Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia.

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site.

Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia.

Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease.

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System.

Disturbed functional connectivity is assumed to cause neurocognitive deficits in patients suffering from schizophrenia. A Glutamate N-methyl-D-aspartate receptor (NMDAR) dysfunction has been suggested as a possible mechanism underlying altered connectivity in schizophrenia, especially in the gamma- and theta-frequency range. The present study aimed to investigate the effects of the NMDAR-antagonist ketamine on resting-state power, functional connectivity, and schizophrenia-like psychopathological changes in healthy volunteers.

Alterations of oscillatory neuronal activity during reward processing in schizophrenia.

Objectives: Reward system dysfunctions are considered to be a pathophysiological mechanism in schizophrenia. Electrophysiological studies of reward system functions have identified frequency-specific brain networks for the processing of positive (high-beta frequency) and negative (theta frequency) events. Remarkably, midbrain dopaminergic signalling also includes theta and high-beta frequency modes, which have been assumed to reflect tonic and phasic dopamine responses, respectively.

Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.

Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior.

Impact of physical or sexual childhood abuse on plasma DHEA, DHEA-S and cortisol in a low-dose dexamethasone suppression test and on cardiovascular risk parameters in adult patients with major depression or anxiety disorders.

While the impact of childhood trauma on basal and dynamic cortisol regulation has widely been studied, the most abundant steroid hormones dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S have received little attention in this context. One-hundred in-door patients suffering from major depression or an anxiety disorder filled in the Childhood Trauma Questionaire. A low dose dexamethasone suppression test (DST) measuring DHEA, DHEA-S and cortisol was performed.

Glutamatergic Deficits in Schizophrenia - Biomarkers and Pharmacological Interventions within the Ketamine Model.

Background: The observation that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists such as ketamine transiently induce schizophrenia-like positive, negative and cognitive symptoms has led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. NMDAR hypofunction can explain many schizophrenia symptoms directly due to excitatory-to-inhibitory (E/I) imbalance, but also dopaminergic dysfunction itself. However, so far no new drug targeting the NMDAR has been successfully approved.

Alterations in interhemispheric gamma-band connectivity are related to the emergence of auditory verbal hallucinations in healthy subjects during NMDA-receptor blockade.

Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers.

Tibial plateau fracture management: arthroscopically-assisted versus ORIF procedure - clinical and radiological comparison.

Introduction: Tibial plateau fractures are articular injuries that may influence final functional outcome of the knee. Although these fractures comprise only 1% of all fractures, the fracture pattern is usually complex and requires anatomical reduction and absolutely stable fixation to achieve satisfactory results. The development of knee osteoarthritis is a common late complication and it can be strongly influenced by additional, underestimated cartilage defects, and meniscal and ligament tears.

Surgical Treatment of Metastatic Disease of the Vertebral Column.

Spinal metastatic disease is a rather common occurrence and definitely warrants attention and treatment due to the high likelihood of leaving cancer patients severely disabled in their final months of life. Recent developments in the understanding of the behavior of different tumor types, as well as advances in surgical treatment, are allowing for the evolution of treatment algorithms, especially when surgical treatment is to be considered. This paper gives an overview of the decision-making process and the array of surgical options currently available.

Glutamatergic deficit and schizophrenia-like negative symptoms: new evidence from ketamine-induced mismatch negativity alterations in healthy male humans.

Background: Targeting the -methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine.

[Hip arthroscopy].

In the last ten years, hip arthroscopy has been developing intensively and it is rapidly gaining primacy in the treatment of various injuries and damages to the hip itself and its immediate vicinity. The basic advantage of hip arthroscopy surgery versus classic open surgery is avoiding an open dislocation of the hip and, thus, reducing patient's morbidity and accelerating his/her rehabilitation, which leads to a quicker return to everyday activities. The success of arthroscopic surgery depends on the correct indication for the surgery and on the experience and the skill of the operator.

Current practice variations in the management of anterior cruciate ligament injuries in Croatia.

Aim: To investigate current preferences and opinions on the diagnosis, treatment and rehabilitation of patients with anterior cruciate ligament (ACL) injury in Croatia.

Methods: The survey was conducted using a questionnaire which was sent by e-mail to all 189 members of the Croatian Orthopaedic and Traumatology Association. Only respondents who had performed at least one ACL reconstruction during 2011 were asked to fill out the questionnaire.