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31.
Wang D Belakhov V Kandasamy J Baasov T Li SC Li YT Bedwell DM Keeling KM 《Molecular genetics and metabolism》2012,105(1):116-125
Suppression therapy utilizes compounds that suppress translation termination at in-frame premature termination codons (PTCs) to restore full-length, functional protein. This approach may provide a treatment for diseases caused by nonsense mutations such as mucopolysaccharidosis type I-Hurler (MPS I-H). MPS I-H is a lysosomal storage disease caused by severe α-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. MPS I-H represents a good target for suppression therapy because the majority of MPS I-H patients carry nonsense mutations, and restoration of even a small amount of functional α-L-iduronidase may attenuate the MPS I-H phenotype. In this study, we investigated the efficiency of suppression therapy agents to suppress the Idua-W392X nonsense mutation in an MPS I-H mouse model. The drugs tested included the conventional aminoglycosides gentamicin, G418, amikacin, and paromomycin. In addition, the designer aminoglycosides NB54 and NB84, two compounds previously designed to mediate efficient PTC suppression with reduced toxicity, were also examined. Overall, NB84 suppressed the Idua-W392X nonsense mutation much more efficiently than any of the other compounds tested. NB84 treatment restored enough functional α-L-iduronidase activity to partially reverse abnormal GAG accumulation and lysosomal abundance in mouse embryonic fibroblasts derived from the Idua-W392X mouse. Finally, in vivo administration of NB84 to Idua-W392X mice significantly reduced urine GAG excretion and tissue GAG storage. Together, these results suggest that NB84-mediated suppression therapy has the potential to attenuate the MPS I-H disease phenotype. 相似文献
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Kandasamy K Prawez S Choudhury S More AS Ahanger AA Singh TU Parida S Mishra SK 《Shock (Augusta, Ga.)》2011,36(1):76-82
Hyporeactivity to vasoconstrictors is one of the clinical manifestations of sepsis in man and experimental animals. The objective of the investigation was to examine whether atorvastatin can prevent hyporeactivity to norepinephrine (NE) in mouse aorta in sepsis, and if so, what are the mechanisms involved. Sepsis in mice was induced by cecal ligation and puncture. The aorta was harvested for tension experiment, nitric oxide (NO) and cyclic guanosine monophosphate measurements, and inducible NO synthase (iNOS) and α(1D)-adrenoceptor mRNA expression studies. In comparison with sham-operated controls, sepsis significantly decreased the contractile response to NE in the mouse aorta. Pretreatment with atorvastatin of septic animals completely restored NE-induced contractions to levels similar to those of sham-operated controls and significantly increased survival time and mean arterial pressure. Atorvastatin also attenuated iNOS-induced overproduction of NO, as well as iNOS mRNA expression. Accordingly, hyporeactivity to NE was not evident in tissues pretreated with selective iNOS inhibitor 1400W in sepsis. Although basal cyclic guanosine monophosphate accumulation in the aorta was reduced in sepsis, pretreatment of the tissues with soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ) partially restored the reactivity to NE. Interestingly, hyporeactivity to NE in sepsis was associated with a decreased α(1D)-adrenoceptor mRNA expression in the mouse aorta. Atorvastatin pretreatment, however, prevented the decrease in α(1D)-adrenoceptor mRNA expression in septic animals. In conclusion, atorvastatin seems to prevent hyporeactivity to vasoconstrictor NE in the aorta from septic mice through attenuation of overproduction of NO as well as improved α(1D)-adrenoceptor mRNA expression. The findings of the present study may explain the beneficial effects of atorvastatin on improved hemodynamic functions in sepsis. 相似文献
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Nagarajan Sakthiguru Murugaiyan Manimohan Govindan Jaganathan Kandasamy Manivannan Mohamed Aboobucker Sithique 《Sustainable Chemistry and Pharmacy》2021
A biocomposite composed of Chitosan (Cs), Zinc oxide (ZnO), Acalypha indica (AI) was fabricated by simple chemical precipitation method. The achieved biocomposite was characterized by Fourier Transmission Infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), Scanning electron microscope (SEM) with Energy dispersive X-ray analysis spectroscopy (EDAX) and Transmission electron microscope (TEM). The phytochemical constituents in the AI leaf extract were also studied by Gas chromatography mass spectrometer (GC-MS) analysis. The anti-inflammatory and antioxidant studies were studied using Diclofenac sodium and ascorbic acid as standard by Fetal bovine serum denaturation and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) DPPH radical scavenging method. The effective bactericidal action of the composite was evaluated against both gram-negative, gram-positive bacteria such as Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). The hemolysis activity was studied using Triton x 100 as negative and Phosphate buffer solution (PBS) as positive control. The biocompatibility nature was evaluated by the MTT (3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay and Fluorescence staining method using mouse fibroblast cells (L929). Additionally, the in-vitro wound healing potential was also assessed by scratch wound assay with L929 mouse fibroblast cells. Hence, these obtained results suggest that the Cs/ZnO/AI biocomposite can act as a suitable candidate in wound care applications. 相似文献
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Double trisomy is rare and the only case reported in the literature died soon after birth. We present another case of double trisomy (48XYY, +18) in a male neonate, who was born to a 28-year-old gravida three parity one mother at 35 weeks of gestation. The baby had features of trisomy 18. Karyotype of the patient showed 48, XYY, +18, Ish (DYZ3*2), (D18Z1*3), nuc ish (DYZ3*2), (D18Z1*3) . The patient had clinical features of trisomy 18. There was no family history of diabetes mellitus and no exposure to chemicals. It has been suggested that the rarity of Y-chromosome involvement in trisomy 18 may be due to discrepancy between the sexes. 相似文献
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Prospective Validation of a Screening Tool to Identify Older Adults in Need of a Driving Evaluation
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