The molecular basis of acid insensitivity in the African naked mole-rat.

Science.gov (United States)

Smith, Ewan St John; Omerbašić, Damir; Lechner, Stefan G; Anirudhan, Gireesh; Lapatsina, Liudmila; Lewin, Gary R

2011-12-16

Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.

Science.gov (United States)

Smith, Ewan St John; Blass, Gregory R C; Lewin, Gary R; Park, Thomas J

2010-05-24

Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

Directory of Open Access Journals (Sweden)

Lewin Gary R

2010-05-01

Full Text Available Abstract Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

Stress resistance in the naked mole-rat: the bare essentials - a mini-review.

Science.gov (United States)

Lewis, Kaitlyn N; Mele, James; Hornsby, Peter J; Buffenstein, Rochelle

2012-01-01

Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ~8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD(50) values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and progression of physiological declines

High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

Directory of Open Access Journals (Sweden)

Shanmin Zhao

2014-02-01

Full Text Available Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old and adult C57BL/6 mice (eight weeks old have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

Stress Resistance in the Naked Mole-Rat: The Bare Essentials – A Mini-Review

Science.gov (United States)

Lewis, Kaitlyn N.; Mele, James; Hornsby, Peter J.; Buffenstein, Rochelle

2012-01-01

Background Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ∼8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. Objectives We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Results Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD50 values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Conclusion Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and

Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age

Science.gov (United States)

Ruby, J Graham; Smith, Megan

2018-01-01

The longest-lived rodent, the naked mole-rat (Heterocephalus glaber), has a reported maximum lifespan of >30 years and exhibits delayed and/or attenuated age-associated physiological declines. We questioned whether these mouse-sized, eusocial rodents conform to Gompertzian mortality laws by experiencing an exponentially increasing risk of death as they get older. We compiled and analyzed a large compendium of historical naked mole-rat lifespan data with >3000 data points. Kaplan-Meier analyses revealed a substantial portion of the population to have survived at 30 years of age. Moreover, unlike all other mammals studied to date, and regardless of sex or breeding-status, the age-specific hazard of mortality did not increase with age, even at ages 25-fold past their time to reproductive maturity. This absence of hazard increase with age, in defiance of Gompertz’s law, uniquely identifies the naked mole-rat as a non-aging mammal, confirming its status as an exceptional model for biogerontology. PMID:29364116

Sex, social status, and CRF receptor densities in naked mole-rats.

Science.gov (United States)

Beery, Annaliese K; Bicks, Lucy; Mooney, Skyler J; Goodwin, Nastacia L; Holmes, Melissa M

2016-02-01

Naked mole-rats (Heterocephalus glaber) live in groups that are notable for their large size and caste structure, with breeding monopolized by a single female and a small number of males. Recent studies have demonstrated substantial differences between the brains of breeders and subordinates induced by changes in social standing. Corticotropin-releasing factor (CRF) receptors-which bind the hormone CRF as well as related peptides-are important regulators of stress and anxiety, and are emerging as factors affecting social behavior. We conducted autoradiographic analyses of CRF1 and CRF2 receptor binding densities in female and male naked mole-rats varying in breeding status. Both globally and in specific brain regions, CRF1 receptor densities varied with breeding status. CRF1 receptor densities were higher in subordinates across brain regions, and particularly in the piriform cortex and cortical amygdala. Sex differences were present in CRF2 receptor binding densities, as is the case in multiple vole species. CRF2 receptor densities were higher in females, both globally and in the cortical amygdala and lateral amygdalar nucleus. These results provide novel insights into the neurobiology of social hierarchy in naked mole-rats, and add to a growing body of work that links changes in the CRF system with social behavior. © 2015 Wiley Periodicals, Inc.

The Naked Mole Rat Genome Resource : facilitating analyses of cancer and longevity-related adaptations

OpenAIRE

Keane, Michael; Craig, Thomas; Alfoldi, Jessica; Berlin, Aaron M; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M; de Magalhaes, Joao Pedro

2014-01-01

MOTIVATION: The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. RESULTS: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat's extraordinary traits, inc...

Membrane phospholipid composition may contribute to exceptional longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun lipidomics.

Science.gov (United States)

Mitchell, Todd W; Buffenstein, Rochelle; Hulbert, A J

2007-11-01

Phospholipids containing highly polyunsaturated fatty acids are particularly prone to peroxidation and membrane composition may therefore influence longevity. Phospholipid molecules, in particular those containing docosahexaenoic acid (DHA), from the skeletal muscle, heart, liver and liver mitochondria were identified and quantified using mass-spectrometry shotgun lipidomics in two similar-sized rodents that show an approximately 9-fold difference in maximum lifespan. The naked mole rat is the longest-living rodent known with a maximum lifespan of >28 years. Total phospholipid distribution is similar in tissues of both species; DHA is only found in phosphatidylcholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS), and DHA is relatively more concentrated in PE than PC. Naked mole-rats have fewer molecular species of both PC and PE than do mice. DHA-containing phospholipids represent 27-57% of all phospholipids in mice but only 2-6% in naked mole-rats. Furthermore, while mice have small amounts of di-polyunsaturated PC and PE, these are lacking in naked mole-rats. Vinyl ether-linked phospholipids (plasmalogens) are higher in naked mole-rat tissues than in mice. The lower level of DHA-containing phospholipids suggests a lower susceptibility to peroxidative damage in membranes of naked mole-rats compared to mice. Whereas the high level of plasmalogens might enhance membrane antioxidant protection in naked mole-rats compared to mice. Both characteristics possibly contribute to the exceptional longevity of naked mole-rats and may indicate a special role for peroxisomes in this extended longevity.

Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species.

Science.gov (United States)

Taylor, Kyle R; Milone, Nicholas A; Rodriguez, Carlos E

2017-01-01

The naked mole-rat (Heterocephalus glaber) is widely acclaimed to be cancer-resistant and of considerable research interest based on a paucity of reports of neoplasia in this species. We have, however, encountered four spontaneous cases of neoplasia and one presumptive case of neoplasia through routine necropsy and biopsy of individuals in a zoo collection of nonhybrid naked mole-rats bred from a single pair. One case each of metastasizing hepatocellular carcinoma, nephroblastoma (Wilms' tumor), and multicentric lymphosarcoma, as well as presumptive esophageal adenocarcinoma (Barrett's esophagus-like) was identified postmortem among 37 nonautolyzed necropsy submissions of naked mole-rats over 1-year-old that were submitted for necropsy between 1998 and August 2015. One incidental case of cutaneous hemangioma was also identified antemortem by skin biopsy from one naked mole-rat examined for trauma. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Jørgensen, Kristine B; Krogh-Jensen, Karen; Pickering, Darryl S; Kanui, Titus I; Abelson, Klas S P

2016-01-01

The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1-5 of the naked mole-rat were compared to that of the house mouse (Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [(3)H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.

RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

Science.gov (United States)

Yu, Chuanfei; Li, Yang; Holmes, Andrew; Szafranski, Karol; Faulkes, Chris G; Coen, Clive W; Buffenstein, Rochelle; Platzer, Matthias; de Magalhães, João Pedro; Church, George M

2011-01-01

The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

Directory of Open Access Journals (Sweden)

Chuanfei Yu

Full Text Available The naked mole-rat (Heterocephalus glaber is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam, a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m, and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

Science.gov (United States)

Peterson, Bethany L; Park, Thomas J; Larson, John

2012-01-11

Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Multidimensional MRI-CT atlas of the naked mole-rat brain

Directory of Open Access Journals (Sweden)

Fumiko eSeki

2013-12-01

Full Text Available Naked mole-rats have a variety of distinctive features such as the organisation of a hierarchical society (known as eusociality, extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI. Advanced MRI techniques such as diffusion tensor imaging (DTI, which generates high contrast images of fibre structures, can characterise unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography (CT were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualisation of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber)

DEFF Research Database (Denmark)

Jørgensen, Kristine B.; Krogh-Jensen, Karen; Pickering, Darryl S

2016-01-01

The present study investigated the cholinergic system in the African naked mole-rat (Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M1 and M4. The protein sequences for the subtypes m 1–5 of the naked mole-rat were compared to that of the house mouse (Mus...... musculus) using basic local alignment search tool (BLAST). The presence and function of M1 and M4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies...

Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

Science.gov (United States)

LaVinka, Pamela Colleen; Park, Thomas J

2012-01-01

Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%), and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%), naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2).

Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

Directory of Open Access Journals (Sweden)

Pamela Colleen LaVinka

Full Text Available Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%, and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%, naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2.

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.

Science.gov (United States)

Azpurua, Jorge; Ke, Zhonghe; Chen, Iris X; Zhang, Quanwei; Ermolenko, Dmitri N; Zhang, Zhengdong D; Gorbunova, Vera; Seluanov, Andrei

2013-10-22

The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice.

Science.gov (United States)

Andziak, Blazej; Buffenstein, Rochelle

2006-12-01

A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P naked mole-rats is independent of oxidative stress parameters.

Social structure predicts genital morphology in African mole-rats.

Directory of Open Access Journals (Sweden)

Marianne L Seney

2009-10-01

Full Text Available African mole-rats (Bathyergidae, Rodentia exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure.We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate.The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

Social structure predicts genital morphology in African mole-rats.

Science.gov (United States)

Seney, Marianne L; Kelly, Diane A; Goldman, Bruce D; Sumbera, Radim; Forger, Nancy G

2009-10-15

African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition

Science.gov (United States)

Rodriguez, Karl A.; Osmulski, Pawel A.; Pierce, Anson; Weintraub, Susan T.; Gaczynska, Maria; Buffenstein, Rochelle

2015-01-01

The naked mole-rat maintains robust proteostasis and high levels of proteasome-mediated proteolysis for most of its exceptional (~31y) life span. Here, we report that the highly active proteasome from the naked mole-rat liver resists attenuation by a diverse suite of proteasome-specific small molecule inhibitors. Moreover, mouse, human, and yeast proteasomes exposed to the proteasome-depleted, naked mole-rat cytosolic fractions, recapitulate the observed inhibition resistance, and mammalian proteasomes also show increased activity. Gel filtration coupled with mass spectrometry and atomic force microscopy indicates that these traits are supported by a protein factor that resides in the cytosol. This factor interacts with the proteasome and modulates its activity. Although HSP72 and HSP40 (Hdj1) are among the constituents of this factor, the observed phenomenon, such as increasing peptidase activity and protecting against inhibition cannot be reconciled with any known chaperone functions. This novel function may contribute to the exceptional protein homeostasis in the naked mole-rat and allow it to successfully defy aging. PMID:25018089

Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

Science.gov (United States)

Schuhmacher, Laura-Nadine; Smith, Ewan St John

2016-12-13

Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

Directory of Open Access Journals (Sweden)

Antje Brand

Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

Science.gov (United States)

Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

2010-12-21

Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

Naked mole-rat acid-sensing ion channel 3 forms nonfunctional homomers, but functional heteromers.

Science.gov (United States)

Schuhmacher, Laura-Nadine; Callejo, Gerard; Srivats, Shyam; Smith, Ewan St John

2018-02-02

Acid-sensing ion channels (ASICs) form both homotrimeric and heterotrimeric ion channels that are activated by extracellular protons and are involved in a wide range of physiological and pathophysiological processes, including pain and anxiety. ASIC proteins can form both homotrimeric and heterotrimeric ion channels. The ASIC3 subunit has been shown to be of particular importance in the peripheral nervous system with pharmacological and genetic manipulations demonstrating a role in pain. Naked mole-rats, despite having functional ASICs, are insensitive to acid as a noxious stimulus and show diminished avoidance of acidic fumes, ammonia, and carbon dioxide. Here we cloned naked mole-rat ASIC3 (nmrASIC3) and used a cell-surface biotinylation assay to demonstrate that it traffics to the plasma membrane, but using whole-cell patch clamp electrophysiology we observed that nmrASIC3 is insensitive to both protons and the non-proton ASIC3 agonist 2-guanidine-4-methylquinazoline. However, in line with previous reports of ASIC3 mRNA expression in dorsal root ganglia neurons, we found that the ASIC3 antagonist APETx2 reversibly inhibits ASIC-like currents in naked mole-rat dorsal root ganglia neurons. We further show that like the proton-insensitive ASIC2b and ASIC4, nmrASIC3 forms functional, proton-sensitive heteromers with other ASIC subunits. An amino acid alignment of ASIC3s between 9 relevant rodent species and human identified unique sequence differences that might underlie the proton insensitivity of nmrASIC3. However, introducing nmrASIC3 differences into rat ASIC3 (rASIC3) produced only minor differences in channel function, and replacing the nmrASIC3 sequence with that of rASIC3 did not produce a proton-sensitive ion channel. Our observation that nmrASIC3 forms nonfunctional homomers may reflect a further adaptation of the naked mole-rat to living in an environment with high-carbon dioxide levels. © 2018 by The American Society for Biochemistry and Molecular

Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia

Directory of Open Access Journals (Sweden)

Philip G. Cox

2014-06-01

Full Text Available The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape–both important adaptations for a life dominated by digging with the incisors.

Multidimensional MRI-CT atlas of the naked mole-rat brain (Heterocephalus glaber).

Science.gov (United States)

Seki, Fumiko; Hikishima, Keigo; Nambu, Sanae; Okanoya, Kazuo; Okano, Hirotaka J; Sasaki, Erika; Miura, Kyoko; Okano, Hideyuki

2013-01-01

Naked mole-rats have a variety of distinctive features such as the organization of a hierarchical society (known as eusociality), extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI). Advanced MRI techniques such as diffusion tensor imaging (DTI), which generates high contrast images of fiber structures, can characterize unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D) images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualization of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

Science.gov (United States)

Rodriguez, Karl A; Edrey, Yael H; Osmulski, Pawel; Gaczynska, Maria; Buffenstein, Rochelle

2012-01-01

The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

Science.gov (United States)

Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

2017-12-01

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

Challenging the inbreeding hypothesis in a eusocial mammal: population genetics of the naked mole-rat, Heterocephalus glaber.

Science.gov (United States)

Ingram, Colleen M; Troendle, Nicholas J; Gill, Clare A; Braude, Stanton; Honeycutt, Rodney L

2015-10-01

The role of genetic relatedness in the evolution of eusociality has been the topic of much debate, especially when contrasting eusocial insects with vertebrates displaying reproductive altruism. The naked mole-rat, Heterocephalus glaber, was the first described eusocial mammal. Although this discovery was based on an ecological constraints model of eusocial evolution, early genetic studies reported high levels of relatedness in naked mole-rats, providing a compelling argument that low dispersal rates and consanguineous mating (inbreeding as a mating system) are the driving forces for the evolution of this eusocial species. One caveat to accepting this long-held view is that the original genetic studies were based on limited sampling from the species' geographic distribution. A growing body of evidence supports a contrary view, with the original samples not representative of the species-rather reflecting a single founder event, establishing a small population south of the Athi River. Our study is the first to address these competing hypotheses by examining patterns of molecular variation in colonies sampled from north and south of the Athi and Tana rivers, which based on our results, serve to isolate genetically distinct populations of naked mole-rats. Although colonies south of the Athi River share a single mtDNA haplotype and are fixed at most microsatellite loci, populations north of the Athi River are considerably more variable. Our findings support the position that the low variation observed in naked mole-rat populations south of the Athi River reflects a founder event, rather than a consequence of this species' unusual mating system. © 2015 John Wiley & Sons Ltd.

Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

Directory of Open Access Journals (Sweden)

Karl A Rodriguez

Full Text Available The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber, maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L activity and a two-fold increase in trypsin-like (T-L in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Sarko, Diana K; Leitch, Duncan B; Catania, Kenneth C

2013-01-01

The naked mole-rat (Heterocephalus glaber) is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats' behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors). These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

NARCIS (Netherlands)

S.L. Macrae (Sheila L.); Q. Zhang (Quanwei); C. Lemetre (Christophe); I. Seim (Inge); R.B. Calder (Robert B.); J.H.J. Hoeijmakers (Jan); Y. Suh (Yousin); V.N. Gladyshev (Vadim N.); A. Seluanov (Andrei); V. Gorbunova (Vera); J. Vijg (Jan); Z.D. Zhang (Zhengdong D.)

2015-01-01

textabstractGenome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM

Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats.

Science.gov (United States)

Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C

2015-11-01

Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age.

Science.gov (United States)

Stoll, Elizabeth A; Karapavlovic, Nevena; Rosa, Hannah; Woodmass, Michael; Rygiel, Karolina; White, Kathryn; Turnbull, Douglass M; Faulkes, Chris G

2016-12-19

The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades.

Androgen receptor distribution in the social decision-making network of eusocial naked mole-rats.

Science.gov (United States)

Holmes, Melissa M; Van Mil, Spencer; Bulkowski, Camila; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

2013-11-01

Naked mole-rats are highly social rodents that live in large groups and exhibit a strict reproductive and social hierarchy. Only a few animals in each colony breed; the remainder are non-reproductive and are socially subordinate to breeders. We have examined androgen receptor immunoreactive (AR+) cells in brain regions comprising the recently described social decision-making network in subordinate and breeder naked mole-rats of both sexes. We find that subordinates have a significantly higher percentage of AR+ cells in all brain regions expressing this protein. By contrast, there were no significant effects of sex and no sex-by-status interactions on the percentage of AR+ cells. Taken together with previous findings, the present data complete a systematic assessment of the distribution of AR protein in the social decision-making network of the eusocial mammalian brain and demonstrate a significant role for social status in the regulation of this protein throughout many nodes of this network. Copyright © 2013 Elsevier B.V. All rights reserved.

Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber

Directory of Open Access Journals (Sweden)

Diana K Sarko

2013-11-01

Full Text Available The naked mole-rat (Heterocephalus glaber is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats’ behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors. These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber)

DEFF Research Database (Denmark)

Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K

2014-01-01

The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in ...

Social status and sex effects on neural morphology in Damaraland mole-rats, Fukomys damarensis.

Science.gov (United States)

Anyan, Jeff J; Seney, Marianne L; Holley, Amanda; Bengston, Lynn; Goldman, Bruce D; Forger, Nancy G; Holmes, Melissa M

2011-01-01

We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf's nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew. 2011 S. Karger AG, Basel.

Naked mole-rat cortical neurons are resistant to acid-induced cell death

OpenAIRE

Husson, Zoé; Smith, Ewan S

2018-01-01

Abstract Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+ permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are ...

Cessation of reproduction-related spine elongation after multiple breeding cycles in female naked mole-rats.

Science.gov (United States)

Dengler-Crish, Christine M; Catania, Kenneth C

2009-01-01

The breeding female or "queen" naked mole-rat has a uniquely elongated body morphology attributed to the lengthening of the lumbar vertebral column that occurs during pregnancy. It is unknown whether this vertebral growth is a continuous process, or associated only with early reproductive experience. We compared pregnancy-related bone elongation in nascent primiparous queens and established queens to determine if this vertebral expansion was a lifelong process in these females. We also investigated the impact of lactation on vertebral elongation in these mole-rats because it is known to be a time of significant bone loss in other mammals. Our data show that after eight or more pregnancies, established queens no longer experienced a net gain in lumbar spine length over the reproductive cycle, whereas the nascent breeders demonstrated significant spine lengthening over this time. Despite the lack of net spine lengthening in established breeders, our results indicated that these queens still experienced some pregnancy-specific vertebral elongation. In naked mole-rats, pregnancy-induced bone elongation may serve the dual purposes of first lengthening the spine, and then once optimal spine size is achieved, serving as a homeostatic mechanism that prepares the spine for the mineral demands of lactation. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

Endocrine function and neurobiology of the longest-living rodent, the naked mole-rat.

Science.gov (United States)

Edrey, Yael H; Park, Thomas J; Kang, Hyesin; Biney, Adriana; Buffenstein, Rochelle

2011-01-01

Animals that have evolved exceptional capabilities, such as extraordinary longevity may reveal pertinent and potentially critical insights into biomedical research that are not readily apparent in standard laboratory animals. Naked mole-rats (Heterocephalus glaber; NMRs) are extremely long-lived (30 years) mouse-sized rodents. They clearly have evolved superior anti-aging mechanisms as evident by the markedly attenuated age-related decline in physiological function, sustained reproductive capacity and pronounced cancer resistance throughout their long-lives. These eusocial rodents, like the social insects, live in colonies with breeding restricted to one female and a few males. Subordinates are sexually monomorphic, yet retain the ability to become breeders, and can undergo growth surges and neural modifications at any time throughout their life. This plasticity in physiological and behavioral aspects may have contributed to their long-lives. Naked mole-rats show numerous adaptations to life underground including extreme tolerance of hypoxia, acid insensitivity, as well as independence of photoendocrine systems. Here we review what is known about their unique social structure, sensory systems, endocrinology and neurobiology, and highlight areas that may be pertinent to biogerontology. Copyright © 2010 Elsevier Inc. All rights reserved.

The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

Science.gov (United States)

Kurz, Susanne; Thieme, René; Amberg, Ronny; Groth, Marco; Jahnke, Heinz-Georg; Pieroh, Philipp; Horn, Lars-Christian; Kolb, Marlen; Huse, Klaus; Platzer, Matthias; Volke, Daniela; Dehghani, Faramarz; Buzdin, Anton; Engel, Kathrin; Robitzki, Andrea; Hoffmann, Ralf; Gockel, Ines; Birkenmeier, Gerd

2017-01-01

Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

Science.gov (United States)

Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

2017-02-01

In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dominance and queen succession in captive colonies of the eusocial naked mole-rat, Heterocephalus glaber.

Science.gov (United States)

Clarke, F M; Faulkes, C G

1997-07-22

Naked mole-rat colonies exhibit a high reproductive skew, breeding being typically restricted to one female (the 'queen') and one to three males. Other colony members are reproductively suppressed, although this suppression can be reversed following the removal or death of the queen. We examined dominance and queen succession within captive colonies to investigate the relationship between urinary testosterone and cortisol, dominance rank and reproductive status; and to determine if behavioural and/or physiological parameters can be used as predictors of queen succession. Social structure was characterized by a linear dominance hierarchy before and after queen removal. Prior to queen removal, dominance rank was negatively correlated with body weight and urinary testosterone and cortisol titres in males and females. Queen removal results in social instability and aggression between high ranking individuals. Dominance rank appears to be a good predictor of reproductive status: queens are the highest ranking colony females and are succeeded by the next highest ranking females. The intense dominance-related aggression that accompanies reproductive succession in naked mole-rats provides empirical support for optimal skew theory.

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain.

Science.gov (United States)

Holmes, Melissa M; Goldman, Bruce D; Forger, Nancy G

2008-08-01

Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.

A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence.

Science.gov (United States)

Lewis, Kaitlyn N; Rubinstein, Nimrod D; Buffenstein, Rochelle

2018-04-20

Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives.

Low sulfide levels and a high degree of cystathionine β-synthase (CBS activation by S-adenosylmethionine (SAM in the long-lived naked mole-rat

Directory of Open Access Journals (Sweden)

Maja Dziegelewska

2016-08-01

Full Text Available Hydrogen sulfide (H2S is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS, an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration.

The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

Directory of Open Access Journals (Sweden)

Susanne Kurz

Full Text Available Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

Low sulfide levels and a high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat.

Science.gov (United States)

Dziegelewska, Maja; Holtze, Susanne; Vole, Christiane; Wachter, Ulrich; Menzel, Uwe; Morhart, Michaela; Groth, Marco; Szafranski, Karol; Sahm, Arne; Sponholz, Christoph; Dammann, Philip; Huse, Klaus; Hildebrandt, Thomas; Platzer, Matthias

2016-08-01

Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

Science.gov (United States)

St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-08-15

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Differential effects of chronic fluoxetine on the behavior of dominant and subordinate naked mole-rats.

Science.gov (United States)

Mongillo, Daniel L; Kosyachkova, Ekaterina A; Nguyen, Tam M; Holmes, Melissa M

2014-01-01

Naked mole-rats are eusocial rodents that live in large subterranean colonies with a strict reproductive and social hierarchy. The breeding female (referred to as the queen) and 1 to 3 breeding males are the only reproductive members of the colony. Breeders are socially dominant and all other colony members are non-reproductive subordinates. The effects of manipulating the serotonergic neurotransmitter system on aggression and dominance behaviors are well studied in many species, but not in eusocial rodents like the naked mole-rat. The current study investigated how the serotonergic system influences aggressive/dominant behaviors in this species. To do this, two separate but related experiments were conducted: the effects of fluoxetine hydrochloride (FLX) on status-specific behaviors of subordinates (Experiment 1) and dominant queens (Experiment 2) were evaluated both in-colony and in a social-pairing paradigm. In accordance with our main hypothesis, chronic treatment of FLX attenuated the frequency and duration of aggression in queens, but not subordinates, when paired with an unfamiliar conspecific. Further exploration of pharmacological manipulation on status-specific behaviors of this eusocial species may elucidate the neurobiological mechanisms underlying their unique and rigid social hierarchy. Copyright © 2013 Elsevier B.V. All rights reserved.

The long gestation of the small naked mole-rat (Heterocephalus glaber Ruppell, 1842 studied with ultrasound biomicroscopy and 3D-ultrasonography.

Directory of Open Access Journals (Sweden)

Kathleen Roellig

Full Text Available The naked mole-rat (Heterocephalus glaber is one of the two known mammalian species that live in a eusocial population structure. Here we investigate the exceptionally long gestation period of 70 days observed in the mole-rat queen. The course of seven successful pregnancies in two individuals was recorded in a colony of captive naked mole-rats using ultrasound biomicroscopy (UBM and 3D-ultrasonography. We establish a catalogue of basic reference ultrasound data for this species by describing the ultrasonographic appearance of reproductive organs, calculating growth curves to predict gestational age and defining ultrasonographic milestones to characterize pregnancy stages. Mean litter size was 10.9±2.7, of which 7.2±1.5 survived the weaning period. Mean interbirth interval was 128.8±63.0 days. The reproductive success in our colony did not differ from previously published data. In the queen the active corpora lutea had an anechoic, fluid filled centre. Using UBM, pregnancy could be detected 53 days before parturition. The period of embryonic development is assumed to last until 30 days before parturition. Embryonic resorptions were detected frequently in the queen, indicating that this might be an ordinary event in this species. We discuss the extraordinary long gestation period of this small rodent and postulate that the long gestation is beneficial to both the eusocial structure and longevity. An increased litter size, twice as large as for other rodents of similar size, seemingly compensates for the doubling of pregnancy length. We demonstrate that the lifetime reproductive effort of a naked mole-rat queen is equivalent to the mass of offspring that would be produced if all of the females of a colony would be reproducing.

Functional characteristics of the naked mole rat μ-opioid receptor.

Directory of Open Access Journals (Sweden)

Melanie Busch-Dienstfertig

Full Text Available While humans and most animals respond to µ-opioid receptor (MOR agonists with analgesia and decreased aggression, in the naked mole rat (NMR opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1 can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.

Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

Science.gov (United States)

Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

2016-01-01

Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber.

Directory of Open Access Journals (Sweden)

Nikodemus Gessele

Full Text Available Naked mole-rats (Heterocephalus glaber live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

The long gestation of the small naked mole-rat (Heterocephalus glaber Rüppell, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography.

Science.gov (United States)

Roellig, Kathleen; Drews, Barbara; Goeritz, Frank; Hildebrandt, Thomas Bernd

2011-03-07

The naked mole-rat (Heterocephalus glaber) is one of the two known mammalian species that live in a eusocial population structure. Here we investigate the exceptionally long gestation period of 70 days observed in the mole-rat queen. The course of seven successful pregnancies in two individuals was recorded in a colony of captive naked mole-rats using ultrasound biomicroscopy (UBM) and 3D-ultrasonography. We establish a catalogue of basic reference ultrasound data for this species by describing the ultrasonographic appearance of reproductive organs, calculating growth curves to predict gestational age and defining ultrasonographic milestones to characterize pregnancy stages. Mean litter size was 10.9±2.7, of which 7.2±1.5 survived the weaning period. Mean interbirth interval was 128.8±63.0 days. The reproductive success in our colony did not differ from previously published data. In the queen the active corpora lutea had an anechoic, fluid filled centre. Using UBM, pregnancy could be detected 53 days before parturition. The period of embryonic development is assumed to last until 30 days before parturition. Embryonic resorptions were detected frequently in the queen, indicating that this might be an ordinary event in this species. We discuss the extraordinary long gestation period of this small rodent and postulate that the long gestation is beneficial to both the eusocial structure and longevity. An increased litter size, twice as large as for other rodents of similar size, seemingly compensates for the doubling of pregnancy length. We demonstrate that the lifetime reproductive effort of a naked mole-rat queen is equivalent to the mass of offspring that would be produced if all of the females of a colony would be reproducing.

Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae.

Directory of Open Access Journals (Sweden)

Matthew J Mason

Full Text Available Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle. Heterocephalus deviates morphologically from the other bathyergids examined in that it has a more complex mastoid cavity structure, poorly-ossified processes of the malleus and incus, a 'columelliform' stapes and fewer cochlear turns. Bathyergids have semicircular canals with unusually wide diameters relative to their radii of curvature. How the lateral semicircular canal reaches the vestibule differs between species. Heterocephalus has much more limited high-frequency hearing than would be predicted from its small ear structures. The spongy bone forming its ossicular processes, the weak incudo-stapedial articulation, the columelliform stapes and (compared to other bathyergids reduced cochlear coiling are all potentially degenerate features which might reflect a lack of selective pressure on its peripheral auditory system. Substantial intraspecific differences were found in certain middle and inner ear structures, which might also result from relaxed selective pressures. However, such interpretations must be treated with caution in the absence of experimental evidence.

Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae).

Science.gov (United States)

Mason, Matthew J; Cornwall, Hannah L; Smith, Ewan St J

2016-01-01

Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus) were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle. Heterocephalus deviates morphologically from the other bathyergids examined in that it has a more complex mastoid cavity structure, poorly-ossified processes of the malleus and incus, a 'columelliform' stapes and fewer cochlear turns. Bathyergids have semicircular canals with unusually wide diameters relative to their radii of curvature. How the lateral semicircular canal reaches the vestibule differs between species. Heterocephalus has much more limited high-frequency hearing than would be predicted from its small ear structures. The spongy bone forming its ossicular processes, the weak incudo-stapedial articulation, the columelliform stapes and (compared to other bathyergids) reduced cochlear coiling are all potentially degenerate features which might reflect a lack of selective pressure on its peripheral auditory system. Substantial intraspecific differences were found in certain middle and inner ear structures, which might also result from relaxed selective pressures. However, such interpretations must be treated with caution in the absence of experimental evidence.

case of natural queen succession in a captive colony of naked mole ...

African Journals Online (AJOL)

Naked mole-rats occur in large colonies where usually a single queen monopolizes reproduction. Queen succession occurs from within usually as a result of aggressive encounters with subordinate females that queue for reproductive succession following colony instability, which inevitably results in death of either the ...

Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

Science.gov (United States)

Yosida, Shigeto; Okanoya, Kazuo

2012-02-01

Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

Social condition and oxytocin neuron number in the hypothalamus of naked mole-rats (Heterocephalus glaber).

Science.gov (United States)

Mooney, S J; Holmes, M M

2013-01-29

The naked mole-rat is a subterranean colonial rodent. In each colony, which can grow to as many as 300 individuals, there is only one female and 1-3 males that are reproductive and socially dominant. The remaining animals are reproductively suppressed subordinates that contribute to colony survival through their cooperative behaviors. Oxytocin is a peptide hormone that has shown relatively widespread effects on prosocial behaviors in other species. We examined whether social status affects the number of oxytocin-immunoreactive neurons in the paraventricular nucleus and the supraoptic nucleus by comparing dominant breeding animals to subordinate non-breeding workers from intact colonies. We also examined these regions in subordinate animals that had been removed from their colony and paired with an opposite- or same-sex conspecific for 6 months. Stereological analyses indicated that subordinates had significantly more oxytocin neurons in the paraventricular nucleus than breeders. Animals in both opposite- and same-sex pairs showed a decreased oxytocin neuron number compared to subordinates suggesting that status differences may be due to social condition rather than the reproductive activity of the animal per se. The effects of social status appear to be region specific as no group differences were found for oxytocin neuron number in the supraoptic nucleus. Given that subordinate naked mole-rats are kept reproductively suppressed through antagonism by the queen, we speculate that status differences are due either to oxytocin's anxiolytic properties to combat the stress of this antagonism or to its ability to promote the prosocial behaviors of subordinates. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

Directory of Open Access Journals (Sweden)

Irmgard eAmrein

2014-05-01

Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

Science.gov (United States)

Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

2014-01-01

African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species.

Science.gov (United States)

Buffenstein, Rochelle

2008-05-01

Aging refers to a gradual deterioration in function that, over time, leads to increased mortality risk, and declining fertility. This pervasive process occurs in almost all organisms, although some long-lived trees and cold water inhabitants reportedly show insignificant aging. Negligible senescence is characterized by attenuated age-related change in reproductive and physiological functions, as well as no observable age-related gradual increase in mortality rate. It was questioned whether the longest living rodent, the naked mole-rat, met these three strict criteria. Naked mole-rats live in captivity for more than 28.3 years, approximately 9 times longer than similar-sized mice. They maintain body composition from 2 to 24 years, and show only slight age-related changes in all physiological and morphological characteristics studied to date. Surprisingly breeding females show no decline in fertility even when well into their third decade of life. Moreover, these animals have never been observed to develop any spontaneous neoplasm. As such they do not show the typical age-associated acceleration in mortality risk that characterizes every other known mammalian species and may therefore be the first reported mammal showing negligible senescence over the majority of their long lifespan. Clearly physiological and biochemical processes in this species have evolved to dramatically extend healthy lifespan. The challenge that lies ahead is to understand what these mechanisms are.

Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

OpenAIRE

Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase act...

The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K; Maloiy, Geoffrey M; Abelson, Klas S P

2014-01-01

The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.

Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Liang, Sitai; Mele, James; Wu, Yuehong; Buffenstein, Rochelle; Hornsby, Peter J

2010-08-01

The naked mole-rat (NMR, Heterocephalus glaber) is a long-lived mammal in which spontaneous cancer has not been observed. To investigate possible mechanisms for cancer resistance in this species, we studied the properties of skin fibroblasts from the NMR following transduction with oncogenes that cause cells of other mammalian species to form malignant tumors. Naked mole-rat fibroblasts were transduced with a retrovirus encoding SV40 large T antigen and oncogenic Ras(G12V). Following transplantation of transduced cells into immunodeficient mice, cells rapidly entered crisis, as evidenced by the presence of anaphase bridges, giant cells with enlarged nuclei, multinucleated cells, and cells with large number of chromosomes or abnormal chromatin material. In contrast, similarly transduced mouse and rat fibroblasts formed tumors that grew rapidly without crisis. Crisis was also observed after > 40 population doublings in SV40 TAg/Ras-expressing NMR cells in culture. Crisis in culture was prevented by additional infection of the cells with a retrovirus encoding hTERT (telomerase reverse transcriptase). SV40 TAg/Ras/hTERT-expressing NMR cells formed tumors that grew rapidly in immunodeficient mice without evidence of crisis. Crisis could also be induced in SV40 TAg/Ras-expressing NMR cells by loss of anchorage, but after hTERT transduction, cells were able to proliferate normally following loss of anchorage. Thus, rapid crisis is a response of oncogene-expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth. The unique reaction of NMR cells to oncogene expression may form part of the cancer resistance of this species.

Subcaste differences in neural activation suggest a prosocial role for oxytocin in eusocial naked mole-rats.

Science.gov (United States)

Hathaway, Georgia A; Faykoo-Martinez, Mariela; Peragine, Deane E; Mooney, Skyler J; Holmes, Melissa M

2016-03-01

The neuropeptide oxytocin (OT) influences prosocial behavior(s), aggression, and stress responsiveness, and these diverse effects are regulated in a species- and context-specific manner. The naked mole-rat (Heterocephalus glaber) is a unique species with which to study context-dependent effects of OT, exhibiting a strict social hierarchy with behavioral specialization within the subordinate caste: soldiers are aggressive and defend colonies against unfamiliar conspecifics while workers are prosocial and contribute to in-colony behaviors such as pup care. To determine if OT is involved in subcaste-specific behaviors, we compared behavioral responses between workers and soldiers of both sexes during a modified resident/intruder paradigm, and quantified activation of OT neurons in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) using the immediate-early-gene marker c-fos co-localized with OT neurons. Resident workers and soldiers were age-matched with unfamiliar worker stimulus animals as intruders, and encounters were videorecorded and scored for aggressive behaviors. Colony-matched controls were left in their home colony for the duration of the encounters. Brains were extracted and cell counts were conducted for OT immunoreactive (ir), c-fos-ir, and percentage of OT-c-fos double-labeled cells. Results indicate that resident workers were less aggressive but showed greater OT neural activity than soldiers. Furthermore, a linear model including social treatment, cortisol, and subcaste revealed that subcaste was the only significant predictor of OT-c-fos double-labeled cells in the PVN. These data suggest that in naked mole-rats OT promotes prosocial behaviors rather than aggression and that even within subordinates status exerts robust effects on brain and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

Science.gov (United States)

Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

2014-04-01

The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming

Directory of Open Access Journals (Sweden)

Li Tan

2017-11-01

Full Text Available Naked mole rat (NMR is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming. Analysis of the global histone landscape revealed that NMR had higher levels of repressive H3K27 methylation marks and lower levels of activating H3K27 acetylation marks than mouse. ATAC-seq revealed that in NMR, promoters of reprogramming genes were more closed than mouse promoters, while expression of LT led to massive opening of the NMR promoters. These results suggest that NMR displays a more stable epigenome that resists de-differentiation, contributing to the cancer resistance and longevity of this species.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

Science.gov (United States)

MacRae, Sheila L; Zhang, Quanwei; Lemetre, Christophe; Seim, Inge; Calder, Robert B; Hoeijmakers, Jan; Suh, Yousin; Gladyshev, Vadim N; Seluanov, Andrei; Gorbunova, Vera; Vijg, Jan; Zhang, Zhengdong D

2015-04-01

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat.

