Dendritic Inclusions in the Cerebellar Granular Layer after Long Term Alcohol Consumption in Adult Rats

Whorled multiplanal inclusions up to 1.5 micron in diameter were observed in dendrites of the cerebellar Golgi cells after 6 months of alcohol treatment, increasing in number with time. Inclusions are formed by apposed cytomembranes stacked parallel or in a twisted arrangement. The paired membranes merged into a dense, finely textured material. A close relationship with dendritic smooth endoplasmic reticulum is apparent. A correlation between chronic alcohol intake and the development of these inclusions is shown although, in common with many other types of neuronal cytoplasmic inclusions, their genesis and function remains to be determined.     

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin : Systematic overview of individual data from 96,712 randomized patients

OBJECTIVES

We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA).

BACKGROUND

Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI.

METHODS

This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0–36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial).

RESULTS

Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use.

CONCLUSIONS

Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.     

Early‐onset absence epilepsy caused by mutations in the glucose transporter GLUT1

Absence epilepsies of childhood are heterogeneous with most cases following complex inheritance. Those cases with onset before 4 years of age represent a poorly studied subset. We screened 34 patients with early‐onset absence epilepsy for mutations in SLC2A1, the gene encoding the GLUT1 glucose transporter. Mutations leading to reduced protein function were found in 12% (4/34) of patients. Two mutations arose de novo, and two were familial. These findings suggest GLUT1 deficiency underlies a significant proportion of early‐onset absence epilepsy, which has both genetic counseling and treatment implications because the ketogenic diet is effective in GLUT1 deficiency. Ann Neurol 2009;66:415–419     

Transforming growth factor-β: Recent advances on its role in immune tolerance

Transforming growth factor-β (TGF-β) is a key regulator of immune tolerance. In this paper, we will focus on T cells and natural killer (NK) cells, which are directly regulated by TGF-β in vivo. TGF-β controls T-cell activation and differentiation, and is involved in the suppressive function and generation of regulatory T cells. Recently, TGF-β has also been shown to directly inhibit NK cell activity. These studies demonstrate that TGF-β utilizes multiple mechanisms to ensure immune tolerance, which is critical in a variety of autoimmune and inflammatory disorders. We will also discuss recent advances on the role of TGF-β in immune-mediated diabetes, inflammatory bowel disease, arthritis, and systemic lupus erythematosus.     

The recovery of trust

Much of the social life of many animals depends on cooperation. It is argued that humans are no less reliant on each other. The pseudo‐biological view that social conflict is inevitable under all circumstances is rejected. However, warfare undoubtedly occurs and people certainly risk their lives in attacking others. Explanations must be sought at many different levels. Most indicate an implicit weighing of possible costs against likely benefits which might be performed by individuals or might result from the historical processes of cultural selection and Darwinian evolution. Whatever the processes might have been, their outcomes make no sense in a nuclear age since the benefits of warfare are likely to be non‐existent. Since little can be done to change the way we think, it becomes important to understand the conditions in which we are prepared to risk our lives. It is argued that the key lies in the breakdown of mutual trust and that it is possible to create the conditions in which trust can once again be recovered.