Biomedical subjects

L Medina

Publications and source records attributed to L Medina.

At least 19 recordsLinked to original sources

PubMed2002

Expression patterns of Wnt8b and Wnt7b in the chicken embryonic brain suggest a correlation with forebrain patterning centers and morphogenesis.

The expression patterns of the genes Wnt7b and Wnt8b were analyzed in the brain of chick embryos, having special emphasis in the forebrain. Our results indicated that, at early developmental stages, cWnt8b is expressed in the isthmic organizer and in other areas postulated as forebrain patterning centers, such as the avian cortical hem and the zona limitans intrathalamica (zli). Later in development, cWnt7b becomes expressed in regions neighboring and sometimes overlapping the cWnt8b domains, such as the thalamus on both sides of the zli, or the medial pallium adjacent to the cortical hem. This sequential expression of cWnt8b and cWnt7b is consistent with a role in the patterning and morphogenesis of these forebrain regions.

Animals↗

PubMed2001

Cadherin expression by embryonic divisions and derived gray matter structures in the telencephalon of the chicken.

The expression of three cadherins (cadherin-6B, cadherin-7, and R-cadherin) was studied by immunohistochemistry in the telencephalon of chicken embryos at intermediate stages of development (11 and 15 days of incubation). Expression patterns were related to cytoarchitecture and to previously published data on functional connections and on the expression of gene regulatory proteins. Our results indicate that, like in other regions of the embryonic chicken brain, the expression of each cadherin is restricted to parts of embryonic divisions as well as to particular nuclei, areas or their subdivisions. The expression patterns are largely complementary with partial overlap. The regional expression of the cadherins respects the boundary between the pallium and the subpallium as well as between various pallial and subpallial subdivisions. Novel subdivisions were found in several telencephalic areas. For example, subjacent to the hyperstriatum, the neostriatum contains multiple islands of cells with a profile of cadherin expression that differs from the surrounding matrix ("island fields"). Moreover, the expression of each cadherin is apparently associated with parts of intratelencephalic neural circuits and of thalamopallial and basal ganglia pathways. These results support a role for cadherins in the aggregation and differentiation of gray matter structures within embryonic brain divisions. The cadherin immunostaining patterns are interpreted in the context of a recently proposed divisional scheme of the avian pallium that postulates medial, dorsal, lateral, and ventral divisions as complete radial histogenetic units (Puelles et al. [2000]).

Aging↗

PubMed2001

Expression of R-cadherin and N-cadherin by cell groups and fiber tracts in the developing mouse forebrain: relation to the formation of functional circuits.

The expression of R-cadherin and N-cadherin was mapped in the postnatal forebrain of the mouse by immunohistochemistry and in situ hybridization. Results show that the two molecules are expressed in specific and restricted patterns in numerous brain nuclei, gray matter areas and cortical layers that are widely distributed throughout the mouse forebrain at postnatal day 1. The expression pattern of R-cadherin is clearly distinct from that of N-cadherin, but overlap is observed in many areas. In many cortical areas, the two cadherins have a laminar-specific distribution that varies from region to region. In addition, immunohistochemical data revealed expression of R-cadherin protein and N-cadherin protein in the neuropil of many brain regions as well as in the axons that travel in fiber tracts such as the olfactory tract, the anterior commissure, the corpus callosum, the stria terminalis and the fornix. Often, subsets of axons within the same fiber tract differentially express R-cadherin and N-cadherin, with partial overlap of expression. The targets of the cadherin-immunoreactive fiber bundles often contain neuropil as well as cell bodies of neurons that also express the same type(s) of cadherin, suggesting that R-cadherin and N-cadherin may be involved in target recognition and the establishment of connections. Specifically, the expression of R-cadherin and N-cadherin is related to the maturation of thalamocortical sensory pathways, corticofugal pathways, and pathways associated with the hippocampal complex, the piriform cortex, and the amygdala. It is also related to the development of the cell groups associated with these pathways.Together, the results from the present study indicate the possibility that the selective adhesion of neural structures that express the same type(s) of cadherin contributes to the formation of gray matter areas, neural circuits and functional connections in the postnatal forebrain of the mouse.

Aging↗

PubMed2000

Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways.

