical result of the inverted flap-assisted technique with PRP under air for retinitis pigmentosa complicated with macular hole. METHODS: A 32-year-old woman, previously diagnosed with retinitis pigmentosa, was referred to our department complaining of decreased central vision in her LEFT eye for 4 weeks. At the time of presentation, the optical coherence tomography and fundoscopy examination showed the presence of a macular hole of 620 microns in diameter. The closure of the macular hole was observed after the surgical procedure, but endophthalmitis occurred 5 days postoperatively. RESULTS: In our presented case, the cover flap-assisted technique with PRP under air for retinitis pigmentosa complicated with macular hole resulted in excellent anatomical outcomes with unremarkable visual recovery. CONCLUSION: The physiopathology of full-thickness macular holes in RP patients remains still not fully elucidated. Pars plana vitrectomy with the adjunct of highly concentrated P-PRP have shown successful results.
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The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.
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Nanoestructuras , Dedos de Zinc , Dedos de Zinc/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Perfilación de la Expresión Génica , Proteínas de PlantasRESUMEN
The aim of this investigation was to assess the effects of nonylphenol (NP), an oestrogen-like environmental pollutant, on the vitellogenin (VTG) synthesis in adult males of the aplacental viviparous cartilaginous fish Torpedo marmorata. The VTG recovery in males is considered a biomarker of xeno-oestrogenic pollution as this lipophosphoglycoprotein is physiologically induced by oestrogens only in females of oviparous and ovoviparous vertebrates. Using in situ hybridization and immunohistochemistry, T. marmorata males injected with nonylphenol showed the presence of VTG in the liver and the kidney. In particular, vtg messenger (m)RNA and VTG protein were expressed in the liver, whereas in the kidney cells only the presence of VTG was recorded. By contrast, no expression for VTG was detected in the testis. These results demonstrate that in T. marmorata NP induces the expression of vtg only in the liver; the presence of VTG in the kidney and its absence in the testis are discussed.
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Fenoles/farmacología , Torpedo/metabolismo , Vitelogeninas/biosíntesis , Animales , Inmunohistoquímica , Hibridación in Situ , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Testículo/efectos de los fármacos , Testículo/metabolismo , Contaminantes Químicos del Agua/farmacologíaRESUMEN
Orthognathic surgery and the Le Fort I osteotomy result in noticeable alterations to the nasal/nasolabial anatomy. The alar base cinch technique is a surgical technique to control lateralization of the base of the nose and is well described in the literature. The aim of this scoping review was to identify every unique alar cinch suture technique reported in orthognathic surgery and to propose a classification for the different techniques described. A search was conducted in the PubMed, Cochrane Library, and Scopus electronic databases covering the period May 1980 to July 2020, which identified 10 articles that were eligible for this review. Among these, there were several proposals for modifications to the technique, and different studies to show the effectiveness of one type among all others. Despite observing multiple techniques and variations of these while performing this review, the lack of a classification for alar cinch suture was noticed. Therefore, we propose a classification of the alar cinch suture that includes four types, which cover all of the cinching techniques described. It is believed that the use of a standardized classification may be useful to avoid duplicate publishing of techniques and to set a standard for further studies.
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Cirugía Ortognática , Cefalometría/métodos , Humanos , Maxilar/cirugía , Cartílagos Nasales/cirugía , Osteotomía Le Fort/métodos , Técnicas de Sutura , SuturasRESUMEN
Single (SG-VLN) and double gastroepiploic vascularized lymph node transfer (DG-VLN) have shown promising results for the treatment of extremities' lymphedema. The literature search yields only few other cases describing outcomes following double VLN transfers, but no comparative studies have been produced so far. The aim of this study was to retrospectively examine and compare the effects of SG-VLN versus DG-VLN transfer. All patients diagnosed with extremities' stage II and III lymphedema who had undergone SG-VLN or DG-VLN between January 2012 and December 2018 were identified from two institutions' databases. Demographic and surgical data were collected. The primary endpoint was the comparison of the reduction in limb circumference (CRR) within 12 months post-surgery. Secondary endpoints included the reduction of cellulitis episodes and patients' quality of life improvement. Eighty-nine patients met the inclusion criteria. At 12 months of follow-up, higher CRR values were observed in the double inset group (p<0.05*) both at above elbow/above knee (AE/AK) level (SG-VLN: 70.6% ± 0.6%; DG-VLN: 72.2% ± 0.7%) and at below elbow/below knee level (SG-VLN: 59.1% ± 1.3%; DG-VLN: 61.6% ± 3.7%). Subgroup analyses of the involved limb (upper vs lower) were consistent with the primary treatment effects. The reduction of cellulitis episodes did not differ between the two groups, while the DG-VLN group showed better results in the overall satisfaction function, symptoms, and mood domains of the LYMQoL questionnaire (p=0.04). The study suggests that either single or double transfer can produce excellent results, but double inset of the gastroepiploic VLNT flap may produce greater volume reductions both at 12 and 24 months. Further studies with a larger sample size are warranted to corroborate our results.
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Linfedema , Calidad de Vida , Estudios de Casos y Controles , Celulitis (Flemón) , Humanos , Extremidad Inferior/cirugía , Ganglios Linfáticos/cirugía , Linfedema/patología , Linfedema/cirugía , Estudios RetrospectivosRESUMEN
Malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. We demonstrate that in a simian malaria parasite (Plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. These parasite-killing effects in crisis serum are due to the presence in the serum of cytokines tumor necrosis factor and interferon gamma, which are produced by the host as a result of the malaria infection. The killing activity of each cytokine is absolutely dependent upon the presence of additional, as yet unidentified factor(s) in the crisis serum.
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Interferón gamma/sangre , Malaria/fisiopatología , Plasmodium/patogenicidad , Factor de Necrosis Tumoral alfa/fisiología , Animales , Anopheles , Eritrocitos/parasitología , Técnicas In Vitro , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Lipopolisacáridos/farmacología , Macaca , Malaria/sangre , Plasmodium/efectos de los fármacos , Proteínas Recombinantes/farmacología , Esplenectomía , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala --> Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 microg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose-response experiments in mice, 20 microg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials.