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1.
J Biomech ; 169: 112155, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761746

RESUMO

Acute alcohol ingestion has been found to impact visual functions, including eye movement, but its effects on corneal biomechanical properties remain unclear. This study aimed to investigate the influence of acute alcohol consumption on corneal biomechanical properties using optical coherence elastography (OCE). An air-coupled ultrasound transducer induced elastic waves in mice corneas in vivo, and a high-resolution phase-sensitive optical coherence tomography (OCT) system tracked the mechanical waves to quantify the elastic wave speed. In vivo measurements were performed on three groups of age- and gender-matched mice: control, placebo (administered saline), and alcohol (administered ethanol) groups. Longitudinal measurements were conducted over a one-hour period to assess acute temporal changes in wave speeds, which are associated with inherent biomechanical properties of the cornea. The results showed a significant decrease in wave speed for the alcohol group after 10 min of ingestion in comparison to pre-ingestion values (p = 0.0096), whereas the temporal wave speed changes for the placebo group were statistically insignificant (p = 0.076). In contrast, the control group showed no significant changes in elastic wave speed and corneal thickness. Furthermore, a significant difference was observed between the wave speeds of the placebo and alcohol groups at each measurement time point between 10 and 50 min (p < 0.05), though both groups exhibited a similar trend in corneal thickness change. The findings of this study have important implications for clinical assessments and research in corneal disorders, highlighting the potential of OCE as a valuable tool for evaluating such changes.

2.
Adv Sci (Weinh) ; : e2400089, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526147

RESUMO

Noninvasive monitoring of cardiac development can potentially prevent cardiac anomalies in adulthood. Mouse models provide unique opportunities to study cardiac development and disease in mammals. However, high-resolution noninvasive functional analyses of murine embryonic cardiac models are challenging because of the small size and fast volumetric motion of the embryonic heart, which is deeply embedded inside the uterus. In this study, a real time volumetric optoacoustic spectroscopy (VOS) platform for whole-heart visualization with high spatial (100 µm) and temporal (10 ms) resolutions is developed. Embryonic heart development on gestational days (GDs) 14.5-17.5 and quantify cardiac dynamics using time-lapse-4D image data of the heart is followed. Additionally, spectroscopic recordings enable the quantification of the blood oxygenation status in heart chambers in a label-free and noninvasive manner. This technology introduces new possibilities for high-resolution quantification of embryonic heart function at different gestational stages in mammalian models, offering an invaluable noninvasive method for developmental biology.

3.
J Infect Dev Ctries ; 18(2): 309-314, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38484343

RESUMO

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast, rarely found as a causal agent of invasive fungal infection. In this study, we report a 31-year-old man infected with M. capitatus in the oral cavity, with a history of heroin and amphetamine abuse. M. capitatus was isolated through culture and microscopic analysis and identified by PCR amplification of the ITS DNA region. Based on the in vitro antifungal susceptibility test, the lowest MICs for M. capitatus were recorded for nystatin, itraconazole, and amphotericin, while higher MICs were observed for caspofungin and fluconazole. Treatment with nystatin successfully eliminated M. capitatus and relieved the clinical symptoms. This study presents the first case of M. capitatus in a patient with substance use disorder, manifesting as a plaque-like ulcer in the oral cavity.


Assuntos
Antifúngicos , Saccharomycetales , Masculino , Humanos , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Nistatina , Saccharomycetales/genética , Boca , Fluconazol , Testes de Sensibilidade Microbiana
4.
J Anim Physiol Anim Nutr (Berl) ; 108(2): 493-499, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37997652

RESUMO

It has been documented that adequate maternal manganese (Mn) status is vital for performance and health of ewes and their newborn lambs. However, required level and form of dietary Mn in ruminants are not well defined. The current study was conducted to evaluate the effect of maternal organic Mn supplementation on performance, immunological status, blood biochemical and antioxidant status of Afshari ewes and their newborn lambs in transition period. For this purpose, various organic Mn concentrations were utilized as a supplementary ingredient in formulating the diets of ewes. The ewes were randomly allocated into three groups, fed with 0, and 80 mg/kg organic Mn supplemented diet. At the end of the experiment, the parameters including the performance of newborn lambs, as well as biochemical factors, immune status and antioxidant status in ewes and their newborn lambs were evaluated. The results showed a significant increase in the plasma concentrations of Mn, glucose, insulin, thyroid hormones (T3 , T4 ) and enzymatic antioxidants (SOD, GPX , CAT) in ewes and their newborn lambs that were treated with maternal organic Mn. Moreover, inorganic Mn treatments, the concentration of IgG in newborn lamb's plasma, and colostrum of ewes increased. According to this research, organic Mn acts as a valuable and safe supplementary material that could be exploited for enhancing health of ewes and their newborn lambs.


