Biomedical subjects

Heiko Meyer

Publications and source records attributed to Heiko Meyer.

6 recordsLinked to original sources

PubMed2006

A new synthesis of sulfonamides by aminolysis of p-nitrophenylsulfonates yielding potent and selective adenosine A2B receptor antagonists.

1-Propyl- and 1,3-dimethyl-8-p-sulfophenylxanthine (PSB-1115 and SPT) were used as starting compounds for the development of adenosine A(2B) receptor antagonists with a sulfonamide structure. Since standard reactions for sulfonamide formation failed or resulted in very low yields, we developed a new method for the preparation of sulfonamides. p-Nitrophenoxide was used as a suitable leaving group with well balanced stability-reactivity properties. A large variety of amines, including aniline, benzylamine, phenethylamine, propylamine, butylamine, 2-hydroxyethylamine, aminoacetic acid, and N-benzylpiperazine reacted with p-nitrophenoxysulfonylphenylxanthine derivatives yielding the desired sulfonamides in satisfying to very good yields. The obtained sulfonamides were much more potent at A(2B) receptors than the parent sulfonates. The most active compound of the present series was 8-[4-(4-benzylpiperazide-1-sulfonyl)phenyl]-1-propylxanthine (11, PSB-601) exhibiting a K(i) value of 3.6 nM for the human A(2B) receptor combined with high selectivity versus the other human adenosine receptor subtypes (575-fold versus A(1), 134-fold versus A(2A), and >278-fold versus A(3)).

Adenosine A2 Receptor Antagonists↗

PubMed2005

Changes in upper airway size during tidal breathing in children with obstructive sleep apnea syndrome.

UNLABELLED: We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS. METHODS: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle. RESULTS: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.

Anatomy, Cross-Sectional↗

PubMed2005

Image analysis for assessing molecular activity changes in time-dependent geometries.

In vivo fluorescence molecular imaging and tomography has facilitated monitoring of genomics and proteomics over time and on the same animal. A highly important issue, however, has been the robust registration of animals imaged at different time points to obtain accurate description of activity and location. This paper presents a method for aligning temporal data of small animals based on surface anatomical features and improving the accuracy of monitoring fluorophore distribution. The method can account for differences in the positioning and compression of small animals and can be extended to three-dimensional as well as to other imaging modalities.

Algorithms↗

PubMed2004

K+ transport in the caterpillar intestine epithelium: role of osmolytes for the K+-secretory capacity of the tobacco hornworm midgut.

The midgut of the tobacco hornworm, Manduca sexta, actively secretes potassium ions. This can be measured as short-circuit current (I(sc)) with the midgut mounted in an Ussing chamber and superfused with a high-K(+) saline containing as its major osmolyte 166 mM sucrose. Iso-osmotic substitution of sucrose by non-metabolisable compounds (mannitol, urea, NaCl and the polyethylene glycols 200, 400 and 600) led to a dramatic, though reversible, drop in the current. Acarbose, a specific inhibitor of invertase (sucrase) in vertebrates and insects, had no detectable influence on I(sc). Unexpectedly, after replacing sucrose iso-osmotically with the saccharides glucose, fructose, trehalose or raffinose, the K(+) current could no longer be supported. However, all osmolytes smaller than sucrose (except for NaCl), metabolisable or not, initiated an immediate, quite uniform but transient, increase in I(sc) by about 20%, before its eventual decline far below the control value. Hypo-osmotic treatment by omission of sucrose also transiently increased the K(+) current. Small osmolytes substituted for sucrose caused no transient I(sc) stimulation when the epithelium had been challenged before with hypo-osmolarity; however, the eventual decline in I(sc) could not be prevented. Our data seem inconsistent with a role of sucrose as energiser or simple osmolyte. Rather, we discuss here its possible role as analogous to that of sucrose in lower eukaryotes or plants, as an extra- and/or intracellular "compatible osmolyte" that stabilises structure and/or function of the proteins implicated in K(+) transport.

Animals↗

PubMed2004

Plasticity of cortical activation related to working memory during training.

OBJECTIVE: Although it is well established that cerebral activation increases with higher task load, the potential effects of training have been investigated over brief periods only. Training is of potential clinical relevance since training programs are an essential part of psychiatric therapy. METHOD: Cerebral activation during a visual spatial working memory task was examined before, during, and after 4 weeks of daily training in nine healthy subjects using functional magnetic resonance imaging. RESULTS: All subjects showed a pronounced activation mainly involving the right inferior frontal gyrus and the right intraparietal sulcus. While the respective regions showed activation increases with improved performance after 2 weeks of training, the activation values decreased at the time of consolidation of performance gains after 4 weeks. CONCLUSIONS: Our results suggest that training-related cerebral activation changes follow an inverse U-shaped quadratic function and raise the prospect of investigating cerebral mechanisms underlying training effects.

Adult↗

PubMed2002

Insect midgut K(+) secretion: concerted run-down of apical/basolateral transporters with extra-/intracellular acidity.

In lepidopteran larvae, three transport mechanisms are involved in the active and electrogenic K(+) secretion that occurs in the epithelial goblet cells of the midgut. These consist of (i) basolateral K(+) channels, allowing K(+) entry from the haemolymph into the cytosol, (ii) apical electrogenic K(+)/2H(+) antiporters, which are responsible for secondary active extrusion of K(+) from the cell into the gut lumen via the goblet cavity and (iii) apical V-ATPase-type proton pumps. The latter energize apical K(+) exit by building up a large, cavity-positive electrical potential that drives the antiporters. Net K(+) secretion (I(K)) can be measured as short-circuit current (I(sc)) across the in vitro midgut mounted in an Ussing chamber. We investigated the influence of protons on the transepithelial I(K) and the partial reactions of the basolateral K(+) permeability (P(K)) and the apical, lumped 'K(+) pump' current (I(P)) at various extra- and intracellular pH values. In particular, we wanted to know whether increased cellular acidity could counteract the reversible dissociation of the V-ATPase into its V(1) and V(o) parts, as occurs in yeast after glucose deprivation and in the midgut of Manduca sexta during starvation or moulting, thus possibly enhancing K(+) transport. When intact epithelia were perfused with high-[K(+)] (32 mmol l(-1)) salines with different pH values, I(K) was reversibly reduced when pH values fell below 6 on either side of the epithelium. Attempts to modify the intracellular pH by pulsing with NH(4)(+) or propionate showed that intracellular acidification caused a reduction in I(K) similar to that obtained in response to application of external protons. Treatment with azide, a well-known inhibitor of the mitochondrial ATP synthase, had the same effect as pulsing with ammonium or propionate with, however, much faster kinetics and higher reversibility. Breakdown of the basolateral or apical barrier using the antibiotic nystatin allowed the intracellular pH to be clamped to that of the saline facing the nystatin-treated epithelial border. Cell acidification achieved by this manipulation led to a reduction in both apical I(P) and basolateral P(K). The transepithelial I(K) showed an approximately half-maximal reduction at external pH values close to 5 in intact tissues, and a similar reduction in I(P) and P(K) values was seen at an intracellular pH of 5 in nystatin-permeabilised epithelia. Thus, the hypothesized V(1)V(o) stabilization by cell acidity is not reflected in the pH-sensitivity of I(P). Moreover, all components that transport K(+) are synchronously inhibited below pH 6. The significance of our findings for the midgut in vivo is discussed.

Adenosine Triphosphatases↗