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PubMed2000

Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in meningiomas.

OBJECT: In a prospective study, 28 patients with 32 intracranial meningiomas were examined to determine the role of hydrodynamic interaction between tumor and surrounding brain tissue in the pathogenesis of peritumoral brain edema. METHODS: Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular contrast agent used for routine clinical imaging, remains strictly extracellular without crossing an intact blood-brain barrier. Therefore, it is well suited for investigations of hydrodynamic extracellular mechanisms in the development of brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1-weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd-DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5 cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong correlations of edema volume and the maximum distance of contrast spread from the tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively, p < 0.0001) indicated faster effusion in larger areas of edema. CONCLUSIONS: The results of this study show that significant contrast agent effusion from the extracellular space of the tumor into the interstitium of the peritumoral brain tissue is only found in meningiomas with surrounding edema. This supports the hypothesis that hydrodynamic processes play an essential role in the pathogenesis of peritumoral brain edema in meningiomas.

Adult↗
PubMed2002

Temperature and viscosity dependence of the triplet energy transfer process in porphyrin dimers.

The temperature and viscosity dependence of the triplet energy transfer (TET) process in porphyrin dimers has been studied. A zinc porphyrin (donor) and a free base porphyrin (acceptor) are covalently linked together by rigid bridging chromophores at a center-center distance of 25 A. Due to the large donor-acceptor distance and the weakness of the spin forbidden transitions involved, neither direct (through space) electron exchange nor Coulombic mechanisms are expected to contribute to the observed TET process. The results from transient absorption measurements at temperatures between room temperature and 80 K show that TET occurs with unexpectedly high efficiency in the systems connected by fully conjugated bridges and a pronounced temperature dependence of the process is observed. Comparison of the TET efficiencies in dimers connected by different bridging chromophores correlates well with a transfer reaction governed by a through bond exchange (superexchange) interaction. However, in high viscosity media the TET process is dramatically slowed down. This is attributed to a conformational gating of the TET process where the electronic coupling varies strongly with the relative orientation of the donor and the bridging chromophore. Further, the zinc porphyrin donor offers two distinct donor species, T(1A) and T(1B). At room temperature, the TET rate constant of the T(1A) species is about two orders of magnitude larger than for the T(1B) species. The dimers studied are well suited model systems for materials where the rate of the transfer reactions can be changed by external stimuli.

Journal Article↗
PubMed1995

Omega loops: nonregular secondary structures significant in protein function and stability.

Omega (omega-) loops, a nonregular secondary structure found in globular proteins, are characterized by a polypeptide chain that follows a loop-shaped course in three-dimensional space. They do not contain repeating backbone dihedral angles or regular patterns of hydrogen bonding; however, many omega-loops contain a large number of hydrogen bonds, therefore it is not correct to think of omega-loops as structures lacking in hydrogen bonds. omega-Loops are found almost exclusively at the protein surface and exhibit amino acid preferences consistent with this observation. Since the first description of omega-loops in 1986, experiments have been conducted to probe the role of these structures in protein function, stability, and folding. It has become clear that omega-loops are often involved in protein function and molecular recognition. One motif, an omega-loop lid, that is flexible and mobile until substrate or inhibitor is bound and which probably plays a role in one or more steps of enzymatic catalysis, has been described in a variety of enzymes. Because they lack the periodic hydrogen bonding patterns of the regular secondary structures, some omega-loops are well suited for such functional roles in proteins. However, loops with a higher-than-average number of hydrogen bonds or hydrophobic contacts may play roles in protein stability or folding. Rather than determining further geometric definitions of loops, it may be instructional to group them according to their roles in protein structure, i.e., as categories of functional omega-loops, stability omega-loops, and folding omega-loops.

Amino Acids↗
PubMed2005

Simultaneous beam geometry and intensity map optimization in intensity-modulated radiation therapy.