Assuntos
Antioxidantes , Manganês , Animais , Ovinos , Feminino , Manganês/farmacologia , Animais Recém-Nascidos , Suplementos Nutricionais , Dieta/veterinária
5.
Infez Med ; 31(4): 466-475, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075425

RESUMO

A significant proportion of urinary tract infections (UTIs), typically affecting kidney transplant patients (KTPs), is attributed to the presence of extended-spectrum ß-lactamases (ESBLs) and multi-drug resistance (MDR) in Escherichia coli strains. For this reason, the current meta-analysis was conducted to summarize the frequency of ESBL-producing UPEC among KTPs. A systematic search was conducted to identify studies in the Web of Science, PubMed, Embase, and Scopus electronic databases between 2000 and 2021. Finally, 16 articles were selected for data extraction, and meta-analysis was performed using the metaprop command in the STATA (version 11) software. From those studies, the pooled prevalence of ESBL-producing uropathogenic E. coli (UPEC) isolates was 40%. The subcategory analysis results based on continent indicated that Asian countries had the highest rate of ESBL-producing isolates with 45%, followed by 40%, 28%, and 16% in Europe, South America and North America, respectively. Uncomfortably, high level of UPEC isolates in the current investigation was ESBL-producing isolates. These isolates pose a high serious threat to public health because they can contribute to the spread of antimicrobial resistance in the local population and hasten the ineffectiveness of the majority of commonly prescribed antibiotics for the treatment of UTI in KTPs and other patients.

6.
Biomed Opt Express ; 14(11): 5670-5681, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38021113

RESUMO

Many tissues are composed of layered structures, and a better understanding of the changes in the layered tissue biomechanics can enable advanced guidance and monitoring of therapy. The advent of elastography using longitudinally propagating shear waves (LSWs) has created the prospect of a high-resolution assessment of depth-dependent tissue elasticity. Laser activation of liquid-to-gas phase transition of dye-loaded perfluorocarbon (PFC) nanodroplets (a.k.a., nanobombs) can produce highly localized LSWs. This study aims to leverage the potential of photoactivation of nanobombs to incudce LSWs with very high-frequency content in wave-based optical coherence elastography (OCE) to estimate the elasticity gradient with high resolution. In this work, we used multilayered tissue-mimicking phantoms to demonstrate that highly localized nanobomb (NB)-induced LSWs can discriminate depth-wise tissue elasticity gradients. The results show that the NB-induced LSWs rapidly change speed when transitioning between layers with different mechanical properties, resulting in an elasticity resolution of ∼65 µm. These results show promise for characterizing the elasticity of multilayer tissue with a fine resolution.

7.
Int Immunopharmacol ; 118: 110027, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37011500

RESUMO

The design and development of effective multitargeted agents in treating Alzheimer disease (AD) has always been a hot topic in the field of drug discovery. Since AD is a multifactorial disorder, various key hidden players such as deficit of acetylcholine (ACh), tau-protein aggregation, and oxidative stress have been associated with the incidence and progress of AD. In pursuit of improving efficacy and expanding the range of pharmacological activities of current AD drugs, the molecular hybridization method is also used intensively. Five-membered heterocyclic systems such as thiadiazole scaffolds have previously been shown to have therapeutic activity. Thiadiazole analogs as an anti-oxidant compound have been known to include a wide range of biological activity from anti-cancer to anti-Alzheimer properties. The suitable pharmacokinetic and physicochemical properties of the thiadiazole scaffold have introduced it as a therapeutic target in medicinal chemistry. The current review portrays the critical role of the thiadiazole scaffold in the design of various compounds with potential effects in the treatment of Alzheimer's disease. Furthermore, the rationale used behind hybrid-based design strategies and the outcomes achieved through the hybridization of Thiadiazole analogs with various core structures have been discussed. In addition, the data in the present review may help researchers in the design of new multidrug combinations that may provide new options for the treatment of AD.


