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V Arango

Publications and source records attributed to V Arango.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effect of intestinal permeability on pancreatic enzyme-induced enteropathy in the rat.

BACKGROUND: Fibrosing colonopathy in cystic fibrosis occurs in children 2 to 7 years old and is associated with excess doses of high and regular strength lipase pancreatic enzymes, given for more than 6 months. A rat model was developed to study the effects of excessive doses of pancreatic enzymes equivalent to those producing fibrosing colonopathy in cystic fibrosis patients. METHODS: Five groups of animals were studied after administration of different combinations of pancreatic enzymes, oleic acid, and reserpine. RESULTS: Pancreatic enzymes alone produced minimal damage to the intestine and none to the liver. Excessive doses of pancreatic enzymes in combination with agents that increased intestinal permeability (oleic acid, reserpine) were associated with intestinal eosinophilia and necrosis of the jejunoileal muscle layer and inflammatory nodules in the liver, which increased with duration of insult. CONCLUSIONS: Increased intestinal permeability potentiates damage to the intestine caused by excessive pancreatic enzyme dosage. It is a characteristic of cystic fibrosis that may increase vulnerability to fibrosing colonopathy.

Animals↗
PubMed1997

Postmortem findings in suicide victims. Implications for in vivo imaging studies.

Alterations in serotonergic and noradrenergic receptor binding in membrane homogenates from the brain of suicide victims suggest a biological substrate for the vulnerability to commit suicide. We and others have employed high-resolution quantitative autoradiography of full coronal sections of the prefrontal cortex to map the locus of maximal change in receptor binding. We found alterations in binding to the serotonin transporter, the 5-HT1A, and the 5-HT2A receptors primarily in the ventral and ventrolateral prefrontal cortex of suicide victims. Importantly, these changes are often modest in magnitude and anatomically restricted to one or two Brodmann areas. Furthermore, we have found that care in case selection is essential, because sex, age, drugs, and comorbid diagnoses contribute to receptor binding. The implications for in vivo imaging are considerable, directing the focus of such studies toward the ventrolateral prefrontal cortex. However, because ligands are limited, as is the resolution of current methods, including PET, automated analyses that produce statistical images, rather than manual selection of individual slices, will likely lack the ability to detect the discrete receptor changes found postmortem. Alternatively, the advantages of examining large numbers of subjects, imaging the entire brain, obtaining detailed clinical information in the living patient, and magnifying the changes with neuropharmacological challenges present a promising outlook for making major advances into the identification of brain abnormalities associated with suicide risk.

Brain↗
PubMed1997

Intestinal absorption of proline and leucine in chronically catheterized rats.

BACKGROUND & AIMS: Most studies of intestinal amino acid absorption use methods in which intestinal function is studied immediately after surgical manipulation. The unphysiological experimental conditions present in these studies limit the ability to extrapolate their results to normal physiological conditions. The aim of this study was to determine the rates of proline and leucine absorption under normal physiological conditions. METHODS: Absorption of proline and leucine was measured in long-term catheterized rats using a method of dual infusion of radiolabeled isotopes. RESULTS: The maximum transport velocity and apparent membrane permeability for proline were 16.1 mumol/ min and 0.07 mumol.min-1.mmol/L-1. For leucine, the maximum transport velocity and apparent membrane permeability were 14.9 mumol/min and 0.08 mumol.min-1.mmol/L-1. Surgical bowel manipulation decreased the maximum transport velocities for proline and leucine by > 80%. The adverse effects of surgery were present for 24 hours. CONCLUSIONS: Under normal physiological conditions, most proline and leucine is absorbed by active transport. Measurements of amino acid absorption using methods in which the intestine has been surgically manipulated within the previous 24 hours significantly underestimate proline and leucine absorption and do not reflect absorption under normal physiological conditions.

Anesthesia↗
PubMed1997

Biologic alterations in the brainstem of suicides.

This article reviews the data supporting the notion that there are alterations in serotonin and norepinephrine in the ventral prefrontal cortex and brainstem of suicide victims. Normal amounts of serotonin are found in terminal fields such as the dorsolateral prefrontal cortex, but serotonin responses are defective at least in the hypothalamus. Suicide victims appear to have fewer noradrenergic LC neurons, containing more of the tyrosine hydroxylase enzyme needed for transmitter synthesis. A failure of behavior restraint mechanisms involving the prefrontal cortex as a consequence of alterations in brainstem monoaminergic nuclei may result in a predisposition to suicidal behavior.

Brain Stem↗
PubMed1996

Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results.

Studies of the noradrenergic system in suicide victims have found evidence of alterations in cortical beta- and alpha-adrenergic receptor binding. Since these receptor changes may be secondary to altered noradrenergic input, we sought to determine whether the pigmented neurons of the locus coeruleus (LC), which provide the noradrenergic innervation to the cerebral cortex, are altered in suicide victims. We studied 11 controls without known psychiatric or neurologic disorders and six suicide victims. LC neuron number, LC volume, and neuron density were determined by computer-assisted mapping. The suicide group had 23% fewer LC neurons and a 38% lower density of LC neurons than controls. The reduction in neuron number was localized to the rostral two thirds of the LC. Neither the LC length nor the LC volume in suicide victims differed from controls. Altered brain noradrenergic neurotransmission in suicide victims may be due to fewer noradrenergic neurons in the LC. Further studies are needed to determine whether this noradrenergic neuron loss is associated with an underlying major depression or specifically with suicidal behavior.

Adolescent↗
PubMed1996

Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sites.

Suicide has been associated with decreased serotonin transmission. Measurement of concentrations of serotonin, its precursors tryptophan (TRY) and 5-hydroxytryptophan (5-HTP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), have been used as indices of serotonin activity, and with serotonin transporter binding, are indices of the integrity of serotonin nerve terminals. Most previous studies have not distinguished high affinity transporter binding from a very similar nontransporter binding site, where binding is not dependent on Na+ or Cl- and that does not have a known functional role. We therefore, assayed binding kinetics in prefrontal (PFC) and temporal cortex (TC) in matched pairs of suicide victims and controls using the selective ligand 3H-paroxetine, and employing 1 microM sertraline to define specific binding to the transporter and 10 microM sertraline which also displaces binding to the high affinity, nontransporter site. In addition, we measured concentrations of TRY, 5-HTP, serotonin and 5-HIAA in the same brain areas. The total number of 3H-paroxetine transporter and nontransporter binding sites (Bmax), was lower in the suicide group compared to controls in both Brodmann area 9 (prefrontal cortex; p = 0.02) and in Brodmann area 38 (temporal cortex, p = 0.01). In contrast, no differences were found in the number of high affinity transporter binding sites and concentrations of serotonin, 5-HIAA, 5-HTP or TRY (p > 0.05). We conclude that the number of serotonin transporter sites is not altered in Brodmann area 9 in suicide, and that fewer 3H-paroxetine and 3H-imipramine binding sites found in this region of cerebral cortex of suicides may be explained by a reduction in the nontransporter binding sites.

5-Hydroxytryptophan↗
PubMed1996

Serotonin 5-HT3 receptor binding kinetics in the cortex of suicide victims are normal.

Serotonergic abnormalities have been identified in the brain of suicide victims independent of psychiatric diagnosis. We report the first study of serotonin 5-HT3 receptors in the brain of suicide victims. There were no differences in the number (Bmax) or affinity (KD) of 5-HT3 receptors in the temporal cortex of suicide victims compared to matched controls. There was a negative correlation between brain serotonin levels and receptor number (r = -0.5, p = 0.04) in both groups. This study indicates that alterations in serotonergic function in the brain of suicide victims do not appear to directly involve the 5-HT3 receptor.

Adult↗
PubMed1996

Differential age-related loss of pigmented locus coeruleus neurons in suicides, alcoholics, and alcoholic suicides.

We previously reported fewer locus coeruleus (LC) neurons in both suicide victims and alcoholics than among a group of nonpsychiatric controls. In the present paper we examine the rate of decline in the number of LC neurons with age, looking for possible differential rates among suicide victims, alcoholics, and controls. We also compare these groups with a group of alcoholics who died by suicide, and consider the effects of sex, race, and postmortem interval. LC neuron counts were obtained from a total of 32 subjects. In all groups, the number of neurons decreased with age, but by roughly age 40 the average LC count among the three suicide and/or alcoholic groups was lower than among controls. The rate of LC neuron loss was greater among suicides than among controls, but the rate of loss among alcoholics who were at least 30 years old was the same as that among the controls. Our group of alcoholic suicides had counts that were statistically indistinguishable from those of suicides. Differences among groups appear to be most pronounced in the middle third of the LC. Further studies are needed to determine the mechanisms of noradrenergic neuron loss and whether it is associated with an underlying major depression in suicide victims, or acquired after a period of excessive alcohol consumption.

Adolescent↗
PubMed1995

Long-term effects of chronic social stress on serotonergic indices in the prefrontal cortex of adult male cynomolgus macaques.

We examined the effects of chronic social stress and social rank on monamine concentrations in the prefrontal cortex (PFC) in adult male cynomolgus macaques (Macaca fascicularis). Seventy-five animals were housed in five-member social groups for 28 months and were exposed to three experimental conditions. A 'no-stress' condition was comprised of animals housed in groups of stable membership throughout the study. Animals assigned to a 'past-stress' condition had their group memberships reorganized at monthly intervals during the first (but not last) 14 months of the study, and a third 'recent-stress' condition consisted of social groups reorganized only during the last 14 months. At necropsy, the brains were collected and frozen at -70 degrees C until analyzed. Prefrontal orbital cortex was assayed for monoamines (serotonin (5-HT), dopamine (DA), norepinephrine (NE)), metabolites (5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG)), and tryptophan using high-performance liquid chromatography with electrochemical detection. Animals in the past-stress condition had significantly lower PFC 5-HIAA concentrations compared to those in the no-stress condition (P < 0.05). PFC 5-HT concentrations of animals in the past-stress condition were significantly lower than those in the no-stress and recent-stress conditions (P < 0.01). The concentrations of DA, HVA, NE and MHPG were not altered. These data suggest that exposure to chronic social stress is associated with long-term selective reductions in serotonergic activity in the PFC. This effect may underlie the association in human beings between reduced serotonergic function and conditions such as pathological grief and posttraumatic stress disorder.

Animals↗
PubMed1995

Effect of chemical stimulation of the dorsal raphe nucleus on cerebral blood flow in rat.

We have previously shown that electrical stimulation of the dorsal raphe nucleus (DRN) can increase or decrease cerebral blood flow (CBF). We now sought to determine whether the CBF responses are mediated by DRN neurons or fibers of passage. In anesthetized rat, the DRN was stimulated chemically (L-glutamate, kainate) and CBF in parietal cortex was measured by laser-Doppler flowmetry. Microinjection of kainate (5 nmol), but not L-glutamate, into DRN increased CBF (28 +/- 22%; P < 0.05). Decreased CBF to DRN stimulation was not observed. We conclude that stimulation of DRN neurons increases CBF.

Animals↗
PubMed1995

Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims.

Altered serotonin indices have been reported in the brain of suicide victims. We sought to localize the changes in presynaptic and postsynaptic serotonin receptors and identify an area of prefrontal cortex that may influence suicide risk. Quantitative autoradiography was performed in coronal sections of prefrontal cortex to determine whether serotonin 5-HT1A receptor (postsynaptic in cortex) and serotonin transporter (presynaptic) binding are different in suicide victims compared to matched controls. 5-HT1A receptor binding was higher in 85 of the 103 sampled areas in the suicide group (n = 18 pairs; P < 0.0001). The increase ranged from 17 to 30%. The increase was more pronounced in the ventrolateral prefrontal cortex. Serotonin transporter binding was found to be lower in the suicide group in all but one of the 43 sampled regions (n = 22 pairs; P < 0.0001). The reduction in binding was most pronounced in the ventrolateral prefrontal cortex, where the difference between suicides and controls ranged between 15 and 27%. Serotonin transporter and 5-HT1A binding were negatively correlated (r = -0.35 to -0.44, P = 0.04 to 0.007) within the same brain areas, suggesting common regulatory factors with opposite effects on binding to the two receptors. We conclude that suicide victims have an abnormality in the serotonin system involving predominantly the ventrolateral prefrontal cortex, and hypothesize that the serotonergic dysfunction in this brain region contributes to the risk for suicidal behavior.

Adult↗
PubMed1995

Localization of corticotropin-releasing hormone in the human locus coeruleus and pedunculopontine tegmental nucleus: an immunocytochemical and in situ hybridization study.

The present study utilized immunocytochemistry and in situ hybridization histochemistry to examine the localization of corticotropin-releasing hormone immunoreactivity and messenger RNA in neurons of the human brainstem. A large population of corticotropin-releasing hormone-immunoreactive neurons appeared in the lateral region of the pontomesencephalic tegmentum. These corticotropin-releasing hormone-containing neurons are predominantly located in the compact subnucleus of the pedunculopontine tegmental nucleus. Proceeding caudally, corticotropin-releasing hormone-immunoreactive neurons in the pedunculopontine tegmental nucleus travel in a dorsomedial direction approaching the ventral border of the locus coeruleus in a dispersed fashion and cluster in a region ventromedial to the locus coeruleus which corresponds to the ventral aspect of the laterodorsal tegmental nucleus. Dense corticotropin-releasing hormone-immunoreactive fibers are present in the dorsal portion of the locus coeruleus and are most prominent in the middle to rostral levels of the nucleus. The cellular and regional localization of corticotropin-releasing hormone messenger RNA in the human brainstem is identical to the perikaryal distribution visualized by immunocytochemistry. Neurons in the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus express abundant levels of corticotropin-releasing hormone messenger RNA as revealed by dense silver grains overlying these neurons on the emulsion autoradiograms. Within the locus coeruleus, the cellular expression of corticotropin-releasing hormone-immunoreactive and corticotropin-releasing hormone messenger RNA is exclusively localized to non-pigmented neurons. The present study confirms a previous finding describing dense corticotropin-releasing hormone-immunoreactive fibers innervating the human locus coeruleus and extends these findings by identifying corticotropin-releasing hormone immunoreactive and corticotropin-releasing hormone messenger RNA-containing perikarya in the pedunculopontine tegmental nucleus, in the ventral portion of the laterodorsal tegmental nucleus and in the locus coeruleus proper. From morphological observations, the corticotropin-releasing hormone-containing neurons in human pontomesencephalic tegmentum form a continuous population of neurons that are positioned anatomically to exert a putative neuromodulatory influence on locus coeruleus neurons.

