Meltem Bahcelioglu

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 Cushings 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.

Morphological characteristics of styloid process evaluated by computerized axial tomography.

Morphological characteristics of styloid process and ossified stylohyoid ligament and their overall relationships to age and sex were studied by using computerized axial tomography images. The styloid process and ossified stylohyoid ligaments were classified into seven groups according to their shapes and lengths. The styloid process of a length of 25-40 mm, was the most frequently encountered. The elongated styloid process was mostly seen in males. There was no overall correlation between the types of SP and sex. The progressive increase in length with age was not seen in our study.

Blockade of Angiotensin II Type 1 Receptor and Not of Endothelin Receptor Prevents Hypertension and Cardiovascular Disease in Transgenic (mREN2)27 Rats via Adrenocortical Steroid–Independent Mechanisms

We investigated the role of angiotensin II (Ang II) and endothelin-1 (ET-1) in transgenic (mREN2)27 rats, a model of the monogenic renin-dependent form of severe hypertension and cardiovascular disease. Four-week-old heterozygous male transgenic (mREN2)27 rats (n=24) were matched according to body weight (BW) and blood pressure (BP) and randomly allocated to receive a placebo (group P), the mixed endothelin type A and B receptor antagonist bosentan (100 mg/kg BW PO, group B), the Ang II type 1-specific receptor antagonist irbesartan (50 mg/kg BW PO, group I), or the endothelin type A-selective antagonist BMS-182874 (52 mg/kg BW PO, group BMS). After 4 weeks of treatment, during which BW and BP were measured weekly, animals were euthanized, and the heart, left ventricle, right ventricle, adrenal gland, brain, and kidney were weighed. The plasma levels of adrenocortical steroids were measured by high-performance liquid chromatography. The tension responses of ET-free segments of the thoracic aorta to 5 x 10(-6) mmol/L phenylephrine, 60 mmol/L KCl, and cumulative doses of ET-1 were assessed. The density of ET-1 receptor subtypes in the aorta and vascular structural changes in the mesenteric arterioles (100 to 200 microm ID) were also measured with autoradiography and myography, respectively. Compared with all other groups, group I rats showed significantly (P<0.001) lower systolic BP (group I, 161+/-8 mm Hg; group P, 269+/-23 mm Hg; group B, 275+/-17 mm Hg; and group BMS, 254+/-21 mm Hg), left ventricular weight (2.28+/-0.15 versus 3. 71+/-0.26, 3.38+/-0.27, and 3.96+/-0.51 mg/g BW, respectively), tension responses to vasoconstrictors, and normalized media thickness of the mesenteric arterioles (22.3+/-0.6 versus 25.3+/-0.5, 25.5+/-0.7, and 24.1+/-1.5 microm, respectively). Compared with levels in group P (78+/-25 pmol/mL), plasma aldosterone levels were significantly decreased in group B (51+/-11 pmol/mL) and group I (40+/-16 pmol/mL). Thus, endogenous ET-1 and Ang II contribute to the regulation of aldosterone, but only Ang II is crucial for the development of hypertension and related target organ damage via the Ang II type 1 receptor. Endogenous Ang II does not appear to enhance cardiovascular production of ET-1 in this model of hypertension within the time span of our experiment.

Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland

Adrenomedullin (ADM) is a hypotensive peptide, highly expressed in the mammalian adrenal medulla, which belongs to a peptide superfamily including calcitonin gene-related peptide (CGRP) and amylin. Quantitative autoradiography demonstrated the presence of abundant [125I]ADM binding sites in both zona glomerulosa (ZG) and adrenal medulla. ADM binding was selectively displaced by ADM(22-52), a putative ADM-receptor antagonist, and CGRP(8-37), a ligand that preferentially antagonizes the CGRP1-receptor subtype. ADM concentration-dependently inhibited K+-induced aldosterone secretion of dispersed rat ZG cells, without affecting basal hormone production. Both ADM(22-52) and CGRP(8-37) reversed the ADM effect in a concentration-dependent manner. ADM counteracted the aldosterone secretagogue action of the voltage-gated Ca2+-channel activator BAYK-8644, and blocked K+- and BAYK-8644-evoked rise in the intracellular Ca2+ concentration of dispersed ZG cells. ADM concentration-dependently raised basal catecholamine (epinephrine and norepinephrine) release by rat adrenomedullary fragments, and again the response was blocked by both ADM(22-52) and CGRP(8-37). ADM increased cyclic-AMP release by adrenal-medulla fragments, but not capsule-ZG preparations, and the catecholamine response to ADM was abolished by the PKA inhibitor H-89. Collectively, the present findings allow us to draw the following conclusions: (1) ADM modulates rat adrenal secretion, acting through ADM(22-52)-sensitive CGRP1 receptors, which are coupled with different signaling mechanisms in the cortex and medulla; (2) ADM selectively inhibits agonist-stimulated aldosterone secretion, through a mechanism probably involving the blockade of the Ca2+ channel-mediated Ca2+ influx; (3) ADM raises catecholamine secretion, through the activation of the adenylate cyclase/PKA signaling pathway.

Gluteal Region Morphology: The Effect of the Weight Gain and Aging

Abstract. The gluteal region is an important secondary sexual character itself and it has its place in the concept of the beauty in all communities. Interestingly, as far as we know, there is not any previous study addressing gluteal region morphology in an objective way in the aesthetic surgery literature. The aim of this study was to define the changes of the gluteal region morphology with aging and weight gain.Beside body weight, a total of five distances between predetermined anatomic points in gluteal region were measured on randomly selected 115 female volunteers, with their age ranging from 17 to 48 years (mean 22.7). All the records were analyzed by a correlation matrix using computer-based SPSS 7.5 program.As women grow older, the width of the gluteal region decreases and the gluteal sulcus elongates laterally and inferiorly. Contrary to aging, with weight gain the gluteal region becomes wider as the gluteal sulcus gets shorter.Although the subject does not sound new, our study is the first, documenting the changes in morphology of the gluteal region in relation to weight gain and aging in an objective way.

Effect of fresh and stored botulinum toxin a on muscle and nerve ultrastructure : An electron microscopic study

The aim of this study was to compare the ultrastructural alterations of the muscle and nerve that appear following injection of freshly reconstituted and stored botulinum toxin A. Fifteen New Zealand white rabbits were assigned to 6 groups, and anterior auricular muscle was used for injections. Group 1 did not receive any injection and group 2 received saline injection. Groups 3 and 5 received fresh botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Groups 4 and 6 received stored botulinum; muscles and motor nerves were harvested at 5 days and 12 weeks, respectively. Alterations in muscle and nerve ultrastructure were evaluated with electron microscopy. Degeneration findings in muscle after botulinum toxin injection revealed no significant difference between freshly reconstituted and stored toxin in the early period. When stored toxin was used, atrophic changes in the muscle were less severe than the fresh toxin at 3 months. On nerve evaluation, fresh toxin displays significant acute changes on nerve ultrastructure; however, fresh and stored toxin shows similar degeneration at 12 weeks.

Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat

Methylphenidate is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder of children and young adults. Our aim is to investigate dose-dependent dopamine-2 receptor and glial fibrillary acidic protein expression and ultrastructural changes of the rat brain, to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female prepubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) were treated orally with methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, tissues were removed and sections were collected for immunohistochemical and ultrastructural studies. We believe that methylphenidate causes dose-related activation of the dopaminergic system in several brain regions especially in ventral tegmental area and also causing neuronal degeneration and capillary wall structural changes such as basal membrane thickness and augmentation of the pinostatic vesicle in the endothelial cells. Also, increased dose of Ritalin is inducing astrocytes hypertrophy especially astrogliosis in pia-glial membrane and this is the result of the degenerative changes in prefrontal cortex region due to high dose methylphenidate administration. The dose-related accumulation of the astrocytes in capillary wall might well be a consequence of the need for nutrition of the neuronal tissue, due to transport mechanism deficiency related to neuronal and vascular degeneration. Thus, we believe that the therapeutic dose of methylphenidate must be kept in minimum level to prevent ultrastructural changes.

