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Biomedical subjects

E Horn

Publications and source records attributed to E Horn.

At least 19 recordsLinked to original sources

Morphometric investigations of sensory vestibular structures in tadpoles (Xenopus laevis) after a spaceflight: implications for microgravity-induced alterations of the vestibuloocular reflex.

In lower vertebrates, gravity deprivation by orbital flights modifies the vestibuloocular reflex. Using the amphibian Xenopus laevis, the experiments should clarify to which extent macular structures of the labyrinth are responsible for these modifications. In particular, the shape of otoconia and number and size of sensory macular cells expressing CalBindin were considered. CalBindin is common in mature sensory cells including vestibular hair cells and is probably involved in otoconia formation. Two developmental stages were used for this study: stage 26/27 embryos, which were unable to perform the roll-induced vestibuloocular reflex (rVOR) at onset of microgravity, and stage 45 tadpoles, which had already developed the reflex. The main observations were that the developmental progress of the animals was not affected by microgravity; that in the young tadpole group with normal body shape the rVOR was not modified by microgravity, while in the older group with microgravity experience, the rVOR was augmented; and that significant effects on the shape of otoconia and on the number and size of CalBindin-expressing cells of the labyrinthine maculae cells were absent. In addition, behavioural data were never significantly correlated with morphological features of macular structures such as size and number of CalBindin-expressing cells. It is postulated that mechanisms of vestibular adaptation to microgravity during early development are probably based on mechanisms located in central structures of the vestibular system.

Adaptation, Physiological↗

Nicotine and smoker status moderate brain electric and mood activation induced by ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist.

As the increased smoking prevalence in schizophrenics may be interpreted as an adaptive response to an underlying biological defect, investigations into nicotine's actions within N-methyl-d-aspartate (NMDA) antagonist drug models of schizophrenia may improve our understanding of the role of glutamatergic neurotransmission in initiating and maintaining nicotine dependence in this disorder. In this double-blind, placebo-controlled, randomized study, the electroencephalographic (EEG) and subjective response to a sub-psychotomimetic intravenous dose of the NMDA antagonist ketamine was examined in 20 regular smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain activation (decreased slow wave power) and sedation (decreased fast wave power and frequency), which were not affected by nicotine pretreatment and were evident only in non-smokers. Ketamine increased a number of self-report indices of subjective arousal, some of which were attenuated and potentiated by nicotine in smokers and non-smokers, respectively. These findings suggest that long-term (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine exposure may alter NMDA receptor-mediated arousal and mood systems in a way that promotes nicotine dependence in smokers, and addresses neurobiological deficiencies in smokers with schizophrenia.

Adult↗

The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

Double-Blind Method↗

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3 g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3 g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (micro g). The contrary physiological and behavioral results indicate a facilitation of 1 g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of micro g or 3 g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Adaptation, Physiological↗

Adaptation of the macular vestibuloocular reflex to altered gravitational conditions in a fish (Oreochromis mossambicus).

Young fish (Oreochromis mossambicus) were exposed to microgravity (micro g) for 9 to 10 days, or to hypergravity (hg) for 9 days. For several weeks after termination of micro g and hg, the roll-induced static vestibuloocular reflex (rVOR) was recorded. In stage 11/12-fish, the rVOR amplitude (angle between the maximal up and down movement of an eye during a complete 360 degree lateral roll) of micro g-animals increased significantly by 25% compared to 1 g-controls during the first post-flight week but decreased to the control level during the second post-flight week. Microgravity had no effect in stage 14/16 fish on the rVOR amplitude. After 3 g-exposure, the rVOR amplitude was significantly reduced for both groups compared to their 1 g-controls. Readaptation to 1 g-condition was completed during the second post-3 g week. We postulate a critical period during which the development of the macular vestibuloocular reflex depends on gravitational input, and which is limited by the first appearance of the rVOR. At this period of early development, exposure to microgravity sensitizes the vestibular system while hypergravity desensitizes it.

Adaptation, Physiological↗

Time courses of aspartate and glutamate concentrations in the focus area during penicillin induced epileptiform activity in awake rats.

1. In 16 awake rats, the time courses of cortical aspartate (ASP) and glutamate (GLU) concentrations were investigated before, during and after penicillin-induced epileptiform activity (PCN-EA). The amino acids were collected by means of the microdialysis technique from a site within the motor cortex located close to the PCN focus. PCN-EA was recorded by means of 12 cortical electrodes. 2. The median time courses of ASP and GLU concentrations demonstrated no relation to the time course of PCN-EA. In contrast, the analysis of individual time courses revealed three response types for both ASP and GLU which could not be related to specific sites within the motor cortex. 3. The ASP concentration was i) not affected by epileptiform activity (8 of 16 rats), ii) changed synchronously with the PCN-EA (3 of 16), or iii) increased transiently or in a long-lasting manner during or after disappearance of PCN-EA (5 of 16). 4. The GLU concentration was i) not effected or only slightly affected by epileptiform activity (5 of 16), ii) decreased strongly during the activity (7 of 16), or iii) increased during the epileptiform activity (4 of 16). 5. If all rats were taken into account, the overall observation was absence of a uniform correlation type between the time courses of ASP and GLU concentrations; i.e. epileptiform activity affects the time courses of ASP and GLU concentrations in an independent manner. 6. These results demonstrate that consideration of median values alone can mask significant effects of epileptiform activity on the biochemistry of the brain in individual animals. The study also shows that a consideration of individual time courses of physiological and biochemical parameters is mandatory for the understanding of basic mechanisms of epilepsy. The results support the hypothesis about the activation of neuroprotective mechanisms by epileptiform activity.