Fibroblast growth factor receptors (FGFR) are widely expressed in many tissues and cell types, and the temporal expression of these receptors and their ligands play important roles in the control of development. There are four FGFR family members, FGFR-1-4, and understanding the ability of these receptors to transduce signals is central to understanding how they function in controlling differentiation and development. We have utilized signal transduction by FGF-1 in PC12 cells to compare the ability of FGFR-1 and FGFR-3 to elicit the neuronal phenotype. In PC12 cells FGFR-1 is much more potent in the induction of neurite outgrowth than FGFR-3. This correlated with the ability of FGFR-1 to induce robust and sustained activation of the Ras-dependent mitogen-activated protein kinase pathways. In contrast, FGFR-3 could not induce strong sustained Ras-dependent signals. In this study, we analyzed the ability of FGFR-3 to induce the expression of sodium channels, peripherin, and Thy-1 in PC12 cells because all three of these proteins are known to be induced via Ras-independent pathways. We determined that FGFR-3 was capable of inducing several Ras-independent gene expression pathways important to the neuronal phenotype to a level equivalent of that induced by FGFR-1. Thus, FGFR-3 elicits phenotypic changes primarily though activation of Ras-independent pathways in the absence of robust Ras-dependent signals.

Animals↗

PubMed2000

Pathway tracing using biotinylated dextran amines.

Biotinylated dextran amines (BDA) are highly sensitive tools for anterograde and retrograde pathway tracing studies of the nervous system. BDA can be reliably delivered into the nervous system by iontophoretic or pressure injection and visualized with an avidin-biotinylated HRP (ABC) procedure, followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. High molecular weight BDA (10 k) yields sensitive and exquisitely detailed labeling of axons and terminals, while low molecular weight BDA (3 k) yields sensitive and detailed retrograde labeling of neuronal cell bodies. The detail of neuronal cell body labeling can be Golgi-like. BDA tolerates EM fixation and processing well and can, therefore, be readily used in ultrastructural studies. Additionally, BDA can be combined with other anterograde or retrograde tracers (e.g. PHA-L or cholera toxin B fragment) and visualized either by multi-color DAB multiple-labeling - if permanent labels are desired, or by using multiple simultaneous immunofluorescence - if fluorescence viewing is desired. In the same manner, BDA pathway tracing and neurotransmitter immunolabeling can be combined. Note that BDA pathway tracing can also be combined with anterograde or retrograde labeling with fluorescent dextran amines, if one wishes to exclusively use tracers with the favorable transport properties and sensitivities of dextran amines. In this case, the BDA can be visualized together with the fluorescent dextran amines using fluorescence labeling for the BDA, or the fluorescent dextran amines can be visualized together with the BDA by multicolor DAB labeling via immunolabeling of the fluorescent dextran amines using anti-fluorophore antisera. BDA is, thus, a flexible and valuable pathway tracing tool that has gained widespread popularity in recent years.

Animals↗

PubMed2000

Identification of the anterior nucleus of the ansa lenticularis in birds as the homolog of the mammalian subthalamic nucleus.

In mammals, the subthalamic nucleus (STN) is a glutamatergic diencephalic cell group that develops in the caudal hypothalamus and migrates to a position above the cerebral peduncle. By its input from the external pallidal segment and projection to the internal pallidal segment, STN plays a critical role in basal ganglia functions. Although the basal ganglia in birds is well developed, possesses the same major neuron types as in mammals, and plays a role in movement control similar to that in mammals, it has been uncertain whether birds possess an STN. We report here evidence indicating that the so-called anterior nucleus of the ansa lenticularis (ALa) is the avian homolog of mammalian STN. First, the avian ALa too develops within the mammillary hypothalamic area and migrates to a position adjacent to the cerebral peduncle. Second, ALa specifically receives input from dorsal pallidal neurons that receive input from enkephalinergic striatal neurons, as is true of STN. Third, ALa projects back to avian dorsal pallidum, as also the case for STN in mammals. Fourth, the neurons of ALa contain glutamate, and the target neurons of ALa in dorsal pallidum possess AMPA-type glutamate receptor profiles resembling those of mammalian pallidal neurons. Fifth, unilateral lesions of ALa yield behavioral disturbances and movement asymmetries resembling those observed in mammals after STN lesions. These various findings indicate that ALa is the avian STN, and they suggest that the output circuitry of the basal ganglia for motor control is similar in birds and mammals.

Animals↗

PubMed2000

Light and electron microscopic evidence for projections from the thalamic nucleus rotundus to targets in the basal ganglia, the dorsal ventricular ridge, and the amygdaloid complex in a lizard.

