Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Effects of magnetic resonance imaging diffusion gradient recalled echo on a patient with an intracranial hemorrhage presenting to the emergency department.

Generally, a computed tomography scan is conducted for the diagnosis of stroke in the emergency department, because these scans are easier and faster in the detection of stroke. If there are no signs of hemorrhage on computed tomography scan, an ischemic stroke is diagnosed and treated accordingly. A magnetic resonance imaging scan may be taken in order to verify ischemic stroke. This process may lead to improper treatment and is time consuming. To address this situation, case studies are presented in which magnetic resonance imaging diffusion-weighted imaging and gradient recalled echo were performed to detect hemorrhagic and ischemic stroke and particularly, subarachnoid hemorrhage, which is undetectable with a computed tomography scan.     

Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolmic rats

This study was conducted to investigate the hypocholesterolemic effect of simvastatin (30 mg/kg BW) and antioxidant effect of coenzyme Q10 (CoQ10, 15 mg/kg BW) or green tea (5%) on erythrocyte Na leak, platelet aggregation and TBARS production in hypercholesterolemic rats treated with statin. Food efficiency ratio (FER, ADG/ADFI) was decreased in statin group and increased in green tea group, and the difference between these two groups was significant (p<0.05). Plasma total cholesterol was somewhat increased in all groups with statin compared with control. Plasma triglyceride was decreased in statin group and increased in groups of CoQ10 and green tea, and the difference between groups of statin and green tea was significant (p<0.05). Liver total cholesterol was not different between the control and statin group, but was significantly decreased in the group with green tea compared with other groups (p<0.05). Liver triglyceride was decreased in groups of statin and green tea compared with the control, and the difference between groups of the control and green tea was significant (p<0.05). Platelet aggregation of both the initial slope and the maximum was not significantly different, but the group with green tea tended to be higher in initial slope and lower in the maximum. Intracellular Na of group with green tea was significantly higher than the control or statin group (p<0.05). Na leak in intact cells was significantly decreased in the statin group compared with the control (p<0.05). Na leak in AAPH treated cells was also significantly reduced in the statin group compared with groups of the control and CoQ10 (p<0.05). TBARS production in platelet rich plasma was significantly decreased in the groups with CoQ10 and green tea compared with the control and statin groups (p<0.05). TBARS of liver was significantly decreased in the group with green tea compared with the statin group (p<0.05). In the present study, even a high dose of statin did not show a cholesterol lowering effect, therefore depletion of CoQ10 following statin treatment in rats is not clear. More clinical studies are needed for therapeutic use of CoQ10 as an antioxidant in prevention of degenerative diseases independent of statin therapy.     

Critical size defect in the canine mandible.

OBJECTIVE: The purpose of this study was to determine the minimum size defect in a canine mandible that would not spontaneously heal during the dog's natural life (the critical size defect). STUDY DESIGN: Sixteen adult female mongrel dogs underwent continuity resection on both sides of the mandible to create bilateral defects. In 8 dogs, mandibular defects ranging from 5 to 20 mm were created with periosteal resection. In the other 8 dogs, mandibular defects ranging from 30 to 60 mm were created preserving the periosteum. The dogs were then killed at 6 months and the defects examined using radiographs and histologic analysis. RESULTS: When the periosteum was removed, mandibular defects greater than 15 mm failed to heal across the entire defect. However, when the periosteum was preserved, mandibular defects needed to be greater than 50 mm in order to fail to heal. CONCLUSION: The critical size defect in a canine mandible model is 15 mm when the periosteum is removed and 50 mm when the periosteum is preserved.     

Central metabotropic glutamate receptors differentially participate in interleukin-1beta-induced mechanical allodynia in the orofacial area of conscious rats.

The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. Subcutaneous injection of IL-1beta produced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror-image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder.     

Calcinosis at the site of leakage from extravasation of calcium disodium edetate intravenous chelator therapy in a child with lead poisoning

Painful calcinosis appeared at the wrist of an eight-year-old girl with lead poisoning. Careful history revealed that calcification occurred at the site of previous extravasation of calcium disodium edetate (EDTA) used in chelation therapy. Light microscopic, ultrastructural, electron activation, and X-ray diffraction studies demonstrated apatites with some suggestion of an admixture of octacalcium phosphate.     

Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction

Vascular 18F-FDG uptake marker represents inflammation in atherosclerotic lesions, but whether inflammation can be reversed by risk-modifying interventions has not, to our knowledge, been demonstrated. In this study, we evaluated the change of vascular 18F-FDG uptake in response to lifestyle intervention on serial PET/CT scans and further assessed how the findings relate to atherogenic risk reduction. METHODS: A total of 60 healthy adults underwent 18F-FDG PET/CT scans and atherogenic risk-factor assessment at baseline and again after 17.1 +/- 8.3 mo of practicing lifestyle modification. The PET/CT images were evaluated for the presence of vascular 18F-FDG lesions, and vessel-to-blood-pool 18F-FDG ratios were measured. Indices from summed ratios of positive lesions were compared and correlated to atherogenic risk factors. RESULTS: At follow-up, significant reductions in diastolic blood pressure (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein level (P < 0.05) and an increase in high-density lipoprotein (HDL) level (P < 0.0001) were demonstrated. On the initial PET/CT scan, 50 of 60 subjects showed 1 or more 18F-FDG-positive lesions (5.9 +/- 5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18F-FDG-positive lesions were significantly reduced to 2.1 +/- 2.2 sites per subject (P < 0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18F-FDG-positive rates were significantly reduced for the aorta and iliac arteries. In addition, significant reductions in the whole-body 18F-FDG index from 1.39 +/- 1.23 to 0.53 +/- 0.59 (P < 0.0001) and carotid 18F-FDG index from 0.08 +/- 0.16 to 0.03 +/- 0.06 (P = 0.01) were shown. The whole-body 18F-FDG index correlated with total cholesterol (P < 0.05) and HDL level (P < 0.05), and the magnitude of reduction in the 18F-FDG index closely correlated to the amount of increase in plasma HDL level (P = 0.005). CONCLUSION: Our study demonstrated that vascular 18F-FDG uptake is reversed in response to atherogenic risk reduction by lifestyle intervention and that the magnitude of improvement correlates to increases in plasma HDL levels. Thus, serial 18F-FDG PET/CT may be useful for monitoring improvements in the inflammatory component of atherosclerotic lesions in response to risk modification.