Animals↗

Functional regeneration of a gravity sensory system during development in an insect (Gryllus bimaculatus).

The efficiency of the regenerated cercal gravity sensory system was investigated in adult crickets (Gryllus bimaculatus). Regeneration was induced by amputations of cerci during different periods of development. Numbers of gravity-sensitive (clavate) sensilla on regenerated and intact cerci were identical if amputations were performed up to four times before the 6th instar. If older instars were included, regenerated cerci had fewer clavate sensilla than intact cerci. Compensatory head responses induced by stimulation of either regenerated or intact gravity sense organs were identical if cerci were amputated up to three times. However, four or more amputations caused weaker responses in the regenerated than in the intact sense organs. These experiments make the existence of a sensitive period during development of the cercal gravity sensory system unlikely. They support the postulation that functional regeneration is influenced by neuroplastic processes and proprioceptive gravity sensitive systems.

Aging↗

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma.

To test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P< 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P< 0.001), and serum beta2-microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P< 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P< 0.001, log rank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.

Adult↗

Altered gravitational forces affect the development of the static vestibuloocular reflex in fish (Oreochromis mossambicus).

Young fish (Oreochromis mossambicus) were exposed to microgravity (micro g) for 9 to 10 days during space missions STS-55 and STS-84, or to hypergravity (hg) for 9 days. Young animals (stages 11-12), which had not yet developed the roll-induced static vestibuloocular reflex (rVOR) at micro g- and hg-onset, and older ones (stages 14-16), which had already developed the rVOR, were used. For several weeks afterwards, the rVOR was recorded after termination of mug and hg. Here are the main results: (1) In the stage 11-12 fish, the rVOR gain (response angle/roll angle) measured for roll angles 15 degrees, 30 degrees, and 45 degrees was not affected by microgravity if animals were rolled from the horizontal to the inclined posture, but was increased significantly if animals were rolled in the opposite manner. The rVOR amplitude (maximal eye movement during a complete 360 degrees roll) of micro g animals increased significantly by 25% compared to 1g controls during the first postflight week, but decreased to the control level during the second postflight week. Microgravity had no effect in stage 14-16 fish on either rVOR gain or amplitude. (2) After 3g exposure, both rVOR gain and amplitude were significantly reduced for both stage 11-12 and stage 15 fish. One g readaptation was completed during the second post-3g week. Hypergravity at 2 or 2.5 g had no effect. (3) Hypergravity at all three levels tested (2g, 2.5g, and 3g) accelerated the morphological development as assessed by external morphological markers. Exposure to micro g- or 3g-periods during an early developmental period modifies the physiological properties of the neuronal network underlying the static rVOR; in susceptible developmental stages, these modifications include sensitization by microgravity and desensitization by hypergravity.

Animals↗

Features of vestibuloocular reflex modulations induced by altered gravitational forces in tadpoles (Xenopus laevis).

In Xenopus laevis tadpoles, we studied the static vestibuloocular reflex (rVOR) in relation to modifications of the gravitational environment to find basic mechanisms of how altered gravitational forces (AGF) affect this reflex. Animals were exposed to microgravity during space flight or hypergravity (3g) for 4 to 12 days. Basic observations were that (1)the development of the rVOR is significantly affected by altered gravitational conditions, (2) the duration of 1g-readaptation depends on the strength of the test stimulus, (3) microgravity induces malformations of the body which are related to the rVOR depression. Future studies are based on the hypotheses (1) that the vestibular nuclei play a key roll in the adaptation to AGF conditions, (2) that the stimulus transducing systems in the sense organ are affected by AGF conditions, and (3) that fertilized eggs will be converted to normal adults guided by physiological and morphological set points representing the genetic programs. Developmental retardation or acceleration, or otherwise occurring deviations from standard development during embryonic and postembryonic life will activate genes that direct the developmental processes towards normality.

Adaptation, Physiological↗

Subarachnoid sufentanil for early postoperative pain management in orthopedic patients: a placebo-controlled, double-blind study using spinal microcatheters.

BACKGROUND: Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative. METHODS: Eighty patients randomly received a subarachnoid injection of 10 microg sufentanil, 5 mg bupivacaine, 2.5 microg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 microg sufentanil over 24 h. RESULTS: All drugs provided excellent pain relief within 15 min after injection, lasting 128 +/- 61 min with sufentanil, 146 +/- 74 min with bupivacaine, and 167 +/- 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100-115 min) than after the first injection (198 +/- 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 +/- 167 ng/ml) but were at the level of detection in the plasma. CONCLUSIONS: Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.

