bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psoriasis: In vivo models for topical drug evaluation
Authors: Lowe Nicholas J. 
Published: January 2005

AbstractPsoriasis is a common skin disease characterized by scaling erythematous skin plaques, which in severe cases can cover the entire skin. It affects about 2% of the population of the USA. The etiology is unknown, but the diseased skin shows a benign epidermal hyperplasia and abnormal differentiation plus dermal inflammation. There is no reproducible naturally occurring animal model for psoriasis. As a result, a variety of simulated animal models have been produced that possess some of the characteristic features, e.g., epidermal hyperplasia. These have been used to study epidermal kinetics and biochemical abnormalities associated with epidermal hyperplasia. Some of these models have also been used to study and screen for potentially effective and antipsoriatic drugs. There will always be, however, the need to study effects of new agents in carefully conducted studies on psoriasis patients to confirm efficacy.
Percutaneous drug penetration: Choosing candidates for transdermal development
Authors: Flynn Gordon L. , Stewart Barbra 
Published: January 2005

AbstractThere is currently a high level of interest in using the skin as a route for delivering drugs. One hears the questions: What are the attributes of a drug that make it a serious candidate for transdermal delivery? By what a priori analysis might one zero in on the best transdermal candidate within a family of drugs? Answers to these questions lie in understanding the molecular factors that make a drug a facile permeant of the skin. Among other properties, it must have a high absolute affinity for the skin's phases, which provide for its diffusive conduction. Other factors in evaluation are the potency of the drug and the relative efficiency of the drug's systemic presentation once it has gained access to the body. One also considers the potential for the drug to elicit adverse responses in the skin. Fortunately, parallels between the drug's ability to partition between oil and water and its ease of mass transfer across the skin can be used to ferret out a working mass transfer coefficient. If not already known, solubilities are easily experimentally deduced. The extent of first‐pass metabolism by the oral route, presumed to be a known quantity, is compared with the relative amount of metabolism of the drug in the course of its diffsion through the skin, an experimentally determined quantity, in order to set the transdermal dose. These bits of information can then be used to form an early, reasonably faithful picture of the feasibility of delivering a particular drug transdermally and to make a first estimate of the size of patch required for the drug.
Restoration of microsieve filterability of human red cells after exposure to hyperosmolarity and lactacidosis: Effect of vinpocetine
Authors: Schmid‐Schönbein H. , Grebe R. , Teitel P. , Artmann G. , Eschweiler H. , Schröder Susanne 
Published: January 2005

AbstractA new technique has been utilized to assess quantitatively the filterability (i.e., the ability to pass restricted pores) of leukocyte‐free red blood cell (RBC) suspensions by means of computer‐assisted conductometry of novel precision metal microsieves with uniform pore diameters of 4.2 μm (MyNiPore®). RBCs were exposed to adverse conditions of chemical “stress” (400 mOsmol/liter, pH 6.8), thereafter, the effects of vinpocetine (Methyl‐Apo‐Vipamin, Thiemann‐Arzneimittel GmbH, Waltrop, FRG) were tested. When added in concentrations between 10−5 and 10−2 mol/liter to the “stressed” RBCs, vinpocetine restored the red cell microrheological performance (or behavior) when tested under low shear stresses. The present results suggest that in interpreting vinpocetine's effects in low flow situations, a possible protective microrheological action should be taken into consideration.
Pharmacologic corrections of cerebral blood flow and CO2‐reactivity in cerebrovascular insufficiency
Authors: Weinstein G. B. , Parfenov V. E. , Bodo M. , Gaidar B. V. 
Published: January 2005

AbstractExperiments in brain‐ischemic rabbits were performed in order to study the effects of dimethylaether oxybutric acid (Dimephosphone), chloralhydrate oxypiridin (Emoxipine), and trimethyl hydrasine propionate (THP). These compounds proved to be antihypoxic in measures of cerebral blood flow and CO2‐reactivity.
Correlations between memory, language, gnosia, and praxia in 80 patients with senile dementia of the alzheimer type
Authors: Roudier M. , Marcie P. , Podrabinek N. , Lamour Y. , Davous P. 
Published: January 2005

