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Orexins and adipoinsular axis function in the rat.

Orexin A and B are recently identified as peptides that are derived from the same precursor and their expression is highly specifically localized in neurons located in the lateral hypothalamic area, a region implicated in the feeding behaviour. These peptides appear to be a part of a complex circuit that integrates the aspects of energy metabolism, cardiovascular function, hormone homeostasis and sleep/wake behaviours. The functional linking of orexins with leptin and insulin suggests the possibility of its involvement in the regulation of the adipoinsular axis, and the present investigation was designed to examine the potential role of orexins in this axis regulation. In all the tested doses (8, 16 and 40 nmol/kg body weight (b.w.)), subcutaneous (s.c.) injections of orexin A caused the significant increase in insulin and leptin blood levels. These elevations were observed 60 and 120 min after peptide administration. On the other hand, after the orexin B administration, elevated insulin and leptin blood concentrations were found only at 60 min of the experiment, and in that time point, the increases were comparable to that evoked by orexin A. In comparison with the control animals, the administration of orexins for 7 days resulted in a significant gain in body weight. Prolonged administration of either orexin A or orexin B significantly elevated insulin and leptin blood concentrations. Under these conditions, the orexin A effect on the leptin secretion was more marked than on the insulin secretion, and this difference is reflected by the lowered insulin/leptin molar ratio. These results suggest that orexins play an important role in the adipoinsular axis function and may be a significant regulator of both insulin and leptin secretion. In this regard, we suggest the updated functional model of Kieffer and Habener [Am. J. Physiol.: Endocrinol. Metab. 27 (2000) E1] that proposed the adipoinsular axis. Our model is extended by the probable humoral links between orexins and leptin and orexins and insulin and points on the dependence of the effects evoked by orexins, leptin and insulin on the blood glucose levels.

Adipocytes↗

[Amniotic membrane transplantation and limbic-conjunctival autograft for recurrent pterygium, either invasive or with optic axis involvement].

OBJECTIVE: To evaluate amniotic membrane transplantation with limbic-conjunctival autograft during recurrent pterygium surgery in cases with a risk of stromal defect or with optic axis involvement, in order to limit the corneal defect in pterygium and preserve vision with moderate astigmatism. MATERIALS AND METHODS: Retrospective study of 50 cases. Three clinical aspects were encountered: A, recurrent pterygium after simple surgery (a corrected stromal defect)--six cases; B, primary pterygium at risk of stromal defect - five cases; C, primary pterygium with optic axis involvement--four cases. Each patient underwent ablative surgery followed by ocular surface rebuilding with limbic-conjunctival autograft combined with amniotic membrane graft on the corneal defect. Visual acuity and astigmatism were measured and compared before and after surgery. RESULTS: The mean follow-up was 13 months. At the end of the follow-up, the recurrence rate was 27% (four cases: two in A, two in B, and none in C). Mean visual acuity was improved from 0.7 to 0.8 postoperatively (p=0.041). Astigmatism changed slightly from 1.47 to 1.98 dioptres (p=0.155). DISCUSSION: For recurrent pterygium, with stromal defect or optic axis involvement, amniotic membrane transplantation and limbic-conjunctival autograft seems not to influence the recurrence rate. However, by limiting initial keratectomy, this surgical procedure only slightly modifies visual acuity and astigmatism in the cases where the two parameters are slightly affected. Failure can be easily managed with further surgery such as lamellar keratoplasty. CONCLUSION: Amniotic membrane transplantation and limbic-conjunctival autograft for recurrent pterygium or with optic axis involvement can be useful to integrate in the therapeutic arsenal of pterygium surgery.

Adult↗

Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K and neuropeptide gamma.

Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K, and neuropeptide gamma. PEPTIDES 1999. Neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide gamma (NPG) are members of the family of tachykinins, and act preferentially on NK-2 tachykinin receptors. These peptides are widely distributed and are potent stimulators of smooth muscle contraction, especially in the respiratory and gastrointestinal tract. They also induce vasodilatation and plasma extravasation. Through their effects on the vascular tone, they are also potential regulators of the blood flow and therefore of the function of many organs and tissues. Tachykinins have been demonstrated to influence the secretory activity of endocrine cells, and they may have a physiological role as regulators of endocrine functions. A number of reports have indicated that NPK, NKA and NPG act on the hypothalamo-pituitary gonadal axis to regulate functions related to reproduction. Therefore, we thought that, at this point, it was important to review the available evidence suggesting the role of these tachykinins on reproductive functions by effects exerted at 3 different levels of regulation: the hypothalamus, the anterior pituitary and the gonads. These 3 tachykinin peptides were reported to have effects on reproductive functions, acting on the control of the secretion of gonadotropin and prolactin at the level of the hypothalamo-pituitary axis, and on the steroid secretion by the testes and the ovaries. Acting on the hypothalamus, tachykinins, mainly NPK, were reported to inhibit LH secretion, but this effect is dependent on the presence of gonadal steroids. On the anterior pituitary gland, however, tachykinins were shown to stimulate LH and prolactin secretion, and this effect is also dependent on the presence of gonadal steroids. Tachykinin concentrations in the hypothalamus and pituitary are regulated by steroid hormones. In the hypothalamus, estrogens and testosterone increase tachykinin concentration. In the anterior pituitary gland, estradiol and thyroid hormones markedly depress tachykinin concentrations. Ovariectomy and exposure to short photoperiods significantly increase anterior pituitary tachykinins in the Siberian hamster. In the pineal gland, SP and NK-1 receptors are present and, more recently, the presence of NKA and probably also NPK was demonstrated. Castration and steroid replacement modified the content of tachykinins in the pineal gland. The removal of the superior cervical ganglia was followed by an increase in NKA content in the pineal gland. These results suggest that gonadal steroids may influence tachykinins in the pineal gland. In the gonads, tachykinins stimulated the secretory activity of Sertoli cells, but inhibited testosterone secretion by Leydig cells. There are very few reports on the role of tachykinins in the ovary, but some of them indicated that these peptides are present in some of the ovarian structures, and they may affect the secretion of ovarian steroids. Thus, NKA, NPK and NPG appear to have a modulatory role, mainly acting as paracrine factors, on the hypothalamo-pituitary-gonadal axis.

Animals↗

Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis.

Secretin, glucagon, gastric inhibitory polypeptide (GIP), and parathyroid hormone (PTH) belong, together with vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase (AC)-activating polypeptide, to a family of peptides (the VIP-secretin-glucagon family), which also includes growth hormone-releasing hormone and exendins. All the members of this peptide family possess a remarkable amino-acid sequence homology, and bind to G-protein-coupled receptors, whose signaling mechanism primarily involves AC/protein kinase A and phospholipase C/protein kinase C cascades. VIP and pituitary AC-activating polypeptide play a role in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and in this review we survey findings that also other members of the VIP-secretin-glucagon family may have the same function. Secretin and secretin receptors are expressed in the hypothalamus and pituitary gland, and secretin inhibits adrenocorticotropic hormone (ACTH) release. No evidence is available for the presence of secretin receptors in adrenal glands, but secretin selectively depresses the glucocorticoid response to ACTH of dispersed zona fasciculata-reticularis (ZF/R) cells. Glucagon and glucagon-like peptide-1 are contained in the hypothalamus, and all the components of the HPA axis are provided with glucagon and glucagons-like-1 receptors. These peptides exert a short-term inhibitory effect on stress-induced pituitary ACTH release and depress the ZF/R cell response to ACTH by inhibiting the AC/protein kinase A cascade; they also stimulate hypothalamic arginine-vasopressin release. GIP receptors are present in the ZF/R of the normal adrenals, and are particularly abundant in some types of adrenocortical adenomas and hyperplasias. GIP, through the activation of the AC/protein kinase A cascade, evokes a sizeable glucocorticoid secretagogue effect, leading to the identification of a food/GIP-dependent Cushing's syndrome. PTH and PTH-related protein are expressed in the hypothalamus and pituitary gland, and PTH and PTH-related protein receptors in all the components of the HPA axis. Both peptides enhance ACTH and arginine-vasopressin release, as well as stimulate aldosterone and glucocorticoid secretion of dispersed zona glomerulosa and ZF/R cells, respectively. The involvement of growth hormone-releasing hormone and exendins in the functional regulation of the HPA axis has not yet been extensively investigated.

