Fractures of the medial end of the clavicle

Much is known regarding the epidemiology of clavicle fractures, particularly those of the middle-third and distal clavicle. Medial clavicle fractures are uncommon, and as a result, there is little information available. The purpose of this study is to review retrospectively a case series of medial clavicle fractures treated at a tertiary trauma center. All clavicle fractures treated at our institution over a 5-year period were reviewed by use of all available radiographic studies and medical records. These data were evaluated with respect to several epidemiologic points, including mechanism of injury, associated injuries, fracture orientation, fracture displacement, treatment, and associated injuries. Follow-up data were gathered in 32 of 44 available patients with chart review and telephone survey. We evaluated 57 medial fractures in 55 patients. Patients were typically men in the fifth decade injured as a result of vehicular trauma. Fractures were occasionally missed on chest radiographs but were always identifiable by computed tomography scan. Injuries were most often closed and without neurovascular injury. However, patients almost always had multisystem trauma. Operative treatment was rarely performed, and patients typically had little or no pain at the time of follow-up. Finally, it was found that 11 patients died within 1 month of their injuries, indicating that 20% (11/55) of patients with medial clavicle fractures died as a result of the trauma associated with their injury. Medial clavicle fractures remain a relatively uncommon injury compared with other clavicular fractures. However, they typically are accompanied by significant multisystem trauma and have a high associated mortality rate.     

Bromodeoxyuridine and the detection of neurogenesis

Bromodeoxyuridine (BrdU) is widely used for labeling dividing cells to determine their fate. In particular, the analysis of neurogenesis in the adult mammalian brain has made significant progress through the use of this technique. However; when using BrdU for labeling, there are several issues to consider in order to minimalize possible cytotoxicity or false-positive labeling. This current review summarizes methodological and technical aspects of BrdU administration and detection, compares alternative methods and gives recommendations on how to avoid labeling artifacts.     

Mechanism of the anti-obesity effects induced by a novel Melanin-concentrating hormone 1-receptor antagonist in mice

Background and purpose:

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide expressed in the lateral hypothalamus that is involved in feeding and body weight regulation. Intracerebroventricular infusion of a peptidic MCH1 receptor antagonist ameliorated obesity in murine models. Recently, small molecule MCH1 receptor antagonists have been developed and characterized for the treatment of obesity. However, little is known of the mechanism of the anti-obesity effects of MCH1 receptor antagonists.

Experimental approach:

To examine the mechanisms of action of the anti-obesity effect of MCH1 receptor antagonists more precisely, we conducted a pair-feeding study in mice with diet-induced obesity (DIO), chronically treated with an orally active and highly selective MCH1 receptor antagonist and examined changes in mRNA expression levels in liver, brown and white adipose tissues. We also assessed the acute effects of the MCH1 receptor antagonist in energy expenditure under thermoneutral conditions.

Key results:

Treatment with the MCH1 receptor antagonist at 30 mg·kg⁻¹ for 1 month moderately suppressed feeding and significantly reduced body weight by 24%. In contrast, pair-feeding resulted in a smaller weight reduction of 10%. Treatment with the MCH1 receptor antagonist resulted in a higher body temperature compared with the pair-fed group. TaqMan and calorimetry data suggested that the MCH1 receptor antagonist also stimulated thermogenesis.

Conclusions and implications:

Our results indicate that an MCH1 receptor antagonist caused anti-obesity effects im mice by acting on both energy intake and energy expenditure.     

99th Dahlem Conference on Infection,Inflammation and Chronic Inflammatory Disorders: Immune therapies of type 1 diabetes: new opportunities based on the hygiene hypothesis

Insulin‐dependent (type 1) diabetes is a prototypic organ‐specific autoimmune disease resulting from the selective destruction of insulin‐secreting β cells within pancreatic islets of Langerhans by an immune‐mediated inflammation involving autoreactive CD4⁺ and CD8⁺ T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune‐based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the ‘hygiene hypothesis’, which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial‐derived compounds mediating the protective activity of infections which could be developed therapeutically.     

Regional and cellular gene expression changes in human Huntington's disease brain

Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative diseases.