Adult↗

Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis.

BACKGROUND: Myeloma-induced bone loss is related to an uncoupling of bone formation and bone resorption. The aim of the present study was to assess the potential clinical value of biochemical markers of bone formation in the work up of patients with plasma cell dyscrasias. METHODS: Serum total alkaline phosphatase, bone-specific alkaline phosphatase (BAP), and osteocalcin (OC) were measured in 43 patients with newly diagnosed multiple myeloma (MM), in 40 patients with monoclonal gammopathy of undetermined significance (MGUS), in 40 patients with untreated benign vertebral osteoporosis (OPO), and in 48 healthy adults. RESULTS: In MM and MGUS patients, serum BAP, but not serum OC, was lower than in healthy controls (P<0.05). Serum OC was higher in patients with OPO than in healthy controls (P<0.05). The strongest associations between markers were found in OPO patients and in healthy adults. MM patients with early-stage disease or without detectable osteolysis had decreased serum BAP values (P<0.05). Serum OC was higher in MM patients with stage III disease (P<0.05) than in healthy controls. MM patients with OPO-like bone involvement had lower BAP values than sex- and age-matched MGUS patients with OPO-like bone involvement and patients with benign OPO (P<0.05). CONCLUSIONS: In patients with plasma cell dyscrasias, serum BAP, rather than serum OC, appears to reflect a suppressed bone formation rate and may be helpful in the differentiation between benign and myeloma-induced OPO. However, the overall clinical use of biochemical markers of bone formation in patients with plasma cell dyscrasia appears limited.

Adult↗

Syntheses and structural analysis of 10-monoxy- and -dioxy-5-N-substituted iminothianthrene derivatives and the stereochemical change on their sulfur atom under acidic and thermal conditions.

5-(N-p)-Toluenesulfonyl)iminothianthrenes, whose sulfur atoms are oxidized to a sulfoxide or sulfone at the 10-position, were hydrolysed readily in high yield to N-unsubstituted-sulfilimines by using concentrated H2SO4. During hydrolysis, 10-monoxy-5-N-unsubstituted-sulfilimines were obtained as a separable mixture of the cis and trans isomers. The stereochemical interconversion of these compounds was studied under both hydrolytic and thermal conditions and their structures were elucidated by using X-ray crystallography.

Journal Article↗

(Benzoxazole-2-thiolato-S)(benzoxazole-2-thione-S)bis(triphenylphosph ine)copper(I).

The Cu atom in [Cu(C(7)H(4)NOS)(C(7)H(5)NOS)(C(18)H(15)P)(2)] is tetrahedrally coordinated by a P(2)S(2) donor set. One S atom is derived from neutral benzoxazole-2-thione and the other from the deprotonated form of the ligand. The two sulfur ligands are connected via an N-H.N interaction, leading to the formation of an eight-membered ring.

Journal Article↗

Effect of first treatment with aminobisphosphonates pamidronate and ibandronate on circulating lymphocyte subpopulations.

Up to 60% of patients receiving their first infusion of the bisphosphonate pamidronate experience an acute-phase reaction. In this study, we used flow cytometry to determine the effects of pamidronate treatment on circulating lymphocyte subpopulations, and we investigated whether pamidronate and ibandronate treatment affect lymphocyte subpopulations differently. Twenty patients received a pamidronate infusion, 20 patients received intravenously injected ibandronate, and 10 controls received a clodronate infusion. Pamidronate treatment was followed by a significant increase in median body temperature at the 10-hour measurement and a significant decrease in counts of circulating lymphocytes, natural killer cells, T cells, and CD4+ and CD8+ T-cell subsets. Ibandronate treatment did not affect median body temperature, and it was associated at the 10-hour measurement with maximum increases in total lymphocyte count, B cells, T cells, and CD4+ and CD8+ T-cell subsets. Thus, there is a substantial difference in the hematologic response to initial treatments with pamidronate and ibandronate. Clodronate treatment did not induce changes in body temperature or significantly affect the number of circulating T cells and NK cells. The reduction in lymphocyte subsets after initial pamidronate therapy might be mediated by the release of tumor necrosis factor alpha, whose source in the acute-phase reaction could be T cells.

Adult↗

Self-Assembly of a Radially Functionalized Hexagonal Molecule: Hexakis(4-hydroxyphenyl)benzene.

Two different porous hydrogen-bonded networks are formed by self-assembly of the radially substituted host 1. In the network of type A, formed by 1 small middle dot4 Et(2)O, all OH groups of 1 are involved in hydrogen bonding, and the molecular sheets are stacked without translation to generate extended channels that accommodate the Et(2)O molecules. Four OH groups of 1 are involved in the type B network of 1 small middle dot4 DMF, and lateral translation of the sheets in an ABAB sequence generates large chambers, each of which contains four DMF molecules.

Journal Article↗