22 The BRAC was considered to be clearly expressed clinically early after birth and then, within weeks or months, to become less evident during daytime and mostly seen during sleep, with the alternation between rapid eye movement (REM) and nonREM sleep. Apart from sleep, several physiological functions have an ultradian periodicity of approximately 90 min In man. The buy Crizotinib period of the BRAC might be species-specific since, for example, Inhibitors,research,lifescience,medical luteinizing hormone (LH) blood concentrations oscillate with periods of 20 minutes to 2 hours in different animal

species.23 In mice, there Is an ultradian rhythm for avoidance behavior that Is of 9 min in young mice, near the Inhibitors,research,lifescience,medical period of REM/nonREM sleep, while in adult mice it is of 20 mln.24 In humans, a mean period of the BRAC of

around 90 mln was found In endocrine studies or In studies on dreaming and sleep.25 For example, the secretory pulses of prolactin Into blood In humans have a mean period of 95 mln and are closely associated with the secretory pulses of LH.26 There Is an ultradian rhythm of nasal permeability, with a shift between nostrils that Inhibitors,research,lifescience,medical correlates with changes In controlateral electroencephalogram (EEG) wave amplitude.27 The BRAC has the hypothetical role of coordinating bodily functions, hormones, sleep phases, and perceptual and cognitive capacities. This hypothesis raises Inhibitors,research,lifescience,medical several questions, few of which have yet been solved. First, there have been subsequent negative findings, for example regarding the absence of ultradian rhythms in the cognitive task

of the sentence -verification test.28 Also, many variables show more than one Inhibitors,research,lifescience,medical ultradian period and have superimposed circadian components. Finally, the existence of groups of neurons that govern ultradian periodicities has been demonstrated for gonadotrophin-releasing hormone (GnRH, also called LHRH, for luteizining hormone-releasing hormone) in the preoptic area of the hypothalamus and for the sleep architecture, but not for other rhythms; moreover, a few authors have suggested that evidence for the existence of BRAC might those result from artifacts in protocols and calculations.28 Ultradian clocks have not yet been as clearly delineated, as is the case for the circadian clock in the SCN Reciprocal influences and conpling between biological clocks Many biological functions show more than one rhythm and have superimposed ultradian and circadian components. Moreover, many tissues express endogenous rhythms.

1,54 In two studies, 27% to 31% of individuals with BDD had been completely housebound for at least

1 week due to BDD symptoms, and more than 40% had been psychiatrically hospitalized.52,55 Risk behaviors: suicidality, substance abuse, and violence Rates of suicidal ideation, suicide attempts, and completed suicide appear find more markedly elevated.79 Approximately 80% of individuals with BDD report past or current suicidal ideation, and about one quarter have attempted suicide, which is often attributed to BDD symptoms.42,50,52,79-81 In the only prospective study of the course of BDD, completed suicide was reported in 0.3% of cases per year.82 This Inhibitors,research,lifescience,medical finding should be considered preliminary, because the sample size was relatively Inhibitors,research,lifescience,medical small and the follow-up period was relatively brief; nonetheless, this suicide rate is markedly elevated. While caution should be used in comparing this rate

to that of other disorders, the standardized mortality ratio in this study is higher than that reported for nearly any other mental disorder.83 Approximately one third of people with BDD report violent behavior that they attribute primarily to BDD symptoms (eg, attacking someone or damaging property).1,84 Clinical impressions suggest that anger or violence may be fueled by anger about looking “deformed,” inability to fix the “defect,” delusions of Inhibitors,research,lifescience,medical reference (eg, believing that other people are mocking the “defect”), and feeling rejected by others because of the “defect.” In addition, anger or even violent behavior may be caused by dissatisfaction with cosmetic procedures. According to one survey, 12% of plastic surgeons said that they had been threatened physically by a dissatisfied Inhibitors,research,lifescience,medical BDD patient.85 Inhibitors,research,lifescience,medical There are occasional reports of individuals with probable BDD who attacked and even

killed their plastic surgeon after being distraught by the outcome of a cosmetic procedure.2 Many individuals with BDD abuse alcohol or drugs. In one study,86 48.9% of BDD participants were diagnosed with a lifetime substance-use disorder, with 42.6% reporting an alcohol-use disorder and 30.1% reporting a cannabis-use disorder. Onset of BDD preceded onset of a substance-use disorder by at least 1 year in 60% of Florfenicol the participants, followed onset of the substance-use disorder in 19% of the participants, and began in the same year in 21%. When asked about the relationship between substance use and BDD symptoms, 68% said that BDD symptoms contributed to the substance use becoming problematic.86 Comorbidity BDD is often comorbid with other mental disorders. In the two largest phenomenology studies of individuals ascertained for BDD (n=293 and n=200), which assessed all participants with the Structured Clinical Interview for DSM,14 major depressive disorder was the most common comorbid disorder, with a lifetime prevalence of about 75% in both samples.

