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Cannabinoid medications for treatment of neurological disorders
Published in Betty Wedman-St. Louis, Cannabis, 2018
Juan Sanchez-Ramos, Betty Wedman-St. Louis
Cannabidiol (CBD) has been shown to be effective in the treatment of psychosis and sleep disorders in PD patients [28–30]. Garcia et al. [31] studied the effect of delta-9-THCV (tetrahydrocannabivarin) in an animal disease model that provided neuroprotective and symptom-relief effects. Numerous states within the United States have allowed cannabidiol use as an alternative or add-on therapy for Parkinson's disease.
Specific Diseases of Large Animals and Man
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Similar to other musculoskeletal injuries in human athletes in which a spontaneous animal disease model may be utilized to advance the understanding of disease, tendinopathy occurs in the equine athlete at a relatively high rate. The most commonly injured tendon in the athletic horse is the superficial digital flexor tendon (SDFT), and tendon overstrain injuries can account for up to half of the racetrack limb injuries that occur during racing (Smith 2008). The types of injuries seen in the SDFT can vary from focal or core lesions located in the central region of the tendon, to generalized lesions with tendon thickening and minor fiber disruption, to peripheral injuries directly associated with surrounding peritendinous tissues, and finally, complete rupture. Similar to tendinopathy in man, injury recurrence is also common in the horse. There is evidence that repetitive loading of the tendon may result in degenerative changes within the tendon, or at least impaired healing of microdamage within the tendon substance (Smith 2008; Lui et al. 2011). Tendinopathy in horses has similarities to Achilles tendinopathy in man (Lui et al. 2011). The SDFT and Achilles tendons both function to store large amounts of energy during locomotion and reach strains during athletic use that are very close to their functional strain limits (Bogers and Barrett 2019). Both tendons are prone to overstrain injury associated with cumulative load of the tendon and have high re-injury rates (Smith 2008; Bogers and Barrett 2019). Histologically, fiber disruption, collagen fragmentation, and loss of matrix organization is observed along with hypercellularity, hypervascularity, and potential rounding of cells nuclei into a chondrocyte phenotype, are seen as a result of chronic injury (Lui et al. 2011).
Correction of the Genetic Defect in Alpha-1 Antitrypsin Deficiency by Somatic Gene Therapy
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Randy C. Eisensmith, Savio L. C. Woo
A second problem associated with current recombinant adenoviral vectors is the inability to effectively readminister these vectors. If significant amounts of transgene expression could be periodically introduced, then the lack of persistence could at least be partially overcome. The cause of this problem is not a cellular immune response directed against viral proteins expressed from transduced cells, but rather a humoral immune response directed against the viral proteins present in the vector at the time of infusion (82). Our laboratory and others have shown that systemic readministration of adenoviral vectors in mice (57) and dogs (66) is ineffective for periods of at least 9 months, even in the presence of continuous immunosuppression with cyclosporine A (66). While the cellular immune response may be reduced or eliminated by vector modification, this approach cannot prevent the occurrence of a humoral immune response against the input of viral proteins that are necessary for entiy of the vector into the target cell. Thus, various forms of host immunomodulation may still be useful to permit periodic readministration of vector to compensate for the loss of gene expression that may arise from gradual degradation of vector DNA or turnover of target cells. Two immunomodulatory agents that have been shown to permit some degree of reporter gene expression in lung and liver after readministration of adenoviral vectors are the CD4-depleting antibody GK1.5 (67,68,83) and the cytokine IL-12 (67,68). The administration of CD4-depleting antibodies immediately before, during, and after virus administration reduced the levels of neutralizing antiadenoviral antibodies in Balb/c (83) and C57BL/6 (67,68) mice and permitted some transgene expression following readministration of adenoviral vectors in both lung and liver. However, the efficiency of readministration in all of these studies was only a small fraction of that observed in naive animals. By blocking differentiation of Th2 cells, IL-12 administration was somewhat more successful than the CD4-depleting antibody in permitting readministration of adenoviral vectors to the airway epithelium (67), but was largely ineffective in permitting readministration to the liver (68). Furthermore, the ability of IL-12 to permit reinfusion through its inhibition of Th2 cell differentiation appears to come largely at the expense of a heightened CTL response against virally-transduced cells due to the stimulatory effects of IL-12 on Thl cell differentiation. While this result may be acceptable for readministration of viral vectors lacking expression of potentially immunogenic viral or transgenes, this result would ultimately limit the utility of this approach with existing El-deleted adenoviral vectors. Finally, although promising, none of these studies has yet demonstrated the restoration of a phenotypic correction in an animal disease model following adenovirus-mediated transfer of a therapeutic gene, casting some doubt as to the ultimate significance and eventual utility of these procedures.