Amino Acid Sequence↗

Optimal sagittal motion axis for trunk extension and flexion tests in chronic low back trouble.

OBJECTIVE: To find the optimal height for sagittal motion axis for trunk strength test in chronic low back trouble. DESIGN: Cross-sectional study. BACKGROUND: The strength of trunk muscles of low back pain patients is decreased. The measured strength depends on the height of the sagittal motion axis but the differences between patients and controls are not known. METHODS: 114 (67 female) patients with chronic low back trouble are classified according to Quebec Task Force, 50 (31 female) patients with rheumatic disorder, but without low back trouble, and 33 (22 female) healthy controls, no appreciable physical differences but clear differences in Oswestry score. Isometric trunk extension-flexion test with different heights for the pelvic fulcrum. RESULTS: Force decreased in extension, increased in flexion, and torque increased both in flexion and extension in every group (P<0.001) as the fulcrum was moved caudally. The male controls were stronger than patients with low back trouble (P<0.01). The female controls were stronger only if the fulcrum was set at the hip joint level (P<0.05). There were no differences between patients with rheumatic disorder and low back trouble, except in extension if the fulcrum was at the hip joint level (P<0.02). CONCLUSIONS: The rotation axis in trunk extension-flexion strength test should be set at the level of the hip joint. RELEVANCE: Trunk muscle weakness is a common sign of different rheumatic disorders. Proper setting of sagittal motion axis and concomitant measurement of trunk and hip extensor or flexor muscles increases the specificity of the strength test for low back trouble.

Abdominal Muscles↗

Effects of quetiapine on gonadal axis hormones in male patients with schizophrenia: a preliminary, open study.

PURPOSE: The authors investigated the effects of a novel antipsychotic agent, quetiapine administration on hypothalamo-pituitary-gonadal (HPG) axis hormones in patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were nine male inpatients. We tried to switch the patients from typical antipsychotics to quetiapine. The patients took a mean dose of 636.1 mg quetiapine daily for a mean period of 104.7 days. RESULTS: (i) Although the total Brief Psychiatric Rating Scale score did not show significant changes, no patients needed anticholinergic medications after the switch. (ii) Before the switch, only the prolactin concentration showed a significant difference between the patients and normal subjects. After the switch, neither prolactin nor HPG axis hormone concentrations showed significant differences between the groups. CONCLUSIONS: Our preliminary results indicated that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenia patients with normal levels of HPG axis hormones.

Adult↗

Actions of serotonergic agents on hypothalamic-pituitary-adrenal axis activity in the rat.

1. The effects of ipsapirone, nefazodone, tiaspirone, BMS-20661, buspirone and gepirone on the hypothalamic-pituitary-adrenal (HPA) axis were studied. These drugs were selected because they have serontonin 1A (5-HT1A) receptor-binding capability and have the potential for therapeutic activity in the treatment of major affective or anxiety disorders or both. 2. Plasma corticosterone level was used as the end point for determining the effect of each drug on the HPA axis. Each drug increased the plasma corticosterone levels in a dose-dependent manner. The ED50 values were 0.8 mg/kg for BMS-20661, 3.5 mg/kg for gepirone, 3.9 mg/kg for buspirone, 5.3 mg/ kg for tiaspirone, 10.5 mg/kg for ipsapirone and 73.5 mg/kg for nefazodone. Ipsapirone and buspirone were more efficacious than the other four drugs. 3. The effect of a 10-mg/kg (35 mg/kg for nefazodone) test dose of each drug reached a peak between 30 min and 1 hr, and plasma corticosterone levels generally returned to control levels after 2 hr. 4. When the drugs were given 30 min before decapitation, in conjunction with a rotatory stress, BMS-20661 significantly inhibited the stress-induced rise, whereas ipsapirone and gepirone caused a significant increase in plasma corticosterone levels. However, when the drugs were given 2 hr before decapitation, nefazodone caused a significant decrease, whereas ipsapirone, BMS-20661 and gepirone produced significant increases in HPA axis activity. An 0800 hr dose of 0.1 mg/kg of dexamethasone suppressed the 1500 hr HPA activity by 73.1%. The 0.1-mg/kg dose of dexamethasone significantly reduced the drug-activated HPA axis activity of all of the drugs from their saline-control levels. The rank order, from least to greatest inhibitory effect, produced by this dexamethasone treatment on the drug-control levels was gepirone (-42.6%), tiaspirone (-48.9%), buspirone (-56.1%), nefazodone (-68.5%), insapirone (-70.0%), and BMS-20661 (-74.3%).

