Contribution of early SPECT/CT to 99mTc-MIBI double phase scintigraphy in primary hyperparathyroidism: Diagnostic value and correlation between uptake and biological parameters / Aportación del SPECT/TC precoz a la gammagrafía de doble fase con 99mTc-MIBI en pacientes con hiperparatiroidismo primario: valor diagnóstico y correlación de la captación con parámetros biológicos

Aim. To evaluate the value of 99mTc-MIBI double-phase scintigraphy (DPS) and early SPECT/CT in the pre-surgical assessment of patients with primary hyperparathyroidism (PHPT). Also, to calculate the correlation between uptake and some biological parameters. Material and methods. Forty patients with PHPT were included: 37 solitary adenomas, 1 hyperplasia, and 2 double adenomas. Fifteen patients had ectopic glands. DPS and early SPECT/CT were acquired in all patients. Ultrasound was performed in 31/40. All patients underwent surgery, intra-operative iPTH measurements, and histopathological examinations. Qualitative DPS uptake was assessed and correlated to pre-surgical calcium, iPTH levels, gland weight, and maximum diameter. Results. In the planar study, there were 23 positive cases, 8 doubtful, and 9 negatives. With the SPECT/CT, 8/9 negatives cases were located. All doubtful cases were confirmed as positives. Gland location improved in 16 cases (12 ectopic). DPS+SPECT/CT failed to detect a solitary adenoma and at least one gland in three cases of multiglandular disease (MGD). The sensitivity by patient was: DPS 72.5%, DPS+SPECT/CT 90%, and ultrasound 42%. Ultrasound and scintigraphy (DPS+SPECT/CT) were concordant in 16/31 patients. For the rest of them, scintigraphy proved correct in 14/15, and both techniques failed in one case. There was a significant correlation between level of uptake and iPTH level, gland weight, and maximum diameter. Conclusion. Early SPECT/CT improves sensitivity and the locating of parathyroid pathological glands and increases diagnostic confidence. iPTH level, glandular size, and weight are related to the qualitative assessment of 99mTc-MIBI uptake in early DPS (AU)

Objetivo. Evaluar la gammagrafía de doble fase con 99mTc-MIBI (GDF) y el SPECT/TC precoz, en la valoración prequirúrgica del hiperparatiroidismo primario (HPTP), calculando la correlación entre grado de captación y algunos parámetros biológicos. Material y métodos. Se incluyeron 40 pacientes: 37 adenomas solitarios, dos adenomas dobles, una hiperplasia. Quince tenían glándulas ectópicas. En 40 pacientes se realizaron GDF y SPECT/TC; en 31/40, ecografía. Todos los pacientes fueron intervenidos, realizando determinación de PTHi intraoperatoria y examen histopatológico. Se evaluó cualitativamente la captación en la GDF, correlacionándose con calcio y PTHi prequirúrgicos, peso y diámetro máximo glandulares. Resultados. En el estudio planar se obtuvieron 23 casos positivos, 8 dudosos, y 9 negativos. Con SPECT/TC se localizaron 8/9 de los negativos. Todos los dudosos se confirmaron como positivos. La localización glandular mejoró en 16 casos (12 ectópicos). La GDF+SPECT/TC fallaron en la detección de un adenoma solitario y en la visualización de alguna de las glándulas en tres casos de enfermedad multiglandular (EMG). La sensibilidad por pacientes fue: GDF 72,5%, GDF+SPECT/TC 90%, ecografía 42%. Ecografía y gammagrafía (GDF+SPECT/TC) concordaron en 16/31 pacientes. De los no concordantes, la gammagrafía acertó en 14/15 y ambas técnicas fallaron en uno. Hubo correlación significativa entre captación y PTHi, peso y diámetro máximo glandulares. Conclusion. El SPECT/TC precoz mejora la sensibilidad y la localización de las paratiroides patológicas y aumenta la confianza diagnóstica. PTHi, tamaño y peso glandulares se correlacionan con la valoración cualitativa de la captación precoz de 99mTc-MIBI en la GDF (AU)

Síndrome HaNDL: correlación entre la topografía del déficit neurológico y las alteraciones en electroencefalograma y SPECT en una serie de 5 nuevos casos / HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases

Introducción: El síndrome de cefalea transitoria y déficits neurológicos con linfocitosis de líquido cefalorraquídeo (LCR), conocido por su acrónimo en inglés, HaNDL, se caracteriza por episodios de cefalea de características migrañosas acompañados por síntomas deficitarios motores, sensitivos o de lenguaje. El electroencefalograma (EEG) o la tomografía por emisión de fotón único (SPECT) pueden mostrar anomalías focales consistentes con los déficits neurológicos. Pretendemos evaluar dicha correlación en una serie de 5 nuevos pacientes. Pacientes: Análisis retrospectivo de pacientes atendidos en un hospital terciario (enero del 2010-mayo del 2014, 5 casos [3 varones, 2 mujeres]), de 30,6 ± 7,7 años (21-39). Presentaron 3,4 ± 2,6 (2-8) episodios de cefalea moderada-severa y déficits neurológicos durante un tiempo no superior a 5 semanas. En todos, pleocitosis de LCR (70 a 312 células/mm3, 96,5-100% linfocitos), con estudio etiológico negativo. Resultados: EEG en 4 pacientes y SPECT en 3. Caso 1: 8 episodios, 4 de hemisferio izquierdo, 3 hemisferio derecho y 1 de tronco, 2 EEG con enlentecimiento temporal izquierdo y bitemporal; SPECT normal. Caso 2: 2 cuadros, hemisférico izquierdo y hemisférico derecho respectivamente y SPECT con flujo disminuido temporal izquierdo. Caso 3: 3 episodios hemisféricos izquierdos; EEG con enlentecimiento temporo-frontal bilateral. Caso 4: 2 cuadros con topografía parieto-occipital derecha y EEG con enlentecimiento frontal derecho. Caso 5: 2 episodios, hemisférico derecho y hemisférico izquierdo, EEG con enlentecimiento temporal derecho; SPECT normal. Conclusiones: Existe gran heterogeneidad clínica en los déficits neurológicos del HaNDL; las alteraciones en SPECT y, sobre todo, en EEG no son infrecuentes y no siempre se relacionan con la topografía clínica

Introduction: Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. Patients: We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. Results: At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. Conclusion: The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal deficits

Contribution of early SPECT/CT to 99mTc-MIBI double phase scintigraphy in primary hyperparathyroidism: Diagnostic value and correlation between uptake and biological parameters.

AIM: To evaluate the value of 99mTc-MIBI double-phase scintigraphy (DPS) and early SPECT/CT in the pre-surgical assessment of patients with primary hyperparathyroidism (PHPT). Also, to calculate the correlation between uptake and some biological parameters. MATERIAL AND METHODS: Forty patients with PHPT were included: 37 solitary adenomas, 1 hyperplasia, and 2 double adenomas. Fifteen patients had ectopic glands. DPS and early SPECT/CT were acquired in all patients. Ultrasound was performed in 31/40. All patients underwent surgery, intra-operative iPTH measurements, and histopathological examinations. Qualitative DPS uptake was assessed and correlated to pre-surgical calcium, iPTH levels, gland weight, and maximum diameter. RESULTS: In the planar study, there were 23 positive cases, 8 doubtful, and 9 negatives. With the SPECT/CT, 8/9 negatives cases were located. All doubtful cases were confirmed as positives. Gland location improved in 16 cases (12 ectopic). DPS+SPECT/CT failed to detect a solitary adenoma and at least one gland in three cases of multiglandular disease (MGD). The sensitivity by patient was: DPS 72.5%, DPS+SPECT/CT 90%, and ultrasound 42%. Ultrasound and scintigraphy (DPS+SPECT/CT) were concordant in 16/31 patients. For the rest of them, scintigraphy proved correct in 14/15, and both techniques failed in one case. There was a significant correlation between level of uptake and iPTH level, gland weight, and maximum diameter. CONCLUSION: Early SPECT/CT improves sensitivity and the locating of parathyroid pathological glands and increases diagnostic confidence. iPTH level, glandular size, and weight are related to the qualitative assessment of 99mTc-MIBI uptake in early DPS.

HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases. / Síndrome HaNDL: correlación entre la topografía del déficit neurológico y las alteraciones en electroencefalograma y SPECT en una serie de 5 nuevos casos.

INTRODUCTION: Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. PATIENTS: We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. RESULTS: At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. CONCLUSION: The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal déficits.

Interactions of poly (anhydride) nanoparticles with macrophages in light of their vaccine adjuvant properties.

Understanding how nanoparticles are formed and how those processes ultimately determine the nanoparticles' properties and their impact on their capture by immune cells is key in vaccination studies. Accordingly, we wanted to evaluate how the previously described poly (anhydride)-based nanoparticles of the copolymer of methyl vinyl ether and maleic anhydride (NP) interact with macrophages, and how this process depends on the physicochemical properties derived from the method of preparation. First, we studied the influence of the desolvation and drying processes used to obtain the nanoparticles. NP prepared by the desolvation of the polymers in acetone with a mixture of ethanol and water yielded higher mean diameters than those obtained in the presence of water (250nm vs. 180nm). In addition, nanoparticles dried by lyophilization presented higher negative zeta potentials than those dried by spray-drying (-47mV vs. -35mV). Second, the influence of the NP formulation on the phagocytosis by J774 murine macrophage-like cell line was investigated. The data indicated that NPs prepared in the presence of water were at least three-times more efficiently internalized by cells than NPs prepared with the mixture of ethanol and water. Besides, lyophilized nanoparticles appeared to be more efficiently taken up by J744 cells than those dried by spray-drying. To further understand the specific mechanisms involved in the cellular internalization of NPs, different pharmacological inhibitors were used to interfere with specific uptake pathways. Results suggest that the NP formulations, particularly, nanoparticles prepared by the addition of ethanol:water, are internalized by the clathrin-mediated endocytosis, rather than caveolae-mediated mechanisms, supporting their previously described vaccine adjuvant properties.

SPECT-CT finding of 99mTc-HMDP uptake in abdominal adenopathies in a patient with metastasic breast cancer / Hallazgo mediante SPECT-TC de captación de 99mTc-HMDP en adenopatías abdominales en una paciente con cáncer de mama metastásico

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Valoración mediante SPECT-CT de un timoma y un carcinoma de mama hallados de forma casual en un SPECT de perfusión miocardica con 99mTc-MIBI / Evaluation by SPECT-CT of an incidental finding of a thymoma and breast cancer in a myocardial perfusion SPECT with 99mTc-MIBI

Presentamos una paciente de 78 años, derivada para estudio de angor de esfuerzo, que en el SPECT de perfusión miocárdica presentó captación aumentada del trazador en dos lesiones tumorales sincrónicas: un timoma y un cáncer de mama. Este caso clínico pone de manifiesto la aportación del SPECT-CT en la caracterización de estos hallazgos y su papel esencial para una rápida toma de decisiones. La paciente fue intervenida quirúrgicamente de las dos lesiones, insospechadas previamente a la realización del SPECT miocárdico(AU)

We present a case of a 78-year-old female with effort angina. A myocardial perfusion SPECT (MPS) showed increased tracer uptake in two synchronic tumor lesions, a thymoma and a breast cancer. This case highlights the contribution of SPECT-CT in the characterization of these findings and its essential role in rapid decision-making. The patient underwent surgery of both lesions that had gone undetected prior to the conduction of the MPS(AU)

Nanoparticle-based vaccine for mucosal protection against Shigella flexneri in mice.

Shigellosis is one of the leading causes of diarrhea worldwide with more than 130 million cases annually. Hence, the research of an effective vaccine is still a priority. Unfortunately, a safe and efficacious vaccine is not available yet. We have previously demonstrated the capacity of outer membrane vesicles (OMVs) to protect mice against an experimental infection with Shigella flexneri. Now, we present results on the capacity of this antigenic complex to confer a longer-term protection by oral or nasal routes when encapsulated into nanoparticles. OMVs were encapsulated in poly(anhydride) nanoparticles (NP) prepared by a solvent displacement method with the copolymer poly methyl vinyl ether/maleic anhydride. OMVs loaded into nanoparticles (NP-OMVs) were homogeneous and spherical in shape, with a size of 148nm (PdI=0.2). BALB/c mice were immunized with OMVs either free or encapsulated in nanoparticles by nasal (20µg or 10µg of OMVs) or oral route (100µg or 50µg of OMVs). All immunized animals remained in good health after administration. Challenge infection was performed intranasally on week 8th with a lethal dose of 5×10(7)CFU/mouse of S. flexneri 2a. The number of dead mice after challenge was recorded daily. Results confirmed the value of OMVs as a vaccine. By oral route, the OMV-vaccine was able to protect independently either the dose or the formulation. When vaccine was delivered by nasal route, encapsulation into NPs resulted beneficial in increasing protection from 40% up to 100% when low dose was administered. These results are extraordinary promising and put in relevance the positive effect of nanoencapsulation of the OMV subcellular vaccine.

Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis / Radiolabeling and biodistribution studies of polymeric nanoparticles as adjuvants for ocular vaccination against brucellosis

Objetivo. Optimizar el radiomarcaje con 99mTc de nanopartículas de Gantrez® manosiladas y cargadas con el antígeno de Brucella ovis (Man-NP-HS) y llevar a cabo estudios de biodistribución en un ratón tras la administración de las nanopartículas por vía ocular. Material y métodos. Las Man-NP-HS se obtuvieron por el método de desplazamiento del disolvente. Se purificaron, liofilizaron y caracterizaron. A continuación, se marcaron con 74MBq de 99mTcO4− previamente reducido con una disolución ácida de cloruro de estaño, trabajando en ausencia de oxígeno y con un pH final de 4. El rendimiento del marcaje se evaluó mediante TLC. Los estudios de biodistribución se llevaron a cabo en ratones tras la administración oftálmica de la formulación y de un control de 99mTcO4− libre. Para ello, se sacrificaron los animales a las 2 y a las 24h tras la administración ocular y se contaron los órganos en un contador gamma. Resultados. Se obtuvo un rendimiento de marcaje superior al 90%. Los estudios de biodistribución de 99mTc-Man-NP-HS permitieron detectar la actividad concentrada en la mucosa nasal y ocular y el tracto gastrointestinal tanto a las 2 como a las 24h frente a la biodistribución de 99mTcO4− libre que permaneció concentrado en la piel alrededor del ojo y en el tracto gastrointestinal. Conclusión. Los estudios de biodistribución de 99mTc-Man-NP-HS tras la administración oftálmica han permitido demostrar su biodistribución en las mucosas y el tracto gastrointestinal, característica indispensable como sistema de liberación de antígenos a través de la mucosa ocular. Esto, junto con su elevada respuesta inmune, efectiva protección y no virulencia, convierte a estas nanopartículas en una vacuna ideal antibrucelosis (AU)

Purpose. To optimize radiolabeling with 99mTc of mannosylated Gantrez® nanoparticles loaded with the Brucella Ovis antigen (Man-NP-HS) and to carry out biodistribution studies in mice after ocular administration of the nanoparticles. Material and methods. Man-NP-HS nanoparticles were prepared by the solvent displacement method. They were purified, lyophilized and characterized. Following this, they were radiolabeled with 74 MBq of 99mTcO4− previously reduced with an acidic stannous chloride solution, working in absence of oxygen and at a final pH of 4. Radiolabeling yield was evaluated by TLC. Biodistribution studies were carried out in mice after ocular administration of the formulation and control of free 99mTcO4−. To do so, the animals were humanely killed at 2 and 24hours after the ocular administration and activity in organs was measured in a Gamma counter. Results. Radiolabeling yield obtained was greater than 90%. Biodistribution studies of 99mTc-Man-NP-HS showed radioactivity accumulated at 2 and 24hours in nasal and ocular mucosa and gastrointestinal tract, in contrast to biodistribution of free 99mTcO4− that remained concentrated in the skin around the eye and gastrointestinal tract. Conclusion. Biodistribution studies of 99mTc-Man-NP-HS after ocular instillation have made it possible to demonstrate its biodistribution in nasal mucosa and gastrointestinal tract. This characteristic is essential as an antigenic delivery system throughout the ocular mucosa. This, together with its elevated immune response, effective protection and intrinsic avirulence make them a suitable anti-Brucella vaccine candidate (AU)

[Radiolabeling and biodistribution studies of polymeric nanoparticles as adjuvants for ocular vaccination against brucellosis]. / Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis.