Adult↗
PubMed1994

Fewer pigmented neurons in the locus coeruleus of uncomplicated alcoholics.

Altered noradrenergic function is associated with alcoholism. Reduced brain norepinephrine (NE) concentrations and beta-adrenergic receptor supersensitivity following chronic alcohol consumption suggest a reduced level of noradrenergic neurotransmission. To further elucidate the reason for changes in noradrenergic function, we determined the number of melanin-containing noradrenergic neurons in the locus coeruleus (LC) postmortem from 11 controls and 7 alcoholics. Controls did not have a known history of psychiatric or neurologic disorders and were drug-free by toxicological screen. The diagnosis of alcohol-dependence was based on DSM-III-R criteria. Alcoholics differed from controls in having 23% fewer LC neurons (control: 43,472 +/- 1,021; alcoholic: 33,398 +/- 2184; P < 0.0005) and 46% lower density of neurons (control: 1,227 +/- 89 cells per mm3; alcoholic: 663 +/- 94 cells per mm3; P = 0.001). The reduction in neurons was bilateral and throughout the middle third of the LC. The two groups did not differ with respect to LC length (control: 16.1 +/- 0.6 mm; alcoholic 15.3 +/- 0.9 mm; P = 0.47) or total LC volume (control: 37.3 +/- 2.8 mm3; alcoholic: 46.5 +/- 4.2 mm3; P = 0.09). Changes in noradrenergic neurotransmission in alcoholics may be due to fewer noradrenergic neurons in the locus coeruleus and may contribute to memory loss and depression, common consequences of alcoholism.

Adolescent↗
PubMed1994

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls.

This study used [3H]dizocilpine (MK-801) binding to the N-methyl-D-aspartate (NMDA) receptor to examine glycine, redox and zinc modulatory sites in membranes derived from the frontal and parietal cortex of control subjects (n = 8) and suicide victims (n = 6). [3H]dizocilpine binding in the presence of glutamate and glutamate plus glycine was similar in control and suicide subjects. The sulphydryl redox site was assessed using the oxidizing agent 5,5'-dithio-bis (2-nitrobenzoic acid), which inhibited binding in a dose-dependent fashion. Both redox and zinc sites were unaffected in the frontal and parietal cortex of suicide victims. These data indicate that the NMDA receptor and its glycine, redox and zinc subsites are preserved in the neocortex of suicide victims.

Adult↗
PubMed1993

Quantitative autoradiography of alpha 1- and alpha 2-adrenergic receptors in the cerebral cortex of controls and suicide victims.

Alterations in both serotonergic and noradrenergic indices have been found in the brain of suicide victims. In order to better understand the role of the noradrenergic system in suicide, we carried out quantitative autoradiography of alpha 1- and alpha 2-adrenergic receptors using [3H]prazosin and [3H]-p-aminoclonidine respectively. We compared the distribution and relative density of these receptors in the prefrontal (PFC) and alpha 1-adrenergic receptors in the temporal cortex (TC) of suicide victims and controls matched for postmortem delay, age, side of brain and sex. We found that: (1) the laminar patterns of alpha 1-adrenergic receptors in the PFC (n = 20) and the TC (n = 16) were different (P = 0.022); (2) there was a 37% increase in alpha 1-adrenergic binding corresponding to layers IV-V of PFC of suicide victims compared to controls (P = 0.029); (3) the TC had a greater density of alpha 1-adrenergic binding sites than the PFC across all cortical layers (P = 0.006); (4) alpha 2-adrenergic binding sites had a specific laminar distribution in the PFC (n = 24) which did not differ in controls and suicide victims; (5) binding to alpha 2-adrenergic sites in the PFC of suicide victims did not differ from controls; and (6) norepinephrine concentrations in the same brain areas were elevated in the suicide group compared to controls, but did not correlate with binding to alpha 1- or alpha 2-adrenergic sites. The increase in [3H]prazosin (to alpha 1-adrenergic receptors) but not in [3H]-p-aminoclonidine (to alpha 2-adrenergic receptors), and in norepinephrine concentrations in the brain of suicide victims provides further evidence for an association between suicide and altered brain noradrenergic function. Future studies must determine whether these changes in brain noradrenergic function indicate increased or decreased transmission.

Adolescent↗