Animals↗

Inhalation of 35% CO(2) results in activation of the HPA axis in healthy volunteers.

BACKGROUND: The hypothalamo-pituitary-adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients. We have now investigated whether the simple challenge of a single 35% inhalation of CO(2) activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers. METHODS: Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO(2), in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals. RESULTS: CO(2) inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO(2). The subjects reported short-lived symptoms of fear with the experimental gas. CONCLUSIONS: Single vital capacity inhalation of 35% CO(2) activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.

Administration, Inhalation↗

Increased basal activity of the hypothalamo-pituitary-adrenal axis during pregnancy in rats bred for high anxiety-related behaviour.

In order to test the hypothesis that prenatal hormones influence the emotional maturation of the offspring, the hypothalamo-pituitary-adrenal (HPA) axis activity was studied at the end of pregnancy in two rat breeding lines differing consistently in their innate anxiety-related behaviour in the elevated plus-maze. Virgin and pregnant rats were fitted with a chronic jugular vein catheter and tested 5 days later. The high basal level of anxiety-related behaviour (HAB) described in males and females of the HAB breeding line persists in pregnancy as indicated by a significantly reduced number of entries into and time spent on the open arms of the elevated plus-maze between days 18 and 20 of pregnancy compared with pregnant rats of the breeding line with low anxiety-related behaviour (LAB). In general, an increase in anxiety was found in both breeding lines in pregnancy compared with the respective virgin controls. With respect to HPA axis activity, increased basal levels of adrenocorticotropin (ACTH) and corticosterone have been found in pregnant rats of the HAB line compared with pregnant LAB rats. ACTH and corticosterone secretion in response to emotional and complex physical stressors (exposure to the elevated plus-maze and forced swimming, respectively) did not differ between virgin and pregnant rats of either breeding line. However, independent of the inborn emotionality of the animals, a general attenuation in the HPA axis response to stressors and to exogenous CRH could be confirmed in pregnant rats. The basal and stress-induced activity of the hypothalamo-neurohypophysial system secreting oxytocin and vasopressin was also tested, and no differences were found relating to the emotionality or reproductive state of the animals except for a reduced vasopressin secretion in pregnant HAB rats after forced swimming. The elevated basal activity of the HPA axis, including enhanced circulating concentrations of corticosterone in pregnant HAB rats, may influence both the neuroendocrine and emotional development of their offspring. Thus, the passing-on of maternal behavioural characteristics via prenatal, hormonal 'imprinting' has to be considered as a possible contribution to emotional maturation during an individual's development.

Adrenocorticotropic Hormone↗

Thyroid axis activity and serotonin function in major depressive episode.