To elucidate the organization and evolution of the tectorotundotelencephalic pathways in birds and reptiles, we reinvestigated at both light and electron microscopic levels the efferent projections of nucleus rotundus in a lizard, using the sensitive tracer biotinylated dextran amine. Our results indicate that nucleus rotundus projects to targets in the basal ganglia (lateral parts of striatum and olfactory tubercle and possibly the globus pallidus), the anterior dorsal ventricular ridge (ADVR), and the amygdaloid complex (the central and possibly lateral amygdaloid nuclei). In these targets, the rotundal axon terminals establish asymmetric, presumably excitatory synaptic contacts, usually with dendrites of local cells. In the ADVR, the rotundal projection terminates in two separate radial regions showing distinct cytoarchitecture: 1) a dorsolateral region that extends radially from the dorsolateral ADVR ventricular surface to the ventral part of the lateral cortex and 2) the lateral part of a ventromedial region that extends radially from the dorsomedial and medial ADVR ventricle to a superficial area interposed between the dorsolateral ADVR and the striatum. These two ADVR regions have different connections with the thalamus and telencephalon, which suggests that they may be involved in different degrees of integration. Our study also suggests that the rotundal projection to the ventromedial ADVR field of lizards may be comparable to the rotundoectostriatal/periectostriatal projection of birds. The connections and pathways involving nucleus rotundus suggest that this nucleus conveys visual information which may play a role in visuomotor, emotional, and visceral functions.

Amygdala↗

PubMed2000

Do birds possess homologues of mammalian primary visual, somatosensory and motor cortices?

Recent data on the expression of several homeobox genes in the embryonic telencephalon of mammals, birds and reptiles support the homology of a part of the avian pallium, named the Wulst, and at least the more-medial and superior parts of mammalian neocortex. This conclusion is also supported by previous embryological, topological and hodological data. Furthermore, new evidence on the connections and electrophysiological properties of specific subfields within the avian Wulst, and on the thalamic territories that project to these fields, supports the more-specific conclusion that a primary visual area and a primary somatosensory-somatomotor area are present in the avian Wulst; these areas are likely to be homologous to their counterparts in mammals. In spite of this, developmental, morphological and comparative evidence indicate that some structural and physiological traits that appear to be similar in the Wulst and neocortex (such as the lamination or binocularity) evolved independently in birds and mammals.

Animals↗

PubMed1999

Nucleus accumbens in the lizard Psammodromus algirus: chemoarchitecture and cortical afferent connections.

To better understand the organization and evolution of the basal ganglia of vertebrates, in the present study we have analyzed the chemoarchitecture and the cortical input to the nucleus accumbens in the lacertid lizard Psammodromus algirus. The nucleus accumbens contains many gamma-aminobutyric acid (GABA)-positive neurons and calbindin-positive neurons, the majority of which may be spiny projection neurons, and a few dispersed neuropeptide Y-positive neurons that likely represent aspiny interneurons. The nucleus accumbens contains two chemoarchitectonically different fields: a rostromedial field that stains heavily for substance P, dopamine, GABA(A) receptor, and a caudolateral field that stains only lightly to moderately for them, appearing more similar to the adjacent striatum. Injections of biotinylated dextran amine were placed in either the medial, dorsomedial, or dorsal cortices of Psammodromus. The medial and the dorsal cortices project heavily to the rostromedial field of the accumbens, whereas they project lightly to moderately to the caudolateral field. Cortical terminals make asymmetric, presumably excitatory, synaptic contacts with distal dendrites and the head of spines. Our results indicate that the hippocampal-like projection to the nucleus accumbens is similar between mammals and reptiles in that cortical terminals make mainly excitatory synapses on spiny, putatively projection neurons. However, our results and results from previous investigations indicate that important differences exist between the nucleus accumbens of mammals and reptiles regarding local modulatory interactions between cortical, dopaminergic, and cholinergic elements, which suggest that the reptilian nucleus accumbens may be as a whole comparable to the shell of the mammalian nucleus accumbens.

Afferent Pathways↗

PubMed1999

The distribution of dynorphinergic terminals in striatal target regions in comparison to the distribution of substance P-containing and enkephalinergic terminals in monkeys and humans.

