Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 73 records · Page 4Linked to original sources

PubMed2001

Paraventricular hypothalamic alpha-melanocyte-stimulating hormone and MTII reduce feeding without causing aversive effects.

alpha-Melanocyte-stimulating hormone (alpha-MSH) appears to play a tonic inhibitory role in feeding and energy storage. MTII, a specific synthetic MC3-R/MC4-R agonist, has similar effects on feeding in rats. The current studies demonstrate that PVN administration of alpha-MSH or MTII decreases nocturnal and NPY-stimulated food intake without causing aversive effects. Co-administration with NPY of 600 pmol alpha-MSH or 1 pmol MTII into the PVN caused a significant decrease in NPY-induced feeding. PVN administration of MTII or alpha-MSH at doses effective to suppress feeding did not cause conditioned taste aversion (CTA). ICV administration of alpha-MSH, however, did cause weak CTA. These results indicate that the potent effects on feeding of MC3-R and MC4-R agonists when injected into the PVN are not due to aversive effects.

Animals↗

PubMed2001

Cystoid macular edema after pediatric intraocular lens implantation: fluorescein angioscopy results and literature review.

PURPOSE: To evaluate the occurrence of cystoid macular edema (CME) after lens extraction, anterior vitrectomy, and intraocular lens implantation (IOL) in children using angioscopy after administration of oral fluorescein. SETTING: Centers in Tamil Nadu, India, and Hong Kong, China. METHODS: This study comprised 18 children (28 eyes) who had cataract extraction, posterior capsulorhexis, anterior vitrectomy, and in-the-bag IOL implantation. The presence of CME was evaluated 1 week and 4 to 6 weeks after surgery using fluorescein angioscopy. RESULTS: Anterior chamber fibrin occurred in 4 eyes (14.3%). Fluorescein angioscopy was performed 1 week after surgery in all eyes and after 1 month in 25 eyes (89.3%). No eye demonstrated the presence of CME on fluorescein angioscopy. CONCLUSIONS: Cystoid macular edema did not occur in the early period after pediatric cataract surgery using current surgical techniques. Longer follow-up is required to ascertain the incidence of CME in the late postoperative period.

Capsulorhexis↗

PubMed2001

Nicastrin binds to membrane-tethered Notch.

The presenilins and nicastrin, a type 1 transmembrane glycoprotein, form high molecular weight complexes that are involved in cleaving the beta-amyloid precursor protein (betaAPP) and Notch in their transmembrane domains. The former process (termed gamma-secretase cleavage) generates amyloid beta-peptide (Abeta), which is involved in the pathogenesis of Alzheimer's disease. The latter process (termed S3-site cleavage) generates Notch intracellular domain (NICD), which is involved in intercellular signalling. Nicastrin binds both full-length betaAPP and the substrates of gamma-secretase (C99- and C83-betaAPP fragments), and modulates the activity of gamma-secretase. Although absence of the Caenorhabditis elegans nicastrin homologue (aph-2) is known to cause an embryonic-lethal glp-1 phenotype, the role of nicastrin in this process has not been explored. Here we report that nicastrin binds to membrane-tethered forms of Notch (substrates for S3-site cleavage of Notch), and that, although mutations in the conserved 312-369 domain of nicastrin strongly modulate gamma-secretase, they only weakly modulate the S3-site cleavage of Notch. Thus, nicastrin has a similar role in processing Notch and betaAPP, but the 312-369 domain may have differential effects on these activities. In addition, we report that the Notch and betaAPP pathways do not significantly compete with each other.

Alzheimer Disease↗

PubMed2001

Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP.

Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DGI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.

Asian People↗

PubMed2001

Crumpled structure of the custom hydrophobic lytic peptide cecropin B3.

The solution structure of a custom lytic peptide, cecropin B3 (CB3), having two identical hydrophobic segments on both the N- and C-termini, was investigated by two-dimensional NMR spectroscopy. The need to determine the structure of this peptide is rooted in its specific ability to lyse lipid layers that have a high content of anionic lipid. The lytic activities of CB3 on cell membranes including cancer cells and bacteria is found to be less than cecropin B1. The results show that CB3 has four discrete segments forming alpha helical structures. The crumpled structure of CB3 provides evidence for the lysis of the lipid layer being via a pathway that differs from pore formation. The results in this study provide strong clues towards a rational design for a potent antimicrobial and antitumor peptide.

3T3 Cells↗

PubMed2001

Severe canine hereditary hemolytic anemia treated by nonmyeloablative marrow transplantation.

