The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation

The reasons for the uneven worldwide distribution of Type 1 diabetes mellitus have yet to be fully explained. Epidemiological studies have shown a higher prevalence of Type 1 diabetes in northern Europe, particularly in Scandinavian countries, and Sardinia. Recent animal research has uncovered the importance of the generation of elevated levels of glucose, glycerol and other sugar derivatives as a physiological means for cold adaptation. High concentrations of these substances depress the freezing point of body fluids and prevent the formation of ice crystals in cells through supercooling, thus acting as a cryoprotectant or antifreeze for vital organs as well as in their muscle tissue. In this paper, we hypothesize that factors predisposing to elevated levels of glucose, glycerol and other sugar derivatives may have been selected for, in part, as adaptive measures in exceedingly cold climates. This cryoprotective adaptation would have protected ancestral northern Europeans from the effects of suddenly increasingly colder climates, such as those believed to have arisen around 14,000 years ago and culminating in the Younger Dryas. When life expectancy was short, factors predisposing to Type 1 diabetes provided a survival advantage. However, deleterious consequences of this condition have become significant only in more modern times, as life expectancy has increased, thus outweighing their protective value. Examples of evolutionary adaptations conferring selection advantages against human pathogens that result in deleterious effects have been previously reported as epidemic pathogenic selection (EPS). Such proposed examples include the cystic fibrosis mutations in the CFTR gene bestowing resistance to Salmonella typhi and hemochromatosis mutations conferring protection against iron-seeking intracellular pathogens. This paper is one of the first accounts of a metabolic disorder providing a selection advantage not against a pathogenic stressor alone, but rather against a climatic change. We thus believe that the concept of EPS should now include environmental factors that may be nonorganismal in nature. In so doing we propose that factors resulting in Type 1 diabetes be considered a result of environmental pathogenic selection (EnPS).     

The evaluation of bone changes in patients with rheumatoid arthritis

Some biochemical and radiological parameters of bone loss associated with rheumatoid arthritis were compared with changes observed in patients suffering from osteoarthrosis. In patients with rheumatoid arthritis increased elimination of hydroxyproline correlated with hypercalciuria and elevated total serum alkaline phosphatase were found. It is suggested that in cases where special methods of assessment of bone changes are not available these biochemical values could serve as satisfactory screening method for detection of bone loss.     

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight

Background  

Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.     

Mitochondrial dysfunction in T cells of patients with systemic lupus erythematosus

Activation, proliferation, or programmed cell death of T lymphocytes are dependent on controlled reactive oxygen intermediates (ROI) production and ATP synthesis in mitochondria. The mitochondrial transmembrane potential (Delta Psi(m)) also plays a decisive role in cell survival by controlling activity of redox-sensitive caspases. T lymphocytes of patients with systemic lupus erythematosus (SLE) exhibit mitochondrial hyperpolarization, increased ROI production, diminished intracellular glutathione levels, cytoplasmic alkalinization, and ATP depletion that mediate enhanced spontaneous and diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. These redox and metabolic checkpoints represent novel targets for pharmacological intervention in SLE.     

An outbreak of multidrug-resistant Acinetobacter baumannii associated with pulsatile lavage wound treatment

Context  Pulsatile lavage is a high-pressure irrigation treatment used increasingly in a variety of health care settings to debride wounds. Infection control precautions are not routinely used during the procedure and are not included in pulsatile lavage equipment package labeling. Objectives  To investigate an outbreak of multidrug-resistant Acinetobacter baumannii and to test the hypothesis that pulsatile lavage wound treatment was the mode of transmission for the organism. Design  Outbreak case-control investigation including case identification, review of medical records, environmental cultures, and pulsed-field gel electrophoresis. Setting  A 1000-bed tertiary care hospital in Baltimore, Md, during September and October 2003. Patients  The investigation included 11 patients infected or colonized with multidrug-resistant A baumannii. Seven of these patients met the case definition for the case-control study and were compared with 28 controls randomly selected from a list of inpatients without multidrug-resistant A baumannii who had a wound care consultation. Main Outcome Measure  Infection or colonization with multidrug-resistant A baumannii. Results  Eleven patients had cultures that grew multidrug-resistant A baumannii during the outbreak period. Of the 10 health care–associated cases, 8 had received pulsatile lavage treatment. One strain of multidrug-resistant A baumannii was recovered from all 6 pulsatile lavage patients who had isolates available for pulsed-field gel electrophoresis analysis and from multiple surfaces in the wound care area. Six of 7 cases (86%) were treated with pulsatile lavage vs 4 of 28 controls (14%) (odds ratio, 36; 95% confidence interval, 2.8-1721; P<.001). These results confirm that pulsatile lavage was a significant risk factor for acquisition of multidrug-resistant A baumannii. Conclusions  Transmission was apparently caused by dissemination of multidrug-resistant A baumannii during the pulsatile lavage procedure, resulting in environmental contamination. Appropriate infection control precautions should be used during pulsatile lavage therapy and should be included in pulsatile lavage equipment labeling.      

Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease

Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin-proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD-inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z-lle-Glu(OtBu)-Ala-Leu-al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon-11-labeled 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, alpha-synuclein/ubiquitin-containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness.