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PubMed2006

Adolescent axis I and personality disorders predict quality of life during young adulthood.

PURPOSE: To investigate and compare the prospective association of adolescent Axis I mental disorder and personality disorder (PD) with young adult quality of life (QOL) in the general population. METHODS: Seven hundred fifty mothers and youths participating in a prospective longitudinal community-based study were interviewed. Mental disorders were measured at a mean age 16 years. QOL as the outcome indicators were assessed at a mean age 22. RESULTS: Adolescent Axis I disorder predicted elevated negative affect and higher levels of stress some 6 years later. Adolescent PD predicted elevated negative affect and higher levels of stress, and also problems in social support and relationships, and poorer residential, mobility, and financial and health resources in adulthood. Youths with both Axis I disorder and one or more PDs had the worst outcomes with regard to health problems, stressful occupational or educational settings, and resources, net of the effects of adolescent health problems. Nevertheless, some aspects of adult QOL were not significantly related to adolescent disorder, including a positive perspective on the future, own morale in a chosen occupation or educational setting, or the amount of autonomy experienced in that setting. CONCLUSIONS: Among adolescents in the community, PDs during adolescence may have a more adverse impact on young adult QOL than do Axis I disorders. A combination of Axis I and PD may represent a particular risk for new physical health problems and resource inadequacy, including poor access to health care.

Adolescent↗
PubMed2005

Estimation of the axis of a screw motion from noisy data--a new method based on Plücker lines.

The problems of estimating the motion and orientation parameters of a body segment from two n point-set patterns are analyzed using the Plücker coordinates of a line (Plücker lines). The aim is to find algorithms less complex than those in conventional use, and thus facilitating more accurate computation of the unknown parameters. All conventional techniques use point transformation to calculate the screw axis. In this paper, we present a novel technique that directly estimates the axis of a screw motion as a Plücker line. The Plücker line can be transformed via the dual-number coordinate transformation matrix. This method is compared with Schwartz and Rozumalski [2005. A new method for estimating joint parameters from motion data. Journal of Biomechanics 38, 107-116] in simulations of random measurement errors and systematic skin movements. Simulation results indicate that the methods based on Plücker lines (Plücker line method) are superior in terms of extremely good results in the determination of the screw axis direction and position as well as a concise derivation of mathematical statements. This investigation yielded practical results, which can be used to locate the axis of a screw motion in a noisy environment. Developing the dual transformation matrix (DTM) from noisy data and determining the screw axis from a given DTM is done in a manner analogous to that for handling simple rotations. A more robust approach to solve for the dual vector associated with DTM is also addressed by using the eigenvector and the singular value decomposition.

Acceleration↗
PubMed2005

Estrogen/hypothalamus-pituitary-adrenal axis interactions in the fetus: The interplay between placenta and fetal brain.

OBJECTIVE: The hormonal interactions between the placenta and the fetal hypothalamus-pituitary-adrenal (HPA) axis are reviewed. METHODS: This review addresses data obtained from the chronically catheterized fetal sheep, drawing relevant comparisons to human fetuses. RESULTS: In the sheep, and perhaps in primate species, parturition is initiated by an increase in the activity of the HPA axis. The endogenous mechanisms underlying the increase in activity of the fetal HPA axis are incompletely understood but might involve an interplay between placenta and fetal hypothalamus and pituitary. Various hypotheses have been proposed, involving placental secretion of prostaglandins and various components of the fetal HPA axis. In the sheep, the influence of estradiol appears to be potent, and various experiments have suggested the possibility that, in late gestation, there exists a positive feedback relationship between placental estrogen secretion and pituitary adrenocorticotropin (ACTH) secretion. Estradiol circulates in concentrations known to stimulate fetal ACTH secretion. Additionally, estradiol circulates in the form of estradiol-3-sulfate, a molecular form that is taken up by the fetal brain and deconjugated by steroid sulfatase, which is expressed in the fetal brain. Recent evidence suggests that the interaction between estradiol and ACTH might involve production of paracrine or autocrine substances in the fetal brain. One candidate mediator is prostaglandin E2 (PGE2), highlighted by the action of estradiol on the expression of prostaglandin endoperoxide synthase-2 (PGHS-2 or COX-2) in brain regions known to be important for controlling HPA activity. CONCLUSION: Estradiol, secreted by the placenta in increasing amounts in late gestation, is a potent stimulator of fetal ACTH secretion. The interactions between estradiol and the fetal HPA axis might function as a positive feedback loop that increases the concentrations of both hormones before birth.

Adrenocorticotropic Hormone↗
PubMed2005

A single dose of metyrapone caused long-term dysregulation of the hypothalamic-pituitary-adrenal axis in the rat.

There is evidence that metyrapone (MET), apart from its inhibition of 11-beta steroid hydroxylation, may exert some stress-like effects in the brain, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the induction of c-fos. Since a single exposure to some stressors has been found to exert long-term effects on the HPA axis, we hypothesized that a single dose of MET (200 mg/kg, s.c.) could exert even stronger effects, due to the combination of its stressful properties with the lack of constrain of the HPA axis by glucocorticoids. Whereas the inhibitory effect of the drug on corticosterone secretion lasted less than 24 h, its stimulatory effect on the HPA axis could be seen for at least 2 days after the injection. Surprisingly, on day 8, an exacerbated HPA response to immobilization stress was observed in MET rats, despite complete normalization of resting levels of HPA hormones. At this time it was also observed, under basal conditions, increased levels of mRNA for CRH and arginin-vasopressin in the parvocellular region of the paraventricular nucleus of the hypothalamus (pPVN), along with reduced mRNA for glucocorticoid receptors in dentate gyrus and hippocampus CA1, but not in pPVN or medial prefrontal cortex. These data suggest that a single MET administration can exert a marked and long-lasting dysregulation of both resting and stress-induced activity of the HPA axis. Thus, attention should be paid to these properties when using the drug to study the functional role of glucocorticoids.

Animals↗
PubMed2006

Revisions to tolerances in cylinder axis and in progressive addition lens power in ANSI Z80.1-2005.

BACKGROUND: ANSI Z80.1 (American National Standards Institute) is a voluntary standard that provides tolerance guidelines for ophthalmic lens parameters. The recently approved ANSI Z80.1-2005 changes tolerances for cylinder axis for all ophthalmic lenses and for distance power for progressive addition lenses (PALs). METHODS: The ANSI Z80.1 committee analyzed the amount of unwanted residual cylinder created by rotating a cylinder axis away from its desired orientation for a range of cylinder powers. The limits of axis orientation error that keep the residual unwanted cylinder error within the tolerances for cylinder power were determined. For PALs, a tolerance for distance power error was sought that considers the currently followed standards for front surface power error and the tooling steps used for the rear surface. RESULTS: Tolerances for cylinder axis error were changed to +/-14 degrees for 0.25 diopter (D) cylinders and to +/-7 degrees for 0.50 D cylinders. Tolerance for error in back vertex power of PALs was changed to +/-0.16 D for both sphere and cylinder. CONCLUSION: Tolerances for cylinder axis for low cylinders have been made in ANSI Z80.1-2005 to be consistent with tolerances in cylinder power. Changes in tolerance for power errors in PALs have been made to recognize fabrication challenges.

Equipment Design↗
PubMed2006

Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine.

Although caffeine is the most consumed psychoactive substance in the world, the extents of many of its effects are unknown. High doses of caffeine have been shown to activate the HPA axis while the effects of low to moderate doses have usually not been described in detail. Moreover, although several lines of evidence suggest that low doses of caffeine may restrain some negative affective states, the possible modulatory role of caffeine on HPA axis activation induced by a stressful stimulus has not been described. Thus, the present studies investigated the possible modulatory effects of low to moderate doses of caffeine on moderate to high HPA axis activation induced by different intensities of loud noise. First, in order to test this modulation, time courses for adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone levels peaked 30 min from the onset of noise presentation, and rapidly declined after noise termination. A low caffeine dose of 2 mg/kg significantly increased plasma corticosterone and ACTH levels 30 min following injections, but levels returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and higher elevated plasma hormone levels for at least 2h. Doses of 2 or 10mg/kg, however, did not modulate endocrine responses to loud noise presentation. It is concluded that although caffeine activates the HPA axis, low to moderate doses do not modulate HPA axis responses to stressful stimuli.

