513 research outputs found
De ecclesiola in het Utrechtse castellum. Bouwhistorische interpretatie van de resten van de Heilig-Kruiskapel
The 're-excavation' in 1993 of part of the foundations and above-ground walling of the Heilig-Kruiskapel has revealed new data with respect to the history of its construction. The most important conclusion is that the southern annex of this chapel was a separate unit and as such it was the seventh-century predecessor of the church attached to it later. It is likely that the Heilig- Kruiskapel itself is to be identified with the St Maarten's church built by Willibrord.
This hypothesis on the basis of architectural-historical findings implies that a new architectural structure is to be added to the structure at Dom square in Utrecht we are already acquainted with, a small church which so far had only been known from written sources and the location of which was conjectured to have been outside as well as inside the Castellum. The site and size of the first Christian foundation in Utrecht now localized raise new questions on its original function.
In view of its small size the square chapel or cella may have been a burial chapel or cella memoriae. The existence has been proved of early-medieval burials in stone sarcophagi in and around the earliest Salvator church in Utrecht, which probably date back to the eighth and ninth centuries. More deeply situated burials in wooden coffins could be part of the oldest Christian burial place.
Unfortunately, the medieval burials in and around the Heilig-Kruiskapel have not been researched accurately enough to be able to refer to them as early-medieval burials with any certainty. A number of burials in wooden coffins, just as similar burials around Salvator church situated at a rather large depth and appearing to be somewhat grouped into two strips to the east of the Heilig-Kruiskapel, possibly are among the oldest Christian tombs.
The niche in the eastern wall must have had a funerary function in the use of the place as a burial chapel. Although the internal dimensions of the niche are rather small, one may think of the lay-out of a tomb as ‘arcosolium’ or niche tomb, possibly with an altar placed in front of it. A cella memoriae can also be interpreted in another meaning: the memoria may refer to the presence of one or more relies. At any rate, from the sixth century onwards each altar was provided with at least one relic.
Particularly for a Christian outpost in an area which had to be converted, the presence of a relic may have been an important condition for the success of missionary activities. The question which relic was already present in Utrecht in the early seventh century, however, will have to remain unanswered for the time being. In view of the consecration at any rate in the time of Willibrord, a St Maarten's relic is most likely, but an original consecration to Thomas Apostle is also possible; however, in this respect the Utrecht tradition is very late.
The scarce data on the earliest Christian history of Utrecht are to be supplemented with the foundations and part of the aboveground walling of the first little church in the castellum, referred to as ecclesiola by Boniface. However, all sorts of questions on its use, consecration and incorporation in the later episcopal cluster of church buildings remain unsolved as yet, and it will only be possible to answer them after closer research
Uptake and turnover of mono-iodinated thyroid hormone metabolites by PCCL3 thyrocytes
Tyrosine and phenolic ring de-iodination of thyroid hormones (TH) is crucial
for regulating their physiological activity. Furthermore, reactions such as
de-carboxylation to thyronamines (TAM) and de-amination to thyroacetic acids
(TAc) produce TH metabolites (THM) with distinct biological properties. This
needs to be considered when studying effects of TH and THM. The accurate and
precise quantitative analysis of TH and THM in cell culture supernatants and
cell lysates are key procedures required for studying the in vitro metabolism
of TH. We report here the development of a liquid-liquid extraction/isotope
dilution-liquid chromatography-electrospray tandem mass spectrometry (LC-
MS/MS) method for the quantification of 9 thyronines (TN) and 6 TAM in human
hepatocellular carcinoma Hep G2 cell lysate extracts. In addition, we adapted
the method to quantify TH, TAM and TAc, in cell lysates of FBS-depleted rat
thyroid epithelium PCCL3 cells. The methods for both cell lines were validated
by rigorous assessment of linearity, limits of quantification and detection
(LLOQ and LLOD respectively), intra- and inter-day accuracy, precision,
process efficiency (PE), matrix effect (ME) and relative recovery (RE).
