Initial orthostatic hypotension in teenagers and young adults.

OBJECTIVE: To assess: (1) the frequency of an abnormally large fall in blood pressure (BP) upon standing from supine in patients with initial orthostatic hypotension (IOH); (2) the underlying hemodynamic mechanisms of this fall in BP upon standing from supine and from squatting. METHODS: In a retrospective study of 371 patients (≤30 years) visiting the syncope unit, the hemodynamic response to standing and squatting were studied in 26 patients who were diagnosed clinically with IOH, based on history taking only. In six patients changes in cardiac output (CO) and systemic vascular resistance (SVR) were determined, and the underlying hemodynamics were analyzed. RESULTS: 15/26 (58 %) patients with IOH had an abnormally large initial fall in systolic BP (≥40 mmHg). There was a large scatter in CO and SVR response after arising from supine [ΔCO at BP nadir median -8 % (range -37, +27 %); ΔSVR at BP nadir median -31 % (range -46, +10 %)]. The hemodynamic response after squatting showed a more consistent pattern, with a fall in SVR in all six patients [ΔCO at BP nadir median +23 % (range -12, +31 %); ΔSVR at BP nadir median -42 %, (range -52, -35 %)]. INTERPRETATION: The clinical diagnosis of IOH is based on history taking, as an abnormally large fall in systolic BP can only be documented in 58 %. For IOH upon standing after supine rest, the hemodynamic mechanism can be either a large fall in CO or in SVR. For IOH upon arising from squatting a large fall in SVR is a consistent finding.

MSNA during prolonged post-faint hypotension.

BACKGROUND: Following tilt-induced syncope, blood pressure usually recovers rapidly after tilt back to the horizontal position. However, in some patients, hemodynamic recovery is delayed, a condition recently termed "prolonged post-faint hypotension" (PPFH). The mechanism is thought to be mediated by increased vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have been reported in this condition, so we aimed to confirm that neither vasodilatation nor MSNA withdrawal was responsible. OBJECTIVES: To retrospectively select patients with satisfactory recordings of continuous BP and MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in patients with PPFH to patients with normal recovery (NR) after tilt-back. METHODS: All patients were studied in Christchurch, New Zealand, between 1998 and 2008 using continuous arterial BP monitoring, and microneurographic recordings of MSNA from the right leg. Only patients with satisfactory BP and MSNA data throughout baseline, head-up tilt and presyncope were selected. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived using Modelflow. After baseline measurements, patients were tilted to the head-up 60° position and given GTN spray if asymptomatic after 20 min. Following the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH was defined as systolic BP <85 mmHg for at least 2 min after tilt-back. Measurements were averaged at baseline, early tilt, presyncope, early and late recovery. Within-group comparisons were made between baseline and all other time points. Between-group comparisons were made over all time points. RESULTS: Patients with PPFH (7 males, age 46 ± 5 years, n = 8) and with NR (8 males, age 47 ± 6 years, n = 8) were selected. Presyncope was provoked by GTN in 4/8 patients in each group. In both groups, MAP remained below baseline during early and late recovery: PPFH 84 ± 5 versus 51 ± 5 and 64 ± 5 mmHg (p = 0.001, p = 0.001); NR 104 ± 5 versus 83 ± 5 and 93 ± 5 mmHg (p = 0.001, p = 0.03). However, MAP and HR were lower in the PPFH group (p = 0.004, p = 0.023). During early recovery, CO remained below baseline only in the PPFH group (p = 0.001), whereas TPR remained constant in both groups. In both groups, all MSNA indices tended to remain above baseline levels during early and late recovery. PPFH 25 ± 2 increased to 31 ± 6 and 29 ± 4 bursts/min (p = 0.09, 0.02); NR 23 ± 3 increased to 33 ± 3 and 34 ± 3 bursts/min (p = 0.06, 0.01). CONCLUSIONS: PPFH does not appear to be mediated by exaggerated vasodilatation or sympathetic withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a more likely mechanism.

Prolonged post-faint hypotension can be reversed by dynamic tension.

A severe variant of vasovagal syncope, observed during tilt tests and blood donation has recently been termed "prolonged post-faint hypotension" (PPFH). A 49-year-old male with a life-long history of severe fainting attacks underwent head-up tilt for 20 min, and developed syncope 2 min after nitroglycerine spray. He was unconscious for 40 s and asystolic for 22 s. For the first 2 min of recovery, BP and HR remained low (65/45 mmHg and 40 beats/min) despite passive leg-raising. Blood pressure (and symptoms) only improved following active bilateral leg flexion and extension ("dynamic tension"). During PPFH, when vagal activity is extreme, patients may require central stimulation as well as correction of venous return.

Exceptional cryptic diversity and multiple origins of parthenogenesis in a freshwater ostracod.

The persistence of asexual reproduction in many taxa depends on a balance between the origin of new asexual lineages and the extinction of old ones. This turnover determines the diversity of extant asexual populations and so influences the interaction between sexual and asexual modes of reproduction. Species with mixed reproduction, like the freshwater ostracod (Crustacea) morphospecies Eucypris virens, are a good model to examine these dynamics. This species is also a geographic parthenogen, in which sexual females and males co-exist with asexual females in the circum-Mediterranean area only, whereas asexual females occur all over Europe. A molecular phylogeny of E. virens based on the mitochondrial COI and 16S fragments is presented. It is characterised by many distinct clusters of haplotypes which are either exclusively sexual or asexual, with only one exception, and are often separated by deep branches. Analysis of the phylogeny reveals an astonishing cryptic diversity, which indicates the existence of a species complex with more than 40 cryptic taxa. We therefore suggest a revision of the single species status of E. virens. The phylogeny indicates multiple transitions from diverse sexual ancestor populations to asexuality. Although many transitions appear to be ancient, we argue that this may be an artefact of the existence of unsampled or extinct sexual lineages.

The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis.

The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.

Regulation of the action of the novel cholecystokinin-releasing peptide diazepam binding inhibitor by inhibitory hormones and taurocholate.

Diazepam binding inhibitor (DBI1-86) has recently been isolated in search for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic secretion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and in vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secretion. Somatostatin, peptide YY (PYY) and taurocholate are known to inhibit feedback-stimulated CCK release in the rat. In this study, we investigated the effect of somatostatin, PYY and taurocholate on DBI-stimulated CCK secretion. Dispersed rat intestinal mucosal cells were prepared from the proximal small bowel and continuously perfused. The perfusate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effect at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pretreatment of the cells with pertussis toxin fully reversed the inhibitory effect of somatostatin on DBI-stimulated CCK secretion, suggesting that somatostatin exerts its action by an inhibitory G-protein. In contrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mechanisms to inhibit feedback-stimulated CCK release.

Copper(II) complexes of low molecular weight derivatives of thymopoietin.

Copper(II) complexes of tri- and tetrapeptides containing either carboxylate or amide group in the side chain were studied by potentiometric and spectroscopic methods. The ligands are tri- and tetrapeptide segments of the hormones thymopoietin and splenin. It was found that internal aspartyl residues significantly enhance the metal binding ability of oligopeptides, resulting in the cooperative deprotonation of the amide nitrogens preceding the aspartyl residue, while the subsequent amide groups do not take part in metal ion coordination. Glutamyl residues have no significant effect on the complex formation processes of oligopeptides.

Potentiometric and spectroscopic studies on the copper(II) complexes of peptide hormones containing disulfide bridges.

Copper(II) complexes of oxytocin, 4-Glu-oxytocin, 5-Asp-oxytocin, and GlyGlyGly-Lys8-vasopressin were studied by potentiometric, EPR, and UV-visible spectroscopic methods. The formation of 4N-coordinated complexes was characteristic of all ligands. This type of coordination is especially favored for oxytocin due to the specific conformation of the ring coupled by the disulfide bridge. The coordination of the gamma-carboxylate group of 4-Glu-oxytocin and a disulfide sulfur atom of GlyGlyGly-Lys8-vasopressin was reported to occur in the 2N-complexes over medium pH range.

1H-NMR studies on thymopoietin-type oligopeptides--assignment of the proton resonances and investigation of conformational preferences.

The thymopoietin-type tripeptides TP3 (HArg-Lys-AspOH), TP(D-Asp)3(HArg-Lys-D-AspOH) and tetrapeptide TP4 (HArg-Lys-Asp-ValOH) were studied by one- and two-dimensional, 500 MHz 1H-NMR spectroscopy in H2O and D2O solutions at four different pH values. All proton resonances of the three oligopeptides were assigned by two-dimensional phase-sensitive TOCSY experiments at pH 12.2, 9.1, 5.9 and 3.6. At these pH-values well-defined stages of protonation and concomitant molecular charges exist, allowing different possibilities for intra-molecular and inter-residual orientations. Conformation-sensitive rotating frame nuclear Overhauser enhancement (ROESY) two-dimensional experiments were also performed at the above pH values. These experiments indicated no definite solution conformation of any of the molecules at any pH. Standard one-dimensional experiments were also carried out and three-bond coupling constants were measured for the NH--CH and the Asp CH--CH moieties. The coupling constants provided evidence that non-statistical orientations of the functional groups exist which are changed upon protonation of the basic sites.