Acoustic Stimulation↗
PubMed2004

The HPA axis and the genesis of chronic fatigue syndrome.

Many studies of patients with long-standing chronic fatigue syndrome (CFS) have found alterations to the hypothalamo-pituitary-adrenal (HPA) axis, including mild hypocortisolism, heightened negative feedback and blunted responses to challenge. However, recent prospective studies of high-risk cohorts suggest that there are no HPA axis changes present during the early stages of the genesis of fatiguing illnesses. Moreover, HPA axis changes can be reversed by modifying behavioural features of the illness, such as inactivity, deconditioning and sleep disturbance. Nevertheless, raising levels of cortisol pharmacologically can temporarily alleviate symptoms of fatigue. This article presents the case that there is no specific change to the HPA axis in CFS and that the observed changes are of multifactorial aetiology, with some factors occurring as a consequence of the illness. Nevertheless, the HPA axis might play a role in exacerbating or perpetuating symptoms late on in the course of the illness.

Cohort Studies↗
PubMed2004

ALK4 functions as a receptor for multiple TGF beta-related ligands to regulate left-right axis determination and mesoderm induction in Xenopus.

In Xenopus, several TGF betas, including nodal-related 1 (Xnr1), derriere, and chimeric forms of Vg1, elicit cardiac and visceral organ left-right (LR) defects when ectopically targeted to right mesendoderm cell lineages, suggesting that LR axis determination may require activity of one or more TGF betas. However, it is not known which, if any, of these ligands is required for LR axis determination, nor is it known which type I TGF beta receptor(s) are involved in mediating left-side TGF beta signaling. We report here that similar to effects of ectopic TGF betas, right-side expression of constitutively active activin-like kinase (ALK) 4 results in LR organ reversals as well as altered Pitx2 expression in the lateral plate mesoderm. Moreover, left-side expression of a kinase-deficient, dominant-negative ALK4 (DN-ALK4) or an ALK4 antisense morpholino also results in abnormal embryonic body situs, demonstrating a left-side requirement for ALK4 signaling. To determine which TGF beta(s) utilize the ALK4 pathway to mediate LR development, biochemical and functional assays were performed using an Activin-Vg1 chimera (AVg), Xnr1, and derriere. Whereas ALK4 can co-immunoprecipitate all of these TGF betas, including endogenous Vg1 protein from embryo homogenates, functional assays demonstrate that not all of these ligands require an intact ALK4 signaling pathway to modulate LR asymmetry. When AVg and DN-ALK4 are co-expressed, LR defects otherwise induced by AVg alone are attenuated by DN-ALK4; however, when functional assays are performed with Xnr1 or derriere, LR defects otherwise elicited by these ligands alone still occur in the presence of DN-ALK4. Intriguingly, when any of these TGF betas is expressed at a higher concentration to elicit primary axis defects, DN-ALK4 blocks gastrulation and dorsoanterior/ventroposterior defects that otherwise occur following ligand-only expression. Together, these results suggest not only that ALK4 interacts with multiple TGF betas to generate embryonic pattern, but also that ALK4 ligands differentially utilize the ALK4 pathway to regulate distinct aspects of axial pattern, with Vg1 as a modulator of ALK4 function in LR axis determination and Vg1, Xnr1, and derriere as modulators of ALK4 function in mesoderm induction during primary axis formation.

Activin Receptors↗
PubMed2004

Oral-aboral axis specification in the sea urchin embryo II. Mitochondrial distribution and redox state contribute to establishing polarity in Strongylocentrotus purpuratus.