Assuntos
Doença de Alzheimer , Neoplasias , Tiadiazóis , Humanos , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêutico , Descoberta de Drogas , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-36865743

RESUMO

Alzheimer's disease (AD) which is associated with cognitive dysfunction and memory lapse has become a health concern. Various targets and pathways have been involved in AD's progress, such as deficit of acetylcholine (ACh), oxidative stress, inflammation, ß-amyloid (Aß) deposits, and biometal dyshomeostasis. Multiple pieces of evidence indicate that stress oxidative participation in an early stage of AD and the generated ROS could enable neurodegenerative disease leading to neuronal cell death. Hence, antioxidant therapies are applied in treating AD as a beneficial strategy. This review refers to the development and use of antioxidant compounds based on natural products, hybrid designs, and synthetic compounds. The results of using these antioxidant compounds were discussed with the given examples, and future directions for the development of antioxidants were evaluated.

9.
Reprod Domest Anim ; 58(5): 630-636, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36808661

RESUMO

Equine semen cryopreservation is one of the major procedures for the genetic conservation of rare and endangered genotypes. The current study was conducted to evaluate the effect of egg yolk plasma (EYP) enriched with ß-carotene as an antioxidant supplement on INRA-96 extender regarding freezing Arabic stallion sperm. For this purpose, ß-carotene various concentrations were utilized as a supplementary ingredient in formulating the diets of laying hens. Birds were randomly divided into four groups, fed with 0 (control), 500, 1000 and 2000 mg/kg in a supplemented diet with ß-carotene. Subsequently, various variants of enriched extender (INRA-96 + 2.5% glycerol [G]) were gained by adding 2% EYP from four treatment groups. The sperm characteristics, including motility, viability, morphology, plasma membrane integrity (HOS test), lipid peroxidation (MDA) and DNA fragmentation, were evaluated after thawing. According to the results obtained in this study, the addition of EYP from T2 and T4 (500 and 2000 mg/kg of ß-carotene in hens' diet) to the extender (INRA-96 + 2.5% G) leads to an increase in total motility (50.50% and 49.49%, respectively), progressive motility (32.6% and 31.8%, respectively), viability (68.7% and 66.1%, respectively) and plasma membrane integrity (57.7% and 50.6%, respectively). Moreover, lipid peroxidation (1.3 and 1.4 nmol/mL, respectively) and DNA fragmentation (8.6% and 9.9%, respectively) were diminished using the mentioned treatments. However, sperm morphology was not affected by the treatments. In the current study, we concluded that the optimal concentration of ß-carotene in the laying hen's diet (500 mg/kg) could reveal the best results about sperm quality. So, EYP enriched with ß-carotene acts as a valuable natural and safe supplementary material that could be exploited for enhancing stallion sperm quality in cryopreservation conditions.


Assuntos
Preservação do Sêmen , Sêmen , Animais , Masculino , Cavalos , Feminino , Galinhas , beta Caroteno/farmacologia , Crioprotetores/farmacologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Gema de Ovo , Motilidade dos Espermatozoides , Espermatozoides , Criopreservação/veterinária , Criopreservação/métodos , Dieta/veterinária
10.
Vaccines (Basel) ; 10(7)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35891296

RESUMO

Neuromyotonia is a rare peripheral nerve hyperexcitability syndrome often associated with antibodies directed against contactin-associated protein-like 2 and leucine-rich, glioma inactivated 1. The quadrivalent human papilloma virus vaccine Gardasil®, first approved in 2006, is known to be a highly effective prophylaxis against papillomavirus types 6, 11, 16, and 18. Molecularly, this non-infectious recombinant vaccine is based on purified L1 proteins from the human papilloma virus capsid. Since the approval of this vaccine, several studies have investigated its safety regarding the occurrence of autoimmune conditions following application. Here, we present the first case of neuromyotonia with active Gadolinium enhancing demyelinating central nervous system lesions following vaccination with Gardasil®.

11.
J Fungi (Basel) ; 8(7)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35887512

RESUMO

Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole.