PURPOSE: In current intensity-modulated radiation therapy (IMRT) plan optimization, the focus is on either finding optimal beam angles (or other beam delivery parameters such as field segments, couch angles, gantry angles) or optimal beam intensities. In this article we offer a mixed integer programming (MIP) approach for simultaneously determining an optimal intensity map and optimal beam angles for IMRT delivery. Using this approach, we pursue an experimental study designed to (a) gauge differences in plan quality metrics with respect to different tumor sites and different MIP treatment planning models, and (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around the planning target volume (PTV)--and its use for designing conformal plans. METHODS AND MATERIALS: Our treatment planning models use two classes of decision variables to capture the beam configuration and intensities simultaneously. Binary (0/1) variables are used to capture "on" or "off" or "yes" or "no" decisions for each field, and nonnegative continuous variables are used to represent intensities of beamlets. Binary and continuous variables are also used for each voxel to capture dose level and dose deviation from target bounds. Treatment planning models were designed to explicitly incorporate the following planning constraints: (a) upper/lower/mean dose-based constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within this constrained solution space, five optimization strategies involving clinical objectives were analyzed: optimize total intensity to PTV, optimize total intensity and then optimize conformity, optimize total intensity and then optimize homogeneity, minimize total dose to critical structures, minimize total dose to critical structures and optimize conformity simultaneously. We emphasize that the objectives that include optimizing conformity make use of the critical-normal-tissue-ring. Three tumor sites: head-and-neck, pediatric brain, and prostate are used for comparison. RESULTS: The critical-normal-tissue-ring acts as a good device for enforcing conformity. Trends in the characteristics and quality of plans resulting from each model were observed. Attempts to reduce dose to critical structures tend to worsen PTV conformity (1.542 to 3.092) and homogeneity (1.223 to 1.984), depending on the relative size and spatial distance of the critical structures to the PTV. When the critical structures are relatively small compared with the PTV (as in the case for the pediatric brain tumor, where each is less than 15% in volume), dose reduction to critical structures is accompanied by much worse scores in conformity (2.482) and homogeneity (1.984). When the critical structures are larger, as in the case of head-and-neck (approximately 50%), the conformity and homogeneity deterioration is less significant (1.542 and 1.239, respectively). There is a clear tradeoff between homogeneity, conformity, and minimum dose to organs at risk (OARs). For head-and-neck and pediatric brain tumor, the model that minimizes total dose to critical structures and optimizes conformity simultaneously offers a compromise among these factors, resulting in reduced critical structure dose with conformal and homogeneous plans. In the prostate case, the tumor is smaller than the two large nearby critical structures, and all models provide very homogeneous PTV dose distribution. However, minimizing dose to critical structures worsens conformity, as it spreads the radiation to the area surrounding the PTV. The maximum dose to the critical structures also increases slightly. Compared with plans used in the clinic which generally have uniformly spaced beam angles, the optimal clinically acceptable plans obtained via the methods herein do not have equispaced beams. The optimal beam angles returned appear to be nonintuitive, and depend on PTV size and geometry and the spatial relationship between the tumor and critical structures. CONCLUSIONS: The MIP model described allows simultaneous optimization over the space of beamlet fluence weights and beam and couch angles. Based on experiments with tumor data, this approach can return good plans that are clinically acceptable and practical. This work distinguishes itself from recent IMRT research in several ways. First, in previous methods beam angles are selected before intensity map optimization. Herein, we employ 0/1 variables to model the set of candidate beams, and thereby allow the optimization process itself to select optimal beams. Second, instead of incorporating dose-volume criteria within the objective function as in previous work, herein, a combination of discrete and continuous variables associated with each voxel provides a mechanism to strictly enforce dose-volume criteria within the constraints. Third, using the construct of critical-normal-tissue-ring within the objective function can enhance the achievement of conformal plans. Based on the three tumor sites considered, it appears that volume and spatial geometry with respect to the PTV are important factors to consider when selecting objectives to optimize, and in estimating how well suited a particular model is for achieving a specified goal.

Algorithms↗
PubMed1998

[External stabilization of the metacarpal bones II to V. Anatomic-clinical study].