Single- and double-label immunohistochemical techniques using several different highly specific antisera against dynorphin peptides were used to examine the distribution of dynorphinergic terminals in globus pallidus and substantia nigra in rhesus monkeys and humans in comparison to substance P-containing and enkephalinergic terminals in these same regions. Similar results were observed in monkey and human tissue. Dynorphinergic fibers were very abundant in the medial half of the internal pallidal segment, but scarce in the external pallidal segment and the lateral half of the internal pallidal segment. In substantia nigra, dynorphinergic fibers were present in both the pars compacta and reticulata. Labeling of adjacent sections for enkephalin or substance P showed that the dynorphinergic terminals overlapped those for substance P in the medial half of the internal pallidal segment, but showed only slight overlap with enkephalinergic terminals in the external pallidal segment. The substance P-containing fibers were moderately abundant along the borders of the external pallidal segment, and enkephalinergic fibers were moderately abundant in parts of the internal pallidal segment. Dynorphinergic and substance P-containing terminals overlapped extensively in the nigra, and both extensively overlapped enkephalinergic fibers in medial nigra. Immunofluorescence double-labeling studies revealed that dynorphin co-localized extensively with substance P in individual fibers and terminals in the medial half of the internal pallidal segment and in substantia nigra. Thus, as has been found in non-primates, dynorphin within the striatum and its projection systems appears to be extensively localized to substance P-containing striatopallidal and striatonigral projection neurons. Nonetheless, our results also raise the possibility that a population of substance P-containing neurons that projects to the internal pallidal segment and does not contain dynorphin is present in primate striatum. Our results also suggest the possible existence of populations of striatopallidal and striatonigral projection neurons in which substance P and enkephalin or dynorphin and enkephalin, or all three, are co-localized. Thus, striatal projection neurons in primates may not consist of merely two types, one containing substance P and dynorphin and the other enkephalin.

Animals↗

PubMed1999

The functional anatomy of the basal ganglia of birds.

To study how the basal ganglia can control movement in birds, we have reinvestigated the connections of the pigeon dorsal pallidum. Our results indicate that avian basal ganglia appear to control movement through major projections to several premotor pretectal and tegmental centres which innervate the tectum, and through a minor projection to a possible motor thalamic centre which innervates the Wulst. For such control, separate striatopallidal output circuits appear to exist in birds that are remarkably similar to those described in mammals, suggesting that avian and mammalian basal ganglia may control movement through similar mechanisms, and that the morphological substrate for such control evolved earlier than previously thought.

Animals↗

PubMed1999

Immunohistochemical localization of NMDA- and AMPA-type glutamate receptor subunits in the basal ganglia of red-eared turtles.

Corticostriatal and thalamostriatal projection systems have been shown to utilize glutamate as a neurotransmitter in mammals and birds. Although corticostriatal and thalamostriatal projection systems have been demonstrated in turtles, it is uncertain whether they too use glutamate as their neurotransmitter. Immunohistochemical localization of glutamate and of NMDA- and AMPA-type ionotropic glutamate receptor subunits (NMDAR2A/B, GluR1, GluR2/3, and GluR4) were used to address this issue. Numerous medium-sized neurons that were rich in NMDAR2A/B and GluR2/3 were observed in the striatal part of the basal ganglia of red-eared turtles. Smaller numbers of medium-sized neurons and some large neurons rich in the GluR1 and GluR4 subunits were also observed in the striatum. The striatal neuropil was notably rich in GluR1, GluR2/3 and NMDAR2A/B subunits. The pallidal region was specifically rich in large neurons possessing GluR4 subunits. Consistent with the glutamate receptors on striatal and pallidal neurons, sources of input to the striatum and pallidum in turtle such as the dorsomedial and dorsolateral thalamic nuclei (which appear to correspond to intralaminar thalamic nuclei), telencephalic pallial cell groups, and the apparent subthalamic nucleus homologue were rich in glutamatergic neurons. The results show that the thalamostriatal, corticostriatal and subthalamo-pallidal projection systems of turtles are glutamatergic and that similar basal ganglia cell types in turtles and mammals have largely similar glutamate receptor characteristics.

Animals↗

PubMed1998

Structural and functional evolution of the basal ganglia in vertebrates.