Comprehensive analysis of metabolic changes in spontaneously hypertensive rats
Published in Clinical and Experimental Hypertension, 2023
Yanan Li, Dadi Xie, Luxi Li, Pei Jiang
Although there are differences between the animal model and hypertensive patients, this analysis also showed great consistency with the information on hypertensive patients. The present results show that 5- and 32-week-old SHRs exhibit differences at the metabolic level compared to age-matched WKY rats. This suggests that metabolic changes have occurred in the early stage of hypertension, and the difference can continue and change with increasing age. An analysis of young hypertensive patients showed that amino acid metabolism is altered in the early stages of hypertension (37). Furthermore, glycolysis and fatty acid metabolism can significantly impact hypertension in hypertensive patients (15). Despite some differences between human studies and experimental animal disease model, animal models still offer some clear advantages (38). The results of this analysis with SHR as a subject also provide helpful information for the study of hypertension.
A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351
Published in mAbs, 2021
Chunyin Gu, Xiaodan Cao, Zongda Wang, Xue Hu, Yanfeng Yao, Yiwu Zhou, Peipei Liu, Xiaowu Liu, Ge Gao, Xiao Hu, Yecheng Zhang, Zhen Chen, Li Gao, Yun Peng, Fangfang Jia, Chao Shan, Li Yu, Kunpeng Liu, Nan Li, Weiwei Guo, Guoping Jiang, Juan Min, Jianjian Zhang, Lu Yang, Meng Shi, Tianquan Hou, Yanan Li, Weichen Liang, Guoqiao Lu, Congyi Yang, Yuting Wang, Kaiwen Xia, Zheng Xiao, Jianhua Xue, Xueyi Huang, Xin Chen, Haixia Ma, Donglin Song, Zhongzong Pan, Xueping Wang, Haibing Guo, Hong Liang, Zhiming Yuan, Wuxiang Guan, Su-Jun Deng
The in vivo efficacy of JMB2002 was evaluated using a SARS-CoV-2 infected rhesus macaque model. The result showed that JMB2002 can provide complete protection and potent therapeutic efficacy in the animal disease model. The peak viral load of oropharyngeal swabs in the control group displayed a similar level with that in a rhesus macaque study of SARS-CoV-2 antibody CB6 and MW05/LALA.13,37 CB6 and MW05/LALA also showed a complete prophylactic effect, as JMB2002 did. The viral titer of animal AC2 in the therapeutic group of JMB2002 reduced to less than the detection limit at 3 dpi, which was consistent with the declining trend in the therapeutic group of CB6 and MW05/LALA. Although the group size (n = 1 or 2) was small and variation in the therapeutic group was observed, the viral load in the therapeutic group showed notable reduction when compared to the negative control group, suggesting the potent in vivo efficacy of JMB2002. Moreover, the clinical trial (ChiCTR2100042150) is being conducted to further evaluate JMB2002.
Dengue vaccine: a key for prevention
Published in Expert Review of Vaccines, 2020
Usa Thisyakorn, Terapong Tantawichien
The first dengue vaccines were evaluated in 1929[15]. Development of safe and effective dengue vaccines faces many challenges. The pathogeneses of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are not clearly understood. One debated hypothesis concerning virus virulence is the immune enhancement hypothesis. Although evidence suggests that dengue disease severity may be associated with genetic differences in dengue strains, virus virulence has been difficult to measure because of the lack of in vivo and in vitro models of disease. Infection by one of the four dengue virus serotypes has been shown to confer lasting protection against homotypic re-infection, but only transient protection against a secondary heterotypic infection, which may lead to an increased risk of severe disease [18–20]. Due to these dengue-specific complexities, vaccine development focuses on the generation of a tetravalent vaccine aimed at providing long-term protection against all four dengue virus serotypes. Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty around correlates of protection. In spite of these challenges, vaccine development has made remarkable progress in recent years, and the current dengue vaccine development is advanced, diverse, and overall promising [12–16].