LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning.

The N-Methyl-d-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-II (CaMKII). We confirmed that systemic blockade of kynurenine-3 monooxygenase in conjunction with kynurenine administration results in significant increases in Nrgn phosphorylation and a significant reduction of CaMKII phosphorylation in the mPFC. Consequently, dual-LPS administration induced significant impairments in stimulus processing during Pavlovian conditioning. Taken together, our study indicates that elevations in KYNA in the mPFC can directly regulate NMDA-Nrgn-CaMKII signaling, suggesting that neuroinflammatory conditions affecting this pathway may be associated with cognitive dysfunction.

Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice.

[The sliding technique : a precise method for treating the overprojected nasal tip]. / Die Sliding-Technik : Eine präzise Methode zur Korrektur der überprojizierten Nasenspitze.

BACKGROUND: The aim of the present report is to demonstrate the sliding technique as a reliable and exact method to treat the overprojected nasal tip. METHODS: Between March 2003 and April 2008 we treated 271 patients (198 females, 73 males) using the sliding technique for isolated tip hypertrophy (n=88), rhinomegaly (n=146), asymmetry of the nasal tip (n=29) and ptosis with malformation of the alar cartilages (n=8). RESULTS: Medial sliding was performed in 100 patients, lateral sliding in 121 patients, and combined lateral and medial sliding in 12 patients. In total, 18 patients needed additional skin resection at the columella. After an average follow-up period of 8.4 months 77.1% of the patients (n=209) rated the result as "very good", 21.1% (n=57) as"good" and 1.8% (n=5) patients were"unsatisfied". Only 1.8% (n=5) had to be revised due to nasal tip projection. A retrospective study of our first 80 patients showed an average reduction in projection of around 11%. CONCLUSION: The sliding technique is a precise and effective method to treat the overprojected nasal tip.

[Overresection of the lower lateral cartilage. A frequent cause for revision rhinoplasty]. / Ausgedehnte Resektion der Flügelknorpel. Häufige Ursache für Revisionen nach Rhinoplastiken.

BACKGROUND: Overresection of the lower lateral cartilages to narrow the tip may give rise to a dysfunction of the external nasal valve and aesthetic deformities like alar pinching, alar retraction, tip asymmetry, lack of tip definition and projection, leading to parrot beak deformities resulting from drooping of the tip. PATIENTS AND METHODS: Between 1998 and March 2008 we performed 1670 secondary rhinoplasties on patients who had undergone previous surgery elsewhere. The lower lateral cartilages where found to be missing in 89 patients intraoperatively. It was necessary to rebuild the structure of the nasal framework in order to resolve the deformities. We prefer to use septal cartilage or, if unavailable, costal or auricular cartilage. The deformities were analysed pre- and postoperatively by the operator based on clinical evaluation and standardised photographs. Patient satisfaction was evaluated subjectively. RESULTS: The postoperative results as judged by the surgeon showed a clear improvement in tip definition (100%) and projection (100%), alar pinching (100%), tip deformities (95.2%), tip deviation (77.8%) alar retraction (87.5%) and tip ptosis (85.7%). The function of the external nasal valve as evaluated by the surgeon was completely restored in all cases (100%). The average follow-up period was 13 months. In all, 50 patients (59.6%) stated that the result was "excellent", 28 (33.3%) as "very good", five (5.9%) as "good" and one as "not satisfied" (1.2%). CONCLUSION: In the case of destroyed anatomical structures we completely rebuild the structure of the nasal tip, since only a correct anatomical configuration correlates with ideal aesthetics and physiological function.

[Painful soft-tissue swelling of the upper arm]. / Schmerzhafte Weichteilschwellung am Oberarm.

Cat-scratch disease is an infection by Bartonella henselea and resolves spontaneously. We present a case of untypical Bartonella infection which was misinterpreted by MRI as a soft-tissue sarcoma of the upper arm. The histological findings of an incision biopsy were unspecific, without signs of malignancy. The tumor was excised completely and the final histology, however, showed no evidence of malignant changes. The Bartonella henselae infection could be confirmed by polymerase chain reaction. The untypical presentation of cat-scratch disease should be considered in the differential diagnosis of clinically suspected soft tissue sarcoma.

[Carpo-metacarpal dislocation injuries]. / Karpometakarpale Luxationsverletzungen.

Carpometacarpal dislocations are rare. In most cases, the dislocation is caused by a violent injury, e.g. the crash of a motorcyclist or a fall from great height. A considerable swelling of the back of the hand may mask the characteristic lump at the root of the hand. The diagnosis can be easily missed due to serious associated injuries. The lesion is also often overlooked in the routine X-ray diagnostic. Lateral and oblique views are important for the recognition of the true extent of the lesion. Anatomical reposition is difficult if the dislocation is not fresh and open reposition is necessary. Between 1990 and 1999, altogether 16 patients who had suffered a carpometacarpal dislocation were treated. One patient had a rare dislocation of the III. to V. joints. Simultaneous dislocation of all five carpometacarpal joints was seen in three cases. The treatment mostly consists of closed reduction and temporary Kirschner wire transfixation. Fourteen patients were controlled (clinical examination and X-ray control) after an average follow-up time of three years. In addition, the DASH questionnaire was used. After an average time of 3 years the patients showed in 64% of the cases excellent and good results (eight excellent, one good). The subjective function of the hand was moderate in 29% (four patients), in one patient the subjective function was poor (7%). Five patients had a diminished range of motion of the hand. The average points in the DASH questionnaire were 24. We recommend as therapy of choice after primary closed repositioning, primary surgery by means of short Kirschner wires introduced from distal-dorsal to proximal-palmar. In cases of impossible closed reduction or in cases with local additional injuries, open treatment for fixation, is indicated.

Distribution of lithium in the rat brain after a single administration known to elicit aversive effects.

In order to get insight into the brain areas involved in the initial unpleasant effects resulting from the administration of lithium (Li+), its distribution was mapped in the rat brain using the 6Li(n,alpha)3H nuclear reaction after a single injection of 6Li2SO4 at doses and latencies corresponding to the elicitation of such unpleasant effects. An improved method for visualization and measurement of local Li+ concentrations was used consisting in diffracting light along the tracks left by alpha particles in a dielectric detector. The distribution of Li+ was found less homogeneous than when Li+ was administered chronically. Periaqueductal and periventricular structures were the brain areas containing the highest concentrations of Li+.