ABSTRACT
Tauopathies, including Alzheimer's disease, are characterized by retinal ganglion cell loss associated with amyloid and phosphorylated tau deposits. We investigated the functional impact of these histopathological alterations in the murine P301S model of tauopathy. Visual impairments were demonstrated by a decrease in visual acuity already detectable at 6 months, the onset of disease. Visual signals to the cortex and retina were delayed at 6 and 9 months, respectively. Surprisingly, the retinal output signal was delayed at the light onset and advanced at the light offset. This antagonistic effect, due to a dysfunction of the cone photoreceptor synapse, was associated with changes in the expression of the vesicular glutamate transporter and a microglial reaction. This dysfunction of retinal glutamatergic synapses suggests a novel interpretation for visual deficits in tauopathies and it highlights the potential value of the retina for the diagnostic assessment and the evaluation of therapies in Alzheimer's disease and other tauopathies.
Subject(s)
Alzheimer Disease , Tauopathies , Mice , Animals , Alzheimer Disease/pathology , tau Proteins/metabolism , Mice, Transgenic , Tauopathies/pathology , Synapses/metabolism , Disease Models, AnimalABSTRACT
INTRODUCTION: The search for an animal model capable of reproducing the physiopathology of the COVID-19, and also suitable for evaluating the efficacy and safety of new drugs has become a challenge for many researchers. AREAS COVERED: This work reviews the current animal models for in vivo tests with SARS-CoV-2 as well as the challenges involved in the safety and efficacy trials. EXPERT OPINION: Studies have reported the use of nonhuman primates, ferrets, mice, Syrian hamsters, lagomorphs, mink, and zebrafish in experiments that aimed to understand the course of COVID-19 or test vaccines and other drugs. In contrast, the assays with animal hyperimmune sera have only been used in in vitro assays. Finding an animal that faithfully reproduces all the characteristics of the disease in humans is difficult. Some models may be more complex to work with, such as monkeys, or require genetic manipulation so that they can express the human ACE2 receptor, as in the case of mice. Although some models are more promising, possibly the use of more than one animal model represents the best scenario. Therefore, further studies are needed to establish an ideal animal model to help in the development of other treatment strategies besides vaccines.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Disease Models, Animal , Ferrets , Humans , Mice , ZebrafishABSTRACT
PURPOSE: Recent reports have highlighted the importance of an anatomic tunnel placement for anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the effect of different tunnel positions for single-bundle ACL reconstruction on knee biomechanics. METHODS: Sixteen fresh-frozen cadaver knees were used. In one group (n = 8), the following techniques were used for knee surgery: (1) anteromedial (AM) bundle reconstruction (AM-AM), (2) posterolateral (PL) bundle reconstruction (PL-PL) and (3) conventional vertical single-bundle reconstruction (PL-high AM). In the other group (n = 8), anatomic mid-position single-bundle reconstruction (MID-MID) was performed. A robotic/universal force-moment sensor system was used to test the knees. An anterior load of 89 N was applied for anterior tibial translation (ATT) at 0°, 15°, 30° and 60° of knee flexion. Subsequently, a combined rotatory load (5 Nm internal rotation and 7 Nm valgus moment) was applied at 0°, 15°, 30° and 45° of knee flexion. The ATT and in situ forces during the application of the external loads were measured. RESULTS: Compared with the intact ACL, all reconstructed knees had a higher ATT under anterior load at all flexion angles and a lower in situ force during the anterior load at 60° of knee flexion. In the case of combined rotatory loading, the highest ATT was achieved with PL-high AM; the in situ force was most closely restored with MIDMID, and the in situ force was the highest AM-AM at each knee flexion angle. CONCLUSION: Among the techniques, AM-AM afforded the highest in situ force and the least ATT.
Subject(s)
Anterior Cruciate Ligament Reconstruction/methods , Knee Joint/physiopathology , Stress, Mechanical , Arthroscopy , Biomechanical Phenomena , Cadaver , Humans , Imaging, Three-Dimensional , Knee Joint/diagnostic imaging , Range of Motion, Articular/physiology , Robotics , Rotation , Tendons/transplantation , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance. OBJECTIVES: To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD. METHODS: A randomized, prospective 6-month study which enrolled 90 subjects with probable AD aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27], Education Group (EG) [n = 25], which participated in an education program and Supplementation Group (SG) [n = 26], which received two daily servings of oral nutritional supplementation. Subjects were assessed for anthropometric data (weight, height, BMI, TSF, AC and AMC), biochemical data (total protein, albumin, and total lymphocyte count), CDR (Clinical Dementia Rating), MMSE (Mini-mental state examination), as well as dependence during meals. RESULTS: The SG showed a significant improvement in the following anthropometric measurements: weight (H calc = 22.12, p =< 0.001), BMI (H calc = 22.12, p =< 0.001), AC (H calc = 12.99, p =< 0.002), and AMC (H calc = 8.67, p =< 0.013) compared to the CG and EG. BMI of the EG was significantly greater compared to the CG. There were significant changes in total protein (H calc = 6.17, p =< 0.046), and total lymphocyte count in the SG compared to the other groups (H cal = 7.94, p = 0.019). CONCLUSION: Oral nutritional supplementation is more effective compared to nutrition education in improving nutritional status.
