bluuebunny/crossref_metadata_2025 huggingface dataset:
Ruboxistaurin, a Protein Kinase C β Inhibitor, as an Emerging Treatment for Diabetes Microvascular Complications
Authors: Joy Scott V , Scates Ann C , Bearelly Srilaxmi , Dar Moahad , Taulien Christina A , Goebel Jason A , Cooney Michael J
Published: September 2005

OBJECTIVE:

To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) β, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications.

DATA SOURCES:

Primary literature was obtained via a MEDLINE search (1966–August 2004) and through review of pertinent abstracts and presentations at major medical meetings.

STUDY SELECTION AND DATA EXTRACTION:

Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed.

DATA SYNTHESIS:

PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC β 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC β, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy.

CONCLUSIONS:

Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.
Interferon Gamma-1b in the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Pacanowski Michael A , Amsden Guy W
Published: September 2005

Objective:

To examine the clinical aspects of idiopathic pulmonary fibrosis (IPF) and the efficacy and safety of interferon gamma-1b (IFNγ−1b) in its treatment.

Data Sources:

Epidemiologic, preclinical, and clinical studies published in the English language were identified by a MEDLINE search (1966–January 2005) using the search terms idiopathic pulmonary fibrosis, cryptogenic fibrosing alveolitis, and interferon. Additional citations were identified from the reference lists of related publications.

Study Selection and Data Extraction:

Selected preclinical studies describing the pathophysiologic basis for IFNγ−1b therapy and all clinical studies were included. Additional trials describing other treatment modalities and the determinants of response to therapy in patients with IPF were also reviewed.

Data Synthesis:

IFNγ−1b targets the fibrotic rather than inflammatory processes of IPF. The efficacy of IFNγ−1b in patients with IPF is inconsistent with regard to changes in pulmonary function and mortality, although a modest survival benefit was observed in the largest clinical trial. Adverse events related to IFNγ−1b are frequent although transient. Several cases of respiratory failure occurring subsequent to the administration of IFNγ−1b are documented.

CONCLUSIONS:

To date, although trials suggest that earlier-stage IPF may be responsive to IFNγ−1b, study results overall are inconsistent; further investigation is needed.
Propylene Glycol–Induced Lactic Acidosis in a Patient with Normal Renal Function: A Proposed Mechanism and Monitoring Recommendations
Authors: Neale Bruce W , Mesler Eleanor L , Young Michael , Rebuck Jill A , Weise Wolfgang J
Published: September 2005

OBJECTIVE:

To report a case of severe propylene glycol–induced lactic acidosis not attributable to renal dysfunction that was secondary to administration of high-dose intravenous lorazepam.

CASE SUMMARY:

A 24-year-old female with community-acquired pneumonia presented with severe acute respiratory distress syndrome. To maintain adequate sedation and ventilation and reduce airway pressure, several relaxation strategies were used including high-dose intravenous lorazepam, fentanyl, and cisatracurium. After 18 days of high-dose continuous infusion of lorazepam (maximum dose 50 mg/h), the patient developed severe lactic acidosis secondary to propylene glycol toxicity, the main diluent of lorazepam. The acidosis temporarily resolved with bicarbonate administration and discontinuation of lorazepam. Her renal function remained stable for a time (serum creatinine 0.5 mg/dL, blood urea nitrogen 10 mg/dL, urine output 100–200 mL/h). However, after several more days, the patient's condition deteriorated, and she ultimately died.

DISCUSSION:

Previous cases of propylene glycol toxicity secondary to high-dose lorazepam infusion have occurred in patients with compromised renal function. Our patient's renal function remained stable throughout the hospital course, which caused us to look further for an explanation for the propylene glycol–induced lactic acidosis. Based on the Naranjo probability scale, propylene glycol was determined to be the probable cause of lactic acidosis. Since this case occurred, our intensive care unit has instituted recommendations for the prevention of lorazepam-associated propylene glycol toxicity.

CONCLUSIONS:

Our case highlights the development of propylene glycol–induced lactic acidosis secondary to high-dose lorazepam infusion not associated with renal dysfunction.
Hashimoto Encephalopathy with Pegylated Interferon Alfa-2b and Ribavirin
Authors: Deutsch Melanie , Koskinas John , Tzannos Konstatinos , Vassilopoulos Dimitrios , Mailis Antonis , Tolis George , Hadziyannis Stephanos
Published: September 2005

OBJECTIVE:

To report an instance of Hashimoto encephalopathy probably resulting from pegylated interferon alfa-2b and ribavirin.

CASE SUMMARY:

A 36-year-old woman with a 10-year history of autoimmune thyroiditis presented with symptoms and signs consistent with Hashimoto encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C.

