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Biomedical subjects

M Navarro

Publications and source records attributed to M Navarro.

At least 217 records · Page 12Linked to original sources

Differential effects of chronic treatment with either dopamine D1 or D2 receptor agonists on the acute neuroendocrine actions of the highly potent synthetic cannabinoid HU-210 in male rats.

Acute exposure to delta 9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, produces a well-characterized set of neuroendocrine effects. The recent description of both brain cannabinoid receptors (CB-1) and anandamide, their proposed endogenous ligand, has renewed the interest in cannabinoid actions in the brain. However, the neurobiological mechanisms underlying the neuroendocrine effects of natural cannabinoids are not yet fully understood because of several mechanisms involved in their actions. In this work we have studied the role of hypothalamic dopaminergic receptors in the mediation of the acute neuroendocrine effects of (-)-delta 8-tetrahydrocannabinol-dimethyl-heptyl (HU-210, 20 micrograms/kg), a highly potent agonist of CB-1. The use of this low dose of HU-210 precludes the multiple unspecific effects which appear with an equipotent dose of THC. Rats were exposed during 21 days to either the dopamine (DA) D2 receptor agonist quinpirole (1 mg/kg, daily), the DA D1 receptor agonist SKF 38393 (8 mg/kg, twice a day) or vehicle (twice a day). Twenty-four hours after the last injection, a single dose of HU-210 (20 micrograms/kg) was administered intraperitoneally, and the animals were sacrificed 90 min later. Acute exposure to HU-210 produced both a decrease in plasma prolactin and a rise of plasma corticosterone levels. HU-210 treatment also resulted in both an increase in the L-3,4-dihydroxyphenylacetic acid/DA ratio and a decrease in noradrenaline contents, measured in the medial basal hypothalamus. These neuroendocrine actions were prevented by chronic exposure to quinpirole, but not after chronic SKF 38393 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

[Papillary muscle rupture in myocardial infarction].

We report nine patients with acute mitral regurgitation secondary to post-infarction papillary rupture operated between 1980 and 1992. Seven cases had posterior papillary muscle rupture. All patients were in critical conditions with pulmonary edema at the moment of surgery. In eight cases, mitral valve replacement was performed (4 with mechanical prostheses) and in one, the valve was repaired with papillary muscle reimplantation. Six cases were also subjected to myocardial revascularization with sapheneous vein grafts. Two patients (22%) died during the postoperative period and 4 had postoperative complications. The seven survivors have been followed during 6 to 115 month. Of theses, one died six month after surgery due to congestive heart failure, three are in functional class I and the rest in functional class II. It is concluded that, although mitral valve replacement for papillary muscle rupture has a high operative mortality and morbidity, long term results are satisfactory.

Aged↗

[Multiple cutaneous carcinoma and chronic lymphoid leukemia].

INTRODUCTION: Skin cancer occurs more readily in more aggressive forms in immunodepressed subjects. We report the case of a patient with chronic lymphoid leukaemia and multiple skin carcinomas complicated with carcinomatous lymphangitis. CASE REPORT: A 63 year-old man with chronic lymphoid leukaemia, stage A in the Binet classification, had multiple epidermoid carcinomas on the trunk and face. The skin tumours were complicated with cervical lymph mode metastases, then a prethoracic carcinomatous lymphangitis with a rapidly fatal clinical course. DISCUSSION: Chronic lymphoid leukaemia and lymphomas are associated with a high incidence of skin carcinoma. The immunodepression inherent in the haematologic disease would appear to favor aggressive skin cancers. Our case was particularly severe since the carcinomatous lymphangitis was rapidly fatal.

Basal Cell Carcinoma↗

Vascular architecture of the lactating and non-lactating teat of the bitch: a scanning electron- and light microscope study.

Tissues from fourteen mammary glands of eight bitches were prepared for scanning electron microscopy of vascular corrosion casts and for histology to study the vasculature of the lactating and non-lactating teats. The densely-meshed mammary dermal capillary network formed ridges and troughs. The teat ducts were vascularized by a relatively densely-meshed capillary network which drained into veins longitudinally oriented to the ducts. Between eight and fifteen teat duct openings were seen on the tip of the teat, that were sometimes divided by a septum. The inner vascularization of the teat showed that the main papillary arteries divided into undulating secondary papillary arteries which presented numerous semi-constrictions and loops. Their structure may help during erection of the teat. Arteriovenous anastomoses found at different points may participate in blood flow maintenance during suckling, heat regulation and teat erection. Veins freely anastomosed and ran longitudinally to the axis of the teat. They exhibited numerous bicuspid valves. In non-lactating teats, vessels showed the same main architecture and characteristics mentioned above, although these were considerably less marked. The structure of the vascular elements in the teat of the bitch could favor blood flow during suckling and suggest that vessels adapt to the physiological situation.