Recent studies in depression have reported alterations in both hypothalamic-pituitary-thyroid (HPT) axis activity and serotonin (5-HT) function; however, the functional relationships between the two systems have not been well defined in patients with major depressive episode. Thyrotropin (TSH) response to 0800 and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol, and prolactin (PRL) responses to D-fenfluramine (D-FEN), a specific 5-HT releasing/uptake-inhibiting agent, were examined in 60 drug-free DSM-IV major depressed inpatients and 20 hospitalized controls. Compared with controls, patients showed lower basal serum 2300 h TSH, 2300 h maximum increment in serum TSH above baseline (delta TSH) and difference between 2300 h delta TSH and 0800 h delta TSH (delta delta TSH) levels. The hormonal responses to D-FEN (i.e. delta ACTH, delta cortisol and delta PRL) were interrelated. No significant difference in basal and post-D-FEN ACTH, cortisol or PRL values were found between controls and patients. A negative relationship between hormonal responses to D-FEN and 2300 h delta TSH and delta delta TSH values was observed in the depressed group. When patients were classified on the basis of their delta TSH test status, patients with reduced delta delta TSH values (i.e. with HPT axis abnormality) had hormonal D-FEN responses comparable to those of controls. Patients with normal delta delta TSH values (i.e. without HPT axis abnormality) showed lower ACTH, cortisol and PRL responses to D-FEN than controls and patients with abnormal delta delta TSH values. These results suggest that: (1) pathophysiological mechanisms other than 5-HT dysregulation may be involved in TSH blunting in major depressed patients; (2) 5-HT function is reduced in some depressed patients, especially those without HPT axis abnormality; and (3) HPT dysregulation may be regarded as a compensatory mechanism for diminished central 5-HT activity.

Adolescent↗

Sexual diergism in rat hypothalamic-pituitary-adrenal axis responses to cholinergic stimulation and antagonism.

The hypothalamic-pituitary-adrenal (HPA) axis has differential physiological activity in male and female animals (sexual diergism). Central cholinergic systems stimulate this endocrine axis. In the present study we investigated muscarinic and nicotinic cholinergic influences on HPA axis activity in male and female rats by pretreatment with selective cholinergic receptor antagonists followed by stimulation with physostigmine (PHYSO), an acetylcholinesterase inhibitor. Hormonal measures were plasma arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Male rats had significantly greater AVP and ACTH responses to PHYSO alone than did females. Scopolamine (SCOP) enhanced the AVP response to PHYSO to a greater extent in males than in females. In contrast, mecamylamine (MEC) enhanced the AVP response in females but decreased it in males. SCOP potentiated, and MEC inhibited, the stimulatory effect of PHYSO on ACTH in both sexes, but SCOP potentiation was greater in males, and MEC inhibition was greater in females. Absolute CORT increases following PHYSO were greater in females, but percent increases over baseline were greater in males. Similar to their effects on ACTH responses, MEC attenuated, and SCOP enhanced, CORT responses to PHYSO. These results suggest that cholinergic receptor subtypes may influence HPA axis activity differentially in male and female rats.

Adrenocorticotropic Hormone↗

Estrous cycle influences on sexual diergism of HPA axis responses to cholinergic stimulation in rats.

Central cholinergic systems differentially modulate hypothalamic-pituitary-adrenal (HPA) axis activity in female and male animals (sexual diergism). We previously reported that male rats had significantly greater HPA axis responses to stimulation by physostigmine (PHYSO), an acetylcholinesterase (AChE) inhibitor, compared to females. Females in defined estrous cycle stages, however, were not studied because of sample size limitations. We, therefore, determined HPA axis responses to stimulation by PHYSO in females during all estrous cycle stages (n = 78), and in male rats (n = 75). Plasma arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) were measured. Estrous cycle stage was determined by light microscopy of vaginal smears. Proestrous and estrous females had higher ACTH and CORT responses compared to metestrous and diestrous females. Males had higher ACTH and AVP responses compared to females in all cycle stages. CORT responses followed the ACTH responses, except that females started from a higher baseline in all estrous stages, compared to males. These results suggest that cholinergic regulation of the HPA axis differs among females across stages of the estrous cycle, as well as between males and females. These effects are likely due to differences in circulating sex steroids and their actions within the brain.

Adrenocorticotropic Hormone↗

Three-dimensional myocardial strain analysis based on short- and long-axis magnetic resonance tagged images using a 1D displacement field.