The initial asymmetry that specifies the oral-aboral (OA) axis of the sea urchin embryo has long been a mystery. It was shown previously that OA polarity can be entrained in embryos by imposing a respiratory asymmetry, with the most oxidizing side of the embryo tending to develop as the oral pole. This suggests that one of the earliest observable asymmetries along the incipient OA axis, a redox gradient established by a higher density and/or activity of mitochondria on the prospective oral side of the embryo, might play a causal role in establishing the axis. Here, we examine the origin and functional significance of this early redox gradient. Using MitoTracker Green, we show that mitochondria are asymmetrically distributed in the unfertilized egg of Strongylocentrotus purpuratus, and that the polarity of the maternal asymmetry is maintained in the zygote. Vital staining indicates that the side of the embryo that inherits the highest density of mitochondria tends to develop into the oral pole. This correlation holds when mitochondria are redistributed by centrifugation of eggs or by transfer of purified mitochondria into zygotes, indicating that an asymmetric mitochondrial distribution can entrain OA polarity, possibly through effects on intracellular redox state. In support of this possibility, we find that specification of oral ectoderm is suppressed when embryos are cultured under hypoxic conditions that enforce a relatively reducing redox state. This effect is reversed by overexpression of nodal, an early zygotic marker of oral specification whose localized expression suffices to organize the entire OA axis, indicating that redox state is upstream of nodal expression. We therefore propose that a threshold level of intracellular oxidation is required to effectively activate nodal, and that precocious attainment of this threshold within the blastomeres containing the highest density of mitochondria results in asymmetric nodal activity and consequent specification of the OA axis.

Aldehydes↗
PubMed1999

Hypothalamic-pituitary-adrenal axis effects on plasma homovanillic acid in man.

BACKGROUND: Effects of the hypothalamic-pituitary-adrenal (HPA) axis on central dopaminergic systems have been proposed to underlie the development of psychotic symptoms in depression. This study examined HPA axis hormone effects on plasma levels of homovanillic acid (HVA), the dopamine metabolite, in healthy volunteers, using a placebo-controlled, double-blind, random-assignment, crossover design. On the basis of preliminary studies, we hypothesized that HPA axis hormones would produce delayed effects on plasma HVA levels measured in the afternoon. METHODS: Ten healthy subjects underwent a standard protocol on four occasions and each time received ovine corticotropin-releasing hormone, synthetic adrenocorticotropic hormone (ACTH), cortisol, or placebo. Plasma HVA was measured at 9 AM and 4 PM on Day 1, immediately prior to administration of the test substance at 7 PM, then at 30-60-min intervals until 11 PM. Plasma HVA levels were subsequently obtained at 9 AM and 4 PM on Days 2 and 3. RESULTS: As predicted, there were significant differences between test substances in delayed effects on afternoon HVA levels measured on Days 2 and 3, with cortisol and ACTH producing greater increases in HVA than placebo. Acute effects of HPA axis hormones on HVA were not found, while differences between test substances in delayed effects on morning HVA levels approached significance. CONCLUSIONS: HPA axis hormones exert delayed effects on plasma HVA levels in healthy humans.

Adrenal Cortex Hormones↗
PubMed1999

Patterns of axis I comorbidity in early-onset versus late-onset major depressive disorder.

BACKGROUND: This study of a large clinical sample of depressed patients examined whether childhood onset as compared with adult onset Major Depressive Disorder (MDD) would confer a greater risk for Axis I comorbidity and whether childhood onset MDD would also differ from adult onset MDD in the pattern of comorbid disorders. METHODS: We examined lifetime co-occurrence of Axis I disorders among 381 adult outpatients with MDD by Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P). Subjects were divided into childhood onset (n = 47), adolescent onset (n = 101) and adult onset (n = 233) MDD groups. RESULTS: We found that the two early-onset groups exhibited significantly increased rates of Axis I comorbidity. The childhood onset group accounted for a disproportionately high percentage of depressed adults with two or more comorbid Axis I disorders. Social and simple phobias and alcohol abuse/dependence were significantly more prevalent among individuals with childhood onset MDD than among individuals with adult onset MDD. Alcohol abuse/dependence, but not anxiety disorders, was significantly more prevalent among adolescent onset than adult onset MDD groups. Panic, generalized anxiety, obsessive-compulsive and somatoform disorders were equally distributed across MDD onset groups. Comorbid disorders were much more likely to have followed onset of MDD among individuals with childhood compared with adult onset, except for social phobia which more frequently preceded the depression. The relative ordering among the comorbid conditions with respect to whether they followed or preceded MDD did not vary notably across the three age of onset groups. CONCLUSIONS: We conclude that early-onset MDD is associated with an increased density of Axis I comorbidity that seems to be limited to specific disorders.