12.
Iran J Microbiol ; 14(1): 133-137, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35664717

RESUMO

Background and Objectives: Catalases are a good scavenger of H2O2 which degrades hydrogen peroxide into water and oxygen. They are considered as a virulence factor that are present in both spores and hypha of fungi. There is limited data regarding catalase activity in Aspergillus species. This study aimed to assess the mycelial catalase activity of clinical and environmental isolates of Aspergillus niger, A. tubingensis, A. flavus, A. luchuensis, A. piperis and A. terreus. Materials and Methods: Briefly, clinical and environmental Aspergillus species were used in the current study. Catalase activity was assessed for both groups of isolates including 13 A. flavus (12 clinical, 1 environmental), 13 A. terreus (8 clinical, 5 environmental), 26 A. tubingensis (13 clinical, 13 environmental), and 44 A. niger (25 environmental, 19 clinical) species. Fungal balls of mycelia were separated from the liquid culture and were crushed using homogenizer. The supernatants were collected and used for a catalase activity assay. Results: Totally, in our study 98 Aspergillus including 45 environmental and 53 clinical isolates were assessed for catalase activity. High catalase activity was detected among environmental Aspergillus species (Mean= 1.62 mU/ml) and the mean of mycelial catalase activity among clinical A. terreus isolates was higher than environmental strains. Conclusion: In summary, mycelial catalase activity varied among species and environmental isolates demonstrated higher catalase activity. Totally a significant difference was found between clinical and environmental Aspergillus isolates.

13.
Animals (Basel) ; 12(4)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35203218

RESUMO

This study was conducted to investigate the effect of milk supplemented with organic iron on performance, blood hematology, iron metabolism parameters, biochemical and immunological parameters in suckling lambs. Thirty-six newborn Dalagh lambs were randomly divided into three groups with 12 replications. The control group was fed with milk without organic iron. The other two groups were fed milk supplemented with 25 and 50 mg/d organic iron, respectively. During the experiment, increased daily weight gain and total body weight were observed in the iron-supplemented groups. An increase in the levels of red blood cell, hemoglobin, hematocrit, mean corpuscular hemoglobin, and mean corpuscular concentration in iron supplemented groups was indicated. Consumption of organic iron caused a significant decrease in plasma copper concentration. Total antioxidant status level was lower, but levels of glutathione peroxidase, superoxide dismutase, and catalase were higher in iron supplemented groups. In organic iron supplemented groups, insulin and thyroid hormones levels were significantly increased, and glucose level was significantly decreased. In organic iron supplemented groups, alkaline phosphatase level significantly increased, and aminotransferase level significantly decreased. Overall, the use of organic iron in the milk improved the performance and health in suckling lambs, and since a lower level of supplementation is naturally preferable, supplementation of milk with 25 mg/d organic iron is recommended.

14.
Cells ; 11(4)2022 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-35203385

RESUMO

The Sonic Hedgehog protein (Shh) has been extensively researched since its discovery in 1980. Its crucial role in early neurogenesis and endogenous stem cells of mature brains, as well as its recently described neuroprotective features, implicate further important effects on neuronal homeostasis. Here, we investigate its potential role in the survival, proliferation, and differentiation of neural precursors cells (NPCs) under inflammatory stress as a potential adjunct for NPC-transplantation strategies in spinal cord injury (SCI) treatment. To this end, we simulated an inflammatory environment in vitro using lipopolysaccharide (LPS) and induced the Shh-pathway using recombinant Shh or blocked it using Cyclopamine, a potent Smo inhibitor. We found that Shh mediates the proliferation and neuronal differentiation potential of NPCs in vitro, even in an inflammatory stress environment mimicking the subacute phase after SCI. At the same time, our results indicate that a reduction of the Shh-pathway activation by blockage with Cyclopamine is associated with reduced NPC-survival, reduced neuronal differentiation and increased astroglial differentiation. Shh might thus, play a role in endogenous NPC-mediated neuroregeneration or even be a potent conjunct to NPC-based therapies in the inflammatory environment after SCI.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal , Diferenciação Celular , Proliferação de Células , Proteínas Hedgehog/metabolismo , Humanos , Células-Tronco Neurais/metabolismo , Transdução de Sinais
15.
Eur Arch Otorhinolaryngol ; 279(5): 2665-2669, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34564759