15 The course of a progressive dementia such as Alzheimer disease will often distinguish it from impairment due to head injury or stroke. Notes This work was supported in part by National Institute of Mental Health grants MH43693, MH51459, MH45131, and MH49671, and by the

Department of Veterans Affairs. The first author was supported by 5 T32 MH19934-08.
Dementia has as its central feature impairment in cognitive function. Clinically, the cognitive deficit, will most often manifest selleck kinase inhibitor itself as memory problems and most. usually as difficulties in the ability Inhibitors,research,lifescience,medical to retain new information. However, a number of other areas of cognition are affected and it is important to realize that, memory is but one of the cognitive skills compromised in Inhibitors,research,lifescience,medical dementia. Dementia is thus prima facie a disorder of cognition and it is our cognitive facilities that underlie our abilities to engage successfully in the activities of daily living (ADL). From this it follows that enhancement to cognitive function will facilitate performance of these ADL. The assessment, and understanding of these impairments are crucial to any treatment of the Inhibitors,research,lifescience,medical disorder. Behavioral observation

today has a very limited role to play in the assessment of mental ability, as it is now known that many important aspects of cognitive function are not. readily assessable by this technique. Cognition can only truly be assessed accurately through the direct, use of objective psychometric tests. However, historically the diagnosis of dementia has been largely the province of gerontologists and old-age psychiatrists, who, in the absence of widely accepted tasks, relied primarily on their clinical judgment. Memory deficits Inhibitors,research,lifescience,medical are one of the more obvious aspects of cognitive disorder, both to the patient and the observer; therefore, the marked anterograde amnesia seen in Alzheimer’s and other dementias became the hallmark of the disorders. This legacy remains today and can be evidenced Inhibitors,research,lifescience,medical by inspecting the Diagnostic and Statistical Manual of Disorders, Fourth Edition (DSM-IV) guidelines for any of the dementias.1 Nonetheless, as will emerge

in this chapter, memory deficits are only one of several major aspects of cognitive dysfunction in dementia. Unfortunately, the principal instrument used in most of the major clinical trials of Alzheimer’s disease (AD) in recent years, the Alzheimer’s Disease Assessment Scale-Cognitive Subsection (ADAS-COG), primarily assesses aspects of 17-DMAG (Alvespimycin) HCl memory, which has resulted in other important cognitive deficits in dementia being overlooked. As a consequence, the full therapeutic potential of the treatments studied has not been evaluated. Assessment of cognitive function Cognitive functions are those aspects of mental activity that underpin the quality with which we are able to conduct ADL. A number of these aspects of mental activity are subject, to change in the efficiency with which they operate.

24-40 In our hands, a 0.5-mg subcutaneous injection of scopolamine in young HVs induced impairment, in immediate and delayed word recall, multiple choice reaction time and accuracy, and the digit symbol substitution test. In quantified EEG, it. reduced total power and induced an

increase in S and a decrease in 6, a, and p absolute power; in relative power analysis, the 8 and p band activity was increased and that of the 6 and a bands decreased (Figure 1.) An interesting feature of this model is that is can be reversed or prevented not. only by cholinomimetic drugs, but. also, as we have found, by compounds Inhibitors,research,lifescience,medical without direct, cholinergic effects.30,31,38,41 Figure 1. Effect of scopolamine (0.5 mg subcutaneously)on Bioactive Compound Library nmr electroencephalogram (EEG) in 12 healthy young men. Placebo and scopolamine were administered according to a crossover, double-blind design. Inhibitors,research,lifescience,medical EEG was recorded from 28 electrodes during the first 3 min in … The lorazepam model Benzodiazepines (BZDs) are known to induce sedation, psychomotor impairment, and anterograde amnesia, leaving retention and retrieval spared.42 Although cognitive impairment is