Severe hemolytic anemia in Basenji dogs secondary to pyruvate kinase (PK) deficiency can be corrected by marrow allografts from healthy littermates after a conventional high-dose myeloablative conditioning regimen. The nonmyeloablative conditioning regimen used here, which consisted of a sublethal dose of 200 cGy total body irradiation before and immunosuppression with mycophenolate mofetil and cyclosporine after a dog leukocyte antigen (DLA)-identical littermate allograft, has been found to be effective in establishing stable mixed donor/host hematopoietic chimerism in normal dogs. We explored the feasibility of nonmyeloablative marrow allografts for the treatment of canine PK deficiency and studied the effect of stable allogeneic mixed hematopoietic chimerism on the natural course of the disease. Five affected dogs received transplants, of which 3 dogs had advanced liver cirrhosis and myelofibrosis. Both complications were presumed to be due to iron overload. All 5 dogs showed initial engraftment. Two rejected their grafts after 6 weeks but survived with completeautologous marrow recovery and return of the disease. One died from liver failure on day 27 with 60% donor engraftment. Two dogs have shown sustained mixed donor/host chimerism for more than a year with 85% and 12% donor hematopoietic cells, respectively. Overall clinical response correlated with the degree of donor chimerism. The dog with the low degree of chimerism achieved partial resolution of hemolysis, but the disease symptoms persisted as manifested by increasing iron overload resulting in progression of marrow and liver fibrosis. The dog with the high degree of donor chimerism achieved almost complete resolution of hemolysis with a decrease of marrow iron content and resolution of marrow fibrosis. These observations suggest that mixed hematopoietic chimerism can be relatively safely established in dogs with PK deficiency even in the presence of advanced liver cirrhosis. However, although effective in correcting or delaying the development of myelofibrosis, a low degree of mixed chimerism was not sufficient to prevent continued hemolysis of red blood cells of host origin. Complete donor chimerism appears necessary to achieve a long-term cure.

Anemia, Hemolytic, Congenital↗

PubMed2001

Effects of extending the duration of postgrafting immunosuppression and substituting granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells for marrow in allogeneic engraftment in a nonmyeloablative canine transplantation model.

Stable mixed donor/host hematopoietic chimerism was uniformly achieved in dogs given 200 cGy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) for 28 days and cyclosporine (CSP) for 35 days after transplantation of marrow from dog leukocyte antigen-identical littermates. When the TBI dose was lowered to 100 cGy, donor marrow engraftment in 6 dogs was only transient, lasting 3 to 12 weeks. In this study, we asked whether stable engraftment in this model could be achieved: (1) by substituting recombinant canine granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs) for marrow and (2) by extending CSP administration from 35 to 100 days. Eighteen dogs were given G-PBMC grafts and MMF for 28 days. Eight of the 18 dogs received CSP for 35 days and 10 for 100 days. We found that substituting G-PBMCs for marrow did not increase the incidence of stable allogeneic engraftment (P = .11). However, increasing the duration of posttransplantation immunosuppression with CSP from 35 to 100 days favorably influenced stable donor engraftment (P = .06).

Animals↗

PubMed2001

Analysis of montelukast in mild persistent asthmatic patients with near-normal lung function.

Few studies have specifically evaluated controller therapy in patients with mild persistent asthma. We used a subgroup analysis to investigate the effects of montelukast, a potent cysteinyl leukotriene receptor antagonist, on adult patients on the milder end of the asthma severity spectrum. We have identified seven double-blind, randomized, placebo-controlled studies of adult patients with mild-to-moderate chronic asthma in which montelukast was investigated. Subsets of patients with baseline forced expiratory volume in 1 sec (FEV1) > 80% and > 75% predicted or further restricted by less than daily rescue beta-agonist use were included as four cohorts (A, B, C, D), and efficacy measures, including change in FEV1 rescue-free days, beta-agonist use, nocturnal awakenings and blood eosinophil counts were evaluated. Cohorts A to D comprised 21%, 8%, 11%, and 4%, respectively, of patients from these studies. Mean pretreatment FEV1 ranged from 81% to 84% predicted and daily beta-agonist use from 2.4 to 4.5 puffs day(-1) in the four cohorts. Pooled results demonstrated a treatment effect for montelukast over placebo in all cohorts, for all endpoints. There was a significant improvement in FEV1 in montelukast-treated patients (7-8% over baseline) compared with placebo (1-4% over baseline, between-group difference P < or = 0.02) for all cohorts. Similarly, the percentage of rescue-free days increased substantially more with montelukast (22-30%) than with placebo (8-13%). This subgroup analysis indicates that montelukast produced improvements in parameters of asthma control in patients with milder persistent asthma that should be confirmed in additional prospective trials.

