Effect of chronic vincristine treatment on mechanical withdrawal response and pre-pulse inhibition in the rat

Chemotherapeutic agents are associated with a number of serious side-effects. In addition to the development of peripheral neuropathy, patients often complain of additional symptoms related to attentional mechanisms. Although a great deal of interest is directed towards understanding the mechanisms underlying the development of peripheral neuropathy, there is a paucity of research that has examined the extent of impairment of attention in animals receiving chemotherapeutic agents. Therefore, the purpose of this experiment was to examine attentional mechanisms using the method of pre-pulse inhibition in animals that were chronically treated with vincristine. Although vincristine treated animals developed signs of peripheral neuropathy, there was no associated alteration of pre-pulse inhibition relative to vehicle treated animals. These results highlight the importance of continuing to develop methodology to model symptom burden in patients receiving chemotherapy.     

Clinical approach to normal intraocular pressure glaucoma

Normal intraocular pressure (IOP) glaucoma is a clinical condition characterized by pathologic optic nerve excavation and visual field impairment, defined as optic neuropathy with certain features of a disease known as glaucoma. Glaucomatous optic nerve lesion is characterized by optic disk excavation or depression, however, this feature may greatly vary. The level of IOP is considered only one of the multiple risk factors involved in the disease development. In normal IOP glaucoma, papillary lesions and visual field impairments may differ from those occurring in primary open-angle glaucoma. In modern ophthalmology, the terminology has been modified, so the term low IOP glaucoma has been replaced by the term normal IOP glaucoma. It is now believed that various factors play a role in the development of glaucomatous optic neuropathy in normal IOP glaucoma and show variable interference depending on IOP level. Additional studies are needed to define these interactions and their impact on the mechanism of glaucomatous excavation. This will hopefully pave the way to new therapeutic approaches and help in clinical decisions concerning the prognosis and treatment of individual patients.     

Total and methyl-mercury content in bivalves,Mytilus galloprovincialis lamarck andOstrea edulis linnaeus: Relationship of biochemical composition and body size

Bulletin of Environmental Contamination and Toxicology -     

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.     

"My disease is one of the mind and difficult to define": Robert Walser (1879-1956) and his mental illness

Robert Walser (1878-1956) is among the most prominent German-speaking writers born in Switzerland. His early writings are fascinating due to his intensive affectivity and oneiric experiences; his late work impresses through his idiosyncratic use of language and his micrographs. Due to a psychotic disease he stayed in Swiss Mental State Hospitals (Waldau and Herisau) throughout the final 27?years of his life. According to his case records Robert Walser suffered from a schizophrenic disorder (ICD-10) and from a combined sluggish/manneristic catatonia according to K. Leonhard. Walser's psychotic disorder was characterized by a chronic course with sharp-cut symptomatology with stiff postures, repetitive behaviour, movement mannerisms and omissions (manneristic component) complemented by loss of incentive, severe autism and persistent verbal hallucinations (speech-sluggish component). In the late stages his psychopathology affected the process of thinking and writing in a specific manner: his handwriting became illegibly small, and his train of thoughts did not get to the point. At age 54 he stopped writing when transferred from Waldau to Herisau, and subsequently, due to manneristic omission, he was never again able to restart literary writing. The analysis of Robert Walser's psychotic disease may contribute to a deeper understanding of his literary production, which influenced such classical German authors like Franz Kafka, Hermann Hesse and Robert Musil.     

Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors

We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-ribotide (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (International Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (ii) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca(2+)-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs.     

Lumbar Sympathectomy Attenuates Cold Allodynia But Not Mechanical Allodynia and Hyperalgesia in Rats With Spared Nerve Injury

In certain patients with neuropathic pain, the pain is dependent on activity in the sympathetic nervous system. To investigate whether the spared nerve injury model (SNI) produced by injury to the tibial and common peroneal nerves and leaving the sural nerve intact is a model for sympathetically maintained pain, we measured the effects of surgical sympathectomy on the resulting mechanical allodynia, mechanical hyperalgesia, and cold allodynia. Decreases of paw withdrawal thresholds to von Frey filament stimuli and increases in duration of paw withdrawal to pinprick or acetone stimuli were observed in the ipsilateral paw after SNI, compared with their pre-SNI baselines. Compared with sham surgery, surgical lumbar sympathectomy had no effect on the mechanical allodynia and mechanical hyperalgesia induced by SNI. However, the sympathectomy significantly attenuated the cold allodynia induced by SNI. These results suggest that the allodynia and hyperalgesia to mechanical stimuli in the SNI model is not sympathetically maintained. However, the sympathetic nervous system may be involved, in part, in the mechanisms of cold allodynia in the SNI model. PERSPECTIVE: The results of our study suggest that the SNI model is not an appropriate model of sympathetically maintained mechanical allodynia and hyperalgesia but may be useful to study the mechanisms of cold allodynia associated with sympathetically maintained pain states.     

Effects of pre- and postnatal litter size reduction on development and behavior of rat offspring

Litter size was reduced to 2-5 rat pups either prenatally by unilateral maternal oviduct ligation (Group PRN) or postnatally by removing pups (Group PST). Normal size litters (8-10 pups) of sham ligated (SHM) and intact (CON) mothers served as controls. Weights at 30 days were increased by prenatal or postnatal reduction and reduced by prenatal stress (SHM); the sex difference in weight was most pronounced in PRN rats. At 75 days PRN rats were heaviest, with no differences between the other groups. Relative ovarian weights were reduced in PRN females and absolute testes weights increased in PST males. The PRN and SHM females had smaller relative adrenal weights than CON and PST females. Open-field activity was generally increased by prior avoidance conditioning and effects of treatments were found only in groups tested after avoidance-conditioning: PRN and SHM rats were more active than PST and CON rats, particularly on Days 1 (SHM) and 4 (SHM and PRN) of testing. Passive-avoidance behavior of PRN rats was also more susceptible to previous test experience: they emerged more slowly if they had prior open-field experience. The PST animals, in contrast, emerged more rapidly after prior test experience. Plasma corticosterone levels and shuttlebox conditioning and extinction were unaffected by treatments.