A robust algorithm to estimate three-dimensional strain in the left-ventricular heart wall, based on magnetic resonance (MR) grid-tagging in two sets of orthogonal image planes, is presented. Starting-point of this study was to minimize global interpolation and smoothing. Only the longitudinal displacement was interpolated between long-axis images. Homogeneous strain analysis was performed using small tetrahedrons. The method was tested using a stack of short-axis images and three long-axis images in six healthy volunteers. In addition, the method was subjected to an analytical test case, in which the effect of noise in tag point position on the observed strains was explored for normally distributed noise (0.5 mm RMS). In volunteers, the error in the longitudinal displacement due to interpolation between the long-axis image planes was -0.10 +/- 0. 48 mm (mean +/- SD). The resulting error in the longitudinal strain epsilon(l) was -0.003 +/- 0.02. The analytical test case was used to quantify the effects of three sources of errors on the observed strain. The SD of the difference between homogeneous strain and true strain was 0.06 for epsilon(r.) The error due to the 3-D reconstruction was 0.004 for epsilon(r.) The error in epsilon(r) resulting from simulated noise in the tag point position was 0.10. Equivalent results were obtained for all other strain parameters; thus, the error resulting from noise in the tag point position dominates the error introduced by approximations in the method. Because the proposed method uses a minimum of global interpolation and smoothing, it offers the prospect to detect small regions of aberrant contraction.

Adult↗

Localization of ischemia in canine hearts using tagged rotated long axis MR images, endocardial surface stretch and wall thickening.

Tagged magnetic resonance imaging allows the noninvasive measurement of regional systolic myocardial deformations and helps localize ischemic regions in the left ventricle (LV). The objective of this study was to evaluate the potential accuracy of localizing ischemic regions in the LV using endocardial and epicardial data obtained from tagged rotated long axis images. Nine canine hearts with acute ischemia induced by coronary artery ligation were imaged along four long axis planes rotated around the LV long axis, at end diastole and end systole. Each plane was tagged by four parallel lines perpendicular to the LV long axis. Tracing the endocardial and epicardial intersection points of the tag lines, 24 myocardial cuboids were reconstructed for each LV at end diastole and end systole. Endocardial surface stretch and transmural systolic thickening were calculated for each cuboid. The functional data were compared to perfusion data obtained from postmortem monastral blue staining of the heart. The ability of each functional index to discriminate between ischemic and non-ischemic regions was assessed using the "t"-statistic. The potential accuracy in localizing ischemia was evaluated by studying the corresponding sensitivity-specificity curves. The results demonstrate that adequate discrimination and localization can be obtained with both functional indices. However, endocardial surface stretch is advantageous as it uses only endocardial data and can save 50% of the post-processing time.

Animals↗

Transient right axis deviation during acute anterior wall infarction or ischemia: electrocardiographic and angiographic correlation.

Eleven patients, three with acute anterior myocardial infarction and eight with anterior ischemia, who developed transient right axis deviation with a left posterior hemiblock pattern during the acute phase of myocardial infarction or ischemia are described (study group). A correlation between their electrocardiographic pattern and the angiographic findings was made. The arteriographic findings were compared with those of a group of 24 patients with acute anterior myocardial infarction or ischemia without transient right axis deviation (control group). The main electrocardiographic characteristics of the right axis deviation pattern were: an average shift of the mean frontal axis to the right of 42 degrees (10 degrees to 94 degrees); increased voltage of R waves in leads II, III and a VF and appearance of small Q waves or decreased voltage of Q waves if previously present in the same leads; decreased voltage of R waves and appearance of deep S waves in lead aVL; and inverted T waves and isoelectric ST segments in leads II, III and aVF. Coronary angiography revealed that the study group had a higher incidence of significant right coronary artery obstruction and collateral circulation between the left coronary system and the posterior descending artery than did the control group (100 versus 25% and 73 versus 0%, respectively; p less than 0.01). There were no differences between the groups regarding left anterior descending and circumflex artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse.