DISCUSSION:

Hashimoto encephalopathy is a rare autoimmune condition that occurs in patients with Hashimoto thyroiditis and high titers of antithyroid antibodies. It is characterized by a variety of nonspecific neuropsychiatric symptoms, increased cerebrospinal fluid protein level, and abnormal brain imaging and electroencephalogram. Prompt response to corticosteroids is observed in most cases. As of August 29, 2005, this is the first report of such an association. An objective causality assessment revealed that the Hashimoto encephalopathy was probably caused by the patient's medications.

CONCLUSIONS:

Hashimoto encephalopathy may rarely be triggered by interferon alfa therapy in susceptible patients.
Short-Term Synaptic Depression Causes a Non-Monotonic Response to Correlated Stimuli
Authors: de la Rocha Jaime , Parga Néstor
Published: September 2005

Unreliability is a ubiquitous feature of synaptic transmission in the brain. The information conveyed in the discharges of an ensemble of cells (e.g., in the spike count or in the timing of synchronous events) may not be faithfully transmitted to the postsynaptic cell because a large fraction of the spikes fail to elicit a synaptic response. In addition, short-term depression increases the failure rate with the presynaptic activity. We use a simple neuron model with stochastic depressing synapses to understand the transformations undergone by the spatiotemporal patterns of incoming spikes as these are first converted into synaptic current and afterward into the cell response. We analyze the mean and SD of the current produced by different stimuli with spatiotemporal correlations. We find that the mean, which carries information only about the spike count, rapidly saturates as the input rate increases. In contrast, the current deviation carries information about the correlations. If the afferent action potentials are uncorrelated, it saturates monotonically, whereas if they are correlated it increases, reaches a maximum, and then decreases to the value produced by the uncorrelated stimulus. This means that, at high input rates, depression erases from the synaptic current any trace of the spatiotemporal structure of the input. The non-monotonic behavior of the deviation can be inherited by the response rate provided that the mean current saturates below the current threshold setting the cell in the fluctuation-driven regimen. Afferent correlations therefore enable the modulation of the response beyond the saturation of the mean current.
Comparison of the Effects of Bilateral Orbital Prefrontal Cortex Lesions and Amygdala Lesions on Emotional Responses in Rhesus Monkeys
Authors: Izquierdo Alicia , Suda Robin K. , Murray Elisabeth A.
Published: September 2005

The present study examines the effects of bilateral orbital prefrontal cortex (PFo) lesions on monkeys' emotional responses in two different contexts: in the presence of a rubber snake and in the presence of a human intruder. For comparison, we also assessed the responses of rhesus monkeys with selective amygdala lesions on these same tasks. Monkeys with PFo lesions, like those with amygdala lesions, displayed blunted emotional responses to the fake snake. Unlike monkeys with amygdala lesions, however, monkeys with PFo lesions displayed more mild aggression than controls in the presence of a human intruder. The findings support the idea that the PFo helps integrate sensory signals in the service of choosing among competing responses. In addition, they point to a divergence of the roles of the PFo and amygdala in responding to a social stimulus, the human intruder.
Human Auditory Cortical Processing of Changes in Interaural Correlation
Authors: Chait Maria , Poeppel David , de Cheveigné Alain , Simon Jonathan Z.
Published: September 2005

Sensitivity to the similarity of the acoustic waveforms at the two ears, and specifically to changes in similarity, is crucial to auditory scene analysis and extraction of objects from background. Here, we use the high temporal resolution of magnetoencephalography to investigate the dynamics of cortical processing of changes in interaural correlation, a measure of interaural similarity, and compare them with behavior. Stimuli are interaurally correlated or uncorrelated wideband noise, immediately followed by the same noise with intermediate degrees of interaural correlation. Behaviorally, listeners' sensitivity to changes in interaural correlation is asymmetrical. Listeners are faster and better at detecting transitions from correlated noise than transitions from uncorrelated noise. The cortical response to the change in correlation is characterized by an activation sequence starting from ∼50 ms after change. The strength of this response parallels behavioral performance: auditory cortical mechanisms are much less sensitive to transitions from uncorrelated noise than from correlated noise. In each case, sensitivity increases with interaural correlation difference. Brain responses to transitions from uncorrelated noise lag those from correlated noise by ∼80 ms, which may be the neural correlate of the observed behavioral response time differences. Importantly, we demonstrate differences in location and time course of neural processing: transitions from correlated noise are processed by a distinct neural population, and with greater speed, than transitions from uncorrelated noise.
Bim Is a Direct Target of a Neuronal E2F-Dependent Apoptotic Pathway
Authors: Biswas Subhas C. , Liu David X. , Greene Lloyd A.
Published: September 2005

