Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment.

In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.

Delayed maturation of auditory-evoked responses in growth-restricted fetuses revealed by magnetoencephalographic recordings.

OBJECTIVE: The purpose of this study was to investigate fetal brain development of growth-restricted fetuses with auditory evoked responses (AER) that were recorded by the noninvasive magnetoencephalographic technique. STUDY DESIGN: Serial fetal recordings that started at 27 weeks of gestation were conducted on a fetal magnetoencephalographic device that was especially designed for obstetric assessment. Fifteen normotrophic fetuses were compared with 14 hypotrophic fetuses. After birth, 10 of the hypotrophic fetuses were diagnosed with asymmetric growth restriction; 4 fetuses were classified as symmetrically small for gestational age. RESULTS: Fetal AER latencies in both groups showed an average developmental decrease of 12.74 msec/wk (P = .0035). Hypotrophic fetuses had longer age-adjusted latencies compared with normotrophic fetuses, with a difference of 73.5 msec (P = .034). The subgroup of symmetrically growth-restricted fetuses showed the longest latencies for age, with a difference from the normotrophic fetuses of 120.0 msec (P = .045). CONCLUSION: The results indicate that biomagnetically recorded AER can be used to monitor functional brain development in growth-restricted fetuses.

Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil.

BACKGROUND: Drug treatment is imperative for pregnant women with pregnancy-induced hypertension (PIH) and pre-eclampsia. For more than 40 years, dihydralazine has been the drug of choice for this indication. Another particularly effective and better tolerable antihypertensive is urapidil. Yet only a few studies on limited patient collectives have been published on the clinical experience with urapidil in PIH. METHODS: Urapidil was interindividually compared to dihydralazine in a total of 42 patients, at six participating clinical centres. Patients were randomly assigned to the treatment groups. Urapidil was administered at an initial dose of 12.5-25mg, dihydralazine was administered at a uniform initial dose of 5mg. Patients were closely monitored for the initial 24h of therapy. Until delivery and in the postpartal phase, mother and baby underwent four additional follow-up checks at regular intervals. RESULTS: Either drug was effective in lowering BP. Urapidil treatment proved to be better controllable. There were clear differences as to tolerability. In the urapidil group, one patient complained of headaches. In the dihydralazine group, six patients experienced adverse occurrences. Under dihydralazine treatment, some marked HR increases occurred, interpretable as reflectory tachycardia. CONCLUSIONS: Urapidil proved to be equally effective as dihydralazine in lowering BP in patients with pre-eclampsia, but showed a better controllability and tolerability. Urapidil can hence be recommended as a promising alternative for patients with PIH.

Evaluation of red blood cell deformability and uterine blood flow in pregnant women with preeclampsia or iugr and reduced uterine blood flow following the intravenous application of magnesium.

OBJECTIVE: Red blood cells (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), RBC deformability and, consequently, microcirculation appear to be impaired. Magnesium sulfate is administered to reduce the risk of seizures in PE. The aim of our study was to detect the effect of 24-hour intravenous (IV) magnesium on RBC deformability and on uterine artery blood flow in pregnant patients with preeclampsia or IUGR and pathologic uterine blood flow. METHODS: Magnesium IV (1 g/h) was administered to 25 pregnant women with reduced uterine blood flow for a period of at least 24 hours. The RBC deformability was measured by uterine artery Doppler. Measurements were taken before the start of magnesium therapy and 24 h later. Magnesium plasma levels were measured at the same time. RESULTS: High plasma levels of magnesium improve RBC deformability from E = 0.109 (SD +/- 0.023) to E = 0.115 (SD +/- 0.021) after 24 h IV magnesium (p = 0.043). There is no correlation of E to the plasma magnesium level either before or after 24 h magnesium treatment. Blood volume flow in the uterine arteries increased significantly from 5.09 mL/s (SD +/- 3.03) to 10.02 mL/s (SD +/- 5.86) after 24 h magnesium (p = 0.0002). The differences in the resistance index do not significantly differ from 0 (p = 0.46). CONCLUSION: A high IV dosage of magnesium over a period of 24 hours dilates the uterine arteries of pregnant women with PE and/or IUGR, reduces uterine blood flow and improves the deformability of RBC. Both parameters enhance the oxygen supply to the fetus, a clinical parameter in these pregnancies. Thus magnesium might not only be effective as phrophylaxis against seizures but also in cases of IUGR with a reduced uterine blood flow. The clinically observed beneficial effect of magnesium in PE could be due to the improved blood supply for the fetus.