a class effect, differences between different BZDs have been reported, independently of their elimination half-lives.43-45 A dissociation Inhibitors,research,lifescience,medical between the cognitive and sedative effects of drugs has also been described.46 Lorazepam has dose-related memory- and attention-impairing effects.43,44,47 It has been suggested48 that the profile of lorazepam-induced Inhibitors,research,lifescience,medical cognitive impairment is close to that observed in Korsakoff’s syndrome, whereas scopolamine rather mimics AD. Some studies47,49 were unable to distinguish the effects of lorazepam from those

of scopolamine. Both drugs were Inhibitors,research,lifescience,medical shown to have similar effects on verbal priming50 and in a face-name associative encoding task,51 and as well as on associated functional magnetic resonance imaging (fMRI) activation patterns. On the other hand, differential effects were found on logical reasoning, immediate and delayed recall,52 and priming for human faces.53 BZDs have well-known effects on EEG. Changes in p amplitudes seem to reflect their interaction and intrinsic efficacy at the GABAA-BZD (GABA, y-aminobutyric acid) receptor complex; their effects on p and a activity their anxiolytic, anticonvulsant, and sedative properties; and Carnitine palmitoyltransferase II 8-induced changes their hypnotic action.54 In our hands, an oral dose of 2 mg lorazepam impaired immediate and delayed word recall, multiple choice reaction time and accuracy, and digit, symbol substitution test, but. had no effect, on flicker fusion frequency. In quantified EEG, lorazepam’s effects were dose -dependent in length and intensity, increasing 8 and P power, and decreasing the power of the 6 and a frequency bands (Figure 2.) Figure 2. Effects of three oral doses of lorazepam on electroencephalogram (EEG) in 20 young healthy male volunteers. Lorazepam 0.

Also the use of more than one set of primers in the studies from showed a higher deletion (12, 13) (Table ​(Table33). In case of the study done in Kuwait on different Arabic populations, the percentage was higher than our results (86%) were they used the three sets of primers (14). While the study done on the Moroccan population revealed percentage less than our results (51.3%) (15). With that we conclude the importance of including both sets Inhibitors,research,lifescience,medical A and B primers to cover most of the gene hotspot for more accurate screening

of the deletion within the dystrophin gene, together with the duplication detection as the quantitative PCR proved to be beneficial in our study. Immunohistochemical study for further detection of DMD/BMD patients with point mutation, in the cases with no deletion or duplication is http://www.selleckchem.com/products/Bafilomycin-A1.html necessary Inhibitors,research,lifescience,medical for accurate diagnosis. Acknowledgment The authors express their sincere thanks to Dr. Hideo Sugita (Honorary President of National Center of Neurology and Psychiatry, NCNP, Japan) for his continuous efforts to support this work, Dr. Eijiro Ozawa (Director General Emeritus, National Institute of Neuroscience, NCNP) for his guidance and encouragement and Dr. Narihiro Minami (NCNP) for his teaching

effort.
Although the recessive forms of Charcot-Marie-Tooth disease (AR-CMT) are considered to be much rarer than the autosomal Inhibitors,research,lifescience,medical dominant forms, in countries with a high rate of consanguineous marriages they may account for more than 50% of all forms of CMT (1). The Charcot-Marie-Tooth type 4A locus was mapped to the 8q13 region in 4 Tunisian families (2). After the identification of the Ganglioside-induced differentiation-associated Inhibitors,research,lifescience,medical protein-1 gene (GDAP1), 24 mutations have been identified in patients originating from different regions of the

world (3–5). The majority of GDAP1 mutations segregate with the CMT phenotype as an autosomal recessive trait. To date only one mutation, R120W, has been shown to apparently cause disease in the heterozygous state associated Inhibitors,research,lifescience,medical with a neuropathy transmitted as an autosomal dominant trait in 3 generations from (6). The identification of the pathogenic mutations in GDAP1 provides an opportunity to delineate phenotype-genotype correlations in AR-CMT diseases. CMT4C4 disease is characterized by an early onset, axonal neuropathy with hoarseness (7). Recently, the GDAP1 protein was shown to be present in the outer mitochondrial membrane by colocalization with the mitochondrial marker Mito Tracker (8). The GDAP1 protein was postulated to regulate dynamics of the mitochondrial fission in cooperation with mitofusins 1 and 2 (9). Clinical report The patient, a 32-year-old man, was born from consanguineous parents (first cousins) after an uneventful pregnancy and delivery. He began to walk at the age of 15 months.