Eating quality of European beef assessed at five research institutes.

Loin steaks from 10 animals (five of each of two types) from each of eight European countries were assessed for eating quality at five institutes in Denmark, Ireland, England, France and the Federal Republic of Germany. All panels found wide variation in eating quality and many of the steaks were unacceptably tough. Although attempts to relate quality to production factors were often confounded, differences in post-slaughter handling, particularly between producing countries, dominated eating quality. Breed, sex, age or fatness had relatively little influence on eating quality in this trial. A common eight-category scale of tenderness/toughness was used in addition to each institute's usual descriptive scales for tenderness, flavour, juiciness and overall acceptability, employing four to eleven categories. Within panels, attribute scores were not independent and tenderness and flavour in combination were the best predictors of overall acceptability. Between panels, tenderness was highly interrelated, flavour and juiciness poorly interrelated. These findings, together with estimates of each panel's discrimination and the variation between individual assessors, are discussed in relation to standardisation and equivalence of sensory methodology.

Comparison of chemical composition of meat determined at eight laboratories.

Sixteen minced samples of lean beef M. semimembranosus and M. gracilis were analysed for nitrogen, fat, moisture, collagen, ash and pH using recommended procedures in eight European Communitie' (EC) meat research laboratories. Differences between replicate determinations within laboratories were often larger than suggested in reference methods although they were smaller than the differences between laboratories. Moisture and pH were determined most consistently, collagen least consistently.

Beef quality assessed at European research centres.

Loin steaks and cubes of M. semimembranosus from eight (12 month old) Galloway steers and eight (16-18 month old) Charolais cross steers raised in England and from which the meat was conditioned for 2 or 10 days, were assessed in research centres in Belgium, Denmark, England, France, the Federal Republic of Germany, Ireland, Italy and the Netherlands. Laboratory panels assessed meat by grilling the steaks and cooking the cubes in casseroles according to local custom using scales developed locally and by scales used frequently at other research centres. The meat was mostly of good quality but with sufficient variation to obtain meaningful comparisons. Tenderness and juiciness were assessed most, and flavour least, consistently. Over the 32 meats, acceptability of steaks and casseroles was in general compounded from tenderness, juiciness and flavour. However, when the meat was tough, it dominated the overall judgement; but when tender, flavour played an important rôle. Irish and English panels tended to weight more on flavour and Italian panels on tenderness and juiciness. Juciness and tenderness were well correlated among all panels except in Italy and Germany. With flavour, however, Belgian, Irish, German and Dutch panels ranked the meats similarly and formed a group distinct from the others which did not. The panels showed a similar grouping for judgements of acceptability. French and Belgian panels judged the steaks from the older Charolais cross steers to have more flavour and be more juicy than average and tended to prefer them. Casseroles from younger steers were invariably preferred although the French and Belgian panels judged aged meat from older animals equally acceptable. These regional biases were thought to be derived mainly from differences in cooking, but variations in experience and perception of assessors also contributed.

Inhibitors of lipid peroxidation among new pyrimido[1',6':1,2]pyrido[3,4-b]indoles.

A series of potent inhibitors of NADPH- and Fe(2+)-dependent lipid peroxidation has been found among new pyrimido[1'6':1,2]pyrido[3,4-b]indole derivatives. According to preliminary structure-activity relationship analysis the saturated pyrimidine moiety was responsible for this effect. Some members of this family were effective in a bilateral carotid occlusion model in mice, and some derivatives showed protective effect in a mouse head injury model.

[Screening of modified polyethylene surfaces for tissue engineering of chondrocytes]. / Screening von modifizierten Polyethylenoberflächen für das Tissue-Engineering von Chondrozyten.

BACKGROUND: Reconstructive surgery needs high requirements of substitutes for cartilages. The availability of autologous material is limited. The use of implants can cause inflammatory reactions. Therefore the biocompatibility of porous polyethylene should be improved by masking the synthetic surface with autologous cells. The polyethylene surface was functionalized by collagen, in order to enhance the contact between polyethylene and the surrounding cells. METHODS: The modified surfaces were characterized and tested by an in vitro screening with primary human chondrocytes. RESULTS: The modification of polyethylene surfaces by collagen coating increased the life time of chondrocytes growing at this surface. The effect was independent of the former functionalization. CONCLUSIONS: It is possible to cultivate chondrocytes on polyethylene surfaces. The results have to be proven in a long-term animal experimental study.

No evidence for the 'Meselson effect' in parthenogenetic oribatid mites (Oribatida, Acari).