AbstractA global neuropsychological study has been carried out with 80 in‐patients presenting a syndrome of senile dementia of the Alzheimer type (SDAT):60 scored less than 20 (mild dementia) on the Mini‐Mental Test Examination (MMSE); 20 scored less than 10 (severe dementia). The test battery included a set of tasks exploring memory, language, abstract nonverbal thought, gnosias, and praxias. In patients with mild dementia, the overall MMSE score was statistically correlated with the scores for memory, nonverbal thought, language, and gnosias, but not with the score for praxia. Language score was correlated with the scores for the other higher functions. It is suggested that the SDAT syndrome has to be considered as a unique syndrome affecting every higher function quite similarly, with no evidence of clinical subgroups. With this in mind, new studies should be designed to delineate further the role of the mnesic, linguistic, and/or perceptual factors involved in the dementia process.
Calcium antagonist activity of vinpocetine and vincamine in several models of cerebral ischaemia
Authors: Lamar Jean‐Claude , Poignet Hervé , Beaughard Michèle , Dureng Georges 
Published: January 2005

AbstractThe potency and selectivity (i.e., the central vs. peripheral vascular smooth muscle activity) of the calcium antagonist (CA) effects of vinpocetine and vincamine have been compared with those of the standard CAs: flunarizine, verpamil, diltiazem, and nimodipine in rabbit basilar and splenic artery preparations. The cerebral antiischemic activity of these substances also was evaluated in five well‐documented in vivo models, i.e., hypobaric and normobaric hypoxia, global cerebral ischemia to MgCl2, cytotoxic anoxia with KCN, and cerebral edema induced by triethyl tin. Both vinpocetine and vincamine possess only weak CA activity, the potency order being: nimodipine > diltiazem > flunarizine = verapamil > vinpocetine > vincamine, with vinpocetine and flunarizine, in contrast to other compounds, showing a clear, 6‐ to 13‐fold selectivity for cerebral vascular smooth muscle. In the in vivo models, vinpocetine and flunarizine, together with vincamine, proved most active and had a larger spectrum of activity than the other CAs. These results suggest that the cerebrally selective CA effects of vinpocetine are at most only partly responsible for the effects of this compound in the in vivo models of cerebral ischemia.
Effect of vinpocetine on age‐related differences in brain function of aged fischer rats
Authors: Notvest Ronald R. , Emrey Tracey A. , Inserra John J. 
Published: January 2005

AbstractVinpocetine, an eburnamenine derivative, is under clinical investigation as a cerebral activator for use in Alzheimer's and other diseases characterized by symptomatic cognitive and attentional deficits. In this study, vinpocetine was evaluated by examining its effect on the electrocorticogram (ECoG) of aged (26‐month‐old) Fischer‐344 rats. Significant age‐related differences were apparent for all ECoG parameters examined, suggesting a cerebral deficit in aged rats. Vinpocetine, administered orally (p.o.) over the dose range of 0.3 to 30 mg/kg/day p.o. for 5 days, diminished the age‐related differences in the ECoG. These findings provide evidence that vinpocetine may serve as a useful therapeutic agent in diseases characterized by cerebral deficits.
Animal models for evaluation of age‐related changes in behaviour
Authors: Schulze Gert , Coper Helmut , Jänicke Bernhard 
Published: January 2005

AbstractA larger degree of deterioration of the centrally controlled physiological, motor, and cognitive functions is characteristic of an organism's aging process. This restricted adaptation can be monitored on various organizational and functional levels. Mazes permit registration of cognitive performance in controlled motivation such as memory, spatial orientation, ability to learn, and speed of learning. The total running time is a composite parameter determined by a number of time‐dependent and time‐independent factors. With time‐dependent factors, age‐related differences remain after five repetitions, even when slight effects of training are evident. In most time‐independent factors, age‐related differences can be nearly eliminated by training. An example of the method “testing the limits” is to measure compensative responses under 10% normobaric hypoxia over a period of several days. Young as well as old rats reacted with the same reduction in feed intake and spontaneous activity. Adaptation to normal levels concerning motility and food consumption is accomplished less effectively and more slowly by the old rats than by the young ones. There were no differences between age groups in comparing the blood gas values of O2, CO2, and pH values. If the animals have to learn an operant conditioning schedule (fixed ratio/differential reinforcement of low rates), there are age‐related divergences of performance. Under hypoxic conditions, 27‐month‐old animals need twice as long to reach the test criterion in the “fixed ratio” as 4‐ and 20‐month‐old rats. Only the young and middle‐aged groups accomplished the task called “differential reinforcement of low rates”.
Influence of nootropic drugs on the stimulus‐release relationship of dopaminergic structures
Authors: Wustmann Christian , Fischer Hans‐Dieter , Rudolph Erika , Schmidt Joachim 
Published: January 2005