Animals↗

Repeated stimulation of D1 dopamine receptors enhances (-)-11-hydroxy-delta 8-tetrahydrocannabinol-dimethyl-heptyl-induced catalepsy in male rats.

Dopaminergic and cannabinoid receptors are localized in the outflow nuclei of the basal ganglia. We have investigated the possible interrelation of these receptors in the regulation of motor activity in male rats. To this end we have first studied the behavioural effects of the highly potent cannabinoid receptor agonist (-)11-hydroxy-delta 8-tetrahydrocannabinol-dimethylheptyl (HU-210, 20 micrograms mg) after chronic stimulation of dopamine D1 and D2 receptors. The catalepsy induced by the synthetic cannabinoid, measured as the descent latency in the bar test, was enhanced in male rats chronically treated with the dopamine D1 receptor agonist SKF38393 (8 mg kg-1, twice a day during 21 days). However, animals exposed to the dopamine D2 agonist quinpirole (1 mg kg-1 daily during 21 days) displayed the same degree of catalepsy as those exposed to HU-210 alone. Although a possible involvement of D2 receptors cannot be excluded, this finding suggests a predominant role for dopamine D1 receptors in the regulation of the cataleptic response to cannabinoids. The possible cross-talk between dopamine D1 and cannabinoid receptors is further supported by the decreased responsiveness to the acute behavioural effects of SKF38393 (8 mg kg-1) observed in animals chronically exposed to HU-210 (20 micrograms kg-1 daily during 14 days).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Modifications of mesolimbic and nigrostriatal dopaminergic activities after intracerebroventricular administration of prolactin.

In the present study we examined the effects of intracerebroventricular (i.c.v.) injections of prolactin (PRL) on the presynaptic activity and post-synaptic sensitivity of mesolimbic and nigrostriatal dopaminergic neurons. In addition, the effects of PRL on in vitro release of dopamine (DA) from perifused striatal fragments were examined. Tyrosine hydroxylase (TH) activity and D2 receptor density in the striatum decreased after i.c.v. PRL administration; this was accompanied by an increase in D2 receptor affinity. These effects occurred after i.c.v. administration of PRL to normoprolactinemic rats, although normally they did not appear after administration to animals with pituitary grafting-induced hyperprolactinemia. Thus, in these animals, i.c.v. PRL failed to decrease TH activity and D1 and D2 receptor densities to a significant extent. In the case of D2 receptors, this was probably due to the fact that pituitary grafting-induced hyperprolactinemia itself was able to reduce the density of this receptor. No changes were observed in DA or L-3, 4-dihydroxyphenylacetic acid (DOPAC) contents after i.c.v. administration of PRL to both normo-and hyperprolactinemic animals. Basal and K(+)-evoked DA release in vitro from perifused striatal fragments of normoprolactinemic rats were not affected by the addition of PRL, whereas this hormone enhanced K(+)-evoked DA release when added to perifused striatal fragments from hyperprolactinemic animals. In the limbic forebrain, i.c.v. administration of PRL to normoprolactinemic animals produced a decrease in DA and DOPAC contents and D1 receptor density. Interestingly, none of these effects appeared when PRL was injected to hyperprolactinemic animals. In summary, our results suggest a possible inhibitory role of PRL on the activity of both the nigrostriatal and mesolimbic dopaminergic neuronal systems. These inhibitory effects were reflected in the decreases elicited in a set of neurochemical parameters, indicating either presynaptic activity or postsynaptic sensitivity, after i.c.v.-administered PRL. This observation supports the hypothesis of a possible neuromodulatory role for an extrapituitary PRL on the activity of these neurons, although the fact that most of these effects did not appear when i.c.v. administration was performed in hyperprolactinemic rats also suggests that they are influenced by peripheral PRL levels.

3,4-Dihydroxyphenylacetic Acid↗

Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Motor behavior and nigrostriatal dopaminergic activity in adult rats perinatally exposed to cannabinoids.