Science.gov (United States)

Triplett, Judy C; Swomley, Aaron; Kirk, Jessime; Lewis, Katilyn; Orr, Miranda; Rodriguez, Karl; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

2015-08-01

Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground in a thermally stable ecological niche, NMRs have evolved certain exceptional traits, resulting in sustained health spans, negligible cognitive decline, and a pronounced resistance to age-related disease. Uncovering insights into mechanisms underlying these extraordinary traits involved in successful aging may conceivably provide crucial clues to extend the human life span and health span. One of the most fundamental processes inside the cell is the production of ATP, which is an essential fuel in driving all other energy-requiring cellular activities. Not surprisingly, a prominent hallmark in age-related diseases, such as neurodegeneration and cancer, is the impairment and dysregulation of metabolic pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics approach, alterations in expression and phosphorylation levels of metabolic proteins in the brains of NMRs, aged 2-24 years, were evaluated in an age-dependent manner. We identified 13 proteins with altered levels and/or phosphorylation states that play key roles in various metabolic pathways including glycolysis, β-oxidation, the malate-aspartate shuttle, the Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH production, as well as the production of glutamate. New insights into potential pathways involved in metabolic aspects of successful aging have been obtained by the identification of key proteins through which the NMR brain responds and adapts to the aging process and how the NMR brain adapted to resist age-related degeneration. This study examines the changes in the proteome and phosphoproteome in the brain of the naked mole-rat aged 2-24 years. We identified 13 proteins (labeled in red) with altered expression and/or phosphorylation levels that are conceivably associated with sustained metabolic functions in the oldest NMRs that may promote a sustained health span and life span. �

Walking the oxidative stress tightrope: a perspective from the naked mole-rat, the longest-living rodent.

Science.gov (United States)

Rodriguez, Karl A; Wywial, Ewa; Perez, Viviana I; Lambert, Adriant J; Edrey, Yael H; Lewis, Kaitlyn N; Grimes, Kelly; Lindsey, Merry L; Brand, Martin D; Buffenstein, Rochelle

2011-01-01

Reactive oxygen species (ROS), by-products of aerobic metabolism, cause oxidative damage to cells and tissue and not surprisingly many theories have arisen to link ROS-induced oxidative stress to aging and health. While studies clearly link ROS to a plethora of divergent diseases, their role in aging is still debatable. Genetic knock-down manipulations of antioxidants alter the levels of accrued oxidative damage, however, the resultant effect of increased oxidative stress on lifespan are equivocal. Similarly the impact of elevating antioxidant levels through transgenic manipulations yield inconsistent effects on longevity. Furthermore, comparative data from a wide range of endotherms with disparate longevity remain inconclusive. Many long-living species such as birds, bats and mole-rats exhibit high-levels of oxidative damage, evident already at young ages. Clearly, neither the amount of ROS per se nor the sensitivity in neutralizing ROS are as important as whether or not the accrued oxidative stress leads to oxidative-damage-linked age-associated diseases. In this review we examine the literature on ROS, its relation to disease and the lessons gleaned from a comparative approach based upon species with widely divergent responses. We specifically focus on the longest lived rodent, the naked mole-rat, which maintains good health and provides novel insights into the paradox of maintaining both an extended healthspan and lifespan despite high oxidative stress from a young age.

Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera

Directory of Open Access Journals (Sweden)

Sang-Goo Lee

2017-11-01

Full Text Available Naked mole rats (NMRs are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.

Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

Science.gov (United States)

Delaney, M A; Kinsel, M J; Treuting, P M

2016-03-01

The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

Science.gov (United States)

Oosthuizen, M K; Amrein, I

2016-06-02

Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

Science.gov (United States)

Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

2014-03-01

The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber).

Science.gov (United States)

Delaney, M A; Ward, J M; Walsh, T F; Chinnadurai, S K; Kerns, K; Kinsel, M J; Treuting, P M

2016-05-01

Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research. © The Author(s) 2016.

Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain.

Science.gov (United States)

Orr, Miranda E; Garbarino, Valentina R; Salinas, Angelica; Buffenstein, Rochelle

2016-01-01

The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.

Extended postnatal brain development in the longest-lived rodent: prolonged maintenance of neotenous traits in the naked mole-rat brain

Directory of Open Access Journals (Sweden)

Miranda E. Orr

2016-11-01

Full Text Available The naked mole-rat (NMR is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to three years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At four months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until nine months of age in NMRs, and synaptic protein expression continues to change throughout the first three years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through six weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short

Photic induction of Fos in the suprachiasmatic nucleus of African mole-rats: responses to increasing irradiance.

Science.gov (United States)

Oosthuizen, Maria K; Bennett, Nigel C; Cooper, Howard M

2010-09-01

African mole-rats (family Bathyergidae) are strictly subterranean rodent species that are rarely exposed to environmental light. Morphological and physiological adaptations to the underground environment include a severely reduced eye size and regressed visual system. Responses of the circadian system to light, however, appear to be intact, since mole-rats are able to entrain their circadian activity rhythms to the light-dark cycle and light induces Fos expression in the suprachiasmatic nucleus (SCN). Social organization varies from solitary species to highly elaborated eusocial structures, characterized by a distinct division of labor and in which one reproductive female regulates the behavior and reproductive physiology of other individuals in the colony. The authors studied light-induced Fos expression in the SCN to increasing light intensities in four mole-rat species, ranging from strictly solitary to highly social. In the solitary Cape mole-rat, light induces significant Fos expression in the SCN, and the number of Fos-immunopositive cells increases with increasing light intensity. In contrast, Fos induction in the SCN of social species was slightly greater than, but not statistically different from, the dark-control animals as is typical of most rodents. One species showed a trend for an increase in expression with increased light, whereas a second species showed no trend in expression. In the naked mole-rat, Fos expression appeared higher in the dark-controls than in the animals exposed to light, although the differences in Fos expression were not significant. These results suggest a gradient in the sensitivity of the circadian system to light in mole-rats, with a higher percentage of individuals that are unresponsive to light in correlation with the degree of sociality. In highly social species, such as the naked mole-rat that live in a relatively stable subterranean milieu in terms of food availability, temperature, constant darkness, and devoid of 24-h

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Science.gov (United States)

Brohus, Malene; Gorbunova, Vera; Faulkes, Chris G; Overgaard, Michael T; Conover, Cheryl A

2015-01-01

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

Morphological divergence of breeders and helpers in wild Damaraland mole-rat societies.

Science.gov (United States)

Young, Andrew J; Bennett, Nigel C

2010-11-01

The specialization of body shape to an individual's role within society represents a pinnacle of social evolution. Although commonplace among social insects, divergence in the body shapes of breeders and helpers has to date been documented in just one social vertebrate, the naked mole-rat, Heterocephalus glaber; an extraordinary species in which large colony size and frequent inbreeding may have favored the evolution of such specialization. Here, we present new evidence of morphological divergence between breeders and helpers in the Damaraland mole-rat, Fukomys damarensis; a much less socially extreme species that reflects an independent evolutionary origin of sociality. Using longitudinal data from wild populations, we show that dominant female Damaraland mole-rats, like many social insect queens, have a significantly more elongate body shape than subordinates. This difference arises not from a pre-existing difference in the body shapes of subordinates that do, and those that do not, become dominant, but from a modification to the growth trajectory of subordinates on dominance acquisition. Our findings reveal a wider role for morphological divergence within vertebrate societies and, as Damaraland mole-rats neither live in unusually large groups nor inbreed, suggest that circumstances favoring the evolution of such specializations may be more widespread among vertebrates than previously supposed. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Directory of Open Access Journals (Sweden)

Malene Brohus

Full Text Available Naked mole-rats (Heterocephalus glaber (NMRs are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs, and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A, shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.

Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors.

Science.gov (United States)

Faulkes, Chris G; Bennett, Nigel C

2013-05-19

Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (Heterocephalus glaber and Fukomys damarensis). The common mole-rat (Cryptomys hottentotus) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.

Reaching Out to Send a Message: Proteins Associated with Neurite Outgrowth and Neurotransmission are Altered with Age in the Long-Lived Naked Mole-Rat.

Science.gov (United States)

Triplett, Judy C; Swomley, Aaron M; Kirk, Jessime; Grimes, Kelly M; Lewis, Kaitilyn N; Orr, Miranda E; Rodriguez, Karl A; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

2016-07-01

Aging is the greatest risk factor for developing neurodegenerative diseases, which are associated with diminished neurotransmission as well as neuronal structure and function. However, several traits seemingly evolved to avert or delay age-related deterioration in the brain of the longest-lived rodent, the naked mole-rat (NMR). The NMR remarkably also exhibits negligible senescence, maintaining an extended healthspan for ~75 % of its life span. Using a proteomic approach, statistically significant changes with age in expression and/or phosphorylation levels of proteins associated with neurite outgrowth and neurotransmission were identified in the brain of the NMR and include: cofilin-1; collapsin response mediator protein 2; actin depolymerizing factor; spectrin alpha chain; septin-7; syntaxin-binding protein 1; synapsin-2 isoform IIB; and dynamin 1. We hypothesize that such changes may contribute to the extended lifespan and healthspan of the NMR.

Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease.

Science.gov (United States)

Edrey, Yael H; Medina, David X; Gaczynska, Maria; Osmulski, Pawel A; Oddo, Salvatore; Caccamo, Antonella; Buffenstein, Rochelle

2013-10-01

Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2-20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression. Copyright © 2013 Elsevier Inc. All rights reserved.

A distinct role of the queen in coordinated workload and soil distribution in eusocial naked mole-rats.

Directory of Open Access Journals (Sweden)

Nobuyuki Kutsukake

Full Text Available We investigated how group members achieve collective decision-making, by considering individual intrinsic behavioural rules and behavioural mechanisms for maintaining social integration. Using a simulated burrow environment, we investigated the behavioural rules of coordinated workload for soil distribution in a eusocial mammal, the naked mole-rat (Heterocephalus glaber. We tested two predictions regarding a distinct role of the queen, a socially dominant individual in the caste system: the presence of a queen would increase the workload of other caste individuals, and the cues by a queen would affect the soil distribution. In experiment 1, we placed four individuals of various castes from the same colony into an experimental burrow. Workers exhibited the highest frequency of workload compared to other castes. The presence of a queen activated the workload by other individuals. Individuals showed a consistent workload in a particular direction so as to bias the soil distribution. These results suggest that individuals have a consensus on soil distribution and that the queen plays a distinct role. In experiment 2, we placed the odour of a queen in one of four cells and observed its effect on other individuals' workload and soil distribution. Relative to other cells, individuals frequently dug in the queen cell so the amount of soil in the queen cell decreased. These results suggest that queen odour is an important cue in coordinated workload and soil distribution in this species.

Theoretical paper: exploring overlooked natural mitochondria-rejuvenative intervention: the puzzle of bowhead whales and naked mole rats.

Science.gov (United States)

Prokopov, Arkadi F

2007-12-01

There is an imperative need for exploring and implementing mitochondria-rejuvenative interventions that can bridge the current gap toward the step-by step realization of strategies for engineered negligible senescence (SENS) agenda. Recently discovered in mammals, natural mechanism mitoptosis-a selective "suicide" of mutated mitochondria-can facilitate continuous purification of mitochondrial pool in an organism from the most reactive oxygen species (ROS)-producing mitochondria. Mitoptosis, which is considered to be the first stage of ROS-induced apoptosis, underlies follicular atresia (a "quality control" mechanism in female germline cells that eliminates most germinal follicles in female embryos). Mitoptosis can be also activated in adult postmitotic somatic cells by evolutionary conserved phenotypic adaptations to intermittent oxygen restriction (IOR) and synergistically acting intermittent caloric restriction (ICR). IOR and ICR are common in mammals and seem to underlie extraordinary longevity and augmented cancer resistance in bowhead whales (Balena mysticetus) and naked mole rats (Heterocephalus glaber). Furthermore, in mammals IOR can facilitate continuous stromal stem cells-de-pendent tissue repair. A comparative analysis of IOR and ICR mechanisms in both mammals, in conjunction with the experience of decades of biomedical and clinical research on emerging preventative, therapeutic, and rehabilitative modality-the intermittent hypoxic training/therapy (IHT)-indicates that the notable clinical efficiency of IHT is based on the universal adaptational mechanisms that are common in mammals. Further exploration of natural mitochondria-preserving and -rejuvenating strategies can help refinement of IOR- and ICR-based synergistic protocols, having value in clinical human rejuvenation.

Transcriptome sequencing of the naked mole rat (Heterocephalus glaber and identification of hypoxia tolerance genes

Directory of Open Access Journals (Sweden)

Bang Xiao

2017-12-01

Full Text Available The naked mole rat (NMR; Heterocephalus glaber is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression. In this study, we examined the sequence and transcript abundance data of the muscle transcriptome of NMRs exposed to hypoxia using the Illumina HiSeq 2500 system to clarify the possible genomic adaptive responses to the hypoxic underground surroundings. The RNA-seq raw FastQ data were mapped against the NMR genome. We identified 2337 differentially expressed genes (DEGs by comparison of the hypoxic and control groups. Functional annotation of the DEGs by gene ontology (GO analysis revealed enrichment of hypoxia stress-related GO categories, including ‘biological regulation’, ‘cellular process’, ‘ion transport’ and ‘cell-cell signaling’. Enrichment of DEGs in signaling pathways was analyzed against the Kyoto Encyclopedia of Genes and Genomes (KEGG database to identify possible interactions between DEGs. The results revealed significant enrichment of DEGs in focal adhesion, the mitogen-activated protein kinase (MAPK signaling pathway and the glycine, serine and threonine metabolism pathway. Furthermore, inhibition of DEGs (STMN1, MAPK8IP1 and MAPK10 expression induced apoptosis and arrested cell growth in NMR fibroblasts following hypoxia. Thus, this global transcriptome analysis of NMRs can provide an important genetic resource for the study of hypoxia tolerance in mammals. Furthermore, the identified DEGs may provide important molecular targets for biomedical research into therapeutic strategies for stroke and cardiovascular diseases.

Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

Science.gov (United States)

Pan, Jie; Park, Thomas J; Cutz, Ernest; Yeger, Herman

2014-01-01

The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and

Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

Science.gov (United States)

Gorbunova, Vera; Hine, Christopher; Tian, Xiao; Ablaeva, Julia; Gudkov, Andrei V.; Nevo, Eviatar; Seluanov, Andrei

2012-01-01

Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground. PMID:23129611

Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

Science.gov (United States)

Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with 75Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

Directory of Open Access Journals (Sweden)

Jie Pan

Full Text Available The pulmonary neuroepithelial bodies (NEBs constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+ via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT, and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR, Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates. The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1 NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2 NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3 NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4 NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA and the neurogenic gene (MASH1 indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional

Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

Directory of Open Access Journals (Sweden)

Xiaodong Fang

2014-09-01

Full Text Available Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber. Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.

And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat.

Science.gov (United States)

Grimes, Kelly M; Reddy, Anilkumar K; Lindsey, Merry L; Buffenstein, Rochelle

2014-08-01

The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans.

Removal of reproductive suppression reveals latent sex differences in brain steroid hormone receptors in naked mole-rats, Heterocephalus glaber.

Science.gov (United States)

Swift-Gallant, Ashlyn; Mo, Kaiguo; Peragine, Deane E; Monks, D Ashley; Holmes, Melissa M

2015-01-01

Naked mole-rats are eusocial mammals, living in large colonies with a single breeding female and 1-3 breeding males. Breeders are socially dominant, and only the breeders exhibit traditional sex differences in circulating gonadal steroid hormones and reproductive behaviors. Non-reproductive subordinates also fail to show sex differences in overall body size, external genital morphology, and non-reproductive behaviors. However, subordinates can transition to breeding status if removed from their colony and housed with an opposite-sex conspecific, suggesting the presence of latent sex differences. Here, we assessed the expression of steroid hormone receptor and aromatase messenger RNA (mRNA) in the brains of males and females as they transitioned in social and reproductive status. We compared in-colony subordinates to opposite-sex subordinate pairs that were removed from their colony for either 1 day, 1 week, 1 month, or until they became breeders (i.e., produced a litter). Diencephalic tissue was collected and mRNA of androgen receptor (Ar), estrogen receptor alpha (Esr1), progesterone receptor (Pgr), and aromatase (Cyp19a1) was measured using qPCR. Testosterone, 17β-estradiol, and progesterone from serum were also measured. As early as 1 week post-removal, males exhibited increased diencephalic Ar mRNA and circulating testosterone, whereas females had increased Cyp19a1 mRNA in the diencephalon. At 1 month post-removal, females exhibited increased 17β-estradiol and progesterone. The largest changes in steroid hormone receptors were observed in breeders. Breeding females had a threefold increase in Cyp19a1 and fivefold increases in Esr1 and Pgr, whereas breeding males had reduced Pgr and increased Ar. These data demonstrate that sex differences in circulating gonadal steroids and hypothalamic gene expression emerge weeks to months after subordinate animals are removed from reproductive suppression in their home colony.

Sleep in the Cape Mole Rat: A Short-Sleeping Subterranean Rodent.

Science.gov (United States)

Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R

2016-01-01

The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.

Socially regulated reproductive development: analysis of GnRH-1 and kisspeptin neuronal systems in cooperatively breeding naked mole-rats (Heterocephalus glaber).

Science.gov (United States)

Zhou, Shuzhi; Holmes, Melissa M; Forger, Nancy G; Goldman, Bruce D; Lovern, Matthew B; Caraty, Alain; Kalló, Imre; Faulkes, Christopher G; Coen, Clive W

2013-09-01

In naked mole-rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH-1-ir cell bodies do not differ between gonad-intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH-1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlying puberty or seasonal breeding in other species. Copyright © 2013 Wiley Periodicals, Inc.

H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole-rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway.

Science.gov (United States)

Zhao, Shanmin; Li, Li; Wang, Shiyong; Yu, Chenlin; Xiao, Bang; Lin, Lifang; Cong, Wei; Cheng, Jishuai; Yang, Wenjing; Sun, Wei; Cui, Shufang

2016-12-20

Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308. By contrast, CQ treatment decreased p70S6K, AktSer473, and AktThr308 levels. The Bax/Bcl-2 ratio increased after 12 h of exposure to LY294002 or CQ. These data show that inhibiting the Akt pathway promotes autophagy and apoptosis in NMR skin fibroblasts. Furthermore, LY294002 or CQ treatment decreased caspase-3, p53, and HIF1-α levels, suggesting that serum starvation or H2O2 treatment increase autophagy and apoptosis in NMR skin fibroblasts by inhibiting the PI3K/Akt pathway. CQ-induced inhibition of late autophagy stages also prevented Akt activation and induced apoptosis. Finally, the HIF-1α and p53 pathways were involved in serum starvation- or H2O2-induced autophagy in NMR skin fibroblasts.

Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

Science.gov (United States)

Thieme, René; Kurz, Susanne; Kolb, Marlen; Debebe, Tewodros; Holtze, Susanne; Morhart, Michaela; Huse, Klaus; Szafranski, Karol; Platzer, Matthias; Hildebrandt, Thomas B; Birkenmeier, Gerd

2015-01-01

The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M. Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL) and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL) in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma. We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti

Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

Directory of Open Access Journals (Sweden)

René Thieme

Full Text Available The naked mole-rat (NMR is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M.Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma.We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

Science.gov (United States)

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-02-01

Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of

Extended longevity of reproductives appears to be common in Fukomys mole-rats (Rodentia, Bathyergidae.

Directory of Open Access Journals (Sweden)

Philip Dammann

Full Text Available African mole-rats (Bathyergidae, Rodentia contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive "helpers" in their natal families, often for several years. This "reproductive subdivision" of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli, breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5-2.2fold depending on the sex, irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats.

Locomotor Activity and Body Temperature Patterns over a Temperature Gradient in the Highveld Mole-Rat (Cryptomys hottentotus pretoriae).

Science.gov (United States)

Haupt, Meghan; Bennett, Nigel C; Oosthuizen, Maria K

2017-01-01

African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation. Here we test the effect of ambient temperature on locomotor activity and body temperature, and the relationship between the two parameters, in the highveld mole-rat. We exposed mole-rats to a 12L:12D and a DD light cycle at ambient temperatures of 30°C, 25°C and 20°C while locomotor activity and body temperature were measured simultaneously. In addition, we investigated the endogenous rhythms of locomotor activity and body temperature at different ambient temperatures. Mole-rats displayed nocturnal activity at all three ambient temperatures and were most active at 20°C, but least active at 30°C. Body temperature was highest at 30°C and lowest at 20°C, and the daily cycle was highly correlated with locomotor activity. We show that the mole-rats have endogenous rhythms for both locomotor activity and body temperature. However, the endogenous body temperature rhythm appears to be less robust compared to the locomotor activity rhythm. Female mole-rats appear to be more sensitive to temperature changes than males, increased heterothermy is evident at lower ambient temperatures, whilst males show smaller variation in their body temperatures with changing ambient temperatures. Mole-rats may rely more heavily on behavioural thermoregulation as it is more energy efficient in an already challenging environment.

Burrow architecture of the Damaraland mole-rat ( Fukomys ...

African Journals Online (AJOL)

The burrow architecture (length, internal dimensions, fractal dimension of tunnel systems, number of nesting chambers and surface mounds) was investigated in the Damaraland mole-rat (Fukomys damarensis). A total of 31 animals were caught from five different colonies and their burrow systems were excavated in their ...

Prevention of CCl4 induced hypogonadism with Raphanus sativus seeds in rat.

Science.gov (United States)

Tabassum, Farhana; Khan, Muhammad Rashid

2017-03-01

Raphanus sativus seeds are used as condiment and to treat hypogonadism, various ailments of liver and kidneys. The aim of this study was to evaluate the potential protective effects of methanol extract of R. sativus seeds (RSME) against hypogonadism induced with carbon tetrachloride (CCl 4 ) in Sprague-Dawley male rats. Thirty six rats were divided in to six groups with six animals in each. Animals of Group I were control and treated with saline, Group II, III and IV were given orally CCl 4 (1 ml/kg bw; 10% in corn oil). Rats of Group III and IV were also simultaneously given RSME at 100 mg/kg bw and 200 mg/kg bw respectively. However, Group V and VI received RSME (100; 200 mg/kg bw, respectively) alone. All treatments were given at alternate days for 15 days. Treatment of CCl4 to rats decreased (P < 0.001) the level of CAT, POD, SOD, GST, GSH-Px and GSR antioxidant enzymes in testes of rat. Concentration of lipid peroxides (TBARS) was increased (P < 0.001) whereas concentration of GSH was decreased (P < 0.001) in testes of CCl4 treated animals. Concentration of testosterone, FSH and LH in serum was decreased (P < 0.001) while the level of estradiol and prolactin was increased (P < 0.001) in CCl4 treated rats. Injuries in seminiferous tubules were determined in histopathology of testes. Administration of RSME, dose dependently, markedly ameliorated the oxidative stress of CCl4 thereby restoring the level of antioxidant enzymes, lipid peroxides, reduced glutathione, male hormones and alterations in histopathology.

Genetic signatures for enhanced olfaction in the African mole-rats.

Directory of Open Access Journals (Sweden)

Sofia Stathopoulos

Full Text Available The Olfactory Receptor (OR superfamily, the largest in the vertebrate genome, is responsible for vertebrate olfaction and is traditionally subdivided into 17 OR families. Recent studies characterising whole-OR subgenomes revealed a 'birth and death' model of evolution for a range of species, however little is known about fine-scale evolutionary dynamics within single-OR families. This study reports the first assessment of fine-scale OR evolution and variation in African mole-rats (Bathyergidae, a family of subterranean rodents endemic to sub-Saharan Africa. Because of the selective pressures of life underground, enhanced olfaction is proposed to be fundamental to the evolutionary success of the Bathyergidae, resulting in a highly diversified OR gene-repertoire. Using a PCR-sequencing approach, we analysed variation in the OR7 family across 14 extant bathyergid species, which revealed enhanced levels of functional polymorphisms concentrated across the receptors' ligand-binding region. We propose that mole-rats are able to recognise a broad range of odorants and that this diversity is reflected throughout their OR7 gene repertoire. Using both classic tests and tree-based methods to test for signals of selection, we investigate evolutionary forces across the mole-rat OR7 gene tree. Four well-supported clades emerged in the OR phylogeny, with varying signals of selection; from neutrality to positive and purifying selection. Bathyergid life-history traits and environmental niche-specialisation are explored as possible drivers of adaptive OR evolution, emerging as non-exclusive contributors to the positive selection observed at OR7 genes. Our results reveal unexpected complexity of evolutionary mechanisms acting within a single OR family, providing insightful perspectives into OR evolutionary dynamics.

The reproductive biology of the giant Zambian mole-rat, Cryptomys ...

African Journals Online (AJOL)

1994-09-29

Sep 29, 1994 ... gala (12° 27'S, 2T51'E) in the Copperbelt of northern Zam- hia. ... mole-rat, a pair of animals and a group comprising one male and three females .... Figure 1 Changes In bouy mass of a captive female Cr.vptom.vs mechowi ... The sex distribution was .... 'Ine social Cryptomys species are chmacteril,ed hy.

Non-invasive assessment of glucocorticoid and androgen metabolite levels in cooperatively breeding Damaraland mole-rats (Fukomys damarensis).

Science.gov (United States)

Medger, Katarina; Bennett, Nigel C; Lutermann, Heike; Ganswindt, Andre

2018-05-18

Dominant females of cooperative breeding species often use aggression to suppress reproduction of subordinate females, resulting in subordinates experiencing stress-related increases in glucocorticoid levels, which may cause reproductive down-regulation. This would suggest a general pattern with higher glucocorticoid levels in subordinate compared to dominant individuals; however, the opposite was found in a number of cooperatively breeding species. Furthermore, breeding females of the cooperatively breeding Damaraland mole-rats (Fukomys damarensis) exhibit very high androgen concentrations during the wet season, presumably to support their breeding monopoly. Hormone analysis in Damaraland mole-rats have typically been measured using plasma and urine, but faecal analysis offers additional advantages especially for field studies on this species. The present study examines the suitability of Damaraland mole-rat faecal samples for determining glucocorticoid metabolite (fGCM) and androgen metabolite (fAM) concentrations using enzyme immunoassays. Using these assays, we further evaluated the effects of breeding status on fGCM and fAM concentrations in wild-caught and captive Damaraland mole-rats. Wild-caught breeding and non-breeding males and females exhibited no differences in fAM concentrations. Immunoreactive fGCM concentrations were only high in male breeders and comparatively low in non-breeders and breeding females. Concentrations of fAMs and fGCMs were similar in captive males and females, but fAM concentrations were elevated in captive compared to wild-caught individuals, which may be related to a higher reproductive activity due to removal from the breeding female. The relatively uniform fAM and fGCM concentrations found in wild-caught mole-rats may be explained by a stable colony structure during the dry season during which this study was conducted. Limited dispersal opportunities result in lower aggression and stress levels within a colony and as a result

Effects of ultraviolet radiation on mole rats kidney: A histopathologic and ultrastructural study

Directory of Open Access Journals (Sweden)

Hüseyin Türker

2014-04-01

Full Text Available The purpose of this study was to realize the ultrastructural effects of ultraviolet radiation on the kidney tissue cells of mole rats (Spalax leucodon. The mole rats of 180–200 g body weight were divided into the control and radiation-trial groups. The control group was not given any radiation. The other groups were irradiated with artificially produced UVC radiation for 14, 28 and 60 days. The kidney tissue samples were prepared at the end of experiments and analyzed by the light and electron microscope. Several effects were observed in the kidney tissues cells analyzed in accordance with the dose magnitude of radiation. These results clearly show the detrimental effects of UVC radiation on kidney tissue cells in exposure periods dependent on radiation dose and exposure time.

Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

Science.gov (United States)

Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

2015-12-01

During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Fos expression in the suprachiasmatic nucleus in response to light stimulation in a solitary and social species of African mole-rat (family Bathyergidae).

Science.gov (United States)

Oosthuizen, M K; Bennett, N C; Cooper, H M

2005-01-01

Mole-rats are strictly subterranean rodents that are rarely exposed to environmental light. They are well adapted to their environment and have reduced eyes and a severely regressed visual system. It has been shown, however, that mole-rats do exhibit endogenous circadian rhythms that can be entrained, suggesting an intact and functional circadian system. To determine whether light is the entraining agent in these animals, Fos expression in response to light pulses at different circadian times was investigated to obtain phase response curves. Light is integrated effectively in the suprachiasmatic nucleus of the Cape mole-rat (Georychus capensis), and Fos expression is gated according to the phase of the circadian clock. The Fos response in the Cape mole-rat was comparable to that of aboveground rodents. In contrast, the highveld mole-rat (Cryptomys hottentotus pretoriae) was less sensitive to light and did not show a selective Fos response according to the phase of the circadian cycle. Social species appear to be less sensitive to light than their solitary counterparts, which compares well with results from locomotor activity studies.

Influence of spatial environment on maze learning in an African mole-rat

CSIR Research Space (South Africa)

Du Toit, L

2012-05-01

Full Text Available -1 Anim Cogn DOI 10.1007/s10071-012-0503-0 Influence of spatial environment on maze learning in an African mole-rat Lydia du Toit ? Nigel C. Bennett ? Alecia Nickless ? Martin J. Whiting L. du Toit , A. Nickless , M. J. Whiting (email) School...

O2 binding and CO2 sensitivity in haemoglobins of subterranean African mole rats

DEFF Research Database (Denmark)

Weber, Roy E.; Jarvis, Jennifer U. M.; Fago, Angela

2017-01-01

that predictably safeguard pulmonary loading under hypoxic and hypercapnic burrow conditions. The O2 binding characteristics are discussed in relation to available information on the primary structure of Hbs from adult and developmental stages of mammals subjected to hypoxia and hypercapnia and the molecular......Inhabiting deep and sealed subterranean burrows, mole rats exhibit a remarkable suite of specializations, including eusociality (living in colonies with single breeding queens), extraordinary longevity, cancer immunity and poikilothermy, and extreme tolerance of hypoxia and hypercapnia. With little...... and 2,3-diphosphoglycerate (DPG, the major allosteric modulator of Hb-O2 affinity in red blood cells) in four social and two solitary species of African mole rats (family Bathyergidae) originating from different biomes and soil types across Central and Southern Africa. We found no consistent patterns...

EXPERIMENTAL MODEL OF THE PRIMARY MALE HYPOGONADISM

Directory of Open Access Journals (Sweden)

P. A. Kulikova

2014-01-01

Full Text Available Background: Development of the new methods of treatment of primary male hypogonadism is an urgent medical problem. Its solution requires a suitable experimental model of the disease. Aim: The creation of new experimental model of primary male hypogonadism. Materials and methods: The study was conducted on the male Wistar rats, hypogonadism was modeled by temporary ligation of the distal part of the spermatic cord. Results: It was shown that three-day ligation of the spermatic cord led to persistent disturbance of the testosterone-producing and reproductive functions. These manifestations were reversible at shorter duration of the exposure. Conclusion: The created model of primary male hypogonadism is characterized by the persistent testosterone-producing and reproductive functions disturbance, technical availability, non-toxicity to the other organs and systems. Availability of the model provides new opportunities for the development of approaches to treating diseases of the reproductive organs in men.

Incisors as digging tools in molerats (Bathyergidae)

African Journals Online (AJOL)

1998-03-26

Xa and Vb) at which the upper and lower incisors (lines a- ..... JARVIS. JU.M., BENNETT. N.C. 1991. Introducing the Alriean mole-rats (family Bathyergidae). In: The biology of the naked mole-rat: 66 - 96. (Eds) Sherman. R. W ..

Proč rypoši nestárnou?

OpenAIRE

Jelínková, Alena

2016-01-01

Naked mole rat and blind mole rat are useful model organisms for human age-associated diaseases studies. Unlike human, their long lifespan is not accompanied by physical health impairment. In both species, the genes involved in aging process or carcinogenesis are under positive selection or their regulation differs from the regulatory pattern known in other rodents or human. Some genes are present in higher number of copies, missing or entirely new and not observed in other organisms. In nake...

Hypogonadotropic Hypogonadism Revisited

Directory of Open Access Journals (Sweden)

Renato Fraietta

2013-01-01

Full Text Available Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic. Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism. The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in

Hypogonadotropic Hypogonadism Revisited

Science.gov (United States)

Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

2013-01-01

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific

The eye of the African mole-rat Cryptomys anselli : to see or not to see?

NARCIS (Netherlands)

Cernuda-Cernuda, R; Garcia-Fernandez, JM; Gordijn, MCM; Bovee-Geurts, PHM; DeGrip, WJ; de Grip, W.J.

In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located

The eye of the african mole-rat Cryptomys anselli: to see or not to see?

NARCIS (Netherlands)

Cernuda-Cernuda, R.; Garcia-Fernandez, J.M.; Gordijn, M.C.; Bovee-Geurts, P.H.M.; Grip, W.J. de

2003-01-01

In an attempt to clarify its possible physiological role, we studied the eye of the Zambian mole rat Cryptomys anselli by light, electron and confocal microscopy using conventional staining as well as immunolabelling with rod and cone cell markers. The small eyes of Cryptomys are located

Gis-approach for variability assessment of soil electric conductivity under pedoturbation activity of mole rat (Spalax microphthalmus

Directory of Open Access Journals (Sweden)

T. М. Konovalova

2010-06-01

Full Text Available The results of the investigation of the impact of the mole rat’s activity on soil electric conductivity have been presented. GIS-technology have been shown to be effective for assessment of the pedoturbation activity effect on the soil surface heterogeneity formation. Method of the one-dimension spatial coordinated array transformation into matrix form has been proposed for following multidimension statistic analysis application. The quantity estimation of the mole rats role in formation of the habitat nanorelief-level diversity has been obtained by means of indexes of the landscape complexity and diversity.

Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

Science.gov (United States)

Henning, Yoshiyuki; Mladěnková, Nella; Burda, Hynek; Szafranski, Karol; Begall, Sabine

2018-03-12

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

Directory of Open Access Journals (Sweden)

Yoshiyuki Henning

Full Text Available Ansell's mole-rats (Fukomys anselli are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a their thyroid hormone system shows any peculiarities on the genetic level, b these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs, and c reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

Science.gov (United States)

Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

2014-01-01

Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a male rat hypogonadism model

Directory of Open Access Journals (Sweden)

Zhi-Yuan Zhang

2017-01-01

Full Text Available Androgen deficiency is a physical disorder that not only affects adults but can also jeopardize children′s health. Because there are many disadvantages to using traditional androgen replacement therapy, we have herein attempted to explore the use of human umbilical cord mesenchymal stem cells for the treatment of androgen deficiency. We transplanted CM-Dil-labeled human umbilical cord mesenchymal stem cells into the testes of an ethane dimethanesulfonate (EDS-induced male rat hypogonadism model. Twenty-one days after transplantation, we found that blood testosterone levels in the therapy group were higher than that of the control group (P = 0.037, and using immunohistochemistry and flow cytometry, we observed that some of the CM-Dil-labeled cells expressed Leydig cell markers for cytochrome P450, family 11, subfamily A, polypeptide 1, and 3-β-hydroxysteroid dehydrogenase. We then recovered these cells and observed that they were still able to proliferate in vitro. The present study shows that mesenchymal stem cells from human umbilical cord may constitute a promising therapeutic modality for the treatment of male hypogonadism patients.

Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis).

Science.gov (United States)

Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

2013-01-01

A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar environments and reference memory in the solitary Cape mole-rat (Georychus capensis). Our data showed that both wild and captive animals readily explore open spaces and tunnels. Wild animals were however more active than their captive counterparts. In the Y maze two trial discrimination task, wild animals failed to discriminate between novel and familiar environments, while laboratory housed mole-rats showed preferential spatial discrimination in terms of the length of time spent in the novel arm. The performance of the laboratory and wild animals were similar when tested for reference memory in the Y maze, both groups showed a significant improvement compared to the first day, from the 3rd day onwards. Wild animals made more mistakes whereas laboratory animals were slower in completing the task. The difference in performance between wild and laboratory animals in the Y-maze may be as a result of the lower activity of the laboratory animals. Laboratory maintained Cape mole-rats show classic behaviours resulting from a lack of stimulation such as reduced activity and increased aggression. However, they do display an improved novelty discrimination compared to the wild animals. Slower locomotion rate of the laboratory animals may increase the integration time of stimuli, hence result in a more thorough inspection of the surroundings. Unlike the captive animals, wild animals show flexibility in their responses to unpredictable events, which is an important requirement under

Vocalisations of the silvery mole-rat: comparasion of vocal repertoires in subterrane an rodents with different socials systems

Czech Academy of Sciences Publication Activity Database

Knotková, E.; Veitl, S.; Šumbera, R.; Sedláček, František; Burda, H.

2009-01-01

Roč. 18, č. 3 (2009), s. 241-257 ISSN 0952-4622 Institutional research plan: CEZ:AV0Z60870520 Keywords : silvery mole-rat * bathyergidae * vocal communication Subject RIV: EG - Zoology Impact factor: 1.050, year: 2009

Transcriptome sequencing of the blind subterranean mole rat, Spalax galili: Utility and potential for the discovery of novel evolutionary patterns

KAUST Repository

Malik, Assaf

2011-08-12

The blind subterranean mole rat (Spalax ehrenbergi superspecies) is a model animal for survival under extreme environments due to its ability to live in underground habitats under severe hypoxic stress and darkness. Here we report the transcriptome sequencing of Spalax galili, a chromosomal type of S. ehrenbergi. cDNA pools from muscle and brain tissues isolated from animals exposed to hypoxic and normoxic conditions were sequenced using Sanger, GS FLX, and GS FLX Titanium technologies. Assembly of the sequences yielded over 51,000 isotigs with homology to ~12,000 mouse, rat or human genes. Based on these results, it was possible to detect large numbers of splice variants, SNPs, and novel transcribed regions. In addition, multiple differential expression patterns were detected between tissues and treatments. The results presented here will serve as a valuable resource for future studies aimed at identifying genes and gene regions evolved during the adaptive radiation associated with underground life of the blind mole rat. 2011 Malik et al.