Adult↗
PubMed2000

Melatonin reversal of DOI-induced hypophagia in rats; possible mechanism by suppressing 5-HT(2A) receptor-mediated activation of HPA axis.

Serotonin type 2A (5-HT(2A)) receptor-mediated neurotransmitter is known to activate hypothalamic-pituitary-adrenal (HPA) axis, regulate sleep-awake cycle, induce anorexia and hyperthermia. Interaction between melatonin and 5-HT(2A) receptors in the regulation of the sleep-awake cycle and head-twitch response in rat have been reported. Previous studies have shown that melatonin has suppressant effect on HPA axis activation, decreases core body temperature and induces hyperphagia in animals. However, melatonin interaction with 5-HT(2A) receptors in mediation of these actions is not yet reported. We have studied the acute effect of melatonin and its antagonist, luzindole on centrally administered (+/-)-1-(2, 5-dimethoxy-4-iodophenyl) 2-amino propane (DOI; a 5-HT(2A/2C) agonist)-induced activation of HPA axis, hypophagia and hyperthermia in 24-h food-deprived rats. Like ritanserin [(1 mg/kg, i.p.) 5-HT(2A/2C) antagonist], peripherally administered melatonin (1.5 and 3 mg/kg, i.p.) did not affect the food intake, rectal temperature or basal adrenal ascorbic acid level. However, pretreatment of rats with it significantly reversed DOI (10 microgram, intraventricular)-induced anorexia and activation of HPA axis. But the hyperthermia induced by DOI was not sensitive to reversal by melatonin. Mel(1) receptor subtype antagonist luzindole (5 microgram, intraventricular) did not modulate the DOI effect but antagonized the melatonin (3 mg/kg, i.p.) reversal of 5-HT(2A) agonist response. The present data suggest that melatonin reversal of DOI-induced hypophagia could be due to suppression of 5-HT(2A) mediated activation of HPA axis.

Adrenal Glands↗
PubMed2003

Alterations in hypothalamic-pituitary-adrenal axis activity and in levels of proopiomelanocortin and corticotropin-releasing hormone-receptor 1 mRNAs in the pituitary and hypothalamus of the rat during chronic 'binge' cocaine and withdrawal.

Tolerance to the stimulatory effects of cocaine on the hypothalamic-pituitary-adrenal (HPA) axis develops after chronic 'binge' cocaine exposure in the rat. This blunting of HPA axis activity in response to cocaine is associated with a cocaine-induced reduction of corticotropin-releasing hormone (CRH) mRNA level in the hypothalamus. There is limited information about the effects of withdrawal from chronic cocaine on HPA activity. The present studies were undertaken to determine levels of the HPA hormones adrenocorticotropic hormone (ACTH) and corticosterone across 10 days of withdrawal following chronic 'binge' pattern cocaine administration (3 x 15 mg/kg/day at hourly intervals) for 14 days. Male Fischer rats showed a significantly attenuated HPA axis response to chronic 'binge' pattern cocaine administration 30 min after the last injection on the 14th day, as measured by both plasma ACTH and corticosterone levels at the nadir time point. Twenty-four hours following the final administration of 'binge' cocaine (the 1st day of withdrawal), a significant elevation of plasma ACTH levels and a modest, but significant, elevation of plasma corticosterone levels were found at the nadir time point. This acute withdrawal-related activation of the hormones of the HPA axis was no longer found on the 10th day of withdrawal. In the anterior pituitary, levels of both proopiomelanocortin (POMC) and CRH-receptor 1 (R1) mRNAs were significantly higher than saline controls on the 14th day of chronic 'binge' cocaine and were at control levels on the 4th day of withdrawal. In the neurointermediate lobe of the pituitary, a sustained reduction in POMC mRNA levels was observed on the 3rd, 7th and 14th day of chronic 'binge' cocaine, but POMC mRNA was at control levels by the 4th day of withdrawal. In the hypothalamus, POMC mRNA levels showed a transient decrease on the 1st day of 'binge' cocaine with no change during chronic 'binge' cocaine or its withdrawal. CRH mRNA levels in the hypothalamus were not different from saline controls on the 1st and 4th days of withdrawal. Taken together, the present results show that after development of adaptation or tolerance to chronic 'binge' cocaine there is an increase in HPA activity during acute cocaine withdrawal. In addition to being associated with CRH input from the hypothalamus, the activation of the HPA axis by cocaine withdrawal may be, at least in part, due to the increased POMC and/or CRH-R1 gene expression observed in the anterior pituitary after chronic 'binge' cocaine.

Adrenal Glands↗
PubMedDate not supplied

Axis II comorbidity of borderline personality disorder.

The purpose of this study was to assess the prevalence of a full range of DSM-III-R axis II disorders in a sample of criteria-defined borderline patients and axis II controls. The axis II comorbidity of 504 personality-disordered inpatients was assessed blind to clinical diagnosis using a semistructured research interview. Odd, anxious, and dramatic cluster disorders were each common among borderline patients. However, only odd and anxious cluster disorders were significantly more common among borderline patients (N = 379) than axis II controls (N = 125). Paranoid, avoidant, and dependent personality disorders were the most highly discriminating disorders between borderline patients and controls. In addition, male and female borderline patients exhibited somewhat different patterns of comorbidity. Although the rates of avoidant and dependent personality disorders were similar, male borderlines were significantly more likely than female borderlines to meet DSM-III-R criteria for paranoid, passive-aggressive, narcissistic, sadistic, and antisocial personality disorders. These results suggest that there is a particularly strong relationship between anxious cluster disorders and borderline personality disorder (BPD). They also suggest that gender plays an important role in the expression of axis II comorbidity, particularly with respect to dramatic cluster disorders.

Borderline Personality Disorder↗
PubMed1997

Suppression and recovery of the neonatal hypothalamic-pituitary-adrenal axis after prolonged dexamethasone therapy.

OBJECTIVE: To evaluate the duration and level of hypothalamic-pituitary-adrenal (HPA) axis suppression in premature infants treated with a prolonged course of glucocorticoids for chronic lung disease. STUDY DESIGN: We evaluated HPA axis function in nine very low birth weight (VLBW) infants before and 48 hours after a prolonged (14 to 42 days) dexamethasone (Dex) course. Seven of these infants underwent serial testing in the Clinical Research Center to evaluate the time course of HPA axis recovery. Adrenal function was assessed directly with synthetic adrenocorticotropic hormone (ACTH) stimulation, pituitary function with ovine corticotrophin releasing hormone (oCRH) stimulation, and combined axis function with 3-hour metyrapone testing. RESULTS: Baseline cortisol values were higher before Dex therapy (18.6 +/- 3.9 microg/dl; mean +/- SEM) than after (5.77 +/- 1.45 microg/dl; p < 0.01), as were ACTH-stimulated cortisol levels (24.8 +/- 1.7 microg/dl vs 12.0 +/- 2.2 microg/dl; p < 0.001). ACTH response to oCRH decreased after Dex treatment (22.8 +/- 7.6 pg/ml vs 11.5 +/- pg/ml), but this was not statistically significant (p = 0.18). 11-Deoxycortisol (11-DOC) response to metyrapone dropped from 11.1 +/- 0.5 microg/dl to 4.7 +/- 1.0 microg/dl after Dex therapy (p < 0.0001). Longitudinal testing reveals that adrenal suppression may be short-lived, while recovery of higher centers is more delayed. CONCLUSIONS: Basal cortisol levels may be used as a screening test, but if the level is less than 15 microg/dl, more definitive testing should be performed. The sluggish recovery of higher HPA axis centers is most reliably evaluated by using 11-DOC response to a single dose of metyrapone in VLBW infants after prolonged Dex therapy.

