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Biomedical subjects

F Gonzalez

Publications and source records attributed to F Gonzalez.

At least 55 records · Page 3Linked to original sources
PubMed1999

The contributions of oestrogen and growth factors to increased adrenal androgen secretion in polycystic ovary syndrome.

Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated delta 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the delta 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing delta 5 adrenal androgen secretion, and insulin a greater effect on the delta 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS.

Adrenal Glands↗
PubMed1999

Disposition and tolerance of suxibuzone in horses.

Suxibuzone (SBZ), a nonsteroidal anti-inflammatory drug, was administered to 6 horses at a dose rate of 7.5 mg/kg bwt by intravenous (i.v.) route. Plasma and synovial fluid concentrations of suxibuzone and its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ), were measured simultaneously by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Plasma SBZ concentrations rapidly decreased and were not detectable beyond 20 min after treatment. The parent drug was not detected in any synovial fluid samples. Average maximum plasma concentrations of PBZ (16.43 microg/ml) and OPBZ (2.37 microg/ml) were attained at 0.76 and 7.17 h, respectively. The mean residence time (MRT) of PBZ was 6.96 h in plasma. Oxyphenbutazone plasma concentrations were below those reached by phenylbutazone during the first 12 h after suxibuzone administration, even though its values were detectable for at least 24 h (MRT = 10.65 h). Plasma concentrations of PBZ and OPBZ exceeding EC50 and IC50 of TXB2 and PGE2 were reached by at least 12 h. Synovial fluid concentrations of PBZ and OPBZ were 2.87+/-0.37 microg/ml and 0.97+/-0.08 microg/ml at 9 h after suxibuzone administration and exceeded IC50 of PGE2 for at least this time. In the present study, suxibuzone was well tolerated following i.v. injection.

Animals↗
PubMed1999

Dorzolamide effect on ocular blood flow.

PURPOSE: To evaluate the effect of dorzolamide on ocular blood flow in normal and glaucomatous eyes. METHODS: Twenty-six eyes with documented open-angle glaucoma of 26 patients and 13 normal control eyes of 8 age-matched subjects were included in this study. All eyes underwent color Doppler imaging for measuring peak-systolic velocity, end-diastolic velocity, and resistance index in the ophthalmic and central retinal arteries and the maximal and minimal velocities in the central retinal vein. Eyes were grouped in control and initial and advanced glaucoma categories. Measurements were made in all groups before and after application of topical dorzolamide. Intragroup comparisons between baseline and dorzolamide conditions were made using paired Student's t-test. Intergroup comparisons under baseline conditions between normal and glaucomatous eyes were made by using the one-way ANOVA test. Statistical significance was set at P < 0.05. RESULTS: The peak-systolic velocity of the central retinal artery in glaucomatous eyes and the end-diastolic velocity of the ophthalmic and central retinal arteries in all groups were significantly higher after application of dorzolamide. The minimal velocity of the central retinal vein showed significantly higher values after dorzolamide, whereas the maximal velocity remained unchanged. The peak-systolic velocity of the ophthalmic artery in all groups and the peak-systolic velocity of the central retinal artery in normal eyes also remained unchanged. The resistance index was significantly lower in the ophthalmic and central retinal arteries in all groups after dorzolamide. The intraocular pressure was significantly reduced in all groups after dorzolamide. Under baseline conditions normal control eyes and glaucomatous eyes showed differences in various measurements. Peak-systolic velocity was significantly lower in glaucomatous eyes than in normal control eyes with the exception of the ophthalmic artery in the initial glaucoma group. End-diastolic velocity was lower in glaucomatous eyes than in control eyes in both arteries. Maximal and minimal velocities of the central retinal vein were lower in glaucomatous eyes than in normal control eyes. Resistance index was higher in glaucomatous eyes than in normal control eyes in the ophthalmic artery but not in the central retinal artery. CONCLUSIONS: Most hemodynamic parameters of intraocular and periocular vessels improve after application of topical dorzolamide in both normal control and glaucomatous eyes. Dorzolamide should be regarded as a useful drug for treatment of glaucoma not only because it reduces intraocular pressure but also because it improves the ocular blood supply.

Aged↗
PubMed1998

Modulation of cell responses to horizontal disparities by ocular vergence in the visual cortex of the awake Macaca mulatta monkey.