Testosterone replacement alters the cell size in visceral fat but not in subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism animal model

Directory of Open Access Journals (Sweden)

Abdelhamed A

2015-03-01

Full Text Available Amr Abdelhamed,1,2 Shin-ichi Hisasue,1 Masato Shirai,3 Kazuhito Matsushita,1 Yoshiaki Wakumoto,1 Akira Tsujimura,1 Taiji Tsukamoto,4 Shigeo Horie1 1Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan; 2Department of Dermatology, Venereology and Andrology, Sohag University, Graduate School of Medicine, Sohag, Egypt; 3Department of Urology, Juntendo University Urayasu Hospital, Urayasu, Japan; 4Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Japan Background: Patients with late-onset hypogonadism (LOH benefit from testosterone replacement by improvement in the parameters of the metabolic syndrome, but fat cell morphology in these patients is still unclear. This study aims to determine the effect of testosterone replacement on the morphology of fat cells in subcutaneous and visceral adipose tissue and on erectile function in hypogonadal aged male rats as a model of LOH. Methods: Ten male Sprague-Dawley rats aged 20–22 months were randomly allocated to two groups, ie, aged male controls (control group, n=5 and aged males treated with testosterone replacement therapy (TRT group, n=5. Testosterone enanthate 25 mg was injected subcutaneously every 2 weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP and mean arterial blood pressure (MAP ratio was assessed. Visceral and subcutaneous adipose tissue specimens were collected and analyzed using Image-J software. Results: Body weight at 2, 4, and 6 weeks after TRT was 800.0±35.4 g, 767.5±46.3 g, and 780±40.4 g, respectively (not statistically significant. The ICP/MAP ratio was 0.341±0.015 in the TRT group and 0.274±0.049 in the control group (not statistically significant. The median subcutaneous fat cell size was 4.85×103 (range 0.85–12.53×103 µm2 in the control group and 4.93×103 (range 6.42–19.7×103 µm2 in the TRT group (not statistically significant. In contrast, median visceral fat cell size was significantly

Exceptional Chromosomal Evolution and Cryptic Speciation of Blind Mole Rats Nannospalax leucodon (Spalacinae, Rodentia from South-Eastern Europe

Directory of Open Access Journals (Sweden)

Ivo Savić

2017-10-01

Full Text Available Mole rats are exclusively subterranean and highly specialized rodents. Their long lifespans, remarkable anti-cancer mechanisms, and various distinctive adaptive features make them a useful research model. Moreover, opposing convergence of morphological traits, they have developed extremely high karyotype variability. Thus, 74 chromosomal forms have been described so far and new ones are being revealed continuously. These evolved during the process of rapid radiation and occur in different biogeographical regions. During research into their reproductive biology we have already provided substantial evidence for species-level separation of these taxa. Here, we review diverse chromosomal forms of the lesser blind mole rat, Mediterranean Nannospalax leucodon, distributed in South-eastern Europe, their karyotype records, biogeography, origin, and phylogeny from our extensive research. In the light of new data from molecular genetic studies, we question some former valuations and propose a cryptospecies rank for seven reproductively isolated chromosomal forms with sympatric and parapatric distribution and clear ecogeographical discrepances in their habitats, as well as new experimental and theoretical methods for understanding the courses of speciation of these unique fossorial mammals.

Molecular and Physiological Factors of Neuroprotection in Hypoxia-tolerant Models: Pharmacological Clues for the Treatment of Stroke

Directory of Open Access Journals (Sweden)

Thomas I. Nathaniel

2015-01-01

Full Text Available The naked mole-rat possesses several unique physiological and molecular features that underlie their remarkably and exceptional resistance to tissue hypoxia. Elevated pattern of Epo, an erythropoietin (Epo factor; c-fos; vascular endothelial growth factor (VEGF; and hypoxia-inducible factors (HIF-1α contribute to the adaptive strategy to cope with hypoxic stress. Moreover, the naked mole-rat has a lower metabolic rate than any other eutherian mammal of comparable size that has been studied. The ability to actively reduce metabolic rate represents a strategy widely used in the face of decreased tissue oxygen availability. Understanding the different molecular and physiological factors that induce metabolic suppression could guide the development of pharmacological agents for the clinical management of stroke patient.

ACTIVITY PATTERNS IN THE MOLE-RATS TACHYORYCTES ...

African Journals Online (AJOL)

Heilophoblus spends over 50 % of the day out of its nest, Tachyoryctes, ..... Surface foraging through an open hole and mole-hill formation could be directly ..... Heliophobius fed at irregular intervals throughout the day and night (Jarvis, ...

Obesity-related hypogonadism: a reversible condition.

Science.gov (United States)

Zouras, Stamatios; Stephens, Jeffrey W; Price, David

2017-06-23

Obesity is associated with hypogonadism. While this association is widely accepted, the underlying mechanisms remain unclear. Furthermore, obesity is a risk factor for hypogonadism and conversely hypogonadism may be a risk factor for obesity. We present the case of a morbidly obese man aged 30 years with hypogonadotrophic hypogonadism that underwent a Roux-en-Y gastric bypass operation. Following the surgical treatment of his obesity, the testosterone level returned to normal with improvements in hypogonadal symptoms, which allowed discontinuation of exogenous testosterone therapy. This case report demonstrates reversal of hypogonadism following weight loss with restoration of gonadal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Male hypogonadism (Part 1)

OpenAIRE

Ye.V. Luchytskyy; V.Yе. Luchytskyy; M.D. Tronko

2017-01-01

The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

Stemcell Information: SKIP000887 [SKIP Stemcell Database[Archive

Lifescience Database Archive (English)

Full Text Available NICATIONS 2015 7 11471 ... http://www.ncbi.nlm.nih.gov/pubmed/27161380 ... ...Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Shingo Miyawaki, Hideyuki Okano et al. NATURE COMMU

Hypogonadism and renal failure: An update.

Science.gov (United States)

Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

2015-01-01

The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

Male hypogonadism (Part 1

Directory of Open Access Journals (Sweden)

Ye.V. Luchytskyy

2017-05-01

Full Text Available The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

Parentage analysis of Ansell’s mole-rat family groups indicates a high reproductive skew despite relatively relaxed ecological constraints on dispersal

Czech Academy of Sciences Publication Activity Database

Patzenhauerová, Hana; Šklíba, J.; Bryja, Josef; Šumbera, R.

2013-01-01

Roč. 22, č. 19 (2013), s. 4988-5000 ISSN 0962-1083 R&D Projects: GA AV ČR IAA601410802; GA ČR GAP506/10/0983 Institutional support: RVO:68081766 Keywords : African mole-rat * dispersal * eusociality * Fukomys * mating system * reproductive skew Subject RIV: EH - Ecology, Behaviour Impact factor: 5.840, year: 2013

Male hypogonadism: Symptoms and treatment

OpenAIRE

Peeyush Kumar; Nitish Kumar; Devendra Singh Thakur; Ajay Patidar

2010-01-01

Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty. There is a clear need to increase the awareness of hypogonadism throughout the medical profession, especially in primary care physicians who are usually the first port of call for the patient. Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separatio...

Anabolic steroid induced hypogonadism in young men.

Science.gov (United States)

Coward, Robert M; Rajanahally, Saneal; Kovac, Jason R; Smith, Ryan P; Pastuszak, Alexander W; Lipshultz, Larry I

2013-12-01

The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, panabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Late-onset hypogonadism: beyond testosterone

Directory of Open Access Journals (Sweden)

Carlo Foresta

2015-04-01

Full Text Available Late-onset hypogonadism is defined as a combination of low testosterone (T levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dysfunction. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH and 25-hydroxyvitamin D levels. These markers help in identifying the so-called "subclinical" hypogonadism (normal T, high LH levels. Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l−1 , LH ≥ 8 IU l−1 (n = 26 and subclinical hypogonadism (TT ≥ 12 nmol l−1 , LH ≥ 8 IU l−1 (n = 40 and low 25-hydroxyvitamin D (<50 nmol l−1 . Subjects received cholecalciferol (5000 IU per week (n = 20 or calcidiol (4000 IU per week (n = 46, and 25-hydroxyvitamin D and parathyroid hormone (PTH were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30, whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol, and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.

Variability of space-use patterns in a free living eusocial rodent, Ansell’s mole-rat indicates age-based rather than caste polyethism

Czech Academy of Sciences Publication Activity Database

Šklíba, Jan; Lövy, M.; Burda, H.; Šumbera, R.

2016-01-01

Roč. 6, DEC 06 (2016), č. článku 37497. ISSN 2045-2322 EU Projects: European Commission(XE) 669609 - Diversity6continents Institutional support: RVO:60077344 Keywords : eusocial rodent * mole-rats * Fukomys anselli Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 4.259, year: 2016 https://www.nature.com/articles/srep37497

Male hypogonadism: Symptoms and treatment

Directory of Open Access Journals (Sweden)

Peeyush Kumar

2010-01-01

Full Text Available Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty. There is a clear need to increase the awareness of hypogonadism throughout the medical profession, especially in primary care physicians who are usually the first port of call for the patient. Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separation of couples, leading to divorce. It is also important for doctors to recognize that testosterone is not just a sex hormone. There is an important research being published to demonstrate that testosterone may have key actions on metabolism, on the vasculature, and on brain function, in addition to its well-known effects on bone and body composition. This article has been used as an introduction for the need to develop sensitive and reliable assays for sex hormones and for symptoms and treatment of hypogonadism.

Characteristics of compensated hypogonadism in patients with sexual dysfunction.

Science.gov (United States)

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-07-01

In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. The present data do not support the concept that compensated (subclinical) hypogonadism

Reproduction is associated with a tissue-dependent reduction of oxidative stress in eusocial female Damaraland mole-rats (Fukomys damarensis.

Directory of Open Access Journals (Sweden)

Christina M Schmidt

Full Text Available Oxidative stress has been implicated as both a physiological cost of reproduction and a driving force on an animal's lifespan. Since increased reproductive effort is generally linked with a reduction in survival, it has been proposed that oxidative stress may influence this relationship. Support for this hypothesis is inconsistent, but this may, in part, be due to the type of tissues that have been analyzed. In Damaraland mole-rats the sole reproducing female in the colony is also the longest lived. Therefore, if oxidative stress does impact the trade-off between reproduction and survival in general, this species may possess some form of enhanced defense. We assessed this relationship by comparing markers of oxidative damage (malondialdehyde, MDA; protein carbonyls, PC and antioxidants (total antioxidant capacity, TAC; superoxide dismutase, SOD in various tissues including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between wild-caught reproductive and non-reproductive female Damaraland mole-rats. Reproductive females exhibited significantly lower levels of PC across all tissues, and lower levels of MDA in heart, kidney and liver relative to non-reproductive females. Levels of TAC and SOD did not differ significantly according to reproductive state. The reduction in oxidative damage in breeding females may be attributable to the unusual social structure of this species, as similar relationships have been observed between reproductive and non-reproductive eusocial insects.

In vivo expression of ß-galactosidase by rat oviduct exposed to naked DNA or messenger RNA

Directory of Open Access Journals (Sweden)

MARIANA RIOS

2002-01-01

Full Text Available Intra-oviductal administration of RNA obtained from oviducts of estradiol-treated rats resulted in accelerated egg transport (Ríos et al., 1997. It is probable that estradiol-induced messenger RNA (mRNA entered oviductal cells and was translated into the proteins involved in accelerated egg transport. In order to test this interpretation we deposited in vivo 50 µg of pure ß-galactosidase (ß-gal mRNA, 50 µg of pure DNA from the reporter gene ß-gal under SV40 promoter or the vehicle (control oviducts into the oviductal lumen of rats. Twenty four hours later the ß-gal activity was assayed in oviductal tissue homogenates using o-nitrophenyl-ß-D-galactopyranoside as a substrate. The administration of ß-gal mRNA and pSVBgal plasmid increased ß-gal activity by 71% and 142%, respectively, over the control oviducts. These results indicate that naked DNA and mRNA coding for ß-gal can enter oviductal cells and be translated into an active enzyme. They are consistent with the interpretation that embryo transport acceleration caused by the injection of estradiol-induced RNA in the oviduct involves translation of the injected mRNA

Evaluation and treatment of male hypogonadism in primary care.

Science.gov (United States)

Pickett, Kim Anne

2016-08-18

Male hypogonadism is increasing in prevalence, particularly in the older male population. Signs and symptoms associated with hypogonadism are often nonspecific and may be difficult to categorize. This article discusses parameters for screening patients at risk, reviews how to establish the diagnosis of primary or secondary male hypogonadism, and offers important considerations for treatment of patients with hypogonadism.

Male hypogonadism at a tertiary care hospital in Karachi, Pakistan.

Science.gov (United States)

Ram, Nanik; Asghar, Ali; Hashmi, Fauzan; Islam, Najmul

2012-01-01

Male hypogonadism is defined as 'inadequate gonadal function, manifested by deficiency in gametogenesis and/or secretion of gonadal hormones'. Signs and symptoms of hypogonadism depend primarily on the age of onset. It can be classified according to the site primarily involved: the gonads, the hypothalamus, or the pituitary gland. The objective this study was to determine the presentation and aetiology of male hypogonadism seen in a tertiary care hospital. This cross-sectional study was conducted at Endocrine Clinics, Aga Khan University Hospital Karachi. Data of male patients with hypogonadism who attended clinics during January 2009 to August 2011 were reviewed. All male patients with clinical and biochemical evidence of hypogonadism were included in the study. Patients with Diabetes Mellitus, Metabolic Syndrome, Andropause, AIDS, Chronic Renal Failure, and Cirrhosis were excluded. Mean +/- SD were computed for quantitative variables. Frequency and percentages were computed for qualitative variables. Aetiology of male hypogonadism was categorised as primary and secondary hypogonadism. A total of 85 patients with male hypogonadism attended the endocrine clinic. Mean age of patients was 25 +/- 10 years. Clinical presentations were small genitalia (65%), absent secondary sexual characteristics (53%), not attained puberty (47%), infertility (53%), erectile dysfunction (41%) and loss of libido (29%). Seventy-three (86%) patients had hypogonadotrophic hypogonadism (secondary hypogonadism) and 12 (14%) patients had hypergonadotrophic hypogonadism (primary hypogonadism). Among the patients with hypogonadotrophic hypogonadism 38 had idiopathic hypogonadotrophic hypogonadsim, 7 had pituitary adenoma, 6 had empty sella syndrome, 3 had Kallman's syndrome, and 1 patient had haemosiderosis due to thalassaemia major; 18 patients did not undergo brain imaging. Small genitalia, absent secondary sexual characteristics and infertility were the main presenting features of hypogonad

Obesity and Hypogonadism.

Science.gov (United States)

Lamm, Steven; Chidakel, Aaron; Bansal, Rohan

2016-05-01

The relationship between obesity and hypogonadism is complicated. The relationship is bidirectional and there are numerous causative and correlative factors on both sides of the equation. Obesity is increasing in prevalence in epidemic proportions. Likewise, we are beginning to see the rapid increase in the incidence of male hypogonadism. It is only recently that we are learning the ways in which these 2 conditions exacerbate each other, and we are only beginning to understand how by treating one of these conditions, we can help to treat the other as well. Copyright © 2016 Elsevier Inc. All rights reserved.

An update on male hypogonadism therapy.

Science.gov (United States)

Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

2014-06-01

Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

Adaptation of pelage color and pigment variations in Israeli subterranean blind mole rats, Spalax ehrenbergi [corrected].

Directory of Open Access Journals (Sweden)

Natarajan Singaravelan

Full Text Available Concealing coloration in rodents is well established. However, only a few studies examined how soil color, pelage color, hair-melanin content, and genetics (i.e., the causal chain synergize to configure it. This study investigates the causal chain of dorsal coloration in Israeli subterranean blind mole rats, Spalax ehrenbergi.We examined pelage coloration of 128 adult animals from 11 populations belonging to four species of Spalax ehrenbergi superspecies (Spalax galili, Spalax golani, Spalax carmeli, and Spalax judaei and the corresponding coloration of soil samples from the collection sites using a digital colorimeter. Additionally, we quantified hair-melanin contents of 67 animals using HPLC and sequenced the MC1R gene in 68 individuals from all four mole rat species.Due to high variability of soil colors, the correlation between soil and pelage color coordinates was weak and significant only between soil hue and pelage lightness. Multiple stepwise forward regression revealed that soil lightness was significantly associated with all pelage color variables. Pelage color lightness among the four species increased with the higher southward aridity in accordance to Gloger's rule (darker in humid habitats and lighter in arid habitats. Darker and lighter pelage colors are associated with darker basalt and terra rossa, and lighter rendzina soils, respectively. Despite soil lightness varying significantly, pelage lightness and eumelanin converged among populations living in similar soil types. Partial sequencing of the MC1R gene identified three allelic variants, two of which were predominant in northern species (S. galili and S. golani, and the third was exclusive to southern species (S. carmeli and S. judaei, which might have caused the differences found in pheomelanin/eumelanin ratio.Darker dorsal pelage in darker basalt and terra rossa soils in the north and lighter pelage in rendzina and loess soils in the south reflect the combined results of

Male Hypogonadism

Science.gov (United States)

... the hormone that plays a key role in masculine growth and development during puberty — or has an ... Adulthood In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs ...

Serum vitamin D levels and hypogonadism in men.

Science.gov (United States)

Lerchbaum, E; Pilz, S; Trummer, C; Rabe, T; Schenk, M; Heijboer, A C; Obermayer-Pietsch, B

2014-09-01

There is inconsistent evidence on a possible association of vitamin D and androgen levels in men. We therefore aim to investigate the association of 25-hydroxyvitamin D (25(OH)D) with androgen levels in a cohort of middle-aged men. This cross-sectional study included 225 men with a median (interquartile range) age of 35 (30-41) years. We measured 25(OH)D, total testosterone (TT) and SHBG concentrations. Hypogonadism was defined as TT hypogonadism was 21.5% and lowest in men within 25(OH)D quintile 4 (82-102 nmol/L). We found a significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference) in crude (OR 5.10, 1.51-17.24, p = 0.009) as well as in multivariate adjusted analysis (OR 9.21, 2.27-37.35, p = 0.002). We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L. © 2014 American Society of Andrology and European Academy of Andrology.

Moles and Mole Control on British Farms, Amenities and Gardens after Strychnine Withdrawal

Directory of Open Access Journals (Sweden)

Sandra E. Baker

2016-06-01

Full Text Available Moles are considered pests in Britain, but this issue has been little studied. Lower welfare standards have been tolerated for moles than for most other managed wild mammal species, as use of both the controversial poison, strychnine, and unregulated traps have been permitted. Strychnine was withdrawn in 2006 and there were fears that mole populations would increase as a result. In 2007, we conducted a comprehensive, nationwide survey of land manager perceptions, opinions and behaviour regarding moles and mole control on farms, amenities and domestic gardens in Britain. We surveyed 2150 land managers (achieving a 59% response rate and ground-truthed 29 responses. Moles were reported to be present on most farms and amenities, and 13% of gardens, and were more common in lighter soils. Where present, moles were usually considered pests, this being more likely in Wales, Scotland and northern England, on livestock and mixed farms, and on large, high-value amenities, e.g., racecourses and golf courses. Mole control followed similar patterns to mole presence. More control may occur than is economically, and therefore potentially ethically, justified. Control should be more carefully considered and, where necessary, more effectively targeted. Kill-trapping was the favoured recent and future method on farms and amenities, even if strychnine was to be reintroduced; however, because mole traps are currently unregulated, some might not meet current welfare standards if tested. We found no evidence for an increase in moles since a farm questionnaire survey conducted in 1992; this could have wider implications for future wildlife management policy changes.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Clipboard: Of pungency, pain, and naked mole rats: chili peppers revisited · Renee M Borges · More Details Fulltext PDF. Volume 34 Issue 4 October 2009 pp 605-611 Articles. Phenotypic plasticity and longevity in plants and animals: cause and effect? Renee M Borges · More Details Abstract Fulltext PDF. Immobile plants ...

Spatial and temporal activity patterns of the free-living giant mole-rat (Fukomys mechowii, the largest social bathyergid.

Directory of Open Access Journals (Sweden)

Matěj Lövy

Full Text Available Despite the considerable attention devoted to the biology of social species of African mole-rats (Bathyergidae, Rodentia, knowledge is lacking about their behaviour under natural conditions. We studied activity of the largest social bathyergid, the giant mole-rat Fukomys mechowii, in its natural habitat in Zambia using radio-telemetry. We radio-tracked six individuals during three continuous 72-h sessions. Five of these individuals, including a breeding male, belonged to a single family group; the remaining female was probably a solitary disperser. The non-breeders of the family were active (i.e. outside the nest 5.8 hours per 24h-day with the activity split into 6.5 short bouts. The activity was more concentrated in the night hours, when the animals also travelled longer distances from the nest. The breeding male spent only 3.2 hours per day outside the nest, utilizing less than 20% of the whole family home range. The dispersing female displayed a much different activity pattern than the family members. Her 8.0 hours of outside-nest activity per day were split into 4.6 bouts which were twice as long as in the family non-breeders. Her activity peak in the late afternoon coincided with the temperature maximum in the depth of 10 cm (roughly the depth of the foraging tunnels. Our results suggest that the breeding individuals (at least males contribute very little to the work of the family group. Nevertheless, the amount of an individual's activity and its daily pattern are probably flexible in this species and can be modified in response to actual environmental and social conditions.

Content Validity of the Hypogonadism Impact of Symptoms Questionnaire (HIS-Q): A Patient-Reported Outcome Measure to Evaluate Symptoms of Hypogonadism.

Science.gov (United States)

Gelhorn, Heather L; Vernon, Margaret K; Stewart, Katie D; Miller, Michael G; Brod, Meryl; Althof, Stanley E; DeRogatis, Leonard R; Dobs, Adrian; Seftel, Allen D; Revicki, Dennis A

2016-04-01

Hypogonadism, or low testosterone, is a common disorder. There are currently no patient-reported outcome (PRO) instruments designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment. The purpose of this study was to develop a PRO instrument, the Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) and to assess its content validity. A literature review, expert clinician input, and qualitative concept elicitation with 39 male hypogonadism patients (four focus groups: n = 25; individual interviews: n = 14; mean age 52.3 ± 14.3 years) from the USA were used to develop the draft HIS-Q. Subsequent cognitive interviews (n = 29; mean age 51.5 ± 15.4 years) were used to evaluate content validity. Emergent discussion with participants yielded symptoms within the sexual, physical, energy, sleep, cognition, and mood domains. Low libido and tiredness were most commonly reported. The initial version of the HIS-Q includes 53 items that were consistently understood by the participants, who found the instrument to be relevant to their experiences with hypogonadism and comprehensive in the content coverage of symptoms. The HIS-Q is a comprehensive PRO measure of hypogonadism symptom severity in males. Its design elements, including the response options and recall period, were suitable, and content validity was confirmed.

Visceral fat dysfunction is positively associated with hypogonadism in Chinese men.

Science.gov (United States)

Wang, Ningjian; Zhai, Hualing; Han, Bing; Li, Qin; Chen, Yi; Chen, Yingchao; Xia, Fangzhen; Lin, Dongping; Lu, Yingli

2016-01-22

Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone male: (waist circumference/(39.68 + (1.88 × BMI)) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P hypogonadism (P for trend hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index).

Are naked singularities really visible

Energy Technology Data Exchange (ETDEWEB)

Calvani, M [Padua Univ. (Italy). Ist. di Astronomia; De Felice, F [Alberta Univ., Edmonton (Canada); Nobili, L [Padua Univ. (Italy). Ist. di Fisica

1978-12-09

The question whether a Kerr naked singularity is actually visible from infinity is investigated; it is shown that in fact any signal which could be emitted from the singularity is infinitely red-shifted. This implies that naked singularities would be indistinguishable from a black hole.

Oxidative stress status in congenital hypogonadism: an appraisal.

Science.gov (United States)

Haymana, C; Aydoğdu, A; Soykut, B; Erdem, O; Ibrahimov, T; Dinc, M; Meric, C; Basaran, Y; Sonmez, A; Azal, O

2017-07-01

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases. However, the pathogenesis of increased cardiometabolic risk in patients with hypogonadism is not clear. Oxidative stress plays an important role in the pathogenesis of cardiometabolic diseases. This study aimed to investigate possible differences in oxidative stress conditions between patients with hypogonadism and healthy controls. In this study, 38 male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age: 21.7 ± 1.6 years) and 44 healthy male controls (mean age: 22.3 ± 1.4 years) with almost equal body mass index were enrolled. The demographic parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, homeostatic model assessment of insulin resistance (HOMA-IR) and oxidative stress parameters, such as superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA), were compared between both groups. Compared to the healthy controls, triglycerides (p = .02), insulin levels, HOMA-IR values, CAT activities and MDA levels (p treatment-naïve patients with congenital hypogonadism had an increased status of oxidative stress.

Region-specific associations between sex, social status, and oxytocin receptor density in the brains of eusocial rodents.

Science.gov (United States)

Mooney, S J; Coen, C W; Holmes, M M; Beery, A K

2015-09-10

Naturally occurring variations in neuropeptide receptor distributions in the brain contribute to numerous mammalian social behaviors. In naked mole-rats, which live in large social groups and exhibit remarkable reproductive skew, colony-related social behaviors vary with reproductive status. Here we examined whether variation in social status is associated with variations in the location and/or density of oxytocin binding in this species. Autoradiography was performed to assess forebrain oxytocin receptor (OTR) densities in breeding and non-breeding naked mole-rats of both sexes. Overall, males exhibited higher OTR binding in the medial amygdala in comparison to females. While there were no main effects of reproductive status in any region, a sex difference in OTR binding in the nucleus accumbens was mediated by status. Specifically, breeding males tended to have more OTR binding than breeding females in the nucleus accumbens, while no sex difference was observed in subordinates. These effects suggest that oxytocin may act in a sex- and region-specific way that corresponds to reproductive status and associated social behaviors. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

Science.gov (United States)

Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

2014-02-07

Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

Vitamin D deficiency in type 2 diabetic patients with hypogonadism.

Science.gov (United States)

Bellastella, Giuseppe; Maiorino, Maria Ida; Olita, Laura; Capuano, Annalisa; Rafaniello, Concetta; Giugliano, Dario; Esposito, Katherine

2014-02-01

Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study. © 2013 International Society for Sexual Medicine.

Trend of Complete Hydatidiform Mole

Directory of Open Access Journals (Sweden)

K Thapa

2010-03-01

Full Text Available INTRODUCTION: Complete Hydatidiform mole is one of the most frequent abnormal pregnancies. This review studies the trend of complete mole in Paropakar Maternity and Women's hospital and clinical ability to detect it. METHODS: This is a retrospective study of 504 cases of complete hydatidiform mole recorded at Paropakar maternity and women's hospital, Kathmandu, during 2058-2065 B.S. Medical records were reviewed and incidence, clinical presentation and method of diagnosis were studied. RESULTS: During the study period, there were 13,9117 births and 504 complete moles, 12 partial moles, 48 persistent gestational tumours, six choriocarcinoma and four invasive moles recorded in the hospital. The incidence of complete mole was one per 276 births. It was prevalent among women younger than 29 years (80% and among the primigravidae (36.7%. More than 90% women presented in the first half of their pregnancy and vaginal bleeding was the main complaint (68.3%. Suction evacuation, dilation and evacuation followed by sharp curettage and abdominal hysterectomy were performed in 80.6%, 17.6% and 1.2% of the women respectively. Persistent mole and choriocarcinoma developed in 9.5% and 0.4% respectively. CONCLUSIONS: Complete mole has the highest incidence. It affects mostly younger women and presents with vaginal bleeding most of the time, usually in the first half of their pregnancy. Keywords: complete hydatidiform mole, gestational trophoblastic disease, persistent gestational tumours.

Characterization of gonadotrophin-releasing hormone precursor cDNA in the Old World mole-rat Cryptomys hottentotus pretoriae: high degree of identity with the New World guinea pig sequence.

Science.gov (United States)

Kalamatianos, T; du Toit, L; Hrabovszky, E; Kalló, I; Marsh, P J; Bennett, N C; Coen, C W

2005-05-01

Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as 'mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the 'mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the 'mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic 'mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63-45 million years ago.

Approaches to male hypogonadism in primary care

OpenAIRE

Lawrence, Kristi L.; Stewart, Felicia; Larson, Brandi M.

2017-01-01

Abstract: Evidence suggests that providers are not adhering to current testosterone replacement therapy guidelines when treating male hypogonadism. Understanding the diagnosis and management of this condition is further complicated by conflicting recommendations among available guidelines. NPs must select and follow the best guideline recommendations available to optimally treat male hypogonadism.

Naked singularity, firewall, and Hawking radiation.

Science.gov (United States)

Zhang, Hongsheng

2017-06-21

Spacetime singularity has always been of interest since the proof of the Penrose-Hawking singularity theorem. Naked singularity naturally emerges from reasonable initial conditions in the collapsing process. A recent interesting approach in black hole information problem implies that we need a firewall to break the surplus entanglements among the Hawking photons. Classically, the firewall becomes a naked singularity. We find some vacuum analytical solutions in R n -gravity of the firewall-type and use these solutions as concrete models to study the naked singularities. By using standard quantum theory, we investigate the Hawking radiation emitted from the black holes with naked singularities. Here we show that the singularity itself does not destroy information. A unitary quantum theory works well around a firewall-type singularity. We discuss the validity of our result in general relativity. Further our result demonstrates that the temperature of the Hawking radiation still can be expressed in the form of the surface gravity divided by 2π. This indicates that a naked singularity may not compromise the Hakwing evaporation process.

Quantum dress for a naked singularity

Directory of Open Access Journals (Sweden)

Marc Casals

2016-09-01

Full Text Available We investigate semiclassical backreaction on a conical naked singularity space–time with a negative cosmological constant in (2+1-dimensions. In particular, we calculate the renormalized quantum stress–energy tensor for a conformally coupled scalar field on such naked singularity space–time. We then obtain the backreacted metric via the semiclassical Einstein equations. We show that, in the regime where the semiclassical approximation can be trusted, backreaction dresses the naked singularity with an event horizon, thus enforcing (weak cosmic censorship.

Plasma kisspeptin levels in male cases with hypogonadism.

Science.gov (United States)

Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

2014-01-01

The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

Clinicopathologic assessment of hypogonadism in men with type 2 diabetes mellitus

Science.gov (United States)

Ugwu, Theophilus E.; Ikem, Rosemary T.; Kolawole, Babatope A.; Ezeani, Ignatius U.

2016-01-01

Objective: To determine the prevalence of hypogonadism in men with type 2 diabetes mellitus and evaluate its clinical and pathologic correlates. Subjects and Methods: In a cross-sectional survey of 200 type 2 diabetic males aged 32–69 years, total testosterone (TT), follicle stimulating hormone, luteinizing hormone, waist circumference (WC), glycated hemoglobin, and lipids were measured. Clinical assessment of androgen deficiency was done using the androgen deficiency in aging male (ADAM) questionnaire. Overt hypogonadism was defined as a combination of positive ADAM score and TT hypogonadism was defined as positive ADAM score with TT 8–12 nmol/L. Results: Overt and possible hypogonadism occurred in 29.5% and 23% of the participants, respectively. Majority (76.3%) of the subjects who had overt hypogonadism had the hypogonadotrophic pattern. Hypogonadal subjects were significantly older (P = 0.014) and had higher mean WC (P = 0.009) than eugonadal ones. Erectile dysfunction was the most common symptom, occurring in 79.7% of overtly hypogonadal subjects. There was a significant negative correlation between WC and serum TT (r = −0.41, P = 0.001). Conclusion: There is a high frequency of symptomatic hypogonadism in men with type 2 diabetes and the frequency increases with advancing age and visceral adiposity. PMID:27730078

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

Science.gov (United States)

Iglesias, P; Prado, F; Macías, M C; Guerrero, M T; Muñoz, A; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2014-02-01

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Intrathecal injection of naked plasmid DNA provides long-term expression of secreted proteins.

Science.gov (United States)

Hughes, Travis S; Langer, Stephen J; Johnson, Kirk W; Chavez, Raymond A; Watkins, Linda R; Milligan, Erin D; Leinwand, Leslie A

2009-01-01

Therapeutic benefit has been reported to result from intrathecal (i.t.) injection of transgene vectors, including naked DNA. However, most studies using naked DNA have measured only the transgene expression of intracellular proteins. Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products were repeatedly measured in the cerebrospinal fluid (CSF). Both SEAP and hIL-10 were maximal at 1 and 2 days after the injection and still detectable at 4 months. The utilization of a plasmid having two features that are hypothesized to increase gene expression (matrix attachment regions (MARs) and lack of CpG dinucleotides) resulted in a significant increase in gene expression. Reinjection of SEAP or hIL-10 plasmids after 4 months significantly increased protein levels at 1 and 14 days after the reinjection. SEAP was uniformly distributed between the DNA delivery site (approximately vertebral level T13) and the lumbar puncture site (L5/L6 inter-vertebral space), was reduced at the cisterna magna, and was detectable, though at much lower levels, in serum. These data suggest that naked DNA has the potential to be used as a therapeutic tool for applications that require long-term release of transgenes into the CSF.

Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men

Directory of Open Access Journals (Sweden)

Pranav Dadhich

2017-01-01

Conclusions: Both TST and CC are effective medications in treating hypogonadism; however, our study indicates that TST is more effective in raising serum testosterone levels and improving hypogonadal symptoms. CC remains a viable treatment modality for hypogonadal men but its adverse effect on libido warrant further study.

Reproductive features of the eastern mole (Scalopus aquaticus) and star-nose mole (Condylura cristata).

Science.gov (United States)

Bedford, J M; Mock, O B; Nagdas, S K; Winfrey, V P; Olson, G E

1999-11-01

Since moles are closely related to shrews, the gametes and reproductive tracts of the star-nose mole (Condylura cristata) and the eastern mole (Scalopus aquaticus) were examined to gain further insight into unusual reproductive traits of the Soricidae. Moles display many of these soricid traits, but with some important differences. The cumulus oophorus of Scalopus, ovulated about 16 h after hCG injection, was largely dispersed by hyaluronidase and, though quite dense, was nevertheless more similar to that of higher mammals than to the compact 'ball of the soricid cumulus. Within the female tract in these moles, approximately 85% of the length of the oviduct comprises a narrow ampulla with numerous differentiated crypts that, in shrews, house spermatozoa. However, in contrast to shrews, moles produce considerably larger numbers of spermatozoa, which challenges the proposal that, in shrews, oviductal sperm crypts specifically permit lower sperm production by the males. In the sperm head of these two moles, the acrosome displays the long rostrum that is typical of other Insectivora, and the perforatorium has the barbs by which soricid spermatozoa probably bind to the zona pellucida. Perhaps allied to this, immunoblots indicated that the immunoreactive acrosomal matrix of Scalopus spermatozoa is simpler than the polypeptide complex of the bovine and hamster acrosomal matrix.

INFERTILITY IN MEN WITH PRIMARY HYPOGONADOTROPIC HYPOGONADISM

Directory of Open Access Journals (Sweden)

O. B. Zhukov

2017-01-01

Full Text Available In this study, an analysis data on the etiology, pathogenesis, diagnosis and treatment of male sterility with hypogonadotropic hypogonadism. Examination of the patients requires attention of urologist, andrologist, endocrinologist, neurosurgeon, medical geneticist. Clinical case, described by us, shows the necessity of development of a unified algorithm for working with these patients and search for effective and safe treatment of patients with hypergonadotropic hypogonadism. 

Mole gun injury.

Science.gov (United States)

Pistré, V; Rezzouk, J

2013-09-01

A mole gun is a weapon, which is used to trap and kill moles. This report provides an overview of the state of knowledge of mole gun injuries, comparable to blast injuries caused by fireworks, explosive or gunshot. Over a 2-year period, the authors reported their experience with ten hand injuries caused by mole gun. Radial side of the hand was often concerned, particularly the thumb. The authors explain their choices in the management of such lesions. Surgery was performed primarily and a large debridement currently seemed to offer the best outcome for the patient. Blast, crush, burns and lacerations may explain the higher rate of amputation to the digits. A long period of physiotherapy, specifically of the hand, was needed before the patient could return to work. This ballistic hand trauma encountered by surgeons requires knowledge and understanding of these injuries. It should be in accordance with firearms law because of severe injuries encountered and possible lethal wounds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The prevalence of Hypogonadism among diabetic and non-diabetic men in Jordan.

Science.gov (United States)

Al Hayek, Ayman A; Khawaja, Nahla M; Khader, Yousef S; Jaffal, Sahar K; Ajlouni, Kamel M

2014-01-01

Determine the prevalence of hypogonadism among diabetic and non-diabetic men in Jordan. A cross-sectional study of 1717 men (1089 participants with type 2 diabetes and 628 non-diabetic subjects). Both groups were inquired to answer the Androgen Deficiency for aging male (ADAM) questionnaire. Early morning Total testosterone, prolactin, sex hormone binding globulin, follicle stimulating hormone, leutinizing hormone, HbA1c and fasting blood sugar were measured. Hypogonadism was defined as total testosterone Hypogonadism among all study participants was 18.5%. The prevalence of Hypogonadism in diabetic and non-diabetic men was 24.3% and 8.3%, respectively. The mean (SD) total testosterone concentration of diabetic and non-diabetic men was 3.78 ng/ml (1.7) and 4.92 ng/ml (2.5), respectively (P- value Hypogonadism and symptomatic androgen deficiency were negatively and significantly related to diabetes, monthly income and age (P value Hypogonadism is a prevalent disorder among Jordanian diabetic population. Symptoms of androgen deficiency should be corroborated with testosterone level to establish a multidisciplinary approach for management of hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

Timelike naked singularity

International Nuclear Information System (INIS)

Goswami, Rituparno; Joshi, Pankaj S.; Vaz, Cenalo; Witten, Louis

2004-01-01

We construct a class of spherically symmetric collapse models in which a naked singularity may develop as the end state of collapse. The matter distribution considered has negative radial and tangential pressures, but the weak energy condition is obeyed throughout. The singularity forms at the center of the collapsing cloud and continues to be visible for a finite time. The duration of visibility depends on the nature of energy distribution. Hence the causal structure of the resulting singularity depends on the nature of the mass function chosen for the cloud. We present a general model in which the naked singularity formed is timelike, neither pointlike nor null. Our work represents a step toward clarifying the necessary conditions for the validity of the Cosmic Censorship Conjecture

A Trickster in Disguise: Hyaluronan’s Ambivalent Roles in the Matrix

Directory of Open Access Journals (Sweden)

Lena Bohaumilitzky

2017-10-01

Full Text Available Hyaluronan (HA is a simple but diverse glycosaminoglycan. It plays a major role in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA affects the surrounding tissues greatly depends on the molecular weight of HA. Whereas high molecular weight HA is associated with homeostasis and protective effects, HA fragments tend to be linked to the pathologic state. Furthermore, the interaction of HA with its binding partners, the hyaladherins, such as CD44, is essential for sustaining tissue integrity and is likewise related to cancer. The naked mole rat, a rodent species, possesses a special form of very high molecular weight (vHMW HA, which is associated with the extraordinary cancer resistance and longevity of those animals. This review addresses HA and its diverse facets: from HA synthesis to degradation, from oligomeric HA to vHMW-HA and from its beneficial properties to the involvement in pathologies. We further discuss the functions of HA in the naked mole rat and compare them to human conditions. Though intensively researched, this simple polymer bears some secrets that may hold the key for a better understanding of cellular processes and the development of diseases, such as cancer.

Sex- and brain region-specific patterns of gene expression associated with socially-mediated puberty in a eusocial mammal.

Directory of Open Access Journals (Sweden)

Mariela Faykoo-Martinez

Full Text Available The social environment can alter pubertal timing through neuroendocrine mechanisms that are not fully understood; it is thought that stress hormones (e.g., glucocorticoids or corticotropin-releasing hormone influence the hypothalamic-pituitary-gonadal axis to inhibit puberty. Here, we use the eusocial naked mole-rat, a unique species in which social interactions in a colony (i.e. dominance of a breeding female suppress puberty in subordinate animals. Removing subordinate naked mole-rats from this social context initiates puberty, allowing for experimental control of pubertal timing. The present study quantified gene expression for reproduction- and stress-relevant genes acting upstream of gonadotropin-releasing hormone in brain regions with reproductive and social functions in pre-pubertal, post-pubertal, and opposite sex-paired animals (which are in various stages of pubertal transition. Results indicate sex differences in patterns of neural gene expression. Known functions of genes in brain suggest stress as a key contributing factor in regulating male pubertal delay. Network analysis implicates neurokinin B (Tac3 in the arcuate nucleus of the hypothalamus as a key node in this pathway. Results also suggest an unappreciated role for the nucleus accumbens in regulating puberty.