Adrenocorticotropic Hormone↗
PubMed2003

Repeated citalopram treatment but not stress exposure attenuates hypothalamic-pituitary-adrenocortical axis response to acute citalopram injection.

Many experimental, clinical and epidemiological studies have shown a direct connection between exposure to stress or adverse life events and disease, but little is known about the effect of stress on the action of drugs. The aim of this study was to test the hypothesis that previous exposure to stress changes the action of the antidepressant drug citalopram (10 mg/kg, i.p.) on hypothalamic-pituitary-adrenocortical (HPA) axis function, gene expression of selected neuropeptides and serotonin reuptake. Three different stress models were used, which included immobilization, restraint and unpredictable stress stimuli. Samples of plasma for hormone measurement were taken from conscious cannulated animals. Changes in corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the paraventricular nucleus of the hypothalamus and the anterior pituitary, respectively, and the ability of citalopram to inhibit serotonin reuptake were investigated. The exposure to three different stress models did not influence citalopram action on individual parameters of HPA axis and on serotonin reuptake. On the other hand, repeated administration of the drug led to significant attenuation of ACTH and CRH mRNA responses. The present results allow to suggest that the stressors used did not influence serotonergic neurotransmission to the extent that would modify HPA axis response to citalopram challenge. Activation of HPA axis by acute citalopram treatment was found to be accompanied by increased CRH gene expression in the hypothalamus. Repeated administration of the drug led to the development of tolerance to activation of central and peripheral components of HPA axis, but not to serotonin reuptake inhibition.

Adrenal Cortex↗
PubMed1997

Hypothalamo-pituitary-IGF-1 axis in female rats made obese by overfeeding.

A gender-related impairment of the somatotrophic axis is present in obese Zucker rats, female rats being better preserved than males. We showed that another animal model of obesity, i.e., male rats made obese by feeding a hypercaloric diet had a reduced function of somatotrophic axis which was likely related to impairment of gonadal function. Aim of this work was that of studying the function of somatotrophic axis in female overfed rats and comparing it to that of male rats of the previous study. Sprague-Dawley female rats were fed an energy-rich palatable diet for seven months. At the end of overfeeding, according to the degree of overweight, rats were divided into overtly obese (Obese), overweight (Overweight) and Non-Obese, i.e. rats whose weights were similar to those of controls. Rats fed ad libitum with the standard pellet chow served as controls (Controls). Acute administration of a supramaximal dose of GHRH (2 microg/rat, iv) elicited a plasma GH rise similar to that of Controls in all the groups, except in Obese which had a lower GH response. Growth hormone responses after GHRH administration were inversely related to plasma levels of free fatty acids (FFA). Pituitary GH content and gene expression as well as hypothalamic GHRH and SS mRNA content, were similar in all experimental groups and in Controls and the same was true for plasma concentrations of free IGF-I. These results indicate that, similarly to obese female Zucker rats, also overfed female rats had a better preservation of the somatotrophic axis than their male counterparts. In diet-induced obese rats, also the etiology of the impairment of somatotrophic axis seems to be gender-related i.e. due to a reduction of gonadal function in males and to an elevation of FFA in females.

Animals↗
PubMed1998

Right fetal cardiac axis: clinical significance and associated findings.

OBJECTIVE: To ascertain the clinical significance of right fetal cardiac axis. METHODS: Fetal cardiac axis was assessed prospectively in ultrasound examinations of 16,562 fetuses over a 6-year period. RESULTS: Twenty-two fetuses had a right cardiac axis. When classified by ventricular and atrial configuration, six fetuses had mirror-image hearts with situs inversus, 12 had rotation of the heart axis alone, and four had inversion of the ventricles. Fourteen of the 22 had underlying structural cardiac defects, most of which were atrioventricular septal defects, double outlet right ventricles, or common atria. The chromosomes and/or phenotypes of all 22 were normal. All four fetuses with polysplenia and asplenia died. Major extracardiac defects were few (two) but lethal. CONCLUSION: Right cardiac axis in the fetus is associated with a high incidence of structural cardiac defects. In the absence of severe extracardiac defects, polysplenia, or asplenia, neonatal outcome was good.

Dextrocardia↗