Using this criterion, no significant increase of OC illness among first-degree relatives of 144 obsessional neurotics was observed, although an increased rate of psychiatric illness among these relatives was reported. Unfortunately, no information about OC symptomatology among relatives who were not hospitalized was provided. Direct interview family studies Subsequent to 1986, all family studies collected direct interview from at least some of the relatives in the family. With the exception of one study,52 all available relatives were

Inhibitors,research,lifescience,medical directly interviewed. In the study by McKeon and Murray52 all family members of adult probands with OCD were given the Leyton Obsessional Inventory (LOI), and only those relatives who scored high on the LOI were directly interviewed. Inhibitors,research,lifescience,medical Only one of the NVP-BEZ235 price interviewed relatives met criteria for OC neurosis, suggesting that the disorder is not familial. It is possible that some relatives with OCD may not have been identified with this ascertainment scheme. Low scores on

the LOI can be observed in individuals having only a few obsessions and/or compulsions which consume significant time and cause considerable distress Inhibitors,research,lifescience,medical and result in a diagnosis of OCD. Thus, it is possible that some of the noninterviewed relatives could have scored low on the LOI yet still met criteria for a diagnosis of OCD. In should be noted, however, that these investigators did observe an increased rate of mental illness overall Inhibitors,research,lifescience,medical among the relatives of these OCD probands. The remaining 15 family studies of OCD interviewed all available first-degree relatives with structured psychiatric interviews.38,40-41,53-65 In some of these studies, additional information was obtained from all interviewed relatives about the presence of OCD in all of their first-degree relatives; even those relatives that had been directly interviewed. Thus, both direct interview data and family history data were available for all interviewed individuals in those Inhibitors,research,lifescience,medical family studies. Table II Family studies of OCD. The rates shown refer to the

frequency of these conditions among first-degree relatives. While there were some inconsistent results, most of these studies provided data that are consistent with the hypothesis that some forms of OCD are familial mafosfamide (Table II). In seven studies ascertainment was through children and/or adolescents with OCD (Table II). In the remaining eight studies, ascertainment was through adults with OCD (Table II). Studies of families ascertained through child/adolescent probands In all of the studies in which all available relatives of children and/or adolescents with OCD were interviewed,40-41,61-65 the rates of OCD and subclinical OCD were significantly higher than the population prevalence and/or the rate obtained in controls assessed in the same way.

Under the electron microscope, NFTs can be seen to consist principally of paired helical filaments together with a smaller proportion of straight filaments. These filaments are composed of the microtubule-associated protein tau, present in a highly phosphorylated state, and are abnormal, being found only in dementia. In the normal state, tau is expressed to a significant extent only in neurons where it is present in axons. Here it acts to stabilize microtubules, which are an

essential component of the cellular cytoskeleton and in neurons assume a straight track parallel to axons. Microtubules are essential for fast, axonal transport, the process whereby vesicles and other organelles such as mitochondria are transported Inhibitors,research,lifescience,medical from the cell body to distal parts of the neuron including synapses. The consequences of loss of fast axonal transport, from the neuron or destruction of microtubules are not, fully understood, but would be expected to result, in loss of function of the neuron if not loss of viability. Tau, therefore, has an important role in regulating the stability and function Inhibitors,research,lifescience,medical of neurons. In vitro, tau binds to tubulin (the building block of the microtubule itself) and promotes the formation of tubulin polymers and the extension

of these polymers into microtubules. Six AT7519 purchase different isoforms of tau are generated from a single gene in the central nervous system, and there is some evidence that these isoforms have different Inhibitors,research,lifescience,medical abilities to promote microtubule Inhibitors,research,lifescience,medical assembly in vitro. There is developmental regulation of the expression of these isoforms, as in the fetal forms, which bind microtubules that are in excess relatively weakly, with a change to stronger binding isoforms on maturation. However, such regulation is a