Preserving fertility in the hypogonadal patient: an update

Directory of Open Access Journals (Sweden)

Ranjith Ramasamy

2015-04-01

Full Text Available An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.

Obesity, metabolic syndrome, male hypogonadism and cardiovascular risk

Directory of Open Access Journals (Sweden)

Giovanni Corona

2013-04-01

Full Text Available Background: A large body of evidences indicates that sexual dysfunction, and in particular erectile dysfunction (ED, may represent an early surrogate marker of different disease states such as diabetes mellitus, hypertension, metabolic syndrome (MetS and depression. Furthermore, it has been suggested that ED could also be considered the first sign of a forthcoming coronary heart disease (CHD and an efficient predictor of silent CHD in a diabetic population, independently of glycometabolic control and ED severity. Hypogonadism is frequently associated with MetS both in subjects with or without ED, insulin resistance being the putative pathogenetic link. In subjects with ED hypogonadism can exacerbate sexual dysfunction because of its typical symptoms, such as decreased sexual desire and mood disturbances. However, hypogonadism per se has been associated with an increased risk of cardiovascular and overall mortality. Aim of the study: In this review, a comprehensive literature search was carried out, in order to discuss the relationship between insulin resistance, ED, MetS and hypogonadism, focusing on their possible involvement in the development of cardiovascular diseases.

Cellular Basis for Learning Impairment in Fragile X Syndrome

Science.gov (United States)

2014-08-01

advances in therapy for neurological conditions such as stroke and epilepsy. KEY WORDS: Arctic ground squirrel, Cetacean, Hypoxia, Naked mole-rat...including migration and hibernation. Oxygen levels also vary widely, with animals adapted to sea level, high-altitude, underground and aquatic habitats...adapted for life in specific ecological niches as well as inform advances in therapy for neurological conditions such as stroke and epilepsy. Down for

The role of hypogonadism in Klinefelter syndrome.

Science.gov (United States)

Høst, Christian; Skakkebæk, Anne; Groth, Kristian A; Bojesen, Anders

2014-01-01

Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.

How attractive is the girl next door? An assessment of spatial mate acquisition and paternity in the solitary Cape dune mole-rat, Bathyergus suillus.

Directory of Open Access Journals (Sweden)

Timothy C Bray

Full Text Available Behavioural observations of reproduction and mate choice in wild fossorial rodents are extremely limited and consequently indirect methods are typically used to infer mating strategies. We use a combination of morphological, reproductive, spatial, and genetic data to investigate the reproductive strategy of a solitary endemic species, the Cape dune mole-rat Bathyergus suillus. These data provide the first account on the population dynamics of this species. Marked sexual dimorphism was apparent with males being both significantly larger and heavier than females. Of all females sampled 36% had previously reproduced and 12% were pregnant at the time of capture. Post-partum sex ratio was found to be significantly skewed in favour of females. The paternity of fifteen litters (n = 37 was calculated, with sires assigned to progeny using both categorical and full probability methods, and including a distance function. The maximum distance between progeny and a putative sire was determined as 2149 m with males moving between sub-populations. We suggest that above-ground movement should not be ignored in the consideration of mate acquisition behaviour of subterranean mammals. Estimated levels of multiple paternity were shown to be potentially as high as 26%, as determined using sibship and sire assignment methods. Such high levels of multiple paternity have not been found in other solitary mole-rat species. The data therefore suggest polyandry with no evidence as yet for polygyny.

DOES HYPOGONADISM ON RESULTS TRANSURETHRAL RESECTION OF BENIGN PROSTATIC HYPERPLASIA?

Directory of Open Access Journals (Sweden)

A. V. Sigaev

2013-01-01

Full Text Available Influence of hypogonadism on the results of transurethral resection of the prostate (TURP in patients with benign prostatic hyperplasia (BPH remains unexplored. At the survey included 98 patients with benign prostatic hyperplasia who underwent TURP. Revealed that the postoperative period in patients characterized by a significant decrease in the level of performance testosteronemii in all cases, and against the background of hypogonadism accompanied by the development of more complications. Preoperative correction of hypogonadism for 2 weeks prior to surgery allows a 2-3 times lower risk of postoperative complications. 

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

Science.gov (United States)

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Occurrence, patterns & predictors of hypogonadism in patients with HIV infection in India

Science.gov (United States)

Dutta, Deep; Sharma, Lokesh Kumar; Sharma, Neera; Gadpayle, Adesh K; Anand, Atul; Gaurav, Kumar; Gupta, Ankit; Poondla, Yashwanth; Kulshreshtha, Bindu

2017-01-01

Background & objectives: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. Methods: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (Pmale hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. Interpretation & conclusions: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females. PMID:29067983

Morphological, metabolic and functional repercussions after orchiectomy in rats

Directory of Open Access Journals (Sweden)

Denny Fabrício Magalhães Veloso

2009-03-01

Full Text Available Objective: To study the modifications in lipid profile, blood glucose and pressure, and morphological aspects of the adrenal gland in animals with hypogonadism secondary to total bilateral epididymectomy and orchiectomy. Methods: Young and adult male Wistar rats were distributed into the following groups: Group 1 – control, animals submitted only to scrotal incision and suture. Group 2 – animals submitted to total bilateral epididymectomy and orchiectomy. After these operations, studies were carried out to analyze possible repercussions of hypogonadism. In Study A, serum levels of free testosterone were measured, along with the body weight and cortical thickness of the adrenal gland of 30 adult rats. In Study B, serum values of glucose, triglycerides, total cholesterol, and HDL, LDL and VLDL fractions were measured in 20 young rats and 10 adult rats. In Study C, pressure of the caudal artery was measured by plethysmography in 24 adult animals. Rresults: Total bilateral epididymectomy and orchiectomy reduced serum levels of testosterone regardless of the age of the animal, and apparently does not modify macro- or microscopically the morphology of the adrenal gland. Hypogonadism secondary to total bilateral epididymectomy and orchiectomy did not modify the serum values of glucose, total cholesterol, LDL and HDL fractions. However, orchiectomy reduced the blood levels of triglycerides and VLDL cholesterol when performed in young rats. Testosterone deficiency was related to smaller weight gain and increased arterial pressure. Cconclusions: Castration reduces blood levels of triglycerides and VLDL cholesterol in young rats. In adult animals, it increases arterial pressure and is related to smaller weight gain.

Hypogonadotropic hypogonadism in a female patient with congenital arhinia.

Science.gov (United States)

Hunter, Janel Darcy; Davis, Melissa Ann; Law, Jennifer Rachel

2017-01-01

The association of anosmia and congenital hypogonadotropic hypogonadism (CHH) is well described; however, congenital arhinia is a malformation associated with CHH that occurs much more rarely. There have been three reports of male patients with hypogonadism and congenital arhinia in the literature to date. We present the first case of arhinia associated with CHH in a female patient. A 14 years and 8 months female with congenital arhinia presented with delayed puberty. Physical examination and laboratory evaluation were consistent with hypogonadotropic hypogonadism. She had no other hormone deficiencies and brain magnetic resonance imaging demonstrated a normal pituitary gland. Abdominal ultrasound showed a prepubertal uterus and ovaries. She was subsequently started on sex steroid treatment to induce secondary sexual characteristics. This case demonstrates that abnormalities of nasal development may provide an early diagnostic clue to hypogonadotropic hypogonadism, particularly in female patients who would not manifest classic signs of CHH in infancy (micropenis and cryptorchidism). Early diagnosis of CHH and timely initiation of sex steroid therapy is important to prevent comorbidities related to pubertal delay.

Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

Science.gov (United States)

Kietsiriroje, Noppadol

2015-10-01

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

Naked singularities in higher dimensional Vaidya space-times

International Nuclear Information System (INIS)

Ghosh, S. G.; Dadhich, Naresh

2001-01-01

We investigate the end state of the gravitational collapse of a null fluid in higher-dimensional space-times. Both naked singularities and black holes are shown to be developing as the final outcome of the collapse. The naked singularity spectrum in a collapsing Vaidya region (4D) gets covered with the increase in dimensions and hence higher dimensions favor a black hole in comparison to a naked singularity. The cosmic censorship conjecture will be fully respected for a space of infinite dimension

Dressing up a Kerr naked singularity

Energy Technology Data Exchange (ETDEWEB)

Calvani, M [Padua Univ. (Italy). Ist. di Astronomia; Nobili, L [Padua Univ. (Italy). Ist. di Fisica

1979-06-11

The evolution of a naked singularity surrounded by an accreting disk of matter is studied; two kinds of disks are considered: the standard thin-disk model and the thick barytropic model, for several initial conditions. It is shown that any Kerr naked singularity slows down in a finite time to a maximal Kerr black hole. The final mass, the luminosity and the time of evolution of the singularity are evaluated.

The role of hypogonadism in Klinefelter Syndrome

Directory of Open Access Journals (Sweden)

Christian Høst

2014-04-01

Full Text Available Klinefelter syndrome (KS (47, XXY is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These fi ndings should be a concern as they are not simply laboratory fi ndings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.

Emerging medication for the treatment of male hypogonadism.

Science.gov (United States)

Aydogdu, Aydogan; Swerdloff, Ronald S

2016-09-01

Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. The available literature of T and alternative treatments for male hypogonadism are discussed. Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.

Biological and biochemical properties of human chorionic gonadotropin from urine of patients with hydatidiform mole and its radioimmunoassay

International Nuclear Information System (INIS)

Nishimura, Ryuichiro; Hamamoto, Tamotsu; Tanabe, Keizo; Takemori, Masayuki; Ashitaka, Yoshihiko

1981-01-01

Human chorionic gonadotropin (hCG) was extracted and purified from the urine of four patients with hydatidiform mole. The immunological activities of the hCG-hydatidiform mole by hCG radioimmunoassay (RIA) ranged from 9,380 to 9,700 IU/mg, and the biological activities measured by the immature rat ovarian weight method ranged from 7,250 to 7,780 IU/mg. The results of the amino acid compositions of all the hCG-hydatidiform moles were practically identical with those of hCG-normal pregnancies. The carbohydrate moiety of the hCG-hydatidiform mole was also suspected to be almost similar to that of hCG-normal pregnancies by the results of their in vitro and in vivo biological activities. It was demonstrated that hCG-hydatidiform mole was composed of α and β subunits (similar to a hCG-normal pregnancy) when hCG-hydatidiform mole was separated into subunits by SDS disc electrophoresis after treatment with mercaptoethanol. The RIA system of hCG-hydatidiform mole can be established. The concentrations of hCG in sera of normal pregnant women and patients with trophoblastic diseases assayed by hCG-hydatidiform mole RIA were equivalent to those obtained by a standard hCG RIA. Hence, a standard hCG-immunoassay method used in the management of trophoblastic diseases is considered reasonable so far as the immunoantigenecity of hCG is concerned. (author)

Ultrasonographic findings of hydatidiform mole and missed abortion

International Nuclear Information System (INIS)

Yun, Kwang Myeong; Lee, Yeong Hwan; Chung, Hye Kyeong; Chung, Duck Soo; Kim, Ok Dong

1990-01-01

To establish the sonographic characteristics of the hydatidiform mole and the missed abortion with placental degeneration, we have retrospectively analyzed 12 cases of complete mole, 10 cases of partial mole, and 10 cases of missed abortion with placental hydropic degeneration, collected at Taegu Catholic General Hospital, from January 1986 to December 1989. The results were as follows : 1. Of 12 cases of complete mole, all demonstrated diffuse intrauterine vesicular pattern of internal echo without a gestational sac. Two cases were recurred after D and E. 2. The partial mole was characterized by focal (70%) or diffuse (20%) distribution of hydatidiform placental change and a gestational sac (100%) with or without a macerated fetus. But the striking hydatidiform placental change was not present in one cases of partial mole. 3. The uterus was larger for dates in 9 cases (90%) of complete mole, but smaller for dates in 7 cases (70%) of partial mole. 4. The missed abortion with placental hydropic degeneration was indistinguished from a partial mole due to their similar sonographic appearance : focal or diffuse cystic change of a placenta, a distorted gestational sac with or without a fetus, and a smaller uterus for dates. On conclusion, the complete mole could be easily distinguished from a partial mole or a missed abortion by sonography : a gestational sac or an area of noncystic placenta was not identified in a complete mole. The partial mole was indistinguished from a missed abortion, but if there is the suspicion of trophoblastic proliferation, such as a convex placental surface or a larger uterus for dates, then the diagnosis is probably a partial mole rather than a missed abortion

Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

Science.gov (United States)

Milardi, Domenico; Grande, Giuseppe; Giampietro, Antonella; Vendittelli, Francesca; Palumbo, Sara; Tartaglione, Linda; Marana, Riccardo; Pontecorvi, Alfredo; de Marinis, Laura; Zuppi, Cecilia; Capoluongo, Ettore

2012-01-01

Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

Phase II drugs currently being investigated for the treatment of hypogonadism.

Science.gov (United States)

Udedibia, Emeka; Kaminetsky, Jed

2014-12-01

Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

Treatment of Hypogonadism: Current and Future Therapies [version 1; referees: 2 approved

OpenAIRE

Arthi Thirumalai; Kathryn E. Berkseth; John K. Amory

2017-01-01

The treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits...

Hypogonadism in a male-to-female transsexual with super obesity.

Science.gov (United States)

Ayanian, S; Irwig, M S

2013-08-01

The global obesity epidemic is having a profound impact on the health of populations. From a reproductive standpoint, obesity has been associated with infertility and hypogonadism. We present the case of a 29-year-old male-to-female transsexual with super obesity (body mass index >50) who was found to have profound hypogonadism with total and free testosterone levels in the normal female reference range. There is virtually no literature on the hormonal sequelae of obesity in transsexual people. The patient was prescribed an aromatase inhibitor, letrozole 2.5 mg twice daily for 2 weeks, to determine the role of oestrogen in the hypogonadism. The aromatase inhibitor reduced the serum oestradiol concentration from 125 to 6.9 pm. There were dramatic corresponding rises in total testosterone (2.8 to 10.7 nm), luteinising hormone (4.1 to 20.5 mIU ml(-1) ) and follicle stimulating hormone (1.8 to 15.3 mIU ml(-1) ). This diagnostic test demonstrated the important role of oestrogen in mediating the hypogonadism. After the testing, the patient was started on oestrogen therapy after a careful discussion of the benefits versus risks of oestrogen therapy. We anticipate that similar cases of hypogonadism in male-to-female transsexuals will likely become more common in an era of increased obesity rates. © 2012 Blackwell Verlag GmbH.

Geochemical mole-balance modeling with uncertain data

Science.gov (United States)

Parkhurst, David L.

1997-01-01

Geochemical mole-balance models are sets of chemical reactions that quantitatively account for changes in the chemical and isotopic composition of water along a flow path. A revised mole-balance formulation that includes an uncertainty term for each chemical and isotopic datum is derived. The revised formulation is comprised of mole-balance equations for each element or element redox state, alkalinity, electrons, solvent water, and each isotope; a charge-balance equation and an equation that relates the uncertainty terms for pH, alkalinity, and total dissolved inorganic carbon for each aqueous solution; inequality constraints on the size of the uncertainty terms; and inequality constraints on the sign of the mole transfer of reactants. The equations and inequality constraints are solved by a modification of the simplex algorithm combined with an exhaustive search for unique combinations of aqueous solutions and reactants for which the equations and inequality constraints can be solved and the uncertainty terms minimized. Additional algorithms find only the simplest mole-balance models and determine the ranges of mixing fractions for each solution and mole transfers for each reactant that are consistent with specified limits on the uncertainty terms. The revised formulation produces simpler and more robust mole-balance models and allows the significance of mixing fractions and mole transfers to be evaluated. In an example from the central Oklahoma aquifer, inclusion of up to 5% uncertainty in the chemical data can reduce the number of reactants in mole-balance models from seven or more to as few as three, these being cation exchange, dolomite dissolution, and silica precipitation. In another example from the Madison aquifer, inclusion of the charge-balance constraint requires significant increases in the mole transfers of calcite, dolomite, and organic matter, which reduce the estimated maximum carbon 14 age of the sample by about 10,000 years, from 22,700 years to

Structural studies of human Naked2: A biologically active intrinsically unstructured protein

International Nuclear Information System (INIS)

Hu Tianhui; Krezel, Andrzej M.; Li Cunxi; Coffey, Robert J.

2006-01-01

Naked1 and 2 are two mammalian orthologs of Naked Cuticle, a canonical Wnt signaling antagonist in Drosophila. Naked2, but not Naked1, interacts with transforming growth factor-α (TGFα) and escorts TGFα-containing vesicles to the basolateral membrane of polarized epithelial cells. Full-length Naked2 is poorly soluble. Since most functional domains, including the Dishevelled binding region, EF-hand, vesicle recognition, and membrane targeting motifs, reside in the N-terminal half of the protein, we expressed and purified the first 217 residues of human Naked2 and performed a functional analysis of this fragment. Its circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra showed no evidence of secondary and/or tertiary structure. The fragment did not bind calcium or zinc. These results indicate that the N-terminal half of Naked2 behaves as an intrinsically unstructured protein

A Case of Hypogonadotropic Hypogonadism Caused by Opioid Treatment for Nonmalignant Chronic Pain

Directory of Open Access Journals (Sweden)

Yukiko Tabuchi

2012-01-01

Full Text Available We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.

Normosmic idiopathic hypogonadotrophic hypogonadism due to a rare KISS1R gene mutation

Directory of Open Access Journals (Sweden)

N Chelaghma

2018-04-01

Full Text Available Hypogonadotrophic hypogonadism is due to impaired or reduced gonadotrophin secretion from the pituitary gland. In the absence of any anatomical or functional lesions of the pituitary or hypothalamic gland, the hypogonadotrophic hypogonadism is referred to as idiopathic hypogonadotrophic hypogonadism (IHH. We present a case of a young lady born to consanguineous parents who was found to have IHH due to a rare gene mutation.

Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin.

OpenAIRE

Gill, G. V.

1998-01-01

A case is presented of a young competitive body-builder who abused anabolic steroid drugs and developed profound symptomatic hypogonadotrophic hypogonadism. With the help of prescribed testosterone (Sustanon) he stopped taking anabolic drugs, and later stopped Sustanon also. Hypogonadism returned, but was successfully treated with weekly injections of human chorionic gonadotropin for three months. Testicular function remained normal thereafter on no treatment. The use of human chorionic gonad...

Treatment of Hypogonadism: Current and Future Therapies [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Arthi Thirumalai

2017-01-01

Full Text Available The treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits of androgens whilst minimizing unwanted side effects.

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men.

Science.gov (United States)

Lunenfeld, Bruno; Mskhalaya, George; Zitzmann, Michael; Arver, Stefan; Kalinchenko, Svetlana; Tishova, Yuliya; Morgentaler, Abraham

2015-03-01

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

A practical guide to male hypogonadism in the primary care setting

Science.gov (United States)

Dandona, P; Rosenberg, M T

2010-01-01

There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment. PMID:20518947

Bone benefits of testosterone replacement therapy in male hypogonadism.

Science.gov (United States)

Tirabassi, G; Biagioli, A; Balercia, G

2014-06-01

Osteoporosis is an asymptomatic, systemic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility. Such condition is often underdiagnosed and undertreated, especially in men, therefore considerably increasing the fracture risk. Of note, fracture-related morbidity and mortality is generally higher in men, partly due to greater frailty. On the other hand, male hypogonadism is defined as the failure of the testes to produce androgens, sperm, or both and it is often due to the ageing process. This disorder, in turn, causes many systemic disorders, and it is the condition mainly associated with male osteoporosis. Testosterone replacement therapy (TRT) is usually prescribed to restore optimal hormone levels, but conflicting data are available about the efficacy of TRT treatment on bone mineral density. In this review we extensively examined literature data about the usefulness of TRT in improving hypogonadism-associated low bone mineral density. Furthermore, we considered the complex relationship between male osteoporosis and hypogonadism, by specifically addressing the role of androgens in male bone physiology and the diagnostic approach to male osteoporosis and hypogonadism and also by dealing with some new related aspects such as the new endocrine pathways between bone and testis and the role of androgen receptor CAG polymorphism on bone density.

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

Directory of Open Access Journals (Sweden)

Prasanth N. Surampudi

2012-01-01

Full Text Available Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men.

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

Science.gov (United States)

Surampudi, Prasanth N.; Wang, Christina; Swerdloff, Ronald

2012-01-01

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men. PMID:22505891

The mole

CERN Multimedia

CERN PhotoLab

1974-01-01

The mole continued its way around the SPS ring ... and on 31 July emerged where it started from, having completed its 7 kilometre journey without ever veering more than a couple of centimetres from its schedule path.

A Case of Hypogonadotropic Hypogonadism Caused by Opioid Treatment for Nonmalignant Chronic Pain

OpenAIRE

Tabuchi, Yukiko; Yasuda, Tetsuyuki; Kaneto, Hideaki; Kitamura, Tetsuhiro; Kozawa, Junji; Otsuki, Michio; Imagawa, Akihisa; Nakae, Aya; Matsuda, Youichi; Uematsu, Hironobu; Mashimo, Takashi; Shibata, Masahiko; Shimomura, Iichiro

2012-01-01

We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypog...

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

Science.gov (United States)

Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

2016-01-01

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

Assessment of Hypogonadism in Men With Type 2 Diabetes: A Cross-Sectional Study From Saudi Arabia

Directory of Open Access Journals (Sweden)

Ayman Abdullah Al Hayek

2017-05-01

Full Text Available Background/objectives: A high incidence of hypogonadism in men with type 2 diabetes (T2D has been globally reported. This study aimed to determining the frequency of hypogonadism and related risk factors among men with T2D in a single-site hospital in Saudi Arabia. Design and methods: A cross-sectional study was performed on 157 men with T2D (between 30 and 70 years of age. Using a prestructured questionnaire, the demographic features of these patients were gathered and their medical records were referred to gather information regarding the duration of the diabetes, smoking habits, and the presence of retinopathy, neuropathy, and nephropathy. Besides these, the biochemical parameters, total testosterone (TT, free testosterone, sex hormone–binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin, serum lipids, and glycosylated hemoglobin were also recorded. All the patients submitted the fully completed Androgen Deficiency in Aging Male (ADAM questionnaire. The combination of symptoms (positive ADAM score plus a TT level ⩽8 nmol/L constituted the condition of hypogonadism. Results: The total frequency of hypogonadism was 22.9% (36/157. Of the 157 total patients, 123 (78.3% were shown to be ADAM positive, and of these, 90 (73.2% exhibited decreased libido, 116 (94.3% had weak erections, and 99 (80.5% reported more than 3 symptoms of ADAM. Of these hypogonadic patients, 22.2% (n = 8 revealed primary hypogonadism, whereas 77.8% (n = 28 showed secondary hypogonadism. From the univariate analysis conducted, significant relationship was observed between treatment type, body mass index (BMI, and hypogonadism. The regression analysis showed BMI acting an independent risk factor of hypogonadism. Conclusions: Saudi men with T2D revealed a high incidence of hypogonadism. Body mass index was identified as an independent risk factor for hypogonadism.

Assessment of Hypogonadism in Men With Type 2 Diabetes: A Cross-Sectional Study From Saudi Arabia

Science.gov (United States)

Al Hayek, Ayman Abdullah; Robert, Asirvatham Alwin; Alshammari, Ghazi; Hakami, Husain; Al Dawish, Mohamed Abdulaziz

2017-01-01

BACKGROUND/OBJECTIVES A high incidence of hypogonadism in men with type 2 diabetes (T2D) has been globally reported. This study aimed to determining the frequency of hypogonadism and related risk factors among men with T2D in a single-site hospital in Saudi Arabia. DESIGN AND METHODS A cross-sectional study was performed on 157 men with T2D (between 30 and 70 years of age). Using a prestructured questionnaire, the demographic features of these patients were gathered and their medical records were referred to gather information regarding the duration of the diabetes, smoking habits, and the presence of retinopathy, neuropathy, and nephropathy. Besides these, the biochemical parameters, total testosterone (TT), free testosterone, sex hormone–binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin, serum lipids, and glycosylated hemoglobin were also recorded. All the patients submitted the fully completed Androgen Deficiency in Aging Male (ADAM) questionnaire. The combination of symptoms (positive ADAM score) plus a TT level ⩽8 nmol/L constituted the condition of hypogonadism. RESULTS The total frequency of hypogonadism was 22.9% (36/157). Of the 157 total patients, 123 (78.3%) were shown to be ADAM positive, and of these, 90 (73.2%) exhibited decreased libido, 116 (94.3%) had weak erections, and 99 (80.5%) reported more than 3 symptoms of ADAM. Of these hypogonadic patients, 22.2% (n = 8) revealed primary hypogonadism, whereas 77.8% (n = 28) showed secondary hypogonadism. From the univariate analysis conducted, significant relationship was observed between treatment type, body mass index (BMI), and hypogonadism. The regression analysis showed BMI acting an independent risk factor of hypogonadism. CONCLUSIONS Saudi men with T2D revealed a high incidence of hypogonadism. Body mass index was identified as an independent risk factor for hypogonadism. PMID:28579862

Male and female hypogonadism are highly prevalent in South Africans with Addison's disease.

Science.gov (United States)

Ross, I L; Levitt, N S; Blom, D J; Haarburger, D

2014-09-01

Hypogonadism may complicate Addison's disease (primary hypoadrenalism), but prevalence and metabolic sequelae of hypogonadism in Addison's disease are poorly described. We recruited patients from the South African Addison's disease national registry who received stable replacement doses of hydrocortisone and had no acute illness. Male biochemical testosterone deficiency was defined as an early morning basal testosterone10 or 12 IU/l). Testosterone deficiency did not correlate with age, disease duration or hydrocortisone dose. Untreated male hypogonadal subjects had a higher (mean ± standard deviation) BMI compared to eugonadal subjects 29.2 ± 4.9 kg/m(2) vs. 24.7 ± 3.4 kg/m(2) (p=0.01) and a higher median (interquartile range) high-sensitive-CRP 6.4 (2.5-14.0) mg/l vs. 1.45 (0.6-2.8) mg/l (p=0.002). There were no differences between the 2 groups in lipids, lipoproteins and fasting glucose. The median (interquartile range) DHEAS was lower in the hypogonadal 0.31 (0.27-0.37) μmol/l, compared with the eugonadal group 0.75 (0.50-1.51) μmol/l (p=0.005). POF was documented in 11% of female patients. Male testosterone deficiency was highly prevalent in this cohort and was primarily due to secondary hypogonadism. Only BMI and hs-CRP were increased in untreated male hypogonadal subjects. Male and female hypogonadism appears to be a common complication of Addison's disease and may contribute to its morbidity. © Georg Thieme Verlag KG Stuttgart · New York.

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men

Science.gov (United States)

Lunenfeld, Bruno; Zitzmann, Michael; Arver, Stefan; Kalinchenko, Svetlana; Tishova, Yuliya; Morgentaler, Abraham

2015-01-01

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men. PMID:25657080

The Triglycerides and Glucose Index rather than HOMA-IR is more associated with Hypogonadism in Chinese men.

Science.gov (United States)

Zhang, Kun; Chen, Yi; Liu, Lijie; Lu, Meng; Cheng, Jing; Gao, Fengbin; Wang, Ningjian; Shen, Zhoujun; Lu, Yingli

2017-11-20

Previous studies have reported that insulin resistant and low testosterone are related. The triglyceride and glucose index (TyG) well mirrors insulin sensitivity. No study investigated the application of TyG in male hypogonadism. We aimed to explore whether TyG was associated with hypogonadism, and also evaluate the ability of TyG compared to HOMA-IR as a possible hypogonadism predictor. A total of 4299 male subjects were enrolled from 22 sites in East China. Hypogonadism was defined as total testosterone HOMA-IR (0.68, 95% CI 0.66,0.70). Thus, the TyG was significantly associated with a higher prevalence of hypogonadism in Chinese men. TyG had a better predictive power for hypogonadism than HOMA-IR.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism.

Science.gov (United States)

Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

2014-01-01

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Directory of Open Access Journals (Sweden)

Christopher C Coss

2014-04-01

Full Text Available Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Science.gov (United States)

Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

2014-01-01

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism. PMID:24407183

Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic.

Science.gov (United States)

Öztin, Hasan; Çağıltay, Eylem; Çağlayan, Sinan; Kaplan, Mustafa; Akpak, Yaşam Kemal; Karaca, Nilay; Tığlıoğlu, Mesut

2016-12-01

Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted is under the effect of many hormonal or stimulating factors. Kisspeptin is present in many places of the body, mostly in hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect on the metastasis of many tumors such as breast cancer and malign melanoma metastases, and is called "metastin" for this reason. Kisspeptin is a strong stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology, there is gonadotropic hormone release indeficiency which cannot be clearly described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over 30 years of age who have applied to Haydarpasa Education Hospital Endocrinology and Metabolic Diseases Service were included in the study. Compared to the control group, the effect of kisspeptin on male patients with hypogonatropic hypogonadism and on insulin resistance developing in hypogonadism patients was investigated in our study. A statistically significant difference was detected between average kisspeptin measurements of the groups (p hypogonadism and has less effect on insulin resistance.

Moles: Tool-Assisted Environment Isolation with Closures

Science.gov (United States)

de Halleux, Jonathan; Tillmann, Nikolai

Isolating test cases from environment dependencies is often desirable, as it increases test reliability and reduces test execution time. However, code that calls non-virtual methods or consumes sealed classes is often impossible to test in isolation. Moles is a new lightweight framework which addresses this problem. For any .NET method, Moles allows test-code to provide alternative implementations, given as .NET delegates, for which C# provides very concise syntax while capturing local variables in a closure object. Using code instrumentation, the Moles framework will redirect calls to provided delegates instead of the original methods. The Moles framework is designed to work together with the dynamic symbolic execution tool Pex to enable automated test generation. In a case study, testing code programmed against the Microsoft SharePoint Foundation API, we achieved full code coverage while running tests in isolation without an actual SharePoint server. The Moles framework integrates with .NET and Visual Studio.

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

Science.gov (United States)

Grinspon, Romina P.; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M.; Rey, Rodolfo A.

2014-01-01

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism. PMID:24847309

Spreading the clinical window for diagnosing fetal-onset hypogonadism in boys

Directory of Open Access Journals (Sweden)

Rodolfo eRey

2014-05-01

Full Text Available In early fetal development, the testis secretes –independently of pituitary gonadotropins– androgens and anti-Müllerian hormone (AMH which are essential for male sex differentiation. In the second half of fetal life, the hypothalamic-pituitary axis gains control of testicular hormone secretion. FSH controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas LH regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic-pituitary-gonadal axis in the male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3-6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic-pituitary-testicular axis in boys suspected of fetal-onset hypogonadism.

Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe

DEFF Research Database (Denmark)

Kiess, W; Conway, G; Ritzen, M

2002-01-01

The management of children and adolescents with hypogonadism and in particular the induction of puberty in the hypogonadal girl is subject to controversy. Therefore, under the auspices and through organization of the Drugs and Therapeutics Committee of the European Society of Paediatric Endocrino......The management of children and adolescents with hypogonadism and in particular the induction of puberty in the hypogonadal girl is subject to controversy. Therefore, under the auspices and through organization of the Drugs and Therapeutics Committee of the European Society of Paediatric...... of the results of the questionnaires and discussions of that session to further the discussion on and knowledge of current concepts of induction of puberty in the hypogonadal girl in Europe. It became clear from the data accumulated here that the start of treatment, the aims of therapy and the modalities of how...

Effects of hypogonadism on bone metabolism in female adolescents and young adults.

Science.gov (United States)

Misra, Madhusmita

2012-01-24

Gonadal steroids, including androgens and oestrogens, play a critical part in bone metabolism, and conditions associated with a deficiency of gonadal steroids can reduce BMD in adults and impair bone accrual in adolescents. In addition, other associated hormone alterations, for example, insulin-like growth factor 1 deficiency or high cortisol levels, can further exacerbate the effect of hypogonadism on bone metabolism, as can factors such as calcium and vitamin D deficiency, low body weight and exercise status. This Review discusses the effects of different hypogonadal states on bone metabolism in female adolescents and young adults, with particular emphasis on conditions associated with low energy availability, such as anorexia nervosa and athletic amenorrhoea, in which many factors other than hypogonadism affect bone. In contrast to most hypogonadal conditions, in which replacement of gonadal steroids is sufficient to normalize bone accrual rates and BMD, gonadal steroid replacement may not be sufficient to normalize bone metabolism in these states of energy deficit.

MOLES3: Implementing an ISO standards driven data catalogue

Directory of Open Access Journals (Sweden)

Graham A Parton

2015-02-01

Full Text Available ISO19156 Observations and Measurements (O&M provides a standardised framework for organising information about the collection of information about the environment.  Here we describe the implementation of a specialisation of O&M for environmental data, the Metadata Objects for Linking Environmental Sciences (MOLES3.MOLES3 provides support for organising information about data, and for user navigation around data holdings. The implementation described here, “CEDA-MOLES”, also supports data management functions for the Centre for Environmental Data Archival, CEDA. The previous iteration of MOLES (MOLES2 saw active use over five years, being replaced by CEDA-MOLES in late 2014. During that period important lessons were learnt both about the information needed, as well as how to design and maintain the necessary information systems. In this paper we review the problems encountered in MOLES2; how and why CEDA-MOLES was developed and engineered; the migration of information holdings from MOLES2 to CEDA-MOLES; and, finally, provide an early assessment of MOLES3 (as implemented in CEDA-MOLES and its limitations.Key drivers for the MOLES3 development included the necessity for improved data provenance, for further structured information to support ISO19115 discovery metadata  export (for EU INSPIRE compliance, and to provide appropriate fixed landing pages for Digital Object Identifiers (DOIs in the presence of evolving datasets. Key lessons learned included the importance of minimising information structure in free text fields, and the necessity to support as much agility in the information infrastructure as possible without compromising on maintainability both by those using the systems internally and externally (e.g. citing in to the information infrastructure, and those responsible for the systems themselves. The migration itself needed to ensure continuity of service and traceability of archived assets.

Perfect fluid tori orbiting Kehagias-Sfetsos naked singularities

Science.gov (United States)

Stuchlík, Z.; Pugliese, D.; Schee, J.; Kučáková, H.

2015-09-01

We construct perfect fluid tori in the field of the Kehagias-Sfetsos (K-S) naked singularities. These are spherically symmetric vacuum solutions of the modified Hořava quantum gravity, characterized by a dimensionless parameter ω M^2, combining the gravitational mass parameter M of the spacetime with the Hořava parameter ω reflecting the role of the quantum corrections. In dependence on the value of ω M^2, the K-S naked singularities demonstrate a variety of qualitatively different behavior of their circular geodesics that is fully reflected in the properties of the toroidal structures, demonstrating clear distinction to the properties of the torii in the Schwarzschild spacetimes. In all of the K-S naked singularity spacetimes the tori are located above an "antigravity" sphere where matter can stay in a stable equilibrium position, which is relevant for the stability of the orbiting fluid toroidal accretion structures. The signature of the K-S naked singularity is given by the properties of marginally stable tori orbiting with the uniform distribution of the specific angular momentum of the fluid, l= const. In the K-S naked singularity spacetimes with ω M^2 > 0.2811, doubled tori with the same l= const can exist; mass transfer between the outer torus and the inner one is possible under appropriate conditions, while only outflow to the outer space is allowed in complementary conditions. In the K-S spacetimes with ω M^2 < 0.2811, accretion from cusped perfect fluid tori is not possible due to the non-existence of unstable circular geodesics.

Perfect fluid tori orbiting Kehagias-Sfetsos naked singularities

Energy Technology Data Exchange (ETDEWEB)

Stuchlik, Z.; Pugliese, D.; Schee, J.; Kucakova, H. [Silesian University in Opava, Faculty of Philosophy and Science, Institute of Physics and Research Centre of Theoretical Physics and Astrophysics, Opava (Czech Republic)

2015-09-15

We construct perfect fluid tori in the field of the Kehagias-Sfetsos (K-S) naked singularities. These are spherically symmetric vacuum solutions of the modified Horava quantum gravity, characterized by a dimensionless parameter ωM{sup 2}, combining the gravitational mass parameter M of the spacetime with the Horava parameter ω, reflecting the role of the quantum corrections. In dependence on the value of ωM{sup 2}, the K-S naked singularities demonstrate a variety of qualitatively different behavior of their circular geodesics that is fully reflected in the properties of the toroidal structures, demonstrating clear distinction to the properties of the torii in the Schwarzschild spacetimes. In all of the K-S naked singularity spacetimes the tori are located above an @gantigravity@h sphere where matter can stay in a stable equilibrium position, which is relevant for the stability of the orbiting fluid toroidal accretion structures. The signature of the K-S naked singularity is given by the properties of marginally stable tori orbiting with the uniform distribution of the specific angular momentum of the fluid, l = const. In the K-S naked singularity spacetimes with ωM{sup 2} > 0.2811, doubled tori with the same l = const can exist; mass transfer between the outer torus and the inner one is possible under appropriate conditions, while only outflow to the outer space is allowed in complementary conditions. In the K-S spacetimes with ωM{sup 2} < 0.2811, accretion from cusped perfect fluid tori is not possible due to the non-existence of unstable circular geodesics. (orig.)

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

OpenAIRE

Prasanth N. Surampudi; Christina Wang; Ronald Swerdloff

2012-01-01

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young...

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men.

Science.gov (United States)

Zarotsky, V; Huang, M-Y; Carman, W; Morgentaler, A; Singhal, P K; Coffin, D; Jones, T H

2014-11-01

The objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences. © 2014 American Society of Andrology and European Academy of Andrology.

Avolition in a patient with hypogonadism

NARCIS (Netherlands)

W.M.A. Verhoeven (Wim); S. Tuinier (Siegfried); J.I.M. Egger (Jos); F. van Erp (Femke); J. Tuerlings (Joep)

2008-01-01

textabstractBackground and Objectives: Testosterone deficiency has been implicated in the etiology of depression although there is an ongoing debate on the nature of this association. There is a paucity of data about the psychological impact of hypogonadism in genetic disorders associated with

Avolition in a patient with hypogonadism

NARCIS (Netherlands)

Verhoeven, W.M.A.; Tuinier, S.; Egger, J.I.M.; Erp, C.A. van; Tuerlings, J.H.A.M.

