Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs

Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.     

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220^?CD3^?CD11b^–/loCD115⁺CD117⁺CX3CR1⁺ and possibly also Ter119^?CD11c^?CD135^loLy6C⁺RANK^?. In peripheral blood the OCP population bears the monocytoid phenotype B220^?CD3^?NK1.1^?CD11b⁺Ly6C^hiCD115⁺CX3CR1⁺, presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3^?CD19^?CD56^?), within immature monocyte subset (CD11b⁺CD14⁺CD16^?), expressing receptors for M-CSF and RANKL (CD115⁺RANK⁺). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3^?CD19^?CD56^?CD11b⁺CD14⁺, and the disease activity score (DAS28) in the follow-up samples from patients with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption. Control of the activity and migratory behaviour of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.     

Rapid dopamine transmission within the nucleus accumbens: Dramatic difference between morphine and oxycodone delivery

While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug‐naïve rats using fast‐scan cyclic voltammetry and rapid (1 min) microdialysis coupled with high‐performance liquid chromatography ‐ tandem mass spectrometry (HPLC‐MS). In addition to measuring rapid dopamine transmission, microdialysis HPLC‐MS measures changes in GABA, glutamate, monoamines, monoamine metabolites and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug‐evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid‐induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior.     

“Marina-Trinkkur” and a few more modern-time hydrotherapeutic myths from the Kvarner region of NW Croatia

Purpose. The present paper tries to address the rise and decay of the sea-water “cult” in regional health tourism in NW Croatia, concentrating upon and analysing more thoroughly the example of Marina, chemicaly processed sea water, an invention of Dr Géza Fodor, the Hungarian physician practicing in that part of Croatia.

Method. The original documents and archived items related to the topic were examined. Furthermore, we investigated numerous comunal bulletins and medical authorities' records of respective time.

Results. Our research showed that the sea-water baths, introduced thanks to the influence of balneologists (like J. Glax), and “drinking cures” (advocated by M.-J. Örtel, for instance) were surprisingly popular not only among tourists of the time, but also among the physicians that used them extensively for therapeutical purposes. These baths and “drinking cures” enriched and completed the medical offer of the resorts regardless of their sometimes dubious effectiveness.

Conclusions. This simple distilled sea-water preparation, advertised as a real panacea, demonstrates a paradigm that elucidates the mentality of physicians, merchants, and patients/consumers of the time.     

Mothering begets mothering: the transmission of behavior and its neurobiology across generations

Early experiences exert their effects on adult parental behavior in part by altering the development of neurobiological mechanisms that initiate or support the initiation and sustenance of adult parental behavior. The effects of parental behavior on sensory, perceptual and emotional mechanisms in offspring constitute an experientially based mechanism by which neurobiological factors regulating behavior can be transferred from generation to generation somewhat independently of genetic endowment.     

Sensitization to amphetamine,but not PCP,impairs attentional set shifting: reversal by a D<Subscript>1</Subscript> receptor agonist injected into the medial prefrontal cortex

Rationale Repeated exposure to psychomotor stimulants can lead to sensitization to their effects, and sensitization has been implicated in the pathophysiology of schizophrenia and drug abuse. These disorders are characterized by cognitive deficits, particularly in prefrontally mediated executive function.Objective The present experiments were conducted to investigate the effects of sensitizing regimens of amphetamine and phencyclidine (PCP) on attentional set shifting.Methods Rats received injections of amphetamine, PCP or saline three times per week for 5 weeks. Four weeks later, rats were trained to dig for food in one of two bowls, each bowl having an odour and a texture. Only one dimension (odour or texture) correctly predicted which bowl was baited. Rats were then tested on a series of discriminations including those requiring an intra-dimensional shift (IDS), an extra-dimensional shift (EDS) or a reversal of previously relevant and irrelevant stimuli.Results Rats sensitized to amphetamine performed normally on the IDS, but were impaired on the EDS, as well as on reversal discriminations. PCP-sensitized rats were unaffected on any of the discriminations. In amphetamine-sensitized rats the deficit at the EDS stage was reversed by infusion of the D₁ receptor agonist SKF38393 into the medial prefrontal cortex (mPFC).Conclusions Results show that the amphetamine-sensitized state impairs prefrontally mediated attentional set shifting. This is consistent with cognitive deficits in schizophrenia and addiction, and with the evidence that amphetamine sensitization is accompanied by functional changes in the mPFC. These results further add to a growing literature showing that activating D₁ receptors in the mPFC improves aspects of cognition.     

Neurophysiologic monitoring and pharmacologic provocative testing for embolization of spinal cord arteriovenous malformations

BACKGROUND AND PURPOSE: Embolization of a spinal cord arteriovenous malformation (SCAVM) is still considered risky. We evaluated the efficacy and reliability of pharmacologic provocative testing with neurophysiologic monitoring in the embolization of SCAVMs. METHODS: We retrospectively analyzed results of 60 provocative tests during 84 angiographic procedures (in 52 patients) with intended endovascular embolization. Tests included 47 sodium amytal and 56 lidocaine injections. All procedures were performed with general anesthesia and monitoring of cortical somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs). For provocative testing, 50 mg of amytal and 40 mg of lidocaine were consecutively injected through a microcatheter placed at the position of intended embolization. If SEPs and MEPs did not change, embolization was performed with N-butyl-cyanoacrylate (NBCA). If SEPs or MEPs changed, NBCA embolization was not performed from that catheter position. RESULTS: One false-negative result occurred, with an increase in spasticity after embolization. Nineteen positive results occurred: four after amytal injection and 15 after lidocaine injections. Seven injections in a posterior spinal artery feeder resulted in loss of SEPs or MEPs. Eleven injections in the anterior spinal artery feeder and one in the posterior inferior cerebellar artery feeder resulted in loss of MEPs. CONCLUSION: Provocative testing with amytal and lidocaine combined with neurophysiologic monitoring had a high negative predictive value and was a useful adjunct for SCAVM embolization. Both amytal and lidocaine should be used as provocative agents, and both SEPs and MEPs should be monitored.     

Academic medicine--experiences from Finland and suggestions for the future

This article presents the basic facts about education, health care system, and academic medicine in Finland. The issue of the academic medicine in the world is discussed and Finnish models compared with those of the rest of the world. Possible solutions for the recovery of academic medicine, education, and research are proposed.