The four ulnar metacarpal bones are connected to each other at their proximal and distal ends by strong ligaments. The second and fifth metacarpal bones are the frame of the metacarpus. Surgically, this is of great importance. A fracture of these two bones often requires stabilization, whereas a fracture of the third and fourth metacarpal bones with intact ligaments seldom requires surgery except in cases of severe fragment dislocation. Using external fixation for these purposes it seems to be of utmost interest to define secure pintracks through the soft tissue. In an anatomical study using formalin fixed specimen it clearly could be demonstrated that the second and fifth metacarpal bones are best suited for external fixation. The second metacarpal bone should always be fixed from the radial side because the fixator pins can be inserted within a wide range of angles without the risk of violating the extensor tendons. Variations of tendons and ligaments are seldom located on the radial side of the second metacarpal bone and therefore, finger movement is unhindered after pin application. A similar consideration is true for the fifth metacarpal bone which should be fixed from the ulnar side. With respect to the extensor tendon which covers the entire dorsal surface of the fifth metacarpal bone, the angle of the pins should be 40 to 90 degrees from the dorsal side. For the third metacarpal bone, fixation from the radial side is preferable taking topographical and biomechanical considerations into account. The radial corridor to the fourth metacarpal bone is smaller than the ulnar corridor, but there is much less morphological variability of the extensor tendons than on the ulnar side where strong fibres often cross the fourth intermetacarpal space. Because in the proximal fourth of the metacarpal bones the tendons are located very close to each other, a small skin incision and preparation to the bone surface is advisable to exclude violation of the tendons when inserting fixator screws into the third and fourth metacarpal bones. Using formalin-alcohol fixed cadaver specimens for the research gives an idea of the anatomical situation in the dorsal metacarpus but cannot answer the question whether the tendons in the lax subcutaneous tissue of the living will automatically slip aside when the fixator pin approaches. This should be item to subsequent studies in fresh frozen specimens and follow-up studies in a larger amount of patients treated with external fixation.

External Fixators↗
PubMed1984

A chamber preserving cellular function of the isolated rabbit retina suited for extracellular and intracellular recordings.

The isolated retina of rabbit lies on nylon tissue fixed in a ring, which is placed in a chamber. The lower side of the retina, by choice the receptor or ganglion cell side, is superfused by a plasma saline mixture kept at 35 degrees C. At the upper side of the retina, warm humidified oxygen is added. The two sides are isolated from each other by a rubber joint. ERGs with b waves of about 1 mV indicate a good function of retinal cells. The receptor potential is recorded extracellularly between an intraretinal microelectrode and a reference electrode at the receptor side (amplitude typically about 300 microV). The few intracellular records were hyperpolarizations to white and red light with an initial overshoot and a plateau.

Action Potentials↗
PubMed1998

Molecular and biotechnological aspects of microbial proteases.

Proteases represent the class of enzymes which occupy a pivotal position with respect to their physiological roles as well as their commercial applications. They perform both degradative and synthetic functions. Since they are physiologically necessary for living organisms, proteases occur ubiquitously in a wide diversity of sources such as plants, animals, and microorganisms. Microbes are an attractive source of proteases owing to the limited space required for their cultivation and their ready susceptibility to genetic manipulation. Proteases are divided into exo- and endopeptidases based on their action at or away from the termini, respectively. They are also classified as serine proteases, aspartic proteases, cysteine proteases, and metalloproteases depending on the nature of the functional group at the active site. Proteases play a critical role in many physiological and pathophysiological processes. Based on their classification, four different types of catalytic mechanisms are operative. Proteases find extensive applications in the food and dairy industries. Alkaline proteases hold a great potential for application in the detergent and leather industries due to the increasing trend to develop environmentally friendly technologies. There is a renaissance of interest in using proteolytic enzymes as targets for developing therapeutic agents. Protease genes from several bacteria, fungi, and viruses have been cloned and sequenced with the prime aims of (i) overproduction of the enzyme by gene amplification, (ii) delineation of the role of the enzyme in pathogenecity, and (iii) alteration in enzyme properties to suit its commercial application. Protein engineering techniques have been exploited to obtain proteases which show unique specificity and/or enhanced stability at high temperature or pH or in the presence of detergents and to understand the structure-function relationships of the enzyme. Protein sequences of acidic, alkaline, and neutral proteases from diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology.