Acetates↗

PubMed2001

Monte Carlo dose verification for intensity-modulated arc therapy.

Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan. Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-Ill computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

Dose-Response Relationship, Radiation↗

PubMed2001

Radiosurgical management of benign cavernous sinus tumors: dose profiles and acute complications.

OBJECTIVE: Radiosurgery has emerged as an alternative treatment modality for cranial base tumors in patients deemed not suited for primary surgical extirpation, patients with recurrent or residual tumor after open surgery, or patients who refuse surgical treatment. We review our short-term experience with radiosurgical management of cavernous sinus region tumors with the Leksell gamma knife. METHODS: From August 1994 to February 1999, 69 patients with cavernous sinus lesions were treated in 72 separate treatment sessions. The tumor type distribution was 29 pituitary adenomas, 35 meningiomas, 4 schwannomas, and 1 paraganglioma. The median follow-up was 122 weeks. Lesions were stratified according to a five-level surgical grade. The grade distribution of the tumors was as follows: Grade I, 13; Grade II, 21; Grade III, 19; Grade IV, 12; Grade V, 4. Median tumor volume was 4.7 cm3. The median radiation dose was 15 Gy to the 50% isodose line. Median maximal radiation dose was 30 Gy. RESULTS: Analysis of tumor characteristics and radiation dose to optic nerve and pontine structures revealed a significant correlation between distance and dose. Much lower correlation coefficients were found between tumor volume and dose. One lesion in this series had evidence of transient progression and later regression on follow-up radiographic studies. No other lesions in this series were demonstrated to have exhibited progression. Complications after radiosurgical treatment were uncommon. Two patients had cranial nerve deficits after treatment. One patient with a surgical Grade III pituitary adenoma had VIth cranial nerve palsy 25 months after radiosurgical treatment that spontaneously resolved 10 months later. A patient with a bilateral pituitary adenoma experienced bilateral VIth cranial nerve palsy 3 months after treatment that had not resolved at 35 months after treatment. Six patients with preoperative cranial nerve deficits experienced resolution or improvement of their deficits after treatment. One patient with a prolactin-secreting adenoma experienced normalization of endocrine function with return of menses. CONCLUSION: Radiosurgical treatment represents an important advance in the management of cavernous sinus tumors, with low risk of neurological deficit in comparison with open surgical treatment, even in patients with high surgical grades.

Adolescent↗

PubMed2001

A phantom study of the geometric accuracy of computed tomographic and magnetic resonance imaging stereotactic localization with the Leksell stereotactic system.

OBJECTIVE: To assess the spatial accuracy of magnetic resonance imaging (MRI) and computed tomographic stereotactic localization with the Leksell stereotactic system. METHODS: The phantom was constructed in the shape of a box, 164 mm in each dimension, with three perpendicular arrays of solid acrylic rod, 5 mm in diameter and spaced 30 mm apart within the phantom. In this study, images from two different MRI scanners and a computed tomographic scanner were obtained using the same Leksell (Elekta Instruments, Stockholm, Sweden) head frame placement. The coordinates of the rod images in the three principal planes were measured by using a tool provided with Leksell GammaPlan software (Elekta Instruments, Norcross, GA) and were compared with the physical phantom measurements. RESULTS: The greatest distortion was found around the periphery, and the least distortion (<1.5 mm) was present in the middle and most other areas of the phantom. In the phantom study using computed tomography, the mean values of the maximum errors for the x, y, and z axes were 1.0 mm (range, 0.2-1.3 mm), 0.4 mm (range, 0.1-0.8 mm), and 3.8 mm (range, 1.9-5.1 mm), respectively. The mean values of the maximum errors when using the Philips MRI scanner (Philips Medical Systems, Shelton, CT) were 0.9 mm (range, 0.4-1.7 mm), 0.2 mm (range, 0.0-0.7 mm), and 1.9 mm (range, 1.3-2.3 mm), respectively. Using the Siemens MRI scanner (Siemens Medical Systems, New York, NY), these values were 0.4 mm (range, 0.0-0.7 mm), 0.6 mm (range, 0.0-1.0 mm), and 1.6 mm (range, 0.8-2.0 mm), respectively. The geometric accuracy of the MRI scans when using the Siemens scanner was greatly improved after the implementation of a new software patch provided by the manufacturer. The accuracy also varied with the direction of phase encoding. CONCLUSION: The accuracy of target localization for most intracranial lesions during stereotactic radiosurgery can be achieved within the size of a voxel, especially by using the Siemens MRI scanner at current specifications and with a new software patch. However, caution is warranted when imaging peripheral lesions, where the distortion is greatest.