RESUMO

INTRODUCTION: This study aimed to comparing the effect of peritonsillar infiltration of tramadol and dexmedetomidine in relieving post-tonsillectomy pain. METHODS: In this randomized double blinded clinical trial study, 90 children 5-12 years old undergoing tonsillectomy, involved. Induction of anesthesia was done by fentanyl 1 µg/kg, sodium thiopental 5 mg/kg and atracurium 0.5 mg/kg and intubation was done after 3 min. Anesthesia maintained by nitrous oxide 60% and oxygen 40% with isoflurane (1.2%). Tramadol 2 mg/kg in group A, dexmedetomidine 1 µg/kg in group B, and normal saline in group c were injected into the bed and anterior tonsillar pillar and surgery has begun after 3 min of injection. Time of surgery, all hemodynamic variables, pain intensity and degree of sedation were recorded and evaluated. RESULTS: The results showed that duration of the surgery (p value = 0.28) and duration of anesthesia (p value = 0.43) were not significantly different between the groups but pain score was significantly lower in dexmedetomidine group in comparison to tramadol and placebo group (p value = 0.001). The first time for analgesic request was longer in dexmedetomidine group (p value = 0.001) and Hemodynamic parameters were significantly lower in tramadol and dexmedetomidine group (p value = 0.001). Sedation level was not significantly different between tramadol and dexmedetomidine group (p value = 0.001). CONCLUSION: According to the results peritonsillar infiltration of dexmedetomidine is effective and safe in relieving post-tonsillectomy pain.


Assuntos
Dexmedetomidina , Tonsilectomia , Tramadol , Analgésicos Opioides/uso terapêutico , Criança , Pré-Escolar , Dexmedetomidina/uso terapêutico , Método Duplo-Cego , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Tramadol/uso terapêutico
16.
Am Surg ; 88(1): 98-102, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33371715

RESUMO

INTRODUCTION: The present study was attempted to evaluate the effect of perianal infiltration of tramadol on postoperative pain in patients undergoing hemorrhoidectomy. METHOD: This double-blind clinical trial study was carried out on 90 patients with grade 3 and 4 hemorrhoids undergoing hemorrhoidectomy. Patients were randomly assigned into 3 groups of control or bupivacaine or tramadol. Before the surgery, perianal infiltration of .25% bupivacaine or tramadol or normal saline was prescribed to each group, respectively. Data on pain severity (based on the visual analog scale (VAS), the duration of surgery, sedation score, pain at the first defecation, first request time for additional analgesia, nausea and vomiting, and analgesic intakes) were evaluated and analyzed. RESULTS: Duration of surgery was almost similar in all 3 groups (P = .974). The results showed a significant difference in pain score between 3 groups (P ≤.05) at all times after the surgery. In addition, the means of sedation scores (P = .03), pain score at the first defecation (P = .001), the time to first analgesic request (P = .001), and ketorolac administration times (P = .01) were significantly different between 3 groups. Finally, no complication was reported regarding postoperative nausea and vomiting. CONCLUSION: Given the notable efficacy of tramadol in reducing pain after hemorrhoidectomy and its minor side effects, this medication is suggested as an effective topical anesthetic to decrease pain after hemorrhoidectomy.


Assuntos
Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Hemorroidectomia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Tramadol/administração & dosagem , Adulto , Idoso , Anestesia Local/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Defecação , Método Duplo-Cego , Humanos , Cetorolaco/administração & dosagem , Pessoa de Meia-Idade , Náusea/etiologia , Duração da Cirurgia , Medição da Dor
17.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 3824-3831, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36742531

RESUMO

Introduction: We decided to compare dexmedetomidine with propofol regarding several anesthetic and surgical aspects, during stapedotomy done under conscious sedation. Materials and Method: Thirty patients aged 20-50 years with (American Society of Anesthesiology) ASA class I-II, were assigned to two groups of propofol and dexmedetomidine using a random number table. In dexmedetomidine group, patients received dexmedetomidine infusion (0.5 µg/kg/h) and in the control group, propofol was administered (3 mg/kg/h).Time to reach the desired Ramsey Sedation Score (RSS) and time to reach Aldrete score ≥ 9; incidence of inadvertent movement and amnesia; as well as patients' and surgeons' level of satisfaction and degree of bleeding was recorded. Data on hemodynamic variables were monitored and recorded at several intervals. Results: The mean time taken to reach the RSS (2-4) was 10.3 ± 2.1 min in dexmedetomidine group and 3.1 ± 1.2 min in propofol group. Time to reach Aldrete score ≥ 9 for patients sedated with dexmedetomidine was 8.6 ± 2.1 min and for propofol group was 4.6 ± 1.4 min (p value < 0.05).There were also significant differences between two groups in terms of surgeon's satisfaction with sedation, and the amount of intra operative bleeding. Conclusion: According to the results of this study, it can be concluded that dexmedetomidine is a better choice for conscious sedation than propofol. However, the time to reach the required sedation in the dexmedetomidine group was significantly longer.