2009-01-01

Background and Objectives: Testosterone deficiency has been implicated in the etiology of depression although there is an ongoing debate on the nature of this association. There is a paucity of data about the psychological impact of hypogonadism in genetic disorders associated with testosterone

Male Hypogonadism. A Case Report

Directory of Open Access Journals (Sweden)

Lisandro Hernández Madrazo

2012-07-01

Full Text Available The case of a 26 years old male patient who attended the Internal Medicine consultation at the La Fortaleza Integral Diagnostic Center in Maracaibo, Zulia State, Venezuela because of decreased external genitalia size, with poor development from childhood and swelling of the breasts is presented. Physical examination showed a trunk of feminoid configuration caused by adipose tissue accumulated in the lower abdomen, breast and pubic; wide pelvis; lower limb dominance over higher limbs; enucoid proportions; volume diffusely  increased in both breasts (gynecomastia; deposit of fatty tissue at the pelvic girdle, and absent or sparse facial, axillary and pubic hair. We observed decreased size, poor pigmentation, and soft consistency in penis and testicles. Exam was performed on plasma testosterone, luteinizing hormone and follicle stimulating hormone, thus concluding, by the Endocrinology Service at the Maracaibo University Hospital, to be the case of hypogonadotropic hypogonadism of improvable cause. The clinical diagnosis of hypogonadism in adults is unusual in medical practice, a fact that provides with relevance the case we present.

Naked singularities in self-similar spherical gravitational collapse

International Nuclear Information System (INIS)

Ori, A.; Piran, T.

1987-01-01

We present general-relativistic solutions of self-similar spherical collapse of an adiabatic perfect fluid. We show that if the equation of state is soft enough (Γ-1<<1), a naked singularity forms. The singularity resembles the shell-focusing naked singularities that arise in dust collapse. This solution increases significantly the range of matter fields that should be ruled out in order that the cosmic-censorship hypothesis will hold

Clinical Characteristics, Health Care Utilization and Costs Among Men with Primary or Secondary Hypogonadism in a US Commercially Insured Population.

Science.gov (United States)

Grabner, Michael; Bodhani, Amit; Khandelwal, Nikhil; Palli, Swetha; Bonine, Nicole; Khera, Mohit

2017-01-01

Hypogonadism is broadly associated with increases in chronic comorbid conditions and health care costs. Little is known about the specific impact of primary and secondary hypogonadism on health care costs. To characterize the health care cost and utilization burden of primary and secondary hypogonadism in a population of US men with commercial insurance. Newly diagnosed patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with specific medical conditions known to have a high prevalence of testosterone deficiency (ie, relating to primary or secondary hypogonadism) or who had fills for testosterone replacement therapy from January 1, 2007 through April 30, 2013 were identified in administrative claims data from the HealthCore Integrated Research Database. A cohort of patients without hypogonadism was matched on demographics and comorbidities. The matched hypogonadism and non-hypogonadism cohorts (n = 5,777 in each cohort) were compared during a 12-month follow-up period. Direct health care expenditures and utilization were assessed for all causes and for hypogonadism-related claims. Costs included out-of-pocket patient expenditures and those paid by the insurer. Hypogonadism and matched non-hypogonadism cohorts were similar in demographics (mean age = 50 years) and diagnosed comorbid conditions in the 12 months preceding the index date. In the year after the index date, mean all-cause expenditures for patients with hypogonadism increased by 62% (from $5,425 to $8,813) compared with 25% for the matched controls (from $4,786 to $5,992; P groups). Approximately 16% of total mean costs ($1,377), primarily outpatient and pharmacy costs, were identifiable as related to hypogonadism. These data from a population of US men with commercial insurance coverage showed a greater resource use burden for patients with primary and secondary hypogonadism compared with similar patients without hypogonadism. Additional

Mapping Ad Hoc Communications Network of a Large Number Fixed-Wing UAV Swarm

Science.gov (United States)

2017-03-01

shows like "Agents of S.H.I.E.L.D". Inspiration can come from the imaginative minds of people or from the world around us. Swarms have demonstrated a...high degree of success. Bees , ants, termites, and naked mole rats maintain large groups that distribute tasks among individuals in order to achieve...the application layer and not the transport layer. Real- world vehicle-to-vehicle packet delivery rates for the 50-UAV swarm event were de- scribed in

CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism?

Science.gov (United States)

Francomano, Davide; Greco, Emanuela A; Lenzi, Andrea; Aversa, Antonio

2013-10-01

It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. To describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. A systematic Medline search was conducted using several terms related to and including the terms "androgen receptor," "CAG-repeat polymorphism," "male hypogonadism," "female hypogonadism," and "neurodegenerative disease." Clinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women. © 2013 International Society for Sexual Medicine.

Guidelines for the diagnosis and treatment of testosterone deficiency (hypogonadism in male patients with diabetes mellitus (Draft

Directory of Open Access Journals (Sweden)

Galina Afanas'evna Melnichenko

2017-06-01

Full Text Available Hypogonadism in male patients is defined as a decrease in the serum testosterone level; it is associated with specific symptoms and/or signs (see the detailed description below. It is a common complication in diabetes mellitus. The guidelines do not review all disorders leading to the development of hypogonadism but focus on options for the treatment of hypogonadism, which is generally observed in male patients with diabetes. In the literature, data on the prevalence of hypogonadism in patients with diabetes are available. In the section on diagnostics, the medical history of patients with hypogonadism and diabetes, including the necessary methods for physical and laboratory inspection. Risk factors for and the clinical consequences of hypogonadism are separately considered. In the section on treatment options, variations in treatment using various androgenic therapeutic agents based on patients’ requirements, conservation of their reproductive function, and their risk factors are provided. Special attention is given to indications of, contraindications of and risk factors for androgenic therapy in male patients with diabetes, particularly those in their advanced age. The principles of the clinical monitoring are developed. The favourable effects of androgenic therapy for hypogonadism in male patients with diabetes are shown.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

Science.gov (United States)

Cangiano, B; Cacciatore, C; Persani, L; Bonomi, M

2017-01-01

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal

The role of hypogonadism in Klinefelter syndrome

DEFF Research Database (Denmark)

Høst, Christian; Skakkebæk, Anne; Groth, Kristian A

2014-01-01

and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition...... populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever...... been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome....

Scintigraphy in primary hypogonadism in testicle transplantation

International Nuclear Information System (INIS)

Glejzer, Yu.Ya.; Marinbakh, A.E.; Vasil'ev, V.I.

1979-01-01

A new method of diagnosis, scintigraphy of the testicles with sup(99m)Tc-pertechnetat is presented. The technique of the study is described, the data are processed. 26 patients with primary hypogonadism (cryptorchism, hypo- and aplasia of the testicles) and adrogenic insufficiency were examined before and after allotransplantation of cadaver testicle on arterial-venous pedicle. The advantages of the method lie in its being highly informative and objective and its low toxicity for a patient. Radionuclide examination makes it possible to determine the disposition, size and type of blood supply as well as the functional ability of testicles of patients with primary hypogonadism. Testicle scintigraphy can be significant while estimating the level of vascular network development and the function of a transplanted testicle, as well as in dynamic observations of a graft

Varicocele is associated with hypogonadism and impaired erectile function: a prospective comparative study.

Science.gov (United States)

Ji, B; Jin, X-B

2017-08-01

We conducted this prospective comparative study to examine the hypothesis that varicocele was associated with hypogonadism and impaired erectile function as reflected in International Index of Erectile Function-5 (IIEF-5) scores as well as nocturnal penile tumescence and rigidity (NPTR) parameters. From December 2014 to December 2015, a total of 130 males with varicocele complaining of infertility or scrotal discomfort and 130 age-matched healthy males chosen from volunteer healthy hospital staff as controls were recruited in this study. Serum testosterone (TT) levels and IIEF-5 scores as well as NPTR parameters were evaluated and compared between varicocele and control subjects. All participants were further grouped into hypogonadism based on the cut-off value 300 ng/dL. A total of 45 of 130 patients were identified as hypogonadism, while it was not found in control subjects. A multivariate logistic regression with likelihood ratio test revealed that TT levels as well as grade III and II varicocele posed significant indicators for hypogonadism occurrence (chi-square of likelihood ratio = 12.40, df = 3, p hypogonadism was confirmed in this study and an impaired erectile function correlated with TT levels and infertility duration was also observed. © 2016 Blackwell Verlag GmbH.

CT diagnosis of invasive hydatidiform mole

International Nuclear Information System (INIS)

Lu Mingquan; Jiang Lina; Li Xianxing; Wang Peijun

2000-01-01

Objective: To investigate the CT features and the diagnostic value in invasive mole. Methods: Eleven cases (age, 30 to 53 years, mean 40 years) with invasive mole proved by operation and pathology were studied, including 3 cases during peri-menopausal period of eight months, ten months and twelve months respectively. All cases were scanned by CT and enhanced study was done. Results: All cases showed enlargement of uterus of varying degrees. On CT, the density of uterine cavity was similar to that of water, intermingled with spotty patchy and hazy circular isodense shadows. High density stripe-like bleeding foci were found in 3 cases. The outline of uterine cavity was locally disrupted in all case and the muscle layer was thickened in 3 cases. On enhanced CT scan, the lesions in the uterine cavity appeared markedly hyperdense, just like 'the crater' and the 'mole sign'. The muscle layers at the site of disruption showed inhomogeneous enhancement after contrast injection. Conclusion: The CT features of invasive mole are characteristic, with important diagnostic value, especially for those during peri-menopausal period

Testosterone replacement in male hypogonadism

OpenAIRE

Kalra, Sanjay; Agrawal, Navneet; Kumar, Satish; Sharma, Amit

2010-01-01

Sanjay Kalra1, Navneet Agrawal2, Satish Kumar3, Amit Sharma11Department of Endocrinology, Bharti Hospital, Karnal, India; 2Dept of Medicine, GR Medical College, Gwalior, India; 3Clinical Research, EXCEL Life Sciences, NOIDA, IndiaAbstract: This article contains a review of the clinical aspects of testosterone replacement in androgen deficiency of the aging male.Keywords: testosterone, supplementation, hypogonadism, ADAM

Guidelines for the Diagnosis and Treatment of testosterone deficiency (hypogonadism in male patients with diabetes mellitus

Directory of Open Access Journals (Sweden)

Ivan I. Dedov

2017-12-01

Full Text Available Hypogonadism in men, defined as a reduction in serum testosterone in combination with characteristic symptoms and/or signs (described in detail later, is common in diabetes mellitus (DM. These recommendations do not cover the whole range of pathologies that cause the development of testosterone deficiency (hypogonadism, but focus on its clinical variants and characteristic for men with diabetes. The recommendations provide data on the prevalence of hypogonadism in diabetes, its etiology. In the section "diagnostics" the features of anamnesis of patients with hypogonadism with diabetes, the necessary methods of physical and laboratory examination are presented in detail. The risk factors and clinical consequences of hypogonadism are separately examined. In the section "choice of treatment methods", there are possible treatment options for such patients using various androgenic therapies, taking into account the needs of the man, maintaining his reproductive function and risk factors. Particular attention is paid to indications, contraindications and risk factors for androgen therapy in men with diabetes, especially in old age. With this in mind, principles for monitoring the treatment are developed. Based on a large number of studies, favorable effects of androgen replacement therapy in men with hypogonadism and diabetes have been demonstrated.

The Evaluation of Fibroblast Growth Factor 23 Levels in Hypogonadotropic Hypogonadism

Directory of Open Access Journals (Sweden)

Hakan Demirci

2016-01-01

Full Text Available Aim: Our aim in this study was to investigate serum FGF-23 levels and its relationship with PTH, Ca and P in male patients with hypogonadotropic hypogonadism. Material and Method: Thirty-one male patients with hypogonadotropic hypogonadism and twenty healthy controls were enrolled in the study. The periferic venous blood samples of all the subjects involved in the study were taken for routine laboratory tests and serum testosteron, FSH, LH, PTH, P and Ca levels analysis. The serum samples were collected and stored at deep-freezer for serum FGF-23 level analysis. Results: It was observed that there was increase in serum P levels and there was decrease in PTH levels in patients with hypogonadotropic hypogonadism when compared with control group, however there was no difference in Ca and FGF-23 levels. It was determined that there were statistically significant difference between FGF-23 with P levels and PTH with Ca levels in correlation analysis. Discussion: The previous clinical studies have shown that there were bone metabolism disorders, secondary osteoporosis, changes in serum P and PTH levels in male patients with hypogonadotropic hypogonadism. In this study, we have observed that there is no correlation between all of those changes and one of the major regulators serum P, FGF-23.

Subsurface Sampling and Sensing Using Burrowing Moles

Science.gov (United States)

Stoker, C. R.; Richter, L.; Smith, W. H.

2004-01-01

Finding evidence for life on Mars will likely require accessing the subsurface since the Martian surface is both hostile to life and to preservation of biosignatures due to the cold dry conditions, the strong W environment, and the presence of strong oxidants. Systems are needed to probe beneath the sun and oxidant baked surface of Mars and return samples to the surface for analysis or to bring the instrument sensing underground. Recognizing this need, the European Space Agency incorporated a small subsurface penetrometer or Mole onto the Beagle 2 Mars lander. Had the 2003 landing been successful, the Mole would have collected samples from 1-1.5 m depth and delivered them to an organic analysis instrument on the surface. The de- vice called the Planetary Underground Tool (PLUTO), also measured soil mechanical and thermophysical properties. Constrained by the small mass and volume allowance of the Beagle lander, the PLUTO mole was a slender cylinder only 2 cm diameter and 28 cm long equipped with a small sampling device designed to collect samples and bring them to the surface for analysis by other instrument. The mass of the entire system including deployment mechanism and tether was 1/2 kg. sensor package underground to make in situ measurements. The Mars Underground Mole (MUM) is a larger Mole based on the PLUTO design but incorporating light collection optics that interface to a fiber optic cable in the tether that transmits light to a combined stimulated emission Raman Spectrometer and Short Wave Infrared (SWIR) reflectance Spectrometer with sensitivity from 0.7 to 2.5 micrometers. This instrument is called the Dual Spectral Sensor and uses a Digital Array Scanning Interferometer as the sensor technology, a type of fourier transform interferometer that uses fixed element prisms and thus is highly rugged compared to a Michaelson interferometer. Due to the size limitations of an on-Mole instrument compartment, and the availability of a tether, the sensor head

Agronomic performance of naked oat (Avena nuda L. and faba bean intercropping

Directory of Open Access Journals (Sweden)

Agnieszka Klimek-Kopyra

2015-06-01

Full Text Available The most common cereals for faba bean (Vicia faba L. used in intercrops is conventional oat (Avena sativa L. An alternative to oat may be naked oat (Avena nuda L., whose oil content and quality is double. Here, intercropping of naked oat with two different faba bean cultivars (determinate-high tannin and indeterminate-low tannin was compared with sole crops of each species in 2006-2008. The treatments were: sole naked oat at 500 kernels m², indeterminate sole faba bean at 50 seeds m², determinate sole faba bean at 70 seeds m², and an additive series of 25%, 50%, and 75% of faba bean seeding rate mixed with the naked oat seeding rate. Our results demonstrated that intercropping increased the Land Equivalent Ratio by +3% to +9% over sole cropping. Raising the faba bean seeding rate in a mixture from 25% to 75% reduced oat grain yield from 630 (determinate cultivar to 760 kg ha-1 (indeterminate cultivar but increased faba bean grain yield from 760 kg ha-1. Higher yield and leaf area index (LAI and photosynthetically active radiation (PAR values show that the indeterminate cultivar of faba bean is more suitable in mixture with naked oat. The high value of competition index (CR > 1 indicates domination and aggressiveness of faba bean towards naked oat. Regardless of cultivar type, mixture of faba bean with naked oat is less productive than pure sowing.

Prevalence of Toxoplasma gondii in common moles (Talpa europaea)

NARCIS (Netherlands)

Krijger, I.M.; Cornelissen, J.B.W.J.; Wisselink, H.J.; Meerburg, B.G.

2014-01-01

Background The prevalence of Toxoplasma gondii in common moles, Talpa europaea, was investigated in order to determine whether moles can serve as an indicator species for T. gondii infections in livestock. Findings In total, 86 moles were caught from 25 different sites in the Netherlands. Five

High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction

Science.gov (United States)

Jimenez-Balderas, F Javier; Tapia-Serrano, Rosario; Fonseca, M Eugenia; Arellano, Jorge; Beltran, Arturo; Yañez, Patricia; Camargo-Coronel, Adolfo; Fraga, Antonio

2001-01-01

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P hypogonadism and was associated with marked gonadal failure with very low testosterone levels. PMID:11714390

Wasting syndrome with deep bradycardia as presenting manifestation of long-standing severe male hypogonadotropic hypogonadism: a case series.

Science.gov (United States)

Passeri, Elena; Bonomi, Marco; Dangelo, Francesco; Persani, Luca; Corbetta, Sabrina

2014-09-27

Physiological functioning of the testes is important for cardiac health besides for virilisation, physical strength, behavior and reproduction; moreover, hypogonadism has been demonstrated as a significant risk marker of increased all-cause and cardiovascular mortality. We reported two cases of long-standing hypogonadotropic hypogonadism presenting with wasting, bradycardia and heart failure. The two patients were admitted to emergency department for deep weakness, unresponsive anemia and severe bradycardia, requiring in one case the implanting of a monocameral pace-maker for treatment of heart failure. No previous cardiologic disorders were known and cardiac ischemia was ruled out in both patients. The first patient presented congenital hypogonadotropic hypogonadism combined with mild central hypothyroidism and growth hormone deficiency occurred in the peripubertal age, while the second one was diagnosed with isolated adult-onset severe central hypogonadism. Testosterone deficiency was the main feature in both patients as physical examination revealed clinical stigmata of hypogonadism and testosterone replacement induced a dramatic improvement of general condition. Genetic analysis of genes involved in hypogonadotropic hypogonadism failed to identify alterations. Long-standing hypogonadism in males can be associated with life threatening body alterations including severe bradycardia and heart failure.

Myotonic dystrophy type 1 with diabetes mellitus, mixed hypogonadism and adrenal insufficiency

Directory of Open Access Journals (Sweden)

Ken Takeshima

2018-01-01

Full Text Available Myotonic dystrophy type 1 (DM1 is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.

Genetics of congenital hypogonadotropic hypogonadism in Denmark

DEFF Research Database (Denmark)

Tommiska, Johanna; Känsäkoski, Johanna; Christiansen, Peter

2014-01-01

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized by incomplete/absent puberty caused by deficiency or defective action of gonadotropin-releasing hormone (GnRH). The phenotypic features of patients with CHH vary from genital hypoplasia and absent puberty to reversal...

Hipogonadismo e função tireoidiana em ratas hipertireóideas e eutireóideas Hypogonadism and thyroid function in hyper and euthyroid rats

Directory of Open Access Journals (Sweden)

R. Serakides

2000-12-01

Full Text Available A influência do hipogonadismo sobre a função tireoidiana de ratas hipertireóideas e eutireóideas foi medida com base no perfil sérico dos hormônios tireoidianos, dos esteróides ovarianos e do TSH e na histomorfometria da tireóide. Ratas Wistar, com cinco meses de idade, castradas, foram mantidas em estado eutireóideo ou hipertireóideo por períodos de 30, 60 e 90 dias. Um grupo não castrado foi mantido nas mesmas condições e serviu como controle. O hipertireoidismo foi induzido mediante a administração diária 50µg de L-tiroxina, por sonda gástrica. Ao final de cada período, nove ratas por grupo tiveram suas tireóides inspecionadas, pesadas e processadas para avaliação histomorfométrica e o plasma sangüíneo colhido para dosagem de estradiol, progesterona, T4 total, T4 livre, T3 total e TSH. O hipogonadismo não alterou os valores de T3 total e de TSH, mas aumentou significativamente as concentrações de T4 livre, independente do estado hipertireóideo ou eutireóideo. As concentrações de T4 total sofreram influência da castração apenas no grupo hipertireóideo. O peso das tireóides não sofreu influência do hipogonadismo, mas a altura do epitélio folicular nos animais eutireóideos variou ao longo do experimento, apresentando-se maior aos 30 e 90 dias e menor aos 60 dias. Não se observou correlação entre os níveis de estrógeno e as variáveis estudadas, mas os níveis de progesterona foram inversamente proporcionais à elevação dos níveis de T4 total e T4 livre. Concluiu-se que o hipogonadismo altera a histomorfometria da tireoide em indivíduos eutireóideos, aumenta os valores plasmáticos de T4 livre independentemente do estado funcional da tireóide e potencializa a elevação de T4 total no hipertireoidismo, provavelmente sob influência do hipoprogesteronismo e não do hipoestrogenismo.The effects of hypogonadism on thyroid function of hyper and euthyroid rats were measured based on plasmatic

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

Science.gov (United States)

Houdek, Devon

2017-01-01

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. PMID:28408926

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

Directory of Open Access Journals (Sweden)

Gary Golds

2017-01-01

Full Text Available It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed.

Naked singularities and cosmic censorship: comment on the current situation

International Nuclear Information System (INIS)

Seifert, H.J.

1979-01-01

The current discussion is mainly concerned with how, or indeed, whether space-times possessing naked singularities can be ruled out as being too unrealistic or not being singular at all. The present position is summarized, with references, under the following headings: the Hawking-Penrose existence theorems, hydrodynamical singularities and the strength of naked singularities. (UK)

Anosmia Predicts Hypogonadotropic Hypogonadism in CHARGE Syndrome

NARCIS (Netherlands)

Bergman, Jorieke E. H.; Bocca, Gianni; Hoefsloot, Lies H.; Meiners, Linda C.; van Ravenswaaij-Arts, Conny M. A.

Objective To test the hypothesis that a smell test could predict the occurrence of hypogonadotropic hypogonadism (HH) in patients with CHARGE syndrome, which is a variable combination of ocular coloboma, heart defects, choanal atresia, retardation of growth/development, genital hypoplasia, and ear

46,XY hypergonadotropic hypogonadism and myasthenia gravis.

Science.gov (United States)

Lichiardopol, Corina; Herlea, V; Ioan, Virginia; Tomulescu, V; Mixich, F

2006-01-01

Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.

Diagnosis of hydatidiform mole by hysterography through transabdominal injection

Energy Technology Data Exchange (ETDEWEB)

Kim, Chung Kyu; Park, Chang Yun; Choi, Byung Sook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1972-03-15

Molar pregnancy presents a pathologic condition requiring surgery of the uterus promptly as possible although hydatidiform mole itself is a benign disease. In order to remove the mole as quickly as possible, early diagnosis is desirable. In actual practice, however, definite preoperative diagnosis by clinical manifestation is impossible since which is vague or altogether absent symptoms especially in first trimester. Hysterography by transabdominal injection is very valuable and easy procedure for accurate diagnosis of hydatidiform mole which shows typical honey combed, moth eaten or sponge pattern on roentgenography. We have experienced 68 cases of hydatidiform mole during last five and half years. Among them hysterography by transabdominal route was done on 26 cases and shows 96% diagnostic accuracy. One missed case was turned out to be missed abortion. The absence of accidents indicates the harmlessness of the method. We feel the best approach in making diagnosis of hydatidiform mole among clinically borderline and in conclusive for mole pregnancy and its differential diagnosis is by use of transabdominal hysterography.

Diagnosis of hydatidiform mole by hysterography through transabdominal injection

International Nuclear Information System (INIS)

Kim, Chung Kyu; Park, Chang Yun; Choi, Byung Sook

1972-01-01

Molar pregnancy presents a pathologic condition requiring surgery of the uterus promptly as possible although hydatidiform mole itself is a benign disease. In order to remove the mole as quickly as possible, early diagnosis is desirable. In actual practice, however, definite preoperative diagnosis by clinical manifestation is impossible since which is vague or altogether absent symptoms especially in first trimester. Hysterography by transabdominal injection is very valuable and easy procedure for accurate diagnosis of hydatidiform mole which shows typical honey combed, moth eaten or sponge pattern on roentgenography. We have experienced 68 cases of hydatidiform mole during last five and half years. Among them hysterography by transabdominal route was done on 26 cases and shows 96% diagnostic accuracy. One missed case was turned out to be missed abortion. The absence of accidents indicates the harmlessness of the method. We feel the best approach in making diagnosis of hydatidiform mole among clinically borderline and in conclusive for mole pregnancy and its differential diagnosis is by use of transabdominal hysterography

Spatial variability of soil electrical conductivity under the mole rats (Spalax microphthalmus digging activity at the different scales

Directory of Open Access Journals (Sweden)

A. V. Zhukov

2012-07-01

Full Text Available The soil mounds emerged owing to the mole rats’ digging activity have been shown to be characterised by less electrical conductivity than surrounded soil. This effect is due to the changes of the mounds bulk’s density and moisture. The effect of the mole rats’ digging activity on the soil electrical conductivity has been found not to be restricted by the geometrical border of the mounds. The mounds are surrounded by 1–1.5 m halo of increased soil electrical conductivity. The halo size is increased with the aging of the mound and with the compacting of their aggregation.

Late-onset hypogonadism

Directory of Open Access Journals (Sweden)

Piotr Dudek

2017-06-01

Full Text Available In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH. In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

Science.gov (United States)

Iglesias, P; Prado, F; Muñoz, A; Guerrero, M T; Macías, M C; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2015-04-01

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, phypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, phypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Hypogonadism as a new comorbidity in male patient's selection for bariatric surgery: towards an extended concept of metabolic surgery?

Science.gov (United States)

Lucchese, M; Maggi, M

2013-12-01

Hypogonadism and subfertility can be frequently associated to obesity. These endocrine alterations may have consequences in the health and quality of life of obese men since they may result in impaired fertility and poor sexual life. As many clinical reports suggest, weight loss can ameliorate hypogonadism and, more generally, alterations in sex hormones. This effect is evident even when weight loss is induced by bariatric surgery. The evidence that hypogonadism in morbidly obese patients can regress after bariatric surgery should lead us to consider it as a modifiable comorbidity associated to obesity. This would have as a consequence that obese male patients with symptomatic hypogonadism could be candidates for bariatric surgery even with a BMI hypogonadal males, should be encouraged.

A study to evaluate the prevalence of hypogonadism in Indian males with Type-2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Pankaj Kumar Agarwal

2017-01-01

Full Text Available Background: A high prevalence of hypogonadism in men with Type-2 diabetes mellitus (T2DM has been reported worldwide. Objectives: To evaluate the prevalence of hypogonadism in Indian males with T2DM and assess the primary and secondary hypogonadism along with androgen deficiency. Materials and Methods: In this cross-sectional study, 900 men with T2DM were evaluated using androgen deficiency in aging male questionnaire. They were screened for demographic characteristics, gonadal hormone levels, lipid profile, and glycosylated hemoglobin. Results: The prevalence of hypogonadism in T2DM patients was found to be 20.7% (186 out of 900. Hypogonadism was of testicular origin (primary in 48/186 (25.8% patients, of pituitary or hypothalamic origin (secondary in 14/186 (7.53%, and remaining 124/186 (66.67% patients were found to have low testosterone with the inappropriate normal level of luteinizing hormone and Follicle-stimulating hormone. 451/900 (50.1% patients were only symptomatic but had normal testosterone levels. Further 263 patients out 900 were asymptomatic, of which 51/900 (5.7% patients had low levels of testosterone and 212/900 (23.5% patients had normal testosterone level without symptoms. There were no deaths or other serious adverse events except mild pyrexia which was not related to the study. Conclusion: Hypogonadism diagnosis, at times, might not be validated with the help of androgen deficiency questionnaire or symptoms only. Given the large number of patients of T2DM in India, the incidence of hypogonadism is more in diabetic patients as compared to the general population. Hence, implementation of screening programs in diabetic patients is necessary to understand and detect individuals with low serum total testosterone at any early stage and to supplement testosterone accordingly.

Naked singularity formation in Brans-Dicke theory

Energy Technology Data Exchange (ETDEWEB)

Ziaie, Amir Hadi; Atazadeh, Khedmat [Department of Physics, Shahid Beheshti University, Evin, Tehran 19839 (Iran, Islamic Republic of); Tavakoli, Yaser, E-mail: am.ziaie@mail.sbu.ac.i, E-mail: k-atazadeh@sbu.ac.i, E-mail: tavakoli@ubi.p [Departamento de Fisica, Universidade da Beira Interior, Rua Marques d' Avila e Bolama, 6200 Covilha (Portugal)

2010-04-07

Gravitational collapse of the Brans-Dicke scalar field with non-zero potential in the presence of matter fluid obeying the barotropic equation of state, p = wrho, is studied. Utilizing the concept of the expansion parameter, it is seen that the cosmic censorship conjecture may be violated for w=-1/3 and w=-2/3 which correspond to the cosmic string and domain wall, respectively. We have shown that physically, it is the rate of collapse that governs the formation of a black hole or a naked singularity as the final fate of dynamical evolution and only for these two cases can the singularity be naked as the collapse end state. Also the weak energy condition is satisfied by the collapsing configuration.

Early caries naked-eyed examination

International Nuclear Information System (INIS)

Bakhmutov, D; Gonchukov, S; Voytenok, O; Kharchenko, O; Zubov, B

2008-01-01

In view of its potential for dental diagnostics, noninvasive optical methods have been the object of research for the last years. Different techniques (spectroscopy, microscopy, and tomography) are used to discriminate between caries and sound enamel. The main aim of this paper is to determine a simple way to see incipient caries with the naked eye

Long-lived cancer-resistant rodents as new model species for cancer research

Directory of Open Access Journals (Sweden)

Jorge eAzpurua

2013-01-01

Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

Childhood growth in boys with congenital hypogonadotropic hypogonadism

DEFF Research Database (Denmark)

Varimo, Tero; Hero, Matti; Laitinen, Eeva-Maria

2016-01-01

BACKGROUND: We describe childhood growth patterns in a series of well-characterized patients with congenital hypogonadotropic hypogonadism (CHH) with special emphasis on genotype-phenotype correlation. METHODS: We retrospectively evaluated the growth charts of 36 males with CHH (27 from Finland...

Constraints on the structure of naked singularities in classical general relativity

International Nuclear Information System (INIS)

Newman, R.P.A.; Joshi, P.S.

1988-01-01

The known examples of naked singularities in general relativity are, in a certain sense, either gravitationally or causally innocuous. A cosmic censorship theorem is formulated and proved to the effect that this behaviour is characteristic of naked singularities in general spacetimes which do not deviate too far from spherical symmetry. copyright 1988 Academic Press, Inc

Virtually naked: virtual environment reveals sex-dependent nature of skin disclosure.

Directory of Open Access Journals (Sweden)

Anna M Lomanowska

Full Text Available The human tendency to reveal or cover naked skin reflects a competition between the individual propensity for social interactions related to sexual appeal and interpersonal touch versus climatic, environmental, physical, and cultural constraints. However, due to the ubiquitous nature of these constraints, isolating on a large scale the spontaneous human tendency to reveal naked skin has remained impossible. Using the online 3-dimensional virtual world of Second Life, we examined spontaneous human skin-covering behavior unhindered by real-world climatic, environmental, and physical variables. Analysis of hundreds of avatars revealed that virtual females disclose substantially more naked skin than virtual males. This phenomenon was not related to avatar hypersexualization as evaluated by measurement of sexually dimorphic body proportions. Furthermore, analysis of skin-covering behavior of a population of culturally homogeneous avatars indicated that the propensity of female avatars to reveal naked skin persisted despite explicit cultural norms promoting less revealing attire. These findings have implications for further understanding how sex-specific aspects of skin disclosure influence human social interactions in both virtual and real settings.

Hydatidiform mole in Aminu Kano teaching hospital, northwestern ...

African Journals Online (AJOL)

Background: Hydatidiform mole is a benign tumour of the trophoblast tissue and a relatively common gynaecological emergency. It could resolve spontaneously following evacuation, however 9-20% of patients with complete hydatidiform mole go on to have gestational trophoblast neoplasia. It is potentially curable once the ...

Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

Science.gov (United States)

Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

2016-01-01

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH

DEFF Research Database (Denmark)

Main, Katharina M; Schmidt, Ida M; Toppari, Jorma

2002-01-01

BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins postna...... observed. CONCLUSIONS: Gonadotropin treatment in an infant with hypogonadotropic hypogonadism succeeded in inducing an increase in inhibin B and testicular growth.......BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins...... the normal range (0.05-0.17 IU/l and 79-112 pg/ml respectively). METHODS: From 7.9 to 13.7 months of age, the patient was treated with recombinant human LH and FSH in doses of 20 and 21.3 IU s.c. twice weekly respectively. RESULTS: During treatment concentrations of LH, FSH, inhibin B and estradiol increased...

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

Science.gov (United States)

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-08-15

This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.) Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological basis, confirmed by hormone assays.Hormonal assessment is based on measurement of circulating testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels can be informative, but use of calculated free testosterone is not recommended for clinical decision making.Testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age.Currently, there are limited data from high-quality randomised controlled trials with clinically meaningful outcomes to justify testosterone treatment in older men, usually with chronic disease, who have low circulating testosterone levels but without hypothalamic, pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes are associated with lowering of circulating testosterone level, but without elevation of LH and FSH levels. Whether these are non-specific consequences of non-reproductive disorders or a correctable deficiency state is unknown, but clear evidence for efficacy and safety of testosterone therapy in this setting is lacking.Glucocorticoid and opioid use is associated with possibly reversible reductions in circulating testosterone level, without elevation of LH and FSH levels. Where continuation of glucocorticoid or opioid therapy is necessary, review by an endocrinologist may be warranted.Changes in management as result of the position statement: Men with pathological hypogonadism should

Invariant identification of naked singularities in spherically symmetric spacetimes

International Nuclear Information System (INIS)

Torres, R

2012-01-01

The study of generic naked singularities and their implications for the cosmic censorship conjecture is still an open issue in the framework of general relativity. One of the obstacles can be traced to the procedures for identifying naked singularities. Usually, the methods applied are not only model and coordinate dependent, but they very often rely in some strong assumptions on the degree of differentiability of the physical magnitudes of the model (such as the mass, density, etc) in the singularity. In this paper, we present a coordinate independent framework for identifying naked singularities based on invariants which is also devoid of strong differentiability requirements. The approach is intended to analyse whole families of models and to provide general results related to the cosmic censorship conjecture. Moreover, since the framework has a strict geometrical nature it can be used with alternative theories of gravitation as long as they assume the existence of a Lorentzian manifold. We exemplify its strength by applying it to the study of the collapse of radiation in radiative coordinates and the collapse of dust in comoving coordinates. (paper)

Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

Science.gov (United States)

Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

2016-07-01

This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.

CO2 Monitoring and Background Mole Fraction at Zhongshan Station, Antarctica

Directory of Open Access Journals (Sweden)

Yulong Sun

2014-09-01

Full Text Available Background CO2 mole fraction and seasonal variations, measured at Zhongshan station, Antarctica, for 2010 through 2013, exhibit the expected lowest mole fraction in March with a peak in November. Irrespective of wind direction, the mole fraction of CO2 distributes evenly after polluted air from station operations is removed from the data sets. The daily range of average CO2 mole fraction in all four seasons is small. The monthly mean CO2 mole fraction at Zhongshan station is similar to that of other stations in Antarctica, with seasonal CO2 amplitudes in the order of 384–392 µmol∙mol−1. The annual increase in recent years is about 2 µmol∙mol−1∙yr−1. There is no appreciable difference between CO2 mole fractions around the coast of Antarctica and in the interior, showing that CO2 observed in Antarctica has been fully mixed in the atmosphere as it moves from the north through the southern hemisphere.

Ultrasonographic findings of Myoma, H-mole and Missed abortion

International Nuclear Information System (INIS)

Huh, Nam Yoon; You, H. S.; Seong, K. J.; Park, C. Y.

1982-01-01

Ultrasonography is very important in the diagnosis of various kinds of diseases in Obsterics and Gynecology. It has high diagnostic accuracy in the diagnosis of pelvic masses and widely used for the detection of normal orpathologic pregnancy. But still it is difficult to differentiate degenerated myoma, H-mole and missed abortion by ultrasonography. So the authors analyzed the ultrasonographic findings of 81 patients with myoma(29 cases), H-mole(23 cases), and missed abortion(29 cases) and the results are as follows; 1. Diagnostic accuracy was 8.6% in myoma, 87% in H-mole and 89% in missed abortion. 2. The most typical ultrasonographic finding of myoma was obulated mass contour with nonhomogenous internal echo. 3. The most characteristic finding of H-mole was fine vesicular pattern internal echo with globular enlargement of uterus. 4. The most frequent finding of missed abortion was deformed gestational sac with or without remained fetal echo. 5. Clinical correlation was very important for accurate diagnosis, especially when differential diagnosis was very difficult between myoma with marked cystic degeneration, missed abortion with large distorted gestational sac and H-mole with severe degeneration

MOLE 2.0: Advanced approach for analysis of biomacromolecular channels

OpenAIRE

Sehnal D.; Varekova R.S.; Berka K.; Pravda L.; Navratilova V.; Banas P.; Ionescu C.-M.; Otyepka M.; Koca J.

2013-01-01

Background Channels and pores in biomacromolecules (proteins, nucleic acids and their complexes) play significant biological roles, e.g., in molecular recognition and enzyme substrate specificity. Results We present an advanced software tool entitled MOLE 2.0, which has been designed to analyze molecular channels and pores. Benchmark tests against other available software tools showed that MOLE 2.0 is by comparison quicker, more robust and more versatile. As a new feature, MOLE 2.0 estimates ...

Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome.

Science.gov (United States)

Bogefors, C; Isaksson, S; Bobjer, J; Kitlinski, M; Leijonhufvud, I; Link, K; Giwercman, A

2017-07-01

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone  10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients. © 2017 American Society of Andrology and European Academy of Andrology.

MRI in haemochromatosis: pituitary versus testicular iron deposition in five patients with hypogonadism

International Nuclear Information System (INIS)

Miaux, Y.; Daurelle, P.; Zagdanski, A.M.; Passa, P.; Bourrier, P.; Frija, J.

1995-01-01

Haemochromatosis is a disease characterised by iron deposition in the liver and other organs. Hypogonadism is a commonly associated condition and may be either primary due to testicular lesions or secondary due to pituitary dysfunction. Hypogonadism secondary to pituitary dysfunction is more frequent and is thought to be related to iron deposition in the anterior pituitary. Increased iron content decreases signal intensity of spin-echo MRI images because T2 values are significantly shortened. Our purpose in this study was to evaluate by MRI iron deposition in the liver, testis and pituitary of 6 patients with haemochromatosis and severe hypogonadotrophic hypogonadism. Six subjects served as controls. There was a significant T2 shortening of the liver and pituitary in patients with haemochromatosis compared with control patients. Therefore MRI detected iron overload in the pituitary and no iron in the testis, supporting the hypothesis of hypogonadotrophic pituitary insufficiency due to cellular damage induced by iron overload in the anterior pituitary gland. (orig.)

