5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift.

The stimulation of the AMP-activated kinase (AMPK) by 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) has been associated with antihyperalgesia and the inhibition of nociceptive signaling in the spinal cord in models of paw inflammation. The attenuated nociception comes along with a strongly reduced paw edema, indicating that peripheral antiinflammatory mechanisms contribute to antinociception. In this study, we investigated the impact of AICAR on the immune cell composition in inflamed paws, as well as the regulation of inflammatory and resolving markers in macrophages.

AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids.

Physical exercise has been repeatedly associated with decreased nociceptive responses but the underlying mechanisms have still not been fully clarified. In this study, we investigated exercise-induced effects after a single bout of treadmill running on the mouse model of formalin-induced inflammatory nociception. As potential molecular mediators, we focused on endogenous endocannabinoids as well as AMP-activated protein kinase (AMPK).

Activation of AMPK and its Impact on Exercise Capacity.

Activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) contributes to beneficial effects such as improvement of the hyperglycemic state in diabetes as well as reduction of obesity and inflammatory processes. Furthermore, stimulation of AMPK activity has been associated with increased exercise capacity. A study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) increased the running capacity of mice without any training and thus, prompted the World Anti-Doping Agency (WADA) to include certain AMPK activators in the list of forbidden drugs.

AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically.

TANK-binding kinase 1 (TBK1) modulates inflammatory hyperalgesia by regulating MAP kinases and NF-κB dependent genes.

Background: TANK-binding kinase (TBK1) is a non-canonical IκB kinase (IKK) involved in the regulation of type I interferons and of NF-κB signal transduction. It is activated by viral infections and inflammatory mediators and has therefore been associated with viral diseases, obesity, and rheumatoid arthritis. Its role in pain has not been investigated so far.

LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the AMPK activator AICAR.

AMP-activated kinase is a cellular energy sensor which is activated in stages of increased ATP consumption. Its activation has been associated with a number of beneficial effects such as decreasing inflammatory processes and the disease progress of diabetes and obesity, respectively. Furthermore, AMPK activation has been linked with induction of cell cycle arrest and apoptosis in cancer and vascular cells, indicating that it might have a therapeutic impact for the treatment of cancer and atherosclerosis.

Activation of the AMP-activated protein kinase reduces inflammatory nociception.

Unlabelled: The activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) has been associated with beneficial effects such as improvement of hyperglycemic states in diabetes as well as reduction of obesity and inflammatory processes. Recent studies provide evidence for a further role of AMPK in models of acute and neuropathic pain. In this study, we investigated the impact of AMPK on inflammatory nociception.

Novel findings in pain processing pathways: implications for miRNAs as future therapeutic targets.

miRNAs are small noncoding RNAs that are important players in development, as well as in a number of physiological and pathophysiological processes. Due to their regulatory role in protein expression, it has been assumed that they are associated with peripheral and central sensitization mechanisms in the nervous system after nociceptive insults. However, the study of miRNAs in pain has emerged only recently.

Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice.

microRNAs (miRNAs) are small noncoding RNAs that have been linked to a number of disease-related signal transduction pathways. Several studies indicate that they are also involved in nociception. It is not clear, however, which miRNAs are important and which genes are modulated by miRNA-associated mechanisms.

Altered gene expression in the prefrontal cortex of young rats induced by the ADHD drug atomoxetine.

Atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, is a non-stimulant approved for the treatment of attention deficit/hyperactivity disorder (ADHD). Little is known about the molecular basis for its therapeutic effect. The objective of this animal study was to determine alterations in gene expression patterns in the prefrontal cortex after long-term administration of atomoxetine.

The protein kinase IKKε is a potential target for the treatment of inflammatory hyperalgesia.

Inhibitor-κB kinase ε (IKKε) was only recently identified as an enzyme with high homology to the classical I-κB kinase subunits, IKKα and IKKβ. Despite this similarity, it is mainly discussed as a repressor of viral infections by modulating type I IFNs. However, in vitro studies also showed that IKKε plays a role in the regulation of NF-κB activity, but the distinct mechanisms of IKKε-mediated NF-κB activation are not clear.

[Spine fractures in patients with ankylosing spondylitis: an analysis of 129 fractures after surgical treatment].

Introduction: The ankylosing spondylitis (AS) is a systemic rheumatic disease, which affects the skeleton, joints and internal organs. Attributed to the augmented rigidity of the spine and the concomitant impairment of compensatory mechanism minor force might cause spine fractures. Multilevel stabilization and dorsoventral instrumentation is a well - established procedure.

Two-stage revision of infected total knee arthroplasty using a distraction spacer.

Background: The infection of a total knee arthroplasty (TKA) has remained as one of the most devastating potential complications. In this context we developed a new technique that keeps the spacer in distraction during the cementation process to achieve better weight-bearing stability.

