The effect of retrieval instructions on false recognition: exploring the nature of the gist memory impairment in amnesia

In previous studies, we found that amnesic patients show reduced levels of false recognition in a converging semantic associates paradigm. This finding was interpreted as reflecting an impairment in amnesia in the ability to form, retain and/or retrieve a well-organized representation of the semantic ‘gist’ of studied items. To further explore the nature of amnesics’ impairment in gist memory, the current study compared performance in two retrieval conditions. In a standard retrieval condition, participants were asked to endorse on a recognition test only items that had appeared on the study list. In a meaning retrieval condition, participants were asked to endorse any item that shared the meaning of studied items. Meaning retrieval instructions failed to eliminate the reduction in false recognition in amnesia. These results suggest that amnesics’ impairment in gist memory is not attributable to a failure to access well-formed gist representations when given item-specific retrieval cues. Rather, it suggests that amnesic patients are impaired in their ability to encode, store, or maintain strong gist information.     

Multiple toxicity from 3,4-methylenedioxymethamphetamine ("ecstasy")

There have been no published case series illustrating "ecstasy" (3,4-methylenedioxymethamphetamine [MDMA]) toxicity in a group of patients who have ingested ecstasy in the same environment. We report a series of 7 patients who ingested ecstasy in a nightclub and presented with varying degrees of MDMA toxicity. Three patients presented with features of severe MDMA toxicity. One died within an hour of hospital admission, another died 4 days later, after developing fulminant hepatic failure, and the third recovered after 12 days in intensive care. MDMA was identified in the serum of all 7 patients. High serum MDMA concentrations correlated with severe clinical and biochemical features including coma, hyperpyrexia, cardiovascular compromise, acidosis, and hyperkalaemia. "Poisoned ecstasy" was widely reported by the media as being responsible for the adverse effects observed. This report highlights a relationship between serum concentrations and toxic effects of MDMA, and the ongoing need to educate the public about the dangers of this substance.     

Protracted calciphylaxis,Part I

Calciphylaxis is a serious and often lethal condition that mostly affects patients with renal disease. Patients with calciphylaxis typically have variable degrees of cutaneous necrosis on initial presentation. An unusual, protracted course of calciphylaxis without cutaneous ulcerations has been encountered in the case of a 46-year-old woman. Thirteen additional cases with similar presentation will be discussed in part II of this article. Calciphylaxis may include several clinical presentations, ranging from an acute, rapidly fatal course to an indolent, more benign variant.     

Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in vitro models and their application in hepatotoxicity studies. II. Spheroid cell spreading inhibition as a new cytotoxic marker

Cells in liver spheroids and Hep G2 spheroids transferred from gyrotatory culture conditions and maintained in normal static culture conditions will spread out at the edges. Based on this observation, we developed a new test called the Spheroid Cell Spreading Inhibition Test (SCSIT) to screen hepatic cytotoxicity of xenobiotics and determine the spheroid cell spreading inhibition concentration (SCSIC) of test chemicals. Four model hepatoxicants, D-galactosamine, propranolol, diclofenac, and paracetamol, were studied with SCSIT in both rat liver and HepG2 spheroids. Both liver and HepG2 spheroids were prepared under gyrotatory culture conditions and used at 6 days in vitro. The results showed that all four hepatotoxicants tested inhibited cell spreading in liver spheroids (D-galactosamine at 20 mM, propranolol at 125 microM, diclofenac at 500 microM, and paracetamol at 25 mM) and HepG2 spheroids (D-galactosamine at 16 mM, propranolol at 125 microM, diclofenac at 500 microM, and paracetamol at 25 mM). The SCSIT results agreed with the conventional cytotoxic indicators, release of LDH and/or gamma-GT and the inhibition of glucose secretion from rat liver spheroids. In conclusion, this study, for the first time, described the biological characteristics of liver and HepG2 spheroid cell spreading and demonstrates its application in hepatic cytotoxicity studies. This method may be used in testing in vitro "acute" toxicity, comparing relative cytotoxicity and generating reference concentrations for subsequent studies. Therefore, SCSIT could be a useful tool for screening hepatotoxicity relevant to preclinical lead optimization and compound library screening.     

Reactive oxygen species generation and histamine release by activated mast cells: modulation by nitric oxide synthase inhibition.

1. We have examined the generation of intracellular reactive oxygen species (ROS) and release of histamine by rat peritoneal mast cells (RPMC) in response to stimulation with antigen (ovalbumin), compound 48/80, nerve growth factor (NGF) and substance P (SP). 2. We have also examined the effects of the non-specific nitric oxide synthase inhibitor, L-NAME (100 microM) upon the release of histamine and generation of intracellular ROS in response to the named secretagogues. 3. Ovalbumin (100 - 1000 microg ml-1), compound 48/80 (0.1 - 100 microg ml-1), NGF (0.1 - 100 microg ml-1), and SP (5 - 50 microM), caused a concentration-dependent release of histamine from RPMC. 4. Ovalbumin (1 ng ml-1 - 0.1 microg ml-1), compound 48/80 (1 - 100 microg ml-1), NGF (1 pg ml-1 - 1 microg ml-1), and SP (0.005 - 50 microM) caused a concentration-dependent generation of intracellular ROS by RPMC. 5. Pre-incubation of RPMC with L-NAME (100 microM) caused a significant enhancement of both histamine release and intracellular ROS from RPMC in response to ovalbumin, compound 48/80, NGF and SP. 6. Our data demonstrate that NGF, SP and ovalbumin are capable of causing intracellular ROS generation by RPMC at lower concentrations than those causing significant histamine release and we speculate that this may contribute to the activation of cytokine production. 7. The data also show that NO modulates histamine release, and ROS generation in response to the secretagogues used. This may have significance in pathologies where NO synthesis is decreased, leading to an increased activation of mast cells.