We have recently reported several neurochemical alterations, measured at perinatal and peripubertal ages, in the maturation of nigrostriatal dopaminergic neurons following perinatal hashish exposure. In the present work, we tried to undertake whether these neurochemical changes during ontogeny: a) were accompanied by changes of motor behavior, the main neurobiological process regulated by nigrostriatal dopaminergic neurons; and b) persisted in adulthood, leading to disturbances in the expression of an adult motor activity. To this end, two different experiments were performed. In the first, we examined, by using an actimeter, the ontogeny of spontaneous locomotor activity in immature male and female rats born from mothers perinatally exposed to hashish extract. Results showed a complete absence of significant changes in locomotor activity in females, whereas males presented a constant trend to decrease, although never statistically significant, at all ages studied as a consequence of the perinatal cannabinoid exposure. In the second experiment, we evaluated neurochemical indices--dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents, tyrosine hydroxylase (TH) activity, and number and affinity of D1 and D2 dopaminergic receptors in the striatum--and behavioral parameters--spontaneous locomotor activity and spontaneous and induced stereotypic behavior--both indicating nigrostriatal dopaminergic activity, in adult female and male rats perinatally exposed to hashish extract. Results were as follows. The spontaneous locomotor activity, measured in the actimeter, was not affected by perinatal hashish exposure in both adult males and females. This was also seen in an open-field test as measured by total number of sector crossings. However, when differentiated between internal and external sectors hashish-exposed males presented a higher number of external crossings than controls, which did not appear in females. Moreover, several induced stereotypic behaviors, such as self-grooming and shaking induced by water spraying, were also altered by hashish treatment in a sexually dimorphic manner, whereas the number of spontaneous rears and self-grooms, measured in the open-field test, was unchanged. Thus, the frequency of water spraying-induced self-grooming was significantly increased in both males and females perinatally exposed to hashish, although the increase was more marked in males (200.4%) than females (121.2%). In addition, the frequency of shaking was also markedly increased in males but remained unchanged in females. These behavioral effects were paralleled by modifications in striatal neurochemical parameters. Thus, there was a significant increase in the DOPAC/DA ratio, indicating increased presynaptic activity, in females perinatally exposed to hashish, but compensated by a lower density of D1 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

The use of lectins to characterize and separate living canine spermatozoa: A preliminary study.

This study was designed as a preliminary attempt to develop a methodology for relating the glucidic structure of the sperm membrane to sperm morphology. Differences in plasma membrane glycoconjugates between motile and nonmotile spermatozoa were studied by using 7 lectins. Fresh spermatozoa from 3 dogs were analyzed by fluorescein isothiocyanate (FITC) labeled lectins. The binding of lectins to the sperm membrane and the capability of the lectins to agglutinate spermatozoa were estimated semi-quantitatively by observation with either an epifluorescence or a phase contrast microscope, respectively. All the lectins tested bound to non motile spermatozoa, with Helix pomatia , Pisum sativum and Arachis hypogaea showing intense fluorescence, Triticum vulgare and Glycine maxima showing moderate fluorescence, and Phaseolus vulgaris and Phytolacca americana showing low fluorescence. However, Helix pomatia . and Triticum vulgare also bound to rapid and slow moving spermatozoa, and were the only 2 lectins that induced sperm agglutination. These results suggest that lectins could be a possible tool for characterizing and separating spermatozoa with different rates of motility.

Journal Article↗

Inverted repeat structure and homologous sequences in the LD1 amplicons of Leishmania spp.

In the parasitic trypanosomatids of the genus Leishmania, novel circular (CD) and linear (LD) multicopy genetic elements arise de novo either spontaneously or as a result of drug selection. We report that the LD1 minichromosomes of L. donovani, L. major and L. mexicana (ranging in size from 180 to 230 kb) have an inverted repeat structure and contain homologous sequences located at similar distances from the telomere; one half of the chromosome being the mirror image of the other. They must therefore have originated from a unique conserved source chromosome; the size polymorphism being generated by the point at which inversion occurs. The circular CD1 elements appear to be circularised segments of the LD1 elements. These observations lead to a unified concept of how minichromosomes LD1 and circular CD1 genetic elements emerge within the Leishmania and contribute to evolution of karyotype.

Animals↗

Antibodies to endothelial cells in Behçet's disease: cell-binding heterogeneity and association with clinical activity.

OBJECTIVES: To investigate the prevalence and characteristics of antibodies to endothelial cells (aEC) from large vessel and from microvasculature in a group of patients with Behçet's disease (BD) to determine the relationship of these antibodies with clinical and laboratory features of the disease. METHODS: Thirty patients with BD were prospectively and consecutively studied. The aEC were determined by enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein (large vessel) as well as from retroperitoneal adipose tissue (microvasculature). RESULTS: Fifteen patients (50%) had aEC, either directed to large vessel [8(26%) patients] or microvascular [13(43%) patients] endothelial cells. The percentage of active patients was significantly higher in the aEC-positive group [12(80%) patients] compared with the aEC-negative group [5(33%) patients] (p < 0.05). CONCLUSIONS: Patients with BD have a high prevalence of aEC when microvascular endothelial cells are used in the assay. These antibodies seem to be a marker of disease activity in this condition, previously considered as negative for autoantibodies.