While a basal ganglia with striatal and pallidal subdivisions is 1 clearly present in many extant anamniote species, this basal ganglia is cell sparse and receives only a relatively modest tegmental dopaminergic input and little if any cortical input. The major basal ganglia influence on motor functions in anamniotes appears to be exerted via output circuits to the tectum. In contrast, in modern mammals, birds, and reptiles (i.e., modern amniotes), the striatal and pallidal parts of the basal ganglia are very neuron-rich, both consist of the same basic populations of neurons in all amniotes, and the striatum receives abundant tegmental dopaminergic and cortical input. The functional circuitry of the basal ganglia also seems very similar in all amniotes, since the major basal ganglia influences on motor functions appear to be exerted via output circuits to both cerebral cortex and tectum in sauropsids (i.e., birds and reptiles) and mammals. The basal ganglia, output circuits to the cortex, however, appear to be considerably more developed in mammals than in birds and reptiles. The basal ganglia, thus, appears to have undergone a major elaboration during the evolutionary transition from amphibians to reptiles. This elaboration may have enabled amniotes to learn and/or execute a more sophisticated repertoire of behaviors and movements, and this ability may have been an important element of the successful adaptation of amniotes to a fully terrestrial habitat. The mammalian lineage appears, however, to have diverged somewhat from the sauropsid lineage with respect to the emergence of the cerebral cortex as the major target of the basal ganglia circuitry devoted to executing the basal ganglia-mediated control of movement.

Animals↗

PubMed1998

Evidence for the preferential localization of glutamate receptor-1 subunits of AMPA receptors to the dendritic spines of medium spiny neurons in rat striatum.

Although immunohistochemical studies have typically found the perikarya of striatal projection neurons to be devoid of immunohistochemical labelling for the GluR1 AMPA type glutamate receptor subunit, the striatal neuropil is rich in GluR1 immunolabelling and in situ hybridization histochemistry has indicated the presence of GluR1 message in many striatal neurons. To explore the possibility that GluR1 subunits may be synthesized by many striatal projection neurons, but selectively localized to their dendrites, we have used light-microscopic and electron-microscopic immunohistochemistry in combination with single-cell reverse transcription-polymerase chain reaction. Light-microscopic immunohistochemical studies confirmed the presence of abundant GluR1 immunoreactivity in the striatal neuropil in rats. Perikaryal labelling was restricted to neurons previously identified as parvalbuminergic neurons. Single-cell reverse transcription-polymerase chain reaction for individual striatal neurons in rats confirmed that most striatal projection neurons (i.e. containing either or both substance P message or enkephalin message) make GluR1 message. For example, 94% of enkephalin-containing neurons, 75% of substance P-containing neurons, and 87% of enkephalin and substance P co-containing neurons expressed GluR1 messenger RNA. Electron-microscopic immunohistochemistry revealed that GluR1 immunolabelling was prominent in 61% of dendritic spines and 53% of dendritic shafts. While prominent perikaryal GluR1 immunolabelling was observed only in a small population of interneurons, sparse perikaryal GluR1 immunolabelling was found associated with the rough endoplasmic reticulum, the Golgi apparatus, the outer membranes of the mitochondria, and the outer envelope of the nucleus of about 30% of striatal projection neurons (identified by their non-indented nuclei). These results indicate that striatal projection neurons selectively target GluR1 subunits to their spines and dendritic shafts. Our finding has implications for the functioning of striatal projection neurons and for the general issue of whether neurons can control the subcellular localization of glutamate receptors.

Animals↗

PubMed1998

Immunohistochemical localization of DARPP32 in striatal projection neurons and striatal interneurons in pigeons.

DARPP32 is a D1-receptor associated signaling protein found in striatal projection neurons in mammals, including both substance P-containing (SP+) neurons and enkephalinergic (ENK+) projection neurons. The present study used immunohistochemical single- and double-labeling to examine the cellular localization of DARPP32 in pigeon striatum. Single-label studies revealed that DARPP32 is present in numerous medium-sized striatal perikarya and DARPP32+ axons and terminals were seen to profusely innervate the two major striatal projection targets, the pallidum and the substantia nigra. The single-labeling studies indicated that about 60% of all striatal perikarya labeled for DARPP32+ in striatum, which exceeds the abundance of either SP+ or ENK+ perikarya. Single-labeling studies also showed that the abundance of DARPP32+ fibers and terminals in pallidum exceeds that of either SP+ or ENK+ fibers and terminals in pallidum. Double-labeling found that 30-50% of striatal SP+ perikarya and 7-24% of ENK+ striatal perikarya labeled for DARPP32 in pigeon, and confirmed that DARPP32 was found in both SP+ and ENK+ fibers and terminals in pallidum. In contrast to its prevalence in striatal projection neurons, DARPP32 was virtually absent from cholinergic and NPY+ striatal interneurons, as also true in mammals. Our data are consistent with the interpretation that many SP+ neurons and many ENK+ neurons in avian striatum possess D1-type dopamine receptors and use a DARPP32 signalling pathway, although this may be more common for SP+ than for ENK+ neurons.