Delayed puberty and hypogonadotropic hypogonadism. Differential diagnosis and treatment

NARCIS (Netherlands)

Snoep, Marinus Cornelis

1978-01-01

This thesis describes a method enabling a prospecrive differential diagnosis to be made berween delayed puberty (DP) and hypogonadotropic hypogonadism (HH). The influence of androgen administration on the gonadal feedback sysrem of patients with delayed puberty was also studied. ... Zie: Summary

Basic consensus document on late-onset hypogonadism.

Science.gov (United States)

Becerra Fernández, Antonio; Enríquez Acosta, Luis

2008-01-01

One of the most important elements in men's live is the ability to engage in normal sexual activity; loss of this activity has always been considered especially important. The relationship between sexual activity, as well as other masculine characteristics, and the testicles has been well known since ancient times and has been related to the slow decrease in testosterone secretion with advanced age. Male hypogonadism is one of the most frequent and under-diagnosed endocrine diseases. Several terms have been proposed to refer to clinical situations caused by the age-related decline in male gonadal function; currently, the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a clinical and biochemical syndrome associated with advanced age (in men), characterized by typical symptoms and reduced serum testosterone concentrations, which can affect multiple organs and systems and reduce quality of life. This syndrome can be treated and the alterations produced can be reversed. To achieve this, a diagnostic protocol that approaches the multiple factors related to the risks and benefits of treatment is required. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

Comparative morphology of the penis and clitoris in four species of moles (Talpidae)

Science.gov (United States)

Sinclair, Adriane Watkins; Glickman, Stephen; Catania, Kenneth; Shinohara, Akio; Baskin, Lawrence; Cunha, Gerald R.

2017-01-01

The penile and clitorial anatomy of four species of Talpid moles (broad-footed, star-nosed, hairy-tailed, and Japanese shrew moles) were investigated to define penile and clitoral anatomy and to examine the relationship of the clitoral anatomy with the presence or absence of ovotestes. The ovotestis contains ovarian tissue and glandular tissue resembling fetal testicular tissue and can produce androgens. The ovotestis is present in star-nosed and hairy-tailed moles, but not in broad-footed and Japanese shrew moles. Using histology, 3D reconstruction, and morphometric analysis, sexual dimorphism was examined in regard to a nine feature masculine trait score that included perineal appendage length (prepuce), anogenital distance, and presence/absence of bone. The presence/absence of ovotestes was discordant in all four mole species for sex differentiation features. For many sex differentiation features, discordance with ovotestes was observed in at least one mole species. The degree of concordance with ovotestes was highest for hairy-tailed moles and lowest for broad-footed moles. In relationship to phylogenetic clade, sex differentiation features also did not correlate with the similarity/divergence of the features and presence/absence of ovotestes. Hairy-tailed and Japanese shrew moles reside in separated clades, but they exhibit a high degree of congruence. Broad-footed and hairy-tailed moles reside within the same clade but had one of the lowest correlations in features and presence/absence of ovotestes. Thus, phylogenetic affinity and the presence/absence of ovotestes are poor predictors for most sex differentiation features within mole external genitalia. PMID:28251823

Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

OpenAIRE

Popović, V.; Milosević, Z.; Djukanović, R.; Micić, D.; Nesović, M.; Manojlović, D.; Djordjević, P.; Mićić, J.

1988-01-01

Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

Can treatment of nocturia increase testosterone level in men with late onset hypogonadism?

Science.gov (United States)

Kim, Jong Wook; Chae, Ji Yun; Kim, Jin Wook; Yoon, Cheol Yong; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong; Moon, Du Geon

2014-04-01

To assess the effect of desmopressin on serum testosterone level in men with nocturia and late onset hypogonadism. We prospectively enrolled men with nocturia and symptoms of late onset hypogonadism. Desmopressin (0.1 mg) was administered once daily to patients for 12 weeks, and we then compared serum testosterone levels, electrolytes, frequency volume chart indices, and changes in the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Aging Male's Symptom scales before and after treatment. Patients with a history of cardiovascular disease or hyponatremia, those using hypnotics, and those who had primary hypogonadism or hypogonadotrophic hypogonadism were excluded from the study. Sixty-two men (mean age, 68.4 years) completed pre- and post-treatment questionnaires and underwent laboratory testing. At the end of the study, the testosterone levels in men with low testosterone levels (treatment (2.85 ± 0.58 to 3.97 ± 1.44 ng/mL; P = .001). Mean scores had decreased from 17.7 to 13.9 (IPSS), 3.8 to 3.2 (IPSS-Quality of Life), and 33.7 to 31.1 (Aging Male's Symptom). On the frequency volume chart, nocturnal urine volume, nocturnal polyuria index, actual number of nocturia events, nocturia index, and nocturnal bladder capacity index were significantly decreased. Desmopressin improved nocturia and other urinary symptoms. Moreover, serum testosterone levels increased significantly in men with low testosterone levels after 12-week desmopressin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

Science.gov (United States)

Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

2012-04-01

Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with

How to recognize late-onset hypogonadism in men with sexual dysfunction

Science.gov (United States)

Corona, Giovanni; Rastrelli, Giulia; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2012-01-01

Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels. PMID:22286862

Naked-eye 3D imaging employing a modified MIMO micro-ring conjugate mirrors

Science.gov (United States)

Youplao, P.; Pornsuwancharoen, N.; Amiri, I. S.; Thieu, V. N.; Yupapin, P.

2018-03-01

In this work, the use of a micro-conjugate mirror that can produce the 3D image incident probe and display is proposed. By using the proposed system together with the concept of naked-eye 3D imaging, a pixel and a large volume pixel of a 3D image can be created and displayed as naked-eye perception, which is valuable for the large volume naked-eye 3D imaging applications. In operation, a naked-eye 3D image that has a large pixel volume will be constructed by using the MIMO micro-ring conjugate mirror system. Thereafter, these 3D images, formed by the first micro-ring conjugate mirror system, can be transmitted through an optical link to a short distance away and reconstructed via the recovery conjugate mirror at the other end of the transmission. The image transmission is performed by the Fourier integral in MATLAB and compares to the Opti-wave program results. The Fourier convolution is also included for the large volume image transmission. The simulation is used for the manipulation, where the array of a micro-conjugate mirror system is designed and simulated for the MIMO system. The naked-eye 3D imaging is confirmed by the concept of the conjugate mirror in both the input and output images, in terms of the four-wave mixing (FWM), which is discussed and interpreted.

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.

Science.gov (United States)

Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T; Codner, Ethel

2016-10-01

Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism.

Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels.

Science.gov (United States)

Blick, Gary

2013-03-01

To determine the incidence of hypogonadism in men with human immunodeficiency virus (HIV)/acquired immunodeficiency virus (AIDS), the most useful serum testosterone measurement and threshold for diagnosing hypogonadism, and the comparative efficacy of 2 testosterone replacement therapy (TRT) 1% gels (AndroGel® [Abbott Laboratories] and Testim® [Auxilium Pharmaceuticals, Inc.]). This was a 2-stage observational study. In stage 1, patient records from 2 medical practices specializing in HIV/AIDS were reviewed. Eligible patients were aged ≥ 18 years; had HIV-seropositive status confirmed by enzyme-linked immunosorbent assay and western blot test or HIV-1 viremia confirmed by HIV-1 RNA polymerase chain reaction; and had prior baseline testosterone assessments for hypogonadism (ie, presence of signs/symptoms of hypogonadism as well as total testosterone [TT] and free testosterone [FT] level measurements). Stage 2 included the evaluation of patients from stage 1 who were treated with 5 to 10 g/day of TRT. The stage 2 inclusion criteria were a diagnosis of low testosterone (defined as TT level < 300 ng/dL and/or FT level < 50 pg/mL, as per The Endocrine Society guidelines and presence/absence of hypogonadal signs and symptoms); ≥ 12 months of evaluable sign and symptom assessments and TT/FT level measurements while on TRT with either Testim® or AndroGel®; and ≥ 4 weeks on initial TRT if the initial TRT was switched or discontinued. Four hundred one of 422 patients met the stage 1 inclusion criteria and 167 of 401 patients (AndroGel®, n = 92; Testim®, n = 75) met the stage 2 inclusion criteria. Total testosterone level < 300 ng/dL alone identified 24% (94 of 390) of patients as hypogonadal, but failed to diagnose an additional 111 patients (67.7%) with FT levels < 100 pg/mL and hypogonadal symptoms. Through month 12, AndroGel® increased mean TT levels by +42.8% and FT levels by +66.9%, compared with +178.7% (P = 0.017) and +191% (P = 0.039), respectively, for

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism.

Science.gov (United States)

Ruvolo, Giovanni; Roccheri, Maria Carmela; Brucculeri, Anna Maria; Longobardi, Salvatore; Cittadini, Ettore; Bosco, Liana

2013-04-01

An observational clinical and molecular study was designed to evaluate the effects of the administration of recombinant human FSH on sperm DNA fragmentation in men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In the study were included 53 men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In all patients, sperm DNA fragmentation index (DFI), assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) in situ DNA nick end-labelling (TUNEL) assay, was evaluated before starting the treatment with 150 IU of recombinant human FSH, given three times a week for at least 3 months. Patients' semen analysis and DNA fragmentation index were re-evaluated after the 3-month treatment period. After recombinant human FSH therapy, we did not find any differences in terms of sperm count, motility and morphology. The average DNA fragmentation index was significantly reduced (21.15 vs 15.2, p15 %), while no significant variation occurred in the patients with DFI values ≤ 15 %. Recombinant human FSH administration improves sperm DNA integrity in hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia men with DNA fragmentation index value >15 % .

Ground sounds: Seismic detection in the golden mole

Science.gov (United States)

Narins, Peter M.; Lewis, Edwin R.

2004-05-01

The Namib Desert golden mole is a nocturnal, surface-foraging mammal, possessing a massively hypertrophied malleus which presumably confers low-frequency, substrate-vibration sensitivity through inertial bone conduction. Foraging trails are punctuated with characteristic sand disturbances in which the animal's head dips under the sand. The function of this behavior is not known but it is thought that it may be used to obtain a seismic fix on the next mound to be visited. To test this, we measured the local seismic vibrations both on the top of a mound and on the flats. The spectrum recorded on the flats shows a relatively low-amplitude peak at about 120 Hz, whereas the spectral peak recorded from the mound is nearly 17 dB greater in amplitude and centered at 310 Hz. This suggests that mounds act as seismic beacons for the golden moles that would be detectable from distances corresponding to typical intermound distances of 20-25 m. In addition, out of the 117 species for which data are available, these golden moles have the greatest ossicular mass relative to body size (Mason, personal communication). Functionally, they appear to be low-frequency specialists, and it is likely that golden moles hear through substrate conduction. [Work supported by NIH.

Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism

Science.gov (United States)

Rodriguez, Katherine M.; Pastuszak, Alexander W.; Lipshultz, Larry I.

2016-01-01

Introduction Hypogonadism is a growing concern in an aging male population. Historically treated using exogenous testosterone, concerns about possible adverse effects of testosterone have led physicians to seek alternative treatment approaches. Areas Covered Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist that is FDA-approved for the treatment of ovarian dysfunction in women. Clomiphene citrate has also been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility. Here we review the literature examining the efficacy and safety of enclomiphene citrate in the setting of androgen deficiency. Expert Opinion Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option. PMID:27337642

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

Science.gov (United States)

Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

2017-10-15

Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

International Nuclear Information System (INIS)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Greenspan, S.L.; Rosenthal, D.I.; Crowley, W.F. Jr.

1987-01-01

To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarly decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism

The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy

DEFF Research Database (Denmark)

Niemann, Isa; Hansen, Estrid S; Sunde, Lone

2007-01-01

classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. METHODS: 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis......OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting......-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however...

Late onset hypogonadism of men is not equivalent to the menopause.

Science.gov (United States)

Saad, Farid; Gooren, Louis J

2014-09-01

Some men between the ages 45 and 60 years develop complaints and symptoms reminiscent of menopausal complaints in women. So, parallels were sought between the changes in female and male endocrinology during that period of life. Indeed, men do show a decline of serum testosterone from age 40 to 50 years onwards but it is a slow decline of 1-2% per year and over time it may amount to hypogonadism. The mechanism of a decline in serum testosterone in men does not resemble the menopause; it is partially an aging neuroendocrine system with a less efficient testosterone production but equally or more important, the result of inhibition of testosterone production by metabolic factors in relation to visceral obesity. These effects are in part reversible with weight loss. A hypogonadal state in aging men has deleterious effects. Mortality of all causes is highest in men with low testosterone impacting on their metabolic state leading to diabetes mellitus, cardiovascular disease, osteoporosis, and sexual dysfunction. Normalization of testosterone in aging hypogonadal men has a beneficial effect on the above pathologies. The fear that testosterone treatment of elderly men would lead to prostate disease has not been substantiated in studies. So, while men do not have a 'menopause', testosterone deficiency in old age deserves serious attention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

Science.gov (United States)

Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

2017-07-01

This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

The fields of a naked singularity and a black hole in mutual equilibrium

Science.gov (United States)

Paolino, Armando; Pizzi, Marco

2008-01-01

Recently Alekseev and Belinski have presented a new exact solution of the Einstein-Maxwell equation which describes two Reissner-Nordstrom (RN) sources in reciprocal equilibrium (no struts nor strings) one source is a naked singularity, the other is a black hole. In this paper we use the Alekseev-Belinki solution in the special case in which the charge of the black hole is zero-therefore we have a naked singularity near a neutral black hole. We give the plots of the electric force lines in both the cases in which the naked singularity has a mass comparable with the black hole and in which it is much smaller. The analysis of this latter case confirm the goodness of the Hanni-Ruffini approximation.

Remission of type 2 diabetes in a hypogonadal man under long-term testosterone therapy

Directory of Open Access Journals (Sweden)

Ahmad Haider

2017-09-01

Full Text Available In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes.

An adolescent with 48,xxyy syndrome with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder and renal malformations

OpenAIRE

Prasad Katulanda; J. Rasika D. K. Rajapakse; Jayani Kariyawasam; Rohan Jayasekara; Vajira H. W. Dissanayake

2012-01-01

48,XXYY is a rare sex chromosome aneuploidy affecting 1 in 18,000 to 50,000 male births. They present with developmental delay, hypogonadism, gynecomastia, intention tremors, and a spectrum of neurodevelopmental and psychiatric disorders. At one time this condition was considered a variant of Klinefelter syndrome. In clinically suspected cases, 48,XXYY syndrome can be diagnosed by chromosome culture and karyotyping. This patient presented with hypergonadotrophic hypogonadism, attention defici...

Multi-Institutional Survey of Medical Treatment for Late-Onset Hypogonadism in Japan.

Science.gov (United States)

Taniguchi, Hisanori; Matsuda, Tadashi

2017-03-01

The adequate criteria for late-onset hypogonadism (LOH) diagnosis, including serum testosterone levels, type (total or free testosterone) and duration of androgen replacement therapy, and evaluations of treatment effectiveness remain controversial. To evaluate the current status of medical treatment for LOH in Japan, the first nationwide survey were performed. A total of 35 questionnaires answered by urologists in high-volume facilities were analyzed. The median numbers of patients with hypogonadism-related symptoms per month were 10. Aging Male Symptom Score, International Index of Erectile Function, and International Prostate Symptom Score questionnaires were widely used for questionnaires. The diagnostic criteria for LOH varied. Among the patients who presented with hypogonadism-related symptoms, the mean proportion of patients undergoing treatment for LOH was 62.3%. In Japan, LOH was treated not only with testosterone enanthate injections or testosterone ointment but also with Kampo medicine. In many facilities, LOH treatment effectiveness was assessed after a 3-month period. Efficacy was assessed in different ways. Treatment effectiveness rate ranged from 30% to 80%. The duration of LOH treatment was not fixed and was established individually by both the patient and treating physician. This study showed that the real clinical practices for LOH are very diverse, and a general consensus is needed.

Naked Black Hole Firewalls.

Science.gov (United States)

Chen, Pisin; Ong, Yen Chin; Page, Don N; Sasaki, Misao; Yeom, Dong-Han

2016-04-22

In the firewall proposal, it is assumed that the firewall lies near the event horizon and should not be observable except by infalling observers, who are presumably terminated at the firewall. However, if the firewall is located near where the horizon would have been, based on the spacetime evolution up to that time, later quantum fluctuations of the Hawking emission rate can cause the "teleological" event horizon to have migrated to the inside of the firewall location, rendering the firewall naked. In principle, the firewall can be arbitrarily far outside the horizon. This casts doubt about the notion that firewalls are the "most conservative" solution to the information loss paradox.

Naked Black Hole Firewalls

Science.gov (United States)

Chen, Pisin; Ong, Yen Chin; Page, Don N.; Sasaki, Misao; Yeom, Dong-han

2016-04-01

In the firewall proposal, it is assumed that the firewall lies near the event horizon and should not be observable except by infalling observers, who are presumably terminated at the firewall. However, if the firewall is located near where the horizon would have been, based on the spacetime evolution up to that time, later quantum fluctuations of the Hawking emission rate can cause the "teleological" event horizon to have migrated to the inside of the firewall location, rendering the firewall naked. In principle, the firewall can be arbitrarily far outside the horizon. This casts doubt about the notion that firewalls are the "most conservative" solution to the information loss paradox.

Effects of short-term testosterone replacement on areal bone mineral density and bone turnover in young hypogonadal males

Directory of Open Access Journals (Sweden)

Prasun Deb

2012-01-01

Full Text Available Context: Effect of parenteral testosterone esters administration on bone-mineral density (BMD and bone turnover in young age onset male hypogonadism is not studied in Indian subjects. Aims: To prospectively study the effect of short-term (6 months replacement therapy with parenteral testosterone enanthate-propionate combination on BMD and bone turnover markers in hypogonadal adult patients. Settings and Design: Prospective, tertiary care academic center. Materials and Methods: Thirteen young, otherwise healthy hypogonadal males (age 25.5 ± 4.9 yrs, serum testosterone 2.56 ± 4.29 nmol/l were subjected to BMD measurements (DXA and estimation of urinary Crosslaps™ and serum osteocalcin at baseline. Twelve healthy age and BMI-matched males served as controls for BMD measurements. The hypogonadal patients were administered parenteral testosterone esters (as mixed enanthate and propionate 250 mg i.m. every 2-3 weeks, and prospectively followed for 6 months. BMD and bone markers were studied at the end of 6 months. Statistical Analysis Used: Mann-Whitney nonparametric test, paired t-test and Pearson′s test of two-tail significance. Results: At baseline, BMD was significantly lower in hypogonadal males as compared to that in controls. With testosterone replacement, there was significant improvement in BMD, both at trabecular and cortical sites, There was a decline in bone turnover with treatment (Ur Crosslaps™:creatinine ratio: pretreatment 72.8 ± 40.4, post-treatment 35.5 ± 23.8 μg/mmol, P = 0.098; serum osteocalcin: pre-treatment 41.0 ± 16.8, post-treatment 31.7 ± 2.1 ng/ml, P = 0.393. Conclusions: Short-term parenteral testosterone replacement significantly improves BMD at the hip, lumbar spine and forearm in hypogonadal young males.

The Predictive Power of Evolutionary Biology and the Discovery of Eusociality in the Naked Mole-Rat.

Science.gov (United States)

Braude, Stanton

1997-01-01

Discusses how biologists use evolutionary theory and provides examples of how evolutionary biologists test hypotheses on specific modes of selection and evolution. Presents an example of the successful predictive power of one evolutionary hypothesis. Contains 38 references. (DDR)

The strange case of a patient affected by acromegaly with osteoporomalacia without hypogonadism

Directory of Open Access Journals (Sweden)

S. Caprio

2011-09-01

Full Text Available Acromegaly is a rare disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH- producing tumor of the pituitary. Growth hormone has profound effects on linear bone growth, bone metabolism, and bone mass. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD. Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. The Autors describe a case of patient affected by acromegaly without hypogonadism with serious osteoporosis and biological signs of osteomalacia.

Optical effects related to Keplerian discs orbiting Kehagias-Sfetsos naked singularities

Science.gov (United States)

Stuchlík, Zdeněk; Schee, Jan

2014-10-01

We demonstrate possible optical signatures of the Kehagias-Sfetsos (KS) naked singularity spacetimes representing a spherically symmetric vacuum solution of the modified Hořava gravity. In such spacetimes, accretion structures significantly different from those present in standard black hole spacetimes occur due to the ‘antigravity’ effect, which causes an internal static sphere surrounded by Keplerian discs. We focus our attention on the optical effects related to the Keplerian accretion discs, constructing the optical appearance of the Keplerian discs, the spectral continuum due to their thermal radiation, and the spectral profiled lines generated in the innermost parts of such discs. The KS naked singularity signature is strongly encoded in the characteristics of predicted optical effects, especially in cases where the spectral continuum and spectral lines are profiled by the strong gravity of the spacetimes due to the vanishing region of the angular velocity gradient influencing the effectiveness of the viscosity mechanism. We can conclude that optical signatures of KS naked singularities can be well distinguished from the signatures of standard black holes.

Optical effects related to Keplerian discs orbiting Kehagias–Sfetsos naked singularities

International Nuclear Information System (INIS)

Stuchlík, Zdeněk; Schee, Jan

2014-01-01

We demonstrate possible optical signatures of the Kehagias–Sfetsos (KS) naked singularity spacetimes representing a spherically symmetric vacuum solution of the modified Hořava gravity. In such spacetimes, accretion structures significantly different from those present in standard black hole spacetimes occur due to the ‘antigravity’ effect, which causes an internal static sphere surrounded by Keplerian discs. We focus our attention on the optical effects related to the Keplerian accretion discs, constructing the optical appearance of the Keplerian discs, the spectral continuum due to their thermal radiation, and the spectral profiled lines generated in the innermost parts of such discs. The KS naked singularity signature is strongly encoded in the characteristics of predicted optical effects, especially in cases where the spectral continuum and spectral lines are profiled by the strong gravity of the spacetimes due to the vanishing region of the angular velocity gradient influencing the effectiveness of the viscosity mechanism. We can conclude that optical signatures of KS naked singularities can be well distinguished from the signatures of standard black holes. (paper)

Papapetrou's naked singularity is a strong curvature singularity

International Nuclear Information System (INIS)

Hollier, G.P.

1986-01-01

Following Papapetrou [1985, a random walk in General Relativity ed. J. Krishna-Rao (New Delhi: Wiley Eastern)], a spacetime with a naked singularity is analysed. This singularity is shown to be a strong curvature singularity and thus a counterexample to a censorship conjecture. (author)

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

OpenAIRE

Golds, Gary; Houdek, Devon; Arnason, Terra

2017-01-01

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testoster...

Kallman syndrome versus idiopathic hypogonadotropic hypogonadism at MR imaging

Energy Technology Data Exchange (ETDEWEB)

Vogl, T.J.; Stemmler, J.; Bergman, C.; Balzer, J.O.; Felix, R. [Free Univ. of Berlin (Germany); Heye, B.; Schopohl, J.; Danek, A. [Univ. of Munich (Germany)

1994-04-01

To identify morphologic differences between Kallman syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) and establish a role for magnetic resonance (MR) imaging in these disorders. Twenty-eight patients were compared with 10 eugonal male volunteers. Eighteen patients had KS (hypogonadotropic hypogonadism with anosmia) and 10 had IHH. All participants underwent hormone analysis, a sniff-bottle smell test, and gadolinium-enhanced MR imaging. Changes in the hypothalamic-hypophyseal region and the rhinencephalon were evaluated. MR imaging revealed intracranial morphologic changes in all patients on plain T1-weighted sections. Seventeen patients with KS demonstrated aplasia of an olfactory bulb; one olfactory sulcus was absent in six, rudimentary in four, and normal in eight. Olfactory bulbs were present in all 10 IHH patients and three showed one slightly hypoplastic bulb. Ten patients with KS and three with IHH showed an enlarged paranasal sinus system. Further MR findings were similar. MR imaging demonstrates abnormalities of the rhinencephalon present in KS patients and occasionally absent in IHH patients. 18 refs., 10 figs., 1 tab.

Hypogonadism in patients with chronic obstructive pulmonary disease: relationship with airflow limitation, muscle weakness and systemic inflammation

Directory of Open Access Journals (Sweden)

Rasha Galal Daabis

2016-03-01

Conclusion: Hypogonadism is highly prevalent in clinically stable COPD patients and is particularly related to the severity of the airway obstruction. Systemic inflammation is present in stable COPD patients and its intensity is related to the severity of the underlying disease and it predisposes to skeletal muscle weakness and exercise intolerance. However, we failed to find a significant association between hypogonadism and muscle weakness or systemic inflammation.

Hydatidiform mole: age-related clinical presentation and high rate of severe complications in older women.

Science.gov (United States)

Mangili, Giorgia; Giorgione, Veronica; Gentile, Cinzia; Bergamini, Alice; Pella, Francesca; Almirante, Giada; Candiani, Massimo

2014-05-01

The purpose of this study was to demonstrate differences in clinical presentation of hydatidiform mole between women ≥40 years and younger women. Retrospective study. A tertiary referral unit in northern Italy. Three hundred and sixty-five women with hydatidiform mole were divided into group A (Clinical presentation between groups A and B was analyzed, also considering partial hydatidiform mole and complete hydatidiform mole. Differences in clinical presentation according to woman's age. In group B the diagnosis of hydatidiform mole at ≥12 gestational weeks was more frequent (p presented with vaginal bleeding (p clinical features of hydatidiform mole in women ≥40 years are different from those seen in younger women. Failures in the early detection of hydatidiform mole in older women may expose them to a higher rate of severe complications. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Metrics of a 'mole hole' against the Lobachevsky space background

International Nuclear Information System (INIS)

Tentyukov, M.N.

1994-01-01

'Classical' mole hole are the Euclidean metrics consisting of two large space regions connected by a throat. They are the instanton solutions of the Einstein equations. It is shown that for existence of mole holes in the general relativity theory it is required the energy-momentum tensor breaking energetic conditions. 9 refs., 7 figs

Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

Science.gov (United States)

Zacharin, Margaret

2015-06-01

Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.

Science.gov (United States)

Grossmann, Mathis; Matsumoto, Alvin M

2017-03-01

Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. Literature review from 1970 to October 2016. Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.

Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations.

Science.gov (United States)

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-09-05

Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research. Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre-existing prostate disease, digital rectal examination and prostate-specific antigen testing should be performed before commencing testosterone treatment.Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.

Acanthocephala Parasite (Profilicollis spp.) Loads in Correlation to Pacific Mole Crab (Emerita analoga) Size

Science.gov (United States)

Cheng, T.; Huang, S.; Galathe, M.; Jenkins, M.; Ramirez, A.; Crosby, L.; Barrera, J.; FitzHoward, S.

2013-12-01

Since 2002, San Francisco Bay students have been conducting marine ecosystem monitoring through a joint project with the Long-term Monitoring Program and Experiential Training for Students (LiMPETS), in conjunction with the Gulf of Farallones National Marine Sanctuary. Each year students collect population and demographic data on Pacific mole crabs (Emerita analoga), an indicator species that lives in the sandy beach habitat in temperate regions along the Pacific Ocean. Pacific mole crabs are filter feeding crustaceans that inhabit the intertidal swash zone and are known to be an intermediate host for parasitic ';spiny-headed' worms in the phylum Acanthocephala (Profilicollis spp.). Sampling takes place during their reproductive period, which occurs from spring to fall, and includes measuring total body length of the Pacific mole crabs and dissecting them to determine presence of Acanthocephalan parasites. We hypothesize that due to larger body mass, larger Pacific mole crabs will have a greater number of Acanthocephala parasites.We conducted several analyses using the LiMPETS long-term data. Specifically, we compared body length, crab gender, and parasite abundance from Pacific mole crabs sampled from four beaches located in the county and city of San Francisco. Our results indicated that larger Pacific mole crabs do not necessarily have more parasites, but are more likely to have at least one parasite, while female Pacific mole crabs carrying eggs, have more parasites than males or females without eggs. We also found that parasite loads per mole crab was highest in the spring. Further analysis will be conducted to determine factors affecting Pacific mole crab parasite loads. Studying Pacific mole crabs help evaluate the health of California's intertidal systems and how human activities, geologic changes, and climate changes all make huge impacts to the intertidal ecosystems.

Naked-eye astronomy in mass tourism

Directory of Open Access Journals (Sweden)

Tadić Milutin

2016-01-01

Full Text Available This paper considers the possibility of developing astro-tourism in small countries such as Serbia and other Balkan countries, with "discreet" astro-tourism reduced to naked-eye astronomy as part of mass tourism rather than elite tourism that is realized through specialized programs with spacecraft and space stations, spectacular planetariums and observatories with giant telescopes. The specific relationship between the virtual and the real world is highlighted in this paper especially when considering younger generations. Furthermore, the differences in the way stars are perceived by astronomers and "ordinary" tourists or non-astronomers is also emphasized. Tourists are not enchanted by celestial bodies themselves, but by a complete scene, which consists of integrated skyscapes and landscapes, as a complex stage where in various combinations and forms these celestial bodies are observed, and of their own experience. These complex sky-earth landscapes, astro-landscapes, present astro-tourism resources of the small countries like Serbia, provided that a tourist can "read" their astronomical text. In this regard, Belgrade was used as the example for drafting a "package" of astronomical information that can be easily prepared and adapted according to the needs of a particular group, so that every tourist may know what can be seen, where and when. With the help of a rotating star map (planisphere, visitors may observe the sky with the naked eye.

Two-Laser Interference Visible to the Naked Eye

Science.gov (United States)

Kawalec, Tomasz; Bartoszek-Bober, Dobroslawa

2012-01-01

An experimental setup allowing the observation of two-laser interference by the naked eye is described. The key concept is the use of an electronic phase lock between two external cavity diode lasers. The experiment is suitable both for undergraduate and graduate students, mainly in atomic physics laboratories. It gives an opportunity for…

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

DEFF Research Database (Denmark)

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer...... marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly...... synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells...

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management

Science.gov (United States)

Matsumoto, Alvin M.

2017-01-01

Abstract Context: Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic–pituitary–testicular axis pathology but have functional hypogonadism that is potentially reversible. Evidence Acquisition: Literature review from 1970 to October 2016. Evidence Synthesis: Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency–like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. Conclusions: There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy. PMID:28359097

The Origin of the Mole Concept

Science.gov (United States)

Jensen, William B.

2004-01-01

German Chemist, August Wilhelm Hofmann first introduced the term "molar" (from the Latin moles, meaning "a large mass") into chemistry, around 1865. The particular use of the term molar gained currency in the physics literature, where it was in common use at least through the 1940s.

Sex differences in visuospatial abilities persist during induced hypogonadism.

Science.gov (United States)

Guerrieri, Gioia M; Wakim, Paul G; Keenan, P A; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J; Rubinow, David R; Schmidt, Peter J

2016-01-29

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus

Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism

OpenAIRE

Topaloğlu, A. Kemal

2017-01-01

Traditionally, idiopathic hypogonadotropic hypogonadism (IHH) is divided into two major categories: Kallmann syndrome (KS) and normosmic IHH (nIHH). To date, inactivating variants in more than 50 genes have been reported to cause IHH. These mutations are estimated to account for up to 50% of all apparently hereditary cases. Identification of further causative gene mutations is expected to be more feasible with the increasing use of whole exome/genome sequencing. Presence of more than one IHH-...

High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment.

NARCIS (Netherlands)

Hofstra, J.M.; Loves, S.; Wageningen, B. van; Ruinemans-Koerts, J.; Jansen, I.; Boer, H. de

2008-01-01

BACKGROUND: Obesity can be associated with biochemical evidence of isolated hypogonadotropic hypogonadism (IHH) in men. Prevalence and severity of IHH in obese men are not exactly known. OBJECTIVE: To assess the prevalence of IHH in obese men. DESIGN AND SUBJECTS: Cross-sectional study of 160 obese

Prothrombin G20210A mutation, hypogonadotropic hypogonadism, and generalized vitiligo-related ischemic stroke in a young adult.

Science.gov (United States)

Varoglu, Asuman Orhan; Kocatürk, Idris; Tatar, Abdulgani

2010-06-01

Cerebral infarction is a rare neurological situation in young adults, usually caused by genetic factors. We report here a case of multiple cerebral infarctions with prothrombin G20210A mutation, hypogonadotropic hypogonadism, and generalized vitiligo as a first case report. A 17-year-old female adolescent was admitted to our clinic due to a change in mental status. The patient's neurological examination revealed loss of consciousness and the presence of tetraparesia. Generalized vitiligo was also detected. Magnetic resonance imaging (MRI) and diffusion-weighted investigations (DWIs) showed acute ischemic stroke in the bilateral cerebellum, pons and left occipital regions. Heterozygote prothrombin G20210A mutation was found upon genetic examination. She had never had a menstrual cycle. Laboratory data revealed that the level of luteinizing hormone (LH) was 0.5 mIU/mL (1.1-11.6) and follicle-stimulating hormone (FSH) was 1.7 mIU/mL (2.8-11.3). Therefore, she was diagnosed with hypogonadotropic hypogonadism. The causes of ischemic stroke are heterozygote prothrombin G20210A mutation, generalized vitiligo, and hypogonadotropic hypogonadism. After treatment, the patient's neurological deficit partially improved and she was discharged. In order to identify the etiology of ischemic stroke, we suggest physicians take into account heterozygote prothrombin G20210A mutation and endocrine abnormalities, especially hypogonadotropic hypogonadism and generalized vitiligo.

For Mole Problems, Call Avogadro: 602-1023

Science.gov (United States)

Uthe, R. E.

2002-10-01

General education students who have never encountered Avogadro’s number often have difficulty grasping its magnitude and the resulting implications for sizes and numbers of particles in common materials they see around them. I have surveyed the approaches used by several chemical educators. This article describes the techniques I find best help introductory students in General College at the University of Minnesota become familiar with Avogadro’s number and mole calculations. They involve estimating numbers of common objects and then calculating the length of time needed to count large numbers of them. For example, the immense amount of time required to count a mole of sand grains at one grain per second greatly exceeds the age of the universe. The calculations also reinforce procedures for manipulating exponents and applying problem-solving techniques.

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

Science.gov (United States)

Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

2015-03-01

Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

Hypogonadism and subnormal total testosterone levels in men with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Ogbera, O.A.; Sonny, C.; Olufemi, F.; Wale, A.

2011-01-01

Objective: To determine the frequency of testosterone deficiency syndrome (TDS) in men with type 2 diabetes mellitus (DM). Study Design: A cross-sectional study. Place and Duration of Study: The Gbagada General Hospital, Gbagada Lagos, Nigeria, from December 2009 to May 2010. Methodology: A total of 203 men with type 2 DM aged 30-86 years were evaluated for TDS by a combination of positive ADAM (androgen deficiency in the ageing male) scores and subnormal total testosterone levels. Mild testosterone deficiency referred to total testosterone (TT) levels of 8-12 nmol/L with symptoms of hypogonadism and severe testosterone deficiency referred to TT levels < 8 nmol/L with or without hypogonadal symptoms. Results: Mild and severe TDS were present in 18.3% and 17% respectively of the study subjects. Commonly occurring clinical parameters of the TDS were erectile dysfunction and loss of libido, which were documented in 63% and 60% respectively in the study subjects. The majority of clinical features of the TDS were comparable in men with and without the TDS. Conclusion: About a third of men with type 2 DM had the TDS. The majority of the symptoms of hypogonadism are largely non-specific and their occurrence is comparable in men with and without low testosterone levels; thus, underscoring the need to have testosterone levels determined in men presenting with such symptoms. (author)

Partial hydatidiform mole with false-negative urine human chorionic gonadatropin test in the emergency department.

Science.gov (United States)

Mundangepfupfu, Tichaendepi; Waseem, Muhammad

2014-03-01

Hydatidiform mole (molar pregnancy) is a benign tumor of placental trophoblastic cells, which release human chorionic gonadotropin (hCG). Several case reports have described complete hydatidiform moles with false-negative urine qualitative hCG tests. These negative pregnancy tests have been attributed to the hook effect. We report an unusual presentation of a partial mole and review an alternative explanation for the negative hCG test. As partial moles are usually not associated with a large proliferation of trophoblastic cells, levels of hCG are commonly negative and serum quantitative hCG was 1,094,950 mIU/mL. Pelvic ultrasonography showed a uterine cavity containing a soft-tissue mass with multiple cystic lesions and the hydatidiform mole was extracted with suction curettage. Tissue pathology confirmed partial hydatidiform mole. In addition to the hook effect, we present another possible explanation for the false-negative test; namely the inability of some assays to detect hCG-degradation products, which may be higher in clinical samples from patients with hydatidiform mole. This case underscores the importance of knowing the limitations of the commonly used hCG assays. Copyright © 2014 Elsevier Inc. All rights reserved.

On the nature of naked singularities in Vaidya spacetimes

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, I.H. (Aligarh Muslim Univ. (India). Dept. of Physics); Joshi, P.S. (Tata Inst. of Fundamental Research, Bombay (India))

1989-11-01

The Vaidya-Papapetrou model containing a naked singularity is analysed for outgoing causal geodesics joining the singularity. The curvature growth along these trajectories is examined to show that this is a strong curvature singularity, providing a counter-example to certain forms of cosmic censorship hypotheses. (author).

On the nature of naked singularities in Vaidya spacetimes

International Nuclear Information System (INIS)

Dwivedi, I.H.

1989-01-01

The Vaidya-Papapetrou model containing a naked singularity is analysed for outgoing causal geodesics joining the singularity. The curvature growth along these trajectories is examined to show that this is a strong curvature singularity, providing a counter-example to certain forms of cosmic censorship hypotheses. (author)

Carcass characteristics, physical property and chemical composition of Naked-Neck and Thai indigenous chickens muscles reared under backyard production systems

Directory of Open Access Journals (Sweden)

Songsang, A.

2007-03-01

Full Text Available The objective of this study was to obtain basic knowledge regarding carcass characteristics, physical property and chemical composition of the muscle meat of Naked-Neck and indigenous chickens reared underthe backyard production systems. Ninety heads each of Naked-Neck and indigenous chickens of both sexes at 1.3, 1.5 and 1.8 kg of live weight were used in the study. From this study, there were no significant differences (P>0.05 in the chilled carcass percentage between the two breeds and two sexes. The Naked-Neckchickens had lower breast (Pectoralis major, fillet (Pectoralis minor (P0.05 in drip loss and cooking loss values. The shear value of cooked breast and thigh muscles of Naked-Neck chickens was significantly lower (P0.05, redness (a* (P0.05 in moisture, protein, fat and ash contents. The Naked-Neck chicken contained higher (P0.05 between breeds in soluble collagen percentage of both types of muscles. For the fatty acid composition ofNaked-Neck and indigenous chickens, both breast and thigh muscles contained more saturated fatty acids than unsaturated fatty acids.

Effects of nickel chloride and nickel carbonyl upon glucose metabolism in rats

International Nuclear Information System (INIS)

Horak, E.; Zygowicz, E.R.; Tarabishy, R.; Mitchell, J.M.; Sunderman, F.W. Jr.

1978-01-01

Hyperglycemia, hyperglucagonemia and hyperinsulinemia were observed in fasting rats 0.5 h after ip injection of NiCl 2 (68 μmole per kg). Infusion of somatostatine iv (0.5 mg per rat) did not prevent Ni(II)-mediated hyperglycemia, hyperglucagonemia or hyperinsulinemia. Exposure of rats to inhalation of Ni(CO) 4 (1.2 to 6.4 μmole per liter of air per 15 min) caused acute hyperglycemia, similar to that observed after ip injection of NiCl 2 . Hyperglycemia induced by NiCl 2 and Ni(CO) 4 was not associated with inhibition of erythrocyte glycolysis measured in vitro by erythrocyte uptake of 1- 14 C-glucose and release of 14 CO 2 . These findings indicate that Ni-induced hyperglycemia may be mediated by increased pancreatic release of glucagon, but that Ni stimulation of glucagon release differs from stimulation of glucagon release by arginine or epinephrine, since the Ni effect is not antagonized by somatostatin

Occurrence, patterns & predictors of hypogonadism in patients with HIV infection in India

Directory of Open Access Journals (Sweden)

Deep Dutta

2017-01-01

Interpretation & conclusions: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.

Amount of substance and the proposed redefinition of the mole

Science.gov (United States)

Milton, M. J. T.; Mills, I. M.

2009-06-01

There has been considerable discussion about the merits of redefining four of the base units of the SI, including the mole. In this paper, the options for implementing a new definition for the mole based on a fixed value for the Avogadro constant are discussed. They are placed in the context of the macroscopic nature of the quantity amount of substance and the opportunity to introduce a system for molar and atomic masses with unchanged values and consistent relative uncertainties.

Motivation sphere features of patients with psychoendocrine syndrome on the background of hypogonadism

Directory of Open Access Journals (Sweden)

V.V. Ischuk,

2017-08-01

Full Text Available Background. Psychoneuroendocrinology is the clinical study of hormone fluctuations and their relationship to human behavior. It may be viewed from the perspective of psychiatry, where in certain mood disorders, there are associated neuroendocrine or hormonal changes affecting the brain. It may also be viewed from the perspective of endocrinology, where certain endocrine disorders can be associated with psychiatric illness. This complex blend of psychiatry, neurology and endocrinology is needed to comprehensively understand and treat psychiatric illnesses. The purpose of work was to determine particular motivational-volitional features of patients with psychoendocrine syndrome on the background of hypogonadism in 100 patients in Ukrainian Scientific-Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of Ministry of Health of Ukraine. Materials and methods. Patients were examined using the Buss — Durkee test (Buss — Durkee Hostility Inventory, A.H. Buss, A. Durkee, 1957, BDHI and Plutchik impulsivity scale (Impulsiveness Scale, R. Plutchik, H. M. van Praag, 1989, IS. Results. The study defined a clinical-psychopathological structure of impulsivity in patients with psychoendocrine syndrome on the background of hypogonadism. In patients with moderate compensation hormonal status evasion-vicarious and disprosective correlates of impulsive behaviors prevail. In the decompensation state thymic labile and disretentive correlates prevail. Conclusions. It was found statistically significant predominance of the intensity of aggressive reaction forms among patients with hypogonadism in decompensated state (mediated by the phenomena of aggression, irritability, negativism, resentment, verbal aggression and guilt.

Papapetrou's naked singularity is a strong curvature singularity

Energy Technology Data Exchange (ETDEWEB)

Hollier, G.P.

1986-11-01

Following Papapetrou (1985, a random walk in General Relativity ed. J. Krishna-Rao (New Delhi: Wiley Eastern)), a spacetime with a naked singularity is analysed. This singularity is shown to be a strong curvature singularity and thus a counterexample to a censorship conjecture.

Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling

OpenAIRE

Yan-Min Ma; Kai-Jie Wu; Qiang Dang; Qi Shi; Yang Gao; Peng Guo; Shan Xu; Xin-Yang Wang; Da-Lin He; Yong-Guang Gong

2014-01-01

Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testost...

Growth hormone deficiency and central hypogonadism in retired professional football players

Directory of Open Access Journals (Sweden)

Gábor László Kovács

2016-12-01

Full Text Available Purpose: The aim of this cross-sectional study was to evaluate the possible impact of multiple mild head traumas sustained during a long-term football career on the presence of central hypogonadism and growth hormone (GH deficiency. Methods: Twenty-seven retired, former professional male football players were investigated. All subjects were assessed for serum levels of insulin-like growth factor (IGF-1, luteinizing hormone (LH and total testosterone (TT. Quality of life was quantified using the Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA questionnaire. Results: Subjects had a median age of 48.0 (42.0 – 53.0 years and a median football career of 29.0 years (22.0 – 32.0. One subject had central hypogonadism and none had growth hormone deficiency. Nine subjects reported sport-related head injuries. We found a negative correlation between sport-related head injuries and serum LH (p = -0.459, P = 0.016. Subjects with a history of sport-related head injury had a median LH of 3.3 U/L (2.7 – 3.6, while those without a history of sport-related head injury had a median LH of 4.1 (U/L (3.6 – 5.7, P = 0.017. However, there were no differences in other hormones between the two groups. Moreover, we did not find any correlation between the duration of the player’s career nor their field position with hormone profiles or QoL-AGHDA. Conclusion: Although retired footfall players with a history of sport-related head injury had lower LH levels, we did not find strong evidence of an increased prevalence of central hypogonadism or GH deficiency in these patients. Our results suggest that a long-term football career, which includes headings and repetitive mild head traumas, does not damage the most vulnerable anterior pituitary cells.

Study clarifies associations between hypogonadism and health in aging men.

Science.gov (United States)

Amory, John K

2012-11-01

Tajar and colleagues present the associations between moderate and severe hypogonadism, symptoms of androgen deficiency and the prevelence of end-organ evidence of androgen deficency in 2966 older men in the European Male Aging Study. They find lower muscle mass, reduced bone mineral density, anemia, insulin resistence, metabolic syndrome and cardiovascular disease, with greater risks of these signs of androgen deficiency at lower serum testosterone concentrations.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

Science.gov (United States)

Taylor, Frederick; Levine, Laurence

2010-01-01

The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

They live in the land down under: thyroid function and basal metabolic rate in the Blind Mole Rat, Spalax.

Science.gov (United States)

Avivi, Aaron; Nevo, Eviatar; Cohen, Keren; Sotnichenko, Nick; Hercbergs, Aleck; Band, Mark; Davis, Paul J; Ellis, Martin; Ashur-Fabian, Osnat

2014-01-01

The Israeli blind subterranean mole rat (Spalax ehrenbergi superspecies) lives in sealed underground burrows under extreme, hypoxic conditions. The four Israeli Spalax allospecies have adapted to different climates, the cool-humid (Spalax galili, 2 n = 52 chromosomes), semihumid (S. golani, 2 n = 54) north regions, warm-humid (S. carmeli, 2 n = 58) central region and the warm-dry S. judaei, 2 n = 60) southern regions. A dramatic interspecies decline in basal metabolic rate (BMR) from north to south, even after years of captivity, indicates a genetic basis for this BMR trait. We examined the possibility that the genetically-conditioned interspecies BMR difference was expressed via circulating thyroid hormone. An unexpected north to south increase in serum free thyroxine (FT4) and total 3, 5, 3'-triiodo-L-thyronine (T3) (p BMR measurements. The increases in serum FT4 and T3 were symmetrical, so that the T3:FT4 ratio - interpretable as an index of conversion of T4 to T3 in nonthyroidal tissues - did not support relative decrease in production of T3 as a contributor to BMR. Increased north-to-south serum FT4 and T3 levels also correlated negatively with hemoglobin/hematocrit. North-to-south adaptations in spalacids include decreased BMR and hematocrit/hemoglobin in the face of increasing thyroid hormone levels, arguing for independent control of hormone secretion and BMR/hematocrit/hemoglobin. But the significant inverse relationship between thyroid hormone levels and BMR/hematocrit/hemoglobin is also consistent with a degree of cellular resistance to thyroid hormone action that protects against hormone-induced increase in oxygen consumption in a hostile, hypoxic environment.

An adolescent with 48,xxyy syndrome with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder and renal malformations

Directory of Open Access Journals (Sweden)

Prasad Katulanda

2012-01-01

Full Text Available 48,XXYY is a rare sex chromosome aneuploidy affecting 1 in 18,000 to 50,000 male births. They present with developmental delay, hypogonadism, gynecomastia, intention tremors, and a spectrum of neurodevelopmental and psychiatric disorders. At one time this condition was considered a variant of Klinefelter syndrome. In clinically suspected cases, 48,XXYY syndrome can be diagnosed by chromosome culture and karyotyping. This patient presented with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder, and renal malformatons. Klinefelter syndrome was clinically suspected. The karyotype confirmed the diagnosis of 48,XXYY syndrome. This is the first reported case of 48,XXYY syndrome from Sri Lanka.

Zinc deficiency leads to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats.

Directory of Open Access Journals (Sweden)

Sylvie Julien

Full Text Available BACKGROUND: Age-related macular degeneration (AMD is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. METHODOLOGY/PRINCIPAL FINDINGS: Adult Long Evans (LE rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE. The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. CONCLUSIONS/SIGNIFICANCE: In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.

Examining the effect of the computer-based educational package on quality of life and severity of hypogonadism symptoms in males.

Science.gov (United States)

Afsharnia, Elahe; Pakgohar, Minoo; Khosravi, Shahla; Haghani, Hamid

2018-06-01

The objective of this study was to determine the effect of the computer-based educational package on men's QoL and the severity of their hypogonadism symptoms. A quasi-experimental study was conducted on 80 male employees. The data collection tool included the 'Aging Male Symptoms' (AMS) and 'Short Form-36' (SF36) questionnaires. Four sessions were held for the intervention group over a period of 4 weeks. Two months after training, QoL and the severity of hypogonadism symptoms were measured in both the intervention and control groups. The data were analyzed with SPSS 22 software and statistical tests, such as χ 2 , independent t-test, Fisher's exact test, and paired t-tests. Significant statistical changes were observed in the intervention group before and 2 months after the training in the QoL score in the overall dimensions of physical-psychological health and all its domains except for three domains of emotional role, social function, and pain. Furthermore, the paired t-tests showed significant differences between 2 months before and after the training in all the domains and the overall hypogonadism score in the intervention group. Based on our findings, the computer-based educational package has a positive effect on QoL and reduction of hypogonadism symptoms.

Hypogonadism and man’s infertility at patients with indirect inguinal hernia after hernioplasty

Directory of Open Access Journals (Sweden)

I. S. Sobennikov

2014-11-01

Full Text Available The article estimates hydrologic status and fertility prognosis of 35 year-old reproductive age men with unilateral inguinal hernioplasty in past history from the system syndrome-based approach perspective to the etiology and pathogenesis of indirect inguinal hernia and hypogonadism.

Hypogonadism and man’s infertility at patients with indirect inguinal hernia after hernioplasty

Directory of Open Access Journals (Sweden)

I. S. Sobennikov

2012-01-01

Full Text Available The article estimates hydrologic status and fertility prognosis of 35 year-old reproductive age men with unilateral inguinal hernioplasty in past history from the system syndrome-based approach perspective to the etiology and pathogenesis of indirect inguinal hernia and hypogonadism.

A Mole for Warm Magnetic and Optical Measurements of LHC Dipoles

CERN Document Server

Bottura, L; Deferne, G; Glöckner, C; Jansen, H; Köster, A; Legrand, P; Rijllart, A; Sievers, P

2000-01-01

A new rotating coil probe (a mole) has been developed for the simultaneous measurement of the magnetic field and magnetic axis of warm superconducting LHC dipoles and associated corrector windings. The mole houses a radial rotating coil and travels inside the magnet aperture by means of an externally driven two-way traction belt. The coil is rotated by an on-board piezo motor, being tested in view of future devices for cold measurements as the only type of motor compatible with strong magnetic fields. A virtual light spot is generated in the coil center by a LED source. The position of this light spot is measured from the outside by a system including a telescope, a CCD camera and a DSP. Jigs on reference granite tables are used to transfer the optical measurements to the magnet fiducials. We describe here the main characteristics and performance of the mole

Productive performance of naked neck, frizzle and dwarf laying hens ...

African Journals Online (AJOL)

The productive performance of major genes for feather reduction (naked neck and frizzle) and body size reduction (dwarf) in a dual-purpose layer strain was evaluated in the subtropical coastal region of southeast Africa (Maputo, Mozambique). The experimental material consisted of ight different genetic groups, two diets ...

psychrometry: from partial pressures to mole fractions

African Journals Online (AJOL)

ES Obe

1980-03-01

Mar 1, 1980 ... as an ideal gas mixture. Partial pressures then become identical: to mole fractions and sets of psychometric parameters result from rather elementary thermodynamic relations. Search for more accurate data has long led to the realization that neither dry air nor pure water vapour behaves like an ideal gas,.

[Hypogonadism and the quality of life in male patients with type-2 diabetes mellitus].

Science.gov (United States)

Zhang, Lu-Yao; He, Wei; Wan, Jian-Xin; Yin, Qi-Qi; Cheng, Zhen; Chen, Guan-Ming; Ji, Wen; Li, Hai; Li, Yan-Bing; Liao, Zhi-Hong

2016-12-01

To compare the level of testosterone between type-2 diabetes mellitus (T2DM) patients and healthy controls and to investigate the status of hypogonadism and the influence of hypopgonadism on the quality of life. We collected serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and other clinical data from 166 T2DM patients aged over 30 years and 186 age-matched healthy controls. We investigated the quality of life (QoL) of the two groups of subjects using the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Male Symptoms (AMS), 36-Item Short-Form Health Survey (SF-36), and Special Quality of Life for Diabetes Mellitus (DSQL). The level of calculated FT (cFT) was remarkably lower in the T2DM patients than in the healthy controls (Pmales with hypogonadism showed significant differences from those without in age, height, systolic blood pressure, and creatinine (Phypogonadism was 51.81% in the T2DM patients, 31.58% in the 30－39 yr group, 32.50% in the 40－49 yr group, 50% in the 50－59 yr group, 69.23% in the 60－69 yr group, and 77.27% in the ≥70 yr group, elevated by 77.4% with the increase of 10 years of age (OR = 1.774, Phypogonadism. Age is a main risk factor of hypogonadism. Severer testosterone deficiency symptoms are associated with lower scores of QoL in T2DM males.

Naked singularities in four-dimensional string backgrounds

International Nuclear Information System (INIS)

Mohammedi, N.

1993-04-01

It is shown that gauged nonlinear sigma models can be always deformed by terms proportional to the field strength of the gauge fields (nonminimal gauging). These deformations can be interpreted as perturbations, by marginal operators, of conformal coset models. When applied to the SL(2, R)xSU(2)/U(1)xU(1)) WZWN model, a large class of four-dimensional curved spacetime backgrounds are obtained. In particular, a naked singularity may form at a time when the volume of the universe is different from zero. (orig.)

Role of immunoexpression of cyclin D1, D3, retinoblastoma (Rb mutant and clinical risk factors on complete mole as risk factors of persistent mole

Directory of Open Access Journals (Sweden)

Yudi M Hidayat

2015-10-01

Full Text Available Introduction: Changes in complete hydatidiform mole (CHM that become persistent are difficult to handle because the malignant pathogenesis of CHM is still unclear. The growth of abnormal cells in CHM is thought to be caused by cell cycle abnormalities. Some components that play a role in this phase include cyclin D and retinoblastoma (Rb. The aim of our study was to determine the role of clinical risk factors, as well as cyclin D1, cyclin D3 and Rb-protein, in the occurrence of persistent moles. Materials and Method: This study involves 68 CHM cases at Dr. Hasan Sadikin Hospital from 2007–2011. The protein expression of cyclin D1, cyclin D3, and Rb were determined by immunohistochemistry. The results were analyzed by comparing the two groups of CHM that became persistent to those that returned to normal, as determined by a Mochizuki regression curve assessment. Results: 20 cases (29% of CHM became persistent and that 48 cases (71% returned to normal. Significant clinical variables were age (p 0.05. Conclusion: There is a strong relationship between clinical risk factors of age, excessive proliferation histopathology, serum βhCG levels ≥100,000 mU/mL, cyclin D1 and Rb mutations with the incidence of persistent moles after the evacuation of the CHM. We proposed a model to predict the risks of persistent moles with a cut-off point of 2.384, which can be used as a reference for patients with CHM.

Phage-mediated counting by the naked eye of miRNA molecules at attomolar concentrations in a Petri dish

Science.gov (United States)

Zhou, Xin; Cao, Peng; Zhu, Ye; Lu, Wuguang; Gu, Ning; Mao, Chuanbin

2015-10-01

The ability to count biomolecules such as cancer-biomarker miRNAs with the naked eye is seemingly impossible in molecular diagnostics. Here, we show an ultrasensitive naked-eye-counting strategy for quantifying miRNAs by employing T7 phage--a bacteria-specific virus nanoparticle--as a surrogate. The phage is genetically engineered to become fluorescent and capable of binding a miRNA-capturing gold nanoparticle (GNP) in a one-to-one manner. Target miRNAs crosslink the resultant phage-GNP couple and miRNA-capturing magnetic microparticles, forming a sandwich complex containing equimolar phage and miRNA. The phage is then released from the complex and developed into one macroscopic fluorescent plaque in a Petri dish by plating it in a host bacterial medium. Counting the plaques by the naked eye enables the quantification of miRNAs with detection limits of ~3 and ~5 aM for single-target and two-target miRNAs, respectively. This approach offers ultrasensitive and convenient quantification of disease biomarkers by the naked eye.

The perception of (naked only) bodies and faceless heads relies on holistic processing: Evidence from the inversion effect.

Science.gov (United States)

Bonemei, Rob; Costantino, Andrea I; Battistel, Ilenia; Rivolta, Davide

2018-05-01

Faces and bodies are more difficult to perceive when presented inverted than when presented upright (i.e., stimulus inversion effect), an effect that has been attributed to the disruption of holistic processing. The features that can trigger holistic processing in faces and bodies, however, still remain elusive. In this study, using a sequential matching task, we tested whether stimulus inversion affects various categories of visual stimuli: faces, faceless heads, faceless heads in body context, headless bodies naked, whole bodies naked, headless bodies clothed, and whole bodies clothed. Both accuracy and inversion efficiency score results show inversion effects for all categories but for clothed bodies (with and without heads). In addition, the magnitude of the inversion effect for face, naked body, and faceless heads was similar. Our findings demonstrate that the perception of faces, faceless heads, and naked bodies relies on holistic processing. Clothed bodies (with and without heads), on the other side, may trigger clothes-sensitive rather than body-sensitive perceptual mechanisms. © 2017 The British Psychological Society.

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

Directory of Open Access Journals (Sweden)

Barbara Witek

Full Text Available Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

Science.gov (United States)

Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A.; Hallberg, Bengt; Palmer, Ruth H.

2015-01-01

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis. PMID:25955180

MOSH Syndrome (Male Obesity Secondary Hypogonadism): Clinical Assessment and Possible Therapeutic Approaches.

Science.gov (United States)

De Lorenzo, Antonino; Noce, Annalisa; Moriconi, Eleonora; Rampello, Tiziana; Marrone, Giulia; Di Daniele, Nicola; Rovella, Valentina

2018-04-12

Male obesity secondary hypogonadism (MOSH) impairs fertility, sexual function, bone mineralization, fat metabolism, cognitive function, deteriorates muscle mass and alters body composition. The aim of this pilot study was to evaluate the effect of dietary intervention and physical activity on the MOSH patient's hormonal profile after a 10% weight loss compared to baseline. Fourteen male patients were enrolled. Hormonal, lipid, glycemic profiles and body composition were determined at baseline and after a 10% weight loss. Aging Male Symptoms Scale (AMS) and Yale Food Addiction Scale (YFAS) were administered to patients in order to investigate hypogonadal symptoms and food addiction. Compared to baseline, a significant increase of Total Testosterone (TT) (300.2 ± 79.5 ng/dL vs. 408.3 ± 125.9 ng/dL, p = 0.002, 95% CI 26.8; 167.7) and a reduction of 17-Beta Estradiol level (48.3 ± 14.9 pg/mL vs. 39.2 ± 15.2 pg/mL, p = 0.049, 95% CI 3.1; 0.0) were observed. Total Fat Mass (FM) percentage, android and gynoid fat mass percentage (39.2 ± 6.4% vs. 36.2 ± 5.8%, p = 0.0001, 95% CI 22.5; 62.3; 51.5 ± 6.8% vs. 47.6 ± 6.8%, p = 0.001, 95% CI 0.6; 1.8, vs. 39.2 ± 6.2% vs. 36.5 ± 6.3% p = 0.0001, 95% CI 0.9; 2.0 respectively) were significantly decreased after nutritional intervention. In addition, total Fat Free Mass (FFM) in kg was significantly reduced after 10% weight loss (62.3 ± 2.8 kg vs. 60.3 ± 7.7 kg, p = 0.002, 95% CI 45.0; 93.0). Lifestyle changes, specifically dietotherapy and physical activity, induce positive effects on hypogonadism due to obesity.

Adrenal hypoplasia congenita: a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism

Directory of Open Access Journals (Sweden)

Marta Loureiro

2015-09-01

Full Text Available Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG, confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism.

Incidence and review of hydatidiform mole; chorioadenoma, destruens and chorio carcinoma in Mirza Kochek Khan Hospita

Directory of Open Access Journals (Sweden)

Ghaffari V

1995-04-01

Full Text Available Initial management, incidence and review of hydatidiform mole, chorioadenoma and destruens and chorio carcinoma in Mirza Kochek khan hospital department of ob.gyn and gynecology oncology of women's hospital Tehran-Iran school of medicin from September 1985 to March 1990, 209 patients received primary management for hydatidiform mole at oncology department of Mirza Kochek Khan hospital medical school of Tehran Iran. All of these women HAD complete record available for analysis, of these, 167 women bydatidiform mole, 12 patients chorioadenoma-destruens 30 patients chorio carcinoma a survey was made of factors likely to provide an important clinical perspective patient aye and the status of pregnancy were noted. 41 patient only sharp curettage and 55 patients suction curettage to remove the hydatidiform mole. 97 patient require chemo terapy, suction curettage of the uterus is clearly the best means of management in the most cases their eyperince documents that hydatidiform mole is an high risk pregnancy that requires prompt and in tensive management.

Severe Hand Injuries Caused by a Mole Gun

Directory of Open Access Journals (Sweden)

Serdar Düzgün

2017-10-01

Full Text Available Objective: Injuries by mole guns differ from other firearm injuries primarily because they are close-range, low-energy injuries that are highly contaminated owing to contact with contaminated surfaces and the presence of numerous residual foreign bodies within the wound. The aim of this article is to share our surgical experience regarding the repair of severe hand injuries caused by mole guns. Material and Methods: This retrospective study included 11 patients with hand injuries. Data obtained about the patients, including age, gender, dominant or non-dominant hand, injuries to all vital structures, and reconstructive procedures were assessed, categorized, and recorded. Results: Ten patients had defects in one or several common digital branches of the median nerve in areas ranging from the distal part of the carpal tunnel to the distal palmar crease. All patients had flexor and extensor tendon injuries in all fingers except for the first finger. Reconstruction of soft tissue and skin defects was carried out with an interpolation flap planned from a random-based subpectoral- paraumbilical region in five patients, a SCIA-based groin flap in four patients, a reverse-radial forearm flap in one patient, and an adipofascial flap planned from the forearm in one patient. Conclusion: Mole gun injuries typically include all structures of the hand, and repair procedures involve every anatomic structure of the hand. An early and effective surgical operation followed by prolonged and effective physical therapy protocols is vital for regaining the full spectrum of hand functions.

In vivo silencing of alpha-synuclein using naked siRNA

Directory of Open Access Journals (Sweden)

Charisse Klaus

2008-11-01

Full Text Available Abstract Background Overexpression of α-synuclein (SNCA in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease post-mortem. Genetic variability in SNCA contributes to risk of idiopathic Parkinson's disease (PD, possibly as a result of overexpression. SNCA downregulation is therefore a valid therapeutic target for PD. Results We have identified human and murine-specific siRNA molecules which reduce SNCA in vitro. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked, murine-specific siRNA into the hippocampus significantly reduces SNCA levels. Reduction of SNCA in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion. Conclusion We have developed naked gene-specific siRNAs that silence expression of SNCA in vivo. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of SNCA, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from SNCA overexpression.

In vivo silencing of alpha-synuclein using naked siRNA

Science.gov (United States)

Lewis, Jada; Melrose, Heather; Bumcrot, David; Hope, Andrew; Zehr, Cynthia; Lincoln, Sarah; Braithwaite, Adam; He, Zhen; Ogholikhan, Sina; Hinkle, Kelly; Kent, Caroline; Toudjarska, Ivanka; Charisse, Klaus; Braich, Ravi; Pandey, Rajendra K; Heckman, Michael; Maraganore, Demetrius M; Crook, Julia; Farrer, Matthew J

2008-01-01

Background Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease post-mortem. Genetic variability in SNCA contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. SNCA downregulation is therefore a valid therapeutic target for PD. Results We have identified human and murine-specific siRNA molecules which reduce SNCA in vitro. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces SNCA levels. Reduction of SNCA in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion. Conclusion We have developed naked gene-specific siRNAs that silence expression of SNCA in vivo. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of SNCA, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from SNCA overexpression. PMID:18976489

Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model

National Research Council Canada - National Science Library

Mincheff, Milcho

2003-01-01

...: H-PSMA-T, R-"PSMA"-T, H-PSA, H-PSA-T, H-PAP-T and R"PSMA"-S. Preliminary studies using the Copenhagen rat tumor prostate model showed uniform tumor development in rats that were injected subcutaneously with 100 000 AT3B-lPSMA,PSA cells...

Instrumented Moles for Planetary Subsurface Regolith Studies

Science.gov (United States)

Richter, L. O.; Coste, P. A.; Grzesik, A.; Knollenberg, J.; Magnani, P.; Nadalini, R.; Re, E.; Romstedt, J.; Sohl, F.; Spohn, T.

2006-12-01

Soil-like materials, or regolith, on solar system objects provide a record of physical and/or chemical weathering processes on the object in question and as such possess significant scientific relevance for study by landed planetary missions. In the case of Mars, a complex interplay has been at work between impact gardening, aeolian as well as possibly fluvial processes. This resulted in regolith that is texturally as well as compositionally layered as hinted at by results from the Mars Exploration Rover (MER) missions which are capable of accessing shallow subsurface soils by wheel trenching. Significant subsurface soil access on Mars, i.e. to depths of a meter or more, remains to be accomplished on future missions. This has been one of the objectives of the unsuccessful Beagle 2 landed element of the ESA Mars Express mission having been equipped with the Planetary Underground Tool (PLUTO) subsurface soil sampling Mole system capable of self-penetration into regolith due to an internal electro-mechanical hammering mechanism. This lightweight device of less than 900 g mass was designed to repeatedly obtain and deliver to the lander regolith samples from depths down to 2 m which would have been analysed for organic matter and, specifically, organic carbon from potential extinct microbial activity. With funding from the ESA technology programme, an evolved Mole system - the Instrumented Mole System (IMS) - has now been developed to a readiness level of TRL 6. The IMS is to serve as a carrier for in situ instruments for measurements in planetary subsurface soils. This could complement or even eliminate the need to recover samples to the surface. The Engineering Model hardware having been developed within this effort is designed for accommodating a geophysical instrument package (Heat Flow and Physical Properties Package, HP3) that would be capable of measuring regolith physical properties and planetary heat flow. The chosen design encompasses a two-body Mole

Androgen replacement therapy in late-onset hypogonadism: current concepts and controversies - a mini-review.

Science.gov (United States)

Mäkinen, Juuso I; Huhtaniemi, Ilpo

2011-01-01

Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1-2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental. Copyright © 2010 S. Karger AG, Basel.

Circular geodesics of naked singularities in the Kehagias-Sfetsos metric of Hořava's gravity

Science.gov (United States)

Vieira, Ronaldo S. S.; Schee, Jan; Kluźniak, Włodek; Stuchlík, Zdeněk; Abramowicz, Marek

2014-07-01

We discuss photon and test-particle orbits in the Kehagias-Sfetsos (KS) metric of Hořava's gravity. For any value of the Hořava parameter ω, there are values of the gravitational mass M for which the metric describes a naked singularity, and this is always accompanied by a vacuum "antigravity sphere" on whose surface a test particle can remain at rest (in a zero angular momentum geodesic), and inside which no circular geodesics exist. The observational appearance of an accreting KS naked singularity in a binary system would be that of a quasistatic spherical fluid shell surrounded by an accretion disk, whose properties depend on the value of M, but are always very different from accretion disks familiar from the Kerr-metric solutions. The properties of the corresponding circular orbits are qualitatively similar to those of the Reissner-Nordström naked singularities. When event horizons are present, the orbits outside the Kehagias-Sfetsos black hole are qualitatively similar to those of the Schwarzschild metric.

Naked-Eye Detection of Glucose in Saliva with Bienzymatic Paper-Based Sensor

Directory of Open Access Journals (Sweden)

Luis A. Santana-Jiménez

2018-04-01

Full Text Available The high incidence of Diabetes Mellitus in low-income regions has promoted the development of low-cost alternatives to replace blood-based procedures. In this work, we present a bienzymatic paper-based sensor suitable for the naked-eye detection of glucose in saliva samples. The sensor was obtained by a stamping procedure and modified with chitosan to improve the colorimetric readout. The bienzymatic reaction of GOx-HRP coupled with 2,4,6-tribromo-3-hydroxy benzoic acid was applied for the detection of glucose within a range from 0 to 180 mgdL−1 in buffer and artificial saliva solutions. The visual readout was perceived by the naked eye and registered with an office scanner to evaluate the analytical performance. The results showed a limit of detection of 0.37 mgdL−1 (S/N = 3 with an R.S.D. of 1.69% and a linear range from 1 to 22.5 mgdL−1 with an R2 of 0.99235. The analysis of human saliva samples was performed without pre-processing, achieving recoveries from 92 to 114%. The naked-eye detection was evaluated under two different light settings, showing average recoveries of 108.58 and 90.65% for standard and low illumination. The proposed device showed potential for easy-to-use, sensitive, low-cost, fast, and device-free detection of salivary glucose suitable for untrained personnel operation and limited facilities.

Validation of the German version of the 'Hypogonadism Related Symptom Scale' (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome.

Science.gov (United States)

Alidjanov, J; Wolf, J; Schuppe, H-C; Weidner, W; Diemer, T; Linn, T; Halefeldt, I; Wagenlehner, F; Wiltink, J; Pilatz, A

2014-12-01

As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19-71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman-Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P males with suspected hypogonadism. © 2014 Blackwell Verlag GmbH.

病気の顔貌と容貌（1０） : 男性性腺機能低下症（Male hypogonadism or Eunuchoidism)について

OpenAIRE

佐々木, 悠; 熊谷, 秋三; 二宮, 寛; 福島, 武雄; 上園, 慶子; 川崎, 晃一; 奥村, 恂

1994-01-01

Hypogonadism in the male can be defined as a decrease in either endocrine or spermatogenetic function of the testis or both. Its conditions are frequently classified as being either primary or secondary dependending upon the site of the defect. Primary hypogonadism associated with abnormality of the testis may be subdivided into two groups, these caused by genetic or developmental defects and those related to acquired conditions. On the other hand, secondary hypogonadism refers to hypogonadis...

Hydatidiform moles among patients with incomplete abortion in ...

African Journals Online (AJOL)

SHS

ated risk factors of HM among patients with incomplete abortion evacuated at Bugando Medical ... Konje E, Massinde A, Rambau P. Hydatidiform moles among patients with ... countries (North America, Australia, New Zealand and ... missed as the cause of abortion. .... and duration of cigarette smoking could not be elicited.

The safety of available treatments of male hypogonadism in organic and functional hypogonadism.

Science.gov (United States)

Corona, G; Rastrelli, G; Reisman, Y; Sforza, A; Maggi, M

2018-03-01

In the case of primary male hypogonadism (HG), only testosterone (T) replacement therapy (TRT) is possible whereas when the problem is secondary to a pituitary or hypothalamus alteration both T production and fertility can be, theoretically, restored. We here systematically reviewed and discussed the advantages and limits of medications formally approved for the treatment of HG. Areas covered: Data derived from available meta-analyses of placebo controlled randomized trials (RCTs) were considered and analyzed. Gonadotropins are well-toleratedand their use is mainly limited by higher costs and a more cumbersome treatment schedule than TRT. Available RCTs on TRT suggest that cardiovascular (CV) and venous thromboembolism risk is not a major issue and that prostate safety is guaranteed. The risk of increased hematocrit is mainly limited to the use of short terminjectable preparations. Expert opinion: In the last few years the concept of 'organic' irreversible HG and 'functional' or age- and comorbidity-related HG has been introduced. This definition is not evidence-based. The majority of RCTs enrolled patients with 'functional' HG. Considering the significant improvement in body composition, glucose metabolism and sexual activity, TRT should not be limited to 'organic' HG, but also offered for 'functional'.

Management of pest mole crickets in Florida and Puerto Rico with a nematode and parasitic wasp

International Nuclear Information System (INIS)

Leppla, N.C.; Frank, J.H.; Adjei, M.B.; Vicente, N.E.

2007-01-01

Non-indigenous invasive mole crickets, Scapteriscus vicinus Scudder (Orthoptera: Gryllotalpidae) in Florida and S. didactylus (Latreille) (the 'changa') in Puerto Rico, are being managed with an entomopathogenic nematode, Steinernema scapterisci (Nguyen and Smart) (Rhabditida: Steinernematidae), and a parasitic wasp, Larra bicolor L. (Hymenoptera: Sphecidae). Pest mole cricket populations have declined by 95% in north central Florida since these specialist natural enemies were released and established in the 1980s. Commercial production of the nematode was initiated, nearly 70 billion were applied in 34 Florida counties, and their establishment, spread, and impact on mole crickets were monitored. The infected mole crickets dispersed the nematode rapidly, so that within 6 months these parasites were present in most of the insects trapped in experimental pastures. Three years later, mole cricket populations were reduced to acceptable levels and the bahiagrass had recovered. The nematode was released for the first time in Puerto Rico during 2001 and has persisted; the wasp was introduced in the late 1930s. The geographical distribution of the wasp is being expanded in Florida and Puerto Rico by planting plots of Spermacoce verticillata (L.), a wildflower indigenous to Puerto Rico and widely distributed in southern Florida. Pastures, sod farms, golf courses, landscapes, and vegetable farms in Florida and Puerto Rico are benefiting from biological control of invasive mole crickets. (author) [es

Seasonal abundances of naked amoebae in biofilms on shells of zebra mussels (Dreissena polymorpha) with comparative data from rock scrapings.

Science.gov (United States)

Bischoff, Paul J; Wetmore, Scott

2009-01-01

In North America, zebra mussels (Dreissena polymorpha) are notoriously known as invasive species. The abundance of naked amoebae sampled from the shells of zebra mussels was compared with abundances from rock scrapings at approximately monthly intervals for 1 year. The sites were 2 km apart along the same shoreline. No significant difference in abundance of naked amoebae (F = 1.44; P naked amoebae in winter, followed by peaks in early spring. The percent encysted increased from a low of 1% in the summer to 80% in early winter.

Fatty acid utilization in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

Reibel, D.K.; O'Rourke, B.

1986-01-01

The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H 2 O left atrial filling pressure with a ventricular afterload of 80 cm of H 2 O with buffer containing 1.2 mM 14 C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14 CO 2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14 CO 2 production during this time was 0.728 +/- 0.06 μmoles/min/g dry in control hearts and 0.710 +/- 0.02 μmoles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O 2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 μmoles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH).

Science.gov (United States)

Bonomi, Marco; Vezzoli, Valeria; Krausz, Csilla; Guizzardi, Fabiana; Vezzani, Silvia; Simoni, Manuela; Bassi, Ivan; Duminuco, Paolo; Di Iorgi, Natascia; Giavoli, Claudia; Pizzocaro, Alessandro; Russo, Gianni; Moro, Mirella; Fatti, Letizia; Ferlin, Alberto; Mazzanti, Laura; Zatelli, Maria Chiara; Cannavò, Salvo; Isidori, Andrea M; Pincelli, Angela Ida; Prodam, Flavia; Mancini, Antonio; Limone, Paolo; Tanda, Maria Laura; Gaudino, Rossella; Salerno, Mariacarolina; Francesca, Pregnolato; Maghnie, Mohamad; Maggi, Mario; Persani, Luca

2018-01-01

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH ( n  = 275), KS ( n  = 184), AO-nIHH ( n  = 36) and AO-doIHH (AO-IHH with defective olfaction, n  = 8). 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families. © 2018 European Society of Endocrinology.

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

Science.gov (United States)

Macchiaroli, Annamaria; Kelberman, Daniel; Auriemma, Renata Simona; Drury, Suzanne; Islam, Lily; Giangiobbe, Sara; Ironi, Gabriele; Lench, Nicholas; Sowden, Jane C; Colao, Annamaria; Pivonello, Rosario; Cavallo, Luciano; Gasperi, Maurizio; Faienza, Maria Felicia

2014-01-25

Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management. Copyright © 2013 Elsevier B.V. All rights reserved.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis

Directory of Open Access Journals (Sweden)

B Cangiano

2017-07-01

Full Text Available We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic–pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion.

Evaluation of the MoleMateTM training program for assessment of suspicious pigmented lesions in primary care

Directory of Open Access Journals (Sweden)

Annabel Wood

2008-05-01

Conclusion The MoleMateTM training program is a potentially effective and acceptable informatics tool to teach practitioners to recognise the features of SPLs identified by the MoleMateTM system. It will be used as part of the intervention in a randomised controlled trial to compare the diagnostic accuracy and appropriate referral rates of practitioners using the MoleMateTM system with best practice in primary care.

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion.

Directory of Open Access Journals (Sweden)

Shu-Fan Chou

2015-10-01

Full Text Available The Endosomal Sorting Complex Required for Transport (ESCRT is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV, we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1-147 containing no arginine-rich domain (ARD failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1-147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex.