AbstractBrain slices labelled with radioactive neurotransmitters are a well established system for the investigation of transmitter secretion. The basal outflow of transmitter in the absence of external stimuli is largely due to a passive diffusion from nerve endings. The potassiumstimulated overflow represents a quasiphysiological release with a well defined correlation between stimulus intensity and fractional efflux rate. Upon long‐term exposure of rats to mild hypobaric hypoxia (10 day, 20 hr daily) the stimulus‐release relationship shows a marked ascent in the gradient in comparison to naive animals. Twenty‐four hours after long‐term treatment with piracetam, pyritonol, meclofenoxate, or vinpocetine (twice a day for 3 weeks) only the pretreatment with piracetam (100 mg/kg, twice a day) leads to changes of the stimulus‐release relation comparable to that seen in rats that were exposed to a long‐term hypoxia. These effects continued until 10 days after the last injection of the drug or after cessation of hypoxia. Meclofenoxate, pyritinol, and vinpocetine were without marked effects on the stimulus‐release relation.
Metoprolol monotherapy in the treatment of mild hypertension
Authors: Mahapatra Rajat K. , Mahapatra Dipta , Paul Subir K. , Lal Harbans , Hunter Kenneth W. 
Published: January 2005

AbstractMetoprolol tartrate (MT) as monotherapy was administered orally in 17 patients with mild hypertension. All other drugs were discontinued 2 weeks prior to MT therapy. The present study group consisted of 10 men and 7 women within the age range of 42 to 71 years (mean ± S.D. = 55.8 ± 8). MT was administered at an initial dose of 50 mg twice daily. Subsequently, the dose of MT was titrated on a biweekly basis for a period of 12 weeks until the diastolic blood pressure was < 90 mmHg or a maximum daily dose of 300 mg was administered. The blood‐pressure‐lowering effect of MT was found to be clinically satisfactory and statistically significant (P< 0.05). Mild fatigue and swelling of the extremities were seen in two patients each. Mild headache, transient diarrhea, and mild cloudiness of mind were seen in one patient. From this study it is concluded that MT is a safe and effective first‐step antihypertensive agent. The long‐term effect of MT as a monotherapy in the treatment of mild hypertension needs further clinical evaluation.
Stage‐specific behavioral, cognitive, and in vivo changes in community residing subjects with age‐associated memory impairment and primary degenerative dementia of the Alzheimer type
Authors: Reisberg Barry , Ferris Steven H. , de Leon Mony J. , Franssen Elia Sinaiko Emile , Kluger Alan , Mir Pervez , Borenstein Jeffrey , George Ajax E. , Shulman Emma , Steinberg Gertrude , Cohen Jacob 
Published: January 2005

AbstractStage‐specific relationships between the seven‐stage Global Deterioration Scale (GDS) for age‐associated memory impairment and primary degenerative dementia of the Alzheimerapos;s type and behavioral, cognitive, and neuroradiologic changes were examined in community residing subjects with normal aging or Alzheimerapos;s disease (AD). The results revealed significant decrements between GDS stages 2 and 3; 3 and 4; 4 and 5; and 5 and 6 for most behavioral measures. No decrements were noted between GDS stages 1 and 2. Consequently, the subjective complaints of cognitive decrement, which characterize GDS 2 subjects and which commonly accompany aging, do not appear to be accompanied by objective behavioral or cognitive change. Floor effects for most behavioral and cognitive measures occurred by GDS 6, with nearly uniform bottom scores by GDS stage 7. Computerized tomographic (CT) assessments of brain change revealed significant relationships with global severity on the GDS, but few significant consecutive stage decrements were noted. The magnitude of the relationship between CT assessments of brain change and GDS scores was notably less than the magnitude of the relationship noted between various behavioral measures and GDS. Although behavioral and neurcradiologic measures studied did not reveal decrements in the GDS 2 subjects in comparison with age‐matched GDS 1 subjects who do not have subjective decrements, previous studies of a neuroimmunologic measure (brain reactive antibody levels) do appear to have indicated significant differences between these groups. Consequently, there is some current preliminary evidence for the hypothesis of a physiologic substrate for the subjective deficits characteristic of the GDS 2 stage, as well as clear‐cut behavioral data distinguishing each of the subsequent GDS stages of aging and AD.
Does the brain possess an independent immune compartment?
Authors: Blumenthal Herman T. 
Published: January 2005