Adipose Tissue↗

CD23 antigen density is related to serum gamma globulin level, bone marrow reticulin pattern, and treatment in B chronic lymphocytic leukemia.

The CD23 antigen density was evaluated by a cytofluorometric technique in 55 patients with chronic lymphocytic leukemia. The quantification method was based on the use of biological standards in indirect immunofluorescence. The CD23 antigen density was correlated with the percentage of CD23 positive cells, but antigen density appeared to be a more informative parameter. CD23 antigen density was lower in stage B than in stages A or C patients, and higher in patients undergoing chemotherapy or previously treated than in untreated patients. There was a significant negative correlation between CD23 antigen density and serum gamma globulin and IgG levels, that existed only in patients in an advanced stage of the disease. CD23 antigen density was higher in patients with abnormal bone marrow reticulin pattern. Serum gamma globulin level was lower in these patients, as well as in patients with prognostically unfavorable histologic bone marrow infiltration pattern. These data emphasize the interest of antigen density as an additional parameter and the complex relationship between CD23 expression, hypogammaglobulinemia, bone marrow histologic findings, and treatment in chronic lymphocytic leukemia.

Antibodies, Monoclonal↗

Refinement of the Medicare diagnosis-related groups to incorporate a measure of severity.

This article presents a system under consideration by the Health Care Financing Administration (HCFA) for incorporating a measure of severity of illness into the Medicare diagnosis-related groups (DRGs). DRG assignment is one of the main factors in determining the payment made for hospital inpatient services furnished to Medicare beneficiaries. Specifically, the formula used to calculate payment for a single Medicare hospital inpatient case takes an average payment rate for a typical case and multiplies it by the relative weight of the DRG to which it is assigned. Thus, it is easy to see that the DRG relative weights have a large impact on the payment a hospital receives. In this article, we describe the Medicare DRG prospective payment system (PPS), evaluate the various classification elements available for assessing severity of illness, describe the analyses used in formulating this proposal, and present the proposed DRG severity system.

Centers for Medicare and Medicaid Services, U.S.↗

Leukemia-associated changes identified by quantitative flow cytometry. II. CD5 over-expression and monitoring in B-CLL.

The CD5 antigen density on B cells was studied on fetal spleen, cord blood, and adult peripheral blood (after immunomagnetic bead purification) using an indirect immunofluorescence technique. In fetal spleen, there was a continuum in CD5 expression, whereas all cord blood and less than 20% adult peripheral blood B cells were CD5+. Mean CD5 antigen density on these normal cells was low (3-6 x 10(3) molecules/cell); eight to 20 times lower than on normal T lymphocytes. In adult blood, less than 10% B cells expressed more than 3 x 10(3) CD5 molecules/cell. In chronic malignancies, 34/35 cases had a CD5 antigen density lower than on residual T cells, but mean antigen density was higher (14.8 +/- 2.1 x 10(3) molecules/cell) than on normal B cells. Sixteen cases of chronic lymphocytic leukemia (50%) expressed a CD5 density above 10 x 10(3) molecules/cell. This aberrantly high CD5 expression was used to detect neoplastic cells after dilution in normal lymphocytes, with a limit of detection between 1:100 and 1:1000. Quantitation of the CD5 antigen allows better characterization of the B1 population and should be used for the monitoring of chronic malignancies.

Antigens, CD↗

[The prognosis of patients with posterior urethral valves according to the initial treatment and their urodynamic behavior].

Long-term outcome of 35 boys with severe posterior urethral valves is reviewed, with intention to know if the course of renal function depended on initial treatment and bladder dysfunction. Diagnosis was established during the first month in 15 patients, before one year in 16 and later in 4. Surgical management was initially, upper urinary tract diversion (pyeloureterostomy) in 19 patients (group A) and valve ablation in 15 (group B). The average age for closure of temporary urinary diversion was 17 months. Follow-up ranged from 4-19 years (mean 8.3 years). Twenty one patients had a urodynamic study years after initial treatment and this study showed 8 normal bladder, 7 unstable and 6 non-compliant. In group A, at the end of study, 13 patients (70%) have a glomerular filtration of more than 80 ml/min/1.72 m2 while in group B only 6 (37.5%) and average height after treatment was higher in patients of group A. Noncompliant bladders had worst prognosis (66% renal failure) than unstable bladders (25%) and the prognosis was improved in these types of bladders when initial treatment was upper tract diversion. The results of our study suggest that in patients with severe posterior urethral valves, the renal function improved with early diversion (pyeloureterostomy) and irreversible bladder dysfunction worsen the prognosis in these patients.

Follow-Up Studies↗