It has been hypothesized that in ancient apomictic, nonrecombining lineages the two alleles of a single copy gene will become highly divergent as a result of the independent accumulation of mutations (Meselson effect). We used a partial sequence of the elongation factor-1alpha (ef-1alpha) and the heat shock protein 82 (hsp82) genes to test this hypothesis for putative ancient parthenogenetic oribatid mite lineages. In addition, we tested if the hsp82 gene is fully transcribed by sequencing the cDNA and we also tested if there is evidence for recombination and gene conversion in sexual and parthenogenetic oribatid mite species. The average maximum intra-specific divergence in the ef-1alpha was 2.7% in three parthenogenetic species and 8.6% in three sexual species; the average maximum intra-individual genetic divergence was 0.9% in the parthenogenetic and 6.0% in the sexual species. In the hsp82 gene the average maximum intra-individual genetic divergence in the sexual species Steganacarus magnus and in the parthenogenetic species Platynothrus peltifer was 1.1% and 1.2%, respectively. None of the differences were statistically significant. The cDNA data indicated that the hsp82 sequence is transcribed and intron-free. Likelihood permutation tests indicate that ef-1alpha has undergone recombination in all three studied sexual species and gene conversion in two of the sexual species, but neither process has occurred in any of the parthenogenetic species. No evidence for recombination or gene conversion was found for sexual or parthenogenetic oribatid mite species in the hsp 82 gene. There appears to be no Meselson effect in parthenogenetic oribatid mite species. Presumably, their low genetic divergence is due to automixis, other homogenizing mechanisms or strong selection to keep both the ef-1alpha and the hsp82 gene functioning.

Formation of aminosuccinyl peptides during acidolytic deprotection followed by their transformation to piperazine-2,5-dione derivatives in neutral media.

Prolonged acidic treatment of Boc-Leu-Asp(OBut)-Phe-NH2 with 4N HCl in acetic acid resulted in H-Leu-Asc-Phe-NH2 . HCl(Asc, aminosuccinyl), which transformed partially to cyclo[Leu-Asp(Phe-NH2)] during its purification by column chromatography on silica gel with a mixture of ethyl acetate/pyridine/acetic acid/water = 60:20:6:11, i.e. in neutral medium. Examination of the imide formation was extended to different reaction conditions (no imide derivative was detected in trifluoroacetic acid), to several protected derivatives of L-aspartyl-L-phenylalaninamide and to tripeptides containing an aspartyl residue in the middle position. It was clearly demonstrated that in strongly acidic media the imide derivatives are directly formed from the aspartyl peptides containing a free beta-carboxyl group. The influence of the C-terminal residue was greater than the N-terminal on both the rate of formation of the imide and its further transformation to piperazine-2,5-dione derivative. In aqueous ethanol the X-Asc-Y-NH2 (X, Pro, Leu; Y, Gly, Ala, Val, Phg, Phe) containing N-terminal proline are more readily transformed to piperazine-2,5-dione derivatives, but compared to simple proline dipeptides the rate of this transformation is relatively slow because of the crowdedness of the tricyclic transitional state.

Clonal diversity in the ancient asexual ostracod Darwinula stevensoni assessed by RAPD-PCR.

As Darwinulidae (Ostracoda) are considered to be ancient asexuals with a wide geographical and ecological distribution, they are expected to have accumulated mutations during a long timeframe. However, previous studies on genetic variability suggested a low genetic divergence within the darwinulid species Darwinula stevensoni. Here, overall genotopic diversity of D. stevensoni is estimated with the Random Amplified Polymorphic DNA (RAPD) technique. Using six primers revealing 47 consistently scorable polymorphic loci, substantial clonal diversity within this species is detected. Five of the seven surveyed populations are multiclonal. Moreover, the seven populations have a different clonal composition with almost all of the observed clonal genotypes being restricted to single populations, indicating the absence of a single widespread 'clone'. The observed clonal diversity seems to refute the existence of a widespread general purpose genotype for D. stevensoni. However, in light of previously detected uniformity at functional loci, we reconsider the definition of a GPG. We suggest that it need not imply a genome-wide fixed genotype, but rather consists of a set of ecologically relevant genes.

Arachidonic acid metabolism by perfused ram testis.

1. Arachidonic acid was metabolized by lipoxygenase and prostaglandin synthetase enzymes systems in the perfused ram testis. 2. The major product of the prostaglandin synthetase was 6-keto-PGF1 alpha (6KF). 3. Addition of testosterone resulted in a significant increase in the 6KF. 4. Arachidonic acid (AA) as well as testosterone penetrated the perfused testis. 5. Both 15-HPETE and 15-HETE, the products of the 15-lipoxygenase enzyme, were detected. 6. Addition of 0.1% BSA changed the pattern of the oxidized arachidonic acid metabolism.