18.
Int J Mol Sci ; 22(23)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34884911

RESUMO

Cervical spinal cord injury (SCI) remains a devastating event without adequate treatment options despite decades of research. In this context, the usefulness of common preclinical SCI models has been criticized. We, therefore, aimed to use a clinically relevant animal model of severe cervical SCI to assess the long-term effects of neural precursor cell (NPC) transplantation on secondary injury processes and functional recovery. To this end, we performed a clip contusion-compression injury at the C6 level in 40 female Wistar rats and a sham surgery in 10 female Wistar rats. NPCs, isolated from the subventricular zone of green fluorescent protein (GFP) expressing transgenic rat embryos, were transplanted ten days after the injury. Functional recovery was assessed weekly, and FluoroGold (FG) retrograde fiber-labeling, as well as manganese-enhanced magnetic resonance imaging (MEMRI), were performed prior to the sacrifice of the animals eight weeks after SCI. After cryosectioning of the spinal cords, immunofluorescence staining was conducted. Results were compared between the treatment groups (NPC, Vehicle, Sham) and statistically analyzed (p < 0.05 was considered significant). Despite the severity of the injury, leading to substantial morbidity and mortality during the experiment, long-term survival of the engrafted NPCs with a predominant differentiation into oligodendrocytes could be observed after eight weeks. While myelination of the injured spinal cord was not significantly improved, NPC treated animals showed a significant increase of intact perilesional motor neurons and preserved spinal tracts compared to untreated Vehicle animals. These findings were associated with enhanced preservation of intact spinal cord tissue. However, reactive astrogliosis and inflammation where not significantly reduced by the NPC-treatment. While differences in the Basso-Beattie-Bresnahan (BBB) score and the Gridwalk test remained insignificant, animals in the NPC group performed significantly better in the more objective CatWalk XT gait analysis, suggesting some beneficial effects of the engrafted NPCs on the functional recovery after severe cervical SCI.


Assuntos
Neurônios Motores/fisiologia , Células-Tronco Neurais/transplante , Oligodendroglia/metabolismo , Traumatismos da Medula Espinal/terapia , Animais , Diferenciação Celular , Células Cultivadas , Vértebras Cervicais , Modelos Animais de Doenças , Feminino , Análise da Marcha , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Imageamento por Ressonância Magnética , Células-Tronco Neurais/citologia , Oligodendroglia/fisiologia , Ratos , Ratos Transgênicos , Ratos Wistar , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/fisiopatologia
19.
Front Neurol ; 12: 696807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248832

RESUMO

The Marburg variant of multiple sclerosis (Marburg MS) is the most aggressive form of MS, often leading to death soon after onset. Here we describe the case of a 26-year-old Marburg MS patient presenting with severe neurological deficits requiring intensive care. In spite of more than 100 gadolinium-enhancing MRI lesions, the patient recovered almost completely upon high-dose cyclophosphamide (HiCy) rescue treatment (four consecutive days with 50 mg/kg/day, cumulative absolute dose of 14 g). Following the acute treatment, her disease was stabilized by B cell depletion using ocrelizumab. Clinical amelioration was reflected by a decrease of MRI activity and a marked decline of serum neurofilament light chain levels. HiCy rescue treatment followed by ocrelizumab as a maintenance therapy prevented permanent disability and achieved an almost complete clinical and drastic radiological improvement in this Marburg MS patient.

20.
Eur Spine J ; 30(6): 1509-1520, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33704579

RESUMO

PURPOSE: The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. METHODS: Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). RESULTS: The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. CONCLUSION: Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.


Assuntos
Contusões , Traumatismos da Medula Espinal , Animais , Proteínas Hedgehog , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Recuperação de Função Fisiológica , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico
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