AbstractAn immunoregulatory feedback circuit exists between the CNS and the immune system comparable to other feedback systems that maintain homeostasis in mammals. Moreover, the brain “enjoys” certain privileges and autonomies. The privileges include a redistribution of blood flow, which provides additional blood to the brain under conditions of anoxia, and a redistribution of nutrients so that the brain preferentially receives an additional supply under conditions of starvation. The so‐called immunologic privilege of the brain serves to shield it from systemic immune reactions that may be damaging to neural structures. An example of an autonomy is the independent endocrine capacity of the CNS; but does it also possess an independent immune capacity? Studies on neuron‐binding immunoglobulins (lgs) have revealed that some of these lgs are directed against antigens shared between neural structures and tissues outside the CNS, such as the Thy‐1 antigen of thymic lymphocytes. Other lgs appear to be specific for neural antigens. This suggests that the blood‐brain‐barrier (BBB) may protect neural structures from cross‐reacting with extraneural antibodies. But the BBB would also provide a barrier to the systemic immune system when aberrant antigens are generated within the CNS. Observations such as these have given rise to the hypothesis that antibodies to neural antigens might be generated within the CNS. Evidence is provided here from studies on monkeys, as well as a review of relevant literature, that the CNS contains structures that can provide an independent immune capacity. These include perivascular and glial cells and elements of the choroid plexus. Some of these structures also display markers similar to those displayed by immunocytes. It is proposed here that neuronophagia and the resultant loss of neurons with age may be due to immune reactions confined to the CNS. It is also proposed that certain CNS phenomena associated with Alzheimerapos;s disease may be due to parallel age‐related autoimmune reactions not causally related to AD.
Development of the hippocampal formation in mutant mice
Authors: Nowakowski R. S. 
Published: January 2005

AbstractThe highly laminated structures of the hippocampal formation provide an ideal location for the assessment of the effects of mutant genes on the development of the central nervous system. Presently seven different mutations and one genetic variant (NZB/BINJ) are known to affect the developing hippocampal formation. Each of them affects neuronal migration and/or cell proliferation in a different constellation of cell types and produces a distinct pattern of reorganization. The fact that different mutations, which map to different chromosomal locations, can affect neuronal migration in the hippocampal formation indicates that there is a variety of developmental processes that influence the ultimate destination of a migrating neuron. In addition, the fact that the different mutations do not uniformly affect all populations of migrating cells indicatesd that, in some cases, migrating neurons with different destinations may use different cues to find their final position. Conversely, the overlap in the phenotypes of the various mutations provides insight into the extent of common gene expression during neuronal migration. For example, six of the mutations have ectopic CA3 pyramidal cells. These same six mutations also have ectopic granule cells in the molecular layer of the cerebellar cortex. This association may reflect the existence of common gene expression during the migration of these two diverse cell types. Also, NZB/BINJ mice and four of the single gene mutations have immune system dysfunctions. Thus, there may be common gene expression during the differentiation of the immune system and neuronal migration. These genetic tools provide a significant new way to explore cerebral cortical development, in general, and neuronal migration, in particular.
Peptide t sequences prevent neuronal cell death produced by the envelope protein (gp 120) of the human immunodeficiency virus
Authors: Brenneman Douglas E. , Buzy Jeanine M. , Ruff Michael R. , Pert Candace B. 
Published: January 2005

