Bioorthogonal Stimulated Raman Scattering Imaging Uncovers Lipid Metabolic Dynamics in Drosophila Brain During Aging.

Studies have shown that brain lipid metabolism is associated with biological aging and influenced by dietary and genetic manipulations; however, the underlying mechanisms are elusive. High-resolution imaging techniques propose a novel and potent approach to understanding lipid metabolic dynamics in situ. Applying deuterium water (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy, we revealed that lipid metabolic activity in Drosophila brain decreased with aging in a sex-dependent manner. Female flies showed an earlier occurrence of lipid turnover decrease than males. Dietary restriction (DR) and downregulation of insulin/IGF-1 signaling (IIS) pathway, two scenarios for lifespan extension, led to significant enhancements of brain lipid turnover in old flies. Combining SRS imaging with deuterated bioorthogonal probes (deuterated glucose and deuterated acetate), we discovered that, under DR treatment and downregulation of IIS pathway, brain metabolism shifted to use acetate as a major carbon source for lipid synthesis. For the first time, our study directly visualizes and quantifies spatiotemporal alterations of lipid turnover in Drosophila brain at the single organelle (lipid droplet) level. Our study not only demonstrates a new approach for studying brain lipid metabolic activity in situ but also illuminates the interconnection of aging, dietary, and genetic manipulations on brain lipid metabolic regulation.

Direct Imaging of Lipid Metabolic Changes in Drosophila Ovary During Aging Using DO-SRS Microscopy.

Emerging studies have shown that lipids and proteins play versatile roles in various aspects of aging. High-resolution in situ optical imaging provides a powerful approach to study the metabolic dynamics of lipids and proteins during aging. Here, we integrated D2O probing and stimulated Raman scattering (DO-SRS) microscopy to directly visualize metabolic changes in aging Drosophila ovary. The subcellular spatial distribution of de novo protein synthesis and lipogenesis in ovary was quantitatively imaged and examined. Our Raman spectra showed that early stages follicles were protein-enriched whereas mature eggs were lipid-enriched. DO-SRS imaging showed a higher protein synthesis in the earlier developing stages and an increased lipid turned over at the late stage. Aged (35 days) flies exhibited a dramatic decrease in metabolic turnover activities of both proteins and lipids, particularly, in the germ stem cell niche of germarium. We found an accumulation of unsaturated lipids in the nurse cells and oocytes in old flies, suggesting that unsaturated lipids may play an important role in the processes of oocyte maturation. We further detected changes in mitochondrial morphology and accumulation of Cytochrome c during aging. To our knowledge, this is the first study that directly visualizes spatiotemporal changes in lipid and protein metabolism in Drosophila ovary during development and aging processes. Our study not only demonstrates the application of a new imaging platform in visualizing metabolic dynamics of lipids and proteins in situ but also unravels how the metabolic activity and lipid distribution change in Drosophila ovary during aging.

Intravenous immunoglobulin in antiphospholipid syndrome and maternal floor infarction when standard treatment fails: a case report.

Obstetrical antiphospholipid syndrome (APS) is associated with maternal and fetal morbidity and mortality. Standard treatment with low-dose acetylsalicylic acid and unfractionated heparin has achieved up to a 70 to 80% likelihood of success. Conversely, up to 30% of women with APS will have further pregnancy losses, despite treatment. Intravenous immunoglobulin (IVIG) may be a promising adjuvant when standard treatment fails. We present a case of a 35-year-old woman with obstetrical APS and maternal floor infarction in prior pregnancy losses who continued to have further unsuccessful pregnancies despite standard treatment with acetylsalicylic acid and unfractionated heparin. On an investigational basis, she was prescribed concomitant IVIG and had two subsequent healthy newborns. IVIG appears to be promising in obstetrical patients with APS who are refractory to standard treatment. Prior history of maternal floor infarction may be a prognostic indicator for triple therapy for obstetrical APS.

Expression of cellular adhesion proteins and abnormal glycoproteins in human aberrant crypt foci.

Aberrant crypt foci (ACFs) may be the earliest recognizable histologic precursor lesion for colon cancer. ACF may develop from a complex of events, including the development of cryptal hyperproliferation, defects in the rate of apoptosis, and abnormalities in cellular adhesion. In this study, we hypothesized that human ACF would exhibit discrete differences in cell adhesion proteins compared with normal mucosa of biologic markers associated with colon cancer. ACFs were isolated from resected colon mucosa from 45 patients undergoing surgery for colon cancer. We evaluated the protein expression of 3 biologic markers that may be related to the progression of aberrant crypt foci to tumors: carcinoembryonic antigen, E-cadherin, and sialyl Tn antigen. In general, ACFs located near cancers in the right colon were more often hyperplastic than dysplastic; this was more noticeable in the left colon. Carcinoembryonic antigen expression was found to be more intense in apical portions of ACF crypts, with sialyl Tn antigen moderately increased, whereas E-cadherin diffusely stained throughout crypts within ACFs. There are significant biologic changes in potential tumor markers that accompany the early transformation of the normal glandular epithelium, some of which are expressed very early in the colon at the stage of appearance of ACF.

Methamphetamine-associated burn injuries: a retrospective analysis.

Methamphetamine production and use has increased dramatically during the past 10 years. Methamphetamine production requires combining hazardous and volatile chemicals that expose the manufacturer to burn injuries from explosions and chemical spills. We sought to review the epidemiology of burn injuries in a rural burn center secondary to the use of amphetamine or methamphetamine and/or the manufacture of methamphetamine. Review of the records of 507 patients who were admitted to our burn unit from December 1, 1998, to December 31, 2001, revealed 34 patients who were involved in the use of amphetamines or methamphetamines and/or the manufacture of methamphetamine. Thirty-one patients tested positive for either amphetamine (n = 2) or methamphetamine (n = 29) on routine admission urine drug screens. Twenty of these patients were involved in the manufacture of methamphetamines. Three additional patients were identified as methamphetamine manufacturers but tested negative for the use of methamphetamines. The mean age of the study population was 31.88 +/- 7.65 years, with a male:female ratio of 10.3:1. The average burn size was 18.86 +/- 20.72, with the majority secondary to flame (n = 26). Patient burn admission histories were vague, and the patient's involvement in the manufacture of methamphetamine was often only later confirmed by media, the fire marshal, family members, or the patient. Fifteen patients showed the usual withdrawal pattern of agitation and hypersomnolence, with seven patients requiring detoxification with benzodiazepines. Two were admitted acutely to the psychiatric ward for uncontrollable agitation. Eighteen patients were offered chemical dependency treatment, and two completed therapy. There was one mortality. The mean cost per person was US 77,580 dollars (range, US 112 dollars - US 426,386 dollars). The increasing use of and manufacture of methamphetamine presents new challenges for the burn team because these patients can become violent and frequently need assistance with detoxification. Routine drug screens are mandatory in identifying methamphetamine use to alert burn unit personnel to particular management problems and target individuals who may be receptive to drug rehabilitation.