Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

The Use of 99mTc-Mononuclear Leukocyte Scintigraphy for Necrotizing External Otitis Diagnosis.

BACKGROUND: Necrotizing external otitis (NEO) is a severe infectious disease in the external acoustic meatus (EAM) and mastoid that may extend to the cranial base. Due to the lack of a gold standard examination technique, the diagnosis is often difficult and delayed. This study aimed to evaluate the sensitivity and specificity of 99mTc-mononuclear leukocyte scintigraphy associated with 99mTc-phytate in suspected NEO compared to 99mTc-MDP and 67Ga-citrate. METHODS: A prospective study (32 patients) was conducted between 2011 and 2016. RESULTS: At the end, twenty-four patients remained for the study conduction; nineteen had confirmed NEO diagnosis, one had sarcoma, one had EAM cholesteatoma, one had diffuse simple external otitis, and two had an inconclusive diagnosis. 99mTc-mononuclear leukocyte scintigraphy plus 99mTc-phytate was as sensitive as 99mTc-MDP bone scintigraphy (19/19X9/19), and more sensitive than 67Ga scintigraphy (19/19 x 17/19). Regarding specificity, it was superior to bone scintigraphy, 100% × 40% (5/5 × 2/5), and 67Ga scintigraphy, 100% × 20% (5/5 × 1/5). After the infection resolution, all NEO patients had their leukocyte scintigraphy negativized. To the best of our knowledge, this is the first study that evaluates this technique in patients with suspected NEO. CONCLUSIONS: 99mTc-mononuclear leukocyte was revealed to be the best option for NEO because of its specificity.

Rat thyroid graft transplantation after cryopreservation with scintigraphic standardization for an experimental study.

PURPOSE: Budget cuts among other factors undermine the use of state-of-the-art equipment by many research groups. This doesn't mean that their scientific data are not reliable or top-notch. Resort to adaptations is a recurrent need in their reality. The aim of this study was to assess whether scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. MATERIAL AND METHODS: 24 rats were randomly distributed into 3 groups: Control Group (CG), without surgical procedure, Hypothyroidism Group (HTG), submitted to total thyroidectomy, and Transplanted Group (TG), with total thyroidectomy and cryopreservation of the thyroid gland for 7 days followed by grafting of a thyroid lobe. A protocol using a gamma camera imaging was conducted fourteen weeks after transplantation, and the whole body 99mTc, focusing on the topic of heterotopic thyroid uptake was evaluated. RESULTS: The images acquired had good quality with no noise and artifacts that could jeopardize its analysis. On the 14th day, HTG displayed no thyroid uptake, and the TG had a clear uptake of the thyroid graft in the topography of the biceps femoris muscle. Presented data also showed that both equipment spatial resolution and alignment (4.375 mm) did not interfere with the physiological uptake of 99mTc by the thyroid graft. CONCLUSION: The viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy were successfully accessed by the scintigraphy protocol developed.

Rat thyroid graft transplantation after cryopreservation with scintigraphic standardization for an experimental study

Abstract Purpose: Budget cuts among other factors undermine the use of state-of-the-art equipment by many research groups. This doesn't mean that their scientific data are not reliable or top-notch. Resort to adaptations is a recurrent need in their reality. The aim of this study was to assess whether scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. Material and methods: 24 rats were randomly distributed into 3 groups: Control Group (CG), without surgical procedure, Hypothyroidism Group (HTG), submitted to total thyroidectomy, and Transplanted Group (TG), with total thyroidectomy and cryopreservation of the thyroid gland for 7 days followed by grafting of a thyroid lobe. A protocol using a gamma camera imaging was conducted fourteen weeks after transplantation, and the whole body 99mTc, focusing on the topic of heterotopic thyroid uptake was evaluated. Results: The images acquired had good quality with no noise and artifacts that could jeopardize its analysis. On the 14th day, HTG displayed no thyroid uptake, and the TG had a clear uptake of the thyroid graft in the topography of the biceps femoris muscle. Presented data also showed that both equipment spatial resolution and alignment (4.375 mm) did not interfere with the physiological uptake of 99mTc by the thyroid graft. Conclusion: The viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy were successfully accessed by the scintigraphy protocol developed. HIGHLIGHTS Adaptations in validated methods are a recurrent trend due to limited budgets which does not diminish their functionality. Scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. It is possible to adapt human SPECT for other animals for clinical and research purposes.

Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice.

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration's impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 µg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells' presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.

A cost-effective way to reduce the equivalent eye lens dose fromYttrium-90 radiopharmaceuticals.

PURPOSE: We analyzed the effect of the use of Eye Protective Equipment (EPE) and the best position to use individual dosimeters to estimate the eye lens radiation dose to a medical staff that works with yttrium-90. METHODS: Three Alderson-Head-Phantoms were exposed to 58MBq of 90Y for 24h, in two different experiments: (1) at different dosimeter placements and (2) with and without the use of EPE. The measurements were carried on by thermoluminescent technique. RESULTS: Doses received by dosimeters on both lenses were more closely represented by the ones placed between the eyes than those on the temples, which underestimated the doses by a factor of 3. Also, the transmission factors showed that the EPE was able to reduce the Hp(3) values from about 78% to 92%. CONCLUSIONS: This study demonstrated that the use of EPE can optimize the 90Y eye lens dose. An individual dosimeter should be worn between the eyes for an appropriate estimate of this equivalent dose.

Development of 131I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies.

Tissue factor (TF), a blood coagulation protein, plays an important role in tumor growth, invasion, and metastasis. Ixolaris, a tick-derived non-immunogenic molecule that binds to TF, has demonstrated in vivo inhibitory effect on murine models of melanoma, including primary growth and metastasis. This work aimed to: I) develop an efficient and stable labeling technique of ixolaris with Iodine-131(131I); II) compare the biodistribution of 131I and 131I-ixolaris in tumor-free and melanoma-bearing mice; III) evaluate whether 131I-ixolaris could serve as an antimetastatic agent. Ixolaris radioiodination was performed using iodogen, followed by liquid paper chromatography. Labeling stability and anticoagulant activity were measured. Imaging studies were performed after intravenous administration of free 131I or 131I-ixolaris in a murine melanoma model employing the B16-F10 cell line. Animals were divided in three experimental groups: the first experimental group, D0, received a single-dose of 9.25 MBq of 131I-ixolaris at the same day the animals were inoculated with melanoma cells. In the second group, D15, a single-dose of 9.25 MBq of 131I-ixolaris or free 131I was applied into mice on the fifteenth day after the tumor induction. The third group, D1-D15, received two therapeutic doses of 9.25 MBq of 131I-ixolaris or 131I. In vitro studies demonstrated that 131I-ixolaris is stable for up to 24 h and retains its inhibitory activity on blood coagulation. Biodistribution analysis and metastasis assays showed that all treatment regimens with 131I-ixolaris were effective, being the double-treatment (D1/D15) the most effective one. Remarkably, treatment with free 131I showed no anti-metastatic effect. 131I-ixolaris is a promising theranostic agent for metastatic melanoma.

Intravenous Human Umbilical Cord-Derived Mesenchymal Stromal Cell Administration in Models of Moderate and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.

Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study.

Millions of plastic surgeries are performed worldwide every year with the objective of correcting lipodystrophies stemming from lesions, tumor resections, birth defects, and AIDS-associated antiretroviral therapy. Besides that, a large number of clinical research have assessed the outcome of procedures that rely on combinations of dermal fillers and autologous cells. However, little is known about the safety of these combinations and the localization of the injected cells. The aim of this study was to test the toxicity of a solution containing 1% hyaluronic acid (HA) and adipose-derived stromal cells (ASCs) from the human adipose tissue and to assess the localization of the injected cells, with and without HA, labeled with technetium-99m. Rats received subcutaneous and intraperitoneal injections of a solution containing 1% HA/adipose-derived stromal cells isolated from the human fat tissue. The animals were then observed for up to forty-two days. The solution tested in this study did not result in systemic, biochemical, or anatomic alterations that could represent toxicity symptoms. The association of HA and ASCs labeled with technetium-99m remained at the site of the injection within a period of twenty-four hours, as demonstrated by a whole-body imaging software fusion of SPECT and CT. In conclusion, our study shows that the subcutaneous and intraperitoneal injection of HA associated with adipose-derived stromal cells (ASCs) is safe. The association of HA and ASCs did not induce local or systemic toxicity. Thus, the administration of volume equal to or less than 0.2 mL of the agent filler (1 × 106 ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects.