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

Science.gov (United States)

Chou, Shu-Fan; Tsai, Ming-Lin; Huang, Jyun-Yuan; Chang, Ya-Shu; Shih, Chiaho

2015-01-01

The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1–147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1–147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex. PMID

effects of naked-neck and frizzle genes on growth performance and ...

African Journals Online (AJOL)

User

cockerels (birds) do not reach their full genetic potential in terms of growth, body weight or carcass yields because their feathers hinder the dissipation of their excessively produced inter- nal heat. It is against this background that the use of major heat-tolerant genes like naked- neck and frizzle is advocated (Horst and.

Naked singularities are not singular in distorted gravity

Energy Technology Data Exchange (ETDEWEB)

Garattini, Remo, E-mail: Remo.Garattini@unibg.it [Università degli Studi di Bergamo, Facoltà di Ingegneria, Viale Marconi 5, 24044 Dalmine (Bergamo) (Italy); I.N.F.N. – sezione di Milano, Milan (Italy); Majumder, Barun, E-mail: barunbasanta@iitgn.ac.in [Indian Institute of Technology Gandhinagar, Ahmedabad, Gujarat 382424 (India)

2014-07-15

We compute the Zero Point Energy (ZPE) induced by a naked singularity with the help of a reformulation of the Wheeler–DeWitt equation. A variational approach is used for the calculation with Gaussian Trial Wave Functionals. The one loop contribution of the graviton to the ZPE is extracted keeping under control the UltraViolet divergences by means of a distorted gravitational field. Two examples of distortion are taken under consideration: Gravity's Rainbow and Noncommutative Geometry. Surprisingly, we find that the ZPE is no more singular when we approach the singularity.

Naked singularities are not singular in distorted gravity

Science.gov (United States)

Garattini, Remo; Majumder, Barun

2014-07-01

We compute the Zero Point Energy (ZPE) induced by a naked singularity with the help of a reformulation of the Wheele-DeWitt equation. A variational approach is used for the calculation with Gaussian Trial Wave Functionals. The one loop contribution of the graviton to the ZPE is extracted keeping under control the UltraViolet divergences by means of a distorted gravitational field. Two examples of distortion are taken under consideration: Gravity's Rainbow and Noncommutative Geometry. Surprisingly, we find that the ZPE is no more singular when we approach the singularity.

Naked singularities are not singular in distorted gravity

International Nuclear Information System (INIS)

Garattini, Remo; Majumder, Barun

2014-01-01

We compute the Zero Point Energy (ZPE) induced by a naked singularity with the help of a reformulation of the Wheeler–DeWitt equation. A variational approach is used for the calculation with Gaussian Trial Wave Functionals. The one loop contribution of the graviton to the ZPE is extracted keeping under control the UltraViolet divergences by means of a distorted gravitational field. Two examples of distortion are taken under consideration: Gravity's Rainbow and Noncommutative Geometry. Surprisingly, we find that the ZPE is no more singular when we approach the singularity

Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe

DEFF Research Database (Denmark)

Kiess, W; Conway, G; Ritzen, M

2002-01-01

of the results of the questionnaires and discussions of that session to further the discussion on and knowledge of current concepts of induction of puberty in the hypogonadal girl in Europe. It became clear from the data accumulated here that the start of treatment, the aims of therapy and the modalities of how...... to treat the hypogonadal girl vary amongst pediatric endocrinologists in Europe. For example, a chronological age > or =11 years was considered appropriate for the start of estrogen therapy by 40.4% (out of 188 answers), while 47.8 and 7.5% felt that a chronological age > or =13 and > or =15 years...... respectively was appropriate. In respect to the form and route of estrogen administration, the audience was asked for their common estrogen replacement practice: 31.9% used oral 17beta-estradiol treatment, while 10% would prescribe 17beta-estradiol transdermal patches. Another 12.2% would recommend conjugated...

Hypogonadism and Male Obesity: Focus on Unresolved Questions.

Science.gov (United States)

Grossmann, Mathis

2018-04-23

Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men, and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic-pituitary-testicular axis (HPT) suppression. HPT axis suppression is likely mediated via pro-inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether estradiol-mediated negative hypothalamic-pituitary feedback plays a pathogenic role requires further study. Although the obesity-hypogonadism relationship is bi-directional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis. In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomised controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short-term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer-term, larger RCTs designed for patient-important outcomes and potential risks are required. Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity-associated non-classical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimisation of comorbidities remain first line. This article is protected by copyright. All

Excited state intramolecular charge transfer reaction in binary mixtures of water and tertiary butanol (TBA): alcohol mole fraction dependence.

Science.gov (United States)

Pradhan, Tuhin; Ghoshal, Piue; Biswas, Ranjit

2008-02-07

The excited state intramolecular charge transfer reaction of 4-(1-azetidinyl)benzonitrile (P4C) has been studied in water-tertiary butanol (TBA) mixtures at different alcohol mole fractions by using steady state and time-resolved fluorescence spectroscopy. The ratio between the areas under the locally excited (LE) and charge transferred (CT) emission bands is found to exhibit a sharp rise at alcohol mole fraction approximately 0.04, a value at which several thermodynamic properties of this mixture is known to show anomalous change due to the enhancement of H-bonding network. The radiative rate associated with the LE emission also shows a maximum at this TBA mole fraction. Although the structural transition from the water-like tetrahedral network to the alcohol-like chain is reflected in the red shift of the absorption spectrum up to TBA mole fraction approximately 0.10, the emission bands (both LE and CT) show the typical nonideal alcohol mole fraction dependence at all TBA mole fractions. Quantum yield, CT radiative rate as well as transition moments also exhibit a nonideal alcohol mole fraction dependence. The time-resolved emission decay of P4C has been found to be biexponential at all TBA mole fractions, regardless of emission collection around either the LE or the CT bands. The time constant associated with the slow component (tau(slow)) shows a minimum at TBA mole fraction approximately 0.04, whereas such a minimum for the fast time constant, tau(fast) (representing the rate of LE --> CT conversion reaction) is not observed. The nonobservation of the minimum in tau(fast) might be due to the limited time resolution employed in our experiments.

Oviposition and egg quality traits of dwarf and naked neck layers ...

African Journals Online (AJOL)

Oviposition and egg quality traits were studied in dwarf and naked neck layers in Maputo (Mozambique) during a 28-d period at 35 weeks of age. Birds were caged individually in a laying house with natural light and ventilation. Average daylight length during the study was 11.2 hr and minimum and maximum temperature ...

Analysis of internal doses to Mole voles inhabiting the East-Ural radioactive trace

Energy Technology Data Exchange (ETDEWEB)

Malinovsky, G.; Yarmoshenko, I. [Institute of Industrial Ecology UB RAS (Russian Federation); Chibiryak, M.; Vasil' ev, A. [Institute of Plant and Animal Ecology UB RAS (Russian Federation)

2014-07-01

Substantial task of development of approaches to radiation protection of non-human biota is investigation of relationships of exposure to dose, and dose to effects. Small mammals inhabiting territory of the East-Ural Radioactive Trace (EURT) are affected to ionizing radiation for many generations after accident at Mayak plutonium production in 1957. According to results of numerous studies a number of effects of exposure are observed. It is remarkable that the revealed effects are both negative and adaptive. In particular, the analysis of the variability of morphological structures of the axial skull and lower jaw in the population of northern mole vole (Ellobius talpinus Pall.), the burrowing rodent inhabiting the EURT, is of great interest. At the same time there is no reliable assessment of the radiation doses to these animals. Earlier we developed the approach to assess internal doses to mouse-like rodents (mice and voles) caused by incorporated {sup 90}Sr, which is the main dose contributing radionuclide at the EURT. Dose assessments are based on the results of beta-radiometry of intact bone. Routine methods for measuring the activity concentration of {sup 90}Sr in skeleton require ashing of samples, however in morphometric studies the destruction of material should be avoided: the skulls of mole voles are stored in the environmental samples depository of IPAE. Coefficients linking results of beta-radiometry of intact bone and activity concentration of {sup 90}Sr in skull of mouse was obtained basing on comparison of results of beta-radiometry of intact bone and bone ash. Obtained coefficients cannot be directly applied for calculating activity concentration of {sup 90}Sr in mole vole skulls because they are significantly larger. Therefore the additional study is required to assess proper coefficient of conversion from beta-radiometry to activity concentration of {sup 90}Sr. Developed dose assessment procedure includes application of the published values of

Radioimmunoassay of β sub unit HCG following hydatidiform mole or chorionic carcinoma

International Nuclear Information System (INIS)

Tscherne, G.; Puerstner, P.

1979-01-01

The radioimmunoassay of Beta Sub Unit HCG in the serum heralds a marked improvement in the diagnosis of gestational trophoblastic disease. In nine cases of hydatidiform mole and three cases of chorionic carcinoma serial examinations of the Beta Sub Unit HCG were performed. When the immunologic pregnancy test became negative following a hydatidiform mole or following treatment of chorionic carcinoma, the HCG excretion remained above detectable values for several more weeks. The decrease of Beta Sub Unit serum HCG was either linear or in fluctuations. The detection of fluctuations or a secondary rise in the Beta Sub Unit HCG titre permits the early diagnosis of invasive trophoblastic disease following hydatidiform mole or of insufficient treatment or recurrence in cases of chorionic carcinoma. Our results suggest that the optimal follow-up with Beta Sub Unit serum HCG is by weekly determinations until four consecutive determinations remained negative. This is followed by two determinations at bi-weekly intervals and thereafter monthly follow-up examinations. (orig.) 891 AJ/orig. 892 BRE [de

Prevalence and Factors Associated with Hydatidiform Mole among Patients Undergoing Uterine Evacuation at Mbarara Regional Referral Hospital

Directory of Open Access Journals (Sweden)

Olivier Mulisya

2018-01-01

Full Text Available Objective. We sought to determine the prevalence of and factors associated with hydatidiform molar gestations amongst patients undergoing uterine evacuation at Mbarara Regional Referral Hospital (MRRH, Mbarara, Uganda. Methods. This was a cross-sectional study carried out from November 2016 to February 2017. All patients admitted for uterine evacuation for nonviable pregnancy were included. The study registered 181 patients. Data were collected on sociodemographics, medical conditions, obstetrics, and gynecological factors. The evacuated tissue received a full gross and histopathologic examination. Cases of pathologically suspected complete hydatidiform mole were confirmed by p57 immunohistochemistry. Data were analyzed using STATA 13. Results. The prevalence of hydatidiform mole was 6.1% (11/181. All detected moles were complete hydatidiform moles, and there were no diagnosed partial hydatidiform moles. Clinical diagnosis of molar pregnancy was suspected in 13 patients, but only 69.2% (9/13 were confirmed as molar pregnancies histologically. Two cases were clinically unsuspected. Factors that had a significant relationship with complete hydatidiform mole included maternal age of 35 years and above (aOR 13.5; CI: 1.46–125.31; p=0.00, gestational age beyond the first trimester at the time of uterine evacuation (aOR 6.2; CI: 1.07–36.14; p=0.04, and history of previous abortion (aOR 4.3; CI: 1.00–18.57; p=0.05. Conclusion. The prevalence of complete hydatidiform mole was high at 6.1%. Associated risk factors included advanced maternal age (35 years and above, history of previous abortions, and gestational age beyond the first trimester at the time of evacuations. Recommendations. We recommend putting in place capacity to do routine histopathological examination of all products of conception especially those at high risk for a molar gestation either by clinical suspicion or by risk factors including advanced maternal age, advanced gestational

Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

Directory of Open Access Journals (Sweden)

Yusuke Kemmochi

2013-01-01

Full Text Available Spontaneously Diabetic Torii Leprfa (SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

Science.gov (United States)

Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

2016-02-01

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Hardness evaluation of cured urea-formaldehyde resins with different formaldehyde/urea mole ratios using nanoindentation method

Science.gov (United States)

Byung-Dae Park; Charles R. Frihart; Yan Yu; Adya P. Singh

2013-01-01

To understand the influence of formaldehyde/urea (F/U) mole ratio on the properties of urea–formaldehyde (UF) resins, this study investigated hardness of cured UF resins with different F/U mole ratios using a nanoindentation method. The traditional Brinell hardness (HB) method was also used...

A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats.

Science.gov (United States)

Allan, George F; Tannenbaum, Pamela; Sbriscia, Tifanie; Linton, Olivia; Lai, Muh-Tsann; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Zhang, Xuqing; Sui, Zhihua; Lundeen, Scott G

2007-08-01

Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-28330835 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle, stimulating maximal growth at a dose of 10 mg/kg. At the same time, JNJ-28330835 reduced prostate weight in intact rats by a mean of 30% at 10 mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging (MRI) to monitor body composition, it prevented half of the loss of lean body mass associated with orchidectomy, and restored about 30% of lost lean mass to aged orchidectomized rats. It had agonist effects on markers of both osteoclast and osteoblast activity, suggesting that it reduces bone turnover. In a model of sexual behavior, JNJ-28330835 enhanced the preference of ovariectomized female rats for sexually intact male rats over nonsexual orchidectomized males. JNJ-28330835 is a prostate-sparing SARM with the potential for clinically beneficial effects in muscle-wasting diseases and sexual function disorders.

Definition of the mole (IUPAC Recommendation 2017)

OpenAIRE

Marquardt, Roberto; Meija, Juris; Mester, Zoltán; Towns, Marcy; Weir, Ron; Davis, Richard; Stohner, Jürgen

2018-01-01

In 2011 the General Conference on Weights and Measures (CGPM) noted the intention of the International Committee for Weights and Measures (CIPM) to revise the entire International System of Units (SI) by linking all seven base units to seven fundamental physical constants. Of particular interest to chemists, new definitions for the kilogram and the mole have been proposed. A recent IUPAC Technical Report discussed these new definitions in relation to immediate consequences for the chemical co...

Efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score to predict gestational trophoblastic tumor from hydatidiform mole

Directory of Open Access Journals (Sweden)

Khrismawan Khrismawan

2004-03-01

Full Text Available A prospective longitudinal analytic study assessing the efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score in predicting malignancy after hydatidiform mole had been performed. Of the parameter evaluated; age of patients, type of hydatidiform mole, uterine enlargement, serum hCG level, lutein cyst, and presence of complicating factors were significant risk factors for malignancy after hydatidiform mole were evacuated (p<0.032. The study were done on 50 women diagnosed with hydatidiform mole with 1 year observation (January 2001-December 2002 at the Department of Obstetrics and Gynecology, Mohammad Hoesin Hospital, Palembang. The results showed that the NETDC prognostic index score predicted malignancy in 50% of high risk group and 10% in low risk group (p<0.05. This showed a higher number than that found by the WHO (19%-30%. The risk for incidence of  malignancy after hydatidiform mole in the high risk group is 9.0 times higher compared to that of the low risk group (CI: 1.769-45.786. (Med J Indones 2004; 13: 40-6 Keywords: New England Trophoblastic Disease Center (NETDC, gestational trophoblastic tumor, hydatidiform mole, high and low risk

Current transport mechanism in graphene/AlGaN/GaN heterostructures with various Al mole fractions

Science.gov (United States)

Pandit, Bhishma; Seo, Tae Hoon; Ryu, Beo Deul; Cho, Jaehee

2016-06-01

The current transport mechanism of graphene formed on AlxGa1-xN/GaN heterostructures with various Al mole fractions (x = 0.15, 0.20, 0.30, and 0.40) is investigated. The current-voltage measurement from graphene to AlGaN/GaN shows an excellent rectifying property. The extracted Schottky barrier height of the graphene/AlGaN/GaN contacts increases with the Al mole fraction in AlGaN. However, the current transport mechanism deviates from the Schottky-Mott theory owing to the deterioration of AlGaN crystal quality at high Al mole fractions confirmed by reverse leakage current measurement.

Current transport mechanism in graphene/AlGaN/GaN heterostructures with various Al mole fractions

Directory of Open Access Journals (Sweden)

Bhishma Pandit

2016-06-01

Full Text Available The current transport mechanism of graphene formed on AlxGa1−xN/GaN heterostructures with various Al mole fractions (x = 0.15, 0.20, 0.30, and 0.40 is investigated. The current–voltage measurement from graphene to AlGaN/GaN shows an excellent rectifying property. The extracted Schottky barrier height of the graphene/AlGaN/GaN contacts increases with the Al mole fraction in AlGaN. However, the current transport mechanism deviates from the Schottky-Mott theory owing to the deterioration of AlGaN crystal quality at high Al mole fractions confirmed by reverse leakage current measurement.

Study of Biometric Identification Method Based on Naked Footprint

Directory of Open Access Journals (Sweden)

Raji Rafiu King

2013-10-01

Full Text Available The scale of deployment of biometric identity-verification systems has recently seen an enormous increase owing to the need for more secure and reliable way of identifying people. Footprint identification which can be defined as the measurement of footprint features for recognizing the identity of a user has surfaced recently. This study is based on a biometric personal identification method using static footprint features viz. friction ridge / texture and foot shape / silhouette. To begin with, naked footprints of users are captured; images then undergo pre processing followed by the extraction of two features; shape using Gradient Vector Flow （GVF） snake model and minutiae extraction respectively. Matching is then effected based on these two features followed by a fusion of these two results for either a reject or accept decision. Our shape matching feature is based on cosine similarity while the texture one is based on miniature score matching. The results from our research establish that the naked footprint is a credible biometric feature as two barefoot impressions of an individual match perfectly while that of two different persons shows a great deal of dissimilarity. Normal 0 false false false IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Doi: 10.12777/ijse.5.2.29-35 How to cite this article: King

Naked-eye sensor for rapid determination of mercury ion.

Science.gov (United States)

Liu, Jing; Wu, Dapeng; Yan, Xiaohui; Guan, Yafeng

2013-11-15

A naked-eye paper sensor for rapid determination of trace mercury ion in water samples was designed and demonstrated. The mercury-sensing rhodamine B thiolactone was immobilized in silica matrices and the silica matrices were impregnated firmly and uniformly in the filter paper. As water samples flow through the filter paper, the membrane color will change from white to purple red, which could be observed obviously with naked eye, when concentration of mercury ions equals to or exceeds 10nM, the maximum residue level in drinking water recommended by U.S. EPA. The color change can also be recorded by a flatbed scanner and then digitized, reducing the detection limit of Hg(2+) down to 1.2 nM. Moreover, this method is extremely specific for Hg(2+) and shows a high tolerance ratio of interferent coexisting ions. The presence of Na(+) (2 mM), K(+) (2 mM), Fe(3+) (0.1 mM), Zn(2+) (0.1 mM), Mg(2+) (0.1 mM), Ni(2+) (50 μM), Co(2+) (50 μM), Cd(2+) (50 μM), Pb(2+) (50 μM), Cu(2+) (50 μM) and Ag(+) (3.5 μM) did not interfere with the detection of Hg(2+) (25 nM). Finally, the present method was applied in the detection of Hg(2+) in mineral water, tap water and pond water. Copyright © 2013 Elsevier B.V. All rights reserved.

Productive performance of naked neck chickens that were fed leaf meal shrubs

Directory of Open Access Journals (Sweden)

Santos M Herrera G.

2015-12-01

Full Text Available Objective. To compare the productive performance of naked neck chickens (phases of initiation, growth and final that were fed meals Gliricidia sepium, Cajanus cajan and Morus alba leaves. Materials and methods. 192 chickens, 1-84 days of age were distributed in a randomized block design with three experimental groups (5% of shrub in the diet, 48 animals/ group, eight replicates/ treatment, six animals/ reply and three animals/ sex in each replicate were used. The control group consumed diet based on corn and soybeans. They were reared on floor. Weighed every seven days. Weight gain, voluntary intake, conversion, balance and efficiency of feed utilization were calculated. Results. The highest total feed intake and average daily gain in rearing were 37.43g 9509.96 g respectively for M. alba (p<0.05, which also presented the best efficiency of energy and protein. Meanwhile, G. sepium showed the lowest values. Conclusions. It is possible to replace 5% of corn and soy in the diet of naked neck chickens, with the inclusion of leaf meal M. alba and get a favorable productive behavior.

Very low-energy and low-fluence ion beam bombardment of naked plasmid DNA

International Nuclear Information System (INIS)

Norarat, R.; Semsang, N.; Anuntalabhochai, S.; Yu, L.D.

2009-01-01

Ion beam bombardment of biological organisms has been recently applied to mutation breeding of both agricultural and horticultural plants. In order to explore relevant mechanisms, this study employed low-energy ion beams to bombard naked plasmid DNA. The study aimed at simulation of the final stage of the process of the ion beam bombardment of real cells to check whether and how very low-energy and low-fluence of ions can induce mutation. Argon and nitrogen ions at 5 keV and 2.5 keV respectively bombarded naked plasmid DNA pGFP to very low-fluences, an order of 10 13 ions/cm 2 . Subsequently, DNA states were analyzed using electrophoresis. Results provided evidences that the very low-energy and low-fluence ion bombardment indeed altered the DNA structure from supercoil to short linear fragments through multiple double strand breaks and thus induced mutation, which was confirmed by transfer of the bombarded DNA into bacteria Escherichia coli and subsequent expression of the marker gene.

David Cronenberg, author of naked lunch: Intersemiotic translation as transcreation

Directory of Open Access Journals (Sweden)

Rosângela Fachel de Medeiros

2016-05-01

Full Text Available This paper presents and analyzes the intersemiotic translation process performed by filmmaker David Cronenberg of William Burroughs' novel Naked Lunch, and the intertextual bifurcations involved in this process. Investigating the similarities and differences between the creative worlds of both artists and how they reframe each other. For this, are used as the theoretical the idea of transcreation proposed by Haroldo de Campos, and the notion of the translator as a reader proposed by Jorge Luis Borges.

Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy.

Science.gov (United States)

Salman, Mahmoud; Yassin, Dany-Jan; Shoukfeh, Huda; Nettleship, Joanne Elisabeth; Yassin, Aksam

2017-03-01

We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA 1C ), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.

Performance and Heterosis of Indigenous Chicken Crossbreed (Naked Neck x Frizzled Feather In The Humid Tropics

Directory of Open Access Journals (Sweden)

Jeremiah Monday Nwenya

2017-12-01

Full Text Available Forty-four (44 birds (about 50 weeks old male and female inbred naked necked and frizzle feathered chickens were crossed to generate F1 crossbred chicken that were used to evaluate the performance and heterosis effects. Data taken on 180 chicks (97 NN and 83 FF day-old chick weight (BWT0, body weight (BWT, daily average feed intake (AFI, feed conversion ratio (FCR, brooding and rearing mortalities, linear body measurements (LBM: body length, wing length, keel length, shank length and breast width were used to estimate heterosis and performance of F1 progenies. Results of the experiment showed positive heterosis with significant differences among the F1 progenies over their parents in body weight, average feed intake and feed conversion ratio. The reciprocal cross (i.e. frizzle feather rooster x naked neck hen showed a significant improvement in their performances genetically, explaining that better results are achieved through crossbreeding of these indigenous breeds. With reference to their body linear parameters, the reciprocal cross of naked neck and frizzle feathered chickens developed higher body length, whereas the main crosses performed better in their wing length, keel length, shank length and body width respectively, mainly after 8 weeks suggesting that earlier performance was attributable to maternal influences.

[Hypogonadism caused by Gorlin-Goltz syndrome].

Science.gov (United States)

Marín Romero, Olivia; Hernández Marín, Imelda; Ayala Ruiz, Aquiles R

2006-09-01

The Gorlin-Goltz syndrome is a dominant autosomic disorder characterized by cancerigenic predisposition and multiple development defects, apparently without reproductive compromise. The complex is characterized by four primary symptoms, which include nevoid basal cell epitheliomas malignantly prone, keratocystic jaw, skeletal abnormalities and intracranial calcifications. Apparently, reproductive problems reported had been rarely associated with this syndrome. We present the case of a patient with clinic stigmatae of Gorlin-Goltz syndrome, who had a characteristic progress as seen in the literature; he was the fifth product of a 43 year-old female (father was 48 years old); who at birth disclosed right eye microftalmy, bilateral cryptorchidism surgically treated at age of six. At puberty, an odontogenic cyst of the jaw was noted and enucleated. He also showed facial nevi in neck, thorax and abdomen. When he was admitted being 14 years old in our clinic, he had recurrent bilateral cryptorchidism, sexual immatturity and infertility. It is important to take into consideration Gorlin-Goltz stigmatae in cases of hypogonadism in order to recognize a further genetic influence.

Progression of puberty after initiation of androgen therapy in patients with idiopathic hypogonadotropic hypogonadism

Directory of Open Access Journals (Sweden)

Bindu Kulshreshtha

2013-01-01

Full Text Available Background: Onset of puberty in boys usually occurs by 14 years of age. Some boys may exhibit delayed sexual maturation till about 17-18 years of age. However, pubertal onset beyond 18 years of age is exceedingly rare. Materials and Methods: Patients diagnosed as idiopathic hypogonadotropic hypogonadism (IHH who had onset of puberty (increase in testicular volume >10 ml while on androgen therapy were studied. These patients were evaluated prospectively. Results: There were nine subjects that were included in the study. The pre-therapy testicular volumes ranged from 3 to 6 ml. Luteinizing hormone (LH levels increased from 1.2 ± 0.96 to 2.8 ± 1.0 IU/L, follicular stimulating hormone (FSH levels increased from 1.5 ± 0.79 to 3.5 ± 1.9 IU/L, and testosterone increased from 0.36 ± 0.16 to 3.4 ± 2.1 ng/ml. Three out of nine patients had testosterone levels below 3 ng/ml. Conclusion: Our present study indicates that pubertal development can occur in patients presenting with hypogonadotropic hypogonadism after 18 years of age. However, acquired pubertal status may be subnormal

New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism

Energy Technology Data Exchange (ETDEWEB)

Yanase, Toshihiko; Takayanagi, Ryoichi; Oba, Koichi [Kyushu Univ., Fukuoka (Japan)] [and others

1996-02-01

Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for the mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients` genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. 31 refs., 4 figs., 2 tabs.

Osteopenia and bone fractures in a man with anorexia nervosa and hypogonadism

Energy Technology Data Exchange (ETDEWEB)

Rigotti, N.A.; Neer, R.M.; Jameson, L.

1986-07-18

Women with anorexia nervosa have reduced skeletal mass. Both anorexia and osteopenia are less common in men. We describe a 22-year-old man with anorexia nervosa and severe osteopenia involving both cortical and trabecular bone who developed a pelvic fracture and multiple vertebral compression fractures. He was found to have secondary hypogonadotropic hypogonadism that was reversible with weight gain. This case illustrates the need to consider osteopenia as a potential complication of anorexia nervosa in males as well as females.

Osteopenia and bone fractures in a man with anorexia nervosa and hypogonadism

International Nuclear Information System (INIS)

Rigotti, N.A.; Neer, R.M.; Jameson, L.

1986-01-01

Women with anorexia nervosa have reduced skeletal mass. Both anorexia and osteopenia are less common in men. We describe a 22-year-old man with anorexia nervosa and severe osteopenia involving both cortical and trabecular bone who developed a pelvic fracture and multiple vertebral compression fractures. He was found to have secondary hypogonadotropic hypogonadism that was reversible with weight gain. This case illustrates the need to consider osteopenia as a potential complication of anorexia nervosa in males as well as females

Indium mole fraction effect on the structural and optical properties of quaternary AlInGaN epilayers

International Nuclear Information System (INIS)

Liu, J P; Jin, R Q; Zhang, J C; Wang, J F; Wu, M; Zhu, J J; Zhao, D G; Wang, Y T; Yang, H

2004-01-01

AlInGaN quaternary epilayers with varying In mole fraction were investigated using triple-axis x-ray diffraction and photoluminescence measurements. The indium compositional fluctuation is enhanced with increasing In mole fraction, whereas the mosaicity of the AlInGaN epilayers is determined through the GaN template quality. Based on the analysis of the temperature dependence of the PL peak position, it is found that the localization effect strengthens with increasing In mole fraction due to the larger fluctuations of the In distribution. Increasing the influence of the localized state results in increasing the emission intensity and FWHM with the In content

Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

Science.gov (United States)

Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

2014-01-01

Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering

Experimental Investigation of InSight HP3 Mole Interaction with Martian Regolith Simulant. Quasi-Static and Dynamic Penetration Testing

Science.gov (United States)

Marshall, Jason P.; Hudson, Troy L.; Andrade, José E.

2017-10-01

The InSight mission launches in 2018 to characterize several geophysical quantities on Mars, including the heat flow from the planetary interior. This quantity will be calculated by utilizing measurements of the thermal conductivity and the thermal gradient down to 5 meters below the Martian surface. One of the components of InSight is the Mole, which hammers into the Martian regolith to facilitate these thermal property measurements. In this paper, we experimentally investigated the effect of the Mole's penetrating action on regolith compaction and mechanical properties. Quasi-static and dynamic experiments were run with a 2D model of the 3D cylindrical mole. Force resistance data was captured with load cells. Deformation information was captured in images and analyzed using Digitial Image Correlation (DIC). Additionally, we used existing approximations of Martian regolith thermal conductivity to estimate the change in the surrounding granular material's thermal conductivity due to the Mole's penetration. We found that the Mole has the potential to cause a high degree of densification, especially if the initial granular material is relatively loose. The effect on the thermal conductivity from this densification was found to be relatively small in first-order calculations though more complete thermal models incorporating this densification should be a subject of further investigation. The results obtained provide an initial estimate of the Mole's impact on Martian regolith thermal properties.

Stationary spherical shells around Kerr-Newman naked singularities

International Nuclear Information System (INIS)

Zdenek Stuchlik; Stanislav Hledik

1998-01-01

It is shown that in the field of some Kerr-Newman naked singularities a stationary spherical shell of charged dust can exist, with the specific charge being the same for all particles of the dusty shell. Gravitational attractions acting on the particles are balanced by electromagnetic repulsion in such a way that the shell is stable against radial perturbations. Particles of the shell move along orbits with constant latitude and radius. Rotation of the shell is differential. The shell is corotating relative to static observers at infinity, but it is counter rotating relative to the family of locally non-rotating observers. No such a shell can exist in the field of Kerr-Newman black holes. (authors)

Nonspecific nature of the vanadate inhibition of rat ileal (Na, K)-ATPase

International Nuclear Information System (INIS)

Hajjar, J.J.; Rowe, W.A.; Tomicic, T.K.

1988-01-01

Vanadate has been suggested as an intracellular regulator of (Na+ + K+)-ATPase. To test this hypothesis the authors examined the stimulatory and inhibitory effects of vanadate on 86 Rb efflux and influx (measurements of the activity of the Na-pump) in rat ileum under conditions of normal, reduced and increased (Na+ + K+)-ATPase activity. The half maximal inhibition of the Rb efflux and the half maximal inhibition of the Rb influx were not different in the three conditions tested. This suggests that vanadate does not have a regulatory effect on the activity of the Na-K-transport enzyme. The vanadate effect seem rather, to be nonspecific in terms of being unrelated, on a mole per mole basis, to the activity of the (Na+ + K+)-ATPase enzyme

Nonspecific nature of the vanadate inhibition of rat ileal (Na, K)-ATPase

Energy Technology Data Exchange (ETDEWEB)

Hajjar, J.J.; Rowe, W.A.; Tomicic, T.K.

1988-01-01

Vanadate has been suggested as an intracellular regulator of (Na+ + K+)-ATPase. To test this hypothesis the authors examined the stimulatory and inhibitory effects of vanadate on /sup 86/Rb efflux and influx (measurements of the activity of the Na-pump) in rat ileum under conditions of normal, reduced and increased (Na+ + K+)-ATPase activity. The half maximal inhibition of the Rb efflux and the half maximal inhibition of the Rb influx were not different in the three conditions tested. This suggests that vanadate does not have a regulatory effect on the activity of the Na-K-transport enzyme. The vanadate effect seem rather, to be nonspecific in terms of being unrelated, on a mole per mole basis, to the activity of the (Na+ + K+)-ATPase enzyme.

Factors in Early Adolescence Associated With a Mole-Prone Phenotype in Late Adolescence.

Science.gov (United States)

Xu, Haoming; Marchetti, Michael A; Dusza, Stephen W; Chung, Esther; Fonseca, Maira; Scope, Alon; Geller, Alan C; Bishop, Marilyn; Marghoob, Ashfaq A; Halpern, Allan C

2017-10-01

Nevi are important phenotypic risk factors for melanoma in adults. Few studies have examined the constitutional and behavioral factors associated with a mole-prone phenotype in adolescents. To identify host, behavioral, and dermoscopic factors in early adolescence (age, 14 years) that are associated with a mole-prone phenotype in late adolescence (age, 17 years). A prospective observational cohort study from the Study of Nevi in Children was conducted from January 1, 2009, to December 31, 2014, with a 2- to 3-year follow-up. A total of 569 students from the school system in Framingham, Massachusetts, were enrolled in the 8th or 9th grade (baseline; mean [SD] age, 14.4 [0.7] years). The overall retention rate was 73.3%, and 417 students were reassessed in the 11th grade. Mole-prone phenotype in the 11th grade, defined as total nevus count of the back and 1 randomly selected leg in the top decile of the cohort or having any nevi greater than 5 mm in diameter. Of the 417 students assessed at follow-up in the 11th grade (166 females and 251 males; mean [SD] age, 17.0 [0.4] years), 111 participants (26.6%) demonstrated a mole-prone phenotype: 69 students (62.2%) with 1 nevus greater than 5 mm in diameter, 23 students (20.7%) with total nevus count in the top decile, and 19 students (17.1%) with both characteristics. On multivariate analysis, baseline total nevus count (adjusted odds ratio, 9.08; 95% CI, 4.0-23.7; P adolescents for higher-intensity counseling about sun protection and skin self-examination.

Rationale, design and methods of the ESPRIT study: Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy, in hypogonadal men.

Science.gov (United States)

Behre, Hermann M; Heinemann, Lothar; Morales, Alvaro; Pexman-Fieth, Claire

2008-06-01

Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality, and also affect quality of life. The ESPRIT study (Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy) is a 6-month, multinational, open label, observational study in hypogonadal men being treated with transdermal AndroGel in usual daily clinical practice; 1,700-2,400 patients will be enrolled in Canada, Germany, Central and Eastern Europe, Russia and the Middle East. The main objective will be to evaluate the effect of AndroGel on symptoms of hypogonadism and quality of life as assessed by the Aging Males' Symptoms scale. Further objectives include evaluating the effect and time to onset of improvement in erectile dysfunction and libido/sexual desire (International Index of Erectile Function), fatigue (Multi-dimensional Fatigue Index) and body composition (waist circumference, body mass index). Subgroup analyses will be performed: or = 50 years; absence versus presence of metabolic syndrome. The safety of AndroGel will also be assessed. The study population will consist of newly diagnosed hypogonadal men (age > or = 18 years), in whom testosterone deficiency has been confirmed by clinical features and biochemical tests according to international guidelines, who are currently being prescribed AndroGel (testosterone 1% gel, starting dose 50 mg testosterone per day).

Particle Collision Near 1 + 1-Dimensional Horava-Lifshitz Black Hole and Naked Singularity

Directory of Open Access Journals (Sweden)

M. Halilsoy

2017-01-01

Full Text Available The unbounded center-of-mass (CM energy of oppositely moving colliding particles near horizon emerges also in 1+1-dimensional Horava-Lifshitz gravity. This theory has imprints of renormalizable quantum gravity characteristics in accordance with the method of simple power counting. Surprisingly the result obtained is not valid for a 1-dimensional Compton-like process between an outgoing photon and an infalling massless/massive particle. It is possible to achieve unbounded CM energy due to collision between infalling photons and particles. The source of outgoing particles may be attributed to an explosive process just outside the horizon for a black hole and the naturally repulsive character for the case of a naked singularity. It is found that absence of angular momenta in 1+1-dimension does not yield unbounded energy for collisions in the vicinity of naked singularities.

Twin pregnancy with both complete hydatiform mole and coexistent alive fetus: Case report

Directory of Open Access Journals (Sweden)

Achour Radhouane

2015-12-01

Full Text Available Twin pregnancy consisting of a complete hydatidiform mole coexisting with a live fetus is a rare condition with an incidence of 1 in 22000 to 1 in 100000 pregnancies. Clinical information is limited and management is difficult due to the risk of pregnancy complications such as fetal death, vaginal bleeding, preeclampsia, hyperthyroidism, and the risk of persistent gestational trophoblastic disease. Thus, the report described about the change of size and implantation site of the molar mass coexisting with a live fetus is rare especially about sonographic findings such as echo patterns. Recently we experienced a case of complete hydatidiform mole with a healthy infant delivered at term.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

Science.gov (United States)

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.

Science.gov (United States)

Bolze, Pierre-Adrien; Patrier, Sophie; Cheynet, Valérie; Oriol, Guy; Massardier, Jérôme; Hajri, Touria; Guillotte, Michèle; Bossus, Marc; Sanlaville, Damien; Golfier, François; Mallet, François

2016-03-01

Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?

Science.gov (United States)

Nahata, Leena; Yu, Richard N; Bhasin, Shalender; Cohen, Laurie E

2015-05-01

Male hypogonadism is a common disorder that is associated with low bone density, poor muscle mass, anemia, and sexual dysfunction. The Endocrine Society recently published a Clinical Practice Guideline for testosterone therapy in androgen-deficient men. Because treatment is frequently initiated in adolescence, the goal of this quality improvement initiative was to assess whether pediatric endocrinologists at a large tertiary care center follow these guidelines and to identify opportunities for improvement. We performed a retrospective chart review at Boston Children's Hospital. Inclusion criteria were as follows: current age ≥16 years, diagnosis of hypogonadism, and testosterone replacement therapy. Data were collected about current age, age at treatment initiation, diagnoses, pre- and on-treatment testosterone levels, route of testosterone administration and dose, bone density, hematocrit levels, and adherence with therapy. Fifty-nine patients were included. Fourteen (24%) were prescribed lower testosterone doses than those recommended in the Clinical Practice Guideline. Seven (12%) had no pre-treatment testosterone levels, and 10 (17%) had no on-treatment levels. In 49 patients with on-treatment testosterone levels, 36 had at least one value that was lower than the adult reference range. Ten (28%) of the 36 men with low testosterone levels had no dose adjustments. Thirty-seven (63%) of the 59 patients had no dual-energy X-ray absorptiometry scans, and 18 (31%) did not have hematocrit levels. Pediatric endocrinologists in this review did not consistently follow the Clinical Practice Guideline for testosterone therapy in hypogonadal adult males. Strategies that improve adherence to guidelines could help maximize the benefits of therapy and minimize treatment-associated risks.

Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

Science.gov (United States)

Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

2015-01-01

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

A preliminary phylogeny of the Palearctic naked-toed geckos (Reptilia: Squamata: Gekkonidae) with taxonomic implications.

Science.gov (United States)

Bauer, Aaron M; Masroor, Rafaqat; Titus-McQuillan, James; Heinicke, Matthew P; Daza, Juan D; Jackman, Todd R