The inappropriate expression/activation of cell-cycle-related molecules is associated with neuron death in many experimental paradigms and human neuropathologic conditions. However, the means whereby this links to the core apoptotic machinery in neurons have been unclear. Here, we show that the pro-apoptotic Bcl-2 homology 3 domain-only molecule Bcl-2 interacting mediator of cell death (Bim) is a target of a cell-cycle-related apoptotic pathway in neuronal cells. Induction of Bim in NGF-deprived cells requires expression and activity of cyclin-dependent kinase 4 (cdk4) and consequent de-repression of E2 promoter binding factor (E2F)-regulated genes including members of the myb transcription factor family. The Bim promoter contains two myb binding sites, mutation of which abolishes induction of a Bim promoter-driven reporter by NGF deprivation or E2F-dependent gene de-repression. NGF deprivation significantly increases endogenous levels of C-myb and its occupancy of the endogenous Bim promoter. These findings support a model in which apoptotic stimuli lead to cdk4 activation, consequent de-repression of E2F-regulated mybs, and induction of pro-apoptotic Bim.
Absence of Fyn and Src Causes a Reeler-Like Phenotype
Authors: Kuo Gloria , Arnaud Lionel , Kronstad-O'Brien Priscilla , Cooper Jonathan A.
Published: September 2005

Nonreceptor protein tyrosine kinases of the Src family regulate the survival, proliferation, differentiation, and motility of many cell types, but their roles in brain development are unclear. Biochemical andin vitroexperiments implicate Src and Fyn in the Reelin-dependent tyrosine phosphorylation of Dab1, which controls the positioning of radially migrating neurons in many brain regions. However, genetic evidence that either Src or Fyn mediates Reelin-dependent migrationsin vivohas been lacking. Here, we report that, although Src is dispensable and although the absence of Fyn causes an intermediate phenotype, the combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab1 and causes defects in the fetal cortex and cerebellum very similar to those ofdab1mutants of the same age. Neurogenesis is not detectably affected, but the layering of neurons in the cortex is inverted, and the formation of the Purkinje plate is impaired. This implies that Src and Fyn are needed for Reelin-dependent events during brain development.
Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine
Authors: Uslaner Jason M. , Yang Pengwei , Robinson Terry E.
Published: September 2005

The subthalamic nucleus (STN) is traditionally thought to be involved in motor control, and dysfunction of the STN is thought to contribute to movement disorders. Here, we show that the STN also plays an important role in motivational processes and the response to drugs of abuse. Specifically, bilateral STN lesions produced a dose-dependent increase in the psychomotor-activating effects of cocaine, the rate at which animals acquired cocaine self-administration, and the motivation for cocaine assessed using a progressive ratio schedule. Furthermore, bilateral STN lesions enhanced the ability of cocaine to induce gene expression in the nucleus accumbens and caudate–putamen, two structures known to be involved in mediating the psychomotor-activating and incentive motivational effects of drugs of abuse. These findings suggest that engagement of the STN serves to dampen the psychomotor-activating and incentive motivational effects of drugs of abuse. Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence.
Versican in the Developing Brain: Lamina-Specific Expression in Interneuronal Subsets and Role in Presynaptic Maturation
Authors: Yamagata Masahito , Sanes Joshua R.
Published: September 2005

Chondroitin sulfate proteoglycans (CSPGs) of the extracellular matrix help stabilize synaptic connections in the postnatal brain and impede regeneration after injury. Here, we show that a CSPG of the lectican family, versican, also promotes presynaptic maturation in the developing brain. In the embryonic chick optic tectum, versican is expressed selectively by subsets of interneurons confined to the retinorecipient laminae, in which retinal axons arborize and form synapses. It is a major receptor for theVicia villosaB4lectin (VVA), shown previously to inhibit invasion of the retinorecipient lamina by retinal axons (Inoue and Sanes, 1997).In vitro, versican promotes enlargement of presynaptic varicosities in retinal axons. Depletion of versicanin ovo, by RNA interference, results in retinal arbors with smaller than normal varicosities. We propose that versican provides a lamina-specific cue for presynaptic maturation and discuss the related but distinct effects of versican depletion and VVA blockade.
A Null Mutation for the α3 Nicotinic Acetylcholine (ACh) Receptor Gene Abolishes Fast Synaptic Activity in Sympathetic Ganglia and Reveals That ACh Output from Developing Preganglionic Terminals Is Regulated in an Activity-Dependent Retrograde Manner
Authors: Rassadi Siamak , Krishnaswamy Arjun , Pié Brigitte , McConnell Russell , Jacob Michele H. , Cooper Ellis
Published: September 2005

In vertebrates, synaptic activity exerts an important influence on the formation of neural circuits, yet our understanding of its role in directing presynaptic and postsynaptic differentiation during synaptogenesis is incomplete. This study investigates how activity influences synaptic differentiation as synapses mature during early postnatal life. Specifically, we ask what happens to presynaptic terminals when synapses develop without functional postsynaptic receptors and without fast synaptic transmission.