Calibration curves covering 11 concentrations (based on 400 μl of lysate) were
linear in the range 0.016–50 nM and 0.010–50 nM for Hep G2 and PCCL3 cells
respectively. The lower limits of quantification were in the range 0.031 to 1
nM. We applied the PCCL3 version of the LC-MS/MS method to the analysis of
lysed cell extracts from PCCL3 cells that had been incubated with
3-iodo-L-thyronine (T1), 3-iodothyronamine (3-T1AM) and 3-iodothyroacetic acid
(3-T1Ac). Over the course of 30 minutes incubation 3-T1AM was de-iodinated to
4-[4-(2-aminoethylphenoxy)]phenol (thyronamine, T0AM) and de-aminated to
3-T1Ac respectively, whilst T1 underwent de-iodination to T0. This data
indicates avid metabolism of these mono-iodinated compounds and the utility of
LC-MS/MS to quantify such cellular metabolism
Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats
Background There is substantial evidence both in humans and in animals that a
prolonged reduction in plasma thyroid hormone concentration leads to
reproductive problems, including disturbed folliculogenesis, impaired
ovulation and fertilization rates, miscarriage and pregnancy complications.
The objective of the present study is to examine the consequences of chronic
hypothyroidism, induced in adulthood, for the size of the ovarian follicle
pool. In order to investigate this, adult female rats were provided either a
control or an iodide deficient diet in combination with perchlorate
supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later
animals were sacrificed. Blood was collected for hormone analyses and ovaries
were evaluated histologically. Results At the time of sacrifice, plasma
thyroid-stimulating hormone concentrations were 20- to 40-fold increased,
thyroxine concentrations were negligible while tri-iothyronin concentrations
were decreased by 40% in the hypothyroid group, confirming that the animals
were hypothyroid. Primordial, primary and preantral follicle numbers were
significantly lower in the hypothyroid ovaries compared to the euthyroid
controls, while a downward trend in antral follicle and corpora lutea numbers
was observed. Surprisingly the percentage of atretic follicles was not
significantly different between the two groups, suggesting that the reduced
preantral and antral follicle numbers were presumably not the consequence of
increased degeneration of these follicle types in the hypothyroid group.
Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation
with the growing follicle population represented by the total ovarian number
of primary, preantral and antral follicles, suggesting that also under
hypothyroid conditions AMH can serve as a surrogate marker to assess the
growing ovarian follicle population. Conclusions The induction of a chronic
hypothyroid condition in adult female rats negatively affects the ovarian
follicular reserve and the size of the growing follicle population, which may
impact fertility
Alternation between short- and long photoperiod reveals hypothalamic gene regulation linked to seasonal body weight changes in Djungarian hamsters (Phodopus sungorus)
This work was funded by the German Research Foundation (DFG, Emmy-Noether HE6383 to AH) and the British Society for Neuroendocrinology (Research grant to JB). The authors declare that they have no conflicts of interest.Peer reviewedPostprin
71 Pharmacokinetics of nasal administered tobramycin in patients with cystic fibrosis
Recent studies showed that the paranasal sinuses can constitute a niche for bacteria. To date no effective treatment for these bacteria is available. Off label administration of nasal antibiotics may be an option. However, first safety of this treatment has to be established. Objectives: With this pilot study in two patients the pharmacokinetic parameters of nasal administered tobramycin were investigated. Methods: In two hospitalised CF-patients, treated with intravenous tobramycin, after a wash-out period, 320 mg of tobramycin, dissolved in 200 ml isotonic saline, was administered to the nose using nasal lavage. Eleven venous blood samples were collected and with a Liquid Chromatography Tandem Mass Spectometer (LCMSMS) method, serum tobramycin concentrations were determined. Tobramycin pharmacokinetic parameters were calculated using the MW\Pharm software package. Systemic absorption was calculated by dividing AUC after nasal administration by AUC after intravenous administration corrected for the administered dose. Results: In patient 1, a female of 32 years old, the maximum concentration (Cmax) of tobramycin was 0.027 mg/L. This Cmax was reached 30 minutes after the nasal lavage with tobramycin (tmax). In total 0.20% (0.62 mg) of the tobramycin was systemically absorbed. In patient 2, a male of 36 years old, the Cmax was 0.029 mg/L. The tmax was 45 minutes and in total 0.16% (0.51 mg) of tobramycin was absorbed. Conclusion: Nasal lavage with 320 mg tobramycin did not result in toxic serum levels. The results of two patients showed a fast absorption of tobramycin and a slow elimination. Approximately 0.20% of the tobramycin was absorbed by the sinonasal mucosa
Intranasal cold dry air is superior to histamine challenge in determining the presence and degree of nasal hyperreactivity in nonallergic noninfectious perennial rhinitis
The objective of the study was to compare cold dry air (CDA) and histamine
in differentiating patients with nonallergic noninfectious perennial
rhinitis (NANIPER) from control subjects. Nasal reactivity (nasal patency,
mucus production, and sneezing) in 16 symptomatic nonsmoking patients with
NANIPER and seven nonsmoking control subjects was measured with
standardized CDA and histamine provocation series in a randomized
crossover study. Intranasal CDA resulted in increased mucus production and
nasal blockage in a dose-dependent manner in patients with NANIPER but not
in control subjects. Sneezing did not occur. The reproducibility of CDA
for patency and mucus production was good. Sen
Sex-specific associations of serum selenium and selenoprotein P with type 2 diabetes mellitus and hypertension in the Berlin Aging Study II
Background: Selenium is essential for expression and proper function of a set of redox active selenoproteins implicated in aging-relevant diseases, e.g. type 2 diabetes mellitus (T2D) and hypertension. However, data in cohorts of older adults, particularly with respect to different Se biomarkers and sex-specific analyses are sparse.
