Sabine Schwarz

A characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity. A 24-hour recovery period in lactic acid-free medium restored CTL function. CTLs infiltrating lactic acid-producing multicellular tumor spheroids showed a reduced cytokine production. Pretreatment of tumor spheroids with an inhibitor of lactic acid production prevented this effect. Activated T cells themselves use glycolysis and rely on the efficient secretion of lactic acid, as its intracellular accumulation disturbs their metabolism. Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function. We conclude that high lactic acid concentrations in the tumor environment block lactic acid export in T cells, thereby disturbing their metabolism and function. These findings suggest that targeting this metabolic pathway in tumors is a promising strategy to enhance tumor immunogenicity.

Population-based studies showed that non-alcoholic hepatic steatosis is less common in women than in men. Anti-oestrogens double the risk of non-alcoholic steatohepatitis,1 which may be interpreted as indirect evidence for a protective role of endogenous oestrogens against steatohepatitis. Experimental evidence further suggests that oestradiol causes a reduction of hepatic steatosis in mice unable to produce oestrogens.2 We thus hypothesised that the menopause as a natural state of oestrogen deficiency might increase the risk of hepatic steatosis. The Study of Health in Pomerania is a cross-sectional population-based survey in northeast Germany.3 We restricted our analyses to 808 women aged 40–59 years without seropositivity to hepatitis B antigen and anti-hepatitis C virus. The study was approved by the ethics committee of the University of Greifswald. All participants gave written informed consent. Menopause was defined as 12 consecutive months of amenorrhoea or cessation of menstruation after iatrogenic intervention. Serum glutamate oxaloacetate …

BACKGROUND: Tooth loss predicts total and circulatory mortality. The reasons for the increased mortality in subjects with a low number of teeth may be related to enhanced atherosclerosis, elevated arterial pressure and more frequent hypertension. The present study was designed to investigate whether there is an association between the number of teeth and arterial pressure or hypertension. METHODS: We used data of 4185 adult subjects (2150 women) collected for the population-based Study of Health in Pomerania. The number of teeth was counted by trained and certified dentists. Hypertension was defined as systolic blood pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg or use of antihypertensive medication. Multivariable analyses were adjusted for relevant confounders. RESULTS: The adjusted mean (standard error) systolic blood pressure in men having 0-6 teeth was 149.6 mmHg (1.3 mmHg) compared to 142.6 mmHg (1.2 mmHg) in men having 27-28 teeth (P < 0.05). The adjusted odds for hypertension in men with 0-6 teeth compared to men with 27-28 teeth were 1.91 (95% confidence interval 1.21; 3.02, P < 0.05). In women no such relations were found. CONCLUSION: There is an inverse association between the number of teeth and systolic blood pressure and hypertension in men but not in women. The present findings partly explain the relation between tooth loss and mortality.