To address this issue, we investigated cholinergic nicotinic synapses in sympathetic ganglia of mice with a null mutation for the α3 nicotinic ACh receptor gene. Disrupting the α3 gene completely eliminates fast excitatory synaptic potentials on postganglionic sympathetic neurons, establishing a crucial role for α3-containing postsynaptic receptors in synaptic transmission. Interestingly, the preganglionic nerve terminals form morphologically normal synapses with sympathetic neurons, and these synapses persist without activity in postnatal animals. Surprisingly, when stimulating the preganglionic nerve at physiological rates, we discovered a significant decrease in ACh output from the presynaptic terminals in these α3–/–sympathetic ganglia. We show that this decrease in ACh output from the presynaptic terminals results, in part, from a lack of functional high-affinity choline transporters. We conclude the following: (1) fast synaptic transmission in mammalian SCG requires α3 expression; (2) in the absence of activity, the preganglionic nerve forms synapses that appear morphologically normal and persist for several weeks; and (3) to sustain transmitter release, developing presynaptic terminals require an activity-dependent retrograde signal.
The Vitamin D3 Pathway in Human Skin and its Role for Regulation of Biological Processes
Authors: Lehmann Bodo
Published: September 2005

The skin is the only tissue yet known in which the complete ultraviolet‐B (UV‐B)‐induced pathway from 7‐dehydrocholesterol to hormonally active calcitriol (1α,25‐dihydroxyvitamin D3) occurs under physiological conditions. Epidermal synthesis of calcitriol could be of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their antiproliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. The known antipsoriatic effect of UV‐B light could, at least in part, be mediated via UV‐B‐induced synthesis of calcitriol. In addition, mounting evidence indicates that cutaneous vitamin D3 synthesis is of high importance for the prevention of a broad variety of diseases, including various malignancies. New but controversially discussed sun‐protection guidelines were established for the prevention of internal cancers. A better understanding of the metabolism of vitamin D in the skin opens new perspectives for therapeutic applications of vitamin D analogs.
Soil Water Extraction with a Suction Cup: Results of Numerical Simulations
Authors: Weihermüller Lutz , Kasteel Roy , Vanderborght Jan , Pütz Thomas , Vereecken Harry
Published: September 2005

Porous cups are widely used to extract soil water for monitoring solute transport. However, it is not yet clear how the suction cup influences the matric potential in the surrounding soil and which part of the soil is sampled. This research was designed to numerically evaluate the activity domain, the extraction domain, and sampling area of a suction cup under constant infiltration. A finite‐element model (HYDRUS‐2D) was used to simulate the effect of various applied suctions at two infiltration rates on the water status in three soils (clay loam, sandy clay, and sand). Particle tracking was used to track the streamlines that define the sampling area and extraction domain of the suction cup. In general, the activity domain, the extraction domain, and sampling area of the suction cup depend primarily on the soil hydraulic parameters and the upper boundary, and secondarily on the applied suction. Results showed that the activity domain, the extraction domain, and the sampling area are largest for highest ambient hydraulic conductivities. The activity domain and the sampling area also decrease with increasing infiltration rates. Further, the activity domain of the suction cup depends strongly on the duration of water extraction. Soil heterogeneity seems to play a minor role with respect to the activity domain and sampling area of the cup.
Stochastic Analysis of Solute Mass Flux in Gravity‐Dominated Flow through Bimodal Heterogeneous Unsaturated Formations
Authors: Russo David
Published: September 2005

First‐order analysis, based on a stochastic continuum presentation of flow and a general Lagrangian description of transport, was used to investigate the effects of several characteristics of a bimodal, spatially heterogeneous, variably saturated formation, on solute breakthrough curves, under steady‐state, gravity‐dominated unsaturated flow conditions. The bimodal formation was viewed as a mixture of two populations (background soil and embedded soil) of differing hydraulic properties and differing spatial structures. Results of the present analysis, restricted to relatively small inclusions' volume fraction, suggest that as in saturated flow, for a formation of given statistics and mean water saturation, both the spreading of the mean solute breakthrough curve and the uncertainty in its prediction may be appreciable, especially in bimodal formations in which: (i) the contrast between the mean properties of the two subdomains is relatively large, (ii) the inclusions' volume fraction is relatively large, and (iii) the characteristic length scales of the inclusions are relatively large as compared with those of the heterogeneity of the background soil. Results of this study, unique to unsaturated flow conditions, stem from the inherent concave nature of the log‐conductivity variance–mean pressure head relationships in bimodal, variably saturated formations. Consequently, under unsaturated flow conditions, both the spreading of the mean solute discharge and the uncertainty in its prediction are concave functions of mean saturation. Starting with saturated formation, they initially decrease with decreasing mean saturation, reach their minima, and then increase as mean saturation further decreases, exceeding their counterparts in saturated flow conditions. Implications of the results with respect to the problem of groundwater contamination where risk assessment is required, are briefly discussed.
Phase separation of liquid‐liquid two‐phase flow at a T‐junction
Authors: Yang L. , Azzopardi B. J. , Belghazi A. , Nakanishi S.
Published: September 2005