Objective: To assess associations of serum Se and selenoprotein P (SELENOP) concentrations with T2D and hypertension in a cohort of older females and males.
Methods: This study included 1500 participants from the Berlin Aging Study II. Diagnosis of T2D was made in case of antidiabetic medication, self-reported T2D, or laboratory parameters. Diagnosis of hypertension was based on self-report, blood pressure measurement, or anti-hypertensive medication. Se was measured by spectroscopy, and SELENOP by ELISA. Multiple adjusted regression models quantified dose-dependent associations.
Results: Participants had a median(IQR) age of 68 (65,71) years, and 767 (51%) were women. 191 (13%) participants had T2D and 1126 (75%) had hypertension. Se and SELENOP correlated significantly (r = 0.59, p < 0.001), and were elevated in those with self-reported Se supplementation. Serum Se and SELENOP were not associated with T2D in the whole cohort. In men, SELENOP was positively associated with T2D, OR (95%CI) for one mg/L increase in SELENOP was 1.22 (1.00,1.48). Se was non-linearly associated with hypertension, comparing to the lowest quartile (Q1), and participants with higher Se levels (Q3) had a lower OR (95%CI) of 0.66 (0.45,0.96), which was specific for men. SELENOP positively associated with hypertension, and OR (95%CI) per one mg/L increase was 1.15 (1.01,1.32).
Conclusions: The data suggest a sex-specific interrelationship of Se status with T2D and hypertension, with apparent biomarker-specific associations
Dual Effect on Adult-Type Leydig Cell and Sertoli Cell Development
Transient neonatal 6-propyl-2-thiouracil (PTU) induced hypothyroidism affects
Leydig and Sertoli cell numbers in the developing testis, resulting in
increased adult testis size. The hypothyroid condition was thought to be
responsible, an assumption questioned by studies showing that uninterrupted
fetal/postnatal hypothyroidism did not affect adult testis size. Here, we
investigated effects of transient hypothyroidism on Leydig and Sertoli cell
development, employing a perinatal iodide-deficient diet in combination with
sodium perchlorate. This hypothyroidism inducing diet was continued until days
1, 7, 14, or 28 postpartum (pp) respectively, when the rats were switched to a
euthyroid diet and followed up to adulthood. Continuous euthyroid and
hypothyroid, and neonatal PTU-treated rats switched to the euthyroid diet at
28 days pp, were included for comparison. No effects on formation of the
adult-type Leydig cell population or on Sertoli cell proliferation and
differentiation were observed when the diet switched at/or before day 14 pp.
However, when the diet was discontinued at day 28 pp, Leydig cell development
was delayed similarly to what was observed in chronic hypothyroid rats.
Surprisingly, Sertoli cell proliferation was 6- to 8-fold increased 2 days
after the diet switch and remained elevated the next days. In adulthood,
Sertoli cell number per seminiferous tubule cross-section and consequently
testis weight was increased in this group. These observations implicate that
increased adult testis size in transiently hypothyroid rats is not caused by
the hypothyroid condition per se, but originates from augmented Sertoli cell
proliferation as a consequence of rapid normalization of thyroid hormone
concentrations
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