Amino Acid Sequence↗
PubMed1997

[Evaluation of the antinociceptive effect of xylazine after epidural administration in dogs under general anesthesia with isoflurane].

Seven dogs anaesthetized with isoflurane in oxygen (1.9 Vol.-% ET) were examined before and after lumbosacral injection of xylazine (0.25 mg/kg) into the epidural space. Over a 240 minute period the dogs were first stimulated in a visceral manner (extension of the colon descendens by a balloon-catheter) every 15 minutes. In a second part, the dogs were stimulated somatically by pressure to the interdigital skin of a hindlimb. Heart rate and mean arterial pressure were used to determine the analgesic properties of epidurally injected xylazine. Furthermore, plasma xylazine concentration was controlled in both series. Before epidural anaesthesia, heart rate and mean arterial pressure increased during stimulation significantly in both groups. After epidural injection of xylazine, hemodynamic reactions were distinctly diminished, in the somatically stimulated group more than in the viscerally stimulated group. Up to 30 minutes after epidural injection, plasma xylazine concentrations of about 100 ng/ml were found in both groups. Up to 60 minutes after epidural injection, plasma xylazine concentrations of more than 60 ng/ml still were found. From the 120th minute on, xylazine concentration decreased below 30 ng/ml. From these results, it can be concluded that there is a well-suited analgesic effect of epidurally applicated xylazine for approximately 240 minutes.

Analgesia↗
PubMed2006

Mapping age-related elasticity changes in porcine lenses using bubble-based acoustic radiation force.

Bubble-based acoustic radiation force aims to measure highly localized tissue viscoelastic properties. In the current investigation, acoustic radiation force was applied to laser-induced bubbles to measure age-related changes in the spatial distribution of elastic properties within in vitro porcine lenses. A potential in vivo technique to map lens elasticity is crucial to understanding the onset of presbyopia and develop new treatment options. Bubble-based acoustic radiation force was investigated as a technique to measure the spatial elasticity distribution of the lens in its natural state without disrupting the lens capsule. Laser-induced optical breakdown (LIOB) generated microbubbles in a straight line across the equatorial plane of explanted porcine lenses with 1mm lateral spacing. Optical breakdown occurs when sufficiently high threshold fluence is attained at the focus of femtosecond pulsed lasers, inducing plasma formation and bubble generation. A two-element confocal ultrasonic transducer applied 6.5 ms acoustic radiation force-chirp bursts with the 1.5 MHz outer element while monitoring bubble position within the lens using pulse-echoes with the 7.44 MHz inner element. A cross-correlation method was used to measure bubble displacements and determine exponential time constants of the temporal responses. Maximum bubble displacements are inversely proportional to the local Young's modulus, while time constants are indicative of viscoelastic properties. The apparent spatial elasticity distributions in 41 porcine lenses, ranging from 4 months to 5 years in age, were measured using bubble-based acoustic radiation force. Bubble displacements decrease closer to the porcine lens center, suggesting that the nucleus is stiffer than the cortex. Bubble displacements decrease with increasing lens age, suggesting that porcine lenses become stiffer with age. Bubble-based acoustic radiation force may be well-suited as a potential in vivo technique to spatially map elastic properties of the lens and guide therapeutic procedures aimed at restoring accommodation.

Aging↗
PubMed1998

Determining the number of independent sources of the EEG: a simulation study on information criteria.

The separation of signal and noise is an important problem in the analysis of EEG and MEG data. Furthermore, many source localisation strategies need the number of independent signal components as input parameter (e.g., dipole fit, multiple signal classification). Information criteria offer a relatively objective way to separate the space spanned by the principal components of the data covariance matrix into a signal and a noise part. Eighteen such criteria were extensively tested by simulations. They differ with respect to the statistical model of the data, the assumptions on the noise, and the correction term. In the simulations, different dipole sources were used to generate EEG, which was then distorted by Gaussian correlated or uncorrelated noise. The noise level, the accuracy of the noise covariance matrix used by the criteria, the numbers of channels and time samples, and the stochastic or deterministic nature of the source waveforms were varied. The performance of the criteria was very variable. For each criterion, limits for the noise level and the relative inaccuracy of the noise covariance matrix could be established. Taking more channels or time steps did increase the criteria's ability to tolerate noise, but at the same time, made them more vulnerable to inaccuracies in the (estimated) noise covariance matrices. Out of the eighteen criteria investigated, we recommend two criteria that are best suited for the cases of (1) high noise and accurate covariances and (2) low noise and less accurate covariances.