relatively slow process and real-time regulation of the properties Inhibitors,research,lifescience,medical of tau is almost certainly altered by the phosphorylation state of tau. Tau phosphorylation – regulation of microtubule stability and role in Alzheimer’s disease Tau is a highly phosphorylated protein, and its ability to bind microtubules is regulated by this phosphorylation – the more phosphates, the less tau promotes microtubule assembly.49 There is some controversy as to whether new it is the amount of phosphorylation that is important or whether there are specific sites in tau that are critical in tau-tubulin interactions.50 In the fetus, tau is very highly phosphorylated, and even in normal adult human brain examined in biopsy samples the amount of phosphorylation is relatively high.51,52 It is likely that acute regulation by a combination of kinases and phosphatases of tau phosphorylation controls the properties of neurons, which in turn alters the rate of transport within the neuron and, perhaps, other, structural, properties of tau. Even though tau is phosphorylated in normal adult neurons, and more so in normal fetal neurons, in the PHF-tau aggregates of AD, tau is even more phosphorylated.

These concepts can be approached theoretically as well as in nonclinical pharmacological studies. While efficacy and safety in humans cannot be assured by studies in animals, some comfort level can be achieved by the use of animal models of toxicology. The second element, is for the program to be run with solid medical principles, or “good medicine.” The main principle is to do no harm. Inhibitors,research,lifescience,medical No clinical program should knowingly put, any clinical trial subject at risk of harm. Proper

clinical trial designs should be based on acceptable methods with a profound understanding of the disease under study. When adverse events appear, a conscientious evaluation of their significance to the individual patient as well as to the population at large, must be performed. The third element in drug development is to assure compliance with regulatory requirements, Inhibitors,research,lifescience,medical or “good regulations.” Fulfillment of regulatory requirements is in addition to fulfillment of the requirements of “good science” and “good medicine.” The regulations ensure that regulatory bodies such as the Food and Drug Administration (FDA) can

properly review and evaluate a drug development program in a standardized manner. The team The drug development team includes a diverse group of individuals Inhibitors,research,lifescience,medical with different philosophies and approaches to the development process. All team members must work closely together to ensure that a drug is both safe and efficacious. Discovery/development The discovery and development groups are comprised Inhibitors,research,lifescience,medical of the basic scientists and chemists who created the new molecule. This group synthesizes drug substances for “drug-screening,” pharmacology, and toxicology studies, and also prepares clinical supplies. Nonclinical pharmacology and toxicology This group studies the drug product in animal models of efficacy and safety in order to identify potential efficacy and safety issues in humans. It is critical for the clinical and development groups to work closely with the lexicologists in the design of animal studies to ensure their relevance

to the clinical environment. Clinical Inhibitors,research,lifescience,medical research Clinical research has the ultimate responsibility for testing drug products in humans: the monitoring of drug safety rests MEK inhibitor squarely on the shoulders of clinical research. Clinical trials must be science-based with proper statistical methodologies and have clinically relevant end points. Clinical research interacts directly with the FDA and however is responsible for the generation of study reports with input from biostatisticians and regulatory affairs. Clinical research can also generate the publications necessary for the marketing of any drug product. Regulatory affairs The regulatory affairs department is the interface with the FDA. It is their responsibility to ensure compliance with the rules and regulations established by the Federal Food Drug and Cosmetic Act (FDCA)1 and its amendments.

The realization of maybe future, more complex

liposome structures with advanced efficacy will to a great extent dependent on those achievements.
Mononuclear phagocytes such as monocytes, macrophages, and dendritic cells are intrinsically involved in innate immunity. As the designation denotes, the chief role of these cells is phagocytosis whereby cells will engulf and destroy apoptotic cells, pathogens, and other targets. This occurs either through employing opsonin receptor-dependent CT99021 ic50 mechanisms via complement- and Fc-receptors, or opsonin receptor-independent mechanisms via lectin-receptors, scavenger receptors, stearylamine receptors or CD14 [1]. Due Inhibitors,research,lifescience,medical to its pivotal Inhibitors,research,lifescience,medical role in inflammation, the mononuclear phagocytic system (MPS) is an important target for drug delivery to treat disease. For certain diseases such as chronic obstructive pulmonary disease (COPD), asthma, atherosclerosis, and

cancer [2–4] and for pathogenic infections including tuberculosis [5], human immunodeficiency virus (HIV), and Leishmaniasis Inhibitors,research,lifescience,medical [6], the inflammatory process is a key driver of both disease progression as well as pathogenesis. Thus strategies aimed at targeting the MPS are highly attractive. In general however these cells are reputed to be difficult targets [7], particularly where intracellular delivery of the active is required such as for gene delivery [8]. Therefore the development of delivery systems that can target Inhibitors,research,lifescience,medical monocytes/macrophages intracellularly is crucial and could potentially open up new treatment paradigms for a range of diseases. Liposomes are the most widely investigated delivery system for phagocyte-targeted therapies providing advantages such as low immunogenicity, biocompatibility, cell specificity and drug protection. However, there are also shortcomings such as poor scale-up, cost, short shelf life, and in some cases toxicity and off target effects. Parenterally administered liposomes are naturally

