The decreased availability of metabolizable energy resources in the central nervous system is hypothesized to be a key factor in the pathogenesis of Alzheimer’s disease. More specifically, the age-related decline in the ability of glucose to cross the blood-brain barrier creates a metabolic stress that shifts the normal, benign processing of amyloid-β protein precursor toward pathways associated with the production of amyloid-β plaques and tau-containing neurofibrillary tangles that are characteristic of the disease. The neuroenergetic hypothesis provides insight into the etiology of Alzheimer’s disease and illuminates new approaches for diagnosis, monitoring, and treatment.

Total pancreatic insulin, dynamic insulin response to glucose (325 mg/dl), or tolbutamide (40 mg/dl) using the isolated perfused pancreas preparation and body composition were determined for 2- and 4-wk-old homozygous lean Fa/Fa, heterozygous lean Fa/fa, unknown lean Fa/??, and homozygous obese fa/fa female Zucker rats. At 2-wk, obese rats (body fat greater than 16%) released significantly more insulin than homozygous lean rats during first (min 10-16) and second phases (min 17-70) (61 vs. 30 ng and 637 vs. 255 ng, respectively). Plasma insulinemia was 177 microU/ml in obese, compared with 51 microU/ml in homozygous lean rats. The dynamic response of unknown lean followed the pattern of either the homozygous lean or the obese rats. There was no significant difference in total pancreatic insulin among any of the groups at 2 wk of age (Fa/Fa, 1.72; Fa/??, 2.01; and Fa/Fa, 1.80 micrograms). At 4 wk, the dynamic response by obese (2.98 micrograms) was similar to that of heterozygous (3.31 micrograms), both being significantly greater than the homozygous lean (1.14 micrograms) or unknown lean rats (1.77 microgram). Total pancreatic insulin in 4-wk obese (19.8 micrograms) was greater than homozygous lean rats (14.5 micrograms). Tolbutamide-stimulated insulin release was significantly greater in 4-wk obese than homozygous lean rats. Exposure to tolbutamide reduced by 60% the second-phase insulin release in both obese and homozygous lean rats during a subsequent 40-min glucose (325 mg/dl) perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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We read with interest the Grand Round by Nicole Salazar-Austin and colleagues, 1 who reported a young child with extensively drug-resistant tuberculosis after returning from India to the USA.Recently, we admitted a previously healthy man aged 20 years to our hospital in Germany who developed fever and productive cough 3 months after returning from Chennai, India, where he worked for 1 year as a teacher in a community project. The symptoms were initially misdiagnosed as community-acquired pneumonia and it took at least 14 days until a chest radiograph was done and 3 weeks until drug-resistant Mycobacterium tuberculosis was detected in sputum by molecular methods.Genotypic drug-resistance testing (GenoType MTBC, Hain Lifescience, Nehren, Germany) on sputum identified bacillary mutations in codon S315T1 of katG gene (isoniazid resistance), in codon S531L of rpoB gene (rifampicin resistance), in codon D94G of gyrA gene (fl uoroquinolone resistance), and in codon A1401G of rrs gene (amikacin, capreomycin, and kanamycin resistance). Phenotypic detection of drug resistance confi rmed I declare no competing interests.

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