Endotoxin-Induced Emphysema Exacerbation: A Novel Model of Chronic Obstructive Pulmonary Disease Exacerbations Causing Cardiopulmonary Impairment and Diaphragm Dysfunction.

Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma which also involves extrapulmonary manifestations, such as cardiovascular impairment, diaphragm dysfunction, and frequent exacerbations. The development of animal models is important to elucidate the pathophysiology of COPD exacerbations and enable analysis of possible therapeutic approaches. We aimed to characterize a model of acute emphysema exacerbation and evaluate its consequences on the lung, heart, and diaphragm. Twenty-four Wistar rats were randomly assigned into one of two groups: control (C) or emphysema (ELA). In ELA group, animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. The C group received saline under the same protocol. Five weeks after the last instillation, C and ELA animals received saline (SAL) or E. coli lipopolysaccharide (LPS) (200 µg in 200 µl) intratracheally. Twenty-four hours after saline or endotoxin administration, arterial blood gases, lung inflammation and morphometry, collagen fiber content, and lung mechanics were analyzed. Echocardiography, diaphragm ultrasonography (US), and computed tomography (CT) of the chest were done. ELA-LPS animals, compared to ELA-SAL, exhibited decreased arterial oxygenation; increases in alveolar collapse (p < 0.0001), relative neutrophil counts (p = 0.007), levels of cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and vascular endothelial growth factor in lung tissue, collagen fiber deposition in alveolar septa, airways, and pulmonary vessel walls, and dynamic lung elastance (p < 0.0001); reduced pulmonary acceleration time/ejection time ratio, (an indirect index of pulmonary arterial hypertension); decreased diaphragm thickening fraction and excursion; and areas of emphysema associated with heterogeneous alveolar opacities on chest CT. In conclusion, we developed a model of endotoxin-induced emphysema exacerbation that affected not only the lungs but also the heart and diaphragm, thus resembling several features of human disease. This model of emphysema should allow preclinical testing of novel therapies with potential for translation into clinical practice.

Outpatient treatment for haemophilic arthropathy with radiosynovectomy: Radiation dose to family members.

One of the key features of good practice in medicine is the doctor-patient communication. Radiation protection standards for radiosynovectomy (RS) is limited. Yttrium-90 is a beta-emitting radioisotope used in RS to treat joint pain from haemophilic arthritis. ICRP 94 states that if a patient is treated with up to 200 MBq, there is no need for further precautions when it comes to public exposure, however, activities can go up to 370 MBq in RS for the knee. This study analysed 119 family members' safety (16.7% pregnant women). The ambient dose equivalent rate was measured within four distances. A survey was carried analysing risk groups and time spent next to patients. Results showed that family members should be advised to remain at 1.0 m from the patient to decrease accumulated dose by 97.6%. The dose per activity factors estimated in this study is also a useful tool during the risk assessment and doctor/patient communication. Pamphlets were distributed with radiation protection recommendations. Ambient dose equivalent was low enough to show that RS is a safe procedure for family members, which is essential to promote adherence to RS in countries where it is needed but not performed due to lack of information on radiation safety.

Qualitative and quantitative scintigraphy in sialorrhea before and after botulinum toxin injection.

OBJECTIVES/HYPOTHESIS: Sialorrhea is excessive saliva production and its usual escape of from the oral cavity. The use of botulinum toxin has been preconized, but its effectiveness until now has been unreliably measured. Our objective was to qualitatively and quantitatively determine the effectiveness of botulinum toxin injection in the reduction of saliva production by the parotid gland. STUDY DESIGN: Outcomes research. METHODS: Patients with moderate-to-critical sialorrhea had one of the parotid glands injected with 50 U of botulinum toxin, leaving the other as the control. Fifteen days after the toxin injection, they underwent scintigraphic analyses with intravenous injection of 10 mCi (37 MBq) of Tc-99 m (sodium pertechnetate). After this, the noninjected gland was treated for therapeutic complementation. RESULTS: The glands injected with botulinum toxin showed uptake reduction in 100% of patients. The uptake reduction in counts per second varied from 8% to 36%. The Wilcoxon paired test comparing the control glands with those injected showed a significant difference for the action of botulinum toxin (P = .0039). CONCLUSIONS: The scintigraphic study of parotid glands shows that botulinum toxin is effective in reducing sodium pertechnetate uptake. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:2521-2526, 2019.

Technetium-99m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy.

It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders.

EXPLORING CORTICAL BONE DENSITY THROUGH THE ULTRASOUND INTEGRATED REFLECTION COEFFICIENT.

OBJECTIVE: This work evaluates the relationship between ultrasonic reflection and bone density from fourteen cylindrical bovine cortical bone samples (3.0-cm thick). METHODS: Twenty US reflection signals per sample were acquired along the bone surface (2.0-mm step). The Integrated Reflection Coefficient (IRC) from each signal was compared to Quantitative Computed Tomography (QCT). RESULTS: Seven IRC and QCT curves presented Pearson's Correlation R-values above 0.5. For weak correlation curves, QCT and IRC showed similar trends in several segments. CONCLUSION: IRC was sensitive to bone density variation. Level of Evidence: Experimental Study, Investigating a Diagnostic Test.

OBJETIVO: Este estudo avalia a relação entre a reflexão ultrassônica e a densidade óssea de 14 amostras cilíndricas de osso cortical bovino (3,0 cm de espessura). MÉTODOS: Foi realizada a aquisição de 20 sinais de reflexão ultrassônica por amostra (passo de 2,0 mm), ao longo da superfície óssea. O Coeficiente de Reflexão Integrado (IRC) de cada sinal foi comparado por Tomografia Computadorizada Quantitativa (QCT). RESULTADOS: Sete curvas de IRC e QCT apresentaram valor de Correlação R de Pearson acima de 0,5. Para curvas de correlação fraca, QCT e IRC apresentaram tendências semelhantes em vários segmentos. CONCLUSÃO: O IRC foi sensível à variação da densidade óssea. Nível de evidência: Estudo Experimental, Investigação de Exame Diagnóstico.

Monitoring bone changes due to calcium, magnesium, and phosphorus loss in rat femurs using Quantitative Ultrasound.

Bone mineral density is an important parameter for the diagnosis of bone diseases, as well as for predicting fractures and treatment monitoring. Thus, the aim of the present study was to evaluate the potential of Quantitative Ultrasound (QUS) to monitor bone changes after calcium, phosphorus, and magnesium loss in rat femurs in vitro during a demineralization process. Four quantitative ultrasound parameters were estimated from bone surface echoes in eight femur diaphysis of rats. The echo signals were acquired during a decalcification process by Ethylenediaminetetraacetic Acid (EDTA). The results were compared to Quantitative Computed Tomography (QCT) and inductively coupled plasma optical emission spectrometry measurements for validation. Integrated Reflection Coefficient (IRC) reflection parameters and Frequency Slope of Reflection Transfer Function (FSRTF) during demineralization tended to decrease, while the backscattering parameter Apparent Integrated Backscatter (AIB) increased and Frequency Slope of Apparent Backscatter (FSAB) showed an oscillatory behavior with no defined trend. Results indicate a clear relation between demineralization and the corresponding decrease in the reflection parameters and increase in the scattering parameters. The trend analysis of the fall curve of the chemical elements showed a better relationship between IRC and QCT. It was possible to monitor bone changes after ions losses, through the QUS. Thus, it is an indication that the proposed protocol has potential to characterize bone tissue in animal models, providing consistent results towards standardization of bone characterization studies by QUS endorsing its use in humans.