Animals↗

PubMed1998

Calf thymus high mobility group proteins are nonenzymatically glycated but not significantly glycosylated.

Over the past decade, there have been many reports suggesting the presence of complex carbohydrates on nuclear and cytoplasmic proteins in mammalian cells. Some of the most often cited of these reports deal with the glycosylation of the high mobility group (HMG) proteins. These are relatively abundant chromosomal proteins that are known to be associated with nucleosomes and actively transcribed regions of chromatin. The original report describing HMG protein glycosylation presented several lines of evidence suggesting that these proteins are glycosylated, including carbohydrate compositional analysis and periodic-acid Schiff staining. We have attempted to repeat these observations with more highly purified protein than was utilized in the original study. Using carbohydrate compositional analysis performed by high pH anion exchange chromatography coupled to pulsed-amperometric detection, we saw no evidence for significant glycosylation of these proteins. In addition, we found no evidence for the presence of O-GlcNAc, a well known form of nuclear glycosylation. The HMG proteins did react with periodate, suggesting the presence of a modification containing cis-diols on the protein. Several tryptic peptides isolated from HMG 14 and 17 which retained the periodate reactivity had in common lysine residues, suggesting a potential modification of the straightepsilon-amino groups of lysines such as nonenzymatic glycation. Western blot analysis of the HMG proteins using anti-advanced glycation endproducts (AGE) antibodies confirmed the presence of glycation products on the HMG proteins.

Acetylglucosamine↗

PubMed1998

SV40 large T antigen is modified with O-linked N-acetylglucosamine but not with other forms of glycosylation.

SV40 large T antigen has been reported to be modified with several different sugars including N-acetylglucosamine, galactose, and mannose. In this report we have reexamined the glycosylation of T antigen and found that while we could detect modification with N-acetylglucosamine, we could not detect any other sugars on the protein. Surprisingly, even though [3H]galactose could be metabolically incorporated into the protein, analysis showed that all of the radioactivity in T antigen had been converted to other species. The N-acetylglucosamine was demonstrated to be linked to the protein in the form of O-linked N-acetylglucosamine, the best characterized form of nuclear and cytoplasmic glycosylation in mammalian systems. We have localized the major site of glycosylation to the amino terminal portion of the molecule. Analysis of mutated T antigen where serines 111/112 were substituted with alanine suggest that these residues constitute a glycosylation site on the protein. These two serines fall within a typical O-linked N-acetylglucosamine glycosylation site (PSS) and are also known to be phosphorylated. Thus, it is likely that competition between phosphorylation and glycosylation occurs at this site.

Acetylglucosamine↗

PubMed1998

Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide.

In several studies of patients with neurocysticercosis under treatment with albendazole the pharmacokinetic data were difficult to interpret, probably because of slow and erratic drug dissolution response and absorption problems in-vivo. Because there is no information available about the physicochemical properties of the drug, the aim of this work was to explain this erratic behaviour by fully characterizing the solution behaviour of the drug and its metabolite. To accomplish this, the physicochemical properties, pKa and solubility, and in-vitro plasma binding of albendazole and its main metabolite, albendazole sulphoxide, were studied by conventional methods. The intestinal and gastric absorption and dissolution behaviour of albendazole were also studied. The solubility of both compounds is very low. Both are amphoteric molecules with two ionization steps, with pKa values of 10.26 and 2.80 for albendazole and 9.79 and 0.20 for albendazole sulphoxide; low pKa values were obtained by performing linear free energy relationship calculations. On the other hand, protein binding studies showed that albendazole is 89-92% bound to plasma proteins whereas for albendazole sulphoxide the figure is 62-67%. This metabolite is bound by albumin and to alpha1-glycoprotein. Absorption of albendazole occurs along the gastrointestinal tract and is limited by its solubility. Good dissolution profiles were observed when 0.1 M HCl was used as dissolution medium. The results show that 0.1 M HCl enables discrimination between the drug-release characteristics of different products.

Albendazole↗