Agmatine mitigates behavioral abnormalities and neurochemical dysregulation associated with 3-Nitropropionic acid-induced Huntington's disease in rats.

Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats. Rats were pre-treated with 3-NP (10 mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 - 20 µg/rat, i.c.v.) from day-8 to day-27 of the treatment protocol. 3-NP-induced cognitive impairment was associated with declined in agmatine levels within prefrontal cortex, striatum, and hippocampus. Further, the 3-NP-treated rats showed an increase in IL-6 and TNF-α and a reduction in BDNF immunocontent within these brain areas. Agmatine treatment not only improved the 3-NP-induced motor incoordination, depression-like behavior, rota-rod performance, and learning and memory impairment but also normalized the GABA/glutamate, BDNF, IL-6, and TNF-α levels in discrete brain areas. Similarly, various agmatine modulators, which increase the endogenous agmatine levels in the brain, such as L-arginine (biosynthetic precursor), aminoguanidine (diamine oxidase inhibitor), and arcaine (agmatinase inhibitor) also demonstrated similar effects exhibiting the importance of endogenous agmatinergic pathway in the pathogenesis of 3-NP-induced HD like symptoms. The present study proposed the possible role of agmatine in the pathogenesis and treatment of HD associated motor incoordination, and psychiatric and cognitive complications.

Titanium Elastic Nailing with Temporary External Fixator versus Bridge Plating in Comminuted Pediatric Femoral Shaft Fractures: A Comparative Study.

BACKGROUND: High-velocity trauma, associated injuries, risk of iatrogenic devascularization of fragments and need for maintaining alignment upto union make comminuted fracture in pediatric femur a formidable fracture to treat. This comparative study was conducted to evaluate the outcomes of two modes of management in such cases: titanium elastic nailing supplemented with external fixator and submuscular bridge plating (BP). MATERIALS AND METHODS: Thirty eight children (aged 6-12 years) with comminuted fracture shaft femur who were randomized into two groups underwent systematic evaluation. One group was operated with titanium nailing with temporary external stabilization by fixators (titanium nailing with external [TNE] group) for 4 weeks. The other underwent submuscular BP with locked plates (BP group). Clinical and radiological outcomes, operative time, blood loss, radiation exposure, difficulties in removal and complications were evaluated. RESULTS: Both groups achieved union (10.7 ± 1.9 weeks BP, 11 ± 1.6 weeks TNE), satisfactory knee flexion (138.2 ± 6.4° BP, 136 ± 7.3° TNE), and painless weight bearing (7.3 ± 0.9 weeks vs. 7.3 ± 1.4 weeks) in acceptable alignment. Functional outcomes were excellent in majority of both BP (15 of 19) and nail external fixator groups (15 of 18). Operating time and radiation exposure (69.5 ± 14.5 s vs. 50.9 ± 12.9 s) were more in TNE than in BP (P < 0.01). However, implant removal was more difficult in BP (56.4 ± 12.4 min in BP vs. 30.1 ± 8.8 min TNE). Pin-tract infections (n = 3) and hardware prominence (n = 2) in TNE group and deep infections (n = 2) in BP group were notable complications. CONCLUSION: Two groups were similar in radiological and functional outcomes. Inserting elastic nails and external fixator was a more exacting surgery, while removal was more difficult in BP group. Both techniques had acceptable success and complication rates.