Artifacts↗
PubMed2006

FCMAC-Yager: a novel Yager-inference-scheme-based fuzzy CMAC.

The cerebellum is a brain region important for a number of motor and cognitive functions. It is able to generate error correction signals to drive learning and for the acquisition of memory skills. The cerebellar model articulation controller (CMAC) is a neural network inspired by the neurophysiologic theory of the cerebellum and is recognized for its localized generalization and rapid algorithmic computation capabilities. The main deficiencies in the basic CMAC structure are: (1) it is difficult to interpret the internal operations of the CMAC network and (2) the resolution (quantization) problem arising from the partitioning of the input training space. These limitations lead to the synthesis of a fuzzy quantization technique and the mapping of a fuzzy inference scheme onto the CMAC structure. The discrete incremental clustering (DIC) technique is employed to alleviate the quantization problem in the CMAC structure, resulting in the fuzzy CMAC (FCMAC) network. The Yager inference scheme (Yager), which possesses firm fuzzy logic foundation and maps closely to the logical implication operations in the classical (binary) logic framework, is subsequently mapped onto the FCMAC structure. This results in a novel fuzzy neural architecture known as thefuzzy cerebellar model articulation controller-Yager (FCMAC-Yager) system. The proposed FCMAC-Yager network exhibits learning and memory capabilities of the cerebellum through the CMAC structure while emulating the human way of reasoning through the Yager. The new FCMAC-Yager network employs a two-phase training algorithm consisting of structural learning based on the DIC technique and parameter learning using hebbian learning (associative long-term potentiation). The proposed FCMAC-Yager architecture is evaluated using an extensive suite of real-life applications such as highway traffic-trend modeling and prediction and performing as an early warning system for bank failure classification and medical diagnosis of breast cancer. The experimental results are encouraging.

Algorithms↗
PubMed1993

RNA based evolutionary optimization.

The notion of an RNA world has been introduced for a prebiotic scenario that is dominated by RNA molecules and their properties, in particular their capabilities to act as templates for reproduction and as catalysts for several cleavage and ligation reactions of polynucleotides and polypeptides. This notion is used here also for simple experimental assays which are well suited to study evolution in the test tube. In molecular evolution experiments fitness is determined in essence by the molecular structures of RNA molecules. Evidence is presented for adaptation to environment in cell-free media. RNA based molecular evolution experiments have led to interesting spin-offs in biotechnology, commonly called 'applied molecular evolution', which make use of Darwinian trial-and-error strategies in order to synthesize new pharmacological compounds and other advanced materials on a biological basis. Error-propagation in RNA replication leads to formation of mutant spectra called 'quasispecies'. An increase in the error rate broadens the mutant spectrum. There exists a sharply defined threshold beyond which heredity breaks down and evolutionary adaptation becomes impossible. Almost all RNA viruses studied so far operate at conditions close to this error threshold. Quasispecies and error thresholds are important for an understanding of RNA virus evolution, and they may help to develop novel antiviral strategies. Evolution of RNA molecules can be studied and interpreted by considering secondary structures. The notion of sequence space introduces a distance between pairs of RNA sequences which is tantamount to counting the minimal number of point mutations required to convert the sequences into each other. The mean sensitivity of RNA secondary structures to mutation depends strongly on the base pairing alphabet: structures from sequences which contain only one base pair (GC or AU are much less stable against mutation than those derived from the natural (AUGC) sequences. Evolutionary optimization of two-letter sequences in thus more difficult than optimization in the world of natural RNA sequences with four bases. This fact might explain the usage of four bases in the genetic language of nature. Finally we study the mapping from RNA sequences into secondary structures and explore the topology of RNA shape space. We find that 'neutral paths' connecting neighbouring sequences with identical structures go very frequently through entire sequence space. Sequences folding into common structures are found everywhere in sequence space.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed2005

Quantitative assessment of pleural effusion in critically ill patients by means of ultrasonography.