The main characteristic of the postnatal development of the stress system in the rat is the so-called stress hypo-responsive period (SHRP). Lasting from postnatal day (pnd) 4 to pnd 14, this period is characterized by very low basal corticosterone levels and an inability of mild stressors to induce an enhanced ACTH and corticosterone release. During the last years, the mouse has become a generally used animal in stress research, also due to the wide availability of genetically modified mouse strains. However, very few data are available on the ontogeny of the stress system in the mouse. This study therefore describes the postnatal ontogeny of peripheral and central aspects of the hypothalamic-pituitary-adrenal (HPA) axis in the mouse. We measured ACTH and corticosterone in blood and CRH, urocortin 3 (UCN3), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) transcripts in the brain at postnatal days 1, 2, 4, 6, 9, 12, 14 and 16. Our results show that we can subdivide the postnatal development of the HPA axis in the mouse in two phases. The first phase corresponds to the SHRP in the rat and lasts from right after birth (pnd 1) until pnd 12. Basal corticosterone levels were low and novelty exposure did not enhance corticosterone or ACTH levels. This period is further characterized by a high expression of CRH in the paraventricular nucleus (PVN) of the hypothalamus. Expression levels of GR in the hippocampus and UCN3 in the perifornical area are low at birth but increase significantly during the SHRP, both reaching the highest expression level at pnd 12. In the second phase, the mice have developed past the SHRP and were now exhibiting enhanced corticosterone basal levels and a response of ACTH and corticosterone to mild novelty stress. CRH expression was decreased significantly, while expression of UCN3 and GR remained high, with a small decrease at pnd 16. The expression of MR in the hippocampus was very dynamic throughout the postnatal development of the HPA axis and changed in a time and subregion specific manner. These results demonstrate for the first time the correlation between the postnatal endocrine development of the mouse and gene expression changes of central regulators of HPA axis function.

Adrenocorticotropic Hormone↗

Femoral pulse as a guide to the mechanical axis in total knee arthroplasty.

The anatomic relationship of the center of the femoral head to the femoral artery was studied in 140 hips in 70 patients. The coronal plane distance between the femoral artery 2.5 cm below the inguinal ligament and the center of the femoral head was measured on pelvic arteriograms. The femoral artery was found an average of 7.7 +/- 5 mm medial (range, -3-22 mm) to the center of the femoral head. The femoral artery was within 15 mm of the center of the femoral head in 93% of cases reviewed. A 76-cm theoretical mechanical axis was used in estimating clinical angular changes in the axis for a given coronal plane difference. By use of this model, the range of variability translates into a maximum change in the mechanical axis of 1.66 degrees and up to only 1.2 degrees in 95% of the cases reviewed. A marker placed just lateral to the palpable femoral pulse approximately 2 to 3 cm below the inguinal ligament is suitable as a guide to locate the center of the femoral head when determining the mechanical axis during total knee arthroplasty.

Aged↗

Digital overlay technique for documenting toric intraocular lens axis orientation.

PURPOSE: To describe a digital overlay technique for documenting toric intraocular lens (IOL) axis alignment. SETTING: Jules Stein Eye Institute and the Department of Ophthalmology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA. METHODS: Digital overlay imaging was used to evaluate the alignment of Staar toric IOLs in 4 eyes of 3 patients who had regular corneal astigmatism at the time of cataract surgery. Lens axes were determined by computerized analysis of digitally scanned retroillumination photographs. A stock digital image of a Staar AA4203TF toric IOL was superimposed on corneal topography images to document IOL alignment with the steep corneal meridian. RESULTS: Digital overlay images demonstrated that 3 IOLs in the sample group were within 5 degrees and 1 was within 20 degrees of the intended axis at the time of the final postoperative examination. Slitlamp lens axis estimations were 3 to 18 degrees different from that determined by this technique. CONCLUSION: Digital overlay imaging of correctly oriented toric IOLs on computerized corneal topography maps represents an intuitive, accurate, and visually appealing method of documenting toric IOL axis alignment.

Aged↗