Horizontal retinal disparity is the most important cue for stereopsis. However, accurate stereoscopic perception requires additional information on fixation distance. The ocular vergence angle may provide information on fixation distance and therefore may be used to calibrate horizontal disparities. We studied the responses of cells from cortical visual area V1 of one macaca mulatta monkey to dynamic random dot stereograms at different ocular vergence angles. We observed that in about half of cells sensitive to horizontal disparity the vergence angle modifies the cell responses to horizontal disparities. These results suggest that vergence angle may be used to calibrate horizontal disparities for fixation distance.

Animals↗
PubMed1998

Neural mechanisms underlying stereoscopic vision.

The progressive frontalization of both eyes in mammals causes overlap of the left and right visual fields, having as a consequence a region of binocular field with single vision and stereopsis. The horizontal separation of the eyes makes the retinal images of the objects lying in this binocular field have slight horizontal and vertical differences, termed disparities. Horizontal disparities are the main cue for stereopsis. In the past decades numerous physiological studies made on monkeys, which have in many aspects a similar visual system to humans, showed that a population of visual cells are capable of encoding the amplitude and sign of horizontal disparity. Such disparity detectors were found in cortical visual areas V1, V2, V3, V3A, VP, MT (V5) and MST of monkeys and in the superior colliculus of the cat and opossum. According to their disparity tuning function, these cells were first grouped into tuned excitatory, tuned inhibitory, near and far sub-groups. Subsequent studies added two more categories, tuned near and tuned far cells. Asymmetries between left and right receptive field position, on and off regions, and intra-receptive field wiring are believed to be the neural mechanisms of disparity detection. Because horizontal disparity alone is insufficient to compute reliable stereopsis, additional information about fixation distance and angle of gaze is required. Thus, while there is unequivocal evidence of cells capable of detecting horizontal disparities, it is not known how horizontal disparity is calibrated. Sensitivity to vertical disparity and information about the vergence angle or eye position may be the source of this additional information.

Depth Perception↗
PubMed1998

Indocyanine green angiography in isolated primary retinal arterial macroaneurysms.

PURPOSE: The study was carried out to describe the indocyanine green angiographic findings in isolated primary retinal arterial macroaneurysms and their contribution to the diagnosis of this condition. METHODS: Fluorescein and indocyanine green angiography examination techniques were used to study isolated primary retinal arterial macroaneurysms in 8 consecutive patients with retinal or preretinal haemorrhage over a period of 12 months. RESULTS: The fluorescein angiography examination showed the macroaneurysm in four cases; pulsatility was not observed in any case. Indocyanine green angiography disclosed the macroaneurysm in six cases; pulsatility was observed in two cases. CONCLUSION: Indocyanine green angiography allows better visualization of arterial macroaneurisms in the first examination and therefore facilitates the diagnosis, follow-up and laser treatment of this vascular abnormality.

Aged↗
PubMed1998

Chronic desipramine treatment desensitizes the rat to anesthetic and antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine.

INTRODUCTION: The effects of long-term administration of the tricyclic antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic-sparing, and central norepinephrine turnover suppressant action of short-term dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in rats. METHODS: Rats were given a 3- or 4-week course of twice daily administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of loss of righting reflex was determined. The tail flick latency response was determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic concentration of halothane and the central norepinephrine turnover rate were determined before and after administration of 30 microg/kg dexmedetomidine. Changes in the affinity and density of the alpha2-adrenergic receptor in locus coeruleus and spinal cord also were determined. RESULTS: Treatment with desipramine decreased dexmedetomidine-induced loss of righting reflex duration by 67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine produced a 55% decrease in minimum anesthetic concentration in the control group but no reduction in desipramine-treated rats. Desipramine did not change the receptor density or binding affinity of alpha2 receptors at the site for hypnotic (locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the central norepinephrine turnover rate was noted in the locus coeruleus of dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1-adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic concentration reduction), almost completely (antinociceptive), or partially (hypnotic) restored responsiveness to normal. CONCLUSIONS: These data indicate that treatment with desipramine induces hyporesponsiveness to the hypnotic, analgesic, and minimum anesthetic concentration-reducing, but not to the suppression of central norepinephrine turnover, properties of dexmedetomidine. The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.

Adrenergic alpha-Agonists↗
PubMed1998

Depth perception in random dot stereograms is not affected by changes in either vergence or accommodation.