Methods: We present a case of a 75-year-old male patient, who was treated in our hospital with an infected total knee replacement (TKR) using the distraction spacer.

[Temporary percutaneous spondylodesis C1/2 and halo vest immobilisation. An alternative treatment of complex injuries of the upper cervical spine].

Dislocated combined injuries of the upper cervical spine such as C 1/2 fractures require occipitocervical fusion, especially if the dislocation can not be redressed using halo vest immobilisition. We report on the clinical course and outcome of a young woman who sustained complex cervical spine injuries. Closed reduction and a percutaneous transfixation of C 1/2 with k-wires (Magerl) and an additional halo vest immobilisition was performed to avoid permanent fusion.

[Surgical management of spondylodiscitis. An analysis of 78 cases].

Spondylodiscitis is a rare bacterial infection of the spine with an inflammatory, destructive course. To obtain further information on the therapeutic management and clinical course of spondylodiscitis, we retrospectively investigated 78 patients after surgical intervention. Mean age was 64 years (+/-4.

[Osteomyelitis of the spine].

Spinal infections are rare, occurring most often in elderly patients with urinary tract infections or diabetes. With the increasing number of patients with immune suppression, and also the increasing number of immigrants in the population, spinal infections are seen more frequently, especially in young adults. Typically spinal infections are monomicrobial, Staphylococcus aureus being the most common organism.

[Prognostic factors for avascular necrosis following talar fractures].

Aim: We performed an investigation of factors for avascular necroses after talus fracture and on the reliability of the Hawkins Sign.

Method: From 1984 until 1997 a total of 98 patients with 99 talus fractures were surgically treated. Of these, 79 patients with 80 fractures were examined clinically and radiologically.

Surgical treatment of talus fractures: a retrospective study of 80 cases followed for 1-15 years.

We retrospectively reviewed 79 patients (80 talar fractures) operated on between 1994 and 1997. The average follow-up was 6 (1-15) years. 15 patients had a Marti/Weber fracture type I, 14 patients a type II, 32 patients a type III, and 19 patients a type IV fracture.

[Complications in the use of the halo fixator].

50 patients out of a total of 88 who underwent treatment using a halo-fixateur between 1987 and 1997 were available for a follow-up interview reviewing local complications and quality of life. Marginal discomfort was observed in 54% of patients, moderate complaints/transitory pain in 30%, prolonged and severe discomfort and pain in 16%. 62% of patients took no analgetics, 22% infrequently, and 16% continuously throughout treatment.

[Anterior screw fixation for odontoid fractures].

The results of anterior screw fixation of odontoid fractures in 28 patients are presented. There were 27 type II- and 1 type III-injuries. Non-union with persistent instability had to be notified in one patient (3.

Management of odontoid fractures in the elderly.

Odontoid fractures are frequent in patients over 70 years of age, and in patients over 80 years of age they form the majority of spinal fractures. In a retrospective analysis of 23 geriatric (> 70 years) patients with a fracture of the odontoid, we compared some of the clinical features to a contemporary series of patients younger than 70 years of age. Whereas in the younger patients high-energy trauma accounted for the majority of the fractures, low-energy falls were the underlying cause in 90% of the odontoid fractures in the elderly.

[Accident-induced pseudarthroses of the dens axis. Etiology, follow-up and therapy].

In a retrospective analysis the significance of internal fixation of unstable and symptomatic non-union of the odontoid was evaluated. In all but one cases a type II fracture of the odontoid was the underlying cause for the pseudarthrosis. The time interval between trauma and definitive diagnosis varied between 6 months and 30 years.

Playground accidents.

To study the causes and sequelae of playground accidents we analysed, in a retrospective study, 374 playground accidents. Questionnaires were sent to the parents and 103 parents (28%) provided detailed information on the playground accidents of their children. Thirty-one percent of the children injured in playground accidents sustained fractures of the extremities or concussion of the brain.

[The recognition of osteofibrous dysplasia Campanacci. Morphology, radiology, clinical picture and therapy].

Radiologically osteofibrous dysplasia of the tibia is characterized by an eccentrically localized osteolytic lesion in the diaphysis with the appearance of ground glass. However, this is a very rare lesion, making a correct diagnosis difficult, especially since fibrous dysplasia and adamantinoma of the tibia have to be taken into account in the differential diagnosis of the disease. A definitive diagnosis can only be made histologically.

[Complications after surgical management of scaphoid pseudarthroses].

The Matti-Russe technique yields a 95% success rate in treating scaphoid non-unions diagnosed in the first years after trauma and without osteoarthrosis of the radiocarpal joint. Between October 1981 and December 1989, 215 patients were treated by Matti-Russe procedure at the University Hospital of "Bergmannsheil" Bochum. In ten cases, this operation did not lead to osseous consolidation.