Inhibitors,research,lifescience,medical cleared by the MPS. Liposomal delivery over systems targeting other cell types outside the MPS are modified to evade phagocytosis; for example, “stealth liposomes” include poly-ethylene-glycol (PEG) into their formulations to shield the liposomes from the MPS and increase their circulatory lifespan [9]. Consequently, numerous studies have been carried out to develop formulations that avoid monocyte/macrophage clearance, the corollary of which is that there is now greater knowledge of the mechanisms of binding and uptake that can be harnessed for drug targeting to monocyte/macrophage cells. 2. Monocytes and Macrophages Cell origin, lineage, and function in the MPS are complex and remain under considerable investigation.

1% BSA. Immunoreactive signals were detected using the enhanced chemiluminescence system (Millipore, Bedford, MA). To quantify the relative click here amount of ChAT protein, the blots were stripped and reprobed with an antibody against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [1:2000] (Biodesign, Saco, ME) for 1 h, followed by a horseradish peroxidase Inhibitors,research,lifescience,medical conjugated antibody [1:2000]. The ChAT and GAPDH

bands were quantified using the Genetools Analysis Software (Syngene, Cambridge, UK). ChAT immunoreactivity was normalized to GAPDH and the relative amount of ChAT protein in L1-deficient mice was expressed as a percent of ChAT present in wild-type littermates. ChAT activity ChAT activity was measured as previously described (Burgess and Aubert 2006; Burgess

et al. 2009), using the method of Fonnum (1969), modified by Tucek (1978). Briefly, each sample dissected from septal and striatal regions was homogenized, diluted, and incubated with [14C] acetyl CoA at 37°C for 30 min. Homogenates prepared from septal Inhibitors,research,lifescience,medical cells in vitro were incubated for 50 min. The reaction was then stopped, and the newly formed [14C]acetylcholine was extracted, counted, and expressed as nanomoles of acetylcholine produced per milligram of protein per hour (nmol ACh/mg prot/h). The final Inhibitors,research,lifescience,medical value for each sample represents an average of duplicates. Immunostaining Coronal brain sections were cut at 50 μm on a freezing microtome, collected serially Inhibitors,research,lifescience,medical in 96-well plates filled with cryoprotectant, and stored at −20°C. Sections from L1-deficient mice and their wild-type littermates were processed simultaneously using standard immunostaining procedures for fluorescence microscopy (Aubert et al. 1998) and stereology (Ypsilanti et al. 2008). For immunofluorescence staining, sections were rinsed in 0.1 M Tris-buffered saline

(TBS, pH 7.4) and incubated in TBS with 5% normal donkey serum and 0.25% Triton X-100 for 1 h at room Inhibitors,research,lifescience,medical temperature. For the combined detection of ChAT and L1, the goat anti-ChAT antibody [1:100] (AB144P, Chemicon) and the rabbit anti-L1 antibody [1:1000] (a generous gift from Dr. Stallcup et al. 1985) were used overnight at 4°C. Sections were rinsed and incubated with donkey anti-goat and donkey anti-rabbit secondary antibodies [1:200] (Jackson ImmunoResearch) coupled to biotin Resveratrol and indocarbocyanine (Cy3), respectively, for 2 h at room temperature in the dark. Sections were rinsed and incubated for 2 h in the dark with streptavidin-Alexa 488 and the nucleic acid staining cyanine dye monomer TO-PRO-3 iodide (2 μM). Sections were rinsed and mounted on presubbed slides, allowed to dry briefly, and coverslipped with a 10% solution of polyvinyl alcohol containing 2.5% 1,4-diazabicyclo-2,2,2-octane (PVA/DABCO, both from Sigma, St. Louis, MO).