OBJECTIVE: To assess the ability of ultrasonography to identify the presence and assess the volume of pleural effusion in the intensive care unit setting. DESIGN: Prospective descriptive clinical study. SETTING: Medical-surgical intensive care unit of a teaching hospital. PATIENTS: Initial study group (group I) consisted of 97 patients (mean [+/-SD] Simplified Acute Physiology Score II, 40 +/- 14) with clinically suspected pleural effusion. Fifty-one patients were mechanically ventilated and 55 patients underwent a unilateral or bilateral thoracentesis (58 procedures). All patients underwent supine chest radiography and pleural ultrasonography at bedside. The testing group (group II) consisted of 19 additional patients (17 under ventilation) who underwent thoracentesis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal interpleural distance was measured at the base and apex of the pleural space, at both end-expiration and end-inspiration. In group I, interpleural distances were compared to actual volume of fluid in the subset of patients who underwent a complete thoracentesis (n = 49). Prediction of the volume of pleural effusion was subsequently tested prospectively in group II (25 complete thoracenteses). Portable chest radiography and pleural ultrasonography yielded discordant results for 47 patients (48%) in the diagnosis of pleural effusion. The expiratory interpleural distance measured at the thoracic base with ultrasonography was significantly correlated with the volume of fluid (p < .0001; coefficient of determination: right, 0.78; left, 0.51). A pleural effusion > or =800 mL was predicted when this distance was >45 mm (right) or >50 mm (left), with a sensitivity of 94% and 100% and a specificity of 76% and 67%, respectively. In group II, the mean bias between the predicted and observed volumes of pleural effusion determined by thoracentesis was 24 +/- 355 mL, and this decreased to 28 +/- 146 mL for the prediction of pleural effusion <1400 mL. CONCLUSIONS: Bedside ultrasonography is well suited for the quantitative assessment of unloculated pleural effusions in intensive care unit patients.

Female↗
PubMed2005

Bilateral hearing loss following a retrobulbar block.

PURPOSE: Regional anesthesia is the most commonly used ophthalmological anesthetic technique in Canada and the United States. Brainstem anesthesia is not an uncommon complication of retrobulbar blocks. Anesthesiologists are a prominent element in the ophthalmology suite, in part due to the complications possible with regional anesthesia. This is the first reported case of complete bilateral hearing loss following a retrobulbar block. CLINICAL FEATURES: A 46-yr-old male with type 1 diabetes mellitus presenting for ophthalmological surgery had a retrobulbar block performed by the ophthalmologist. Local anesthetic was injected through a 25 G, 1.5 inch needle, entering the orbit inferiorly on the temporal third of the lower lid. Shortly after the block was completed the patient experienced sudden hearing loss. On examination the hearing loss appeared to be complete and bilateral. The patient was alert and oriented; the remainder of the cranial nerve exam was normal. The patient's hearing loss gradually improved and three hours after the block his hearing had subjectively returned to normal. CONCLUSION: Brainstem anesthesia is not a rare complication of regional anesthesia for ophthalmological surgery. Symptoms include confusion, mental agitation, dizziness, blurred vision or blindness, ophthalmoplegia, deafness, tinnitus, dysphagia, dysarthria, respiratory depression to apnea, and/or limb paralysis. A connection between the subdural and subarachnoid spaces and the optic sheath exists. The effect on the central nervous system depends upon the amount of local anesthetic injected and the area to which it spreads.

Anesthesia, Conduction↗
PubMed2003

The simultaneous in vivo perilymphatic perfusion of avian auditory and vestibular end organs.