Humans↗

PubMed2001

Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme that produces cholesteryl esters in various tissues. In mammals, two ACAT genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophage foam-cell formation, in absorbing dietary cholesterol, and in supplying cholesteryl esters as part of the core lipid for lipoprotein synthesis and assembly. The key difference in tissue distribution of ACAT1 and ACAT2 between humans, mice and monkeys is that, in adult human liver (including hepatocytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. There is compelling evidence implicating a role for ACAT1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption. However, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron synthesis/assembly process.

Animals↗

PubMed2001

An image fusion study of the geometric accuracy of magnetic resonance imaging with the Leksell stereotactic localization system.

A special acrylic phantom designed for both magnetic resonance imaging (MRI) and computed tomography (CT) was used to assess the geometric accuracy of MRI-based stereotactic localization with the Leksell stereotactic head frame and localizer system. The acrylic phantom was constructed in the shape of a cube, 164 mm in each dimension, with three perpendicular arrays of solid acrylic rods, 5 mm in diameter and spaced 30 mm apart within the phantom. Images from two MR scanners and a CT scanner were obtained with the same Leksell head frame placement. Using image fusion provided by the Leksell GammaPlan (LGP) software, the coordinates of the intraphantom rod positions from two MRI scanners were compared to that of CT imaging. The geometric accuracy of MR images from the Siemens scanner was greatly improved after the implementation of a special software patch provided by the manufacturer. In general, much better accuracy was achieved in the transverse plane where images were acquired. Most distortion was found around the periphery while least distortion was present in the middle and most other parts of the phantom. For most intracranial lesions undergoing stereotactic radiosurgery, accuracy of target localization can be achieved within size of a voxel, especially with the Siemens scanner. However, extra caution should be taken for imaging of peripheral lesions where the distortion is the greatest.

Humans↗

PubMed2001

A translational couch technique for total body irradiation.

We have constructed a computer controlled translational couch to administer total body irradiation reproducibly and safely. The system has replaced the previous stationary anterior-posterior technique in our institution and 30 plus patients have been treated with it so far. In this technique, patients comfortably lie on a couch in supine and prone positions and are transported slowly through a narrow beam with the gantry in an upright position. Dose to the patient is determined by the couch velocity that is calculated based on physical parameters such as patient's dimensions, beam geometry, and machine dose rate. In our design, the couch velocity is continuously updated to compensate for machine dose rate fluctuations. The translational couch technique provides better dose uniformity within the patient compared to fixed beam techniques, and allows a more precise shielding block placement for organs at risk. At the same time, it presents a special challenge for dosimetry calculations. A dosimetry parameter is introduced that converts the moving beam output to the fixed beam output factor. Based on this factor, a simple dosimetry calculation method has been developed that takes advantage of conventional dosimetry parameters, eliminating extensive dosimetry measurements. Multiple point dose measurements within a phantom confirmed the validity of the calculation method.

Dose Fractionation, Radiation↗

PubMed2001

Sequence-dependent potentiation of paclitaxel-mediated apoptosis in human leukemia cells by inhibitors of the mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathway.

Effects of inhibitors of the mitogen-activated protein kinase kinase/mitogen-activated protein kinase (MEK/MAPK) cascade have been examined in relation to paclitaxel-induced apoptosis in human monocytic leukemia cells (U937). Cells treated with paclitaxel (250 nm; 6 h) followed by PD98059 [corrected] exhibited a significant increase in mitochondrial dysfunction (e.g., cytochrome c release), caspase activation, poly ADP-ribose polymerase cleavage, and apoptosis, whereas pretreatment of cells with PD98059 reduced lethality. Similar results were obtained with other MEK/MAPK inhibitors (e.g., U0126 and PD184352). Subsequent exposure of paclitaxel-treated cells to PD98059 did not enhance dephosphorylation/activation of p34(cdc2) but diminished expression of the antiapoptotic protein Mcl-1. The caspase inhibitor ZVAD-fmk opposed potentiation of paclitaxel-induced loss of mitochondrial membrane potential (Deltapsi(m)) and apoptosis by PD98059, but not cytochrome c release. Paclitaxel treatment induced sustained phosphorylation/activation of MAPK, an effect prevented by subsequent, but not prior, exposure to PD98059. Paclitaxel treatment also induced c-Jun N-terminal kinase phosphorylation, but this effect was enhanced only slightly by subsequent PD98059 administration. Although paclitaxel alone failed to induce p38 MAPK activation, subsequent (but not prior) exposure to PD98059 induced a dramatic increase in p38 MAPK phosphorylation. Moreover, coadministration of the p38 MAPK inhibitors SB203580 and SB202190 abrogated the increase in paclitaxel-mediated apoptosis induced by PD98059. Finally, subsequent PD98059 exposure increased, whereas prior exposure decreased inhibition of clonogenicity by paclitaxel. Together, these findings suggest that subsequent exposure of paclitaxel-treated U937 cells to MEK/MAPK inhibitors induces perturbations in signaling pathways, particularly the p42/44 MAPK and p38 MAPK cascades, that lower the threshold for mitochondrial injury and induction of cell death.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Activation of NF-kappaB by hepatitis B virus X protein through an IkappaB kinase-independent mechanism.

