Comment on the 'pilot' GRACIA-2 randomized trial: reply

We thank Dr Villata et al. for their thought-provoking comments.Their concern about the suitableness to choose combined endpointsin clinical trials deserves some comment.     

Changes in microtubule-associated protein-2 (MAP2) expression during development and after status epilepticus in the immature rat hippocampus

In this study, we analyzed the spatiotemporal expression patterns of the high-molecular weight (MAP2a and b) and low-molecular weight (MAP2c and d) cytoskeletal microtubule-associated protein-2 (MAP2) isoforms with Western blotting, and the cellular localization of the high-molecular weight MAP2 isoforms with immunocytochemistry in the hippocampi of 1- to 21-day-old rats. Moreover, the temporal profile (from 30 min to 1 week) of MAP2 isoform reactivity to kainic acid-induced status epilepticus was studied in P9 rats. During development, the expression of the high-molecular weight MAP2 isoforms significantly increased, while the low-molecular weight isoforms decreased, the most prominent changes occurring during the second postnatal week. This developmental increase in the high-molecular weight MAP2 expression was also confirmed with immunocytochemistry, which showed increased immunoreactivity, particularly in the molecular layers of the dentate gyrus, and in CA1 and CA3 stratum radiatum. In 9-day-old rats, status epilepticus resulted in a rapid transient increase (about 210%) in the high-molecular weight MAP2 expression, without any effect on the low-molecular weight MAP2. Moreover, disturbed dendritic structure in the CA1 and CA3 stratum radiatum was manifested as formation of varicosities 3h after the kainic acid treatment. The strictly developmentally regulated MAP2 isoform expression suggests different functional roles for these proteins during the postnatal development in the rat hippocampus. Moreover, high-molecular weight MAP2s may play a role in nerve cell survival during cell stress.     

Adverse drug reactions in internal medicine units and associated risk factors

Objectives  

This study was designed to assess the prevalence of adverse drug reactions (ADRs) in the internal medicine wards of two teaching Hospitals, identify the most common ADRs, the principal medications involved, and determine the risk factors implicated in the occurrence of such ADRs.     

Binding units (BU) and the area under binding isotherms (AUI) new indices of effector-target conjugation

New methods for simplified quantitation of effector-target conjugation have been developed. The binding unit (BU) is defined as the number of target cells required to bind a specified percentage of effector cells. The number of binding units is determined from binding isotherms in which effector conjugate frequencies are measured by holding constant the number of effector cells and by varying the number of target cells. Alternately, a binding unit can be defined as the number of effector cells required to bind a specified percentage of target cells. In this case, BU is computed from binding isotherms in which target conjugate frequencies are measured at different values of effector cells by holding constant the number of target cells. Also, the area under the curve (AUI) of these isotherms is another index that can be used as an overall measure of the binding capacity in an effector-target system. The experimental values of BU and AUI determined from effector and target isotherms agree well with theoretical predictions based on our previously developed binding model (J. Immunol. Methods (1992) 155, 133–147). The relationship between BU and AUI, and procedures to determine these parameters are shown. The value of these indices to express effector-target conjugation quantitatively has been confirmed by determining the values of BU and AUI for the NK-K562 effector-target system.     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.