AbstractPeptide T, an octapeptide sequence found in the external evelope protein (gp 120) of the ARV isolate of human immunodeficiency virus (HIV), was investigated for its action in preventing neuronal death observed in mouse hippocampal cultures treated with purified gp 120. Cell counts of neuronspecific enolase‐identified neurons revealed that peptide T application completely and potently antagonized gp 120‐induced death. Analogs of the core pentapeptide sequence of pepptide T, TTNYT, found in the second variable region of all gp 120 isolates sequenced to date, were also tested and found to be similarly active. Investigations of structure activity relationships of related peptides suggested that the second and fourth positions in the core pentapeptide sequence were critical for biological activity in the neuronal survival assay. Antiserum against the peptide T sequence found in the the ARV isolate was found to prevent neuronal cell death in cultures treated with purified gp 120 from the IIIB isolate of HIV. These data indicate that the peptide T sequence is effective in preventing neuronal cell death associated with the envelope protein and provide a rationale for peptide T to be evaluated as a potential therapeutic agent for the neuropsychiatric and neurological sequelae of acquired immune deficiency syndrome.
Perceptual masking of drug stimuli
Authors: Gauvin David V. , Young Alice M. 
Published: January 2005

AbstractThree separate drug‐discrimination experiments, using pigeon subjects, were designed to assess the modification of a morphine (MS) stimulus by d‐amphetamine (AMPH). Experiment 1 examined the drug mixture in a two‐choice discriminative procedure in three groups of subjects trained to one of three doses of MS (1.0, 3.2, or 10 mg/kg) vs. saline (SAL). Blockade of the MS stimulus by concomitant AMPH administration was training dose‐dependent. Complete blockade was found in the high‐MS (10 mg/kg) training dose (TD) group; partial blockade was found in the intermediate‐TD (3.2 mg/kg) group; and complete generalization was found in the low‐TD (1.0 mg/kg) group. Experiment 2 was designed to assess whether the MS‐AMPH mixture resulted in the creation of a functionally new stimulus. With a three‐choice drug‐discrimination procedure, two new groups were trained to discriminate between 3.2 mg/kg MS, SAL, and 1.8 mg/kg AMPH. Once training criteria were met, subjects were divided into two groups and one group's MS training dose was faded up to 10 mg/kg. Data clearly indicated that MS‐AMPH combinations did not produce novel stimuli. Experiment 3 was designed to assess the MS‐AMPH combinations in a three‐choice quantitative discrimination using 1.8 mg/kg MS vs. SAL vs. 10 mg/kg MS as discriminative stimuli. Data suggested that if masking does occur, it is a result of shifting the dose‐response function to the left (i.e., to a nondiscriminable dose). We conclude that perceptual masking of drug stimuli can occur, but the phenomenon seems dependent on training dose and/or drug and behavioral history.
A pentylenetetrazol‐like stimulus during cocaine withdrawal: Blockade by diazepam but not haloperidol
Authors: Wood Douglas M. , Laraby Patrick R. , Lal Harbans 
Published: January 2005

AbstractIn the present experiment, rats were trained to discriminate the stimulus properties of an anxiogenic drug, pentylenetetrazol (PTZ), 20 mg/kg, from saline using a food‐rewarded two‐lever choice task. Following training, substitution tests were performed, and rats selected the PTZ‐appropriate lever after PTZ in a dose‐dependent manner. Cocaine (5–20 mg/kg) did not substitute for PTZ. Subsequently, testing and training were halted, and cocaine, 20 mg/kg/8 hr, was administered to three groups of ten rats per group for 3, 7, and 14 days. Withdrawal from cocaine produced a PTZ‐like stimulus that increased in intensity proportionally to the duration of chronic cocaine exposure. The selection of the PTZ lever by these subjects during withdrawal was reversed following administration of diazepam, 5 mg/kg, but not by haloperidol, 0.64 mg/kg. Stimulus control tests performed 2 weeks following the last withdrawal test demonstrated a return to baseline responding, with no significant loss of stimulus control. These data demonstrate the development of a PTZ‐like interoceptive stimulus during withdrawal from cocaine, which suggests the possibility of an anxiety‐like stimulus during cocaine withdrawal. This anxiety‐like component appears to be influenced by the duration of cocaine exposure.