Perilymphatic perfusion is a method that allows the control of fluid parameters throughout the perilymphatic space of the inner ear. We have evaluated a new method for continuous perilymphatic perfusion of the auditory and vestibular end organs with artificial perilymph (APL) in chickens. Perfusate temperature (39.0 degrees C), pH (7.4), osmolarity (328 +/- 2 mosm), and flow rate (2 microl/min) were carefully controlled. Independent functional tests of vestibular and auditory sensory systems were made throughout perfusion periods by recording peripheral compound action potentials (CAPs). The recordings provided a means of monitoring the status of hair cell transduction, synaptic transmission and collective primary afferent activation in response to auditory or vestibular gravity receptor stimuli. Auditory and vestibular responses were stable during perfusion. No significant changes occurred in vestibular or auditory CAP amplitudes during long-term perfusion (50-80 min, n=7) and responses remained stable in one animal perfused for over 3 h. To our knowledge, there have been no reports evaluating vestibular function under these conditions. This technique enables us to systematically study receptor pharmacology in the peripheral vestibular and auditory systems virtually simultaneously in vivo. The model is well suited for use in the study of the pharmacology and toxicology of inner ear sensory systems.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1987

Estriol in the postmenopause.

Estriol is regarded as a mild and brief-acting hormone and, as such, has been prescribed for over four decades as a therapeutic agent for postmenopausal women with urogenital disorders. The dosages administered and the results obtained have varied considerably in earlier studies. Pharmacokinetic studies of estriol and the effects induced on the target tissues have been contradictory. The pharmacokinetics of unconjugated estriol after vaginal and oral medication was studied. One mg estriol applied vaginally resulted in plasma estriol concentrations similar to those obtained when 10 mg estriol was given orally. The clinical importance of the enterohepatic recirculation on plasma estriol concentrations after orally administered estriol was demonstrated. Factors that influence the pharmacokinetics of estriol are the time of estriol administration, fat-rich food, as well as the spacing of meals. Thus, the enterohepatic recirculation of estriol affects the plasma estriol elevation time and thereby the potency of estriol. The enterohepatic recirculation seemed to be less important in vaginal administration of estriol as the first liver passage is circumvented. Instantaneous and substantial conjugation of estriol in the liver is thereby avoided. By cytological assessment of the vaginal and the urethral epithelium in 40 patients treated in a geriatric hospital, the commonly recommended maintenance dosages of estriol (0.5 mg vaginally 1-2 times per week) were found to be too low to cure vaginal and urethral atrophy in very old women. This study suggests that estriol is a biologically potent estrogen by both oral and vaginal administration. The route and the time of administration, the food habits as well as the dosages given are factors which contribute to the estrogenicity of estriol. In clinical use, vaginal treatment seems preferable because the first liver passage is avoided. Vaginal administration allows a more standardized estriol regimen, while the oral treatment is more difficult to tailor for suit most women's needs.

Administration, Oral↗
PubMed2002

Assessment of age-associated cognitive deficits in rats: a tricky business.

Every living organism is affected by changes as a consequence of aging. Perhaps the most appropriate concept to describe age-related changes is that of 'functional age'. Laboratory rodents are especially suited as models of cognitive aging in humans, because they have a relatively short life-span and because many tests have been developed to investigate their cognitive performance. Examples from studies using the Morris water escape task were chosen to describe and discuss factors which must be considered before drawing conclusions about age-related cognitive deficits. In particular, the roles of rearing and housing conditions, of sensorimotor impairments, and of motivational differences between young and old rats are discussed. Conclusions are drawn about how aging studies should be conceived and performed.

Aging↗
PubMed2003

Atmospheric transport of mold spores in clouds of desert dust.

Fungal spores can be transported globally in clouds of desert dust. Many species of fungi (commonly known as molds) and bacteria--including some that are human pathogens--have characteristics suited to long-range atmospheric transport. Dust from the African desert can affect air quality in Africa, Europe, the Middle East, and the Americas. Asian desert dust can affect air quality in Asia, the Arctic, North America, and Europe. Atmospheric exposure to mold-carrying desert dust may affect human health directly through allergic induction of respiratory stress. In addition, mold spores within these dust clouds may seed downwind ecosystems in both outdoor and indoor environments.

Air Microbiology↗