PURPOSE: To optimize radiolabeling with (99m)Tc of mannosylated Gantrez(®) nanoparticles loaded with the Brucella Ovis antigen (Man-NP-HS) and to carry out biodistribution studies in mice after ocular administration of the nanoparticles. MATERIAL AND METHODS: Man-NP-HS nanoparticles were prepared by the solvent displacement method. They were purified, lyophilized and characterized. Following this, they were radiolabeled with 74 MBq of (99m)TcO4(-) previously reduced with an acidic stannous chloride solution, working in absence of oxygen and at a final pH of 4. Radiolabeling yield was evaluated by TLC. Biodistribution studies were carried out in mice after ocular administration of the formulation and control of free (99m)TcO4(-). To do so, the animals were humanely killed at 2 and 24hours after the ocular administration and activity in organs was measured in a Gamma counter. RESULTS: Radiolabeling yield obtained was greater than 90%. Biodistribution studies of (99m)Tc-Man-NP-HS showed radioactivity accumulated at 2 and 24hours in nasal and ocular mucosa and gastrointestinal tract, in contrast to biodistribution of free (99m)TcO4(-) that remained concentrated in the skin around the eye and gastrointestinal tract. CONCLUSION: Biodistribution studies of (99m)Tc-Man-NP-HS after ocular instillation have made it possible to demonstrate its biodistribution in nasal mucosa and gastrointestinal tract. This characteristic is essential as an antigenic delivery system throughout the ocular mucosa. This, together with its elevated immune response, effective protection and intrinsic avirulence make them a suitable anti-Brucella vaccine candidate.

Evaluation by SPECT-CT of an incidental finding of a thymoma and breast cancer in a myocardial perfusion SPECT with 99mTc-MIBI.

We present a case of a 78-year-old female with effort angina. A myocardial perfusion SPECT (MPS) showed increased tracer uptake in two synchronic tumor lesions, a thymoma and a breast cancer. This case highlights the contribution of SPECT-CT in the characterization of these findings and its essential role in rapid decision-making. The patient underwent surgery of both lesions that had gone undetected prior to the conduction of the MPS.

Towards a non-living vaccine against Shigella flexneri: from the inactivation procedure to protection studies.

Shigellosis is one of the leading causes of diarrhea worldwide with more than 165 million cases annually. Hence, a vaccine against this disease is a priority, but no licensed vaccine is still available. Considering target population as well as intrinsic risks of live attenuated vaccines, non-living strategies appear as the most promising candidates. Remarkably, the preservation of antigenic properties is a major concern since inactivation methods of bacteria affect these qualities. We previously reported the use of a subcellular antigen complex for vaccination against shigellosis, based on outer membrane vesicles (OMVs) released from Shigella flexneri. Now, we describe in more detail the employment of binary ethylenimine (BEI) for inactivation of Shigella and its subsequent effect on the antigenic conservation of the vaccinal product. Results demonstrate the effectiveness of BEI treatment to completely inactivate Shigella cells without disturbing the antigenicity and immunogenicity of the OMVs. Thus, OMVs harvested after BEI inactivation were able to protect mice against an experimental infection with S. flexneri.

SPECT-CT in the localization of an ectopic retropharyngeal parathyroid adenoma as a cause for persistent primary hyperparathyroidism.

A common cause for surgical failure of primary hyperparathyroidism (pHPT) is the non-detection of an ectopic adenoma during the intervention. We present a case of a patient with pHPT in whom an ectopic gland was found in the right retropharyngeal space by means of a double phase (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy and early SPECT-CT after several surgeries and imaging tests. The addition of a tomography to the planar scintigraphy increases its sensitivity and improves pathological parathyroid glands localization. The hybrid imaging is sometimes essential to obtain surgical success, as in the case of ectopic adenomas.