The phase separation of liquid‐liquid two‐phase flow at a T‐junction has been studied using kerosene and deionized water as working fluids and a T‐junction with a horizontal main pipe and a vertically upward side arm. Separation data are evaluated by a new criterion: separation efficiency. The results show that the T‐junction is highly efficient at separating two immiscible liquids when the flows approaching the T‐junction are stratified and when the fractional mass take offs close to the inlet kerosene mass fraction. A new model has been proposed for the phase separation. Comparison between the model and the experimental data shows that the data is well represented by the model. © 2005 American Institute of Chemical Engineers AIChE J, 2006
On a recent purported determination of individual ion activity coefficients
Authors: Malatesta Francesco
Published: September 2005

In a recent article “On the activity of ions and the junction potential: Revised values for all data,” G. Wilczek‐Vera, E. Rodil, and J. H. Vera proposed the amended version of a controversial method to derive ion activity coefficients from electromotive force data. Here we show that their method is incorrect. Using precise data available for HCl, we show that their approach does not identify an unequivocal single set of ion activity coefficients, but as many sets as those that are introduced as the input in the evaluation of the liquid junction potentials. That is, an infinite number of self‐consistent sets. Indeed, the “ion activity coefficients” found echo the starting assumptions, with no relationship to the actual, but unknown real values. © 2005 American Institute of Chemical Engineers AIChE J, 2006
The geometry of separation boundaries: I. Basic theory and numerical support
Authors: Lucia Angelo , Taylor Ross
Published: September 2005

Separation has always been an important task in the chemical industry. Even with the recent shift in emphasis and efforts to unify the physical and biological sciences, separation will remain an important workhorse in production and product/process design. The theory of simple distillation and residue curve maps has a long history—roughly 100 years—and has made a significant impact in the way many new separation processes are synthesized and designed. The key synthesis/design concept in this approach centers on understanding the ways in which constant boiling mixtures (or azeotropes) define separation boundaries. It is now well established that these azeotropes (or eutectics in melt or fractional crystallization and other solid–liquid separations) often define curved separation boundaries that place limitations on the degree of separation that can be achieved. Despite this, there remains no clear and exact understanding of separation boundaries and no straightforward way of accurately computing them in practice. A geometric methodology is presented that shows that exact separation boundaries can be defined through the use of differential geometry and dynamical systems theory and formulated as a constrained global optimization problem. Our novel approach is based on the observation that, for ternary homogeneous liquids, separation boundaries correspond to local maxima in the line integral within a given separation region. In addition, it is shown that these local maxima in the line integral correspond to one‐sided cusps and that global optimization is absolutely necessary, given that several local maxima can exist within any separation region. Several numerical examples are presented that show that the proposed geometric approach can accurately find separation boundaries for homogeneous and heterogeneous mixtures. Finally, it is shown that our new methodology is very general and readily extends to mixtures with four or more components, reactive separations, nonequilibrium models, and other processes such as crystallization and vapor degreasing. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Advances in field‐based studies of primate behavioral endocrinology
Authors: Strier Karen B. , Ziegler Toni E.
Published: September 2005

The papers in this issue were inspired by a symposium we organized for the 27th Annual Meeting of the American Society of Primatologists, held in June 2004. The purpose of the symposium was to highlight some of the new ways in which noninvasive techniques for measuring steroids are being employed to investigate the relationships between hormones and behavior in wild primates. Endocrinological data from the field provide new insights and more precise interpretations of behavioral data on topics ranging from social and reproductive strategies to seasonality, reproductive suppression, concealed ovulation, and development. Advances in the development of methods for extracting steroids from urine and feces have increased the options available to field workers, who can now select the most appropriate methodology for their study subjects, field conditions, and specific research questions. Field‐based studies of behavioral endocrinology have spread to include a wide diversity of primate species. As the scope of these studies continues to grow, we anticipate the emergence of a dynamic new field in which comparative models of primate behavioral endocrinology contribute new perspectives on primates. Am. J. Primatol. 67:1–4, 2005. © 2005 Wiley‐Liss, Inc.
Effects of reproductive and social variables on fecal glucocorticoid levels in a sample of adult male ring‐tailed lemurs (Lemur catta) at the Beza Mahafaly Reserve, Madagascar
Authors: Gould Lisa , Ziegler Toni E. , Wittwer Daniel J.
Published: September 2005