Morphometric Study of a Horseshoe Kidney

Objective: To describe a horseshoe kidney, a congenital anomaly of the upper urinary tract. Clinical Presentation: A case study of horseshoe kidney harvested from a 62-year-old cadaver at Gazi University Medical School is presented. Results: The right and left kidneys were fused at their lower poles by a parenchymal isthmus located ventral to the abdominal aorta and formed a U-shape with two unequal arms.The isthmus of the ectopic kidney was placed obliquely to the left at the level of the fourth and fifth lumbar vertebra. The left kidney was larger and longer than the right one. The kidneys were supplied by three renal arteries arising from the abdominal aorta. Two arteries on the right side supplied blood of the two kidneys, while the third artery that directly originated from the aorta, above the origin of inferior mesenteric artery, supplied the isthmus. Venous drainage of the both kidneys and the isthmus were drained by three veins that opened independently into the inferior vena cava. The right ureter was duplicated in origin. Conclusion: This report shows that knowledge of anomalies such as this is very important in planning and conducting surgical procedures.

Age-Related Immunohistochemical and Ultrastructural Changes in Rat Oculomotor Nerve

During ageing process, multiple changes occur on nervous tissue composed of cells and extracellular matrix. Changes on nervous tissues are usually known as degenerative changes on axon structure and connective tissue covering the nerve such as a decrease in the number of fibre or general structural changes. For this purpose, we have studied age‐dependent ultrastructural changes in the rat oculomotor nerve with electron microscopy and also demonstrated collagen structure of the neural sheaths with immunohistochemical techniques. This study was conducted in Gazi University Faculty of Medicine, Department of Anatomy with a total of nine Wistar albino rats. We observed strong collagen type I immunoreactivity in endoneurium and slight to moderate reactivity in fibroblast cytoplasm in 3‐month‐ and 12‐month‐old groups and mild reactivity in 24‐month‐old group. Collagen type IV immunoreactivity was stronger in endoneurium and perineurium in the 3‐month‐ and 12‐month‐old groups compared with collagen type I and fibroblast cytoplasm showed a very strong reactivity. On the other hand, in the 24‐month‐old group, there was slight reactivity in endoneurium and a strong reactivity in perineurium. NGF staining showed moderate to strong reactivity on Schwann cells of the 3‐month‐old group. The immunoreactivity decreased in the 12‐month‐ and 24‐month‐old groups. In the 3‐month‐old rat group, Schwann cell cytoplasm, mitochondrial structure and neurofilaments were normal. In the 12‐month‐old group, there were no changes in organelle distribution, mitochondrial structure and neurofilaments, but there was an increase in the connective tissue. An inconsiderable number of degenerated myelinated nerves were observed. We detected an important decrease in the collagen type I immunoreactivity, which could suggest that the endoneurium, perineurium and epineurium are less resistant to the age‐related collagen loss and that the peripheral nerve is protected by a weaker barrier in the old group. The collagen type IV immunoreactivity was significantly decreased with age. NGF synthesis decreases with age because of Schwann cell structural degeneration or for different reasons. Thus, this could explain the diminished capacity of regeneration and damage of the myelination of the peripheral nerve.

Innervation of the Rat Anterior Abdominal Wall as Shown by Modified Sihler’s Stain

Objective: The purpose of this study was to use the modified Sihler’s staining technique to demonstrate detailed distribution of the rat anterior abdominal wall nerves and test the value of Sihler’s technique in demonstrating such a complex muscle-nerve relationship. Materials and Methods: The anterior abdominal walls of 5 Wistar rats were isolated by making a deep incision from the costal arches on each side down to the inguinal region and processed using a modified Sihler’s stain technique. Results: This technique was successfully applied to visualize the innervation of the anterior abdominal wall muscles of the rat. The segmental nerves of T6–L1 and their terminal branches were shown and possible motor and sensory fibers identified. Conclusions: This technique is valuable in understanding the complex nature of final branching of the nerve endings, and it may be useful for studying experimental nerve models.