Background: Platelet-rich plasma (PRP) has emerged as the forerunner among disease-modifying treatment options for early osteoarthritis (OA) of the knee. However, no consensus is available regarding optimum dosing schedules. Purpose: To determine whether multiple injections of PRP (3 injections) provide better short-term and long-term results than a single injection of PRP in a guinea pig model of knee OA. Study Design: Controlled laboratory study. Methods: 36 Dunkin-Hartley guinea pigs (weighing ~600-800 g) were chosen for this study. The animals were assigned to group DC (disease control group), group G1 (single-PRP group), and group G2 (multiple-PRP group) containing 10, 10, and 12 animals, respectively. Another 4 animals were used for preparation of allogenic PRP. Groups G1 and G2 received 1 and 3 injections of PRP, respectively, at weekly intervals in the intervention knee while the contralateral knee was injected with normal saline. Group DC received no intervention in either knee. Half of the animals from each group (subgroups DC.3, G1.3, and G2.3) were sacrificed at 3 months, and the remaining half (subgroups DC.6, G1.6, and G2.6) were sacrificed at 6 months after intervention. Both knee joints were harvested for histological assessment of articular cartilage and synovium. Results: The mean synovial scores for groups G1 and G2 were significantly better than those for group DC at 3 months. No difference was found between groups G1 and G2 at 3 months. At 6 months, group G2 had significantly better mean synovial scores than group G1 and group DC. The mean articular cartilage scores in group G2 were significantly better than those in group DC at 3 months. However, at 6 months, no significant difference was found among any of the groups in terms of mean articular scores. Conclusion: Both single and multiple injections of PRP exert similar anti-inflammatory effects on the synovium in the short term. However, this effect is sustained in the long term only for multiple injections. Multiple injections of PRP exert a chondroprotective effect, but only in the short term. This effect is not seen with a single injection of PRP. Clinical Relevance: This study provides insight into the histological basis for the superiority of multiple injections of PRP.
The differential expression of the petunia 1-aminocyclopropane-1-carboxylate (ACC) oxidase gene family during flower development and senescence was investigated. ACC oxidase catalyzes the conversion of ACC to ethylene. The increase in ethylene production by petunia corollas during senescence was preceded by increased ACC oxidase mRNA and enzyme activity. Treatment of flowers with ethylene led to an increase in ethylene production, ACC oxidase mRNA, and ACC oxidase activity in corollas. In contrast, leaves did not exhibit increased ethylene production or ACC oxidase expression in response to ethylene. Gene-specific probes revealed that the ACO1 gene was expressed specifically in senescing corollas and in other floral organs following exposure to ethylene. The ACO3 and ACO4 genes were specifically expressed in developing pistil tissue. In situ hybridization experiments revealed that ACC oxidase mRNAs were specifically localized to the secretory cells of the stigma and the connective tissue of the receptacle, including the nectaries. Treatment of flower buds with ethylene led to patterns of ACC oxidase gene expression spatially distinct from the patterns observed during development. The timing and tissue specificity of ACC oxidase expression during pistil development were paralleled by physiological processes associated with reproduction, including nectar secretion, accumulation of stigmatic exudate, and development of the self-incompatible response.
The imbalance between excitatory and inhibitory neurotransmitters is explicitly related to the pathophysiology of autism spectrum disorder (ASD). The role of an NMDA receptor antagonist, dextromethorphan, was studied in ameliorating the ASD-like symptoms by regulating the excitatory and inhibitory imbalance using the valproic acid (VPA) model of ASD. Female Wistar rats were administered VPA [600 mg/kg on embryonic day ED-12.5] through intraperitoneal (ip) injection to induce ASD in pups. Autistic pups were then given dextromethorphan (10, 15, and 30 mg/kg; ip) and risperidone (2.5 mg/kg; ip) from PND 23 to 43 in different groups. Behavioral tests (three chamber sociability, self-grooming, Morris water maze, elevated plus maze, open field, rotarod, grip strength), oxidative stress and inflammatory markers, histological evaluation (H&E, Nissil staining), and NMDA and ERK1/2 expression by immunohistochemistry and RT-PCR were done. The in silico modeling of dextromethorphan against PPDA, TCN-201, MK-22, EVT-101 on NMDA receptors was also performed. Dextromethorphan (30 mg/kg) rescued the impaired behavioral patterns including social excitability, hyperactivity, repetitive and restricted behaviors as well as mitigation of the memory and motor coordination. The levels of various oxidative stress markers (GSH, SOD, catalase, MDA) and inflammatory markers (IL-1β, IL-6, IL-10, TNF-α) were ameliorated by different doses of dextromethorphan. It also reduced the neuronal injury score and rescued the overly expressed pERK1/2 and NMDA signaling in both the prefrontal cortex and hippocampus of the autistic pups. In silico results showed favorable binding of dextromethorphan against TCN-201 and MK-22 binding sites. The present study provided experimental evidence for the potential therapeutic role of dextromethorphan in attenuating autism symptomatology in the ASD model of rats. Thus, modulation of the glutamatergic signaling can be a potential target for ASD treatment.
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