Glucocorticoids, a group of adrenal hormones, are secreted in response to stress. In male primates, variables such as breeding seasonality, dominance hierarchy stability, and aggressive and affiliative interactions can affect glucocorticoid levels. In this study, we examined interindividual differences in mean fecal glucocorticoid (fGC) levels among males in three groups of wild ring‐tailed lemurs to better understand the physiological costs of group living for males in a female‐dominant species that exhibits strict reproductive seasonality. Fecal and behavioral data samples were collected during one mating and two postmating seasons (2001 and 2003). The mean fGC levels were examined in relation to reproductive season, male rank, number of resident males, intermale and female–male agonism, and affiliative behavior with females. The mean fGC levels were not significantly elevated during mating season compared to the postmating period. During the mating season, male dominance hierarchies broke down and rank effects could not be tested; however, there was no relationship between male rank and fGC levels in the postmating periods. In 2001, males that resided in the group with the fewest males exhibited lower fGC levels during the postmating period. They also affiliated more with females than did males in the other groups. During the mating season of 2003, males engaged in more affiliative behaviors with females compared to the postmating season, but female–male agonism did not differ by season. However, rates of intermale agonism were significantly higher during mating compared to postmating periods, but such heightened agonism did not translate to a higher stress response. Thus, neither male–male competition for mates nor heightened agonism between males during the breeding season affected male fGC levels. Fewer males residing in a group, however, did have some effect on male–female affiliation and male fGC levels outside of the mating period. Males that live in a group with only a few (two or three) males may experience less physiological stress than those that live in groups with more males. Am. J. Primatol. 67:5–23, 2005. © 2005 Wiley‐Liss, Inc.
Variation in the resumption of cycling and conception by fecal androgen and estradiol levels in female Northern Muriquis (Brachyteles hypoxanthus)
Authors: Strier Karen B. , Ziegler Toni E.
Published: September 2005

We measured fecal androgen (T+DHT) and estradiol (E2) levels in female northern muriquis (Brachyteles hypoxanthus) at the Estação Biológica de Caratinga/RPPN Feliciano Miguel Abdala, Minas Gerais, Brazil, to evaluate the hormonal bases underlying individual variation in the resumption of cycling and conception. We found that androgen levels were significantly lower in females than in males, and that there were no consistent patterns in female androgen levels across precycling or cycling conditions. Females that resumed cycling earlier in the study (weeks 4–8) had higher precycling E2 levels and correspondingly lower precycling androgen/E2 ratios than females that resumed cycling later (weeks 12–16). There were no differences in female precycling androgen levels, but cycling females that conceived during or immediately after the study period had lower androgen levels and threefold higher E2 peaks than the one cycling female that failed to conceive. These results suggest that minimum E2 thresholds are necessary for both the resumption of ovarian cycling and conception. Individual variation in these components of fertility may be regulated by differences in E2 levels, which affect androgen/E2 ratios, rather than by androgen levels per se. Further research into the relative concentrations of T vs. DHT will be necessary to fully evaluate whether androgens affect cycling and conception in this species. Am. J. Primatol. 67:69–81, 2005. © 2005 Wiley‐Liss, Inc.
Coming of age: steroid hormones of wild immature baboons (Papio cynocephalus)
Authors: Gesquiere Laurence R. , Altmann Jeanne , Khan Memuna Z. , Couret Jannelle , Yu Jennifer C. , Endres Courtney S. , Lynch Jessica W. , Ogola Patrick , Fox Elizabeth A. , Alberts Susan C. , Wango Emmanuel O.
Published: September 2005

Large gaps exist in our knowledge about common patterns and variability in the endocrinology of immature nonhuman primates, and even normal hormonal profiles during that life stage are lacking for wild populations. In the present study we present steroid profiles for a wild population of baboons (Papio cynocephalus) from infancy through reproductive maturation, obtained by noninvasive fecal analyses. Fecal concentrations of glucocorticoid (fGC) and testosterone (fT) metabolites for males, and of fGC, estrogen (fE), and progestin (fP) metabolites for females were measured by radioimmunoassay (RIA). In males, infancy was characterized by high and declining levels of fGC and fT, whereas steroid concentrations were low during the juvenile years. During the months immediately prior to testicular enlargement, fT (but not fGC) concentration tended to increase. Males that matured early consistently had higher fT and fGC concentrations than those that matured late, but not significantly so at any age. Individual differences in fT concentrations were stable across ages, and average individual fT and fGC concentrations were positively correlated. For females, high and declining levels of fE characterized infancy, and values increased again after 3.5 years of age, as some females reached menarche by that age. Both fP and fGC were relatively low and constant throughout infancy and the juvenile period. During the months immediately prior to menarche, fGC concentration significantly decreased, while no changes were observed for fE levels. fP exhibited a complicated pattern of decrease that was subsequently followed by a more modest and nonsignificant increase as menarche approached. Early‐ (EM) and late‐maturing (LM) females differed only in fP concentration; the higher fP concentrations in EM females reached significance at 4–4.5 years of age. Maternal rank at offspring conception did not predict concentrations of any hormone for either sex. Our results demonstrate the presence of individual endocrine variability, which could have important consequences for the timing of sexual maturation and subsequently for individual reproductive success. Further evaluation of the factors that affect hormone concentrations during the juvenile and adolescent periods should lead to a better understanding of mechanisms of life‐history variability. Am. J. Primatol. 67:83–100, 2005. © 2005 Wiley‐Liss, Inc.
Radioimmunoassay of estrone conjugates from urine dried on filter paper
Authors: Knott Cheryl D.
Published: September 2005