PURPOSE: To test the hypothesis that extraretinal cues related to vergence angle and lens accommodation are used to scale horizontal disparities for fixation distance. METHODS: Depth perception of random dot stereograms was studied in 10 healthy adult subjects with normal visual acuity by modifying retinal disparity, fixation distance, vergence angle, and accommodation. Statistical analysis was used to compare the data. RESULTS: Depth perception increased with fixation distance. The increment of depth perception persisted even when horizontal retinal disparity was kept constant. The magnitude of depth perception was independent of vergence angle. Depth perception did not vary with changes in accommodation. CONCLUSIONS: Extraretinal cues related to vergence angle and accommodation seem to be not necessary to scale horizontal disparities for viewing distance.

Accommodation, Ocular↗
PubMed1998

Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis.

The aryl-hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the biological effects of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). In mouse embryo fibroblasts, TCDD activates expression of multiple genes, including CYP1B1, the predominant cytochrome P450 expressed in these cells. Here, we analyze constitutive functions of the AhR in primary mouse embryo fibroblasts (MEFs) and spontaneously immortalized MEF cell lines derived from wild-type (WT) C57BL/6 mice and also from congenic mice with a targeted disruption of the AhR gene (AhR-/-). After multiple passages, primary MEFs exhibit spontaneous differentiation, growth cessation and senescence. Eventually, colonies of immortalized MEFs arise to provide clonal lines. The senescent phase occurs much earlier for AhR-/- MEFs, while immortalization is substantially delayed. Comparison of AhR-/- and WT MEFs also indicates that constitutive AhR activity is required for basal expression of CYP1B1 and suppresses lipogenesis in subconfluent cultures. Primary WT and AhR-/- MEFs and the corresponding lines undergo adipogenesis when treated at confluence with the appropriate hormonal inducers. Addition of TCDD before or concurrent with hormonal induction suppressed PPAR gamma mRNA and adipogenesis, as measured by lipid accumulation, glycerol phosphate dehydrogenase activity and stearoyl CoA desaturase type 1 mRNA expression. This effect of TCDD treatment was absent in AhR-/- MEFs, establishing the role of AhR in hormone-induced adipogenesis. Such hormonal activation of confluent MEFs and preadipocytes results in a limited proliferative expansion followed by irreversible growth arrest. TCDD-treated MEFs undergo the mitotic expansion but fail to exit the cell cycle. In AhR-/- MEFs, there is no such effect of TCDD. These findings implicate the AhR as a constitutive inhibitor of triglyceride synthesis, and as an early regulator of adipocyte differentiation. AhR interference with cell-cycle arrest in differentiation may be linked to the increased rate of senescence.

3T3 Cells↗
PubMed1997

Selenocysteine tRNA[Ser]Sec levels and selenium-dependent glutathione peroxidase activity in mouse embryonic stem cells heterozygous for a targeted mutation in the tRNA[Ser]Sec gene.

To investigate the effect of a reduced level of selenocysteine (Sec) tRNA[Ser]Sec in selenoprotein biosynthesis, two mouse embryonic stem (ES) cell lines heterozygous for the corresponding gene were generated by homologous recombination of the host genome with targeting vectors encoding a deleted or a disrupted tRNA[Ser]Sec gene. The presence of a single functional gene in ES cells afforded us an opportunity to determine directly in the cell line the effect of reduced gene dosage on (1) the levels of the Sec tRNA[Ser]Sec population, (2) the distributions of the isoacceptors within the Sec tRNA population, and (3) selenoprotein biosynthesis. We therefore determined the amounts and distributions of the two major tRNA[Ser]Sec isoacceptors, designated mcm5U and mcm5Um, within the Sec tRNA population and determined the activity of the anti-oxidant, selenium-containing glutathione peroxidase (GPx) in the heterozygotes and in wild type cells grown in media with and without added selenium. The level of the Sec tRNA[Ser]Sec population in the heterozygotes was approximately 60% of that of wild type cells grown in media under normal conditions, while the ratio of the mcmU isoacceptor in wild type vs mutant cells was approximately 2:1 and of the mcmUm isoacceptor approximately 1:1. In the presence of media supplemented with selenium, the Sec tRNA[Ser]Sec population increased about 20% in wild type cells and virtually not all in heterozygous cells, and the level of the Sec tRNA[Ser]Sec population was, therefore, approximately 50% of that of wild type cells. GPx activity was indistinguishable among these cell lines in either selenium-supplemented or unsupplemented media, indicating that the resultant changes in tRNA[Ser]Sec levels did not have a measurable effect on GPx biosynthesis.

