Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota.

Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.

A fast and inexpensive method for N-terminal fluorescein-labeling of peptides.

A new method has been developed to synthesize fluorescein labeled peptides, compounds of increasing importance in bioorganic chemistry, cell biology, pharmacology, drug targeting and medicinal chemistry. We show, that 4(5)-carboxyfluorescein is much more efficient than the hitherto predominantly utilized reagents 4(5)-carboxyfluorescein-N-succinimidylester and 4(5)-fluoresceinisothiocyanate.

Essential lessons of gerontology and geriatrics.

BACKGROUND: As clinicians, adult children of aging parents, taxpayers, and future retirees, optometrists have multiple reasons for wanting to know more about aging and for wanting to communicate better with older people. METHODS: Fundamental principles emerging from gerontological and geriatrics research are reviewed. Suggestions are offered for improving clinical approaches and practice settings. RESULTS: Population heterogeneity is the rule with aging due to sociocultural as well as biophysiological changes. Follow through with treatment regimens depends on the availability of financial and human resources and on what else is going on with the older patient at the time. CONCLUSIONS: Diseases should be treated at all ages. Particular attention should be devoted to medications management, to compensating environmentally for normal age changes in sensory functioning, and to avoiding iatrogenic consequences of treatment.

Respite care: temporary relief for caregivers.

Recent respite care research is reviewed, advantages and disadvantages of respite- and home-based care are presented, and some recommendations are introduced. It may be more cost-effective to invest in caregivers' physical, financial, and emotional well-being than to provide the care required when caregivers become "patients." Practical and policy issues are raised regarding the desirability of investment in respite care.

Attitudes toward aging, old age, and old people.

People of all ages hold aging-related attitudes. Even very young children recognize age differences and evidence attitudes that appear to be generation-specific. Since attitudes presumably affect behavior and since long life has recently become the rule rather than the exception, interaction with old persons and personal attitudes toward growing old may well be influenced by one's general aging-related attitudes. The availability, accessibility, adequacy, and acceptability of human services intended for use by old persons are also influenced by the attitudes of younger persons. The aging-related attitudes of decision-makers, services personnel, and tax-payers are particularly important in this regard. Much of the U.S. research literature on aging-related attitudes will be reviewed here. Only the highlights of individual articles will be presented, however. Therefore, this paper might best be regarded as a reference to the literature rather than as a restatement of it.