In a prospective randomised study, the effect of acupuncture on sham feeding stimulated gastric acid secretion was investigated. In eight healthy volunteers (five men, three women, mean (SEM) age 26-3 (4.7) years) various methods of acupuncture were performed. Apart from the sham procedure, the acupuncture was performed at the classic acupuncture points. Electroacupuncture reduced gastric acid secretion expressed as median (range) significantly during the first 30 minute period to 1-6 (0-5.2) mmol compared with 3-8 (2.3-14-5) mmol (p<0.05) during control period (sham feeding without acupuncture). Inhibition of gastric acid secretion by electroacupuncture was also significant during the second 30 minute period (0-2 (0-5.6) v 3-6 (0.3-9.1) mmol; p<0.05) and for peak acid output (0.8 (0.2-5.1) v 7'6 (3.4.12-1) mmol; p<0.05). Transcutaneous electrical nerve stimulation also resulted in significant reduction of gastric acid secretion during the first 30 minute period (1-0 (0-3.6) mmol v 3-8 (2.3-14.5) mmol; p<005), and peak acid output (3-6 (1*2-12*0) v 7*6 (3.4-12-1) mmol; p<0.05). The classic needle acupuncture, laser acupuncture, and sham acupuncture had no significant effect on gastric acid secretion. This study shows firstly that in healthy volunteers, only the versio;is of acupuncture using more pronounced stimulation (electroacupuncture, transcutaneous electrical nerve stimulation), but not those with only mild stimulation of the nerves (classic needle acupuncture, laser acupuncture), and secondly only acupuncture performed at defined points lead to significant reduction in gastric acid secretion. (Gut 1994; 35: 1026- MethodsEight healthy subjects (five men, three women, mean (SEM) age 26-3 (4.7) years) took part in the study. As one participant failed to complete the study, the data of seven volunteers were considered for evaluation. Different methods of acupuncture used included needle acupuncture, electroacupuncture, laser acupuncture, and transcutaneous electric nerve stimulation. Apart from sham acupuncture the acupuncture was performed at the classic acupuncture points. For the control period sham feeding without acupuncture was given in all subjects in the study.The subjects gave their written informed consent, and the study protocol was accepted by the ethics commission

SummaryWe report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity‐correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported. The five genes with the greatest impact on lifespan (>20% extension) encode the enzyme kynureninase (kynu‐1), a neuronal leucine‐rich repeat protein (iglr‐1), a tetraspanin (tsp‐3), a regulator of calcineurin (rcan‐1), and a voltage‐gated calcium channel subunit (unc‐36). Knockdown of each gene extended healthspan without impairing reproduction. kynu‐1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and Huntington's disease. Each gene displayed a distinct pattern of interaction with known aging pathways. In the context of published work, kynu‐1, tsp‐3, and rcan‐1 are of particular interest for immediate follow‐up. kynu‐1 is an understudied member of the kynurenine metabolic pathway with a mechanistically distinct impact on lifespan. Our data suggest that tsp‐3 is a novel modulator of hypoxic signaling and rcan‐1 is a context‐specific calcineurin regulator. Our results validate C. elegans as a comparative tool for prioritizing human candidate aging genes, confirm age‐associated gene expression data as valuable source of novel longevity determinants, and prioritize select genes for mechanistic follow‐up.

Recently, it has been shown that higher plasma serine concentrations are a possible biological marker for psychoses including schizophrenia. The present study was carried out in order to investigate plasma serine levels in 123 depressed subjects (41 minor; 47 simple major; 35 melancholic depressives) and 50 normal controls. It was found that plasma serine concentrations were significantly higher in depressed subjects than in normal controls. There were no significant correlations between plasma serine and postdexamethasone cortisol values. Dexamethasone administration had a significant suppressive effect on plasma serine levels in depression but not in normal controls. In the latter – but not in depressed subjects – there were significant positive correlations between plasma serine and L-tryptophan concentrations.

Mesangial matrix expansion is an important process in the initiation of chronic kidney disease, yet the genetic factors driving its development are unknown. Our previous studies have implicated Far2 as a candidate gene associated with differences in mesangial matrix expansion between mouse inbred strains. Consistent with the hypothesis that increased expression of Far2 leads to mesangial matrix expansion through increased production of platelet-activating factor precursors, we show that FAR2 is capable of mediating de novo platelet-activating factor synthesis in vitro and driven by the transcription factor NKX3.2. We demonstrate that knockdown of Far2 in mice delays the progression of mesangial matrix expansion with at least six months (equivalent to ~15 yr in human). Furthermore, we show that increased FAR2 expression in human patients is associated with diabetic nephropathy, lupus nephritis, and IgA nephropathy. Taken together, these results highlight FAR2's role in the development of mesangial matrix expansion and chronic kidney disease.

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The metabolism of tryptophan to nicotinamide adenine dinucleotide (NAD+) through the kynurenine pathway is increasingly linked to aging and age-associated disease. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses, cellular redox homeostasis, and energy production. Aberrant kynurenine metabolism is observed during normal aging and has been implicated in a range of age-associated pathologies, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. In previous work, we and others identified three genes-kynu-1, tdo-2, and acsd-1-encoding kynurenine pathway enzymes for which decreasing expression extends lifespan in invertebrate models. Here we report that knockdown of haao-1, a fourth kynurenine pathway gene encoding the enzyme 3-hydroxyanthranilic acid dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated decline in health in Caenorhabditis elegans. This lifespan extension is mediated by increased physiological levels of the HAAO substrate 3-hydroxyanthranilic acid (3HAA). 3HAA increases resistance to oxidative stress during aging by directly degrading hydrogen peroxide and activating the Nrf2/SKN-1 oxidative stress response. Aging mice fed a diet supplemented with 3HAA are similarly long-lived. Our results identify HAAO and 3HAA as novel therapeutic targets for age-associated disease. This works provides a foundation for more detailed examination of the molecular mechanisms underlying the benefits of 3HAA, and how these mechanisms interact with other interventions both within and beyond the kynurenine pathway. We anticipate that these findings will bolster growing interest in developing pharmacological strategies to target tryptophan metabolism to improve health aging.

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Results of treatment of bacterial endocarditis in the period from 1966 to 1972 are compared with previously reported results from the same institution for earlier time periods. The main differences between these two series was the greater emphasis on early detection and laboratory studies during treatment in the later period. Also, the development of cardiac surgery has led to the appearance of a great number of cases of infectious endocarditis in operated patients. Although the increased attention for the problems of infectious endocarditis was accompanied by a significant decrease in the mortality of patients which had not undergone cardiac surgery, the mortality in patients who have been operated remained frightful. In this latter series, the length of time which elasped between the operation and the development of endocarditis suggested that the infection did not occur at the time of operation in the greatest number of cases.