Animals↗
PubMed1997

Evaluation and management of heterotopic ossification in patients with spinal cord injury.

Sixty-three patients with paralysis secondary to spinal cord injury (SCI) were screened for heterotopic ossification (HO) by bone scintigraphy 27 +/- 14 (mean +/- SD) days after SCI. There were four female and 59 male patients, 36 had paraplegia and 27 tetraplegia. The age of patients was 28 +/- 9 years. Bone scintigraphy was obtained with a 3-phase test using 99m-technetium labeled diphosphonate, and the positive third phase was used as a criterion for diagnosis of HO. Bone scintigraphy was negative for HO in 27 patients (14 tetraplegic and 13 paraplegic) and positive in 36 patients (13 tetraplegic and 23 paraplegic). The patients with positive HO were treated with etidronate, first with an intravenous dose of 300 mg/day for 3 days, and then with an oral dose of 20 mg/kg/day for 6 months. The follow-up of patients consisted of clinical and radiographic evaluations every 2-4 months. The extent of HO was classified radiographically. In the treated group of patients who completed the entire course of etidronate therapy one patient developed HO, the remaining 28 (97%) patients had no radiographic evidence of HO during the follow-up of 10.6 +/- 4.5 months after initiation of therapy. Our data indicate that: (a) early HO can be detected in the asymptomatic patients using bone scintigraphy on the average of 4 weeks (27 +/- 14 days) after SCI and (b) the therapy with etidronate might be effective in the prevention of HO in majority of patients when the treatment is initiated in an early stage of heterotopic bone formation.

Adolescent↗
PubMed1997

Adrenal involvement in polycystic ovary syndrome.

The etiology of hyperandrogenic chronic anovulation is heterogeneous and relatively unknown in the majority of cases. Affected individuals in this latter segment are considered to have polycystic ovary syndrome (PCOS) of which 50 to 60% exhibit androgen excess of adrenal origin. An understanding of normal adrenal function provides insight into the factors that contribute to adrenal androgen excess in PCOS. Since pituitary ACTH secretion promotes developmental growth and overall steroidogenic efficiency within the adrenal cortex, it is probable that these actions of ACTH along with the adrenal's unique centripetal circulation play a major role in the induction of adrenarche. This latter phenomenon is characterized by alterations in adrenocortical morphology and steroidogenic enzyme activities culminating in increases in adrenal androgens to normal circulating adult levels. Thus, it is not surprising that adrenal dynamic testing has revealed increased 17,20 lyase activity or adrenal androgen hyper-responsiveness to ACTH as the two abnormalities leading to adrenal androgen excess in PCOS. Whereas 17,20 lyase hyperactivity diagnosed by defined criteria in response to pharmacological ACTH may be an intrinsic genetic defect, increases in 17,20 lyase activity and adrenal androgen hyper-responsiveness to ACTH in response to physiological ACTH may be promoted by the functional elevation of estrogen of ovarian origin in PCOS. The latest in vitro data suggest the estrogen may elicit its effect on the adrenal cortex through a receptor mediated mechanism. Therefore, the currently available data indicate that adrenal androgen excess in PCOS is also heterogeneous in etiology.

Adrenal Cortex↗
PubMed1997

Treatment of heterotopic ossification after spinal cord injury.

A new protocol in management of heterotopic ossification (HO) was evaluated in 46 patients after spinal cord injury (SCI). A group of 24 paraplegic and 22 tetraplegic patients was involved in a prospective study. Diagnosis of HO was made by bone scintigraphy and radiographic evaluation. Patients were divided into two groups. Group I was made up of 33 patients with positive bone scintigraphy and negative evidence of HO and Group II was made up of 13 patients with positive bone scintigraphy and positive radiographic evidence of HO. Etidronate was started intravenously (300 mg/day) for three days followed by oral therapy for six months (20 mg/kg/day). Follow-up of patients was 15.7 +/- 8 months after SCI. In Group I, etidronate therapy prevented the development of HO in 79 percent of patients; in 21 percent of patients, a low degree of tissue ossification was found which was not clinically significant. In Group II, there was an inhibitory effect of etidronate on progression of soft tissue ossification in six patients. The remaining seven patients did not respond to therapy and showed an increased growth of HO. Our data indicate that etidronate may prevent HO in the majority of patients when administered at an early stage of HO development and in higher doses than are routinely recommended.

Administration, Oral↗