Hormonal analysis of urine from free‐ranging primates has been limited due to the difficulty of preserving samples under field conditions. Drying urine on filter paper is an alternative for field preservation. This study describes a new laboratory method for eluting steroids from filter paper with methanol, along with a series of experiments used to develop and validate this method. The overall elution recovery of estrone sulfate (ES) from filter paper was 86.4%. Estrone conjugate (E1C) levels in humans and captive orangutans were analyzed by radioimmunoassay (RIA). Values from samples dried on filter paper were significantly correlated with values from matched frozen samples, with elution efficiencies ranging between 97.1% and 102.4%. Creatinine (Cr) measurements from frozen urine compared to urine dried on filter paper were also significantly correlated (r=0.96) with an elution efficiency of 101.7%. After the samples were stored for 2 years, the absolute values of E1C and Cr were significantly lower but were still significantly correlated with frozen urine values. These data demonstrate the effectiveness of filter paper as a medium for preserving urinary steroid samples, and the efficiency of methanol as a solvent for eluting E1C and Cr. This method thus provides a viable alternative to the traditional procedure of freezing urine for field studies, where freezers are not available. Am. J. Primatol. 67:121–135, 2005. © 2005 Wiley‐Liss, Inc.
Reproductive endocrinology of wild female Chimpanzees (Pan troglodytes schweinfurthii): methodological considerations and the role of hormones in sex and conception
Authors: Emery Thompson Melissa
Published: September 2005

Fecal and urine samples were collected from 81 female East African chimpanzees (Pan troglodytes schweinfurthii) in three major study populations in Gombe National Park, Tanzania, and Budongo Forest Reserve and Kibale National Park, Uganda. In this study I evaluated issues related to sample storage and assay reliability, and used these methods to investigate the significance of ovarian hormone levels in terms of conception success and sexual behavior. Drying of feces proved to be an effective technique and resulted in hormonal concentrations that were significantly correlated with concentrations in frozen feces. Estimates of ovarian steroid production based on urine and fecal sampling were significantly correlated with each other. The ovarian cycle profiles obtained, which were aligned relative to sexual swelling detumescence, corroborate previous findings in wild west African chimpanzees [Deschner et al., Animal Behaviour 66:551–560, 2003] in suggesting that the fertile period is limited to the last week of tumescence, but that ovulatory timing is not as precise as previously thought. A comparison across cycles confirmed the hypothesis that higher ovarian steroid levels are associated with an increased probability of conception. Females that did conceive with relatively low hormone levels had poor reproductive outcomes. Sexual behavior was tied to the probability of conception both within and across cycles. Copulatory activity within cycles closely followed the estrogen profile and was timed to coincide, on average, with the peak fertile period of females. Further, rates of copulation were significantly higher during the fertile periods of cycles that led to conception than those that did not. Am. J. Primatol. 67:137–158, 2005. © 2005 Wiley‐Liss, Inc.
Fecal steroid research in the field and laboratory: improved methods for storage, transport, processing, and analysis
Authors: Ziegler Toni E. , Wittwer Daniel J.
Published: September 2005