pX, the hepatitis B virus-encoded transcription coactivator, is involved in viral infection in vivo. pX stimulates the activity of several transcription factors including nuclear factor-kappaB (NF-kappaB), but the mechanism of activation is poorly understood. The IkappaB kinase complex (IKK) mediates activation of NF-kappaB in response to various extracellular stimuli, including inflammatory cytokines like tumor necrosis factor and interleukin 1, human T cell lymphoma virus 1 Tax protein, and tumor promoters like phorbol esters. It is not known whether IKK also mediates activation of NF-kappaB by pX. Here we report that IKK was not essential for activation of NF-kappaB by pX. Expression of pX resulted in the degradation of IkappaBalpha in the absence of its phosphorylation at Ser(32) and Ser(36) residues. Although pX stimulated the activity of cotransfected IKK-beta when it was overexpressed, it failed to activate endogenous IKK. Furthermore, expression of pX stimulated NF-kappaB nuclear translocation and transcriptional activity in IKK-gamma-null fibroblast 5R cells. Our data indicate that pX stimulates NF-kappaB activity through a mechanism that is dependent on IkappaBalpha degradation but not on IKK activation.

Cell Line↗

PubMed2001

Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction.

Studies were conducted on isolated rat gracilis muscle arterioles to examine the role of vascular heme oxygenase (HO)-derived carbon monoxide (CO) on myogenic constrictor responses to stepwise increments in intraluminal pressure. The arterioles express HO-2 but not HO-1 and manufacture CO. Both HO-2 protein expression and CO production are reduced in arterioles maintained for 18 h before experimentation in media containing HO-2 antisense oligodeoxynucleotides (AS-ODN). Pressurization of arterioles mounted on a myograph over the pressure range of 40--100 mmHg elicits reduction of internal diameter. At pressures >40 mmHg, the internal diameter of vessels treated with either HO-2 AS-ODN, the HO inhibitor chromium mesoporphyrin (CrMP), or the K(+) channel blocker tetraethylammonium (TEA) are smaller than the corresponding control values. The inclusion of exogenous CO, but not of biliverdin, in the superfusion buffer attenuates pressure-induced vasoconstriction in CrMP-treated vessels. However, exogenous CO does not attenuate pressure-induced vasoconstriction in vessels treated with both CrMP and TEA. Collectively, these data suggest that CO of vascular origin attenuates pressure-induced arteriolar constriction via a mechanism involving a TEA-sensitive K(+) channel.

Animals↗

PubMed2001

Prenatal glucocorticoid modifies hypothalamo-pituitary-adrenal regulation in prepubertal guinea pigs.

We hypothesized that exposure to synthetic glucocorticoid during rapid brain growth (d50-52, birth = 68 days) in fetal guinea pigs modifies hypothalamo-pituitary-adrenal (HPA) function after birth, and that this involves changes in central corticosteroid receptor regulation. On the basis of our previous studies, we proposed that this effect is sex-specific. Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on d50-51 of gestation, and juvenile offspring were euthanized at rest or following isolation stress on postnatal day 18. Dexamethasone increased the length of gestation (1.5 days) and altered body and organ (brain, heart, adrenal) growth. Resting plasma cortisol concentrations were significantly elevated in young male, but not female guinea pigs exposed to dexamethasone as fetuses. In female offspring born to dexamethasone-treated mothers, cortisol responses to isolation stress were attenuated. In males, elevated basal cortisol levels were not increased further by isolation. In the brain, hippocampal glucocorticoid receptor (GR) mRNA levels were significantly lower (10-25%) in females exposed to dexamethasone in utero. In contrast, GR mRNA levels were elevated (10-20%) in males from this prenatal treatment group. Mineralocorticoid receptor mRNA in the limbic system and GR mRNA levels in the pars distalis were unaffected. Pro-opiomelanocortin mRNA was significantly lower (30%) in the male pars intermedia following dexamethasone exposure. In conclusion, prenatal glucocorticoid exposure affects growth and HPA function as well as limbic and hypothalamic GR expression in juvenile offspring, and these effects are highly sex-specific.

Animals↗