Utilising fluorescent reporters to probe the mode of action of norbornen-7-one CO releasing molecules.

The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.

Diagnostic Ultrasonographic Diagnosis of Posttraumatic Osteolysis of the Distal Clavicle in a 24-Year-Old Bodybuilder: A Case Report With Correlative Radiographs and Magnetic Resonance Imaging.

OBJECTIVE: The purpose of this case study is to demonstrate the strength of diagnostic ultrasound in the evaluation of posttraumatic osteolysis of the distal clavicle (PTOC) when compared with radiographs and magnetic resonance imaging (MRI). CLINICAL FEATURES: The patient is a 24-year-old male bodybuilding athlete with focal tenderness of the left acromioclavicular joint. After a plain film examination, both diagnostic ultrasound and MRI were performed. Each form of imaging demonstrated frank fragmentation of the distal clavicular margin of the acromioclavicular joint, with evidence of hyperemia shown on both. INTERVENTION AND OUTCOME: After the diagnosis of PTOC was established, the patient was successfully led through conservative measures that included activity and weight-training modification, rest, anti-inflammatory modalities, and kinesio taping. CONCLUSION: This case report adequately demonstrates the value of diagnostic musculoskeletal ultrasound in diagnosing PTOC, with comparison to radiographs and MRI.

Magnetic resonance imaging zygapophyseal joint space changes (gapping) in low back pain patients following spinal manipulation and side-posture positioning: a randomized controlled mechanisms trial with blinding.

OBJECTIVE: The purpose of this study was to quantify lumbar zygapophyseal (Z) joint space separation (gapping) in low back pain (LBP) subjects after spinal manipulative therapy (SMT) or side-posture positioning (SPP). METHODS: This was a controlled mechanisms trial with randomization and blinding. Acute LBP subjects (N = 112; four n = 28 magnetic resonance imaging [MRI] protocol groups) had 2 MRI appointments (initial enrollment and after 2 weeks of chiropractic treatment, receiving 2 MRI scans of the L4/L5 and L5/S1 Z joints at each MRI appointment. After the first MRI scan of each appointment, subjects were randomized (initial enrollment appointment) or assigned (after 2 weeks of chiropractic treatment appointment) into SPP (nonmanipulation), SMT (manipulation), or control MRI protocol groups. After SPP or SMT, a second MRI was taken. The central anterior-posterior joint space was measured. Difference between most painful side anterior-posterior measurements taken postintervention and preintervention was the Z joint "gapping difference." Gapping differences were compared (analysis of variance) among protocol groups. Secondary measures of pain (visual analog scale, verbal numeric pain rating scale) and function (Bournemouth questionnaire) were assessed. RESULTS: Gapping differences were significant at the first (adjusted, P = .009; SPP, 0.66 ± 0.48 mm; SMT, 0.23 ± 0.86; control, 0.18 ± 0.71) and second (adjusted, P = .0005; SPP, 0.65 ± 0.92 mm; SMT, 0.89 ± 0.71; control, 0.35 ± 0.32) MRI appointments. Verbal numeric pain rating scale differences were significant at first MRI appointment (P = .04) with SMT showing the greatest improvement. Visual analog scale and Bournemouth questionnaire improved after 2 weeks of care in all groups (both P < .0001). CONCLUSIONS: Side-posture positioning showed greatest gapping at baseline. After 2 weeks, SMT resulted in greatest gapping. Side-posture positioning appeared to have additive therapeutic benefit to SMT.

Evaluating the relationship among cavitation, zygapophyseal joint gapping, and spinal manipulation: an exploratory case series.

OBJECTIVE: This project determined the feasibility of conducting larger studies assessing the relationship between cavitation and zygapophyseal (Z) joint gapping following spinal manipulative therapy (SMT). METHODS: Five healthy volunteers (average age, 25.4 years) were screened and examined against inclusion and exclusion criteria. High-signal magnetic resonance imaging (MRI) markers were fixed to T12, L3, and S1 spinous processes. Scout images were taken to verify the location of the markers. Axial images of the L4/L5 and L5/S1 levels were obtained in the neutral supine position. Following the first MRI, accelerometers were placed over the same spinous processes; and recordings were made from them during side-posture positioning and SMT. The accelerometers were removed, and each subject was scanned in side-posture. The greatest central anterior to posterior Z joint spaces (gap) were measured from the first and second MRI scans. Values obtained from the first scan were subtracted from those of the second, with a positive result indicating an increase in gapping following SMT (positive gapping difference). Gapping difference was compared between the up-side (SMT) joints vs the down-side (non-SMT) joints and between up-side cavitation vs up-side noncavitation joints. RESULTS: Greater gapping was found in Z joints that received SMT (0.5 ± 0.6 mm) vs non-SMT joints (-0.2 ± 0.6 mm), and vertebral segments that cavitated gapped more than those that did not cavitate (0.8 ± 0.7 vs 0.4 ± 0.5 mm). CONCLUSIONS: A future clinical study is quite feasible. Forty subjects (30 in an SMT group and 10 in a control group) would be needed for appropriate power (0.90).