Subject(s)
Alzheimer Disease/complications , Dietary Supplements , Health Education , Nutritional Status , Aged , Alzheimer Disease/diet therapy , Dementia , Female , Humans , Male , Nutrition Therapy , Prospective Studies , Weight LossABSTRACT
There are few studies of language and speech in patients with Sydenham's chorea (SC). We have done an acoustic analysis of fundamental frequency (F0), duration and intensity of declarative and interrogative sentences made by 20 SC patients, 20 patients with rheumatic fever (RF) without chorea, and compared them with 20 healthy age-matched controls (CO). Each group included 12 females. We found that there is no difference between the RF and CO groups in all studied parameters. Patients with SC, however, presented with a speech characterized by decreased F0 range (difference between minimum and maximum F0), shorter duration of sentences, and higher intensity of the first syllable of sentences. The findings were not influenced by the nature of the sentences (i.e. , declarative or interrogative), but for all variables they were significantly more severe in males than females. In conclusion, we have demonstrated that patients with acute SC have an impairment of modulation of F0 and longer duration of emission of sentences, resulting in a monotone and slow speech. This pattern is similar to what has been described in other basal ganglia illnesses, such as Parkinson's disease, Huntington's disease and Wilson's disease.
Subject(s)
Chorea/physiopathology , Rheumatic Fever/physiopathology , Speech Acoustics , Speech Perception/physiology , Verbal Behavior/physiology , Acute Disease , Case-Control Studies , Child , Female , Humans , MaleABSTRACT
There are few studies of language and speech in patients with Sydenham's chorea (SC). We have done an acoustic analysis of fundamental frequency (F0), duration and intensity of declarative and interrogative sentences made by 20 SC patients, 20 patients with rheumatic fever (RF) without chorea, and compared them with 20 healthy age-matched controls (CO). Each group included 12 females. We found that there is no difference between the RF and CO groups in all studied parameters. Patients with SC, however, presented with a speech characterized by decreased F0 range (difference between minimum and maximum F0), shorter duration of sentences, and higher intensity of the first syllable of sentences. The findings were not influenced by the nature of the sentences (i.e. , declarative or interrogative), but for all variables they were significantly more severe in males than females. In conclusion, we have demonstrated that patients with acute SC have an impairment of modulation of F0 and longer duration of emission of sentences, resulting in a monotone and slow speech. This pattern is similar to what has been described in other basal ganglia illnesses, such as Parkinson's disease, Huntington's disease and Wilson's disease.
Há poucos estudos sobre linguagem e fala em pacientes com coréia de Sydenham (CS). Fizemos uma análise acústica da freqüência fundamental (F0), duração e intensidade de sentenças declarativas e interrogativas feitas por 20 pacientes com CS, 20 pacientes com febre reumática (FR) sem coréia, comparando-os com 20 controles saudáveis e pareados por idade (CO). Cada grupo incluiu 12 mulheres. Foi encontrado que não há diferença entre os grupos FR e CO quanto a todos parâmetros estudados. Pacientes com CS, contudo, apresentaram-se com fala caracterizada pela redução da variação de F0 (diferença entre F0 mínima e máxima), duração mais curta das sentenças e maior intensidade da primeira sílaba das sentenças. Os achados não foram influenciados pela natureza das sentenças (i.e. , declarativas ou interrogativas), mas os achados foram mais evidentes em todas as variáveis em homens em contraste com mulheres. Em conclusão, demonstramos que pacientes com CS aguda têm prejuízo da modulação da F0 e duração mais longa da emissão de sentenças, resultando em fala mais lenta e monótona. Esse padrão é semelhante ao que tem sido descrito em outras fecções dos núcleos da base, tais como doença de Parkinson, doença de Huntington e doença de Wilson.
Subject(s)
Child , Female , Humans , Male , Chorea/physiopathology , Rheumatic Fever/physiopathology , Speech Acoustics , Speech Perception/physiology , Verbal Behavior/physiology , Acute Disease , Case-Control StudiesABSTRACT
Despite treatment with valproic acid and neuroleptics, a significant proportion of patients with Sydenham chorea (SC) remain with chorea. We evaluated the effect of intravenous methyl-prednisolone followed by oral prednisone in patients with SC refractory to conventional treatment. Patients were enrolled in the study if they failed to improve with conventional treatment, despite the development of side effects. Chorea was rated on a 0 to 4 score. Five patients, 3 of them women, were included in the study. The median pretreatment rating score of the chorea was 3 (range, 3-4) and dropped to 1 (range, 0-2) after a median follow-up of 7 months (range, 3-7 months). Two patients developed Cushing syndrome. Our data suggest that intravenous methyl-prednisolone followed by oral prednisone is an effective and well-tolerated treatment of refractory SC.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Chorea/drug therapy , Methylprednisolone/therapeutic use , Adolescent , Adult , Anti-Inflammatory Agents/administration & dosage , Child , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Injections, Intravenous , Male , Methylprednisolone/administration & dosage , Middle Aged , Treatment OutcomeABSTRACT
Com o objetivo de avaliar o papel da determinacao da atividade da enzima adenosina deaminase (ADA) no diagnostico da peritonite tuberculosa, foram estudados 44 pacientes. De acordo com os resultados das determinacoes bioquimicas, citologicas, histopatologicas e microbiologicas, os pacientes foram divididos em dois grupos: G1 - ascite tuberculosa (n=8); G2 - neoplasica (n=13); G3 - peritonite baracteriana espontanea (n=6); G4 - ascite pancreatica (n=2); G5 - miscelania (n=15). A concentracao de ADA no grupo de pacientes com peritonite tuberculosa foi de 133.50+-24.74 U/l, significantemente mais elevada que nos outros grupos (G2=41.85+-52.07; G3=10.63+-5.87; G4=18.00+-7.07; G5=11.23+-7.66). Com um limite de corte de 31 U/l, a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para diagnostico de tuberculose foram, respectivamente 100, 92, 72 e 100 por cento...