Valor de la SPECT-TAC en la localización de un adenoma de paratiroides ectópico retrofaríngeo como causa de hiperparatiroidismo primario persistente / SPECT-CT in the localization of an ectopic retropharyngeal parathyroid adenoma as a cause for persistent primary hyperparathyroidism

Una causa frecuente de fracaso de la cirugía del hiperparatiroidismo primario (HPTp) es la existencia de un adenoma ectópico no detectado en la intervención. Presentamos a una paciente con HPTp en la que, tras sucesivas intervenciones y pruebas de imagen, se encuentra una glándula ectópica en el espacio retrofaríngeo derecho mediante gammagrafía de doble fase con 99mTc-metoxi-isobutil-isonitrilo (99mTc-MIBI) y SPECT-TAC precoz. La adición de una tomografía al estudio gammagráfico planar, aumenta su sensibilidad y mejora la localización de las paratiroides patológicas. En ciertas ocasiones, como es el caso de adenomas ectópicos, la imagen híbrida será esencial para conseguir el éxito quirúrgico(AU)

A common cause for surgical failure of primary hyperparathyroidism (pHPT) is the non-detection of an ectopic adenoma during the intervention. We present a case of a patient with pHPT in whom an ectopic gland was found in the right retropharyngeal space by means of a double phase 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy and early SPECT-CT after several surgeries and imaging tests. The addition of a tomography to the planar scintigraphy increases its sensitivity and improves pathological parathyroid glands localization. The hybrid imaging is sometimes essential to obtain surgical success, as in the case of ectopic adenomas(AU)

Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice.

Vaccination appears to be the only rational prophylactic approach to control shigellosis. Unfortunately, there is still no safe and efficacious vaccine available. We investigated the protection conferred by a new vaccine containing outer membrane vesicles (OMVs) from Shigella flexneri with an adjuvant based on nanoparticles in an experimental model of shigellosis in mice. OMVs were encapsulated in poly(anhydride) nanoparticles prepared by a solvent displacement method with the copolymer PMV/MA. OMVs loaded into NPs (NP-OMVs) were homogeneous and spherical in shape, with a size of 197nm (PdI=0.06). BALB/c mice (females, 9-week-old, 20±1g) were immunized by intradermal, nasal, ocular (20µg) or oral route (100µg) with free or encapsulated OMV. Thirty-five days after administration, mice were infected intranasally with a lethal dose of S. flexneri (1×10(7)CFU). The new vaccine was able to protect fully against infection when it was administered via mucosa. By intradermal route the NP-OMVs formulation increased the protection from 20%, obtained with free extract, to 100%. Interestingly, both OMVs and OMV-NP induced full protection when administered by the nasal and conjuntival route. A strong association between the ratio of IL-12p40/IL-10 and protection was found. Moreover, low levels of IFN-γ correlate with protection. Under the experimental conditions used, the adjuvant did not induce any adverse effects. These results place OMVs among promising candidates to be used for vaccination against Shigellosis.

Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators.

Adjuvant research is being oriented to TLR-agonists, but complement activation has been relatively unexplored. In previous studies it was demonstrated that poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (PVMA NPs) used as adjuvant differentially activate dendritic cells through toll like receptors (TLR) stimulation, however, a high dose of these NPs was used. Now, we demonstrated a dose-response effect, with a concentration as low as 20µg/mL able to stimulate TLR2 and TLR4 transfected dendritic cells. In addition, we investigated whether PVMA NPs are able to exploit also the immunomodulatory benefits of complement activation. Results indicated that the hydroxylated surface of these NPs highly activated the complement cascade, as measured by adsorption studies and a complement fixation bioassay. Stable binding of C3b to NPs was confirmed as indicated by lability to SDS treatment after washing resistance. Complement consumption was confirmed as the lytic capacity of complement exposed to NPs was abolished against antibody-sensitized sheep erythrocytes, with a minimal inhibitory concentration of 50µg NPs, equivalent to a surface of 1cm(2). On the contrary, nanoparticles prepared with poly(lactic-co-glycolic acid) (PLGA), used as a reference, did not consume complement at a concentration ≥3mg NPs (≥40cm(2)). Complement consumption was inhibited when PVMA NPs were cross-linked with diamino groups (1,3-diaminopropane), indicating the role of hydroxyl groups as responsible of the phenomenon. These results favour a model whereby PVMA NPs adjuvant activate complement on site to attract immature antigen presenting cells that are activated through TLR2 and TLR4.