Since the pioneering paper “Measurement of Excreted Steroids in Macaca nemestrina” [Risler et al., American Journal of Primatology 12:91–100, 1987] was first published, field primatologists have been using fecal extraction techniques to examine adrenal and gonadal hormones. These techniques have allowed investigators to determine reproductive conditions in wild primates without causing any disruption to the populations. Over the years, many techniques have been developed to improve the ease of analysis, transportation, and purification. More of the processing can now be done in the field. This paper describes the methodology developed or adapted at the Wisconsin National Primate Research Center, and the factors involved in preparing fecal samples for steroid analysis. We provide information on the steps involved in extracting and purifying steroids from feces for measurement. The latest methods include field processing of samples, such as drying collected material or separating steroids from the fecal material by solid phase extraction (SPE). How samples are processed in the field determines the requirements for international transportation and the methods used in the laboratory. The pros and cons of the different processing methods are discussed. We also report on recent advances in laboratory quantification, with implications for steroid isolation prior to analysis. The different processes involved in isolating and measuring fecal steroids discussed here will enable investigators to understand the components necessary to ensure accurate and reliable results. Am. J. Primatol. 67:159–174, 2005. © 2005 John Wiley & Sons, Ltd.
High‐performance liquid chromatography method development and validation for simultaneous determination of five model compounds, antipyrine, metoprolol, ketoprofen, furosemide and phenol red, as a tool for the standardization of rat in situ intestinal permeability studies using timed wavelength detection
Authors: Chawla Sonia , Ghosh Soma , Sihorkar Vaibhav , Nellore Ranjani , Kumar T. R. Shantha , Srinivas Nuggehally R.
Published: September 2005

A simple, precise, accurate and rugged reversed‐phase high‐performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of five permeability model compounds, viz. antipyrine, metoprolol, ketoprofen, furosemide and phenol red. The method was intended to standardize rat in situ single‐pass intestinal perfusion studies to assess the intestinal permeability of drugs in the market as well as new chemical entities. Optimum resolution was achieved by gradient elution on a Symmetry Shield C‐18 analytical column with the mobile phase consisting of a mixture of aqueous potassium dihydrogen orthophosphate (pH 5.5; 0.01 m) and methanol at a flow rate of 1.5 mL/min. The retention times of antipyrine, metoprolol, ketoprofen, phenol red and furosemide were about 9, 12, 13, 16 and 17 min, respectively. Data acquisition was carried out using a photo diode array detector in the wavelength range 210–600 nm. Extraction of chromatograms was carried out by timed wavelength. Data obtained in all studies indicated that the method was suitable for the intended purpose. The validated method was found to be linear and precise in the working range. Suitability of storage under various conditions and freeze/thaw impact at cold temperature were established to ensure complete sample recovery without any stability issues. Recovery very close to the spiked amounts indicated that the method was highly accurate and suitable for use on routine basis. Copyright © 2005 John Wiley & Sons, Ltd.
High‐performance liquid chromatographic method for simultaneous quantification of eight major biologically active ingredients in ‘Da‐Chai‐Hu‐Tang’ Preparation
Authors: Li Chia‐Ying , Chiu Chiung‐Hui , Huang Ho‐Shin , Lin Chung‐Hua , Wu Tian‐Shung
Published: September 2005

A simple, sensitive and specific high‐performance liquid chromatographic method has been developed for the first time to simultaneously determine the eight major biologically active ingredients, namely paeoniflorin, naringin, sennoside A, baicalin, baicalein, saikosaponin a, rhein and emodin of the Chinese herbal formula Da‐Chai‐Hu‐Tang. The contents of these marker substances in Da‐Chai‐Hu‐Tang extract could be easily determined within 85 min. The assay was reproducible and accurate with overall intra‐day variations and accuracy of less than 2% and more than 97.9%, respectively. Results indicate that the developed HPLC assay can be successfully utilized as a quality control method for simultaneous determination of eight representative substances in Da‐Chai‐Hu‐Tang. Copyright © 2005 John Wiley & Sons, Ltd.
Ultra high‐speed sorting
Authors: Leary James F.
Published: September 2005

Background

Cell sorting has a history dating back approximately 40 years. The main limitation has been that, although flow cytometry is a science, cell sorting has been an art during most of this time. Recent advances in assisting technologies have helped to decrease the amount of expertise necessary to perform sorting.

Methods

Droplet‐based sorting is based on a controlled disturbance of a jet stream dependent on surface tension. Sorting yield and purity are highly dependent on stable jet break‐off position. System pressures and orifice diameters dictate the number of droplets per second, which is the sort rate limiting step because modern electronics can more than handle the higher cell signal processing rates.

Results

Cell sorting still requires considerable expertise. Complex multicolor sorting also requires new and more sophisticated sort decisions, especially when cell subpopulations are rare and need to be extracted from background. High‐speed sorting continues to pose major problems in terms of biosafety due to the aerosols generated.

Conclusions

Cell sorting has become more stable and predictable and requires less expertise to operate. However, the problems of aerosol containment continue to make droplet‐based cell sorting problematical. Fluid physics and cell viability restraints pose practical limits for high‐speed sorting that have almost been reached. Over the next 5 years there may be advances in fluidic switching sorting in lab‐on‐a‐chip microfluidic systems that could not only solve the aerosol and viability problems but also make ultra high‐speed sorting possible and practical through massively parallel and exponential staging microfluidic architectures. © 2005 International Society for Analytical Cytology