Simultaneous influence of sex and age on blood pressure difference between supine and sitting body positions.

OBJECTIVES: Doctors' offices and outpatient departments typically measure blood pressure (BP) with the patient in a sitting position, whereas inpatient departments also use the supine position. As sex and age influence the autonomic function associated with BP regulation our study compared BP measurements in supine and sitting positions for men and women of different ages. METHODS: We included 91 men and 118 women (≥18 years) without severe diseases. Hypertension was not an exclusion criterion because it is common in older persons. Mean left brachial BP and heart rate were determined by a digital sphygmomanometer in supine position as well as in sitting position before and after hand force measurement. RESULTS: In a supine position women had slightly lower diastolic BP values than men. After sitting up, the diastolic BP increased in nearly all subjects. This increase was greater in women older than 50 years than for aged-matched men. In contrast to diastolic BP the systolic BP increased after sitting up in only two thirds of the subjects. Especially in women younger than 50 years the systolic BP often did not increase but decreased in response to postural change. The pulse pressure was mostly reduced after sitting up. This reduction was more pronounced in women than men independent of age and physical effort (i.e. hand force measurement). The sitting position also caused an increased heart rate, which was independent of sex and age. CONCLUSION: Postural changes in the systolic and diastolic BP simultaneously depend on sex and age that needs to be considered for BP measurements in supine and sitting body positions.

Sex-related differences in human plasma NAD+/NADH levels depend on age.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic reactions and cosubstrate in signaling pathways of cells. While the intracellular function of NAD is well described, much less is known about its importance as an extracellular molecule. Moreover, there is only little information about the concentration of extracellular NAD and the ratio between its oxidized (NAD+) and reduced (NADH) form in humans. Therefore, our study aimed at the analysis of total NAD and NAD+/NADH ratio in human plasma depending on sex and age. First, an enzymatic assay was established for detecting NAD+ and NADH in human plasma samples. Then, plasma NAD was analyzed in 205 probands without severe diseases (91 men, 114 women) being 18-83 years old. The total plasma NAD concentration was determined with median 1.34 µM (0.44-2.88 µM) without difference between men and women. Although the amounts of NAD+ and NADH were nearly balanced, women had higher plasma NAD+/NADH ratios than men (median 1.33 vs. 1.09, P<0.001). The sex-related difference in the plasma NAD+/NADH ratio reduces with increasing age, an effect that was more obvious for two parameters of the biological age (skin autofluorescence, brachial-femoral pulse wave velocity (PWV)) than for the chronological age. However, plasma values for total NAD and NAD+/NADH ratio did not generally alter with increasing age. In conclusion, human plasma contains low micromolar concentrations of total NAD with higher NAD+/NADH redox ratios in adult but not older women compared with same-aged men.

Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report.

BACKGROUND: Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. CASE PRESENTATION: A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 µg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found. For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered. CONCLUSIONS: Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity.