Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

Science.gov (United States)

Hornberger, Troy A; McLoughlin, Thomas J; Leszczynski, Jori K; Armstrong, Dustin D; Jameson, Ruth R; Bowen, Phyllis E; Hwang, Eun-Sun; Hou, Honglin; Moustafa, Mohamed E; Carlson, Bradley A; Hatfield, Dolph L; Diamond, Alan M; Esser, Karyn A

2003-10-01

Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.

Pregnancy and paroxysmal nocturnal hemoglobinuria

NARCIS (Netherlands)

Bais, J.; Pel, M.; von dem Borne, A.; van der Lelie, H.

1994-01-01

A patient is described who developed symptoms of paroxysmal nocturnal hemoglobinuria (PNH) in her first pregnancy. This was uneventful except for a spontaneous preterm delivery. The second pregnancy was complicated by severe anemia and a hemolytic crisis with Budd-Chiari syndrome at 31 weeks'

Benign paroxysmal positional vertigo treatment

DEFF Research Database (Denmark)

West, Niels; Hansen, Søren; Bloch, Sune Land

2017-01-01

Benign paroxysmal positional vertigo (BPPV) remains the most frequent cause of vertigo. The TRV chair is a mechanical device suited for optimization of managing complex cases of BPPV. Although the use of repositioning devices in the management of BPPV is increasing, no applicable guide for the TRV...

Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.

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Takaaki Inaba

Full Text Available Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice. We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.

An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice.

Science.gov (United States)

Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Kukuia, Kennedy K E; Karikari, Thomas K; Nyarko, Alexander K

2017-09-26

Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin's test. No lethality was observed after 24 h post-treatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.

Telomerase-Deficient Mice Exhibit Bone Loss Owing to Defects in Osteoblasts and Increased Osteoclastogenesis by Inflammatory Microenvironment

DEFF Research Database (Denmark)

Saeed, H.; Abdallah, B. M.; Ditzel, N.

2011-01-01

Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we...... studied the phenotype of telomerase-deficient mice (Terc(-/-)).Terc(-/-) mice exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months of follow-up revealed by dual-energy X-ray absorptiometric (DXA) scanning and by micro-computed tomography (mu CT). Bone...... histomorphometry revealed decreased mineralized surface and bone-formation rate as well as increased osteoclast number and size in Terc(-/-) mice. Also, serum total deoxypyridinoline (tDPD) was increased in Terc(-/-) mice. MSCs and osteoprogenitors isolated from Terc(-l-) mice exhibited intrinsic defects...

Genetic Forms of Epilepsies and other Paroxysmal Disorders

Science.gov (United States)

Olson, Heather E.; Poduri, Annapurna; Pearl, Phillip L.

2016-01-01

Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including Tuberous Sclerosis Complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of singe gene causes or susceptibility factors associated with several epilepsy syndromes, including the early onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look towards the future of epilepsy genetics. PMID:25192505

Mice lacking Brinp2 or Brinp3, or both, exhibit behaviours consistent with neurodevelopmental disorders

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Susie Ruth Berkowicz

2016-10-01

Full Text Available Background: Brinps 1 – 3, and Astrotactins (Astn 1 and 2, are members of the Membrane Attack Complex / Perforin (MACPF superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1-/- mice exhibit behaviour reminiscent of autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD.Method: We created Brinp2-/- mice and Brinp3-/- mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behaviour. Additionally, Brinp2-/-Brinp3-/- double knock-out mice were generated by interbreeding Brinp2-/- and Brinp3-/- mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioural examination. Brinp1-/-Brinp2-/-Brinp3-/- triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1-/- mice, and examined by weight and histological analysis.Results: Brinp2-/- and Brinp3-/- mice differ in their behaviour: Brinp2-/- mice are hyperactive, whereas Brinp3-/- mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3-/- mice also show evidence of altered sociability. Both Brinp2-/- and Brinp3-/- mice have normal short-term memory, olfactory responses, pre-pulse inhibition and motor learning. The double knock-out mice show behaviours of Brinp2-/- and Brinp3-/- mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2-/- and Brinp3-/- genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.

A case of congenital myopathy masquerading as paroxysmal dyskinesia

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Harsh Patel

2014-01-01

Full Text Available Gastroesophageal reflux (GER disease is a significant comorbidity of neuromuscular disorders. It may present as paroxysmal dyskinesia, an entity known as Sandifer syndrome. A 6-week-old neonate presented with very frequent paroxysms of generalized stiffening and opisthotonic posture since day 22 of life. These were initially diagnosed as seizures and he was started on multiple antiepileptics which did not show any response. After a normal video electroencephalogram (VEEG was documented, possibility of dyskinesia was kept. However, when he did not respond to symptomatic therapy, Sandifer syndrome was thought of and GER scan was done, which revealed severe GER. After his symptoms got reduced to some extent, a detailed clinical examination revealed abnormal facies with flaccid quadriparesis. Muscle biopsy confirmed the diagnosis of a specific congenital myopathy. On antireflux measures, those episodic paroxysms reduced to some extent. Partial response to therapy in GER should prompt search for an underlying secondary etiology.

Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome

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Marie Mongin

2016-03-01

Full Text Available Background: Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Phenomenology Shown: Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. Educational Value: Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable.

Ocular vestibular evoked myogenic potential in patients with benign paroxysmal positional vertigo

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Mozhgan Masoom

2014-06-01

Full Text Available Background and Aim: Since utricle is the main damaged organ in benign paroxysmal positional vertigo (BPPV, ocular vestibular evoked myogenic potential (oVEMP may be an appropriate method to evaluate the utricule dysfunction and the effect of disease recurrence rate on it. This study aimed to record myogenic potential in patients with benign paroxysmal positional vertigo.Methods: In a cross-sectional study, ocular myogenic potential was recorded in 25 healthy subjects and 20 patients with benign paroxysmal positional vertigo using 500 Hz-tone bursts (95 dB nHL.Results: In the affected ear, mean amplitude was lower and mean threshold was higher than those in the unaffected ear and in the normal group (p<0.05. Mean amplitude asymmetry ratio of patients was more than the healthy subjects (p0.05. Frequencies of abnormal responses in the affected ears were higher than in unaffected ears and in the normal group (p<0.05. Furthermore, the patients with recurrent vertigo showed more abnormalities than the patients with non-recurrent (p=0.030.Conclusion: In the recurrent benign paroxysmal positional vertigo, ocular vestibular evoked myogenic potential showed more damage in the utricle, suggesting this response could be used to evaluate the patients with benign paroxysmal positional vertigo.

Strategi Pengembangan Kota Surakarta Menjadi Kota Mice (Meeting, Incentive, Convention, Exhibition)

OpenAIRE

Mahadi, Khairul; Hidayat, Teguh

2013-01-01

Seiring dengan berkembangnnya sistem transportasi yang ada di dunia baik transportasi laut, darat, dan udara dimana dapat memudahkan seseorang atau sebuah kelompok berpergian dari satu wilayah ke wilayah lain, dari sinilah MICE (meeting, incentive, convention, exhibition) dilihat sebagai peluang bisnis dimana seseorang atau kelompok melakukan sebuah pertemuan atau konferensi conference). Indonesia sudah berkembang menjadi salah satu negara tujuan bisnis dan wisata. Hal itu dibuktikan dengan p...

Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo

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Mukadder Korkmaz

Full Text Available ABSTRACT INTRODUCTION: Benign paroxysmal positional vertigo (BPPV is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. OBJECTIVE: The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning procedures for treatment. METHODS: Data were obtained from the clinical records of 153 patients diagnosed with benign paroxysmal positional vertigo. Patients were treated by repositioning maneuvers. Demographic data and the factors including age, sex, canal type, duration of symptoms, comorbidities and number of repositioning maneuvers for relief were documented for statistical analysis. RESULTS: Age, sex, canal type and the duration of symptoms had no impact on the number of maneuvers. The most common comorbidity was spine problems. Hypertension was the only comorbidity that significantly associated with increased number of maneuvers. CONCLUSION: The presence of hypertension is a risk factor for repeated maneuvers in benign paroxysmal positional vertigo treatment. Physicians should be aware of the increased probability of repeated repositioning maneuvers in these group of patients. The role of comorbidities and vascular factors need to be further clarified in the course of benign paroxysmal positional vertigo.

Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo.

Science.gov (United States)

Korkmaz, Mukadder; Korkmaz, Hakan

2016-01-01

Benign paroxysmal positional vertigo (BPPV) is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning procedures for treatment. Data were obtained from the clinical records of 153 patients diagnosed with benign paroxysmal positional vertigo. Patients were treated by repositioning maneuvers. Demographic data and the factors including age, sex, canal type, duration of symptoms, comorbidities and number of repositioning maneuvers for relief were documented for statistical analysis. Age, sex, canal type and the duration of symptoms had no impact on the number of maneuvers. The most common comorbidity was spine problems. Hypertension was the only comorbidity that significantly associated with increased number of maneuvers. The presence of hypertension is a risk factor for repeated maneuvers in benign paroxysmal positional vertigo treatment. Physicians should be aware of the increased probability of repeated repositioning maneuvers in these group of patients. The role of comorbidities and vascular factors need to be further clarified in the course of benign paroxysmal positional vertigo. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity

DEFF Research Database (Denmark)

Iba, K; Durkin, M E; Johnsen, L

2001-01-01

and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were...... in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material...... in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population....

Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

Science.gov (United States)

Toque, Haroldo A; Nunes, Kenia P; Yao, Lin; Xu, Zhimin; Kondrikov, Dmitry; Su, Yunchao; Webb, R Clinton; Caldwell, Ruth B; Caldwell, R William

2013-01-01

Elevated arginase (Arg) activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC) from Akita mice. Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT) mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP) was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC) compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH) reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177) (in aorta and CC) and nNOS expression (in CC) were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks. Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

Directory of Open Access Journals (Sweden)

Haroldo A Toque

Full Text Available Elevated arginase (Arg activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO synthase (NOS and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC from Akita mice.Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177 (in aorta and CC and nNOS expression (in CC were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks.Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis.

Directory of Open Access Journals (Sweden)

Yohsuke Hanaoka

Full Text Available Tissue inhibitors of metalloproteinases (TIMPs regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme, its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.

Functional jerks, tics, and paroxysmal movement disorders

NARCIS (Netherlands)

Dreissen, Y. E. M.; Cath, D C; Tijssen, M A J; Hallet, Mark; Stone, Jon; Carson, Alan

2017-01-01

Functional jerks are among the most common functional movement disorders. The diagnosis of functional jerks is mainly based on neurologic examination revealing specific positive clinical signs. Differentiation from other jerky movements, such as tics, organic myoclonus, and primary paroxysmal

Repositioning chairs in benign paroxysmal positional vertigo

DEFF Research Database (Denmark)

West, Niels; Hansen, Søren; Møller, Martin Nue

2016-01-01

The objective was to evaluate the clinical value of repositioning chairs in management of refractory benign paroxysmal positional vertigo (BPPV) and to study how different BPPV subtypes respond to treatment. We performed a retrospective chart review of 150 consecutive cases with refractory vertigo...

Paroxysmal non-kinesigenic dyskinesia in antiphospholipid syndrome

NARCIS (Netherlands)

Engelen, Marc; Tijssen, Marina A. J.

2005-01-01

We report on a patient with a mixed movement disorder classifiable as a paroxysmal nonkinesigenic dyskinesia, occurring as the first manifestation of primary antiphospholipid syndrome (PAPS). Possible pathophysiology is discussed based on recent literature, and we stress that PAPS must be considered

Paroxysmal non-kinesigenic dyskinesia in antiphospholipid syndrome

NARCIS (Netherlands)

Engelen, M; Tijssen, MAJ

We report on a patient with a mixed movement disorder classifiable as a paroxysmal nonkinesigenic dyskinesia, occurring as the first manifestation of primary antiphospholipid syndrome (PAPS). Possible pathophysiology is discussed based on recent literature, and we stress that PAPS must be considered

Paroxysmal kinesigenic choreoathetosis in hyperthyroidism.

OpenAIRE

Drake, M. E.

1987-01-01

Paroxysmal kinesigenic choreoathetosis is an unusual movement disorder often triggered by attempts to use the limbs, and has sometimes been associated with diffuse or focal brain injury. We report its occurrence in hyperthyroidism, with which choreoathetosis has rarely been described in the past without known cause. Choreoathetosis has also occurred with other metabolic and toxic disorders, and the mechanism is uncertain. The development of involuntary movements activated by limb motion durin...

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

Science.gov (United States)

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

DIAGNOSIS AND MANAGEMENT BENIGN PAROXYSMAL POSITIONAL VERTIGO (BPPV

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Putu Prida Purnamasari

2013-05-01

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Benign Paroxysmal Positional Vertigo (BPPV is one of the most frequent Neurotology disorders. Benign Paroxysmal Positional Vertigo is a vestibular disorder in which 17% -20% of patients complained of vertigo. In the general population the prevalence of BPPV is between 11 to 64 per 100,000 (prevalence 2.4%. Benign Paroxysmal Positional Vertigo is a disturbance in the inner ear with positional vertigo symptoms that occur repeatedly with the typical nystagmus paroxysmal. The disorders can be caused either by canalithiasis or cupulolithiasis and could in theory be about three semicircular canals, although superior canal (anterior is very rare. The most common is the form of the posterior canal, followed by a lateral. The diagnosis of BPPV can be enforced based on history and physical examination, including some tests such as Dix-Hallpike test, caloric test, and Supine Roll test. The diagnosis of BPPV is also classified according to the types of channels. Management of BPPV include non-pharmacological, pharmacological and operations. Treatment is often used non-pharmacological includes several maneuvers such as Epley maneuver, Semount maneuver, Lempert maneuver, forced prolonged position and Brandt-Daroff exercises. /* 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:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; 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;}

Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo

OpenAIRE

Korkmaz, Mukadder; Korkmaz, Hakan

2016-01-01

ABSTRACT INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. OBJECTIVE: The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning proced...

99mTc-HM-PAO SPECT of epileptic patients showing focal paroxysm on electroencephalography

International Nuclear Information System (INIS)

Takaishi, Yasuko; Hashimoto, Kiyoshi; Fujino, Osamu; Kamayachi, Satoshi; Fujita, Takehisa; Enokido, Hisashi; Komatsuzaki, Hideki; Kawakami, Yasuhiko; Hirayama, Tsunenori

1995-01-01

The usefulness of 99m Tc-HM-PAO SPECT in diagnosing epilepsy was studied. The subjects were 33 epileptic patients, ranging in age from 5 years and 5 months to 28 years and 3 months, who showed focal paroxysm on electroencephalograms. Lowered accumulation site was found on SPECT in 19 patients. Four patients with abnormal findings on X-ray CT or MRI showed lowered accumulation and focal paroxysm at the same site. Of 29 patients with normal X-ray CT or MRI findings, 15 (52%) showed lowered accumulation. Five patients showed a focal paroxysm at the site of lowered accumulation. In 8 patients the focal paroxysm site was partly coincided with the accumulation site. In some patients the focal site predicted by the findings of clinical symptoms and the lowered accumulation site coincided. SPECT is therefore a useful method in diagnosing a focal site in epilepsy and considered to reflect the severity of disease. (Y.S.)

The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.

NARCIS (Netherlands)

Hillmen, P.; Young, N.S.; Schubert, J.; Brodsky, R.A.; Socie, G.; Muus, P.; Roth, A.; Szer, J.; Elebute, M.O.; Nakamura, R.; Browne, P.; Risitano, A.M.; Hill, A.; Schrezenmeier, H.; Fu, C.L.; Maciejewski, J; Rollins, S.A.; Mojcik, C.F.; Rother, R.P.; Luzzatto, L.

2006-01-01

BACKGROUND: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: We conducted a double-blind, randomized,

Paroxysmal supraventricular tachycardia in an octogenarian.

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Lutwak, Nancy; Dill, Curt

2012-09-01

Paroxysmal supraventricular tachycardia is a common dysrhythmia that occurs at all ages. Its management is determined by presenting symptoms and previous history of the patient. Patients present with a continuum of symptoms ranging from palpitations to syncope. The incidence of supraventricular tachycardia increases with age. To discuss the etiology, precipitating factors, and acute management of supraventricular tachycardia; and to discuss nodal reentry circuits and representative electrocardiographic findings. We present the case of an 84-year-old man with gallstone pancreatitis, choledolcholithiasis, and cholecystitis complicated by paroxysmal supraventricular tachycardia. We review this dysrhythmia, emphasizing its significance in elderly patients. Supraventricular tachycardia is a common dysrhythmia that can result in syncope or myocardial infarction. We present a case of an elderly man with new-onset atrioventricular (AV) nodal reentry tachycardia, possibly precipitated by overdrive of his autonomic nervous system due to pain and infection. As the percentage of the elderly in our population is growing rapidly and the incidence of AV nodal reentry tachycardia increases with age, emergency physicians should be familiar with this dysrhythmia-its etiology, precipitating factors, presentations, and treatment. It will present more frequently in the future. Published by Elsevier Inc.

Subjective visual vertical after treatment of benign paroxysmal positional vertigo

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Maristela Mian Ferreira

Full Text Available Abstract Introduction: Otolith function can be studied by testing the subjective visual vertical, because the tilt of the vertical line beyond the normal range is a sign of vestibular dysfunction. Benign paroxysmal positional vertigo is a disorder of one or more labyrinthine semicircular canals caused by fractions of otoliths derived from the utricular macula. Objective: To compare the subjective visual vertical with the bucket test before and immediately after the particle repositioning maneuver in patients with benign paroxysmal positional vertigo. Methods: We evaluated 20 patients. The estimated position where a fluorescent line within a bucket reached the vertical position was measured before and immediately after the particle repositioning maneuver. Data were tabulated and statistically analyzed. Results: Before repositioning maneuver, 9 patients (45.0% had absolute values of the subjective visual vertical above the reference standard and 2 (10.0% after the maneuver; the mean of the absolute values of the vertical deviation was significantly lower after the intervention (p < 0.001. Conclusion: There is a reduction of the deviations of the subjective visual vertical, evaluated by the bucket test, immediately after the particle repositioning maneuver in patients with benign paroxysmal positional vertigo.

Factitious psychogenic nonepileptic paroxysmal episodes

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Alissa Romano

2014-01-01

Full Text Available Mistaking psychogenic nonepileptic paroxysmal episodes (PNEPEs for epileptic seizures (ES is potentially dangerous, and certain features should alert physicians to a possible PNEPE diagnosis. Psychogenic nonepileptic paroxysmal episodes due to factitious seizures carry particularly high risks of morbidity or mortality from nonindicated emergency treatment and, often, high costs in wasted medical treatment expenditures. We report a case of a 28-year-old man with PNEPEs that were misdiagnosed as ES. The patient had been on four antiseizure medications (ASMs with therapeutic serum levels and had had multiple intubations in the past for uncontrolled episodes. He had no episodes for two days of continuous video-EEG monitoring. He then disconnected his EEG cables and had an episode of generalized stiffening and cyanosis, followed by jerking and profuse bleeding from the mouth. The manifestations were unusually similar to those of ES, except that he was clearly startled by spraying water on his face, while he was stiff in all extremities and unresponsive. There were indications that he had sucked blood from his central venous catheter to expel through his mouth during his PNEPEs while consciously holding his breath. Normal video-EEG monitoring; the patient's volitional and deceptive acts to fabricate the appearance of illness, despite pain and personal endangerment; and the absence of reward other than remaining in a sick role were all consistent with a diagnosis of factitious disorder.

Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria

NARCIS (Netherlands)

Kelly, R.J.; Hochsmann, B.; Szer, J.; Kulasekararaj, A.; Guibert, S. de; Roth, A.; Weitz, I.C.; Armstrong, E.; Risitano, A.M.; Patriquin, C.J.; Terriou, L.; Muus, P.; Hill, A.; Turner, M.P.; Schrezenmeier, H.; Peffault de Latour, R.

2015-01-01

BACKGROUND: Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab

Paroxysmal Kinesigenic Dyskinesia.

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Mallik, Ritwika; Nandi, Sitansu Sekhar

2016-04-01

We present a case of paroxysmal kinesigenic dyskinesia (PKD) in a 21 year old girl, with no family history of similar episodes. The episodes were short (lasting less than a minute), frequent, occurring 5 to 10 times a day, self-limiting dystonia of her right upper limb precipitated by sudden movement. She also had a past history of partial seizures with secondary generalization in her childhood. She responded to phenytoin, with cessation of events after 1 month of treatment. This case impresses upon the hypothesis stating the association between seizure activity and PKD probably due to a common foci of origin. Awareness of this condition is required as it is easily treatable but frequently misdiagnosed. © Journal of the Association of Physicians of India 2011.

[Expressive language disorder and focal paroxysmal activity].

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Valdizán, José R; Rodríguez-Mena, Diego; Díaz-Sardi, Mauricio

2011-03-01

In cases of expressive language disorder (ELD), the child is unable to put his or her thoughts into words. Comorbidity is present with difficulties in repeating, imitating or naming. There are no problems with pronunciation, as occurs in phonological disorder, it may present before the age of three years and is crucial between four and seven years of age. Electroencephalogram (EEG) studies have been carried out not only in ELD, but also in clinical pictures where the language disorder was the main symptom or was associated to another neurodevelopmental pathology. We conducted a retrospective study involving a review of 100 patient records, with patients (25 girls and 75 boys) aged between two and six years old who had been diagnosed with ELD (according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revised) and were free of seizures and not receiving treatment. They were submitted to an EEG and received treatment with valproic acid if EEG findings were positive. Only six patients (males) presented localised spike-wave paroxysmal EEG activity in the frontotemporal region. This 6% is a percentage that is higher than the one found in the normal children's population (2%), but lower than the value indicated in the literature for language disorders, which ranges between 20% and 50%. These patients responded positively to the treatment and both expressive language and EEG findings improved. It is possible that in ELD without paroxysms there may be a dysfunction in the circuit made up of the motor cortex-neostriatum prior to grammatical learning, whereas if there are paroxysms then this would point to neuronal hyperactivity, perhaps associated to this dysfunction or not, in cortical areas. In our cases valproic acid, together with speech therapy, helped the children to recover their language abilities.

Paroxysmal Atrial Fibrillation in a Mission-Assigned Astronaut

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Bauer, Peter A.; Polk, J. D.

2010-01-01

This presentation will explore the clinical and administrative conundrums faced by the flight surgeon upon discovering asymptomatic paroxysmal atrial fibrillation seven months prior to scheduled long duration spaceflight. The presenter will discuss the decision-making process as well as the clinical and operational outcomes.

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

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Hasen, Nina S; Gammie, Stephen C

2011-03-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

Pulmonary vein dimensions and variation of branching pattern in patients with paroxysmal atrial fibrillation using magnetic resonance angiography

International Nuclear Information System (INIS)

Takase, Bonpei; Nagata, Masayoshi; Matsui, Takemi

2004-01-01

Pulmonary veins are the most frequent origin of focal and paroxysmal atrial fibrillation. Although radiofrequency ablation has been attempted for the treatment of focal and paroxysmal atrial fibrillation, the anatomy of the pulmonary vein is still not fully understood. To investigate the dimensions and anatomical variation of the pulmonary vein in patients with paroxysmal atrial fibrillation, we performed breath-hold gadolinium enhanced magnetic resonance (MR) angiography using a 1.5 T cardiac MR imager (GE CV/i) in 32 patients with paroxysmal atrial fibrillation (61±8 years old), 11 patients with chronic atrial fibrillation (64±9 years old), and 26 patients with normal sinus rhythm (55±15 years old). Three-dimensional images of the pulmonary veins were thus obtained, and the diameters of the most proximal portion of the left or right superior pulmonary vein and left or right inferior pulmonary vein were measured. Pulmonary vein branching variations were determined by a visual qualitative analysis by two separate readers' agreements, who were blinded to any clinical information. We focused on the existence of a complex-branching pattern draining into the orifice of four pulmonary veins. Patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation showed larger superior pulmonary veins than those with normal sinus rhythm (mean±SD; in the left superior pulmonary vein, 20±3 mm 23±3 mm vs 16±3 mm, P<0.05; in right superior pulmonary vein, 19±4 mm, 19±2 mm vs 16±2 mm, P<0.05). Complex-branching pattern was frequently observed in inferior pulmonary veins in patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation; 25/32 patients with paroxysmal atrial fibrillation, 11/11 patients with chronic atrial fibrillation, compared to 7/26 patients with normal sinus rhythm. Complex-branching patterns were not observed in superior pulmonary veins in any patients in this cohort. In patients with paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke

DEFF Research Database (Denmark)

Christensen, L M; Krieger, D W; Højberg, S

2014-01-01

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrilla......BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial...... lasting predominantly between 1 and 4 h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC). CONCLUSIONS: One in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role...

[Comparative analysis of phenomenology of paroxysms of atrial fibrillation and panic attacks].

Science.gov (United States)

San'kova, T A; Solov'eva, A D; Nedostup, A V

2004-01-01

To study phenomenology of attacks of atrial fibrillation (AF) and to compare it with phenomenology of panic attacks for elucidation of pathogenesis of atrial fibrillation and for elaboration of rational therapeutic intervention including those aimed at correction of psychovegetative abnormalities. Patients with nonrheumatic paroxysmal AF (n=105) and 100 patients with panic attacks (n=100). Clinical, cardiological and neurological examination, analysis of patients complaints during attacks of AF, and comparison them with diagnostic criteria for panic attack. It was found that clinical picture of attacks of AF comprised vegetative, emotional and functional neurological phenomena similar to those characteristic for panic attacks. This similarity as well as positive therapeutic effect of clonazepam allowed to propose a novel pathogenic mechanism of AF attacks. Severity of psychovegetative disorders during paroxysm of AF could be evaluated by calculation of psychovegetative iudex: Psychovegetative index should be used for detection of panic attack-like component in clinical picture of AF paroxysm and thus for determination of indications for inclusion of vegetotropic drugs, e. g. clonazepam, in complex preventive therapy.

INTERFERON BETA IN TREATMENT OF DISSEMINATED SCLEROSIS IN ADOLESCENTS — INFLUENCE ON NEUROPSYCHOLOGICAL STATUS AND PAROXYSMAL STATES

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A.N. Platonova

2010-01-01

Full Text Available Disseminated sclerosis is chronic progressive disease of central nervous system, which is characterized by demyelination, degeneration of nerve fibers and polymorphous clinical symptoms. According to literature data, 2–10% of patients have onset of a disease in childhood and adolescence. Frequent clinical symptoms of disseminated sclerosis, especially in adolescents, are paroxysmal states and neuropsychological disorders. Drugs containing interferon beta which are used for immunomodulating treatment, can increase the rate of paroxysmal neuropsychological disorders in patients with disseminated sclerosis. Present study with participation of 78 adolescents analyzed frequency and spectrum of neuropsychological disorders and paroxysmal states in patients 12–17 years old and relation of revealed disorders with a treatment with interferon beta.Key words: adolescents, disseminated sclerosis, interferon beta, treatment, depression, paroxysmal states, anxiety, neuropsychological testing.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:34-39

Diagnosing Paroxysmal Atrial Fibrillation in Patients With Ischemic Strokes and Transient Ischemic Attacks Using Echocardiographic Measurements of Left Atrium Function

DEFF Research Database (Denmark)

Skaarup, Kristoffer Grundtvig; Christensen, Hanne Krarup; Høst, Nis

2016-01-01

Twenty-five to 35 percentage of stroke cases are cryptogenic, and it has been demonstrated that paroxysmal atrial fibrillation (AF) is the causal agent in up to 25% of these incidents. The purpose of this study was to investigate if left atrial (LA) parameters have value for diagnosing paroxysmal...... with paroxysmal AF. However, the atrial measurements evaluating LA function (min LA volume and LA emptying fraction) were significantly different (LA emptying fraction: 45% ± 10% vs 50% ± 10%, p = 0.004; minimal LA volume: 30.2 ml ± 17.3 ml vs 24 ml ± 10 ml, p = 0.035 in patients with paroxysmal AF, even after...

Paroxysmal atrioventricular block: Electrophysiological mechanism of phase 4 conduction block in the His-Purkinje system: A comparison with phase 3 block.

Science.gov (United States)

Shenasa, Mohammad; Josephson, Mark E; Wit, Andrew L

2017-11-01

Paroxysmal atrioventricular (A-V) block is relatively rare, and due to its transient nature, it is often under recognized. It is often triggered by atrial, junctional, or ventricular premature beats, and occurs in the presence of a diseased His-Purkinje system (HPS). Here, we present a 45-year-old white male who was admitted for observation due to recurrent syncope and near-syncope, who had paroxysmal A-V block. The likely cellular electrophysiological mechanisms(s) of paroxysmal A-V block and its differential diagnosis and management are discussed. Continuous electrocardiographic monitoring was done while the patient was in the cardiac unit. Multiple episodes of paroxysmal A-V block were documented in this case. All episodes were initiated and terminated with atrial/junctional premature beats. The patient underwent permanent pacemaker implantation and has remained asymptomatic since then. Paroxysmal A-V block is rare and often causes syncope or near-syncope. Permanent pacemaker implantation is indicated according to the current guidelines. Paroxysmal A-V block occurs in the setting of diseased HPS and is bradycardia-dependent. The detailed electrophysiological mechanisms, which involve phase 4 diastolic depolarization, and differential diagnosis are discussed. © 2017 Wiley Periodicals, Inc.

PRRT2: from Paroxysmal Disorders to Regulation of Synaptic Function.

Science.gov (United States)

Valtorta, Flavia; Benfenati, Fabio; Zara, Federico; Meldolesi, Jacopo

2016-10-01

In the past few years, proline-rich transmembrane protein (PRRT)2 has been identified as the causative gene for several paroxysmal neurological disorders. Recently, an important role of PRRT2 in synapse development and function has emerged. Knock down of the protein strongly impairs the formation of synaptic contacts and neurotransmitter release. At the nerve terminal, PRRT2 endows synaptic vesicle exocytosis with Ca 2+ sensitivity by interacting with proteins of the fusion complex and with the Ca 2+ sensors synaptotagmins (Syts). In the postsynaptic compartment, PRRT2 interacts with glutamate receptors. The study of PRRT2 and of its mutations may help in refining our knowledge of the process of synaptic transmission and elucidating the pathogenetic mechanisms leading to derangement of network function in paroxysmal disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unipolar Depression in Paroxysmal Schizophrenia

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Alexander S. Bobrov

2013-12-01

Full Text Available Based on the current study, the clinical characteristics of unipolar depression in the clinical picture of schizophrenia with the paroxysmal type of disease course are presented. Given the concomitant depression with phobic symptoms, the following clinical variants are marked: depression with generalized social phobia and/or anthropophobia and depression with generalized pathological body sensations and hypochondriacal phobias. In other words, we are talking about a necessity to allocate a special type of schizophrenia with affective structure episodes and comorbid neurosis-like symptoms. Information on the basic treatment strategy of schizophrenia with depressive structure episodes and comorbid neurosis-like symptoms in everyday psychiatric practice is also provided.

The meetings, incentives, conferences, and exhibitions (MICE industry: Determinants of Thai organizational effectiveness

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Songsiri Bandhuseve

2018-01-01

Full Text Available Studies have shown that there is more money in business tourism than leisure travel, and on average, business travellers spend more money. To understand this phenomenon, this study aimed to investigate the effect of relationships between capacity management, customer relationship management, information computer technology (ICT, service quality, supplier relationship management, and supply chain management on Thailand’s meetings, incentives, conferences, and exhibitions (MICE industry organizational effectiveness. The researchers embraced a descriptive survey methodology designed to assess how the 500 managers surveyed viewed their organization’s effectiveness. The design employed the self-administration of questionnaires to a sample of individuals which was aimed at finding each individual’s attitudes and opinion about how the 21 observed variables impacted their operations. Of the 10 hypotheses and 21 observed variables, nine hypotheses were proven, with the findings confirming that service quality and information computer technology having a significant effect on MICE organizational effectiveness.

Insights into horizontal canal benign paroxysmal positional vertigo from a human case report.

Science.gov (United States)

Aron, Margaret; Bance, Manohar

2013-12-01

For horizontal canal benign paroxysmal positional vertigo, determination of the pathologic side is difficult and based on many physiological assumptions. This article reports findings on a patient who had one dysfunctional inner ear and who presented with horizontal canal benign paroxysmal positional vertigo, giving us a relatively pure model for observing nystagmus arising in a subject in whom the affected side is known a priori. It is an interesting human model corroborating theories of nystagmus generation in this pathology and also serves to validate Ewald's second law in a living human subject. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior

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Atsushi Tsujimura

2008-09-01

Full Text Available KF-1 was originally identified as a protein encoded by human gene with increased expression in the cerebral cortex of a patient with Alzheimer’s disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-lox recombination. The resulting kf-1−/− mice were normal and healthy in appearance. Behavioral analyses revealed that kf-1−/− mice showed significantly increased anxiety-like behavior compared with kf-1+/+ littermates in the light/dark transition and elevated plus maze tests; however, no significant differences were observed in exploratory locomotion using the open field test or in behavioral despair using the forced swim and tail suspension tests. These observations suggest that KF-1 suppresses selectively anxiety under physiological conditions probably through modulating protein levels of its unknown target(s. Interestingly, kf-1−/− mice exhibited significantly increased prepulse inhibition, which is usually reduced in human schizophrenic patients. Thus, the kf-1−/− mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds.

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

Science.gov (United States)

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

Italian survey on benign paroxysmal positional vertigo

OpenAIRE

Messina, A.; Casani, A.P.; Manfrin, M.; Guidetti, G.

2017-01-01

SUMMARY Benign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. BPPV often relapses after the first episode, with a recurrence rate between 15% and 50%. To date both the aetiopathogenetic processes that lead to otoconia detachment and the factors that make BPPV a relapsing disease are still unclear, but recent epidemiological studies have shown a possible association with cardiovascular risk factors. The aim of the present study (Sesto Senso Survey) was to e...

Left Atrial Linear Ablation of Paroxysmal Atrial Fibrillation Guided by Three-dimensional Electroanatomical System

DEFF Research Database (Denmark)

Zhang, Dai-Fu; Li, Ying; Qi, Wei-Gang

2005-01-01

Objective To investigate the safety and efficacy of Left atrial linear ablation of paroxysmal atrial fibrillation guided by three-dimensional electroanatomical system. Methods 29 patients with paroxysmal atrial fibrillation in this study. A nonfluoroscopic mapping system was used to generate a 3D...... electroanatomic LA mapping, and all pulmonary vein ostia were marked under the help of pulmonary veins angiography on the 3D map. Radiofrequency (RF) energy was delivered to create continuous linear lesions encircling the pulmonary veins, it was delivered with a target temperature of 43¿, a maximal power limit...

Paroxysmal sympathetic hyperactivity: An entity to keep in mind.

Science.gov (United States)

Godoy, D A; Panhke, P; Guerrero Suarez, P D; Murillo-Cabezas, F

2017-12-15

Paroxysmal sympathetic hyperactivity (PSH) is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries. It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge. The diagnosis is based on the clinical findings, and high alert rates are required. No widely available and validated homogeneous diagnostic criteria have been established to date. There have been recent consensus attempts to shed light on this obscure phenomenon. Its physiopathology is complex and has not been fully clarified. However, the excitation-inhibition model is the theory that best explains the different aspects of this condition, including the response to treatment with the available drugs. The key therapeutic references are the early recognition of the disorder, avoiding secondary injuries and the triggering of paroxysms. Once sympathetic crises occur, they must peremptorily aborted and prevented. of the later the syndrome is recognized, the poorer the patient outcome. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

The polyuria of paroxysmal atrial tachycardia

Science.gov (United States)

Kinney, M. J.; Stein, R. M.; Discala, V. A.

1974-01-01

Two patients with paroxysmal atrial fibrillation and an associated polyuria were studied to delineate the mechanism of the increase in urine flow. A striking saluresis was noted in both patients. The increased sodium excretion was probably due to decreased sodium reabsorption, perhaps at proximal tubular nephron sites. This inhibition of sodium reabsorption could explain both the saluresis and some part or all of the polyuria. Re-evaluation of earlier case reports reveals patterns of concomitant salt and water excretion consistent with this mechanism. The saluresis cannot be explained by the previously favored hypothesis of antidiuretic hormone inhibition.

Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

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Aunis Dominique

2010-12-01

Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats.

Science.gov (United States)

Wang, Sa A; Pozdnyakova, Olga; Jorgensen, Jeffrey L; Medeiros, L Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A

2009-01-01

The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16(-)CD66b(-) clones being larger than those of CD55(-)CD59(-) (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD

Treatment of paroxysmal nocturnal hemoglobinuria

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I. A. Lisukov

2014-07-01

Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is a rare, life‑threatening clonal hematological disorder caused by an acquired mutation in the phosphatidylinositol glucan (PIG-A gene. PNH is characterized by chronic intravascular hemolysis, marrow failure, thrombophilia and other severe clinical syndromes. Until recently, the treatment of PNH has been symptomatic with blood transfusions, anticoagulation and supplementation with folic acid or iron. The only potentially curative treatment is allogeneic stem cell transplantation, but this has severe complications with high mortality rates. A new targeted treatment strategy is the inhibition of the terminal complement cascade with anti‑C5 monoclonal antibody (eculizumab. Eculizumab has shown significant efficacy in controlling of intravascular hemolysis resulting in improving quality of life and survival.

Treatment of paroxysmal nocturnal hemoglobinuria

Directory of Open Access Journals (Sweden)

I. A. Lisukov

2012-01-01

Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is a rare, life‑threatening clonal hematological disorder caused by an acquired mutation in the phosphatidylinositol glucan (PIG-A gene. PNH is characterized by chronic intravascular hemolysis, marrow failure, thrombophilia and other severe clinical syndromes. Until recently, the treatment of PNH has been symptomatic with blood transfusions, anticoagulation and supplementation with folic acid or iron. The only potentially curative treatment is allogeneic stem cell transplantation, but this has severe complications with high mortality rates. A new targeted treatment strategy is the inhibition of the terminal complement cascade with anti‑C5 monoclonal antibody (eculizumab. Eculizumab has shown significant efficacy in controlling of intravascular hemolysis resulting in improving quality of life and survival.

Clinical commentary on "Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis" and "Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients".

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Pareés, Isabel

2017-11-01

This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger studies to better understand this unusual clinical association.

Efficacy and safety of ablation for people with non-paroxysmal atrial fibrillation.

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Nyong, Jonathan; Amit, Guy; Adler, Alma J; Owolabi, Onikepe O; Perel, Pablo; Prieto-Merino, David; Lambiase, Pier; Casas, Juan Pablo; Morillo, Carlos A

2016-11-22

The optimal rhythm management strategy for people with non-paroxysmal (persistent or long-standing persistent) atrial fibrilation is currently not well defined. Antiarrhythmic drugs have been the mainstay of therapy. But recently, in people who have not responded to antiarrhythmic drugs, the use of ablation (catheter and surgical) has emerged as an alternative to maintain sinus rhythm to avoid long-term atrial fibrillation complications. However, evidence from randomised trials about the efficacy and safety of ablation in non-paroxysmal atrial fibrillation is limited. To determine the efficacy and safety of ablation (catheter and surgical) in people with non-paroxysmal (persistent or long-standing persistent) atrial fibrillation compared to antiarrhythmic drugs. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, conference abstracts, clinical trial registries, and Health Technology Assessment Database. We searched these databases from their inception to 1 April 2016. We used no language restrictions. We included randomised trials evaluating the effect of radiofrequency catheter ablation (RFCA) or surgical ablation compared with antiarrhythmic drugs in adults with non-paroxysmal atrial fibrillation, regardless of any concomitant underlying heart disease, with at least 12 months of follow-up. Two review authors independently selected studies and extracted data. We evaluated risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous data with 95% confidence intervals (CIs) a using fixed-effect model when heterogeneity was low (I² 40%). Using the GRADE approach, we evaluated the quality of the evidence and used the GRADE profiler (GRADEpro) to import data from Review Manager 5 to create 'Summary of findings' tables. We included three randomised trials with 261 participants (mean age: 60 years) comparing RFCA (159 participants) to antiarrhythmic drugs (102) for non-paroxysmal

Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

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Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

2015-10-23

HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. Copyright © 2015 Elsevier Inc. All rights reserved.

Heart-specific overexpression of (pro)renin receptor induces atrial fibrillation in mice.

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Lian, Hong; Wang, Xiaojian; Wang, Juan; Liu, Ning; Zhang, Li; Lu, Yingdong; Yang, Yanmin; Zhang, Lianfeng

2015-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. The renin-angiotensin system (RAS) has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is the last identified member of RAS. However, the role of (p)RR in AF is still unknown. Circulating levels of (p)RR were determined using an immunosorbent assay in 22 patients with AF (paroxysmal or persistent) and 22 healthy individuals. The plasma levels of (p)RR increased 3.6-fold in AF patients (Patrial flutter since 2 months, then spontaneously converted to atrial fibrillation by 10 months. The atria of the transgenic mice demonstrated significant dilation and fibrosis, and exhibited a high incidence of sudden death. Additionally, the genes of SERCA and HCN4, which are involved in the electrophysiology of AF, were significantly down-regulated and up-regulated respectively in transgenic mice atria. The phosphorylation of Erk1/2 significantly increased in the atria of the transgenic mice, and the activated Erk1/2 was found predominantly in cardiac fibroblasts, suggesting that the transgenic (p)RR gene may induce atrial fibrillation by activation of Erk1/2 in the cardiac fibroblasts of the atria. (p)RR promotes atrial structural and electrical remodeling in vivo, which indicates that (p)RR plays an important role in the pathological development of AF. Copyright © 2015. Published by Elsevier Ireland Ltd.

G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses

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Tarrant, Teresa K.; Billard, Matthew J.; Timoshchenko, Roman G.; McGinnis, Marcus W.; Serafin, D. Stephen; Foreman, Oded; Esserman, Denise A.; Chao, Nelson J.; Lento, William E.; Lee, David M.; Patel, Dhavalkumar; Siderovski, David P.

2013-01-01

Chemokine receptor interactions coordinate leukocyte migration in inflammation. Chemokine receptors are GPCRs that when activated, are phosphorylated by GRKs to turn off G protein-mediated signaling yet recruit additional signaling machinery. Recently, GRK3 was identified as a negative regulator of CXCL12/CXCR4 signaling that is defective in human WHIM syndrome. Here, we report that GRK3−/− mice exhibit numerous features of human WHIM, such as impaired CXCL12-mediated desensitization, enhanced CXCR4 signaling to ERK activation, altered granulocyte migration, and a mild myelokathexis. Moreover, GRK3−/− protects mice from two acute models of inflammatory arthritis (K/BxN serum transfer and CAIA). In these granulocyte-dependent disease models, protection of GRK3−/− mice is mediated by retention of cells in the marrow, fewer circulating granulocytes in the peripheral blood, and reduced granulocytes in the joints during active inflammation. In contrast to WHIM, GRK3−/− mice have minimal hypogammaglobulinemia and a peripheral leukocytosis with increased lymphocytes and absent neutropenia. Thus, we conclude that the loss of GRK3-mediated regulation of CXCL12/CXCR4 signaling contributes to some, but not all, of the complete WHIM phenotype and that GRK3 inhibition may be beneficial in the treatment of inflammatory arthritis. PMID:23935208

STRATEGI PENINGKATAN PENDAPATAN ASLI DAERAH, INVESTASI DAN PERTUMBUHAN EKONOMI KOTA SEMARANG MELALUI MICE (MEETING, INCENTIVE, CONVENTION DAN EXHIBITION)

OpenAIRE

Tika Putri Pratiwi

2015-01-01

Abstrak ___________________________________________________________________ Semarang sebagai ibukota Provinsi Jawa Tengah memiliki potensi yang besar dalam mengembangkan sektor industri dan pariwisata. Langkah awal pemerintah yang serius dalam mengolah kedua industri ini yaitu dengan menjadikan Kota Semarang sebagai salah satu destinasi MICE (Meeting, Incentive, Convention, Exhibition). Penelitian ini bertujuan untuk memilih strategi apa yang dapat dilakukan dalam pembangunan Kota...

Alzheimer’s Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

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Maria José Menal

2018-01-01

Full Text Available BackgroundEvidence from patients and animal models suggests that obstructive sleep apnea (OSA may increase the risk of Alzheimer’s disease (AD and that AD is associated with reduced brain tissue stiffness.AimTo investigate whether intermittent hypoxia (IH alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.MethodsSix-eight month old (B6C3-Tg(APPswe,PSEN1dE985Dbo/J AD mutant mice and wild-type (WT littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day or normoxia for 8 weeks. After euthanasia, the stiffness (E of 200-μm brain cortex slices was measured by atomic force microscopy.ResultsTwo-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT, but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.ConclusionAD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

Short and middle term outcome of radiofrequency catheter ablation for paroxysmal and sustained atrial fibrillation

International Nuclear Information System (INIS)

Okamoto, Mitsunori; Sueda, Takashi; Hashimoto, Masaki; Fukuda, Yukihiro; Iwamoto, Akimichi; Matsumoto, Takeshi; Shintani, Yumiko; Iwasaki, Toshitaka; Kinoshita, Hiroki

2009-01-01

The aim of this study was to assess short and middle term outcome of radiofrequency catheter ablation for drug-refractory paroxysmal and sustained atrial fibrillation. Subjects were 30 patients of atrial fibrillation (19 paroxysmal, 11 sustained) who underwent extensive pulmonary vein isolation from January 2007 to August 2009 in our department. Twenty three men and seven women, aged from 44 to 76 years, were enrolled. Follow-up period was one to 32 months. Drug free success was 33%, but symptoms and electrocardiogram (EGG) findings were improved in 93 % of the patients by administration of anti-arrhythmic agents. Five of the six patients with bradycardia-tachycardia syndrome was free from pacemaker implantation. Left ventricular ejection fraction was improved in two patients with dilated cardiomyopathy (DCM)-like left ventricular dysfunction. One case had cardiac tamponade and transient ST elevation due to right coronary air embolism were observed in two cases. There were no death and no cerebrovascular events during the procedures and follow-up periods. In conclusion, radiofrequency catheter ablation for paroxysmal and sustained atrial fibrillation in our department may be highly acceptable new method for improving the symptoms and clinical signs of the patients. (author)

Paroxysmal occipital discharges suppressed by eye opening: Spectrum of clinical and imaging features at a tertiary care center in India

OpenAIRE

Bhavna Kaul; Garima Shukla; Vinay Goyal; Achal Srivastava; Madhuri Behari

2012-01-01

Background: Paroxysmal occipital discharges (PODs) demonstrating the phenomena of fixation-off sensitivity have classically been described in childhood epilepsies with occipital paroxysms. Aim: We attempted to delineate the demographic, clinical and imaging characteristics of patients whose interictal electroencephalograms (EEGs) showed occipital discharges with fixation-off sensitivity at our center. Materials and Methods: During the period between 2003 and 2005, patients whose interictal EE...

Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

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Margulescu, Andrei D; Mont, Lluis

2017-08-01

Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved spatial memory and deficits in contextual memory.

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Albarran-Zeckler, Rosie G; Brantley, Alicia Faruzzi; Smith, Roy G

2012-06-15

Although the hormone ghrelin is best known for its stimulatory effect on appetite and regulation of growth hormone release, it is also reported to have beneficial effects on learning and memory formation in mice. Nevertheless, controversy exists about whether endogenous ghrelin acts on its receptors in extra-hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and we have shown that a subset of GHS-R1a, which are not occupied by the agonist (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine signaling in vitro and in vivo. To determine the consequences of ghsr ablation on brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in the Morris water maze, but show deficits in contextual fear conditioning. Copyright © 2012 Elsevier B.V. All rights reserved.

Clinical Case of Newly Diagnosed Hypoglycemic Paroxysm Complicated by Severe Neurological Disorders

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L.V. Shkala

2013-02-01

Full Text Available The paper presents a case of hypoglycemic paroxysm, manifested as epilepsy, in 53-year-old man, suffering from diabetes mellitus type 1, complicated by steatohepatosis following excretory and endocrine pancreatic insufficiency, disorders of renal excretory function, triggered by the lack of food after insulin administration.

Benign paroxysmal torticollis in infancy

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Dimitrijević Lidija

2006-01-01

Full Text Available Background. Benign paroxysmal torticollis (BPT is an episodic functional disorder of unknown etiology, characterized by the periods of torticollic posturing of the head, that occurs in the early months of life in healthy children. Case report. We reported two patients with BPT. In the first patient the symptoms were observed at the age of day 20, and disappeared at the age of 3 years. There were 10 episodes, of which 2 were followed by vomiting, pallor, irritability and the abnormal trunk posture. In the second patient, a 12-month-old girl, BPT started from day 15. She had 4 episodes followed by vomiting in the first year. Both girls had the normal psychomotor development. All diagnostical tests were normal. Conclusion. The recognition of BPT, as well as its clinical course may help to avoid not only unnecessary tests and the treatment, but also the anxiety of the parents.

Mice with an Oncogenic HRAS Mutation are Resistant to High-Fat Diet-Induced Obesity and Exhibit Impaired Hepatic Energy Homeostasis

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Daiju Oba

2018-01-01

Full Text Available Costello syndrome is a “RASopathy” that is characterized by growth retardation, dysmorphic facial appearance, hypertrophic cardiomyopathy and tumor predisposition. >80% of patients with Costello syndrome harbor a heterozygous germline G12S mutation in HRAS. Altered metabolic regulation has been suspected because patients with Costello syndrome exhibit hypoketotic hypoglycemia and increased resting energy expenditure, and their growth is severely retarded. To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (HrasG12S/+ mice as a mouse model of Costello syndrome. On a high-fat diet, HrasG12S/+ mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under starvation conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.

Characterization of Paroxysmal Gluten‐Sensitive Dyskinesia in Border Terriers Using Serological Markers

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Garden, O.A.; Hadjivassiliou, M.; Sanders, D.S.; Powell, R.; Garosi, L.

2018-01-01

Background Paroxysmal gluten‐sensitive dyskinesia (PGSD) in border terriers (BTs) results from an immunologic response directed against transglutaminase (TG)2 and gliadin. Recent evidence suggests that PGSD is only one aspect of a range of possible manifestations of gluten sensitivity in the breed. Hypothesis/Objectives Gluten sensitivity in BTs is a heterogeneous disease process with a diverse clinical spectrum; to characterize the phenotype of PGSD using TG2 and gliadin autoantibodies as diagnostic markers. Animals One hundred twenty‐eight client‐owned BTs with various disorders. Methods Prospective study. BTs with paroxysmal episodes and a normal interictal examination were phenotyped using footage of a representative episode and assigned to 3 groups: idiopathic epilepsy (IE), paroxysmal dyskinesia (PD), or other. Owners of each dog completed a questionnaire to obtain information regarding clinical signs. Healthy BTs formed a control group. Serum antibodies against TG2 and AGA were measured in all dogs. Results One hundred twenty‐eight BTs were enrolled; 45 with PD, 28 with IE, 35 with other conditions, and 20 controls. Three overlapping phenotypes were identified; PD, signs suggestive of gastrointestinal disease, and dermatopathy. AGA‐IgG concentrations were increased in PD, compared with IE (P = 0.012), controls (P < 0.0001) and other (P = 0.018) conditions. Anti‐canine TG2‐IgA concentrations were increased in PD, compared with IE (P < 0.0001), controls (P < 0.0001) and other (P = 0.012) conditions. Serological markers are highly specific for PGSD but lack sensitivity. Conclusions PGSD appears part of a syndrome of gluten intolerance consisting of episodes of transient dyskinesia, signs suggestive of gastrointestinal disease, and dermatological hypersensitivity. PMID:29424456

Effectiveness of Otolith Repositioning Maneuvers and Vestibular Rehabilitation exercises in elderly people with Benign Paroxysmal Positional Vertigo: a systematic review

OpenAIRE

Ribeiro, Karyna Figueiredo; Oliveira, Bruna Steffeni; Freitas, Raysa V.; Ferreira, Lidiane M.; Deshpande, Nandini; Guerra, Ricardo O.

2018-01-01

Abstract Introduction Benign Paroxysmal Positional Vertigo is highly prevalent in elderly people. This condition is related to vertigo, hearing loss, tinnitus, poor balance, gait disturbance, and an increase in risk of falls, leading to postural changes and quality of life decreasing. Objective To evaluate the outcomes obtained by clinical trials on the effectiveness of Otolith Repositioning Maneuver and Vestibular Rehabilitation exercises in the treatment of Benign Paroxysmal Positional Ve...

Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria.

NARCIS (Netherlands)

Hillmen, P.; Muus, P.; Duhrsen, U.; Risitano, A.M.; Schubert, J.; Luzzatto, L.; Schrezenmeier, H.; Szer, J.; Brodsky, R.A.; Hill, A.; Socie, G.; Bessler, M.; Rollins, S.A.; Bell, L.; Rother, R.P.; Young, N.S.

2007-01-01

Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated

Pelaksanaan Manajemen Mice (Meeting Incentive Convention Exhibition) di Hotel Pangeran Pekanbaru

OpenAIRE

Achmnes, Syofia; Siregar, Damara Saputra

2014-01-01

Implementation of MICE management operationalize theoretical concepts inthe book P.Hasibuan Terry GR (2005) that state that the management process consistsof: planning, organizing, actuating, and controlling.Growing MICE industry in Indonesia, including the city of Pekanbaru. CityGoverment continues to initiate Pekanbaru city as MICE city in Sumatera. One of theleading institutions that have a major role in the realization of this idea is thePangeran hotel Pekanbaru. which is a four-star hote...

[Clinical study of aged patients with secondary benign paroxysmal positional vertigo].

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Zhu, Z J; Wei, L P; Xu, Z X; Xu, H J; Liu, Q; Luo, N

2017-09-07

Objective: To investigate the clinical features and evaluate the efficacy of manual reduction in treatment of age patients with secondary benign paroxysmal positional vertigo (s-BPPV). Methods: Thirty-two cases of aged patients ( the s-BPPV group: including 19 cases of female and 13 males, age from 60 to 86 years old)with secondary benign paroxysmal positional vertigo from Jul. 2013 to Sep. 2015 in our hospital were retrospectively analyzed. The results were compared with 121 patients( the primary group: including 82 cases of female and 39males, aged from 60 to 86 years old)with aged primary benign paroxysmal positional vertigo(p -BPPV). All the patients were followed up for 12 months. Statistical data analysis was carried out with SPSS 19.0. Results: 20.92%(32/153)of all the observed elderly patients with BPPV was the aged s-BPPV. The sex ratio and onset age had no significant difference between the two groups(χ(2)=0.79, P >0.05; t =0.37, P >0.05). The rate of two or more semicircular canal involvement in the secondary group(21.88%) was higher than that in primary group(6.61%)(χ(2)=6.67, P manual reduction was 57.50%(23/40)in secondary group and 82.31%(107/130)in primary group, the difference was significant(χ(2)=10.46, P manual reduction in secondary group and 91.54%(119/130) in primary group, the difference was not significant(χ(2)= 0.59, P >0.05). The numbers of circulation of the first successful manual reduction management were (3.9±1.3)times in secondary group and (2.1±1.1)times in primary group, the difference was significant( t =3.15, P manual reduction of secondary BPPV is lower than primary BPPV, it's needed more circulation of first success in manual reduction management. The total effective rates are not significant in two groups and recurrence rate is relatively high in secondary group.

Verapamil eliminates the hierarchical nature of activation frequencies from the pulmonary veins to the atria during paroxysmal atrial fibrillation.

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Kushiyama, Yasunori; Osaka, Toshiyuki; Yokoyama, Eriko; Hasebe, Hideyuki; Kuroda, Yusuke; Kamiya, Kaichiro; Kodama, Itsuo

2010-05-01

There is evidence that verapamil promotes the persistence of paroxysmal atrial fibrillation (AF). Little is known about the underlying mechanisms. The purpose of this study was to determine the effect of verapamil on dominant frequencies (DFs) in the pulmonary veins (PVs) and atria during paroxysmal AF with reference to its potential arrhythmogenicity. Forty-three patients with paroxysmal AF were studied. Bipolar electrograms were recorded simultaneously during AF from the right atrial free wall (RAFW), coronary sinus (CS) and three PVs, or two PVs and the left atrial appendage (LAA). The DFs were obtained by fast Fourier transform analysis before and after infusion of verapamil (0.1 mg/kg, intravenously). At baseline, the maximum DF among the PVs (6.9 +/- 0.9 Hz) was significantly higher than the DF in the RAFW (6.2 +/- 0.7 Hz), CS (5.7 +/- 0.5 Hz), or LAA (5.9 +/- 0.7 Hz) (Patrial DF gradient (RAFW 0.7 +/- 0.9, CS 1.1 +/- 0.7, LAA 0.7 +/- 0.9 Hz). Verapamil increased the atrial DF to 6.9 +/- 0.8, 6.6 +/- 0.7, and 7.2 +/- 1.0 Hz in the RAFW, CS, and LAA, respectively (Patrial DF gradient was eliminated after verapamil (RAFW 0.2 +/- 0.8, CS 0.5 +/- 0.6, LAA -0.4 +/- 0.8 Hz; Patrial DF gradient during paroxysmal AF. Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.

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Germanò, Eva; Gagliano, Antonella; Magazù, Angela; Sferro, Caterina; Calarese, Tiziana; Mannarino, Erminia; Calamoneri, Filippo

2005-05-01

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (pmemory abilities (psupports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.

BENIGN PAROXYSMAL POSITIONAL VERTIGO- A PROSPECTIVE STUDY

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Herman Guild Manayil John

2017-03-01

Full Text Available BACKGROUND Benign Paroxysmal Positional Vertigo (BPPV is one of the most common disorders of the vestibular system, which maybe unilateral or involve both labyrinths. It can be effectively treated by Canalith Repositioning Manoeuvers (CRM, but lack of awareness leads to delay in effective treatment. MATERIALS AND METHODS Study was conducted in a tertiary care center where 184 patients with BPPV were subjected to positional test and CRM. RESULTS M:F ratio was 1:2.1. 85% of BPPV patients were relieved of symptoms with one sitting of CRM. CONCLUSION CRM is very effective in treatment of BPPV. General practitioners and specialists should be more educated about this condition, which will reduce the delay in correct diagnosis and proper treatment.

Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

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Nicole Purrier

Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

Predictors for benign paroxysmal positional vertigo with positive Dix?Hallpike test

OpenAIRE

Noda, Kazutaka; Ikusaka, Masatomi; Ohira, Yoshiyuki; Takada, Toshihiko; Tsukamoto, Tomoko

2011-01-01

Kazutaka Noda, Masatomi Ikusaka, Yoshiyuki Ohira, Toshihiko Takada, Tomoko TsukamotoDepartment of General Medicine, Chiba University Hospital, Chiba, JapanObjective: Patient medical history is important for making a diagnosis of causes of dizziness, but there have been no studies on the diagnostic value of individual items in the history. This study was performed to identify and validate useful questions for suspecting a diagnosis of benign paroxysmal positional vertigo (BPPV).Methods: Constr...

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

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Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

The Internationalization of the Meetings - Incentives - Conventions - and Exhibitions - (MICE industry: Its Influences on the Actors in the Tourism Business Activity

Directory of Open Access Journals (Sweden)

Natalia Smagina

2017-02-01

Full Text Available This article is aimed to analyze the link between internationalization and Meetings-, Incentives-, Conventions- and Exhibitions (MICE industry which is refer to the destination development. A comprehensive review of the totality of the processes associated with the regional market of business tourism, allowed to develop a number of actual tools that make it possible to obtain important practical results. One of these tools is a so called public-private partnership (PPP, to strengthen the trust between government and business representatives on regional level. This article reveals the cooperation process between foreign private companies and the local government in organizing the development of the industry connected to MICE. This vision may help all parties connected to the MICE industry to achieve a new level of understanding of the business tourism destination as a result of internationalization processes.

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation

DEFF Research Database (Denmark)

Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

2014-01-01

AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model......, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain...... of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness...

Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

Science.gov (United States)

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Shota; Ohashi, Takuya; Tsuji, Aki; Mano, Toshiaki

2018-04-15

Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72±6 vs. 66±10, plow-voltage areas than without (36% vs. 6%, pLow-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p=0.001). The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. Copyright © 2017 Elsevier B.V. All rights reserved.

Chiropractic management of a patient with benign paroxysmal positional vertigo

DEFF Research Database (Denmark)

Nørregaard, Anette R; Lauridsen, Henrik H; Hartvigsen, Jan

2009-01-01

OBJECTIVE: This article describes and discusses the case of a patient with benign paroxysmal positional vertigo (BPPV) characterized by severe vertigo with dizziness, nausea, and nystagmus, treated without the use of spinal manipulation by a doctor of chiropractic. CLINICAL FEATURES: A 46-year......-old woman presented for care with complaints of acute vertigo and dizziness. INTERVENTION AND OUTCOME: The patient was examined and diagnosed with left posterior canalolithiasis by means of the Dix-Hallpike maneuver. She was treated successfully with the Epley maneuver once and subsequently discharged...

Benign paroxysmal positional vertigo after use of noise-canceling headphones.

Science.gov (United States)

Dan-Goor, Eric; Samra, Monica

2012-01-01

Benign paroxysmal positional vertigo (BPPV) is a common cause of vertigo. We describe a case of a woman presenting acutely with a severe episode of disabling positional vertigo. Although she had no known etiologic risk factors, this attack followed 12 hours of continuously wearing digital noise-canceling headphones. This is the first such reported association between BPPV and the use of this gadget. We also provide a short review of BPPV and speculate on the possible pathogenic mechanisms involved. Copyright © 2012 Elsevier Inc. All rights reserved.

Predicting Paroxysmal Atrial Fibrillation in Cerebrovascular Ischemia Using Tissue Doppler Imaging and Speckle Tracking Echocardiography

DEFF Research Database (Denmark)

Olsen, Flemming Javier; Jørgensen, Peter Godsk; Møgelvang, Rasmus

2016-01-01

BACKGROUND: Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit. AIM: The objective of the study is to investigate whether advanced echocardiography improves the diagnostic ap...

The application of nonlinear metrics to assess organization differences in short recordings of paroxysmal and persistent atrial fibrillation

International Nuclear Information System (INIS)

Alcaraz, Raúl; Rieta, José Joaquín

2010-01-01

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. In the first stages of the disease, AF may terminate spontaneously and it is referred to as paroxysmal AF. The arrhythmia is called persistent AF when external intervention is required to its termination. In the present work, a method to non-invasively assess AF organization has been applied to discern between paroxysmal and persistent AF episodes at any time. Previous works have suggested that the probability of AF termination is inversely related to the number of reentries wandering throughout the atrial tissue. Given that it has also been hypothesized that the number of reentries is directly correlated with AF organization, a fast and robust method able to assess organization differences in AF could be of great interest. In fact, the distinction between paroxysmal and persistent episodes in patients without previously known AF history, making use of short ECG recordings, could contribute to taking earlier decisions on AF management in daily clinical practice, without the need to require 24 h or 48 h Holter recordings. The method was based on a nonlinear regularity index, such as sample entropy (SampEn), and evidenced to be a significant discriminator of the AF type. Its diagnostic accuracy of 91.80% was demonstrated to be superior to previously proposed parameters, such as dominant atrial frequency (DAF) and fibrillatory waves amplitude, and to others analyzed for the first time in this context, such as atrial activity mean power, 3 dB bandwidth around the DAF, first harmonic frequency, harmonic exponential decay, etc. Additionally, according to previous invasive works, paroxysmal AF episodes (0.0716 ± 0.0143) presented lower SampEn values and, consequently, more organized activity, than persistent episodes (0.1080 ± 0.0145)

STRATEGI PENINGKATAN PENDAPATAN ASLI DAERAH, INVESTASI DAN PERTUMBUHAN EKONOMI KOTA SEMARANG MELALUI MICE (MEETING, INCENTIVE, CONVENTION DAN EXHIBITION

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Tika Putri Pratiwi

2015-05-01

Full Text Available Abstrak ___________________________________________________________________ Semarang sebagai ibukota Provinsi Jawa Tengah memiliki potensi yang besar dalam mengembangkan sektor industri dan pariwisata. Langkah awal pemerintah yang serius dalam mengolah kedua industri ini yaitu dengan menjadikan Kota Semarang sebagai salah satu destinasi MICE (Meeting, Incentive, Convention, Exhibition. Penelitian ini bertujuan untuk memilih strategi apa yang dapat dilakukan dalam pembangunan Kota Semarang Melalui MICE. Data yang digunakan dalam penelitian ini adalah data primer dan data sekunder. Data primer bersumber dari hasil pengisian kuesioner oleh pihak dinas dan Swasta. Data sekunder dalam penelitian ini berupa data-data yang diperoleh dari dinas terkait serta Badan Pusat Statistik (BPS Provinsi Jawa Tengah dan Kota Semarang dan jurnal serta literatur yang berkaitan dengan penelitian. Metode analisis yang digunakan yaituAnalitical Hierarki Process (AHP dan diolah menggunakan expert choice versi 9.0. Hasil penelitian ini menunjukkan bahwa strategi pembangunan Kota Semarang melalui MICE dapat mengutamakan pada kriteria (1 peningkatan sektor investasi dengan bobot tertinggi yaitu sebesar 0,614 dan dilanjutkan dengan (2 memperbaiki pertumbuhan ekonomi kota dengan bobot 0,260, sehingga akan membantu dalam (3 peningkatan Pendapatan Asli Daerah Kota Semarang melalui MICE dengan bobot 0,126. Berdasarkan temuan tersebut, saran yang dapat disampaikan yaitu Memperkenalkan Kota Semarang melalui jalur promosi dengan menggunakan media-media sosal dan media elektronik. Hal tersebut merupakan salah satu alternatif membuka investasi yang lebih luas di Kota Semarang, sehingga tidak hanya masyarakat dalam negeri namun masyarakat internasional juga dapat lebih mengenal Kota Semarang. Memperbanyak even berskala nasional maupun internasional yang diselenggarakan di Kota Semarang dan lebih memperkenalkan Kota Semarang baik di dalam maupun di luar negeri. Memberikan pelatihan

[Formation of paroxysmal brain activity in the liquidators of the consequences of the Chernobyl nuclear disaster].

Science.gov (United States)

Podsonnaya, I V; Shumacher, G I; Efremushkin, G G; Gelobetskaya, E D

2015-01-01

To investigate the effect of ionizing radiation on the formation of paroxysmal brain activity (PBA) in the liquidators of the consequences of the Chernobyl nuclear disaster in view of their age on the date of exposure to radiation. EEG examinations were performed in 105 liquidators of the consequences of the nuclear disaster (LCND) and 90 people without radiation anamnesis (control group). It has been determined that the formation of paroxysmal brain activity in LCND occurs 3.5 times more frequent (p<0.001) and 15-17 years earlier (p<0.001) than in the control group and mainly during the first 10 years after the exposure to radiation. The history of the exposure to ionizing radiation is associated with the increased risk of the development of convulsive PBA as focal seizures by 5.5 times (p<0.001), interictal epileptiform discharges (IED) in EEG by 3.3 times (p<0.001). Radiation effect on LCND under 30 years old increases (as compared to the control group) the risk of the formation of elevated paroxysmal brain activity by 19 times (p<0.001), convulsive epileptic seizures by 33.3 times (p<0.001), interictal epileptiform discharges in EEG by 12 times (p<0.001), asymptomatic focal epileptoid nidus in EEG by 9.3 times (p<0.001). Stimulating effect of ionizing radiation on the development of PBA related to the age on the date of exposure to radiation was found.

Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo

OpenAIRE

Webster, Guilherme; Sens, Patrícia Maria; Salmito, Márcio Cavalcante; Cavalcante, José Diogo Rijo; Santos, Paula Regina Bonifácio dos; Silva, Ana Lívia Muniz da; Souza, Érica Carla Figueiredo de

2015-01-01

INTRODUCTION: Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo.OBJECTIVE: To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV.METHODS: A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal.RESULT...

Neutrophil activation and nucleosomes as markers of systemic inflammation in paroxysmal nocturnal hemoglobinuria: effects of eculizumab

NARCIS (Netherlands)

Bijnen, S.T. van; Wouters, D.; Mierlo, G.J. van; Muus, P.; Zeerleder, S.

2015-01-01

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis and a high risk of life-threatening venous and arterial thrombosis. Uncontrolled complement activation and the release of cell-free heme may result in systemic inflammation, neutrophil activation,

The 2007 and 2014 eruptions of Stromboli at match: monitoring the potential occurrence of effusion-driven basaltic paroxysmal explosions from a volcanic CO2 flux perspective

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Liuzzo, Marco; Aiuppa, Alessandro; Salerno, Giuseppe; Burton, Mike; Federico, Cinzia; Caltabiano, Tommaso; Giudice, Gaetano; Giuffrida, Giovanni

2015-04-01

The recent effusive unrests of Stromboli occurred in 2002 and 2007 were both punctuated by short-lived, violent paroxysmal explosions generated from the volcano's summit craters. When effusive activity recently resumed on Stromboli, on 6 August 2014, much concern was raised therefore on whether or not a paroxysm would have occurred again. The occurrence of these potentially hazardous events has stimulated research toward understanding the mechanisms through which effusive eruptions can perturb the volcano's plumbing system, to eventually trigger a paroxysm. The anomalously large CO2 gas emissions measured prior to the 15 March 2007 paroxysmal explosion of Stromboli [1] have first demonstrated the chance to predict days in advance the effusive-to-explosive transition. Here 2007 and 2014 volcanic CO2 flux records have been compared for exploring causes/conditions that had not triggered any paroxysm event in the 2014 case. We show that the 2007 and 2014 datasets shared both similarities and remarkable differences. The pre-eruptive trends of CO2 and SO2 flux emissions were strikingly similar in both 2007 and 2014, indicating similar conditions within the plumbing system prior to onset of both effusive crises. In both events, the CO2 flux substantially accelerated (relative to the pre-eruptive mean flux) after onset of the effusion. However, this CO2 flux acceleration was a factor 3 lower in 2014 than in 2007, and the excess CO2 flux (the fraction of CO2 not associated with the shallowly emplaced/erupted magma, and therefore contributed by the deep magmatic system) never returned to the very high levels observed prior to the 15 March 2007 paroxysm. We conclude therefore that, although similar quantities of magma were effusively erupted in 2007 and 2014, the deep magmatic system was far less perturbed in the most recent case. We speculate that the rate at which the deep magmatic system is decompressed, rather than the level of de-compression itself, determine if the deep

Neutrophil activation and nucleosomes as markers of systemic inflammation in paroxysmal nocturnal hemoglobinuria: effects of eculizumab

NARCIS (Netherlands)

van Bijnen, S. T. A.; Wouters, D.; van Mierlo, G. J.; Muus, P.; Zeerleder, S.

2015-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis and a high risk of life-threatening venous and arterial thrombosis. Uncontrolled complement activation and the release of cell-free heme may result in systemic inflammation, neutrophil activation, and the

Late onset of atypical paroxysmal non-kinesigenic dyskinesia with remote history of Graves′ disease

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Abdul Qayyum Rana

2013-01-01

Full Text Available Paroxysmal non-kinesigenic dyskinesia (PNKD is a rare hyperkinetic movement disorder and falls under the category of paroxysmal movement disorders. In this condition, episodes are spontaneous, involuntary, and involve dystonic posturing with choreic and ballistic movements. Attacks last for minutes to hours and rarely occur more than once per day. Attacks are not typically triggered by sudden movement, but may be brought on by alcohol, caffeine, stress, fatigue, or chocolate. We report a patient with multiple atypical features of PNKD. She had a 7-year history of this condition with onset at the age of 59, and a remote history of Graves′ disease requiring total thyroidectomy. The frequency of attacks in our case ranged from five to six times a day to a minimum of twice per week, and the duration of episode was short, lasting not more than 2 min. Typically, PNKDs occur at a much younger age and have longer attack durations with low frequency. Administering clonazepam worked to reduce her symptoms, although majority of previous research suggests that pharmacological interventions have poor outcomes.

Late onset of atypical paroxysmal non-kinesigenic dyskinesia with remote history of Graves' disease.

Science.gov (United States)

Rana, Abdul Qayyum; Nadeem, Ambreen; Yousuf, Muhammad Saad; Kachhvi, Zakerabibi M

2013-10-01

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare hyperkinetic movement disorder and falls under the category of paroxysmal movement disorders. In this condition, episodes are spontaneous, involuntary, and involve dystonic posturing with choreic and ballistic movements. Attacks last for minutes to hours and rarely occur more than once per day. Attacks are not typically triggered by sudden movement, but may be brought on by alcohol, caffeine, stress, fatigue, or chocolate. We report a patient with multiple atypical features of PNKD. She had a 7-year history of this condition with onset at the age of 59, and a remote history of Graves' disease requiring total thyroidectomy. The frequency of attacks in our case ranged from five to six times a day to a minimum of twice per week, and the duration of episode was short, lasting not more than 2 min. Typically, PNKDs occur at a much younger age and have longer attack durations with low frequency. Administering clonazepam worked to reduce her symptoms, although majority of previous research suggests that pharmacological interventions have poor outcomes.

Focal epilepsy presenting as a bath-induced paroxysmal event/breath-holding attack

OpenAIRE

Stutchfield, C.J.; Loh, N.R.

2014-01-01

Bath-induced paroxysmal events in infants and children can be triggered by various etiologies, including cardiological, neurological, and metabolic causes. It is important to ascertain the underlying cause for such events as this significantly affects the child's management and prognosis. We present the case of a 19-month-old boy who presented with recurrent episodes of apnea, cyanosis, and reduced level of consciousness in response to bathing. Through detailed history and investigation, the ...

On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

International Nuclear Information System (INIS)

Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.; Sitnikova, E.; Rijn, C.M. van

2006-01-01

In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested

Intraplate paroxysms

Science.gov (United States)

Fonseca, João

2017-04-01

Earthquake science received a decisive boost from Reid's elastic rebound model in 1910 and from plate tectonics in the sixties. Both theories highlight the first-order accumulation of elastic strain energy near 2D discontinuities of the material properties of the crust. The second-order process whereby stresses build-up within 3D crustal blocks has remained obscure, because the available seismological data are swamped by interplate events. That notwithstanding, highly destructive earthquakes have originated away from plate boundaries or other previously identified faults. This includes the most destructive earthquake in human history - the Shanxi earthquake of 1556, with 830K fatalities - and more recent events such as the Tangshan earthquake of 1976 with 250K fatalities. In 2012, an intraplate earthquake of magnitude 8.6 provided unprecedented data for this type of phenomenon, revealing striking differences with respect to common observations pertaining to interplate earthquakes. Of paramount relevance is the role of a very complex network of disconnected structures, spreading the moment release over a broad footprint. I propose the name of "intraplate paroxysm" for this type of great (M>8) earthquake, to stress that it has distinctive characteristics, and most likely distinctive nucleation processes that beg investigation. In this paper, I explore the observations that pertain to the 2012 Indian Ocean earthquake to discuss the data concerning the 1755 Lisbon earthquake, arguing that this event must be regarded, at least in part, as an intraplate rupture, and may share some of the features. The need to analyze this class of phenomena without the constraints of the interplate model is highlighted. In particular, magnitude estimation for historical intraplates earthquakes is particularly challenging, possibly because of inadequate premises. I argue that the observations of 1755 do not imply such an extreme moment magnitude as is often adopted (8.5-8.7) if some

[Sleep paroxysmal events in children in video/polysomnography].

Science.gov (United States)

Zajac, Anna; Skowronek-Bała, Barbara; Wesołowska, Ewa; Kaciński, Marek

2010-01-01

It is estimated that about 25% of children have sleep disorders, from short problems with falling asleep to severe including primary sleep disorders. Majority of these problems are transitory and self-limiting and usually are not recognized by first care physicians and need education. Analysis of sleep structure at the developmental age and of sleep disorders associated with different sleep phases on the basis of video/polysomnography results. Literature review and illustration of fundamental problems associated with sleep physiology and pathology, with special attention to paroxysmal disorders. Additionally 4 cases from our own experience were presented with neurophysiological and clinical aspects. Discussion on REM and NREM sleep, its phases and alternating share according to child's age was conducted. Sleep disorders were in accordance with their international classification. Parasomnias, occupying most of the space, were divided in two groups: primary and secondary. Among primary parasomnias disorders associated with falling asleep (sleep myoclonus, hypnagogic hallucinations, sleep paralysis, rhythmic movement disorder, restless legs syndrome) are important. Another disorders are parasomians associated with light NREM sleep (bruxism, periodic limb movement disorder) and with deeper NREM sleep (confusional arousals, somnabulism, night terrors), with REM sleep (nightmares, REM sleep behavior disorder) and associated with NREM and REM sleep (catathrenia, sleep enuresis, sleep talking). Obstructive sleep apnea syndrome and epileptic seizures occurring during sleep also play an important role. Frontal lobe epilepsy and Panayiotopoulos syndrome should be considered in the first place in such cases. Our 4 cases document these diagnostic difficulties, requiring video/polysomnography examination 2 of them illustrate frontal lobe epilepsy and single ones myoclonic epilepsy graphy in children is a difficult technique and requires special device, local and trained

CHRONIC HEPATITIS OR «DISGUISE» PAROXYSMAL NOCTURAL HEMOGLOBINURIA?

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D. A. Dolgopolova

2015-01-01

Full Text Available Objective is description of a case of diagnostics of a paroxysmal nocturnal haemoglobinuria. Subjects and methods. The male patient of 50 years asked for medical care with complaints to emergence of yellowness a skin, urine darkening, not expressed general weakness. To the patient examination was conducted: clinical and biochemical blood tests, urine, miyelogramm, definition of an index of sphericity of erythrocytes, definition of free hemoglobin of plasma of blood, urine, gemosiderinuriya, flow citometry, immunological markers of rheumatic diseases, tool inspection, etc. Results. On the basis of complaints, a clinical picture of a disease, data of objective and tool inspections the final diagnosis is made: a paroxysmal nocturnal haemoglobinuria, a classical haemolytic form (on the International classification of diseases of the 10th revision – B 59.5. The comorbid diagnoses: anemia of heavy degree; transfusion dependence; thrombosis of a subclavial vein on the right (11.2011; cholelithiasis; chronic calculous cholecystitis in remission; chronic hepatitis of the mixed genesis (alcoholic, metabolic, moderate degree of activity. By the main diagnostic method which allowed to verify the diagnosis became flow citometry. According to an flow citometry erythrocytes I Tip (normal expression of CD59 – 87,0 %, II Type (partial deficiency of CD59 – 0,3 %, III Type (full deficiency of CD59 – 12,7 %; monocytes with deficiency of FLAER/CD14 – 93,3 %; granulocytes with deficiency of FLAER/CD24 – 97,7 %. Flow citometry was revealed by availability of APG-clone among erythrocytes, granulocytes and monocytes. Judging by the huge size of a clone (on granulocytes 97,7 %, it is possible to draw a conclusion that the patient was in the highest zone of risk of APG of crises. Conclusion. Practical interest of this supervision is caused by a rarity of this hematologic disease, the analysis of modern opportunities of diagnostics and complexity of a choice of

Correlation between perceived stigma and EEG paroxysmal abnormality in childhood epilepsy.

Science.gov (United States)

Kanemura, Hideaki; Sano, Fumikazu; Ohyama, Tetsuo; Sugita, Kanji; Aihara, Masao

2015-11-01

We investigated the relationship between abnormal electroencephalogram (EEG) findings such as localized EEG paroxysmal abnormality (PA) and the perception of stigma to determine EEG factors associated with perceived stigma in childhood epilepsy. Participants comprised 40 patients (21 boys, 19 girls; mean age, 14.6 years) with epilepsy at enrollment. The criteria for inclusion were as follows: 1) age of 12-18 years, inclusive; 2) ≥6 months after epilepsy onset; 3) the ability to read and speak Japanese; and 4) the presence of EEG PA. Fifteen healthy seizure-free children were included as a control group. Participants were asked to rate how often they felt or acted in the ways described in the items of the Child Stigma Scale using a 5-point scale. Electroencephalogram paroxysms were classified based on the presence of spikes, sharp waves, or spike-wave complexes, whether focal or generalized. Participants showed significantly higher stigma scores than healthy subjects (pstigma. The average total scores of patients presenting with EEG PA at generalized, frontal, RD, midtemporal, and occipital regions were 2.3, 4.0, 2.4, 3.2, and 2.2, respectively. The scores of all questions were higher in the frontal group than those in other regions (pstigma than children presenting with nonfrontal EEG PA (pstigma. Further studies are needed to confirm whether frontal EEG PA may function as a mediator of emotional responses such as perceived stigma in childhood epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Vertigo in patients with benign paroxysmal positional vertigo.

Science.gov (United States)

Kentala, E; Pyykkö, I

2000-01-01

We retrieved information on 59 patients, 19 men and 40 women, with benign paroxysmal positional vertigo (BPPV) from the database of the otoneurologic expert system (ONE). The original number of patients was greater, but we excluded all those with hearing loss of any origin. The patients filled in a questionnaire concerning their symptoms, earlier diseases, accidents and tobacco and alcohol use. This information was then integrated with results of audiometric, otoneurologic and imaging studies. The mean age at onset of symptoms was 44 years. Most patients had had vertiginous spells for anxiety than the others [r(53) = 0.40, p floating sensation. The floating vertigo was most often provoked by pressure changes [r(54) = 0.41, p < 0.01] or changes in visual surroundings [r(54) = 0.52, p < 0.01].

Canal switch after canalith repositioning procedure for benign paroxysmal positional vertigo.

Science.gov (United States)

Lin, Giant C; Basura, Gregory J; Wong, Hiu Tung; Heidenreich, Katherine D

2012-09-01

Canal switch is a complication following canalith repositioning procedure (CRP) for posterior canal benign paroxysmal positional vertigo (BPPV). Instead of being returned to the utricle, the loose otoconia migrate into the superior or horizontal semicircular canal. Patients remain symptomatic, and treatment can be ineffective unless the switch is recognized and additional repositioning maneuvers directed toward the appropriate semicircular canal are performed. This report provides the first videographic documentation of canal switch involving conversion of unilateral posterior semicircular canal BPPV to geotropic horizontal canalithiasis. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry

NARCIS (Netherlands)

Almeida, A.M.; Bedrosian, C.; Cole, A.; Muus, P.; Schrezenmeier, H.; Szer, J.; Rosse, W.F.

2017-01-01

BACKGROUND: Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). AIMS: To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) >/= 1.5 upper limit

Effectiveness of Otolith Repositioning Maneuvers and Vestibular Rehabilitation exercises in elderly people with Benign Paroxysmal Positional Vertigo: a systematic review

Directory of Open Access Journals (Sweden)

Karyna Figueiredo Ribeiro

Full Text Available Abstract Introduction Benign Paroxysmal Positional Vertigo is highly prevalent in elderly people. This condition is related to vertigo, hearing loss, tinnitus, poor balance, gait disturbance, and an increase in risk of falls, leading to postural changes and quality of life decreasing. Objective To evaluate the outcomes obtained by clinical trials on the effectiveness of Otolith Repositioning Maneuver and Vestibular Rehabilitation exercises in the treatment of Benign Paroxysmal Positional Vertigo in elderly. Methods The literature research was performed using PubMed, Scopus, Web of Science and PEDro databases, and included randomized controlled clinical trials in English, Spanish and Portuguese, published during January 2000 to August 2016. The methodological quality of the studies was assessed by PEDro score and the outcomes analysis was done by critical revision of content. Results Six studies were fully reviewed. The average age of participants ranged between 67.2 and 74.5 years. The articles were classified from 2 to 7/10 through the PEDro score. The main outcome measures analyzed were vertigo, positional nystagmus and postural balance. Additionally, the number of maneuvers necessary for remission of the symptoms, the quality of life, and the functionality were also assessed. The majority of the clinical trials used Otolith Repositioning Maneuver (n = 5 and 3 articles performed Vestibular Rehabilitation exercises in addition to Otolith Repositioning Maneuver or pharmacotherapy. One study showed that the addition of movement restrictions after maneuver did not influence the outcomes. Conclusion There was a trend of improvement in Benign Paroxysmal Positional Vertigo symptomatology in elderly patients who underwent Otolith Repositioning Maneuver. There is sparse evidence from methodologically robust clinical trials that examined the effects of Otolith Repositioning Maneuver and Vestibular Rehabilitation exercises for treating Benign Paroxysmal

Early Fever As a Predictor of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

Science.gov (United States)

Hinson, Holly E; Schreiber, Martin A; Laurie, Amber L; Baguley, Ian J; Bourdette, Dennis; Ling, Geoffrey S F

Paroxysmal sympathetic hyperactivity (PSH) is characterized by episodic, hyperadrenergic alterations in vital signs after traumatic brain injury (TBI). We sought to apply an objective scale to the vital sign alterations of PSH in order to determine whether 1 element might be predictive of developing PSH. We conducted an observational study of consecutive TBI patients (Glasgow Coma Scale score ≤12) and monitored the cohort for clinical evidence of PSH. PSH was defined as a paroxysm of 3 or more of the following characteristics: (1) tachycardia, (2) tachypnea, (3) hypertension, (4) fever, (5) dystonia (rigidity or decerebrate posturing), and (6) diaphoresis, with no other obvious causation (ie, alcohol withdrawal, sepsis). The Modified Clinical Feature Severity Scale (mCFSS) was applied to each participant once daily for the first 5 days of hospitalization. Nineteen (11%) of the 167 patients met criteria for PSH. Patients with PSH had a higher 5-day cumulative mCFSS score than those without PSH (median [interquartile range] = 36 [29-42] vs 29 [22-35], P = .01). Of the 4 components of the mCFSS, elevated temperature appeared to be most predictive of the development of PSH, especially during the first 24 hours (odds ratio = 1.95; 95% confidence interval, 1.12-3.40). Early fever after TBI may signal impending autonomic dysfunction.

Benign paroxysmal positional vertigo and comorbid conditions.

Science.gov (United States)

Cohen, Helen S; Kimball, Kay T; Stewart, Michael G

2004-01-01

To determine the prevalence of comorbid disease in patients with benign paroxysmal positional vertigo (BPPV) and the relationship of comorbid disease to symptoms of vertigo, disequilibrium, and anxiety. Patients who had posterior semicircular canal BPPV and who had been referred for vestibular rehabilitation at a tertiary care center completed a health status questionnaire and the Vertigo Symptom Scale, answered questions about level of vertigo, and were tested on computerized dynamic posturography. Subjects had high rates of diabetes, mild head trauma, and probable sinus disease. Balance was generally impaired, worse in diabetics and subjects with significant vestibular weakness. Subjects who smoked or had had mild head trauma had higher levels of anxiety. Comorbid conditions, particularly diabetes, mild head trauma, and sinus disease, are unusually prevalent in BPPV patients. Message: Patients with comorbid disease are at risk for having increased vertigo, anxiety, and disequilibrium compared to other patients. Copyright 2004 S. Karger AG, Basel

CM 40907: a structurally novel anticonvulsant in mice, rats and baboons

International Nuclear Information System (INIS)

Chambon, J.P.; Brochard, J.; Hallot, A.; Heaulme, M.; Brodin, R.; Roncucci, R.; Biziere, K.

1985-01-01

CM 40907 [3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine] is a chemically original compound which possesses the pharmacological properties of a potent, p.o. active anticonvulsant. The anticonvulsant activity of CM 40907 was examined in mice, rats and photosensitive Papio-papio baboons and compared to that of phenobarbital, diphenylhydantoin, carbamazepine, sodium valproate and ethosuximide. In mice, CM 40907 antagonized electroconvulsive shock and chemically induced seizures with an overall potency comparable to that of carbamazepine and a therapeutic ratio (ED50 rotorod/ED50 electroshock) superior to that of ethosuximide, sodium valproate, phenobarbital and carbamazepine. In the rat CM 40907 suppressed completed kindled amygdaloid seizures and was approximately as active as phenobarbital. In naturally photosensitive Senegalese Papio-papio baboons CM 40907 antagonized myoclonus and cortical paroxysmal discharges. In this model CM 40907 was approximately one-fourth as potent as phenobarbital, twice as potent as carbamazepine and 6 times more potent than sodium valproate. In mice CM 40907, at anticonvulsant doses, increased the affinity of [ 3 H]flunitrazepam for its central receptor site. Based on these results it is postulated that CM 40907 is a potent and relatively nonsedative anticonvulsant and may be of therapeutic benefit in epileptic disorders

Medan Convention & Exhibition Center (Arsitektur Ekspresionisme)

OpenAIRE

Iskandar, Nurul Auni

2015-01-01

Medan is one of the third largest city in Indonesia, which is currently being developed, and a city with lots of activities. In the city of Medan has a high investment opportunities for a convention, because of its strategic position in Southeast Asia and also supported by the facility and the potential for tourism in North Sumatra, Medan city has the potential for industrial MICE (Meeting, Incentive, Conference, Exhibition). The construction of Medan Convention & Exhibition Cente...

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

Science.gov (United States)

Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

2017-02-01

The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

International Nuclear Information System (INIS)

Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai; Hu, Ji-Wei; Ouyang, Pin

2014-01-01

Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB +/− mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

Energy Technology Data Exchange (ETDEWEB)

Wu, Hsu-Pin; Hsu, Shu-Yuan [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Wu, Wen-Ai; Hu, Ji-Wei [Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Ouyang, Pin, E-mail: ouyang@mail.cgu.edu.tw [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Taiwan (China)

2014-01-03

Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

Benign Paroxysmal Positional Vertigo after Dental Procedures: A Population-Based Case-Control Study

OpenAIRE

Chang, Tzu-Pu; Lin, Yueh-Wen; Sung, Pi-Yu; Chuang, Hsun-Yang; Chung, Hsien-Yang; Liao, Wen-Ling

2016-01-01

Background Benign paroxysmal positional vertigo (BPPV), the most common type of vertigo in the general population, is thought to be caused by dislodgement of otoliths from otolithic organs into the semicircular canals. In most cases, however, the cause behind the otolith dislodgement is unknown. Dental procedures, one of the most common medical treatments, are considered to be a possible cause of BPPV, although this has yet to be proven. This study is the first nationwide population-based cas...

Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria

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Pusem Patir

2015-01-01

Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is a rare, progressive, and life-threatening hematopoietic stem cell disorder characterized by complement-mediated intravascular hemolysis and a prothrombotic state. Patients with PNH might have slightly increased risk of infections due to complement-associated defects subsequent to CD59 deficiency. Here, we report a rare case of a 65-year-old male patient with necrotic ulcers on both legs, where the recognition of pancytopenia and microthrombi led to the diagnosis of PNH based on FLAER (FLuorescent AERolysin flow cytometric analysis. He was subsequently started on eculizumab therapy, with starting and maintenance doses set as per drug labelling. Progression of the patient’s leg ulcers during follow-up, with fulminant tissue destruction, purulent discharge, and necrotic patches, led to a later diagnosis of necrotizing fasciitis due to Pseudomonas aeruginosa and Klebsiella pneumonia infection. Courses of broad-spectrum antibiotics, surgical debridement, and superficial skin grafting were applied with successful effect during ongoing eculizumab therapy. This case highlights the point that it is important to maintain treatment of underlying disorders such as PNH in the presence of life-threatening infections like NF.

Torsades de Pointes associated with QT prolongation after catheter ablation of paroxysmal atrial fibrillation

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Yae Min Park

2017-09-01

Full Text Available A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP. Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator.

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

International Nuclear Information System (INIS)

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

2013-01-01

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

Energy Technology Data Exchange (ETDEWEB)

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency

NARCIS (Netherlands)

Schmitt, B.; Baumgartner, M.; Mills, P.B.; Clayton, P.T.; Jakobs, C.; Keller, E.; Wohlrab, G.

2010-01-01

Aim: We report on seizures, paroxysmal events, and electroencephalogram (EEG) findings in four female infants with pyridoxine-dependent epilepsy (PDE) and in one female with pyridoxine phosphate oxidase deficiency (PNPO). Method: Videos and EEGs were analysed and compared with videos of seizures and

Corrected QT dispersion as a predictor of the frequency of paroxysmal tachyarrhythmias in patients with Wolff–Parkinson–White syndrome

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Eid M. Daoud

2014-04-01

Conclusion: Calculation of QTcd in patients with WPW syndrome presented with paroxysmal tachyarrhythmias is a simple noninvasive clinical test for risk stratification of those patients and hence detecting patients at higher risk for frequent and recurrent tachyarrhythmias.

Pacing for the Suppression of Paroxysmal Atrial Fibrillation in an 87-year-old Patient

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Adel El-Bialy

2003-04-01

Full Text Available Background: Sinus node dysfunction, atrioventricular (AV block and atrial fibrillation (AF are associated with advanced age. Required therapy commonly includes pacemaker implantation. Methods: We report the course of therapy for an 87-year-old with symptomatic sinus node dysfunction and paroxysmal atrial fibrillation who was intolerant of drug therapy. Results: The patient received a pacemaker for treatment of sick sinus syndrome. She continued to have symptomatic episodes of AF and was intolerant of pharmacologic therapy despite adequate rate support provided by the pacemaker. The AF suppression algorithm in the pacemaker was enabled, resulting in the elimination all AF episodes effectively eliminating the need for antiarrhythmic medication. If this continues to stabilize her atrium, withdrawal of anticoagulation therapy is anticipated. Conclusions: The clinical presentation of sinus node dysfunction and related conduction abnormalities is common in the elderly. Pharmacologic management is often a challenge in the presence of the advanced age and concomitant disease processes. In individuals who have paroxysmal atrial fibrillation or are likely to develop this and who need a pacemaker for standard indications, the availability of an AF Suppression™ algorithm may facilitate their management without needed to use medications or being able to utilize lower doses of those medications.

Is there still a role for additional linear ablation in addition to pulmonary vein isolation in patients with paroxysmal atrial fibrillation? An Updated Meta-analysis of randomized controlled trials.

Science.gov (United States)

Hu, Xiaoliang; Jiang, Jingzhou; Ma, Yuedong; Tang, Anli

2016-04-15

The benefits and risks of additional left atrium (LA) linear ablation in patients with paroxysmal atrial fibrillation (AF) remain unclear. Randomized controlled trials were identified in the PubMed, Web of Science, Embase and Cochrane databases, and the relevant papers were examined. Pooled relative risks (RR) and 95% confidence interval (95% CI) were estimated using random effects models. The primary endpoint was the maintenance of sinus rhythm after a single ablation. Nine randomized controlled trials involving 1138 patients were included in this analysis. Additional LA linear ablation did not improve the maintenance of the sinus rhythm following a single procedure (RR, 1.03; 95% CI, 0.93-1.13; P=0.60). A subgroup analysis demonstrated that all methods of additional linear ablation failed to improve the outcome. Additional linear ablation significantly increased the mean procedural time (166.53±67.7 vs. 139.57±62.44min, Plinear ablation did not exhibit any benefits in terms of sinus rhythm maintenance for paroxysmal AF patients following a single procedure. Additional linear ablation significantly increased the mean procedural, fluoroscopy and RF application times. This additional ablation was not associated with a statistically significant increase in complication rates. This finding must be confirmed by further large, high-quality clinical trials. Copyright © 2016. Published by Elsevier Ireland Ltd.

Effectiveness of Otolith Repositioning Maneuvers and Vestibular Rehabilitation exercises in elderly people with Benign Paroxysmal Positional Vertigo: a systematic review.

Science.gov (United States)

Ribeiro, Karyna Figueiredo; Oliveira, Bruna Steffeni; Freitas, Raysa V; Ferreira, Lidiane M; Deshpande, Nandini; Guerra, Ricardo O

2017-06-29

Benign Paroxysmal Positional Vertigo is highly prevalent in elderly people. This condition is related to vertigo, hearing loss, tinnitus, poor balance, gait disturbance, and an increase in risk of falls, leading to postural changes and quality of life decreasing. To evaluate the outcomes obtained by clinical trials on the effectiveness of Otolith Repositioning Maneuver and Vestibular Rehabilitation exercises in the treatment of Benign Paroxysmal Positional Vertigo in elderly. The literature research was performed using PubMed, Scopus, Web of Science and PEDro databases, and included randomized controlled clinical trials in English, Spanish and Portuguese, published during January 2000 to August 2016. The methodological quality of the studies was assessed by PEDro score and the outcomes analysis was done by critical revision of content. Six studies were fully reviewed. The average age of participants ranged between 67.2 and 74.5 years. The articles were classified from 2 to 7/10 through the PEDro score. The main outcome measures analyzed were vertigo, positional nystagmus and postural balance. Additionally, the number of maneuvers necessary for remission of the symptoms, the quality of life, and the functionality were also assessed. The majority of the clinical trials used Otolith Repositioning Maneuver (n=5) and 3 articles performed Vestibular Rehabilitation exercises in addition to Otolith Repositioning Maneuver or pharmacotherapy. One study showed that the addition of movement restrictions after maneuver did not influence the outcomes. There was a trend of improvement in Benign Paroxysmal Positional Vertigo symptomatology in elderly patients who underwent Otolith Repositioning Maneuver. There is sparse evidence from methodologically robust clinical trials that examined the effects of Otolith Repositioning Maneuver and Vestibular Rehabilitation exercises for treating Benign Paroxysmal Positional Vertigo in the elderly. Randomized controlled clinical trials with

Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

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Yoshitaka Kondo

2014-01-01

Full Text Available Superoxide dismutase 1 (SOD1 is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30 is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1 higher plasma levels of triglyceride and aspartate aminotransferase; (2 severe accumulation of hepatic triglyceride and total cholesterol; (3 higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4 decreased mRNA and protein levels of Apolipoprotein B (ApoB in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.

The Rare Painful Phenomena - Chronic Paroxysmal Hemicrania-tic Syndrome as a Clinically Isolated Syndrome of the Central Nervous System.

Science.gov (United States)

Ljubisavljevic, Srdjan; Prazic, Ana; Lazarevic, Miodrag; Stojanov, Dragan; Savic, Dejan; Vojinovic, Slobadan

2017-02-01

The association of paroxysmal hemicrania with trigeminal neuralgia (TN) has been described and called paroxysmal hemicrania-tic syndrome (PH-tic). We report the case of a patient diagnosed as having chronic PH-tic (CPH-tic) syndrome as a clinically isolated syndrome of the central nervous system (CNS) (CIS).A forty year old woman was admitted to our hospital suffering from right facial pain for the last 2 years. The attacks were paroxysmal, neuralgiform, consisting of throb-like sensations, which developed spontaneously or were triggered by different stimuli in right facial (maxilar and mandibular) areas. Parallel with those, she felt a throbbing orbital and frontal pain with homolateral autonomic symptoms such as conjunctival injection, lacrimation, and the feeling that the ear on the same side was full. This pain lasted most often between 15 and 20 minutes. Beyond hemifacial hypoesthesia in the region of right maxilar and mandibular nerve, the other neurological finding was normal. Magnetic resonance imaging (MRI) study showed a T2-weighted multiple hyperintense paraventricular lesion and hyperintense lesion in the right trigeminal main sensory nucleus and root inlet, all of them being hypointense on T1-weighted image. All of these lesions were hypointense in gadolinium-enhanced T1-weighted images. Neurophysiological studies of trigeminal nerve (somatosensory evoked potentials and blink reflex) correlated with MRI described lesions. The patient's pain bouts were improved immediately after treatment with indomethacin, and were completely relieved with lamotrigine for a longer period. According to the actual McDonald's criteria, clinical state was defined as CIS which was clinically presented by CPH-tic syndrome.Even though it is a clinical rarity and its etiology is usually idiopathic, CPH-tic syndrome can also be symptomatic. When dealing with symptomatic cases, like the one described here, when causal therapy is not possible due to the nature of the primary

Comorbidities and recurrence of benign paroxysmal positional vertigo: personal experience.

Science.gov (United States)

Picciotti, P M; Lucidi, D; De Corso, E; Meucci, D; Sergi, B; Paludetti, G

2016-01-01

The aim of this study is to evaluate the correlation between clinical features of benign paroxysmal positional vertigo (BPPV) and age, sex, trauma, presence of one or more comorbidities such as cardiovascular, neurological, endocrinological, metabolic, psychiatric diseases. Retrospective review of medical records (chart review). A total of 475 patients aged from 14 to 87 years, affected by BPPV. Recurrence of BPPV occurred in 139/475 patients (29.2%). The recurrence rate was significantly higher in female and older patients. Comorbidities were present in 72.6% of subjects with recurrent BPPV vs. 48.9% of patients with no recurrence (p disorders, followed by neurological and vascular diseases. Collecting a complete medical history is important for prognostic stratification and detection of potential underlying pathological conditions.

Paroxysmal Kinesigenic Dyskinesia Caused by 16p11.2 Microdeletion

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Pichet Termsarasab

2014-11-01

Full Text Available Background: Four cases of paroxysmal kinesigenic dyskinesia (PKD have been reported in individuals with proximal 16p11.2 microdeletions that include PRRT2. Case Report: We describe a fifth patient with PKD, features of Asperger’s syndrome, and mild language delays. Sanger sequencing of the PRRT2 gene did not identify any mutations implicated in PKD. However, microarray‐based comparative genomic hybridization (aCGH detected a 533.9‐kb deletion on chromosome 16, encompassing over 20 genes and transcripts. Discussion: This case underscores the importance of aCGH testing for individuals with PKD who do not have PRRT2 mutations, particularly when developmental delays, speech problems, intellectual disability, and/or autism spectrum disorder are present.

Report of a case of paroxysmal nocturnal hemoglobinuria (PNH) with complex evolution and liver transplant

OpenAIRE

Alencar,Railene Célia B.; Guimarães,Andréa M.; Brito Junior,Lacy C.

2016-01-01

ABSTRACT The paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease, with thrombotic episodes and frequent pancytopenia. We report the case of a 32 year-old female PNH patient with bone marrow aplasia, which followed a complex course, diagnosed with aplastic anemia associated with PNH, evolving in three years with Budd-Chiari syndrome and liver transplantation. Post-transplant complications, hepatic arterial thrombosis, graft rejection, liver retransplantation and treatment of P...

Paroxysmal postprandial atrial fibrilation suppressed by laparoscopic repair of a giant paraesophageal hernia compressing the left atrium.

Science.gov (United States)

Cristian, Daniel A; Constantin, Alin S; Barbu, Mariana; Spătaru, Dan; Burcoș, Traean; Grama, Florin A

2015-03-01

We present the case of a patient with a giant paraesophageal hernia associated with paroxysmal postprandial atrial fibrillation that was suppressed after surgery. The imaging investigations showed the intrathoracic displacement of a large part of the stomach, which pushed the left atrial wall causing atrial fibrillation. The laparoscopic surgical repair acted as sole treatment for this condition.

Application of DSA and ultrasonic blood rheography (Doppler) to benign paroxysmal positional vertigo

International Nuclear Information System (INIS)

Fujita, Nobuya; Wada, Yoshiro; Suzumura, Shigeo; Matsunaga, Takashi

1990-01-01

Fourteen cases of benign paroxysmal positional vertigo (BPPV) were studied with cervical circulation using DSA and Doppler. DSA study showed 7 abnormal cases out of 10 cases of BPPV. The abnormal findings included 5 cases of stenosis and 5 cases of coiling and kinking in cervical vertebral arteries. Doppler study showed that vertebral a. and also carotid a. had low volume and high laterality of cervical blood circulation in parameter of flow and velocity. These findings suggest the cervical circulation disorder was one of background factors in pathogenesis of BPPV. (author)

Application of DSA and ultrasonic blood rheography (Doppler) to benign paroxysmal positional vertigo

Energy Technology Data Exchange (ETDEWEB)

Fujita, Nobuya; Wada, Yoshiro; Suzumura, Shigeo; Matsunaga, Takashi (Nara Medical Univ., Kashihara (Japan))

1990-03-01

Fourteen cases of benign paroxysmal positional vertigo (BPPV) were studied with cervical circulation using DSA and Doppler. DSA study showed 7 abnormal cases out of 10 cases of BPPV. The abnormal findings included 5 cases of stenosis and 5 cases of coiling and kinking in cervical vertebral arteries. Doppler study showed that vertebral a. and also carotid a. had low volume and high laterality of cervical blood circulation in parameter of flow and velocity. These findings suggest the cervical circulation disorder was one of background factors in pathogenesis of BPPV. (author).

Predictors for benign paroxysmal positional vertigo with positive Dix–Hallpike test

Directory of Open Access Journals (Sweden)

Noda K

2011-12-01

Full Text Available Kazutaka Noda, Masatomi Ikusaka, Yoshiyuki Ohira, Toshihiko Takada, Tomoko TsukamotoDepartment of General Medicine, Chiba University Hospital, Chiba, JapanObjective: Patient medical history is important for making a diagnosis of causes of dizziness, but there have been no studies on the diagnostic value of individual items in the history. This study was performed to identify and validate useful questions for suspecting a diagnosis of benign paroxysmal positional vertigo (BPPV.Methods: Construction and validation of a disease prediction model was performed at the outpatient clinic in the Department of General Medicine of Chiba University Hospital. Patients with dizziness were enrolled (145 patients for construction of the disease prediction model and 61 patients for its validation. This study targeted BPPV of the posterior semicircular canals only with a positive Dix–Hallpike test (DHT + BPPV to avoid diagnostic ambiguity. Binomial logistic regression analysis was performed to identify the items that were useful for diagnosis or exclusion of DHT + BPPV.Results: Twelve patients from the derivation set and six patients from the validation set had DHT + BPPV. Binomial logistic regression analysis selected a "duration of dizziness ≤15 seconds" and "onset when turning over in bed" as independent predictors of DHT + BPPV with an odds ratio (95% confidence interval of 4.36 (1.18–16.19 and 10.17 (2.49–41.63, respectively. Affirmative answers to both questions yielded a likelihood ratio of 6.81 (5.11–9.10 for diagnosis of DHT + BPPV, while negative answers to both had a likelihood ratio of 0.19 (0.08–0.47.Conclusion: A "duration of dizziness ≤15 seconds" and "onset when turning over in bed" were the two most important questions among various historical features of BPPV.Keywords: benign paroxysmal positional vertigo, likelihood ratio, diagnosis, screening, prediction rules

Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: A study based on interviews with 100 patients seeking hospital assistance

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Madsen-Härdig Bjarne

2004-08-01

Full Text Available Abstract Background Surprisingly little information on symptoms of paroxysmal atrial fibrillation is available in scientific literature. Using questionnaires, we have analyzed the symptoms associated with arrhythmia attacks. Methods One hundred randomly-selected patients with idiopathic paroxysmal atrial fibrillation filled in a structured questionnaire. Results Psychic stress was the most common factor triggering arrhythmia (54%, followed by physical exertion (42%, tiredness (41% coffee (25% and infections (22%. Thirty-four patients cited alcohol, 26 in the form of red wine, 16 as white wine and 26 as spirits. Among these 34, red wine and spirits produced significantly more episodes of arrhythmia than white wine (p = 0.01 and 0.005 respectively. Symptoms during arrhythmia were palpitations while exerting (88%, reduced physical ability (87%, palpitations at rest (86%, shortage of breath during exertion (70% and anxiety (59%. Significant differences between sexes were noted regarding swollen legs (women 21%, men 6%, p = 0.027, nausea (women 36%, men 13%, p = 0.012 and anxiety (females 79%, males 51%, p = 0.014. Conclusion Psychic stress was the commonest triggering factor in hospitalized patients with paroxysmal atrial fibrillation. Red wine and spirits were more proarrhythmic than white wine. Symptoms in women in connection with attacks of arrhythmia vary somewhat from those in men.

Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

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Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

2005-03-01

Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

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Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2004-07-01

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Significance of cardiac sympathetic nervous system abnormality for predicting vascular events in patients with idiopathic paroxysmal atrial fibrillation

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Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Kawamura, Mitsuharu; Asano, Taku; Hamazaki, Yuji; Tanno, Kaoru; Kobayashi, Youichi; Suyama, Jumpei; Shinozuka, Akira; Gokan, Takehiko

2010-01-01

Neuronal system activity plays an important role for the prognosis of patients with atrial fibrillation (AF). Using 123 I metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy, we investigated whether a cardiac sympathetic nervous system (SNS) abnormality would be associated with an increased risk of vascular events in patients with paroxysmal AF. 123 I-MIBG scintigraphy was performed in 69 consecutive patients (67 ± 13 years, 62% men) with paroxysmal AF who did not have structural heart disease. SNS integrity was assessed from the heart to mediastinum (H/M) ratio on delayed imaging. Serum concentration of C-reactive protein (CRP) was measured before 123 I-MIBG study. During a mean of 4.5 ± 3.6 years follow-up, 19 patients had myocardial infarction, stroke or heart failure (range: 0.2-11.5 years). SNS abnormality (H/M ratio <2.7) and high CRP (≥0.3 mg/dl) were associated with the vascular events (58.3% in 14 of 24 patients with SNS abnormality vs 11.1% in 5 of 45 patients without SNS abnormality, p < 0.0001, 52.4% in 11 of 21 patients with high CRP vs 16.7% in 8 of 48 patients without high CRP, p < 0.0001). After adjustment for potential confounding variables such as age, left atrial dimension and left ventricular function, SNS abnormality was an independent predictor of vascular events with a hazard ratio of 4.1 [95% confidence interval (CI): 1.3-12.6, p = 0.014]. Further, SNS abnormality had an incremental and additive prognostic power in combination with high CRP with an adjusted hazard ratio of 4.1 (95% CI: 1.5-10.9, p = 0.006). SNS abnormality is predictive of vascular events in patients with idiopathic paroxysmal AF. (orig.)

Significance of cardiac sympathetic nervous system abnormality for predicting vascular events in patients with idiopathic paroxysmal atrial fibrillation

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Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Kawamura, Mitsuharu; Asano, Taku; Hamazaki, Yuji; Tanno, Kaoru; Kobayashi, Youichi [Showa University School of Medicine, Division of Cardiology, Department of Medicine, Tokyo (Japan); Suyama, Jumpei; Shinozuka, Akira; Gokan, Takehiko [Showa University School of Medicine, Department of Radiology, Tokyo (Japan)

2010-04-15

Neuronal system activity plays an important role for the prognosis of patients with atrial fibrillation (AF). Using {sup 123}I metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy, we investigated whether a cardiac sympathetic nervous system (SNS) abnormality would be associated with an increased risk of vascular events in patients with paroxysmal AF. {sup 123}I-MIBG scintigraphy was performed in 69 consecutive patients (67 {+-} 13 years, 62% men) with paroxysmal AF who did not have structural heart disease. SNS integrity was assessed from the heart to mediastinum (H/M) ratio on delayed imaging. Serum concentration of C-reactive protein (CRP) was measured before {sup 123}I-MIBG study. During a mean of 4.5 {+-} 3.6 years follow-up, 19 patients had myocardial infarction, stroke or heart failure (range: 0.2-11.5 years). SNS abnormality (H/M ratio <2.7) and high CRP ({>=}0.3 mg/dl) were associated with the vascular events (58.3% in 14 of 24 patients with SNS abnormality vs 11.1% in 5 of 45 patients without SNS abnormality, p < 0.0001, 52.4% in 11 of 21 patients with high CRP vs 16.7% in 8 of 48 patients without high CRP, p < 0.0001). After adjustment for potential confounding variables such as age, left atrial dimension and left ventricular function, SNS abnormality was an independent predictor of vascular events with a hazard ratio of 4.1 [95% confidence interval (CI): 1.3-12.6, p = 0.014]. Further, SNS abnormality had an incremental and additive prognostic power in combination with high CRP with an adjusted hazard ratio of 4.1 (95% CI: 1.5-10.9, p = 0.006). SNS abnormality is predictive of vascular events in patients with idiopathic paroxysmal AF. (orig.)

Acute Embolic Myocardial Infarction in a Patient with Paroxysmal Atrial Fibrillation Receiving Direct-current Cardioversion

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Tung-Chao Lin

2009-03-01

Full Text Available Coronary embolism with acute myocardial infarction (MI following direct-current (DC cardioversion of atrial fibrillation (AF has rarely been reported. We present the case of a 34-year-old female with severe aortic regurgitation and highly symptomatic paroxysmal AF. Acute embolic MI occurred 4 days after DC cardioversion of AF, although there was no left atrial thrombus detected before this procedure. Insufficient anticoagulation therapy during the post-cardioversion period was the cause, leading to embolic MI.

A Hispanic female patient with heartburn: A rare presentation of Paroxysmal Nocturnal Hemoglobinuria.

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Figueroa-Jiménez, Luis A; González-Márquez, Amy Lee; Alicea-Guevara, Ricardo; Santiago-Casiano, Mónica; de la Paz-López, Maryknoll; Negrón-Garcia, Luis; Báez-Diaz, Luis; Cáceres-Pérkins, William

2015-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant, acquired clonal hematopoietic stem cell disease that can present with bone marrow failure, hemolytic anemia, smooth muscle dystonias, and thrombosis. We present a case of a 32 year-old-female, G2P2A0 with no past medical history of any systemic illnesses who refers approximately 2 months of progressively worsening constant heartburn with associated abdominal discomfort. CBC showed leukopenia (WBC 2.9 x 103 /µL) with neutropenia (segmented neutrophils 48%), macrocytic anemia (Hgb 6.1 g/dL, hematocrit 20%, MCV,113 fL) and thrombocytopenia (platelet count 59 x 109/L). Abdomino-pelvic CT scan revealed a superior mesenterc vein thrombosis, which was treated initially with low-molecular-weight heparih for full anticoagulation. Peripheral blood flow cytometry assays revealed diminished expression of CD55 and CD59 on the erythrocytes, granulocytes and monocytes.' Paroxysmal nocturnal hemoglobinuria is a rare, clonal, hematopoietic stem-cell disorder whose manifestations are almost entirely explained by complement-mediated intravascular hemolysis. The natural history of PNH is highly variable, ranging from indolent to life-threatening. The median survival is 10 to 15 years, but with a wide range. Thrombosis is the leading cause of death, but others may die of complications of bone marrow failure, renal failure, myelodysplastic syndrome, and leukemia. Anticoagulation is only partially effective in preventing thrombosis in PNH; thus, thrombosis is an absolute indication for initiating treatment with Eculizumab. Nevertheless, bone marrow transplantation (BMT) is still the only curative therapy for PNH but is associated with significant morbidity and mortality.

ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

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2013-01-01

Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

Left atrial appendage: morphology and function in patients with paroxysmal and persistent atrial fibrillation.

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Park, Hwan-Cheol; Shin, Jinho; Ban, Ji-Eun; Choi, Jong-Il; Park, Sang-Weon; Kim, Young-Hoon

2013-04-01

The anatomical and functional characteristics of the left atrial appendage (LAA) and its relationships with anatomical remodeling and ischemic stroke in patients with atrial fibrillation (AF) have not been clearly established. The purpose of this study was to determine whether functional and morphological features of the LAA independently predict clinical outcome and stroke in patients with AF who underwent catheter ablation (CA). Two hundred sixty-four patients with AF, including 176 with paroxysmal AF (PAF, 54.0 ± 11.4 years old, M:F = 138:38) and 88 with persistent AF (PeAF, 56.4 ± 9.6 years old, M:F = 74:14) were studied. Of these patients, 31 (11.7 %) had a history of stroke/TIA (transient ischemic attack). The LA and LAA volumes were 124.0 ± 42.4 and 24.9 ± 4.3 ml in PeAF, these values were greater than those in PAF (81.2 ± 24.8 ml and 21.2 ± 5.1 ml, P stroke, stroke patients had larger LA volume (106.9 ± 23.0 vs. 94.0 ± 38.9 ml, P = 0.004) and had lower LAA EF (50.0 ± 11.0 vs. 65.7 ± 13.4 %, P stroke were age (P = 0.002) and LAA EF (P stroke/TIA and recurrence of AF after CA in paroxysmal AF patients. Further large scaled prospective study is required for validation.

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion*

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Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C.; Wang, Tong

2016-01-01

Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk−/− mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1−/− mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1+/+ and Romk1−/− mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1+/+, but such regulation by high K intake was diminished with significant hyperkalemia in Romk1−/− mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K+ secretion in the collecting tubule. PMID:26728465

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

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Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C; Wang, Tong

2016-03-04

Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantitative immunofluorescence microscopy of renal glomeruli from mice exhibiting murien lupus erythematosus

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Jensen, R H [Lawrence Livermore Lab., CA; Greenspan, J S; Moore, D II; Talal, N; Roubinian, J R

1981-01-01

Pathologic changes in renal glomeruli of mice with systemic murine lupus erythematosus were quantified using microfluorophotometry. Cryostat sections were taken from kidneys of affected mice, stained with fluorescein-conjugated anti-mouse immunoglobulin, and the extent of immune complex glomerulonephritis was determined. A subjective microscopic examination procedure, which has been used previously, was compared with quantitative microfluorophotometry and a close correlation between the results using each of the two methods was found. Since the microfluorometric procedure measures the total fluorescence per glomerulus, subjective microscopy must estimate that same quantity in a linear fashion. The present advance in measuring capability indicates good potential for rapid, quantitive measurements for further studies on systemic lupus erythematosus, and on other tissue sections stained with fluorescent antibodies.

Clinical comparative study of efficacy of epley manoeuvre and semont manoeuvre in benign paroxysmal positional vertigo

International Nuclear Information System (INIS)

Majeed, M.A.; Haq, A.U.

2015-01-01

To compare the efficacy of Epley manoeuvre and Semont manoeuvre in the management of benign paroxysmal positional vertigo. Study Design: Randomized controlled trials. Place and Duration of Study: ENT Department Combined Military Hospital (CMH) Kharian and Gilgit from March 2005 to February 2010. Material and Methods: Hundred cases of benign paroxysmal positional vertigo (BPPV) were selected on Dix-Hallpike test by non probability convenient sampling technique and randomly divided into two groups of 50 cases each. Patients in group-1 were treated by Epley manoeuvre and patients in group-2 were treated by Semont manoeuvre. The patients were examined on first day, 3rd day, 7th day and after 01 month and clinical results were observed. Results: In group-1, 68% cases showed immediate resolution of symptoms, 74% cases on 3rd day, 80% cases on 7th day and total 82% cases recovered completely after one month. In group-2, 62% cases showed immediate resolution of symptoms, 68% cases on 3rd day, 74% cases on 7th day and total 78% cases showed complete recovery after 1 month. There was insignificant difference between the two groups regarding recovery at different follow ups. Conclusion: It was concluded that Epley and Semont manoeuvres are equally effective in the management of BPPV. (author)

Self-treatment of benign paroxysmal positional vertigo with DizzyFix, a new dynamic visual device.

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Brehmer, Detlef

2010-09-01

Benign paroxysmal positional vertigo is one of the most common disorders of the vestibular system. It is characterized by episodes of recurrent vertigo triggered by head movements or position changes associated with nystagmus. There is scientific evidence that in the majority of cases this condition responds well to the particle repositioning maneuver (PRM) correctly performed by the physician. However, the PRM needs to be repeated in approximately 30% of the cases. Although the maneuver is simple, patients often find it difficult to perform correctly as self-treatment, with the result that it fails to bring about an improvement in the symptoms. DizzyFix (Clearwater Clinical Limited, Canada) is the name given to a new dynamic visual device designed to provide a visual representation of the PRM based on the canalith theory. The DizzyFiX consists of a specially curved acrylic tube containing a nontoxic viscous fluid and a bead, the purpose of which is to help the patient and the inexperienced physician to perform the PRM correctly. A randomized clinical trial has shown that it reliably enables the maneuver to be performed correctly, and a study investigating the effectiveness of patient self-treatment of benign paroxysmal positional vertigo with the device in comparison with standard office treatment revealed both techniques to be equally effective. The device has now been approved by the US FDA.

Paroxysmal nocturnal hemoglobinuria: a case report of MR, CT findings

International Nuclear Information System (INIS)

Yang, Ik; Chung, Soo Young; Park, Hai Jung; Lee Yul; Chun, Rho Won; Noh, Jung Woo

1995-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease involving multiple hematopoietic cell lines. Characteristics of PNH are intrinsic hemolytic anemia, iron deficiency anemia and venous thrombosis. We report a case of PNH with characterostoc MR and CT findings. The signal intensity of renal cortex was lower than that of medulla on both T1-and T2-weighted MR imaging. On T2 weighted MR images, the liver showed very low signal intensity but the signal intensity of the spleen was normal. On precontrast CT the attenuation of renal cortex was higher than that of renal medulla and the attenuation of liver was higher than that of the spleen. These findings of MR imaging and CT were the result from the deposition of hemosiderin in the cells of proximal convoluted tubules and transfusional hemosiderosis of liver

Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

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Gabriel Nasri Marzuca-Nassr

2017-10-01

Full Text Available The consequences of two-week hindlimb suspension (HS on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA, and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2 and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1 were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively, muscle isotonic and tetanic force (by 29% and 18%, respectively, CSA of the soleus muscle (by 36%, and soleus muscle fibers (by 45%. Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001. Fat-1 mice had lower soleus muscle dry mass loss (by 10% and preserved absolute isotonic force (by 17% and CSA of the soleus muscle (by 28% after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70% and MuRF-1 content decreased (by 50% in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

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Douglas S. Kernodle

2013-01-01

Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

[Primary Study on Predicting the Termination of Paroxysmal Atrial Fibrillation Based on a Novel RdR RR Intervals Scatter Plot].

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Lu, Hongwei; Zhang, Chenxi; Sun, Ying; Hao, Zhidong; Wang, Chunfang; Tian, Jiajia

2015-08-01

Predicting the termination of paroxysmal atrial fibrillation (AF) may provide a signal to decide whether there is a need to intervene the AF timely. We proposed a novel RdR RR intervals scatter plot in our study. The abscissa of the RdR scatter plot was set to RR intervals and the ordinate was set as the difference between successive RR intervals. The RdR scatter plot includes information of RR intervals and difference between successive RR intervals, which captures more heart rate variability (HRV) information. By RdR scatter plot analysis of one minute RR intervals for 50 segments with non-terminating AF and immediately terminating AF, it was found that the points in RdR scatter plot of non-terminating AF were more decentralized than the ones of immediately terminating AF. By dividing the RdR scatter plot into uniform grids and counting the number of non-empty grids, non-terminating AF and immediately terminating AF segments were differentiated. By utilizing 49 RR intervals, for 20 segments of learning set, 17 segments were correctly detected, and for 30 segments of test set, 20 segments were detected. While utilizing 66 RR intervals, for 18 segments of learning set, 16 segments were correctly detected, and for 28 segments of test set, 20 segments were detected. The results demonstrated that during the last one minute before the termination of paroxysmal AF, the variance of the RR intervals and the difference of the neighboring two RR intervals became smaller. The termination of paroxysmal AF could be successfully predicted by utilizing the RdR scatter plot, while the predicting accuracy should be further improved.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

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Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-09-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during

[Benign paroxysmal positional vertigo of the anterior semicircular canal: clinical aspects and treatment].

Science.gov (United States)

Lorin, P

2005-01-01

To describe the videonystagmographic characteristics and the treatment of the patients reached with a canalolithiasis or a cupulolithiasis of the anterior semicircular canal. Retrospective study concerning patients treated for a Benign Paroxysmal Positional Vertigo (BPPV) of the anterior semicircular canal. Each patient after analysis under videonystagmoscopy (VNS) and under videonystagmography (VNG) was treated by maneuvers. On 462 observations of typical BPPV 6 cases of VPPB of the anterior semicircular canal were treated concerning 5 patients (1.3%). The BPPV of the anterior semicircular canal are rare. We modified our method of diagnosis, and our therapeutic techniques could be validated with the help of the two-dimensional videonystagmography.

Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

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Eranga S Wijewickrama

2013-01-01

Full Text Available Acute renal failure (ARF is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH. The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham′s test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

[Benign paroxysmal positional vertigo in a female with arterial hypertension and meningioma].

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Bestuzheva, N V; Parfenov, V A; Zamergrad, M V

2014-01-01

Diagnosis of benign paroxysmal positional vertigo (BPPV) often causes difficulties, in particular, in elderly people with concomitant diseases. The article presents a case of a 77 year-old woman with BPPV. A patient's complaint on vertigo was mistakenly diagnosed as brain ischemia because the patient had long suffered from uncontrolled arterial hypertension. MRI-study revealed leucoaraiosis and one lacuna as well as a meningioma which was mistakenly linked to vertigo. The diagnosis of BPPV, use of Epley maneuver with the following vestibular exercises resulted in complete stopping of vertigo. Effective treatment of arterial hypertension with the normalization of arterial pressure, use of aspirin and statins reduced the risk of stroke. Exclusion of BPPV is needed in all cases of vertigo with unclear etiology.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

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Fuka Aizawa

2016-12-01

Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

A Moessbauer study of hemoglobin in paroxysmal nocturnal hemoglobinuria

International Nuclear Information System (INIS)

Zamorano-Ulloa, R.; Yee-Madeira, H.; Flores-Llamas, H.; Perez-Ramirez, J.G.

1991-01-01

The 57 Fe Moessbauer spectra of concentrated hemoglobin (Hb) of normal subjects and six patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) were studied at 300deg K and 77 K. PNH is a very rate autoimmune hematological disease. The possibility of structural alterations of Hb induced by, or as part of the altered PNH-red cell membrane was the objective of this study. The Moessbauer parameters of the Hb of the normal subjects, both at 300 K and at 77 K, are identical to values previously reported. The PNH-Hb spectra show clear differences. They are wider and more asymmetric. At 77 K, an extra doublet grows in with an isomer shift of 0.425 mm/sec. and a quadrupolar splitting of 1.951 mm/sec. The other two doublets have δ's and ΔQ's slightly, but significantly, different from the corresponding values for normal Hb. These results are rationalized in terms of a population of Hb molecules with structures varying very slightly in a narrow range. The spread in structures manifests itself in a wider and more asymmetric Moessbauer spectrum. (orig.)

β2-Adrenergic Receptor Knockout Mice Exhibit A Diabetic Retinopathy Phenotype

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Jiang, Youde; Zhang, Qiuhua; Liu, Li; Tang, Jie; Kern, Timothy S.; Steinle, Jena J.

2013-01-01

There is considerable evidence from our lab and others for a functional link between β-adrenergic receptor and insulin receptor signaling pathways in retina. Furthermore, we hypothesize that this link may contribute to lesions similar to diabetic retinopathy in that the loss of adrenergic input observed in diabetic retinopathy may disrupt normal anti-apoptotic insulin signaling, leading to retinal cell death. Our studies included assessment of neural retina function (ERG), vascular degeneration, and Müller glial cells (which express only β1 and β2-adrenergic receptor subtypes). In the current study, we produced β2-adrenergic receptor knockout mice to examine this deletion on retinal neurons and vasculature, and to identify specific pathways through which β2-adrenergic receptor modulates insulin signaling. As predicted from our hypothesis, β2-adrenergic receptor knockout mice display certain features similar to diabetic retinopathy. In addition, loss of β2-adrenergic input resulted in an increase in TNFα, a key inhibitor of insulin receptor signaling. Increased TNFα may be associated with insulin-dependent production of the anti-apoptotic factor, Akt. Since the effects occurred in vivo under normal glucose conditions, we postulate that aspects of the diabetic retinopathy phenotype might be triggered by loss of β2-adrenergic receptor signaling. PMID:23894672

Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice

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Konger, Raymond L.; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P.

2016-01-01

Hairless albino Crl:SKH1-Hrhr mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyrc-2J Hrhr/J]. Histologically, B6.Cg-Tyrc-2J Hrhr/J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyrc-2J Hrhr/J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas, and epidermal thickening. In response to a single 1500 J/m2 UVB dose, the edema and apoptotic response was equivalent in both mouse strains. However, B6.Cg-Tyrc-2J Hrhr/J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation, and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyrc-2J Hrhr/J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyrc-2J Hrhr/J mice at 24 hours post-UV. A smaller non-significant reduction in Ki67 labeling was observed in SKH1 mice. Finally, at 72 hours post-UV, SKH1 mice, but not B6.Cg-Tyrc-2J Hrhr/J mice, exhibited a significant increase in Ki67 immunolabeling relative to non-irradiated controls. Thus, B6.Cg-Tyrc-2J Hrhr/J mice are suitable for photobiology experiments. PMID:27095432

Co-existence of Benign Paroxysmal Positional Vertigo and Meniere's Syndrome.

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Yetişer, Sertaç

2017-04-01

Recent studies indicate interrelation of benign paroxysmal positional vertigo (BPPV) and Meniere's disease (MD). These two entities may have different clinical characteristics. Five hundred thirty patients with BPPV evaluated between 2009-2015 were enrolled in the study. 351 patients who had no clear problem associated with BPPV (idiopathic) and 17 patients with MD were analyzed in detail. The age, sex, site of involvement, type of BPPV, symptom duration, and treatment outcome were compared. Meniere's disease + BPPV was more common in the female population (2/15; 7.5 v 127/224; 1.8, pvertigo associated with MD presented a divergent picture. It was more frequent in females. Lateral canal involvement was higher. Patients had MD before the development of BPPV and they had prolonged symptoms, which raised a question of diagnostic delay since these two problems were in the same ear in majority of patients. Finally, relief of symptoms required more attempts of repositioning maneuvers.

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome.

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Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M

1991-04-01

Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

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Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

2016-10-01

Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

Science.gov (United States)

Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Analysis of the intestinal microbiota of oligo-saccharide fed mice exhibiting reduced resistance to Salmonella infection

DEFF Research Database (Denmark)

Petersen, Anne; Bergström, Anders; Andersen, Jens Bo

2010-01-01

recently demonstrated a reduced resistance to Salmonella infection in mice fed diets containing fructo-oligosaccharides (FOS) or xylo-oligosaccharides (XOS). In the present study, faecal and caecal samples from the same mice were analysed in order to study microbial changes potentially explaining...... the observed effects on the pathogenesis of Salmonella. Denaturing gradient gel electrophoresis revealed that the microbiota in faecal samples from mice fed FOS or XOS were different from faecal samples collected before the feeding trial as well as from faecal profiles generated from control animals...... of short-chain fatty acids was recorded. In conclusion, diets supplemented with FOS or XOS induced a number of microbial changes in the faecal microbiota of mice. The observed effects of XOS were qualitatively similar to those of FOS, but the most prominent bifidogenic effect was seen for XOS. An increased...

Persistent positional nystagmus: a case of superior semicircular canal benign paroxysmal positional vertigo?

Science.gov (United States)

Heidenreich, Katherine D; Kerber, Kevin A; Carender, Wendy J; Basura, Gregory J; Telian, Steven A

2011-08-01

Involvement of the superior semicircular canal (SSC) in benign paroxysmal positional vertigo (BPPV) is rare. SSC BPPV is distinguished from the more common posterior semicircular canal (PSC) variant by the pattern of nystagmus triggered by the Dix-Hallpike position: down-beating torsional nystagmus in SSC BPPV versus up-beating torsional nystagmus in PSC BPPV. SSC BPPV may be readily treated at the bedside, which is a key component in excluding central causes of down-beating nystagmus. We present an unusual video case report believed to represent refractory SSC BPPV based on the pattern of nystagmus and the absence of any other central signs. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

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Mitsue Ishisaka

Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice.

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Martynhak, Bruno Jacson; Hogben, Alexandra L; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R

2017-01-10

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3 -/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3 -/- ) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3 -/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3 -/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3 -/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.

Optimizing radiofrequency ablation of paroxysmal and persistent atrial fibrillation by direct catheter force measurement-a case-matched comparison in 198 patients.

Science.gov (United States)

Sigmund, Elisabeth; Puererfellner, Helmut; Derndorfer, Michael; Kollias, Georgios; Winter, Siegmund; Aichinger, Josef; Nesser, Hans-Joachim; Martinek, Martin

2015-02-01

Sufficient electrode-tissue contact is crucial for adequate lesion formation in radiofrequency catheter ablation (RFCA). We assessed the impact of direct catheter force measurement on acute procedural parameters and outcome of RFCA for paroxysmal and persistent atrial fibrillation (AF). Ninety-nine consecutive patients (70% men) with paroxysmal (63.6%) or persistent AF underwent left atrial RFCA using a 3.5-mm open-irrigated-tip (OIT) catheter with contact force measurement capabilities (group 1). For comparison a case-matched cohort with standard OIT catheters was used (99 patients; group 2). Case matching included gender, type of AF, number or RFCA procedures, and type of procedure. Procedural data showed a significant decline in radiofrequency ablation time from 52 ± 20 to 44 ± 16 minutes (P = 0.003) with a remarkable mean reduction in overall procedure time of 34 minutes (P = 0.0001; 225.8 ± 53.1 vs 191.9 ± 53.3 minutes). In parallel, the total fluoroscopy time could be significantly reduced from 28.5 ± 11.0 to 19.9 ± 9.3 minutes (P = 0.0001) as well as fluoroscopy dose from 74.1 ± 58.0 to 56.7 ± 38.9 Gy/cm(2) (P = 0.016). Periprocedural complications were similar in both groups. The use of contact force sensing technology is able to significantly reduce ablation, procedure, and fluoroscopy times as well as dose in RFCA of AF in a mixed case-matched group of paroxysmal and persistent AF. Energy delivery is substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact. Additionally 12-month outcome data showed increased efficacy. Such time saving and equally safe technology may have a relevant impact on laboratory management and increased cost effectiveness. © 2014 Wiley Periodicals, Inc.

The Use Of Oral Ranolazine To Convert New Or Paroxysmal Atrial Fibrillation: A Review Of Experience With Implications For Possible "Pill In The Pocket" Approach To Atrial Fibrillation

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David K Murdock

2009-09-01

Full Text Available Background: Atrial fibrillation (AF is the most common arrhythmia requiring treatment. High dose oral anti-arrhythmics may cardiovert some paroxysmal AF. This "pill in pocket" approach has allowed patients to treat themselves on an as needed basis. Pro-arrhythmic concerns have limited the usefulness of this approach to patients without structural heart disease. Ranolazine is an anti-anginal agent, which inhibits abnormal late Na+ channel currents in cardiomyocytes and decreases sodium-calcium overload. Ranolazine is a potent inhibitor of after-depolarizations, which have been implicated in the initiation and propagation of AF. Because ranolazine has no known pro-arrhythmic effects, it could be useful as a safe "pill in the pocket" agent if it were effective in converting AF. We describe our experience using oral ranolazine to convert new or paroxysmal AF. Method: 2000 mg of ranolazine were administered to 18 patients with new (11 patients or paroxysmal (7 patients AF of at least 3, but not greater than 48 hours duration. Most patients (14 were in the hospital at the time ranolazine was administered. Age, sex, echocardiographic data, associated health conditions and structural heart disease were recorded. Successful conversion was defined as restoring sinus rhythm within 6 hours of ranolazine administration. Results: All but 1 patient had some form of structural heart disease and all but 2 patients had left atrial enlargement. Thirteen of 18 patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived intolerance (other than constipation were noted. The 72% conversion rate was comparable to other reported "pill in the pocket" protocols. Conclusion: High dose oral ranolazine shows utility as a possible safe agent to convert new or paroxysmal AF. Lack of blinded controls and small numbers limits the power of this observation.

Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy.

Science.gov (United States)

Marzuca-Nassr, Gabriel Nasri; Murata, Gilson Masahiro; Martins, Amanda Roque; Vitzel, Kaio Fernando; Crisma, Amanda Rabello; Torres, Rosângela Pavan; Mancini-Filho, Jorge; Kang, Jing Xuan; Curi, Rui

2017-10-06

The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

[Left atrial function and left atrial appendage flow velocity in hypertrophic cardiomyopathy: comparison of patients with and without paroxysmal atrial fibrillation].

Science.gov (United States)

Akasaka, K; Kawashima, E; Shiokoshi, T; Ishii, Y; Hasebe, N; Kikuchi, K

1998-07-01

The involvement of left atrial (LA) appendage flow velocity in reduced left atrial function was investigated in 24 patients with hypertrophic cardiomyopathy, who retained sinus rhythm at the examination. Patients were divided into 11 with a history of paroxysmal atrial fibrillation [PAf(+)] and 13 without such history [PAf(-)]. Transthoracic echocardiography was performed to evaluate LA fractional shortening (LA%FS) and mean velocity of circumferential LA fiber shortening (LAmVcf), as contractile functions of the left atrium at the phase of active atrial contraction. Transesophageal echocardiographic Doppler examination was performed in all patients to measure the LA appendage velocity. In all patients, significant positive correlations were observed between the LA appendage velocity and LA%FS (r = 0.50, p fibrillation were significantly lower than in those without (0.84 +/- 0.15 vs 1.28 +/- 0.37 circ/sec, 44 +/- 12 vs 65 +/- 20 cm/sec, both p fibrillation. These results indicate that there is a close relationship between LA appendage velocity and LA contractile function in patients with hypertrophic cardiomyopathy with paroxysmal atrial fibrilation, and these patients have potential risk of cerebral infarction.

Successful Catheter Ablation for Paroxysmal Atrial Fibrillation in a Patient with Double-chambered Right Ventricle.

Science.gov (United States)

Shioji, Keisuke; Kurita, Takashi; Kawai, Takafumi; Uegaito, Takashi; Motoki, Koichiro; Matsuda, Mitsuo; Miyazaki, Shunichi

2016-01-01

We herein describe an adult case of double-chambered right ventricle (DCRV) with symptomatic drug-intolerant paroxysmal atrial fibrillation (PAf). The woman was referred to undergo radiofrequency ablation (RFA), and mapping of the pulmonary veins (PVs) demonstrated that a spontaneous spike potential originating from the left inferior PV (LIPV) induced sustained Af in the second procedure. Accordingly, the LIPV was regarded as the arrhythmogenic PV. Since complete isolation of the PVs, the sinus rhythm has been maintained for at least two years. This is the first report to describe that RFA for drug-intolerant PAf was useful in a patient with DCRV.

Paroxysmal occipital discharges suppressed by eye opening: spectrum of clinical and imaging features at a tertiary care center in India.

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Kaul, Bhavna; Shukla, Garima; Goyal, Vinay; Srivastava, Achal; Behari, Madhuri

2012-01-01

Paroxysmal occipital discharges (PODs) demonstrating the phenomena of fixation-off sensitivity have classically been described in childhood epilepsies with occipital paroxysms. We attempted to delineate the demographic, clinical and imaging characteristics of patients whose interictal electroencephalograms (EEGs) showed occipital discharges with fixation-off sensitivity at our center. During the period between 2003 and 2005, patients whose interictal EEGs showed PODs were included in the study. A detailed history, clinical examination and EEG findings along with imaging characteristics were analyzed. Of the 9,104 interictal EEGs screened during the study period, 11 patients (6 females and 5 males) aged between 5 and 17 years were identified to have PODs with fixation-off sensitivity. Five had history of generalized tonic-clonic seizures. Three patients could be classified under Panayiotopoulos syndrome; the remaining 8 (72.2%) patients had symptomatic epilepsy. This study suggests that the phenomenon of fixation-off sensitivity is found not only in patients of idiopathic focal epilepsies, but also in a substantial number of patients of symptomatic epilepsy. The high proportion of symptomatic epilepsy with phenomenon of fixation-off sensitivity may be related to the referral pattern.

Paroxysmal supraventricular tachycardia: physiopathology and management

Directory of Open Access Journals (Sweden)

Paola Neroni

2014-06-01

Full Text Available Paroxysmal supraventricular tachycardia (PSVT is the most frequent arrhythmia in newborns and infants. Most supraventricular tachycardias affect structurally healthy hearts. Apart from occasional detection by parents, most tachycardias in this age group are revealed by heart failure signs, such as poor feeding, sweating and shortness of breath. The main symptom reported by school-age children is palpitations. The chronic tachycardia causes a secondary form of dilative cardiomyopathy. Treatment of acute episode usually has an excellent outcome. Vagal manoeuvres are effective in patients with atrioventricular reentrant tachycardia. Adenosine is the drug of choice at all ages for tachycardias involving the atrioventricular node. Its key advantage is its short half life and minimum or no negative inotropic effects. Verapamil is not indicated in newborns and children as it poses a high risk of electromechanical dissociation. Antiarrhythmic prophylaxis of PSVT recurrence is usually recommended in the first year of life, because the diagnosis of tachycardia may be delayed up to the appearance of symptoms. Digoxin can be administered in all forms of PSVT involving the atrioventricular node, except for patients with Wolff-Parkinson-White syndrome below one year of age. Patients with atrioventricular reentrant PSVT can be treated effectively by class Ic drugs, such as propaphenone and flecainide. Amiodarone has the greatest antiarrhythmic effect, but should be used with caution owing to the high incidence of side effects. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3−/− mice, but not wildtype mice

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Martynhak, Bruno Jacson; Hogben, Alexandra L.; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N.; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R.

2017-01-01

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are ‘direct’ effects of light on affect, an ‘indirect’ pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3−/− mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3−/−) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2–3 of dim light at night, whereas WT mice did not. Per3−/− mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3−/− nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3−/− phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light. PMID:28071711

Symptomatic paroxysmal atrial fibrillation in a patient with unilateral pulmonary vein atresia

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Sharmila Sehli

2015-01-01

Full Text Available A 52-year-old man with symptomatic paroxysmal atrial fibrillation was offered an atrial fibrillation (AF ablation procedure. His echocardiogram indicated that he had no structural heart disease. A cardiac computed tomographic (CT scan showed enlargement of the right pulmonary veins, absence of the left pulmonary veins, a prominent left atrial appendage, and a hypoplastic left lung. Cardiac CT with an electroanatomic mapping system confirmed a prominent left atrial appendage and the absence of the left pulmonary veins. Due to the limited number of patients with this condition, information about ablation remains very limited, and his ablation was deferred. Unilateral pulmonary vein atresia is a rare condition in adults which results from failure of incorporation of the common pulmonary vein into the left atrium. This case demonstrates the clinical importance of preprocedural imaging prior to AF ablation.

Epidemiology of benign paroxysmal positional vertigo: a population based study.

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von Brevern, M; Radtke, A; Lezius, F; Feldmann, M; Ziese, T; Lempert, T; Neuhauser, H

2007-07-01

To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.

Serum uric acid levels correlate with benign paroxysmal positional vertigo.

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Celikbilek, A; Gencer, Z K; Saydam, L; Zararsiz, G; Tanik, N; Ozkiris, M

2014-01-01

Benign paroxysmal positional vertigo (BPPV) is a frequently encountered condition that can severely affect the quality of life. In this study, we aimed to assess the possible relations between serum uric acid (SUA) levels and BPPV. Fifty patients with BPPV, and 40 age- and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio-vestibular test battery including the Dix-Hallpike maneuver and supine roll test for posterior semicircular canal (PSC) and horizontal semicircular canal, respectively. Routine hematological and biochemical analyses were performed in both groups. In the BPPV group, measurements of SUA levels were repeated 1 month after the vertigo attack. The lipid profiles and SUA levels were higher in patients with BPPV than detected in controls (P multiple logistic regression models (P decrement in SUA level 1 month after the vertigo attack compared with the values obtained during the attack (P 0.05). Elevated SUA is positively correlated with BPPV, requiring further efforts to clarify the exact mechanism. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation

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Shintaro Takano

2016-01-01

Full Text Available Atrial fibrillation (AF is the most common cardiac arrhythmia, but its proarrhythmic mechanism remains to be elucidated. Glutamate (Glu and taurine (Tau are present in the myocardium at substantially higher concentrations than in the plasma, suggesting their active role in myocardium. Here, we tested the hypothesis that the metabolism of Glu and Tau is altered in association with the generation of reactive oxygen species (ROS in patients with AF. Fifty patients with paroxysmal AF and 50 control subjects without a history of AF were consecutively enrolled. Circulating Glu and Tau levels were measured and correlations between Glu/Tau and ROS levels were examined. Glu/Tau content was significantly higher in patients with AF versus controls (Glu: 79.2±23.9 versus 60.5±25.2 nmol/L; Tau: 78.8±19.8 versus 68.5±20.8 nmol/L; mean ± standard deviation (SD, p<0.001 for both. Glu/Tau levels also showed an independent association with AF by multiple logistic regression analysis. Glu and Tau levels both showed significant positive associations with plasma hydroperoxide concentrations. These data suggest a novel pathophysiological role of Glu and Tau in association with ROS production in paroxysmal AF, providing new insights into the elevated amino acid content in cardiac disease.

Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica exhibit distinct immunomodulatory activities in mice.

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Lin, Pei-Lan; Lin, Kuo-Wei; Weng, Ching-Feng; Lin, Kuo-Chih

2009-06-10

The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.

MICE Tourism (Meetings, Incentives, Conferecing and Exhibitions como gerador de Turismo Interno: Analisando a cidade de Pelotas, RS

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Adriana Fumi Chim-Miki

2016-06-01

Full Text Available Este artigo objetiva apresentar as oportunidades do Turismo MICE Interno para as cidades consideradas regionais. Esta modalidade de turismo urbano, em termos mundiais e nacionais tem apresentado expressivo crescimento. Além disso, está sendo indicada como um produto complementar ou substituto ao clássico turismo de Sol e Praia, especialmente para destinos que estão apresentando sintomas da maturidade deste modelo, ou áreas em que não há condições naturais favoráveis a um completo desenvolvimento baseado em Sol e Praia. Objetivando contribuir com a literatura acadêmica, se apresenta uma revisão conceitual e tipológica do turismo MICE, seguido de uma revisão de determinantes ou atributos para destinos MICE. Desta revisão se extrai os principais determinantes da competitividade do turismo MICE regional, aplicando-os em uma análise empírica da cidade de Pelotas como candidata a Destino MICE Regional. A metodologia é qualitativa, sendo um estudo de caso que utiliza dados primários através de informação coletada nos sites de promoção turística oficiais do município. Conclui-se que a cidade de Pelotas, situada no sul do Estado do Rio Grande do Sul, possui condições de tornar-se um Destino MICE Regional, porém se recomenda uma melhoria no planejamento turístico, em términos de focalizar no desenvolvimento dos atributos de competitividade MICE, e especialmente uma melhoria na qualidade e quantidade das informações sobre suas capacidades como Destino MICE.

Recurrent life-threatening reactions to platelet transfusion in an aplastic anaemia patient with a paroxysmal nocturnal haemoglobinuria clone.

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Mohamed, M; Bates, G; Richardson, D; Burrows, L

2014-09-01

A 60-year-old woman was diagnosed with non-severe aplastic anaemia when she presented with anaemia and thrombocytopenia. She developed recurrent life-threatening hypotensive reactions during transfusion of leukodepleted platelet concentrates, and washed platelet concentrates prevented the development of such reactions subsequently. A paroxysmal nocturnal haemoglobinuria clone was detected on investigating for aplastic anaemia, which has been speculated to play a role in the recurrent hypotensive reactions. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

A danger of induction of Brugada syndrome during pill-in-the-pocket therapy for paroxysmal atrial fibrillation

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Yoshiyasu Aizawa

2010-08-01

Full Text Available Yoshiyasu Aizawa, Tomohiro Matsuhashi, Toshiaki Sato, Seiji Takatsuki, Keiichi FukudaDivision of Cardiology, Keio University School of Medicine, Tokyo, JapanAbstract: Rhythm control therapy by sodium channel blockers is widely performed for the ­treatment of paroxysmal atrial fibrillation. Here, we present a case of acquired Brugada ­syndrome by pill-in-the-pocket treatment using pilsicainide. It is important that this therapy should be applied only after confirming the drug safety to the patients.Keywords: syncope, sudden death, drug, rhythm control, pilsicainide, atrial flutter

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

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Hsien-Yang Lee

2012-01-01

Full Text Available Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25 of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

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Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP

Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

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Juteau Jean-Marc

2009-12-01

Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

Paroxysmal anal hyperkinesis: a characteristic feature of proctalgia fugax.

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Rao, S S; Hatfield, R A

1996-10-01

Proctalgia fugax is a common problem, yet its pathophysiology is poorly understood. The objective was to characterise colorectal disturbances in a paraplegic patient with a 10 year history of proctalgia fugax that began two years after an attack of transverse myelitis. Standard anorectal manometry and prolonged 33 hour ambulatory colonic manometry at six sites in the colon were performed together with myoelectrical recording of the anus. Provocative tests designed to simulate psychological and physical stress and two types of meals were included. Anorectal manometry showed normal internal sphincter tone and normal rectoanal inhibitory reflex but an inability to squeeze or to bear down or to expel a simulated stool. Rectal sensation (up to 360 ml inflation) was absent. Pudendal nerve latency was prolonged (4.5 ms (normal 3.2 mv), high frequency (5-50/min) anal myoelectrical activity, particularly after stress tests, meals, and at night. The myoelectrical disturbance only occurred with proctalgia. Intermittently, 16 bursts of 3 cycles/ min phasic rectal contractions were seen, but only six were associated with proctalgia. Colonic motility was reduced compared with normal subjects. The temporal association between a high amplitude, high frequency myoelectrical activity of the anal sphincter, and the occurrence of proctalgia suggests that paroxysmal hyperkinesis of the anus may cause proctalgia fugax.

cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

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Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

2014-10-01

Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. Published by Elsevier Inc.

Prediction of paroxysmal atrial fibrillation using recurrence plot-based features of the RR-interval signal

International Nuclear Information System (INIS)

Mohebbi, Maryam; Ghassemian, Hassan

2011-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of stroke. Predicting the onset of paroxysmal AF (PAF), based on noninvasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic intervention and to minimize risks for the patients. In this paper, we propose an effective PAF predictor which is based on the analysis of the RR-interval signal. This method consists of three steps: preprocessing, feature extraction and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the RR-interval signal is extracted. In the next step, the recurrence plot (RP) of the RR-interval signal is obtained and five statistically significant features are extracted to characterize the basic patterns of the RP. These features consist of the recurrence rate, length of longest diagonal segments (L max  ), average length of the diagonal lines (L mean ), entropy, and trapping time. Recurrence quantification analysis can reveal subtle aspects of dynamics not easily appreciated by other methods and exhibits characteristic patterns which are caused by the typical dynamical behavior. In the final step, a support vector machine (SVM)-based classifier is used for PAF prediction. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database (AFPDB) which consists of both 30 min ECG recordings that end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, positive predictivity and negative predictivity were 97%, 100%, 100%, and 96%, respectively. The proposed methodology presents better results than other existing approaches

Profil Karakteristik Pasien Benign Paroxysmal Positional Vertigo Tahun 2011 sampai 2015 di Rumah Sakit Umum Pusat Haji Adam Malik Medan

OpenAIRE

Marpaung, Melissa S. E.

2016-01-01

Benign Paroxysmal Positional Vertigo is the most common cause of vestibular dysfunction, with the sudden sensation like spinning, nausea, and , which is triggered by specific changes in the head position through the gravitation. BPPV occurs as a result of otoconia’s movement (crystals of calcium carbonate that usually placed in utricle and saccule). When the head moves, the otoconia shift and stimulates the cupula to send false signals to the brain, producing vertigo and tri...

Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol.

Science.gov (United States)

Deutsch, Stephen I; Rosse, Richard B; Connor, Julie M; Burket, Jessica A; Murphy, Mary E; Fox, Fiona J

2008-05-01

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter electrocardiography for detection of paroxysmal atrial fibrillation after stroke.

Science.gov (United States)

Rizos, Timolaos; Güntner, Janina; Jenetzky, Ekkehart; Marquardt, Lars; Reichardt, Christine; Becker, Rüdiger; Reinhardt, Roland; Hepp, Thomas; Kirchhof, Paulus; Aleynichenko, Elena; Ringleb, Peter; Hacke, Werner; Veltkamp, Roland

2012-10-01

Cardioembolism in paroxysmal atrial fibrillation (pxAF) is a frequent cause of ischemic stroke. Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention; the optimal diagnostic modality to detect pxAF on stroke units is unknown. We compared 24-hour Holter electrocardiography (ECG) with continuous stroke unit ECG monitoring (CEM) for pxAF detection. Patients with acute ischemic stroke or transient ischemic attack were prospectively enrolled. After a 12-channel ECG on admission, all patients received 24-hour Holter ECG and CEM. Additionally, ECG monitoring data underwent automated analysis using dedicated software to identify pxAF. Patients with a history of atrial fibrillation or with atrial fibrillation on the admission ECG were excluded. Four hundred ninety-six patients (median age, 69 years; 61.5% male) fulfilled all inclusion criteria (ischemic stroke: 80.4%; transient ischemic attack: 19.6%). Median stroke unit stay lasted 88.8 hours (interquartile range, 65.0-122.0). ECG data for automated CEM analysis were available for a median time of 64.0 hours (43.0-89.8). Paroxysmal AF was documented in 41 of 496 patients (8.3%). Of these, Holter detected pxAF in 34.1%; CEM in 65.9%; and automated CEM in 92.7%. CEM and automated CEM detected significantly more patients with pxAF than Holter (Pstroke on stroke units compared with 24-hour Holter ECG. The comparative usefulness of prolonged or repetitive Holter ECG recordings requires further evaluation.

Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation

DEFF Research Database (Denmark)

Gardella, Elena; Becker, Felicitas; Møller, Rikke S

2016-01-01

by stretching, motor initiation or by emotional stimuli. In one case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortical involvement. INTERPRETATION: Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum...... patient had seizures only at school age. All patients stayed otherwise seizure-free, most without medication. Interictal EEG was normal in all cases but two. Five/16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered...... identified as the major gene in all three conditions, found to be mutated in 80-90% of familial and 30-35% of sporadic cases. METHODS: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed...

Cerebral stroke in a teenage girl with paroxysmal nocturnal hemoglobinuria

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Francesco Gervasi

2017-06-01

Full Text Available We report a case of paroxysmal nocturnal hemoglobinuria (PNH in a 14 year-old girl presenting a cerebral arterial thrombosis. The initial diagnosis was carential anemia due to menarche following identification of slight macrocytic anemia, leucopenia and mild thrombocytopenia at routine blood analysis. The child was eventually referred to a children’s hospital after the onset of progressive fatigue, anorexia and paleness. Severe anemia (hemoglobin 6 g/dL with negative Coombs test, mild leucopenia (white blood cells 4.9×109/L and thrombocytopenia (platelets 97×109/L and high values of lactate dehydrogenase (2855 U/L were identified; a packed red cells transfusion was administered. Her condition worsened and she subsequently presented complete right hemiplegia, aphasia and coma; magnetic resonance imaging revealed a massive ischemic lesion. A diagnosis of PNH was eventually made following high sensitivity flow cytometry, which identified a PNH clone (CD66b negative equal to 93.7% of granulocytes. Fast recovery from neurologic and hematological problems occurred in response to anticoagulant therapy and intravenous therapy with eculizumab. We are convinced that PNH should be included in the differential diagnosis of children presenting with cytopenia.

Visual dependence and spatial orientation in benign paroxysmal positional vertigo.

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Nair, Maitreyi A; Mulavara, Ajitkumar P; Bloomberg, Jacob J; Sangi-Haghpeykar, Haleh; Cohen, Helen S

2018-01-01

People with benign paroxysmal positional vertigo (BPPV) probably have otoconial particles displaced from the utricle into the posterior semicircular canal. This unilateral change in the inertial load distributions of the labyrinth may result in visual dependence and may affect balance control. The goal of this study was to explore the interaction between visual dependence and balance control. We compared 23 healthy controls to 17 people with unilateral BPPV on the Clinical Test of Sensory Interaction and Balance on compliant foam with feet together, the Rod-and-Frame Test and a Mental Rotation Test. In controls, but not BPPV subjects, subjects with poor balance scores had significantly greater visual dependence, indicating that reliance on visual cues can affect balance control. BPPV and control subjects did not differ on the mental rotation task overall but BPPV reaction time was greater at greater orietantions, suggesting that this cognitive function was affected by BPPV. The side of impairment was strongly related to the side of perceived bias in the Earth vertical determined by BPPV subjects, indicating the relationship between the effect of asymmetric otolith unloading with simultaneous canal loading on spatial orientation perception.

Depression, anxiety, and quality of life in paroxysmal kinesigenic dyskinesia patients.

Science.gov (United States)

Tian, Wo-Tu; Huang, Xiao-Jun; Liu, Xiao-Li; Shen, Jun-Yi; Liang, Gui-Ling; Zhu, Chen-Xi; Tang, Wei-Guo; Chen, Sheng-Di; Song, Yan-Yan; Cao, Li

2017-09-05

Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Under the condition of psychological burden, some patients' attacks may get worsened with longer duration and higher frequency. This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population. We performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital, using Symptom Check List-90-Revised (SCL-90-R), World Health Organization Quality of Life-100 (WHOQoL-100), Self-Rating Depression Scale, and Self-Rating Anxiety Scale. We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data (taken from literature) by using the unpaired Student's t-test. We applied multivariate linear regression to analyze the relationships between motor manifestations, mental health, and quality of life among PKD patients. Compared with Chinese normative data taken from literature, patients with PKD exhibited significantly higher (worse) scores across all SCL-90-R subscales (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; P= 0.000 for all) and significantly lower (worse) scores of five domains in WHOQoL-100 (physical domain, psychological domain, independence domain, social relationship domain, and general quality of life; P= 0.000 for all). Nonremission of dyskinesia episodes (P = 0.011) and higher depression score (P = 0.000) were significantly associated with lower levels of quality of life. The rates of depression and anxiety in patients with PKD were 41.2% (68/165) and 26.7% (44/165), respectively. Depression, anxiety, and low levels of quality of life were prevalent in patients with PKD. Co-occurrence of depression and anxiety was common among these patients. Regular mental health

The coexistence of paroxysmal hemicrania and temporomandibular disorder: Importance of multidisciplinary approach

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André Luís Porporatti

2014-01-01

Full Text Available Paroxysmal hemicrania (PH is a trigeminal autonomic cephalalgia, a rare primary headache characterized by unilateral periorbital and/or temporal attacks of severe intensity and short duration. In this situation, the determination of a correct diagnosis is crucial for the establishment of a proper management strategy. In the case of head and facial pain, this step is usually a big challenge since many conditions share the same features, as some primary headaches and temporomandibular disorders (TMD. The relationship between PH and TMD has not been determined. This paper describes a case of a female patient diagnosed with TMD and presenting concomitant headache attacks fulfilling the International Headache Society′s criteria for PH. It is also emphasized the importance of dentist in this scenario, for many times responsible for the initial diagnosis of facial/head pain. Moreover, it is presented an integrated and simultaneously approach of both conditions, PH and TMD.

Horizontal canal benign paroxysmal positional vertigo: diagnosis and treatment of 37 patients

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Eliana Teixeira Maranhão

2015-06-01

Full Text Available Benign paroxysmal positional vertigo (BPPV, the most frequent cause of vertigo is associated with high morbidity in the elderly population. The most common form is linked to debris in the posterior semicircular canal. However, there has been an increasing number of reported BPPV cases involving the horizontal canals. The purpose of this article is to highlight the clinical features, diagnosis, and treatment in 37 patients with horizontal canal BPPV; twenty-six with geotropic nystagmus, and eleven with the apogeotropic form. Treatment consisted of the Gufoni manoeuver in eighteen patients (48.6%, the barbecue 360° maneuver in twelve patients (32.4%, both manoeuvers in four patients (10.8%, both manoeuvers plus head shaking in one patient (2.7%, and the Gufoni maneuver plus head shaking in two patients. Cupulolithiasis patients were asked to sleep in a forced prolonged position. We obtained a complete resolution of vertigo and nystagmus in 30 patients (81.0% on the initial visit.

Spontaneous nystagmus in benign paroxysmal positional vertigo: is it a new sign?

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Hajiabolhassan, Fahimeh; Tavanai, Elham

2013-01-01

Benign Paroxysmal Positional Vertigo (BPPV) is a condition that indicates a benign inner ear disorder. It is generally believed that BPPV is due to the dislodged otoconial particles from otolith organs and unusual collection of them within any of semicircular canals or even in all three semicircular canals. Although the typical features of nystagmus in BPPV have been well-studied, very few studies (just four articles) have highlighted the presence of spontaneous nystagmus in BPPV recently. During the past 10 years, 2850 patients have been examined at the audiology unit of our department, and 254 patients have received diagnoses of BPPV but recently 2 patients presented with BPPV and spontaneous nystagmus, a new symptom that has been never observed in our clinical records. We herein describe this rare symptom in 2 case of BPPV. A 50-year-old woman with BPPV who showed an 18 degree spontaneous nystagmus treated with Epley maneuver and a 53-year-old man with 3 degree spontaneous nystagmus.

Effect of Diets Containing Sucrose vs. D-tagatose in Hypercholesterolemic Mice

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Police, S.; Harris, J; Lodder, R; Cassis, L

2008-01-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr-/-) mice. LDLr-/- male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice.

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Police, Sara B; Harris, J Clay; Lodder, Robert A; Cassis, Lisa A

2009-02-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr(-/-)) mice. LDLr(-/-) male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory response during early pregnancy.

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Heyward, C Y; Sones, J L; Lob, H E; Yuen, L C; Abbott, K E; Huang, W; Begun, Z R; Butler, S D; August, A; Leifer, C A; Davisson, R L

2017-04-01

Preeclampsia is a devastating complication of pregnancy characterized by late-gestation hypertension and proteinuria. Because the only definitive treatment is delivery of the fetus and placenta, preeclampsia contributes to increased morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which spontaneously develops a syndrome strikingly similar to preeclampsia, displays excessive inflammation and suppression of inflammation improves pregnancy outcomes. During early pregnancy, decidual macrophages play an important role in promoting maternal tolerance to fetal antigens and regulating tissue remodeling, two functions that are critical for normal placental development. BPH/5 pregnancies are characterized by abnormal placentation; therefore, we hypothesized that macrophage localization and/or function is altered during early pregnancy at the site of placental formation (the decidua) compared to C57BL/6 controls. At early gestation time points, before the onset of maternal hypertension or proteinuria, there was a reduction in the number of macrophages in BPH/5 decidua and a concomitant increase in activated T cells compared with C57BL/6. BPH/5 decidua also exhibited decreased expression of the immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory, inducible nitric oxide synthase. Together, these data suggest that a reduction in decidual macrophages during pregnancy is associated with immune activation in BPH/5 mice, inadequate placental development and may contribute to adverse pregnancy outcomes in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation

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Young Keith A

2010-11-01

Full Text Available Abstract Background Numerous studies have reported that increased expression of S100B, an intracellular Ca2+ receptor protein and secreted neuropeptide, exacerbates Alzheimer's disease (AD pathology. However, the ability of S100B inhibitors to prevent/reverse AD histopathology remains controversial. This study examines the effect of S100B ablation on in vivo plaque load, gliosis and dystrophic neurons. Methods Because S100B-specific inhibitors are not available, genetic ablation was used to inhibit S100B function in the PSAPP AD mouse model. The PSAPP/S100B-/- line was generated by crossing PSAPP double transgenic males with S100B-/- females and maintained as PSAPP/S100B+/- crosses. Congo red staining was used to quantify plaque load, plaque number and plaque size in 6 month old PSAPP and PSAPP/S100B-/- littermates. The microglial marker Iba1 and astrocytic marker glial fibrillary acidic protein (GFAP were used to quantify gliosis. Dystrophic neurons were detected with the phospho-tau antibody AT8. S100B immunohistochemistry was used to assess the spatial distribution of S100B in the PSAPP line. Results PSAPP/S100B-/- mice exhibited a regionally selective decrease in cortical but not hippocampal plaque load when compared to PSAPP littermates. This regionally selective reduction in plaque load was accompanied by decreases in plaque number, GFAP-positive astrocytes, Iba1-positive microglia and phospho-tau positive dystrophic neurons. These effects were not attributable to regional variability in the distribution of S100B. Hippocampal and cortical S100B immunoreactivity in PSAPP mice was associated with plaques and co-localized with astrocytes and microglia. Conclusions Collectively, these data support S100B inhibition as a novel strategy for reducing cortical plaque load, gliosis and neuronal dysfunction in AD and suggest that both extracellular as well as intracellular S100B contribute to AD histopathology.

Infanticide: accounting for genetic variation in mice.

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Svare, B; Kinsley, C H; Mann, M A; Broida, J

1984-07-01

Infanticide, the killing of young, is one of a number of sexually-dimorphic traits in mice that is dependent upon androgen stimulation during perinatal life and during adulthood. Genotype also influences infanticide in that males of some strains of mice (C57BL/6J) exhibit high levels of this behavior while males of other strains (DBA/2J) seldom kill young. The experiments conducted here show that strain differences in pup killing behavior exhibited by males are not related to postweaning social factors nor are they due to differences in perinatal, pubertal, or adult levels of circulating hormones. These results, in combination with those previously reported, suggest that strain differences in the tendency of mice to kill young may instead depend upon the interaction of genotypic features such as prenatal hormone titers and/or sensitivity to these hormones, as well as on extra organismic factors such as intrauterine position. A model for understanding the manner in which genes and hormones may interact to influence infanticide and other hormone dependent sexually-dimorphic behaviors in mice is presented.

Select cognitive deficits in Vasoactive Intestinal Peptide deficient mice

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Hagopian Arkady

2008-07-01

Full Text Available Abstract Background The neuropeptide vasoactive intestinal peptide (VIP is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions. Results In the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice. Conclusion Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.

Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

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Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

2015-02-01

The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

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Kim, Soochan; Han, Sinsuk; Lee, Ye Eun; Jung, Woong-Jae; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

2016-01-01

The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells. Copyright © 2015. Published by Elsevier GmbH.

Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

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Grider, A. Jr.

1986-01-01

The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the 109 Cd-saturation/hemolysate method, and by the 65 Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the 65 Zn-MT binding assay (3-fold) and by the 109 Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of 65 Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age

Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

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Grider, A. Jr.

1986-01-01

The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the /sup 109/Cd-saturation/hemolysate method, and by the /sup 65/Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the /sup 65/Zn-MT binding assay (3-fold) and by the /sup 109/Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of /sup 65/Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age.

Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

International Nuclear Information System (INIS)

Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

1990-01-01

Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus.

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Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte; Ostachowicz, Beata; Nowak, Gabriel

2014-10-31

Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis. In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn(2+)-sensing receptor in the pathophysiology of depression with component of anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

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Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

2011-11-01

We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (Pknock-in mice compared with wild-type mice (Pknock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; Pknock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

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Alex Langford-Smith

Full Text Available Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

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Langford-Smith, Alex; Langford-Smith, Kia J; Jones, Simon A; Wynn, Robert F; Wraith, J E; Wilkinson, Fiona L; Bigger, Brian W

2011-01-01

Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A), is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

Italian survey on benign paroxysmal positional vertigo.

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Messina, A; Casani, A P; Manfrin, M; Guidetti, G

2017-08-01

Benign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. BPPV often relapses after the first episode, with a recurrence rate between 15% and 50%. To date both the aetiopathogenetic processes that lead to otoconia detachment and the factors that make BPPV a relapsing disease are still unclear, but recent epidemiological studies have shown a possible association with cardiovascular risk factors. The aim of the present study (Sesto Senso Survey) was to evaluate in the Italian population through an observational survey, the main demographic and clinical characteristics of patients with BPPV (first episode or recurrent) with particular focus on the potential cardiovascular risk factors. The survey was conducted in 158 vestibology centres across Italy on 2,682 patients (mean age 59.3 ± 15.0 years; 39.1% males and 60.9% females) suffering from BPPV, from January 2013 to December 2014. The results showed a high prevalence of cardiovascular risk factors such as high blood pressure (55.8%), hypercholesterolaemia (38.6%) and diabetes (17.7%), as well as a family history of cardiovascular disease (49.4%). A high percentage of patients also had hearing loss (42.9%), tinnitus (41.2%), or both (26.8%). The presence of hypertension, dyslipidaemia and pre-existing cardiovascular comorbidities were significantly related to recurrent BPPV episodes (OR range between 1.84 and 2.31). In addition, the association with diabetes and thyroid/autoimmune disease (OR range between 1.73 and 1.89) was relevant. The survey results confirm the significant association between cardiovascular comorbidities and recurrent BPPV and identify them as a potential important risk factor for recurrence of BPPV in the Italian population, paving the way for the evaluation of new therapeutic strategies in the treatment of this disease. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice.

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Kruse, Robert L; Shum, Thomas; Tashiro, Haruko; Barzi, Mercedes; Yi, Zhongzhen; Whitten-Bauer, Christina; Legras, Xavier; Bissig-Choisat, Beatrice; Garaigorta, Urtzi; Gottschalk, Stephen; Bissig, Karl-Dimiter

2018-04-06

Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection. We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice. HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups. HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Assessment of sleep quality in benign paroxysmal positional vertigo recurrence.

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Wang, Yun; Fei Xia, Fei; Wang, Wei; Hu, Wenli

2018-06-08

Despite the availability of highly effective treatments, there is a significant recurrence rate of benign paroxysmal positional vertigo (BPPV). This study is aimed to quantitatively measure sleep quality in BPPV patients and correlate it with the recurrence of BPPV. In this longitudinal cohort study, the clinical records of 67 elderly or middle-aged adult patients who were diagnosed with BPPV at Neurology Clinic, Beijing Chaoyang Hospital affiliated to Capital Medical University between 2013 and 2014. The "Recurrent" and "Non-recurrent" BPPV were respectively defined. Primary data collection included the medical history, blood test and Pittsburgh sleep quality index measurement. Among the total 67 patients after successful treatment, recurrent BPPV is observed in 37.31% patients (n = 25) within 2 years. Among all 11 variables analyzed between recurrent and non-recurrent groups, only the Pittsburgh Sleep Quality Index (PSQI) scores showed significant difference (P quality, sleep latency, sleep duration, the use of sleep-aid medication and daytime dysfunctions (all P quality) had higher risk of BPPV recurrence (OR = 1.17, 95% CI: 1.04-1.32, P= 0.0082). The sleep quality in patients with BPPV recurrence is significantly poorer compared to non-recurrent patients. Our result suggested sleep quality as measured by PSQI is an independent risk factor of BPPV recurrence.

Radiation carcinogenesis in scid mice

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Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

1999-06-01

Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

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Naoya eYamashita

2013-12-01

Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

Cystathionine-gamma-lyase deficient mice are protected against the development of multiorgan failure and exhibit reduced inflammatory response during burn.

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Ahmad, Akbar; Druzhyna, Nadiya; Szabo, Csaba

2017-08-01

Considering the role of H 2 S in critical illness, the aim of this study was to compare the outcome of burn in wild-type mice and in mice deficient in CSE, one of the principal mammalian H 2 S-generating enzymes. Animals were subjected to scald burn. Outcome variables included indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. Plasma levels of H 2 S significantly increased in response to burn in wild-type mice, but remained unchanged in CSE -/- mice. Expression of the three H 2 S-producing enzymes (CSE, CBS and 3-MST) in the lung and liver, and the capacity of tissue homogenates to produce H 2 S, however, was not affected by burn. In CSE deficient mice there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart, lung, liver and kidney and significantly lower degree of malon dialdehyde accumulation in the heart, lung and kidney than in wild-type mice. CSE deficient mice, compared to wild-type mice, showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and blood urea nitrogen and creatinine levels, indicative of protective effects of CSE deficiency against burn-induced hepatic, and renal functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1β, IL-4, IL-6, IL-10 and IL-12) were significantly lower in the plasma of CSE -/- animals after burn than in the plasma of wild-type controls subjected to burns. In conclusion, CSE deficiency improves organ function and attenuates the inflammatory response in a murine model of burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Therapeutic potential of flurbiprofen against obesity in mice.

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Hosoi, Toru; Baba, Sachiko; Ozawa, Koichiro

2014-06-20

Obesity is associated with several diseases including diabetes, nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease, and cancer. Therefore, anti-obesity drugs have the potential to prevent these diseases. In the present study, we demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited therapeutic potency against obesity. Mice were fed a high-fat diet (HFD) for 6 months, followed by a normal-chow diet (NCD). The flurbiprofen treatment simultaneously administered. Although body weight was significantly decreased in flurbiprofen-treated mice, growth was not affected. Flurbiprofen also reduced the HFD-induced accumulation of visceral fat. Leptin resistance, which is characterized by insensitivity to the anti-obesity hormone leptin, is known to be involved in the development of obesity. We found that one of the possible mechanisms underlying the anti-obesity effects of flurbiprofen may have been mediated through the attenuation of leptin resistance, because the high circulating levels of leptin in HFD-fed mice were decreased in flurbiprofen-treated mice. Therefore, flurbiprofen may exhibit therapeutic potential against obesity by reducing leptin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

[The roles of otolith organs in the recurrence primary benign paroxysmal positional vertigo].

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Zhou, Xiaowei; Yu, Youjun; Wu, Ziming; Liu, Xinjian; Chen, Xianbing

2015-09-01

To explore the roles of otolith organs in the occurrence and recurrence of primary benign paroxysmal positional vertigo (BPPV) by vestibular evoked myogenic potential (VEMP) test. We enrolled 17 recurrent primary BPPV patients and 42 non-recurrent primary BPPV patients between September 2014 and November 2014. All patients underwent VEMP tests, including cervical vestibular evoked myogenic potential (cVEMP and ocular vestibular evoked myogenic potential (oVEMP) tests. The abnormal case was defined as non-elicitation or asymmetry rate between bilateral sides is larger than 29%. Significant difference was found in abnormal rate between cVEMP and oVEMP (P 0.05). No significant difference was found in sex and age between recurrent and non-recurrent groups (P > 0.05). The impairment of otolith organs, especially the utricle, is related to primary BPPV. Dysfunction of utricle may play a role in recurrence of BPPV. Recurrence of BPPV is not correlated with sex and age.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

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Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

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Takuto Oyama

2016-06-01

Full Text Available Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA. MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF and low-biofilm formers (L-BF. These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections.

Behavioural endophenotypes in mice lacking the auxiliary GABAB receptor subunit KCTD16.

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Cathomas, Flurin; Sigrist, Hannes; Schmid, Luca; Seifritz, Erich; Gassmann, Martin; Bettler, Bernhard; Pryce, Christopher R

2017-01-15

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABA B receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABA B receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12 -/- ) exhibit increased auditory fear learning and that Kctd12 +/- mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons. KCTD16 has been demonstrated to influence neuronal excitability by regulating GABA B receptor-mediated gating of postsynaptic ion channels. In the present study we investigated for behavioural endophenotypes in Kctd16 -/- and Kctd16 +/- mice. Compared with wild-type (WT) littermates, auditory and contextual fear conditioning were normal in both Kctd16 -/- and Kctd16 +/- mice. When fear memory was tested on the following day, Kctd16 -/- mice exhibited less extinction of auditory fear memory relative to WT and Kctd16 +/- mice, as well as more contextual fear memory relative to WT and, in particular, Kctd16 +/- mice. Relative to WT, both Kctd16 +/- and Kctd16 -/- mice exhibited normal circadian activity. This study adds to the evidence that auxillary KCTD subunits of GABA B receptors contribute to the regulation of behaviours that could constitute endophenotypes for hyper-reactivity to aversive stimuli in neuropsychiatric disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison between epleys maneuvre and prochlorperazine maleate in treatment of benign paroxysmal positional vertigo

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Niazi, K.O.K.; Dastgir, M.

2015-01-01

The objective is to compare the efficacy of Epley's maneuver and vestibular sedative, prochlorperazine maleate in the management of benign paroxysmal positional vertigo (BPPV). Study Design: Randomized Control Trial. Place and Duration of Study: ENT department, Combined Military Hospital, Rawalpindi from 1st May 2011 to 1st November 2011. Patients and Methods: After consent, 60 patients of BPPV fulfilling the inclusion criteria were randomly allotted two groups. Group A was treated with Epley's maneuver (n=30) while group B with prochlorperazine maleate (n=30). Outcomes were analyzed on disappearance of vertigo at follow-up examination. Results: 24 (80%) cases managed by Epley's maneuver showed relief of symptoms while only 14 (47%) treated by rochlorperazine maleate showed recovery after 15 days. Conclusion: Epley's maneuver was more effective than vestibular sedatives like prochlorperazine maleate in treating patients of BPPV. (author)

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

DEFF Research Database (Denmark)

Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

Impaired bone formation in Pdia3 deficient mice.

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Yun Wang

Full Text Available 1α,25-Dihydroxyvitamin D3 [1α,25(OH2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3 mediates 1α,25(OH2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/- heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/- mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/- mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/- mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/- heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH2D3's actions in regulating skeletal development.

Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages.

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Khoa D Tran

Full Text Available In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δkharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δkharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δkharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δkharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis.

Mice deficient in cryptochrome 1 (Cry1-/- exhibit resistance to obesity induced by a high fat diet

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Guy eGriebel

2014-04-01

Full Text Available Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD-induced obesity in mice. Despite similar caloric intake, Cry1-/- mice on HFD gained markedly less weight (-18 % at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT littermates (-61 %, suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1-/- and WT mice. Both Cry1-/- and Cry2-/- mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for antiobesity therapy.

Mice deficient in cryptochrome 1 (cry1 (-/-)) exhibit resistance to obesity induced by a high-fat diet.

Science.gov (United States)

Griebel, Guy; Ravinet-Trillou, Christine; Beeské, Sandra; Avenet, Patrick; Pichat, Philippe

2014-01-01

Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY) family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study, we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD)-induced obesity in mice. Despite similar caloric intake, Cry1 (-/-) mice on HFD gained markedly less weight (-18%) at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT) littermates (-61%), suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1 (-/-) and WT mice. Both Cry1 (-/-) and Cry2 (-/-) mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for anti-obesity therapy.

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

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Mariko Umemura

2017-07-01

Full Text Available Activating transcription factor 5 (ATF5 is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/- mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.

AGEMAP: a gene expression database for aging in mice.

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Jacob M Zahn

2007-11-01

Full Text Available We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1 a pattern common to neural tissues, (2 a pattern for vascular tissues, and (3 a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different.

IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.

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Sherry L Kurtz

Full Text Available Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.

Catalase deletion promotes prediabetic phenotype in mice.

Science.gov (United States)

Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

2017-02-01

Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

Mice from lines selectively bred for high voluntary wheel running exhibit lower blood pressure during withdrawal from wheel access.

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Kolb, Erik M; Kelly, Scott A; Garland, Theodore

2013-03-15

Exercise is known to be rewarding and have positive effects on mental and physical health. Excessive exercise, however, can be the result of an underlying behavioral/physiological addiction. Both humans who exercise regularly and rodent models of exercise addiction sometimes display behavioral withdrawal symptoms, including depression and anxiety, when exercise is denied. However, few studies have examined the physiological state that occurs during this withdrawal period. Alterations in blood pressure (BP) are common physiological indicators of withdrawal in a variety of addictions. In this study, we examined exercise withdrawal in four replicate lines of mice selectively bred for high voluntary wheel running (HR lines). Mice from the HR lines run almost 3-fold greater distances on wheels than those from non-selected control lines, and have altered brain activity as well as increased behavioral despair when wheel access is removed. We tested the hypothesis that male HR mice have an altered cardiovascular response (heart rate, systolic, diastolic, and mean arterial pressure [MAP]) during exercise withdrawal. Measurements using an occlusion tail-cuff system were taken during 8 days of baseline, 6 days of wheel access, and 2 days of withdrawal (wheel access blocked). During withdrawal, HR mice had significantly lower systolic BP, diastolic BP, and MAP than controls, potentially indicating a differential dependence on voluntary wheel running in HR mice. This is the first characterization of a cardiovascular withdrawal response in an animal model of high voluntary exercise. Copyright © 2013. Published by Elsevier Inc.

Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

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Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

2017-03-01

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

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Hyo Geun Kim

2015-01-01

Full Text Available Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities.

D-penicillamine exhibits a higher radioprotective effect in suckling mice than in grown-up animals

International Nuclear Information System (INIS)

Oroszlan, Gy.; Lakatos, L.; Dezsi, Z.; Hatvani, I.; Pintye, E.; Karmazsin, L.; Orvostudomanyi Egyetem, Debrecen; Orvostudomanyi Egyetem, Debrecen

1982-01-01

Grown-up and suckling mice were exposed to whole-body 60 Co-irradiation of 6-10 Gy. The survival time was significantly increased in suckling animals by 3000 mg per kg body weight D-penicillamine applied intraperitoneally 60 min before irradiation, whereas the same treatment had no significant effect in grown-up animals. (L.E.)

Crybb2 deficiency impairs fertility in female mice

International Nuclear Information System (INIS)

Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

2014-01-01

Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2 −/− ) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2 −/− mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2 −/− mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2 −/− female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2 −/− mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2 −/− mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells

Crybb2 deficiency impairs fertility in female mice

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Gao, Qian [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Sun, Li-Li [Aviation Medical Evaluation and Training Center of Airforce in Dalian, Dalian, Liaoning Province 116013 (China); Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Xiang, Fen-Fen [Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062 (China); Gao, Li [Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Zhang, Jun-Jie, E-mail: zhangjj910@163.com [Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Li, Wen-Jie, E-mail: wenjieli@pku.org.cn [Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

2014-10-10

Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2{sup −/−}) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2{sup −/−} mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2{sup −/−} mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2{sup −/−} female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2{sup −/−} mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2{sup −/−} mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells.

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

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Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

2013-01-01

We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

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Saki Imai

Full Text Available We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92, and mice with this mutation (MT mice, as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

Role of Fyn-mediated NMDA receptor function in prediabetic neuropathy in mice

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Suo, Meng; Wang, Ping

2016-01-01

Diabetic neuropathy is a common complication of diabetes. This study evaluated the role of Fyn kinase and N-methyl-d-aspartate receptors (NMDARs) in the spinal cord in diabetic neuropathy using an animal model of high-fat diet-induced prediabetes. We found that prediabetic wild-type mice exhibited tactile allodynia and thermal hypoalgesia after a 16-wk high-fat diet, relative to normal diet-fed wild-type mice. Furthermore, prediabetic wild-type mice exhibited increased tactile allodynia and thermal hypoalgesia at 24 wk relative to 16 wk. Such phenomena were correlated with increased expression and activation of NR2B subunit of NMDARs, as well as Fyn-NR2B interaction in the spinal cord. Fyn−/− mice developed prediabetes after 16-wk high-fat diet treatment and exhibited thermal hypoalgesia, without showing tactile allodynia or altered expression and activation of NR2B subunit, relative to normal diet-fed Fyn−/− mice. Finally, intrathecal administrations of Ro 25-6981 (selective NR2B subunit-containing NMDAR antagonist) dose-dependently alleviated tactile allodynia, but not thermal hypoalgesia, at 16 and 24 wk in prediabetic wild-type mice. Our results suggested that Fyn-mediated NR2B signaling plays a critical role in regulation of prediabetic neuropathy and that the increased expression/function of NR2B subunit-containing NMDARs may contribute to the progression of neuropathy in type 2 diabetes. PMID:27146985

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

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Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

2014-01-01

Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

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Zhe Liang

Full Text Available Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis.Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival.In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice.Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

Paroxysmal atrial fibrillation: dynamics of the main antioxidant enzymes--superoxide dismutase and catalase.

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Negreva, Mariya N; Penev, Atanas P; Georgiev, Svetoslav Zh; Aleksandrova, Albena A

2014-01-01

Researchers have a particularly strong interest in the mechanisms implicated in the clinical manifestation of atrial fibrillation. To examine dynamically the activity of the antioxidant enzymes, superoxide dismutase and catalase in patients with paroxysmal atrial fibrillation (duration enzyme activity was determined by a spectrophotometric method. The average duration of atrial fibrillation episodes until the time of hospitalization was 8.14 hours (from 2 to 24 hours). During patient hospitalization the activity of superoxide dismutase and catalase was considerably higher compared to that of the controls (8.46 +/- 0.26 vs 5.81 +/- 0.14 U/mg Hb; 7.36 +/- 0.25 vs 4.76 +/- 0.12 E240/min/mg Hb; P catalase remained increased (5.11 +/- 0.08 vs 4.76 +/- 0.12 E240/min/mg Hb, p catalase even in the early hours of clinical manifestation of the disorder, which then slowly decreased with the restoration of sinus rhythm. Therefore, we can conclude that changes in oxidative status are closely related to the disease and are probably a part of the intimate mechanisms related to its initiation and clinical course.

Design and implementation of an electrocardiographical signal acquisition and digital processing system orientated to the detection of paroxysmal arrhythmias

International Nuclear Information System (INIS)

Braceli, Agustín Iriart; Morani, Jorge Exequiel

2011-01-01

This article describes the design, technical aspects and implementation of a device capable of acquiring electrocardiograph signals; visualize them in real time over a graphic liquid crystal display (GLCD), and the storage of these ECG registers on a SD memory card. It also details a noise suppression algorithm using the Wavelet Transform. This system was specially developed to cover some bankruptcy that presents actual Holters or ECG regarding the detection of paroxysmal arrhythmias. The contribution of this work is settled on its portability and low production cost. The filtering method used provides an ECG signal without any significant noise and appropriate to the diagnosis of cardiac pathologies.

Design and implementation of an electrocardiographical signal acquisition and digital processing system orientated to the detection of paroxysmal arrhythmias

Science.gov (United States)

Iriart Braceli, Agustín; Exequiel Morani, Jorge

2011-12-01

This article describes the design, technical aspects and implementation of a device capable of acquiring electrocardiograph signals; visualize them in real time over a graphic liquid crystal display (GLCD), and the storage of these ECG registers on a SD memory card. It also details a noise suppression algorithm using the Wavelet Transform. This system was specially developed to cover some bankruptcy that presents actual Holters or ECG regarding the detection of paroxysmal arrhythmias. The contribution of this work is settled on its portability and low production cost. The filtering method used provides an ECG signal without any significant noise and appropriate to the diagnosis of cardiac pathologies.

Neuromyelitis optica: association with paroxysmal painful tonic spasms.

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Carnero Contentti, E; Leguizamón, F; Hryb, J P; Celso, J; Pace, J L Di; Ferrari, J; Knorre, E; Perassolo, M B

2016-10-01

Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

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Won, Young-Suk; Song, Ji-Won; Lim, Jong-Hwan; Lee, Mee-Young; Moon, Og-Sung; Kim, Hyoung-Chin; Son, Hwa-Young; Kwon, Hyo-Jung

2016-01-01

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [ 14 C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

Energy Technology Data Exchange (ETDEWEB)

Won, Young-Suk [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Song, Ji-Won [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lim, Jong-Hwan [Huons Research Center, Gyonggido (Korea, Republic of); Lee, Mee-Young [Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Moon, Og-Sung; Kim, Hyoung-Chin [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Son, Hwa-Young [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Kwon, Hyo-Jung, E-mail: hyojung@cnu.ac.kr [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of)

2016-01-15

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

The chondrogenic response to exercise in the proximal femur of normal and mdx mice

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Nye David J

2010-09-01

Full Text Available Abstract Background Submaximal exercise is used in the management of muscular dystrophy. The effects of mechanical stimulation on skeletal development are well understood, although its effects on cartilage growth have yet to be investigated in the dystrophic condition. The objective of this study was to investigate the chondrogenic response to voluntary exercise in dystrophin-deficient mice. Methods Control and dystrophin-deficient (mdx mice were divided into sedentary and exercise-treated groups and tested for chondral histomorphometric differences at the proximal femur. Results Control mice ran 7 km/week further than mdx mice on average, but this difference was not statistically significant (P > 0.05. However, exercised control mice exhibited significantly enlarged femur head diameter, articular cartilage thickness, articular cartilage tissue area, and area of calcified cartilage relative to sedentary controls and exercised mdx mice (P Conclusions Mdx mice exhibit a reduced chondrogenic response to increased mechanical stimulation relative to controls. However, no significant reduction in articular dimensions was found, indicating loss of chondral tissue may not be a clinical concern with dystrophinopathy.

Hyperphagia, lower body temperature, and reduced running wheel activity precede development of morbid obesity in New Zealand obese mice.

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Jürgens, Hella S; Schürmann, Annette; Kluge, Reinhart; Ortmann, Sylvia; Klaus, Susanne; Joost, Hans-Georg; Tschöp, Matthias H

2006-04-13

Among polygenic mouse models of obesity, the New Zealand obese (NZO) mouse exhibits the most severe phenotype, with fat depots exceeding 40% of total body weight at the age of 6 mo. Here we dissected the components of energy balance including feeding behavior, locomotor activity, energy expenditure, and thermogenesis compared with the related lean New Zealand black (NZB) and obese B6.V-Lep(ob)/J (ob/ob) strains (11% and 65% fat at 23 wk, respectively). NZO mice exhibited a significant hyperphagia that, when food intake was expressed per metabolic body mass, was less pronounced than that of the ob/ob strain. Compared with NZB, NZO mice exhibited increased meal frequency, meal duration, and meal size. Body temperature as determined by telemetry with implanted sensors was reduced in NZO mice, but again to a lesser extent than in the ob/ob strain. In striking contrast to ob/ob mice, NZO mice were able to maintain a constant body temperature during a 20-h cold exposure, thus exhibiting a functioning cold-induced thermogenesis. No significant differences in spontaneous home cage activity were observed among NZO, NZB, and ob/ob strains. When mice had access to voluntary running wheels, however, running activity was significantly lower in NZO than NZB mice and even lower in ob/ob mice. These data indicate that obesity in NZO mice, just as in humans, is due to a combination of hyperphagia, reduced energy expenditure, and insufficient physical activity. Because NZO mice differ strikingly from the ob/ob strain in their resistance to cold stress, we suggest that the molecular defects causing hyperphagia in NZO mice are located distal from leptin and its receptor.

Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.

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Long, Kristen B; Burgwin, Chelsea M; Huneke, Richard; Artlett, Carol M; Blankenhorn, Elizabeth P

2014-09-01

Rationale: The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates. Method: We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout. Conclusion: We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.

Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

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Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

2013-02-15

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice.

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Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

2015-01-01

Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS.

Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

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Huan Cai

Full Text Available Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT, ghrelin knockout (ghrelin(-/-, and GOAT knockout (GOAT(-/- mice. Ghrelin(-/- mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/- mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/- and GOAT(-/- mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/- mice, yet potentiated in GOAT(-/- mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/- mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/- and GOAT(-/- mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

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Schouenborg Jens

2008-05-01

Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP knockout mice

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Satoko eHattori

2012-10-01

Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1. Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J x 129SvEv for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased social interaction in Crawley’s three-chamber social approach test, although PACAP KO had no significant impact on social interaction in a home cage. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze and the T-maze, while they did not show any significant abnormalities in the left-right discrimination task in the T-maze. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially

Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice.

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Cordeiro, Aline; de Souza, Luana Lopes; Oliveira, Lorraine Soares; Faustino, Larissa Costa; Santiago, Letícia Aragão; Bloise, Flavia Fonseca; Ortiga-Carvalho, Tania Maria; Almeida, Norma Aparecida Dos Santos; Pazos-Moura, Carmen Cabanelas

2013-02-01

Sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, has been connected to beneficial effects elicited by calorie restriction. Physiological adaptation to starvation requires higher activity of SIRT1 and also the suppression of thyroid hormone (TH) action to achieve energy conservation. Here, we tested the hypothesis that those two events are correlated and that TH may be a regulator of SIRT1 expression. Forty-eight-hour fasting mice exhibited reduced serum TH and increased SIRT1 protein content in liver and brown adipose tissue (BAT), and physiological thyroxine replacement prevented or attenuated the increment of SIRT1 in liver and BAT of fasted mice. Hypothyroid mice exhibited increased liver SIRT1 protein, while hyperthyroid ones showed decreased SIRT1 in liver and BAT. In the liver, decreased protein is accompanied by reduced SIRT1 activity and no alteration in its mRNA. Hyperthyroid and hypothyroid mice exhibited increases and decreases in food intake and body weight gain respectively. Food-restricted hyperthyroid animals (pair-fed to euthyroid group) exhibited liver and BAT SIRT1 protein levels intermediary between euthyroid and hyperthyroid mice fed ad libitum. Mice with TH resistance at the liver presented increased hepatic SIRT1 protein and activity, with no alteration in Sirt1 mRNA. These results suggest that TH decreases SIRT1 protein, directly and indirectly, via food ingestion control and, in the liver, this reduction involves TRβ. The SIRT1 reduction induced by TH has important implication to integrated metabolic responses to fasting, as the increase in SIRT1 protein requires the fasting-associated suppression of TH serum levels.

Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

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Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

2012-01-01

Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

[Analysis of relation between the development of study and literatures about benign positional paroxysmal vertigo published international and domestic].

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Jia, Jianping; Sun, Xiaohui; Dai, Song; Sang, Yuehong

2016-01-01

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that causes vertigo. Study of BPPV has dramatically rapid progress in recent years. We analyze the BPPV growth We searched the international data quantity year by year in database of PubMed, ScienceDirect and WILEY before 2014 respectively, then we searched the domestic data quantity year by year in database of CNKI, VIP and Wanfang Data before 2015 by selecting "Benign paroxysmal positional vertigo" as the keywords. Then we carried out regression analysis with the gathered results in above databases to determine data growth regularity and main factors that affect future development of BPPV. Also, we analyzes published BPPV papers in domestic and international journals. PubMed database contains 808 literatures, ScienceDirect contains 177 database and WILEY contains 46 literatures, All together we collected 1 038 international articles. CNKI contains 440 literatures, VIP contains 580 literatures and WanFang data contains 449 literatures. All together we collected 1 469 domestic literatures. It shows the rising trend of the literature accumulation amount of BPPV. The scattered point diagram of BPPV shows an exponential growing trend, which was growing slowly in the early time but rapidly in recent years. It shows that the development of BPPV has three stages from international arical: exploration period (before 1985), breakthrough period (1986-1998). The deepening stage (after 1998), Chinese literature also has three stages from domestic BPPV precess. Blank period (before the year of 1982), the enlightenment period (1982-2004), the deepening stage (after the year of 2004). In the pregress of BPPV, many outsantding sccholars played an important role in domestic scitifction of researching, which has produced a certain influence in the worldwide.

Failure of post-natal ductus arteriosus closure in prostaglandin transporter-deficient mice

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Chang, Hee-Yoon; Locker, Joseph; Lu, Run; Schuster, Victor L.

2010-01-01

Background Prostaglandin E2 (PGE2) plays a major role both in maintaining patency of the fetal ductus arteriosus (DA) and in closure of the DA after birth. The rate- limiting step in PGE2 signal termination is PGE2 uptake by the transporter PGT. Methods and results To determine the role of PGT in DA closure, we used a gene-targeting strategy to produce mice in which PGT exon 1 was flanked by loxP sites. Successful targeting was obtained since neither mice hypomorphic at the PGT allele (PGT Neo/Neo) nor global PGT knockout mice (PGT −/−) exhibited PGT protein expression; moreover, embryonic fibroblasts isolated from targeted mice failed to exhibit carrier-mediated PGE2 uptake. Although born in a normal Mendelian ratio, no PGT −/− mice survived past post-natal day 1, and no PGT Neo/Neo mice survived past post-natal day 2. Necropsy revealed patent DA with normal intimal thickening but with dilated cardiac chambers. Both PGT Neo/Neo and PGT −/− mice could be rescued through the post-natal period by giving the mother indomethacin before birth. Rescued mice grew normally and had no abnormalities by gross and microscopic post-mortem analysis. In accord with PGT’s known role in metabolizing PGE2, rescued adult PGT −/− mice had lower plasma PGE2 metabolite levels, and higher urinary PGE2 excretion rates, than wild type mice. Conclusions PGT plays a critical role in closure of the DA after birth by ensuring a reduction in local and/or circulating PGE2 concentrations. PMID:20083684

Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice

NARCIS (Netherlands)

Espinosa, J.C.; Andreoletti, O.; Castilla, J.; Herva, M.E.; Morales, M.; Alamillo, E.; San-Segundo, F.D.; Lacroux, C.; Lugan, S.; Salguero, F.J.; Langeveld, J.P.M.; Torres, J.M.

2007-01-01

Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions

Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice

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Ide, Soichiro; Sora, Ichiro; Ikeda, Kazutaka; Minami, Masabumi; Uhl, George R.; Ishihara, Kumatoshi

2014-01-01

The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. In the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female μ-opioid receptor knockout (MOP-KO) mice to reveal the involvement of μ-opioid receptors in stress-induced emotional responses. MOP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice also displayed significantly decreased immobility in a 15 min tail-suspension test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted for 5 consecutive days. The increase in plasma corticosterone concentration induced by tail-suspension, repeated forced swim, or restraint stress was reduced in MOP-KO mice compared with wild-type mice. Corticosterone levels were not different between wild-type and MOP-KO mice before stress exposure. In contrast, although female mice tended to exhibit fewer anxiety-like responses in the tail-suspension test in both genotypes, no significant gender differences were observed in stress-induced emotional responses. These results suggest that MOPs play an important facilitatory role in emotional responses to stress, including anxiety- and depression-like behavior and corticosterone levels. PMID:19596019

Paroxysmal nocturnal haemoglobinuria at Oslo University Hospital 2000-2010.

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Nissen-Meyer, Lise Sofie H; Tjønnfjord, Geir E; Golebiowska, Elzbieta; Kjeldsen-Kragh, Jens; Akkök, Çiğdem Akalın

2015-06-16

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematological disease characterised by chronic haemolysis, pancytopenia and venous thrombosis. The condition is attributable to a lack of control of complement attack on erythrocytes, thrombocytes and leukocytes, and can be diagnosed by means of flow cytometry. In this quality assurance study, we have reviewed information from the medical records of all patients tested for PNH using flow cytometry at our laboratory over a ten-year period. In the period 2000-2010 a total of 28 patients were tested for PNH using flow cytometry at the Department of Immunology and Transfusion Medicine, Oslo University Hospital. We have reviewed the results of these examinations retrospectively together with information from medical records and transfusion data for the patients concerned. Flow cytometry identified 22 patients with PNH: four with classic disease and 18 with PNH secondary to another bone marrow disease. Five patients had atypical thrombosis. Seventeen patients received antithymocyte globulin or drug treatment; of these, six recovered from their bone marrow disease, while six died and five had a need for long-term transfusion. Five patients with life-threatening bone marrow disease underwent allogeneic stem cell transplantation, three of whom died. Six of 22 patients received eculizumab; the need for transfusion has been reduced or eliminated in three patients treated with eculizumab over a longer period. Flow cytometry identified PNH in a majority of patients from whom we obtained samples. Most patients had a PNH clone secondary to bone marrow failure. Atypical thrombosis should be borne in mind as an indication for the test. Treatment with eculizumab is relevant for selected patients with PNH.

The risk factors of acute attack of benign paroxysmal positional vertigo

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Rabiei Sohrab

2010-04-01

Full Text Available ntroduction: Many people suffer from vertigo. Its origin in 85% of cases is otological while in 15% is central etiology. Benign paroxysmal positional vertigo (BPPV is the most common cause of the true vertigo. In this research we evaluated the risk factors of acute attack of BPPV. Materials and Methods: This study was performed on 322 patients, presenting with BPPV. Diagnosis was confirmed by history and Dix-Hallpike manoeuvre. The underling risk factors documented carefully. Data analyzed by SPSS and K.square test. Results: Number of 321 patients (including 201 females and 120 males with BPPV included in our study. Their average age was 41. They showed symptoms for 1 month to 15 years (mean 8 months. Emotional stress was positive in 34% and trauma was the only risk factor in 8.12% patients. Ear surgery and prolonged journey were respectively the main risk factors in 7.2 and 12.8% of patients. Conclusion: The confirmed risk factors of acute attack of BPPV were as trauma, major surgery and ear surgery especially stapedotomy, vestibular  neuronitis and prolonged bedrestriction. Meniere was not considered as risk factor. In our study the psychological conflict was the major risk factor for BPPV. Other new risk factors which introduced for first time included; sleep disorder, fatigue, professional sport, starving and prolonged journey.

Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

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Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

2013-10-15

Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

Inherent and antigen-induced airway hyperreactivity in NC mice

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Tetsuto Kobayashi

1999-01-01

Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

DEFF Research Database (Denmark)

Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

2015-01-01

.05) and peritoneal cavity (80.8% decrease; P challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) ....... knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0...

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

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Yun Seong-Jo

2012-01-01

Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

Effect of single and fractionated x-irradiation on maze learning ability of mice

International Nuclear Information System (INIS)

Aoyama, Takashi; Norimura, Toshiyuki; Nakamura, Takeshi; Yoshikawa, Isao

1976-01-01

Fifty-six-day-old male ddk mice at the starting of the investigation were used as subjects through the experiment for 64 weeks. After 15 days' preliminary training, and 16 times of weekly trial training using complete maze, 15 mice received a single 224 rads of x-rays (S group), another 15 mice received two 112 rads spaced two weeks apart (F group) and another 15 mice were sham-irradiated (Control group). Then those mice were tested on the multiple T-maze with nine-choice points and change of performance was observed in terms of errorchoices by giving one test trial a week. We introduced the concept of ''confusional trials'' as an index for surmising to what extent mice failed to exhibit good maze learning habits. In the results, the F group showed significantly worse performance than the two other groups at early stages, opposite to it the S group exhibited the same, but at late stages after irradiation. The worse performance of F group should be considered to be due to the psychological after-effect to fractionated irradiation and that for S group could be assumed to be due to the acceleration of aging by the irradiation. (auth.)

Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.

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Inoue, Shin-Ichi; Takahara, Shingo; Yoshikawa, Takeo; Niihori, Tetsuya; Yanai, Kazuhiko; Matsubara, Yoichi; Aoki, Yoko

2017-12-01

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of vertebrobasilar artery changes in patients with benign paroxysmal positional vertigo.

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Zhang, Daopei; Zhang, Shuling; Zhang, Hongtao; Xu, Yuming; Fu, Shengqi; Yu, Meng; Ji, Peng

2013-09-11

The aim of this study was to investigate vertebrobasilar artery (VBA) lesions in elderly patients with benign paroxysmal positional vertigo (BPPV) by magnetic resonance angiography. VBA lesions in patients older than 65 years of age with BPPV were prospectively investigated by magnetic resonance angiography. Vascular risk factors, blood vessel changes, and vertigo severity were recorded. Age-matched individuals without BPPV were included in the control group. Of 126 patients screened for this study, 104 were included. Relevant comorbidities included diabetes (12 patients), hypertension (23 patients), and dyslipidemia (20 patients). Findings included left or right vertebral artery (VA) stenosis or occlusion (22 patients, 21.2%), VA tortuosity (25 patients, 24.0%), VA dominance (20 patients, 19.2%), basilar artery (BA) stenosis or occlusion (nine patients, 8.6%), and BA tortuosity (12 patients, 11.5%). These abnormal vessels differed between BPPV patients and the control group (all PVertigo did not differ between the abnormal VA and abnormal BA groups (P>0.05), but did differ between the normal group and the abnormal VA or BA group (PVertigo severity correlated with VA stenosis or occlusion, VA dominance, and unilateral or bilateral VA tortuosity. VBA tortuosity and VA dominance were common in BPPV patients and may contribute toward BPPV.

[Efficacy of Transdermal Patch of Bisoprolol for Paroxysmal Atrial Fibrillation after Open Heart Surgery].

Science.gov (United States)

Yamamoto, Kenji; Yamada, Tomoyuki; Hamuro, Mamoru; Kawatou, Masahide; Enomoto, Sakae

2017-11-01

2014 American Association for Thoracic Surgery (AATS) guidelines recommend beta blocker for prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. In recent years, transdermal patch of bisoprolol (TDPB) has become available in Japan. We examined the efficacy of TDPB for paroxysmal atrial fibrillation (PAF) after open heart surgery. Among 289 patients who had undergone open heart surgery in our hospital from December 2013 to April 2016, 48(16.6%)patients, for whom TDPB was used for PAF, were analyzed retrospectively. The summary of our PAF protocol:HR >80;a sheet of TDPB (4 mg) is pasted, HR≤60;TDPB is removed, HR >140 persisted;another sheet of TDPB is added. Eighteen of the 48 (37.5%) patients recovered sinus rhythm within 24 hours. Six patients( 12.5%), because of persistent tachycardia, shifted to continuous infusion of landiolol. Ten underwent electrical defibrillation during hospitalization. In 3 patients, TDPB was removed due to advanced bradycardia. TDPB could be used safely and feasibly for PAF after open heart surgery.

Perturbed desmosomal cadherin expression in grainy head-like 1-null mice.

Science.gov (United States)

Wilanowski, Tomasz; Caddy, Jacinta; Ting, Stephen B; Hislop, Nikki R; Cerruti, Loretta; Auden, Alana; Zhao, Lin-Lin; Asquith, Stephen; Ellis, Sarah; Sinclair, Rodney; Cunningham, John M; Jane, Stephen M

2008-03-19

In Drosophila, the grainy head (grh) gene plays a range of key developmental roles through the regulation of members of the cadherin gene family. We now report that mice lacking the grh homologue grainy head-like 1 (Grhl1) exhibit hair and skin phenotypes consistent with a reduction in expression of the genes encoding the desmosomal cadherin, desmoglein 1 (Dsg1). Grhl1-null mice show an initial delay in coat growth, and older mice exhibit hair loss as a result of poor anchoring of the hair shaft in the follicle. The mice also develop palmoplantar keratoderma, analogous to humans with DSG1 mutations. Sequence analysis, DNA binding, and chromatin immunoprecipitation experiments demonstrate that the human and mouse Dsg1 promoters are direct targets of GRHL1. Ultrastructural analysis reveals reduced numbers of abnormal desmosomes in the interfollicular epidermis. These findings establish GRHL1 as an important regulator of the Dsg1 genes in the context of hair anchorage and epidermal differentiation, and suggest that cadherin family genes are key targets of the grainy head-like genes across 700 million years of evolution.

Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice.

Science.gov (United States)

Xu, Xin; Shan, Bin; Liao, Cai-Hu; Xie, Jian-Hua; Wen, Ping-Wei; Shi, Jia-Yi

2015-11-01

A water-soluble polysaccharide (MCP) was isolated from the fruits of Momordica charantia L., and the hypoglycemic effects of MCP were investigated in both normal healthy and alloxan-induced diabetic mice. MCP was orally administered once a day after 3 days of alloxan-induction at 100, 200 and 300mg/kg body weight for 28 day. Results showed that fasting blood glucose level (BGL) was significantly decreased, whereas the glucose tolerance was marked improvement in alloxan-induced diabetic mice, and loss in body weight was also prevented in diabetic mice compared to the diabetic control group. The dosage of 300mg/kg body weight exhibited the best effects. In addition, MCP did not exhibit any toxic symptoms in the limited toxicity evaluation in mice. The results suggest that MCP possess significantly dose-dependent anti-diabetic activity on alloxan-induced diabetic mice. Hence, MCP can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Myogenin regulates exercise capacity but is dispensable for skeletal muscle regeneration in adult mdx mice.

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Eric Meadows

Full Text Available Duchenne muscular dystrophy (DMD is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myog(flox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myog(flox/flox mice (mdx, Myog(flox/flox mice (wild-type, and mdx:Myog(floxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted. mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function.

A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice

Science.gov (United States)

Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

2015-01-01

Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS. PMID:26134356

The complex interrelations between two paroxysmal disorders: headache and epilepsy.

Science.gov (United States)

Cianchetti, Carlo; Avanzini, Giuliano; Dainese, Filippo; Guidetti, Vincenzo

2017-06-01

The interrelations between headache/migraine and epileptic seizures are an interesting topic, still lacking a systematization, which is the objective of the present revision. We organize the general setting on: (a) a distinction between pre-ictal, ictal, post-ictal and inter-ictal headaches, assuming "ictal" as epileptic seizure, and (b) the kind of headache, if it is of migraine type or not. Concerning pre-ictal migraine/headache, the necessity of its differentiation from an epileptic headache presenting as an aura of a seizure is stressed; this is connected with the indefiniteness of the term "migralepsy". The term "migraine aura-triggered seizure" should be used only in front of a proven triggering effect of migraine. Epileptic headache (called also "ictal epileptic headache") is a well-characterized entity, in which different types of head pain may occur and an ictal EEG is necessary for the diagnosis. It may present as an isolated event ("isolated epileptic headache"), requiring a differential diagnosis from other kinds of headache, or it may be uninterruptedly followed by other epileptic manifestations being in this case easily identifiable as an epileptic aura. Hemicrania epileptica is a very rare variant of epileptic headache, characterized by the ipsilaterality of head pain and EEG paroxysms. Ictal non-epileptic headache needs to be differentiated from epileptic headache. Post-ictal headaches are a frequent association of headache with seizures, particularly in patients suffering also from inter-ictal headache-migraine. The reported systematization of the topic led us to suggest a classification which is shown in Appendix.

Epidemiology of benign paroxysmal positional vertigo: a population based study

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von Brevern, M; Radtke, A; Lezius, F; Feldmann, M; Ziese, T; Lempert, T; Neuhauser, H

2007-01-01

Objectives To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. Methods Cross‐sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting <1 min without concomitant neurological symptoms and invariably provoked by typical changes in head position. In a concurrent validation study (n = 61) conducted in two specialised dizziness clinics, BPPV was detected by our telephone interview with a specificity of 92% and a sensitivity of 88% (positive predictive value 88%, negative predictive value 92%). Results BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. Conclusion BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs. PMID:17135456

Relationship between the effect of dietary fat on swimming endurance and energy metabolism in aged mice.

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Zhang, Guihua; Shirai, Nobuya; Suzuki, Hiramitsu

2011-10-01

The aim of this study was to investigate the effect of different dietary fats on alterations in endurance, energy metabolism, and plasma levels of interleukin-6 (IL-6) and minerals in mice. Male mice (aged 58 weeks) were fed diets containing 6% safflower oil, fish oil, or lard for 12 weeks. Swimming time to exhaustion, energy metabolism, and plasma IL-6 levels were subsequently determined. Mice fed safflower oil exhibited a marked increase in swimming time compared to the baseline level. Mice fed lard exhibited a significant decrease in swimming time, while mice on a fish oil diet exhibited a small decrease in swimming time. The final swimming time of mice fed safflower oil was significantly longer than that of animals fed lard. This improvement in endurance with dietary safflower oil was accompanied by decreased accumulation of lactate and less glycogen depletion during swimming. In the safflower oil group, muscle carnitine palmitoyltransferase activity increased significantly after swimming, while the plasma non-esterified fatty acid concentration decreased significantly. A trend to increased plasma IL-6 levels was observed in sedentary animals on a safflower oil diet compared to those on a lard diet. These results suggest that dietary safflower oil improves the swimming endurance of aged mice to a greater extent than lard, and that this effect appears to involve glycogen sparing through increased fatty acid utilization. Copyright © 2011 S. Karger AG, Basel.

Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice.

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Pierre, Christina C; Longo, Joseph; Mavor, Meaghan; Milosavljevic, Snezana B; Chaudhary, Roopali; Gilbreath, Ebony; Yates, Clayton; Daniel, Juliet M

2015-09-01

Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine. Copyright © 2015 Elsevier B.V. All rights reserved.

Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long-term follow-up study.

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Gul, Enes E; Pal, Raveen; Caldwell, Jane; Boles, Usama; Hopman, Wilma; Glover, Benedict; Michael, Kevin A; Redfearn, Damian; Simpson, Chris; Abdollah, Hoshiar; Baranchuk, Adrian

2017-07-01

Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet. To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence. Sixty-two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P-wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography. Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty-seven patients were male. During a mean follow-up period of 49.8 ± 22 months (range 12-60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12-9.93; p = .03). IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence. © 2016 Wiley Periodicals, Inc.

GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

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Brown-Borg, Holly M.; Bartke, Andrzej

2012-01-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection

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Liyuan Cui

2017-06-01

Full Text Available Human infants with congenital Zika virus (ZIKV infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus.

[Positioning diagnosis of benign positional paroxysmal vertigo by VNG].

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Wang, Na; Chen, Taisheng; Lin, Peng; Song, Wei; Dong, Hong

2009-07-01

To analyze the value of positioning diagnosis of VNG (Videonystagmograph) in patients with benign paroxysmal positional vertigo (BPPV). One hundred and twenty-six patients with BPPV were enrolled in this retrospective study. Their positional nystagmus recorded by VNG in Dix-Hallpike and roll tests were analyzed to summarize the characteristics of nystagmus on nystagmography of various BPPV. Of 126 patients with BPPV diagnosed in our center, the posterior semicircular canals (PSC) were involved in 98 patients (77.8%), whereas the horizontal semicircular canal (HSC) and anterior semicircular canal (ASC) were involved in 17 (13.5%) and 5 (3.9%), respectively. Six patients (4.8%) confirmed combined-BPPV had HSC-BPPV and ipsilateral PSC-BPPV. Twenty-eight patients with PSC-BPPV had reversal phase on nystagmography. The nystagmus of patients with P/ASC-canalithiasis showed upward/downward on the vertical phase of nystagmography and orientated the opposite side on horizontal phase in the head hanging position, and the nystagmus reversed when returned to sit. Nystagmus on horizontal phase could be provoked when the head turned to both sides of the roll tests in patients with HSC-BPPV. If the nystagmus and the head-turning shared the same direction, then HSC-canalithiasis was confirmed, and the direction of the head-turning which provoked the stronger nystagmus indicates the lesion side. If the nystagmus and the head-turning had the opposite direction, then HSC-cupulolithiasis was confirmed, and the direction of the head-turning which provoked the weaker nystagmus indicates the lesion side. Positional nystagmus can be recorded objectively using VNG, According to which positioning the semicircular canal involved would be easier and more accurate. The recording conserved also could be helpful for clinical diagnosis and repositioning of BPPV.

Preference for and discrimination of paintings by mice.

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Shigeru Watanabe

Full Text Available I measured preference for paintings (Renoir vs. Picasso or Kandinsky vs. Mondrian in mice. In general mice did not display a painting preference except for two mice: one preferred Renoir to Picasso, and the other preferred Kandinsky to Mondrian. Thereafter, I examined discrimination of paintings with new mice. When exposure to paintings of one artist was associated with an injection of morphine (3.0 mg/kg, mice displayed conditioned preference for those paintings, showing discrimination of paintings by Renoir from those by Picasso, and paintings by Kandinsky from those by Mondrian after the conditioning. They also exhibited generalization of the preference to novel paintings of the artists. After conditioning with morphine for a set of paintings consisting of two artists, mice showed discrimination between two sets of paintings also from the two artists but not in association with morphine. These results suggest that mice can discriminate not only between an artist's style but also among paintings of the same artist. When mice were trained to discriminate a pair of paintings by Kandinsky and Renoir in an operant chamber equipped with a touch screen, they showed transfer of the discrimination to new pairs of the artists, but did not show transfer of discrimination of paintings by other artists, suggesting generalization.

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

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Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

2016-11-01

To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

Tetranectin Knockout Mice Develop Features of Parkinson Disease

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Er-song Wang

2014-07-01

Full Text Available Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD. Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN gene (TN-/- and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

Neuronal modulation of lung injury induced by polymeric hexamethylene diisocyanate in mice

International Nuclear Information System (INIS)

Lee, C.-T.; Poovey, Halet G.; Rando, Roy J.; Hoyle, Gary W.

2007-01-01

1,6-Hexamethylene diisocyanate biuret trimer (HDI-BT) is a nonvolatile isocyanate that is a component of polyurethane spray paints. HDI-BT is a potent irritant that when inhaled stimulates sensory nerves of the respiratory tract. The role of sensory nerves in modulating lung injury following inhalation of HDI-BT was assessed in genetically manipulated mice with altered innervation of the lung. Knockout mice with a mutation in the low-affinity nerve growth factor receptor (NGFR), which have decreased innervation by nociceptive nerve fibers, and transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter, which have increased innervation of the airways, were exposed to HDI-BT aerosol and evaluated at various times after exposure. NGFR knockout mice exhibited significantly more, and CCSP-NGF transgenic mice exhibited significantly less injury and inflammation compared with wild-type mice, indicative of a protective effect of nociceptive nerves on the lung following HDI-BT inhalation. Transgenic mice overexpressing the tachykinin 1 receptor (Tacr1) in lung epithelial cells also showed less severe injury and inflammation compared with wild-type mice after HDI-BT exposure, establishing a role for released tachykinins acting through Tacr1 in mediating at least part of the protective effect. Treatment of lung fragments from Tacr1 transgenic mice with the Tacr1 ligand substance P resulted in increased cAMP accumulation, suggesting this compound as a possible signaling mediator of protective effects on the lung following nociceptive nerve stimulation. The results indicate that sensory nerves acting through Tacr1 can exert protective or anti-inflammatory effects in the lung following isocyanate exposure

Recurrence in Benign Paroxysmal Positional Vertigo: A Large, Single-Institution Study.

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Luryi, Alexander L; Lawrence, Juliana; Bojrab, Dennis I; LaRouere, Michael; Babu, Seilesh; Zappia, John; Sargent, Eric W; Chan, Eleanor; Naumann, Ilka; Hong, Robert S; Schutt, Christopher A

2018-04-11

To report rates of recurrence in benign paroxysmal positional vertigo (BPPV) and associated patient and disease factors. Retrospective chart review. Single high-volume otology practice. Patients diagnosed with BPPV from 2007 to 2016 with documented resolution of symptoms. Diagnostic and particle repositioning maneuvers for BPPV. BPPV recurrence, time to recurrence, and ear(s) affected at recurrence. A total of 1,105 patients meeting criteria were identified. Of this population, 37% had recurrence of BPPV in either ear or both ears. Overall same-ear recurrence rate was 28%; 76% of recurrences involved the same ear(s) as initial presentation. Recurrences that occurred after longer disease-free intervals were more likely to involve the opposite ear than early recurrences (p = 0.02). Female sex (40.4% versus 32.7%, p = 0.01) and history of previous BPPV (57.5% versus 32.4%, p diabetes mellitus, and traumatic etiology were not. Approximately, half (56%) of recurrences occurred within 1 year of resolution. A large single-institution study of recurrence in BPPV is presented along with Kaplan-Meier disease-free survival curves. Female sex and history of previous BPPV were associated with increased recurrence, while previously suspected risk factors for recurrence including history of Menière's disease, diabetes, and trauma were not. Remote recurrence is more likely to involve the contralateral ear than early recurrence. These data solidify the expected course of treated BPPV allowing for improved clinical care and patient counseling.

Otolith organ function according to subtype of benign paroxysmal positional vertigo.

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Lee, Sun K; Kim, Su J; Park, Moon S; Byun, Jae Y

2014-04-01

The clinical features and treatment outcomes of benign paroxysmal positional vertigo (BPPV) are known to be different depending on the type of and involved canal. This difference could be due to differences in the functional change of the otolith organ. Case series. Forty-nine patients were diagnosed to primary BPPV; 18 were categorized as posterior canal canalolithiasis (PC canalolithiasis), and 31 were categorized as horizontal canal (HC) BPPV with canalolithiasis or cupulolithiasis (HC canalolithiasis or HC cupulolithiasis). Diagnostic interventions to measure vestibular functions were performed such as electronystagmography (ENG), videonystagmography (VNG), and static and dynamic subjective visual vertical (SVV). BPPV was confirmed with nystagmus during positioning/positional test under ENG and VNG. Static SVV was recorded with a light-emitting diode (LED) bar located in front of the patients before eccentric rotation and dynamic SVV was recorded during eccentric rotation with the LED bar. SVV angles were read by the examiner and analyzed. The measured values were compared to those of normal controls and each other. Dynamic SVV toward the lesion side in all subtypes of BPPV were significantly different from those of the controls; HC cupulolithiasis showed significantly lower values than those of PC canalolithiasis and HC canalolithiasis. HC cupulolithiasis shows a lesser degree of utricular dysfunction compared with other subtypes. It could postulate the difference of pathophysiology between canalolithiasis and cupulolithiasis. 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Inner ear dysfunction in caspase-3 deficient mice

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Woo Minna

2011-10-01

Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

Enhanced susceptibility to stress and seizures in GAD65 deficient mice.

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Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D; Koh, Sookyong

2018-01-01

Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.

Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice.

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Fazal, Loubina; Azibani, Feriel; Bihry, Nicolas; Coutance, Guillaume; Polidano, Evelyne; Merval, Régine; Vodovar, Nicolas; Launay, Jean-Marie; Delcayre, Claude; Samuel, Jane-Lise

2014-06-01

Studies have shown that aldosterone would have angiogenic effects and therefore would be beneficial in the context of cardiovascular diseases. We thus investigated the potential involvement of aldosterone in triggering a cardiac angiogenic response in the context of type-2 diabetes and the molecular pathways involved. Male 3-wk-old aldosterone synthase (AS)-overexpressing mice and their control wild-type (WT) littermates were fed a standard or high-fat, high-sucrose (HFHS) diet. After 6 mo of diet treatment, mice were euthanized, and cardiac samples were assayed by RT-PCR, immunoblotting, and immunohistology. HFHS diet induced type-2 diabetes in WT (WT-D) and AS (AS-D) mice. VEGFa mRNAs decreased in WT-D (-43%, P<0.05 vs. WT) and increased in AS-D mice (+236%, P< 0.01 vs. WT-D). In WT-D mouse hearts, the proapoptotic p38MAPK was activated (P<0.05 vs. WT and AS-D), whereas Akt activity decreased (-64%, P<0.05 vs. WT). The AS mice, which exhibited a cardiac up-regulation of IGF1-R, showed an increase in Akt phosphorylation when diabetes was induced (P<0.05 vs. WT and AS-D). Contrary to WT-D mice, AS-D mouse hearts did not express inflammatory markers and exhibited a normal capillary density (P<0.05 vs. WT-D). To our knowledge, this is the first study providing new insights into the mechanisms whereby aldosterone prevents diabetes-induced cardiac disorders. © FASEB.

Differential replication of foot-and-mouth disease viruses in mice determine lethality

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Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

Impaired spatial and contextual memory formation in galectin-1 deficient mice

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Sakaguchi Masanori

2011-09-01

Full Text Available Abstract Galectins are a 15 member family of carbohydrate-binding proteins that have been implicated in cancer, immunity, inflammation and development. While galectins are expressed in the central nervous system, little is known about their function in the adult brain. Previously we have shown that galectin-1 (gal-1 is expressed in the adult hippocampus, and, in particular, in putative neural stem cells in the subgranular zone. To evaluate how gal-1 might contribute to hippocampal memory function here we studied galectin-1 null mutant (gal-1-/- mice. Compared to their wildtype littermate controls, gal-1-/- mice exhibited impaired spatial learning in the water maze and contextual fear learning. Interestingly, tone fear conditioning was normal in gal-1-/- mice suggesting that loss of gal-1 might especially impact hippocampal learning and memory. Furthermore, gal-1-/- mice exhibited normal motor function, emotion and sensory processing in a battery of other behavioral tests, suggesting that non-mnemonic performance deficits are unlikely to account for the spatial and contextual learning deficits. Together, these data reveal a role for galectin-carbohydrate signalling in hippocampal memory function.

The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice.

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Kim, Jeongjun; Lee, Hyunghee; Lim, Jonghoon; Lee, Haerim; Yoon, Seolah; Shin, Soon Shik; Yoon, Michung

2017-08-01

Increasing evidence indicates that angiogenesis inhibitors regulate obesity. This study aimed to determine whether the lemon balm extract ALS-L1023 inhibits diet-induced obesity and nonalcoholic fatty liver disease (NAFLD) in female ovariectomized (OVX) mice. OVX mice received a low fat diet (LFD), a high fat diet (HFD) or HFD supplemented with ALS-L1023 (ALS-L1023) for 15 weeks. HFD mice exhibited increases in visceral adipose tissue (VAT) angiogenesis, body weight, VAT mass and VAT inflammation compared with LFD mice. In contrast, all of these effects were reduced in ALS-L1023 mice compared with HFD mice. Serum lipids and liver injury markers were improved in ALS-L1023 mice. Hepatic lipid accumulation, inflammatory cells and collagen levels were lower in ALS-L1023 mice than in HFD mice. ALS-L1023 mice exhibited a tendency to normalize hepatic expression of genes involved in lipid metabolism, inflammation and fibrosis to levels in LFD mice. ALS-L1023 also induced Akt phosphorylation and increased Nrf2 mRNA expression in livers of obese mice. Our results indicate that the angiogenesis inhibitor ALS-L1023 can regulate obesity, hepatic steatosis and fibro-inflammation, in part through improvement of VAT function, in obese OVX mice. These findings suggest that angiogenesis inhibitors may contribute to alleviation of NAFLD in post-menopausal women with obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immersive Exhibitions

DEFF Research Database (Denmark)

Achiam, Marianne

2015-01-01

The immersive exhibition is a specialized exhibition genre in museums, which creates the illusion of time and place by representing key characteristics of a reference world and by integrating the visitor in this three-dimensionally reconstructed world (Mortensen 2010). A successful representation...... of the reference world depends on three criteria: whether the exhibition is staged as a coherent whole with all the displayed objects supporting the representation, whether the visitor is integrated as a component of the exhibition, and whether the content and message of the exhibition become dramatized...

Vestibular evoked myogenic potentials and digital vectoelectronystagmography's study in patients with benign paroxysmal positional vertigo

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Lira-Batista, Marta Maria da Silva

2013-04-01

Full Text Available Introduction: Benign Paroxysmal Positional Vertigo (BPPV is a very common vestibular disorder characterized by brief but intense attacks of rotatory vertigo triggered by simple rapid movement of the head. The integrity of the vestibular pathways can be assessed using tests such as digital vectoelectronystagmography (VENG and vestibular evoked myogenic potentials (VEMP. Aim: This study aimed to determine the VEMP findings with respect to latency, amplitude, and waveform peak to peak and the results of the oculomotor and vestibular components of VENG in patients with BPPV. Method: Although this otoneurological condition is quite common, little is known of the associated VEMP and VENG changes, making it important to research and describe these results. Results: We examined the records of 4438 patients and selected 35 charts after applying the inclusion and exclusion criteria. Of these, 26 patients were women and 9 men. The average age at diagnosis was 52.7 years, and the most prevalent physiological cause, accounting for 97.3% of cases, was ductolithiasis. There was a statistically significant association between normal hearing and mild contralateral sensorineural hearing loss. The results of the oculomotor tests were within the normal reference ranges for all subjects. Patients with BPPV exhibited symmetrical function of the semicircular canals in their synergistic pairs (p < 0.001. The caloric test showed statistically normal responses from the lateral canals. The waveforms of all patients were adequate, but the VEMP results for the data-crossing maneuver with positive positioning showed a trend toward a relationship for the left ear Lp13. There was also a trend towards an association between normal reflexes in the caloric test and the inter-peak VEMP of the left ear. It can be concluded that although there are some differences between the average levels of the VENG and VEMP results, these differences were not statistically significant

Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo

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Guilherme Webster

2015-08-01

Full Text Available INTRODUCTION: Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo.OBJECTIVE: To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV.METHODS: A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal.RESULTS: The RR for hyperinsulinism was 4.66 and p = 0.0015. Existing hyperglycemia showed an RR = 2.47, with p = 0.0123. Glucose intolerance had a RR of 0.63, with p = 0.096. When the examination was within normal limits, the result was RR = 0.2225 and p = 0.030.DISCUSSION: Metabolic changes can cause dizziness and vertigo and are very common in people who have cochleovestibular disorders. However, few studies discuss the relationship between idiopathic BPPV and alterations in carbohydrate metabolism. In the present study, we found that both hyperglycemia and hyperinsulinemia are risk factors for the recurrence of BPPV, whereas a normal test was considered a protective factor; all these were statistically significant. Glucose intolerance that was already present was not statistically significant in the group evaluated.CONCLUSION: Hyperinsulinemia and hyperglycemia are risk factors for the recurrence of idiopathic BPPV and a normal exam is considered a protective factor.

[Objective characteristics of nystagmus in horizontal semicircular canal benign paroxysmal positional vertigo].

Science.gov (United States)

Chen, Fei-yun; Chen, Tai-sheng; Wen, Chao; Li, Shan-shan; Lin, Peng; Zhao, Hui; Liu, Qiang

2013-08-01

To discuss the objective characteristics and mechanism of nystagmus direction, intensity and time in horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) . A total of 233 patients with HSC-BPPV, whereas 179 horizontal semicircular canalithasis (HSC-Can) and 54 horizontal semicircular cupulolithiasis (HSC-Cup) were involved respectively. The induced nystagmus in roll tests recorded by video-nystagmograph(VNG) , whose direction, intensity and time characteristics were compared in various BPPV. Horizontal nystagmus was both induced by turning left or right in HSC-BPPV roll tests. The direction of the induced nystagmus was the same with turning in HSC-Can. The latency, duration time and intensity ([AKx(-)D] ± s) turning to lesion and normal side were (1.922 ± 1.501)s and (1.447 ± 0.855)s, (25.620 ± 10.409)s, and (22.110 ± 10.931)s, (56.441 ± 33.168)°/s and (24.239 ± 13.892) °/s in HSC-Can. The latency, duration time and intensity turning to lesion side were larger than normal side (t = 3.715, 15.219 and 4.070, P 0.05). The induced nystagmus intensity of head to two sides in roll tests for HSC-BPPV both follow Ewald's law, and the ratio between stronger and weaker are both 2: 1. These nystagmus parameters of VNG in roll tests are an objective guideline for BPPV diagnosis.

Bex1 knock out mice show altered skeletal muscle regeneration

International Nuclear Information System (INIS)

Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

2007-01-01

Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca 2+ /CaM may be involved in skeletal muscle regeneration

The PRRT2 knockout mouse recapitulates the neurological diseases associated with PRRT2 mutations.

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Michetti, Caterina; Castroflorio, Enrico; Marchionni, Ivan; Forte, Nicola; Sterlini, Bruno; Binda, Francesca; Fruscione, Floriana; Baldelli, Pietro; Valtorta, Flavia; Zara, Federico; Corradi, Anna; Benfenati, Fabio

2017-03-01

Heterozygous and rare homozygous mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia episodic ataxia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function. Recently, an important role for PRTT2 in the neurotransmitter release machinery, brain development and synapse formation has been uncovered. In this work, we have characterized the phenotype of a mouse in which the PRRT2 gene has been constitutively inactivated (PRRT2 KO). β-galactosidase staining allowed to map the regional expression of PRRT2 that was more intense in the cerebellum, hindbrain and spinal cord, while it was localized to restricted areas in the forebrain. PRRT2 KO mice are normal at birth, but display paroxysmal movements at the onset of locomotion that persist in the adulthood. In addition, adult PRRT2 KO mice present abnormal motor behaviors characterized by wild running and jumping in response to audiogenic stimuli that are ineffective in wild type mice and an increased sensitivity to the convulsive effects of pentylentetrazol. Patch-clamp electrophysiology in hippocampal and cerebellar slices revealed specific effects in the cerebellum, where PRRT2 is highly expressed, consisting in a higher excitatory strength at parallel fiber-Purkinje cell synapses during high frequency stimulation. The results show that the PRRT2 KO mouse reproduces the motor paroxysms present in the human PRRT2-linked pathology and can be proposed as an experimental model for the study of the pathogenesis of the disease as well as for testing personalized therapeutic approaches. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

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Amanda Clause

2017-06-01

Full Text Available Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.

Two-year body composition analyses of long-lived GHR null mice.

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Berryman, Darlene E; List, Edward O; Palmer, Amanda J; Chung, Min-Yu; Wright-Piekarski, Jacob; Lubbers, Ellen; O'Connor, Patrick; Okada, Shigeru; Kopchick, John J

2010-01-01

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show that GHR-/- mice have a greater percent fat mass with no significant difference in absolute fat mass throughout life. Lean mass shows an opposite trend with percent lean mass not significantly different between genotypes but absolute mass reduced in GHR-/- mice. Differences in body composition are more pronounced in male than in female mice, and both genders of GHR-/- mice show specific enlargement of the subcutaneous adipose depot. Along with previously published data, these results suggest a consistent and intriguing protective effect of excess fat mass in the subcutaneous region.

Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

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Ho, Horace T. B.; Chung, Sookja K.; Law, Janice W. S.; Ko, Ben C. B.; Tam, Sidney C. F.; Brooks, Heddwen L.; Knepper, Mark A.; Chung, Stephen S. M.

2000-01-01

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus. PMID:10913167

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

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Hale Gregory

2009-11-01

Full Text Available Abstract Background PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.

Otolith dysfunction alters exploratory movement in mice.

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Blankenship, Philip A; Cherep, Lucia A; Donaldson, Tia N; Brockman, Sarah N; Trainer, Alexandria D; Yoder, Ryan M; Wallace, Douglas G

2017-05-15

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiparameter FLAER-based flow cytometry for screening of paroxysmal nocturnal hemoglobinuria enhances detection rates in patients with aplastic anemia.

Science.gov (United States)

Sachdeva, Man Updesh Singh; Varma, Neelam; Chandra, Dinesh; Bose, Parveen; Malhotra, Pankaj; Varma, Subhash

2015-05-01

Flow cytometry is the gold standard methodology for screening of paroxysmal nocturnal hemoglobinuria. In the last few years, proaerolysin conjugated with fluorescein (FLAER) has become an important component of antibody panel used for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clone. This study aimed to compare PNH clone detection by flow cytometry in the pre-FLAER era versus the FLAER era. This was a retrospective analysis of 4 years and included 1004 individuals screened for PNH clone, either presenting as hemolytic anemia or as aplastic anemia. In the pre-FLAER time period, the RBCs and neutrophils were screened with antibodies against CD55 and CD59. With the introduction of FLAER, neutrophils were screened with FLAER/CD24/CD15 and monocytes with FLAER/CD14/CD33 combination. A comparative analysis was done for detection of PNH clone in aplastic anemia patients versus non-aplastic anemia patients, as well as between pre-FLAER and FLAER era. Out of a total of 1004 individuals, 59 (5.8%) were detected to have PNH clone positivity. The frequency of PNH clone detected in aplastic anemia and non-aplastic anemia groups was 12.02 and 3.36%, respectively. The detection rate of PNH clone increased from 4.5% (32/711) in the pre-FLAER era to 9.2% (27/293) with the introduction of FLAER. However, this increase could be attributed to increased detection of PNH clone in the aplastic anemia group, which showed a significant increase from 8.3 to 18.2% after use of FLAER. In the non-aplastic group, PNH clone was detected with similar frequencies before and after use of FLAER (3.2 versus 3.8%, respectively). Mean PNH clone size was lower in the aplastic anemia group when compared with the non-aplastic group. RBCs always showed a lower clone size than neutrophils. PNH clone on neutrophils and monocytes was however similar. Inclusion of FLAER increases the sensitivity of the test which is especially useful in picking up small PNH clones in patients of aplastic anemia.

A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission

DEFF Research Database (Denmark)

Nielsen, Jacob; Fejgin, Kim; Sotty, Florence

2017-01-01

on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1...... and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes, Df(h1q21)/+ mice exhibited reduced...

Microarray Analysis of Iris Gene Expression in Mice with Mutations Influencing Pigmentation

Science.gov (United States)

Trantow, Colleen M.; Cuffy, Tryphena L.; Fingert, John H.; Kuehn, Markus H.

2011-01-01

Purpose. Several ocular diseases involve the iris, notably including oculocutaneous albinism, pigment dispersion syndrome, and exfoliation syndrome. To screen for candidate genes that may contribute to the pathogenesis of these diseases, genome-wide iris gene expression patterns were comparatively analyzed from mouse models of these conditions. Methods. Iris samples from albino mice with a Tyr mutation, pigment dispersion–prone mice with Tyrp1 and Gpnmb mutations, and mice resembling exfoliation syndrome with a Lyst mutation were compared with samples from wild-type mice. All mice were strain (C57BL/6J), age (60 days old), and sex (female) matched. Microarrays were used to compare transcriptional profiles, and differentially expressed transcripts were described by functional annotation clustering using DAVID Bioinformatics Resources. Quantitative real-time PCR was performed to validate a subset of identified changes. Results. Compared with wild-type C57BL/6J mice, each disease context exhibited a large number of statistically significant changes in gene expression, including 685 transcripts differentially expressed in albino irides, 403 in pigment dispersion–prone irides, and 460 in exfoliative-like irides. Conclusions. Functional annotation clusterings were particularly striking among the overrepresented genes, with albino and pigment dispersion–prone irides both exhibiting overall evidence of crystallin-mediated stress responses. Exfoliative-like irides from mice with a Lyst mutation showed overall evidence of involvement of genes that influence immune system processes, lytic vacuoles, and lysosomes. These findings have several biologically relevant implications, particularly with respect to secondary forms of glaucoma, and represent a useful resource as a hypothesis-generating dataset. PMID:20739468

Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection.

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Cui, Liyuan; Zou, Peng; Chen, Er; Yao, Hao; Zheng, Hao; Wang, Qian; Zhu, Jing-Ning; Jiang, Shibo; Lu, Lu; Zhang, Jiayi

2017-06-01

Human infants with congenital Zika virus (ZIKV) infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Kinetics of Hesperetin for Liver Fortification in gamma-Irradiated Mice

International Nuclear Information System (INIS)

Tawfik, S.S.

2011-01-01

Hesperetin (3',5,7-trihydroxy-4'-methoxyflavonone), the aglycone of the flavanone glycosides hesperidin, exerts pharmacological properties such as antioxidation, anti-inflammation, blood lipid and cholesterol lowering is effectively used as a supplemental agent in the treatment protocols of complementary settings. Four groups were prepared: Control group: received 0.5 ml normal saline for 7 days. Hesperetin group: Mice received 7 doses of hesperetin injections (100 mg/ kg body wt/ day). Irradiated group: Mice submitted to total body irradiation with 4 Gy gamma-rays. Protected group (Hesperetin plus irradiation): Mice received hesperetin for 7 days and then submitted to 4 Gy of gamma-rays. The mice were sacrificed at 24 h, 1 week and 2 weeks after the end of the experimental treatments. Irradiated mice exhibited significant hyperglycaemia and augmented hepatic glycogen after the first day and 1 week but significant hypoglycemia and reducing hepatic glycogen after 2 weeks. Also, they exhibited significant increased serum total cholesterol (TC) and triacylglycerols (TG) and decreased hepatic TC and TG after 1 and 2 weeks. This treatment also resulted in a significant dropped in hepatic glucokinase (GK), glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities after 1 and 2 weeks. Hesperetin injections modulated the serum glucose and hepatic glycogen, adjusted TC and TG in both serum and liver and ameliorated the lessening in hepatic GK, G6P and PEPCK. The attending results demonstrated that hesperetn treatment modulated the biochemical symptoms of radiation disorders in mice. In conclusion, administration of hesperetin may have a useful role in modulating oxidative stress induced by exposure to gamma-radiation by improving the natural antioxidant mechanism and fortification liver functions

Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

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Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

2016-12-17

Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1

International Nuclear Information System (INIS)

Wang, Ai-Guo; Seo, Sang-Beom; Moon, Hyung-Bae; Shin, Hye-Jun; Kim, Dong Hoon; Kim, Jin-Man; Lee, Tae-Hoon; Kwon, Ho Jeong; Yu, Dae-Yeul; Lee, Dong-Seok

2005-01-01

It is generally thought that histone deacetylases (HDACs) play important roles in the transcriptional regulation of genes. However, little information is available concerning the specific functions of individual HDACs in disease states. In this study, two transgenic mice lines were established which harbored the human HDAC1 gene. Overexpressed HDAC1 was detected in the nuclei of transgenic liver cells, and HDAC1 enzymatic activity was significantly higher in the transgenic mice than in control littermates. The HDAC1 transgenic mice exhibited a high incidence of hepatic steatosis and nuclear pleomorphism. Molecular studies showed that HDAC1 may contribute to nuclear pleomorphism through the p53/p21 signaling pathway

Diagnosis and Management of Patients with Paroxysmal Sympathetic Hyperactivity following Acute Brain Injuries Using a Consensus-Based Diagnostic Tool: A Single Institutional Case Series.

Science.gov (United States)

Godo, Shigeo; Irino, Shigemi; Nakagawa, Atsuhiro; Kawazoe, Yu; Fujita, Motoo; Kudo, Daisuke; Nomura, Ryosuke; Shimokawa, Hiroaki; Kushimoto, Shigeki

2017-09-01

Paroxysmal sympathetic hyperactivity (PSH) is a distinct syndrome of episodic sympathetic hyperactivities following severe acquired brain injury, characterized by paroxysmal transient fever, tachycardia, hypertension, tachypnea, excessive diaphoresis and specific posturing. PSH remains to be an under-recognized condition with a diagnostic pitfall especially in the intensive care unit (ICU) settings due to the high prevalence of concomitant diseases that mimic PSH. A consensus set of diagnostic criteria named PSH-Assessment Measure (PSH-AM) has been developed recently, which is consisted of two components: a diagnosis likelihood tool derived from clinical characteristics of PSH, and a clinical feature scale assigned to the severity of each sympathetic hyperactivity. We herein present a case series of patients with PSH who were diagnosed and followed by using PSH-AM in our tertiary institutional medical and surgical ICU between April 2015 and March 2017 in order to evaluate the clinical efficacy of PSH-AM. Among 394 survivors of 521 patients admitted with acquired brain injury defined as acute brain injury at all levels of severity regardless of the presence of altered consciousness, including traumatic brain injury, stroke, infectious disease, and encephalopathy, 6 patients (1.5%) were diagnosed as PSH by using PSH-AM. PSH-AM served as a useful scoring system for early objective diagnosis, assessment of severity, and serial evaluation of treatment efficacy in the management of PSH in the ICU settings. In conclusion, critical care clinicians should consider the possibility of PSH and can use PSH-AM as a useful diagnostic and guiding tool in the management of PSH.

Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice

OpenAIRE

Salonurmi, T.; Parikka, M.; Kontusaari, S.; Pirila, E.; Munaut, Carine; Salo, T.; Tryggvason, K.

2004-01-01

We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymograph...

Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice

Directory of Open Access Journals (Sweden)

Yi-Ming Chen

2014-12-01

Full Text Available Fucoidan (FCD is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002 and endurance swimming time (p = 0.0195 in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001 and ammonia (p = 0.0025, and also an increase in glucose level (p < 0.0001 after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.

Exhibit Engineering

DEFF Research Database (Denmark)

Mortensen, Marianne Foss

Science museums define the objectives of their exhibitions in terms of visitor learning outcomes. Yet, exhibit designers lack theoretical and empirical research findings on which to base the creation of such educational environments. Here, this shortcoming is addressed through the development...... of tools and processes to guide the design of educational science exhibits. The guiding paradigm for this development is design-based research, which is characterised by an iterative cycle of design, enactment, and analysis. In the design phase, an educational intervention is planned and carried out based...... on the generation of theoretical ideas for exhibit design is offered in a fourth and parallel research undertaking, namely the application of the notion of cultural border-crossing to a hypothetical case of exhibit design....

Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype.

Science.gov (United States)

Zupan, Bojana; Toth, Miklos

2008-10-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1(+/-)) mothers (H>WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT>WT); here, we show that H>WT offspring are more active than WT>WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1(-/-)) mothers (H>KO/KO>KO). H>WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H>WT as well as in H>KO and KO>KO mice compared to WT>WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux

Directory of Open Access Journals (Sweden)

Pedro Barros

2014-04-01

Full Text Available In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade. About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux.

Science.gov (United States)

Barros, Pedro; Morais, Hugo; Santos, Catarina; Roriz, José; Coutinho, Paula

2014-04-01

In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. To study a new Portuguese family with these characteristics. To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Three of five siblings presented a similar history of paroxysmal cough (5th decade). About a decade later they experienced numbness and paraesthesia in the feet and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

Normal macrophage function in copper deficient mice

International Nuclear Information System (INIS)

Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

1986-01-01

Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice

Science.gov (United States)

Li, Zhenzu; Zhang, Tingting; Lin, Zhuchun; Hou, Congzhe; Zhang, Jian; Men, Yuqin; Li, Huashun

2016-01-01

Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice. PMID:27603780

Strain-typical patterns of pregnancy-induced nestbuilding in mice: maternal and experiential influences.

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Broida, J; Svare, B

1982-07-01

Pregnant C57BL/6J mice incorporate less material into maternal nests and build fewer fully enclosed nests than do pregnant DBA/2J mice. These strain differences are not ameliorated by additional reproductive experience since multiparous animals also exhibit a similar pattern. Reciprocally-crossed hybrid females exhibit DBA-like levels of pregnancy-induced nestbuilding and cross-fostered C57BL and DBA females retain the phenotype of their strain. Experiential and maternal environmental factors apparently are not responsible for strain differences in pregnancy-induced nestbuilding. Differences in ovarian function and/or central neural tissue sensitivity to ovarian hormones may modulate strain differences in pregnancy-induced nestbuilding.

Naïve B cells reduce fungal dissemination in Cryptococcus neoformans infected Rag1-/- mice.

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Dufaud, Chad; Rivera, Johanna; Rohatgi, Soma; Pirofski, Liise-Anne

2018-01-01

IgM and B-1 cell deficient mice exhibit early C. neoformans dissemination from lungs to brain, but a definitive role for B cells in conferring resistance to C. neoformans dissemination has not been established. To address this question, we developed an intranasal (i.n.) C. neoformans infection model in B and T cell deficient Rag1 -/- mice and found they also exhibit earlier fungal dissemination and higher brain CFU than wild-type C57Bl/6 (wild-type) mice. To probe the effect of B cells on fungal dissemination, Rag1 -/- mice were given splenic (intravenously) or peritoneal (intraperitoneally) B cells from wild-type mice and infected i.n. with C. neoformans 7 d later. Mice that received B cells had lung histopathology resembling wild type mice 14 d post-infection, and B-1, not B-2 or T cells in their lungs, and serum and lung IgM and IgG 21 d post-infection. Lung CFU were comparable in wild-type, Rag1 -/-, and Rag1 -/- mice that received B cells 21 d post-infection, but brain CFU were significantly lower in mice that received B cells than Rag1 -/- mice that did not. To determine if natural antibody can promote immunity in our model, we measured alveolar macrophage phagocytosis of C. neoformans in Rag1 -/- mice treated with naive wild-type IgM-sufficient or sIgM -/- IgM-deficient sera before infection. Compared to IgM-deficient sera, IgM-sufficient sera significantly increased phagocytosis. Our data establish B cells are able to reduce early C. neoformans dissemination in mice and suggest natural IgM may be a key mediator of early antifungal immunity in the lungs.

Benign paroxysmal positional vertigo in outpatient practice: Diagnosis and treatment

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N. V. Bestuzheva

2014-01-01

Full Text Available Dizziness is one of the common reasons for visits to physicians of various specialties; the data of foreign investigations show that benign paroxysmal positional vertigo (BPPV is most frequently encountered.Objective: to study the causes of dizziness, to analyze the frequency of BPPV and the efficiency of its treatment in outpatient practice.Patients and methods. The investigation enrolled 80 patients, including 55 (68.7% women and 25 (31.3% men, aged 18 to 75 years (mean age 53.8±12.8 years, who complained of dizziness and sought for medical advice in the Therapeutic-and-Diagnostic Unit, A.Ya. Kozhevnikov Clinic of Nervous System Diseases, I.M. Sechenov First Moscow State Medical University.Results. The most common causes of dizziness in outpatient practice were BPPV (46.2% and postural phobic vertigo (35%. The diagnosis of VPPV, if special positional testing (Dix-Hallpike and McClure-Pagnini tests was carried out, was shown to create no significant difficulties. The diagnosis was not established in the majority (97.5% of the patients; effective treatment was performed in one of the patients. Combined treatment, by performing the positional tests and using betaserc for 2 months, led to complete resolution of positional vertigo in most (97.3% patients.Discussion. The findings indicate the efficiency of examining patients with complaints of dizziness, by using the special otoneurological tests to detect BPPV. The purposeful questioning of patients with BPPV can suspect this disease in the majority of cases. Our investigation shows the high efficiency of rehabilitation maneuvers for BPPV, which agrees well with the data of other authors. Physicians’ poor awareness of BPPV among physicians and the high efficiency of its treatment in outpatient practice are noted.

Clinical roundtable monograph: Paroxysmal nocturnal hemoglobinuria: a case-based discussion.

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Szer, Jeff; Hill, Anita; Weitz, Ilene Ceil

2012-11-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder characterized by chronic intravascular hemolysis as the primary clinical manifestation and morbidities that include anemia, thrombosis, renal impairment, pulmonary hypertension, and bone marrow failure. The prevalence of the PNH clone (from <1-100% PNH granulocytes) is approximately 16 per million, and careful monitoring is required. The average age of onset of the clinical disease is the early 30s, although it can present at all ages. PNH is caused by the acquisition of a somatic mutation of the gene phosphatidylinositol glycan anchor (PIG-A) in a multipotent hematopoietic stem cell (HSC), with clonal expansion of the mutated HSC. The mutation causes a deficiency in the synthesis of glycosylphosphatidylinositol (GPI). In cells derived from normal HSCs, the complement regulatory proteins CD55 and CD59 are anchored to the hematopoietic cell membrane surface via GPI, protecting the cells from complement-mediated lysis. However, in patients with PNH, these 2 proteins, along with numerous other GPI-linked proteins, are absent from the cell surface of red cells, granulocytes, monocytes, and platelets, resulting in complement-mediated intravascular hemolysis and other complications. Lysis of red blood cells is the most obvious manifestation, but as other cell lineages are also affected, this complement-mediated attack contributes to additional complications, such as thrombosis. Eculizumab, a humanized monoclonal antibody against the C5 complement protein, is the only effective drug therapy for PNH patients. The antibody prevents cleavage of the C5 protein by C5 convertase, in turn preventing generation of C5b-9 and release of C5a, thereby protecting from hemolysis of cells lacking the CD59 surface protein and other complications associated with complement activation. Drs. Ilene C. Weitz, Anita Hill, and Jeff Szer discuss 3 recent cases of patients with PNH.

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine

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Cloarec, Robin; Bruneau, Nadine; Rudolf, Gabrielle; Massacrier, Annick; Salmi, Manal; Bataillard, Marc; Boulay, Clotilde; Caraballo, Roberto; Fejerman, Natalio; Genton, Pierre; Hirsch, Edouard; Hunter, Alasdair; Lesca, Gaetan; Motte, Jacques; Roubertie, Agathe; Sanlaville, Damien; Wong, Sau-Wei; Fu, Ying-Hui; Rochette, Jacques; Ptáček, Louis J.

2012-01-01

ABSTRACT Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations. PMID:23077017

Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo.

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Webster, Guilherme; Sens, Patrícia Maria; Salmito, Márcio Cavalcante; Cavalcante, José Diogo Rijo; Santos, Paula Regina Bonifácio dos; Silva, Ana Lívia Muniz da; Souza, Érica Carla Figueiredo de

2015-01-01

Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo. To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV. A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal. The RR for hyperinsulinism was 4.66 and p=0.0015. Existing hyperglycemia showed an RR=2.47, with p=0.0123. Glucose intolerance had a RR of 0.63, with p=0.096. When the examination was within normal limits, the result was RR=0.2225 and p=0.030. Metabolic changes can cause dizziness and vertigo and are very common in people who have cochleovestibular disorders. However, few studies discuss the relationship between idiopathic BPPV and alterations in carbohydrate metabolism. In the present study, we found that both hyperglycemia and hyperinsulinemia are risk factors for the recurrence of BPPV, whereas a normal test was considered a protective factor; all these were statistically significant. Glucose intolerance that was already present was not statistically significant in the group evaluated. Hyperinsulinemia and hyperglycemia are risk factors for the recurrence of idiopathic BPPV and a normal exam is considered a protective factor. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Impaired mental rotation in benign paroxysmal positional vertigo and acute vestibular neuritis.

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Matteo eCandidi

2013-11-01

Full Text Available Vestibular processing is fundamental to our sense of orientation in space which is a core aspect of the representation of the self. Vestibular information is processed in a large subcortical-cortical neural network. Tasks requiring mental rotations of human bodies in space are known to activate neural regions within this network suggesting that vestibular processing is involved in the control of mental rotation. We studied whether mental rotation is impaired in patients suffering from two different forms of unilateral vestibular disorders (Vestibular Neuritis – VN- and Benign Paroxysmal positional Vertigo – BPPV with respect to healthy matched controls (C. We used two mental rotation tasks in which participants were required to: i mentally rotate their own body in space (egocentric rotation thus using vestibular processing to a large extent and ii mentally rotate human figures (allocentric rotation thus using own body representations to a smaller degree. Reaction times and accuracy of responses showed that VN and BPPV patients were impaired in both tasks with respect to C. Significantly, the pattern of results was similar in the three groups suggesting that patients were actually performing the mental rotation without using a different strategy from the control individuals. These results show that dysfunctional vestibular inflow impairs mental rotation of both own body and human figures suggesting that unilateral acute disorders of the peripheral vestibular input massively affect the cerebral processes underlying mental rotations.

Simultaneous and spontaneous reversal of positional nystagmus; an unusual peripheral sign of benign paroxysmal positional vertigo

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Sertac Yetiser, MD

2017-06-01

Full Text Available Direction-changing positional nystagmus is generally thought to be of central origin. Reversal of initial positional nystagmus during maintaining the head position in patients with benign paroxysmal positional vertigo (BPPV is quite unusual and could be a sign of peripheral pathology. Vestibular reflex adaptation, simultaneous co-existence of canalolithiasis and cupulolithiasis in the same or both ears and changing in direction of debris movement have been proposed for the mechanism of this phenomenon. This can be a sign of simultaneous ampullopedal and ampulofugal flows during single head movement. This double-phase pattern of flow causing reversal of positional nystagmus could be related with the amount, location and dispersal of otolithic debris inside the membranous labyrinth. Four patients (3 lateral canal canalolithiasis and 1 posterior canal with reversing spontaneous nystagmus among 530 patients with BPPV have been identified in our clinic. They have been cured with standard re-positioning maneuvers. Endolymphatic reflux theory has been proposed as the underlying mechanism for unusual behavior of otolithic debris.

Technology Exhibition

Energy Technology Data Exchange (ETDEWEB)

Anon.

1979-09-15

Linked to the 25th Anniversary celebrations, an exhibition of some of CERN's technological achievements was opened on 22 June. Set up in a new 600 m{sup 2} Exhibition Hall on the CERN site, the exhibition is divided into eight technology areas — magnets, vacuum, computers and data handling, survey and alignment, radiation protection, beam monitoring and handling, detectors, and workshop techniques.

Masking responses to light in period mutant mice.

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Pendergast, Julie S; Yamazaki, Shin

2011-10-01

Masking is an acute effect of an external signal on an overt rhythm and is distinct from the process of entrainment. In the current study, we investigated the phase dependence and molecular mechanisms regulating masking effects of light pulses on spontaneous locomotor activity in mice. The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of the expression of Per1 and Per2 mRNAs in the suprachiasmatic nuclei (SCN). We assessed the roles of the Per genes in regulating masking by assessing the effects of light pulses on nocturnal locomotor activity in C57BL/6J Per mutant mice. We found that Per1(-/-) and Per2(-/-) mice had robust negative masking responses to light. In addition, the locomotor activity of Per1(-/-)/Per2(-/-) mice appeared to be rhythmic in the light-dark (LD) cycle, and the phase of activity onset was advanced (but varied among individual mice) relative to lights off. This rhythm persisted for 1 to 2 days in constant darkness in some Per1(-/-)/Per2(-/-) mice. Furthermore, Per1(-/-)/Per2(-/-) mice exhibited robust negative masking responses to light. Negative masking was phase dependent in wild-type mice such that maximal suppression was induced by light pulses at zeitgeber time 14 (ZT14) and gradually weaker suppression occurred during light pulses at ZT16 and ZT18. By measuring the phase shifts induced by the masking protocol (light pulses were administered to mice maintained in the LD cycle), we found that the phase responsiveness of Per mutant mice was altered compared to wild-types. Together, our data suggest that negative masking responses to light are robust in Per mutant mice and that the Per1(-/-)/Per2(-/-) SCN may be a light-driven, weak/damping oscillator.

Epsodic paroxysmal hemicrania with seasonal variation: case report and the EPH-cluster headache continuum hypothesis

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Veloso Germany Gonçalves

2001-01-01

Full Text Available Episodic paroxysmal hemicrania (EPH is a rare disorder characterized by frequent, daily attacks of short-lived, unilateral headache with accompanying ipsilateral autonomic features. EPH has attack periods which last weeks to months separated by remission intervals lasting months to years, however, a seasonal variation has never been reported in EPH. We report a new case of EPH with a clear seasonal pattern: a 32-year-old woman with a right-sided headache for 17 years. Pain occurred with a seasonal variation, with bouts lasting one month (usually in the first months of the year and remission periods lasting around 11 months. During these periods she had headache from three to five times per day, lasting from 15 to 30 minutes, without any particular period preference. There were no precipitating or aggravating factors. Tearing and conjunctival injection accompanied ipsilaterally the pain. Previous treatments provided no pain relief. She completely responded to indomethacin 75 mg daily. After three years, the pain recurred with longer attack duration and was just relieved with prednisone. We also propose a new hypothesis: the EPH-cluster headache continuum.

Vestibulo-Ocular Reflex Abnormalities in Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo: A Pilot Study

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Tayyebe Fallahnezhad

2017-09-01

Full Text Available Introduction: Benign paroxysmal positional vertigo (BPPV, involving the semicircular canals, is one of the most common diseases of the inner ear. The video head impulse test (vHIT is a new test that examines the function of the canals. This study aimed to investigate the vestibulo-ocular reflex (VOR gain, gain asymmetry and saccades after stimulating all six canals in patients definitively diagnosed with posterior semicircular canal BPPV (PSC-BPPV.   Materials and Methods: Twenty-nine unilateral PSC-BPPV patients with normal oculographic and caloric results were enrolled in this study. vHIT was performed on six canals, and VOR gain, gain asymmetry and saccades were measured.   Results: Sixteen (55.17% patients had abnormal posterior canal VOR gains in the ipsilesional ear. VOR gains in both horizontal canals were within normal limits. Superior canal VOR gains were mostly lower than normal and were not correlated to PSC abnormalities (P>0.05. No corrective saccades could be observed.   Conclusion: VOR gain in the direction of the posterior semicircular canal may be reduced in PSC-BPPV patients. Evaluation of PSC-VOR parameters could be beneficial, although superior canal measurements should be interpreted with caution.

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

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Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice.

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Liu, Jun-Li; Coschigano, Karen T; Robertson, Katie; Lipsett, Mark; Guo, Yubin; Kopchick, John J; Kumar, Ujendra; Liu, Ye Lauren

2004-09-01

Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR(-/-) mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR(-/-) mice was only one-third of that in wild-type littermates. Total beta-cell mass was reduced 4.5-fold in GHR(-/-) mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.

Virulent variants emerging in mice infected with the apathogenic prototype strain of the parvovirus minute virus of mice exhibit a capsid with low avidity for a primary receptor.

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Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M

2005-09-01

The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of

Clinical phenotype analysis of paroxysmal kinesigenic dyskinesia

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Wo-tu TIAN

2017-07-01

Full Text Available Background Paroxysmal kinesigenic dyskinesia (PKD is a disorder characterized by recurrent and brief dystonic or choreoathetoid attacks that are induced by sudden voluntary movement with highly clinical and genetic heterogeneity. We aimed to investigate the clinical features of PKD in a large Chinese population. Methods One hundred and ninety five patients diagnosed as primary PKD were recruited. For all of the participants, neurological examinations were conducted and clinical manifestations were recorded and summarized in self - made uniform registration form for PKD patients. Clinical characteristics were statistically analyzed and compared between familial and sporadic PKD patients.  Results Among all of the 195 PKD patients in the present study, the gender ratio was 4.42∶1 (male∶ female. The average age of onset was (12.32 ± 3.49 years. There were 162 patients (83.08% manifestated with pure form and 33 (16.92% with complicated form of PKD. Among them 16 patients (8.21% had essential tremor (ET, and 144 patients (73.85% had premonitory symptom. The percentage of patients manifested as dystonia, chorea and mixed form during episodic attacks were 68.72% (134/195, 4.10% (8/195 and 27.18% (53/195 repectively. There were 134 cases (68.72% had facial involvement. It was recorded that 115 (58.97%, 54 (27.69% and 26 (13.33% patients had frequency of attack < 10 times/d, 10-20 times/d and > 20-30 times/d respectively. The percentages of patients whose duration of attack <10 s, 10-30 s and > 30-60 s were 60% (117/195, 29.74% (58/195 and 10.26% (20/195 respectively. There were 64 patietns (32.82% with family history of PKD and 131 (67.18% were sporadic PKD patients. Up to 40% (78/195 of patients did not require/take medications, as they had minor clinical manifestations or concerns about the side effects of anticonvulsants. Among 117 patients (60% prescribed with anticonvulsants, 114 patients showed a good response, including complete control (N

HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

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Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

2015-01-01

The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

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Jeffrey B Carroll

Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

A safe-repositioning maneuver for the management of benign paroxysmal positional vertigo: Gans vs. Epley maneuver; a randomized comparative clinical trial.

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Saberi, Alia; Nemati, Shadman; Sabnan, Salah; Mollahoseini, Fatemeh; Kazemnejad, Ehsan

2017-08-01

Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo. Some repositioning maneuvers have been described for its management. The aim of this study was comparing the therapeutic effect of Epley and Gans maneuvers in BPPV. This randomized clinical trial was performed from September to December 2015. 73 patients with true vertigo diagnosed as BPPV enrolled the study. They randomly assigned in quadripartite blocks to modified Epley maneuver group (E) or Gans maneuver group (G). 1 day and 1 week after intervention, the objective and subjective responses to treatment were assessed. Statistical analysis was performed using the Chi-square test and regression model in the SPSS software version 21. Thirty patients enrolled each group with a mean age of 46.9 ± 13.4 (E group) and 46.7 ± 7.5 year (G group). 23.3 % of E group and 26.7 % of G group were men (p = 0.766). In E and G groups in the first day, subjective outcomes revealed 86.7 and 60 % rate of success (p = 0.02); and 86.7 and 56.7 % of patients exhibited objective improvement, respectively (p = 0.01). After 1 week, the subjective and objective outcomes revealed improvement among 70 % of E group and 46.7 % of G group (p = 0.067). The only complication with significant difference was cervical pain with a higher rate in E group (23.3 vs. 0.0 %, p = 0.005). These results revealed the similar long-term efficacy of Epley and Gans maneuver for the treatment of BPPV. Cervical pain was most frequent complication of Epley maneuver.

Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.

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Egashira, Nobuaki; Iwasaki, Katsunori; Takashima, Akihiko; Watanabe, Takuya; Kawabe, Hideyuki; Matsuda, Tomomi; Mishima, Kenichi; Chidori, Shozo; Nishimura, Ryoji; Fujiwara, Michihiro

2005-10-12

Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSRI), fluvoxamine (100 mg/kg, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depression-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression.

Lactation Defect in a Widely Used MMTV-Cre Transgenic Line of Mice

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Yuan, Taichang; Wang, Yongping; Pao, Lily; Anderson, Steve M.; Gu, Haihua

2011-01-01

Background MMTV-Cre mouse lines have played important roles in our understanding about the functions of numerous genes in mouse mammary epithelial cells during mammary gland development and tumorigenesis. However, numerous studies have not included MMTV-Cre mice as controls, and many investigators have not indicated which of the different MMTV-Cre founder lines were used in their studies. Here, we describe a lactation defect that severely limits the use of one of the most commonly used MMTV-Cre founder lines. Methodology/Principal Findings To explore the role of protein tyrosine phosphatase Shp1 in mammary gland development, mice bearing the floxed Shp1 gene were crossed with MMTV-Cre mice and mammary gland development was examined by histological and biochemical techniques, while lactation competency was assessed by monitoring pup growth. Surprisingly, both the Shp1fl/+;MMTV-Cre and MMTV-Cre female mice displayed a severe lactation defect when compared to the Shp1 fl/+ control mice. Histological and biochemical analyses reveal that female mice expressing the MMTV-Cre transgene, either alone or in combination with floxed genes, exhibit defects in lobuloalveolar expansion, presence of large cytoplasmic lipid droplets in luminal alveolar epithelial cells postpartum, and precocious induction of involution. Using a PCR-based genotyping method, the three different founder lines can be distinguished, and we determined that the MMTV-Cre line A, the most widely used MMTV-Cre founder line, exhibits a profound lactation defect that limits its use in studies on mammary gland development. Conclusions/Significance The identification of a lactation defect in the MMTV-Cre line A mice indicates that investigators must use MMTV-Cre alone mice as control in studies that utilize Cre recombinase to excise genes of interest from mammary epithelial cells. Our results also suggest that previous results obtained in studies using the MMTV-Cre line A line should be re-evaluated if the

CNS activity of Pokeweed Anti-viral Protein (PAP in mice infected with Lymphocytic Choriomeningitis Virus (LCMV

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Tibbles Heather E

2005-02-01

Full Text Available Abstract Background Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV. Methods We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation. Results PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069. Conclusion Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.

Lipid metabolism and body composition in Gclm(-/-) mice

Energy Technology Data Exchange (ETDEWEB)

Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

2011-12-15

In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

DEFF Research Database (Denmark)

Reinert, Line; Harder, Louis Andreas; Holm, Christian

2012-01-01

Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation......, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...

PER1 Phosphorylation Specifies Feeding Rhythm in Mice

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Zhiwei Liu

2014-06-01

Full Text Available Organization of circadian behavior, physiology, and metabolism is important for human health. An S662G mutation in hPER2 has been linked to familial advanced sleep-phase syndrome (FASPS. Although the paralogous phosphorylation site S714 in PER1 is conserved in mice, its specific function in circadian organization remains unknown. Here, we find that the PER1S714G mutation accelerates the molecular feedback loop. Furthermore, hPER1S714G mice, but not hPER2S662G mice, exhibit peak time of food intake that is several hours before daily energy expenditure peaks. Both the advanced feeding behavior and the accelerated clock disrupt the phase of expression of several key metabolic regulators in the liver and adipose tissue. Consequently, hPER1S714G mice rapidly develop obesity on a high-fat diet. Our studies demonstrate that PER1 and PER2 are linked to different downstream pathways and that PER1 maintains coherence between the circadian clock and energy metabolism.

Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.

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Lorenz, Viola; Ramsey, Haley; Liu, Zhi-Jian; Italiano, Joseph; Hoffmeister, Karin; Bihorel, Sihem; Mager, Donald; Hu, Zhongbo; Slayton, William B; Kile, Benjamin T; Sola-Visner, Martha; Ferrer-Marin, Francisca

2017-12-01

Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL –/– mice. Liver MKs in c-MPL –/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL –/– MKs. Platelet counts were lower in c-MPL –/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL –/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL –/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL –/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL –/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL –/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.

[Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents].

Science.gov (United States)

Pevnitskiĭ, L A; Telegin, L Iu; Ir, K N

1985-08-01

It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

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Ching Wen Tseng

Full Text Available Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA, exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD/severe combined immune deficiency (SCID/IL2rγnull (NSG mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

Transgenic Mice Expressing Yeast CUP1 Exhibit Increased Copper Utilization from Feeds

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Chen, Zhenliang; Liao, Rongrong; Zhang, Xiangzhe; Wang, Qishan; Pan, Yuchun

2014-01-01

Copper is required for structural and catalytic properties of a variety of enzymes participating in many vital biological processes for growth and development. Feeds provide most of the copper as an essential micronutrient consumed by animals, but inorganic copper could not be utilized effectively. In the present study, we aimed to develop transgenic mouse models to test if copper utilization will be increased by providing the animals with an exogenous gene for generation of copper chelatin in saliva. Considering that the S. cerevisiae CUP1 gene encodes a Cys-rich protein that can bind copper as specifically as copper chelatin in yeast, we therefore constructed a transgene plasmid containing the CUP1 gene regulated for specific expression in the salivary glands by a promoter of gene coding pig parotid secretory protein. Transgenic CUP1 was highly expressed in the parotid and submandibular salivary glands and secreted in saliva as a 9-kDa copper-chelating protein. Expression of salivary copper-chelating proteins reduced fecal copper contents by 21.61% and increased body-weight by 12.97%, suggesting that chelating proteins improve the utilization and absorbed efficacy of copper. No negative effects on the health of the transgenic mice were found by blood biochemistry and histology analysis. These results demonstrate that the introduction of the salivary CUP1 transgene into animals offers a possible approach to increase the utilization efficiency of copper and decrease the fecal copper contents. PMID:25265503

GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

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Brown-Borg, Holly M; Bartke, Andrzej

2012-06-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice.

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Seibenhener, Michael L; Wooten, Michael C

2015-02-06

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of the most commonly used platforms to measure behaviors in animal models. It is a fast and relatively easy test that provides a variety of behavioral information ranging from general ambulatory ability to data regarding the emotionality of the subject animal. As it relates to rodent models, the procedure allows the study of different strains of mice or rats both laboratory bred and wild-captured. The technique also readily lends itself to the investigation of different pharmacological compounds for anxiolytic or anxiogenic effects. Here, a protocol for use of the open field maze to describe mouse behaviors is detailed and a simple analysis of general locomotor ability and anxiety-related emotional behaviors between two strains of C57BL/6 mice is performed. Briefly, using the described protocol we show Wild Type mice exhibited significantly less anxiety related behaviors than did age-matched Knock Out mice while both strains exhibited similar ambulatory ability.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

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Koji Mizuhashi

Full Text Available Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119, encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice.First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS and osteoid maturation time (Omt, and significantly decreased mineral apposition rate (MAR and bone formation rate per bone surface (BFR/BS. In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant.Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

Science.gov (United States)

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice. First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant. Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

IMPLEMENTASI KONSEP “SUSTAINABLE EVENT MANAGEMENT” DALAM PENGELOLAAN KEGIATAN MICE DI KAWASAN WISATA NUSA DUA, BALI

OpenAIRE

Komang Trisna Pratiwi Arcana

2014-01-01

The growth of MICE (Meeting, Incentive, Conference, and Exhibition) Tourism and a requirement to incorporate the principle of sustainability in the management of tourism sector, bring such a concept of sustainable development for business which called as Sustainable Event Management. This study determines the characteristic of MICE Tourism and discovers the reason why Nusa Dua Resort, Bali, becomes a well known MICE tourism destination. Besides, it tries to obtain a clear picture as well ...

Abnormal grooming activity in Dab1(scm) (scrambler) mutant mice.

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Strazielle, C; Lefevre, A; Jacquelin, C; Lalonde, R

2012-07-15

Dab1(scm) mutant mice, characterized by cell ectopias and degeneration in cerebellum, hippocampus, and neocortex, were compared to non-ataxic controls for different facets of grooming caused by brief water immersions, as well as some non-grooming behaviors. Dab1(scm) mutants were strongly affected in their quantitative functional parameters, exhibiting higher starting latencies before grooming relative to non-ataxic littermates of the A/A strain, fewer grooming bouts, and grooming components of shorter duration, with an unequal regional distribution targeting almost totally the rostral part (head washing and forelimb licking) of the animal. Only bouts of a single grooming element were preserved. The cephalocaudal order of grooming elements appeared less disorganized, mutant and control mice initiating the grooming with head washing and forelimb licking prior to licking posterior parts. However, mutants differed from controls in that all their bouts were incomplete but uninterrupted, although intergroup difference for percentage of the incorrect transitions was not significant. In contrast to grooming, Dab1(scm) mice ambulated for a longer time. During walking episodes, they exhibited more body scratching than controls, possibly to compensate for the lack of licking different body parts. In conjunction with studies with other ataxic mice, these results indicate that the cerebellar cortex affects grooming activity and is consequently involved in executing various components, but not in its sequential organization, which requires other brain regions such as cerebral cortices or basal ganglia. Copyright © 2012 Elsevier B.V. All rights reserved.

Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

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Kyu Sang Joeng

Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

Loss of CDKL5 disrupts respiratory function in mice.

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Lee, Kun-Ze; Liao, Wenlin

2018-01-01

Cyclin-dependent kinase-like 5 (CDKL5) is an X-linked gene encoding a serine-threonine kinase that is highly expressed in the central nervous system. Mutations in CDKL5 cause neurological and psychiatric symptoms, including early-onset seizures, motor dysfunction, autistic features and sleep breathing abnormalities in patients. It remains to be addressed whether loss of CDKL5 causes respiratory dysfunction in mice. Here, we examined the respiratory pattern of male Cdkl5 -/y mice at 1-3 months of age during resting breathing and respiratory challenge (i.e., hypoxia and hypercapnia) via whole body plethysmography. The results demonstrated that the resting respiratory frequency and tidal volume of Cdkl5 -/y mice was unaltered compared to that of WT mice at 1 month of age. However, these mutant mice exhibit transient reduction in tidal volume during respiratory challenge even the reduction was restored at 2 months of age. Notably, the sigh-breathing pattern was changed in Cdkl5 -/y mice, showing a transient reduction in sigh volume at 1-2 month of age and long-term attenuation of peak expiratory airflow from 1 to 3 month of age. Therefore, loss of CDKL5 causes breathing deficiency, supporting a CDKL5-mediated regulation of respiratory function in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

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Ozburn Angela R

2012-10-01

Full Text Available Abstract Background The inability to reduce or regulate alcohol intake is a hallmark symptom for alcohol use disorders. Research on novel behavioral and genetic models of experience-induced changes in drinking will further our knowledge on alcohol use disorders. Distinct alcohol self-administration behaviors were previously observed when comparing two F1 hybrid strains of mice: C57BL/6J x NZB/B1NJ (BxN show reduced alcohol preference after experience with high concentrations of alcohol and periods of abstinence while C57BL/6J x FVB/NJ (BxF show sustained alcohol preference. These phenotypes are interesting because these hybrids demonstrate the occurrence of genetic additivity (BxN and overdominance (BxF in ethanol intake in an experience dependent manner. Specifically, BxF exhibit sustained alcohol preference and BxN exhibit reduced alcohol preference after experience with high ethanol concentrations; however, experience with low ethanol concentrations produce sustained alcohol preference for both hybrids. In the present study, we tested the hypothesis that these phenotypes are represented by differential production of the inducible transcription factor, ΔFosB, in reward, aversion, and stress related brain regions. Results Changes in neuronal plasticity (as measured by ΔFosB levels were experience dependent, as well as brain region and genotype specific, further supporting that neuronal circuitry underlies motivational aspects of ethanol consumption. BxN mice exhibiting reduced alcohol preference had lower ΔFosB levels in the Edinger-Westphal nucleus than mice exhibiting sustained alcohol preference, and increased ΔFosB levels in central medial amygdala as compared with control mice. BxN mice showing sustained alcohol preference exhibited higher ΔFosB levels in the ventral tegmental area, Edinger-Westphal nucleus, and amygdala (central and lateral divisions. Moreover, in BxN mice ΔFosB levels in the Edinger-Westphal nucleus and ventral

Impaired transport of thyroid hormones into livers of obese (ob/ob) mice

International Nuclear Information System (INIS)

Hillgartner, F.B.; Romsos, D.R.

1988-01-01

Obese (ob/ob) mice exhibit impaired hepatic thyroid hormone action that is mediated, at least in part, by a reduced nuclear 3,5,3'-triiodothyronine (T 3 ) receptor occupancy. The possibility that lowered occupancy in obese mice may be caused by decreased transport of T 3 across the hepatic plasma membrane was examined by measuring the unidirectional influx of [ 125 I]T 3 into livers of 8- to 10-wk-old obese and lean mice using a tissue-sampling portal vein-injection technique. Influx of [ 125 I]thyroxine (T 4 ), a substrate for T 4 5'-deiodinase, was also measured. Unidirectional clearance of T 3 and T 4 was 64 and 80% lower, respectively, in obese mice than in lean mice. Hepatic T 3 and T 4 uptake was nonsaturable in both lean and obese mice, suggesting that transport occurs by lipid-mediated free diffusion. Clearance of another lipid-soluble hormone, hydrocortisone, was also lower in obese mice than in lean mice. Decreased membrane permeability to the above hormones in obese mice may result from reported changes in membrane lipid composition. In conclusion, decreased hepatic thyroid hormone uptake may contribute to impaired thyroid hormone action and T 3 production in livers of obese mice

Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight-Bearing Exercise.

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Jeong, Youngjae; Carleton, Stephanie M; Gentry, Bettina A; Yao, Xiaomei; Ferreira, J Andries; Salamango, Daniel J; Weis, MaryAnn; Oestreich, Arin K; Williams, Ashlee M; McCray, Marcus G; Eyre, David R; Brown, Marybeth; Wang, Yong; Phillips, Charlotte L

2015-10-01

Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild-type mice. The +/G610C mice were also able to complete an 8-week treadmill regimen. Biomechanical integrity of control and exercised wild-type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight-bearing exercise regimen as wild-type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice. © 2015 American Society for Bone

Otolith Dysfunction in Persons With Both Diabetes and Benign Paroxysmal Positional Vertigo.

Science.gov (United States)

DʼSilva, Linda J; Staecker, Hinrich; Lin, James; Maddux, Christy; Ferraro, John; Dai, Hongying; Kluding, Patricia M

2017-03-01

Vestibular dysfunction is a well-recognized complication of type 2 diabetes (DM) that may contribute to increased fall risk. The prevalence of benign paroxysmal positional vertigo (BPPV) is higher in people with DM. The impact of DM on the otolith organs of the vestibular system in people with BPPV is unknown. The purpose of this study was to analyze otolith function using vestibular-evoked myogenic potential (VEMP) tests in people with DM and concurrent BPPV (BPPV + DM), and to examine the relationships between VEMP variables and diabetes-related variables. Prospective, cross-sectional study. Tertiary academic medical center. Participants 40 to 65 years were recruited in four groups: controls (n = 20), people with DM (n = 19), BPPV (n = 18), and BPPV + DM (n = 14). Saccule and utricle function were examined using cervical VEMP (cVEMP) and ocular VEMP (oVEMP), respectively. Diabetes-related variables such as HbA1c, duration of diabetes, and presence of sensory impairment due to diabetes were collected. The frequency of abnormal cVEMP responses was higher in the DM (p = 0.005), BPPV (p = 0.003), and BPPV + DM (p diabetes, higher HbA1c levels were correlated with prolonged P1 (p = 0.03) and N1 latencies (p = 0.03). The frequency of abnormal oVEMP responses was not different between groups (p = 0.2). Although BPPV and DM may independently affect utricle and saccule function, they do not seem to have a distinct cumulative effect.

Lovastatin protects against experimental plague in mice.

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Saravanan Ayyadurai

Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

Acetaminophen-induced acute liver injury in HCV transgenic mice

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Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

2013-01-01

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

Acetaminophen-induced acute liver injury in HCV transgenic mice

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Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice.

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Arentsen, Tim; Khalid, Roksana; Qian, Yu; Diaz Heijtz, Rochellys

2018-01-01

Peptidoglycan recognition proteins (PGRPs) are key sensing-molecules of the innate immune system that specifically detect bacterial peptidoglycan (PGN) and its derivates. PGRPs have recently emerged as potential key regulators of normal brain development and behavior. To test the hypothesis that PGRPs play a role in motor control and anxiety-like behavior in later life, we used 15-month old male and female peptidoglycan recognition protein 2 (Pglyrp2) knockout (KO) mice. Pglyrp2 is an N-acetylmuramyl-l-alanine amidase that hydrolyzes PGN between the sugar backbone and the peptide chain (which is unique among the mammalian PGRPs). Using a battery of behavioral tests, we demonstrate that Pglyrp2 KO male mice display decreased levels of anxiety-like behavior compared with wild type (WT) males. In contrast, Pglyrp2 KO female mice show reduced rearing activity and increased anxiety-like behavior compared to WT females. In the accelerated rotarod test, however, Pglyrp2 KO female mice performed better compared to WT females (i.e., they had longer latency to fall off the rotarod). Further, Pglyrp2 KO male mice exhibited decreased expression levels of synaptophysin, gephyrin, and brain-derived neurotrophic factor in the frontal cortex, but not in the amygdala. Pglyrp2 KO female mice exhibited increased expression levels of spinophilin and alpha-synuclein in the frontal cortex, while exhibiting decreased expression levels of synaptophysin, gephyrin and spinophilin in the amygdala. Our findings suggest a novel role for Pglyrp2asa key regulator of motor and anxiety-like behavior in late life. Copyright © 2017. Published by Elsevier Inc.

Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

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Zhang, Shuxiao; Wang, Wei; Li, Juan; Cheng, Ke; Zhou, Jingjing; Zhu, Dan; Yang, Deyu; Liang, Zihong; Fang, Liang; Liao, Li; Xie, Peng

2016-02-15

CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders. Copyright © 2015. Published by Elsevier B.V.

Pavlovian conditioning of multiple opioid-like responses in mice.

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Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

2009-07-01

Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

Alterations in gene expression in mutant amyloid precursor protein transgenic mice lacking Niemann-Pick type C1 protein.

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Mahua Maulik

Full Text Available Niemann-Pick type C (NPC disease, a rare autosomal recessive disorder caused mostly by mutation in NPC1 gene, is pathologically characterized by the accumulation of free cholesterol in brain and other tissues. This is accompanied by gliosis and loss of neurons in selected brain regions, including the cerebellum. Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease, including the presence of neurofibrillary tangles and increased levels of amyloid precursor protein (APP-derived β-amyloid (Aβ peptides in vulnerable brain neurons. To evaluate the role of Aβ in NPC disease, we determined the gene expression profile in selected brain regions of our recently developed bigenic ANPC mice, generated by crossing APP transgenic (Tg mice with heterozygous Npc1-deficient mice. The ANPC mice exhibited exacerbated neuronal and glial pathology compared to other genotypes [i.e., APP-Tg, double heterozygous (Dhet, Npc1-null and wild-type mice]. Analysis of expression profiles of 86 selected genes using real-time RT-PCR arrays showed a wide-spectrum of alterations in the four genotypes compared to wild-type controls. The changes observed in APP-Tg and Dhet mice are limited to only few genes involved mostly in the regulation of cholesterol metabolism, whereas Npc1-null and ANPC mice showed alterations in the expression profiles of a number of genes regulating cholesterol homeostasis, APP metabolism, vesicular trafficking and cell death mechanism in both hippocampus and cerebellum compared to wild-type mice. Intriguingly, ANPC and Npc1-null mice, with some exceptions, exhibited similar changes, although more genes were differentially expressed in the affected cerebellum than the relatively spared hippocampus. The altered gene profiles were found to match with the corresponding protein levels. These results suggest that lack of Npc1 protein can alter the expression profile of selected transcripts as well as proteins, and

[Cardioversion for paroxysmal supraventricular tachycardia during lung surgery in a patient with concealed Wolff-Parkinson-White syndrome].

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Sato, Yoshiharu; Nagata, Hirofumi; Inoda, Ayako; Miura, Hiroko; Watanabe, Yoko; Suzuki, Kenji

2014-10-01

We report a case of paroxysmal supraventricular tachycardia (PSVT) that occurred during video-assisted thoracoscopic (VATS) lobectomy in a patient with concealed Wolff-Parkinson-White (WPW) syndrome. A 59-year-old man with lung cancer was scheduled for VATS lobectomy under general anesthesia. After inserting a thoracic epidural catheter, general anesthesia was induced with intravenous administration of propofol. Anesthesia was maintained with inhalation of desfurane in an air/oxygen mixture and intravenous infusion of remifentanil. Recurrent PSVT occurred three times, and the last episode of PSVT continued for 50 minutes regardless of administration of antiarrhythmic drugs. Synchronized electric shock via adhesive electrode pads on the patient's chest successfully converted PSVT back to normal sinus rhythm. The remaining course and postoperative period were uneventful. An electrophysiological study performed after hospital discharge detected concealed WPW syndrome, which had contributed to the development of atrioventricular reciprocating tachycardia. Concealed WPW syndrome is a rare, but critical complication that could possibly cause lethal atrial tachyarrhythmias during the perioperative period. In the present case, cardioversion using adhesive electrode pads briefly terminated PSVT in a patient with concealed WPW syndrome.

Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice

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Hirota, Yoshihisa; Nakagawa, Kimie; Mimatsu, Shino; Sawada, Natsumi; Sakaki, Toshiyuki; Kubodera, Noboru; Kamao, Maya; Tsugawa, Naoko; Suhara, Yoshitomo; Okano, Toshio

2017-01-01

The active form of vitamin D, 1α,25-dihydroxyvitamin D 3 (1α,25D 3 ), plays an important role in the maintenance of calcium (Ca) homeostasis, bone formation, and cell proliferation and differentiation via nuclear vitamin D receptor (VDR). It is formed by the hydroxylation of vitamin D at the 1α position by 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) in the kidney. However, Cyp27b1 −/− mice, deficient in CYP27B1, and VDR-deficient mice (Vdr −/− ) have not been extensively examined, particularly in a comparative framework. To clarify the physiological significance of 1α,25D 3 and VDR, we produced Cyp27b1 −/− mice and compared their phenotypes with those of Vdr −/− mice. Cyp27b1 −/− mice exhibited hypocalcemia, growth defects, and skeletogenesis dysfunction, similar to Vdr −/− mice. However, unlike Cyp27b1 −/− mice, Vdr −/− mice developed alopecia. Cyp27b1 −/− mice exhibited cartilage mass formation and had difficulty walking on hindlimbs. Furthermore, a phenotypic analysis was performed on Cyp27b1 −/− mice provided a high Ca diet to correct for the Ca metabolic abnormality. In addition, the effects of 1α,25D 3 that are not mediated by Ca metabolic regulatory activity were investigated. Even when the blood Ca concentration was corrected, abnormalities in growth and cartilage tissue formation did not improve in Cyp27b1 −/− mice. These results suggested that 1α,25D 3 directly controls chondrocyte proliferation and differentiation. Using Cyp27b1 −/− mice produced in this study, we can analyze the physiological effects of novel vitamin D derivatives in the absence of endogenous 1α,25D 3 . Accordingly, this study provides a useful animal model for the development of novel vitamin D formulations that are effective for the treatment and prevention of osteoporosis. - Highlights: • We produced Cyp27b1 −/− mice and analyzed their phenotypes. • Vdr −/− mice exhibited alopecia and Cyp27b1 −/− mice exhibited

Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

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Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

1984-01-01

The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

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Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.

2011-01-01

Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465

Strain differences in the somnogenic effects of interferon inducers in mice.

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Toth, L A

1996-12-01

Increased slow-wave sleep accompanies influenza infection in C57BL/6 mice but not BALB/c mice. These strains of mice possess different alleles of the genetic lucus If-1, which codes for high (If-1h; C57BL/6) and low (If-1(1); BALB/c) production of interferon (IFN), a putative sleep-inducing cytokine. To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta. As compared with baseline values, C57BL/6 mice exhibited increased slow-wave sleep after all three challenges, but BALB/c mice did not. Congenic B6.C-H28c mice, which bear the BALB/c allele for low IFN production on the C57BL/6 genetic background, showed enhanced slow-wave sleep after influenza infection but not after NDV. Exogenous IFN did not enhance slow-wave sleep in either C57BL/6 or BALB/c mice. These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease.

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

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Adebayo, O O; Ko, F C; Wan, P T; Goldring, S R; Goldring, M B; Wright, T M; van der Meulen, M C H

2017-12-01

Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Masking Responses to Light in Period Mutant Mice

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Pendergast, Julie S.; Yamazaki, Shin

2013-01-01

Masking is an acute effect of an external signal on an overt rhythm and is distinct from the process of entrainment. In the current study, we investigated the phase dependence and molecular mechanisms regulating masking effects of light pulses on spontaneous locomotor activity in mice. The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of the expression of Per1 and Per2 mRNAs in the suprachiasmatic nuclei (SCN). We assessed the roles of the Per genes in regulating masking by assessing the effects of light pulses on nocturnal locomotor activity in C57BL/6J Per mutant mice. We found that Per1−/− and Per2−/− mice had robust negative masking responses to light. In addition, the locomotor activity of Per1−/−/Per2−/− mice appeared to be rhythmic in the light-dark (LD) cycle, and the phase of activity onset was advanced (but varied among individual mice) relative to lights off. This rhythm persisted for 1 to 2 days in constant darkness in some Per1−/−/Per2−/− mice. Furthermore, Per1−/−/Per2−/− mice exhibited robust negative masking responses to light. Negative masking was phase dependent in wild-type mice such that maximal suppression was induced by light pulses at zeitgeber time 14 (ZT14) and gradually weaker suppression occurred during light pulses at ZT16 and ZT18. By measuring the phase shifts induced by the masking protocol (light pulses were administered to mice maintained in the LD cycle), we found that the phase responsiveness of Per mutant mice was altered compared to wild-types. Together, our data suggest that negative masking responses to light are robust in Per mutant mice and that the Per1−/−/Per2−/− SCN may be a light-driven, weak/damping oscillator. PMID:21793695

Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.

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Holm, Jacob Bak; Rønnevik, Alexander; Tastesen, Hanne Sørup; Fjære, Even; Fauske, Kristin Røen; Liisberg, Ulrike; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

2016-05-01

High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD. Copyright © 2016 Elsevier Inc. All rights reserved.

Short-term fasting protects mice against γ ray radiation

International Nuclear Information System (INIS)

Zhu Shengnan; Gu Xiuling; Song Lian; Tong Jian; Li Jianxiang

2012-01-01

Objective: To investigate the antagonistic effects of short-term fasting against 60 Co γ ray radiation. Methods: After fasting ICR mice were irradiated for 3 min at a dose rate of 2.5 Gy/min and then returned to normal diet. General situation, body weight changes, food consumption and toxic status were observed. WBC, organ index and anti-oxidative ability (ROS, SOD, MDA, T-AOC) were analyzed. Results: After 60 Co γ ray radiation, the mice exhibited severe toxic symptoms before death. The survival rates were 0 for control and 12 h group, 12.5% for 48 h group and 50% for 72 h group respectively. ROS production of 72 h group was reduced compared with 0 h group (P<0.05). Conclusion: Short-term fasting may attenuate radiation induced injuries, evidenced by a significant increase in mice survival rate. (authors)

Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice.

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Thomas E Sussan

Full Text Available BACKGROUND: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2(-/- causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. PRINCIPAL FINDINGS: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2(-/- mice with apoliporotein E-deficient (ApoE(-/- mice. ApoE(-/- and ApoE(-/-Nrf2(-/- mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE(-/-Nrf2(-/- mice exhibited significantly smaller plaque area than ApoE(-/- controls (11.5% vs 29.5%. This decrease in plaque area observed in ApoE(-/-Nrf2(-/- mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL by isolated macrophages from ApoE(-/-Nrf2(-/- mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE(-/-Nrf2(-/- mice exhibited decreased expression of the scavenger receptor CD36. CONCLUSIONS: Nrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARα with clofibrate

International Nuclear Information System (INIS)

Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.; Latendresse, John R.; Mehendale, Harihara M.

2008-01-01

The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPARα via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. 14 C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by 3 H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPARα was tested. PPARα was downregulated in NASH. To investigate whether downregulation of PPARα in NASH is the critical mechanism of compromised liver tissue repair, PPARα was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPARα expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity

Aging and cellular defense mechanisms: age-related changes in resistance of mice to Listeria monocytogenes.

OpenAIRE

Patel, P J

1981-01-01

Age-related changes in resistance of mice to infection with Listeria monocytogenes were investigated. One-month-old mice exhibited the least resistance, and the resistance level increased over the first few months to reach a maximum by 8 months. Increase in age thereafter was accompanied by a slow but progressive decrease in resistance. Thus, 50% lethal doses for 1-, 8-, and 24-month-old mice were 10(4.2), 10(6.6), and 10(5.2), respectively. In spite of differences in resistance, the growth o...

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

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Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

2017-01-01

Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

Directory of Open Access Journals (Sweden)

Julia A Loos

2017-02-01

Full Text Available Metformin (Met is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization.

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Mohun Ramratnam

Full Text Available Most studies of the mechanisms leading to hereditary dilated cardiomyopathy (DCM have been performed in reconstituted in vitro systems. Genetically engineered murine models offer the opportunity to dissect these mechanisms in vivo. We generated a gene-targeted knock-in murine model of the autosomal dominant Arg141Trp (R141W mutation in Tnnt2, which was first described in a human family with DCM. Mice heterozygous for the mutation (Tnnt2R141W/+ recapitulated the human phenotype, developing left ventricular dilation and reduced contractility. There was a gene dosage effect, so that the phenotype in Tnnt2R141W/+mice was attenuated by transgenic overexpression of wildtype Tnnt2 mRNA transcript. Male mice exhibited poorer survival than females. Biomechanical studies on skinned fibers from Tnnt2R141W/+ hearts showed a significant decrease in pCa50 (-log[Ca2+] required for generation of 50% of maximal force relative to wildtype hearts, indicating Ca2+ desensitization. Optical mapping studies of Langendorff-perfused Tnnt2R141W/+ hearts showed marked increases in diastolic and peak systolic intracellular Ca2+ ([Ca2+]i, and prolonged systolic rise and diastolic fall of [Ca2+]i. Perfused Tnnt2R141W/+ hearts had slower intrinsic rates in sinus rhythm and reduced peak heart rates in response to isoproterenol. Tnnt2R141W/+ hearts exhibited a reduction in phosphorylated phospholamban relative to wildtype mice. However, crossing Tnnt2R141W/+ mice with phospholamban knockout (Pln-/- mice, which exhibit increased Ca2+ transients and contractility, had no effect on the DCM phenotype. We conclude that the Tnnt2 R141W mutation causes a Ca2+ desensitization and mice adapt by increasing Ca2+-transient amplitudes, which impairs Ca2+ handling dynamics, metabolism and responses to β-adrenergic activation.

Anterior semicircular canal benign paroxysmal positional vertigo and positional downbeating nystagmus.

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Lopez-Escamez, Jose A; Molina, Maria I; Gamiz, Maria J

2006-01-01

The aim of this study was to describe the clinical features and video-oculographic findings in patients with anterior semicircular canal benign paroxysmal positional vertigo (BPPV). This is a prospective case series. The study was set at an outpatient clinic in a general hospital. Fourteen individuals with symptoms of BPPV and positional downbeating nystagmus (pDBN) were included in the study. The diagnosis was based on a history of brief episodes of vertigo and the presence of pDBN confirmed in the video-oculographic examination during Dix-Hallpike test (DH) or head-hanging maneuver. Patients were treated by particle repositioning maneuver and the effectiveness was evaluated at 7, 30, and 180 days posttreatment. The treatment was repeated up to 4 times if pDBN was persistent. The main outcome measure is the number of patients without pDBN at 30 and 180 days. Video-oculography showed a predominant pDBN in response to DH. Of the 14 patients, 7 had arterial hypertension, and 5 of 14 cases presented abnormalities on the caloric test. Horizontal spontaneous nystagmus was found in 3 of 14 individuals. Positional nystagmus at different positional test was observed in 5 of 14 individuals, suggesting the involvement of several canals. Of the 14 patients, 10 (71%) did not present vertigo, and the positional tests were negative at 30 days. However, 3 cases presented a positive DH with persistence of BPPV episodes and pDBN at 30 days, and another developed a contralateral posterior canal affectation. One of the patients maintained a persistent pDBN at 180 days despite the repeated maneuvers. Video-oculography demonstrates that anterior canal BPPV is characterized by a predominant downbeating nystagmus in response to DH. These individuals may show alterations in the vestibular caloric, and they can have multicanal affectation.

Importance of accurate diagnosis in benign paroxysmal positional vertigo (BPPV) therapy.

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Maslovara, Siniša; Vešligaj, Tihana; Butković Soldo, Silva; Pajić-Penavić, Ivana; Maslovara, Karmela; Mirošević Zubonja, Tea; Soldo, Anamarija

2014-08-01

To determine the importance of accurate topological diagnostics of the otolith and the differentiation of certain clinical forms of benign paroxysmal positional vertigo (BPPV). A prospective study was conducted at the County General Hospital Vukovar in the period from January 2011 till January 2012. A total of 81 patients with BPPV, 59 females (72.84%) and 22 (27.16%) males (p less than 0.001), mean age 60.1 (± 12.1) were examined. The diagnosis was confirmed and documented by videonystagmography (VNG). The disability due to disease and risk of falling were monitored by filling in the Dizziness Handicap Inventory (DHI) and Activities-specific Balance Confidence Scale (ABC) questionnaires at the beginning and at the end of the repositioning treatment. In 79 (97.3%) patients posterior semicircular canal was affected, and in a small number of patients, two (2.47%) the lateral one. After the repositioning procedures were performed, there was a significant reduction or complete elimination of symptoms in the majority of subjects, 76 (93.82%). The median total DHI sum amounted to 50.5 (± 22.2) at the beginning and 20.4 (± 18.5) at the end of the study (p less than 0.00). Similarly, the results of ABC questionnaires at the beginning of the study demonstrated a result of 59.2% (± 22.4%), and at the end of the treatment the average result of examinees was significantly higher, 84.9% (± 15.2%) (p less than 0.00). Although a subjectively positive Dix-Hallpike or a "supine roll" test is sufficient for the diagnosis of BPPV, it is necessary perform the VNG as well in order to precisely determine the exact localization of the otolith, so that an appropriate repositioning procedure can be applied.

Exhibition

CERN Document Server

Staff Association

2017-01-01

A Look of Hope Islam Mahmoud Sweity From 19 to 30 June 2017 CERN Meyrin, Main Building Islam Mahmoud Sweity Islam Mahmoud Sweity was born in 1997 at Beit Awwa, Palestine. She is currently following a course to get an Art diploma of Painting at the college of Fine Arts at An-Najah National University under the supervision of Esmat Al As'aad. Her portraits, landscapes and still life paintings are full of life and shining colours. Charged of emotional empathy they catch the attention of the viewer and are reminding us that life is beautiful and worth living in spite of all difficulties we have to go through. She participated in many exhibitions and has exposed her drawings in 2015 at CERN and in France in the framework of the exhibition "The Origin“, and in 2017 in the Former Yugoslav Republic of Macedonia, Palestina and Jordan. In this exhibition the oil paintings made in the past year will be presented. For more information : staff.association@cern.ch | T&eacu...

Immuno-efficacy of DNA vaccines encoding PLP1 and ROP18 against experimental Toxoplasma gondii infection in mice.

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Chen, Yajun; Yu, Miao; Hemandez, J A; Li, Jiexi; Yuan, Zi-Guo; Yan, Haikuo

2018-05-01

We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines. Copyright © 2018 Elsevier Inc. All rights reserved.

Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice

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Waters, R.Parrish; Pringle, R.B.; Forster, G.L.; Renner, K.J.; Malisch, J.L.; Garland, T.; Swallow, J.G.

2013-01-01

Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders. PMID:23352668

[Effects of nootropic drugs on behavior of BALB/c and C57BL/6 mice in the exploratory cross-maze test].

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Vasil'eva, E V; Salimov, R M; Kovalev, G I

2012-01-01

Exploratory behavior, locomotor activity, and anxiety in inbred mice of C57BL/6 and BALB/c strains subchronically treated with placebo or various types of nootropic (cognition enhancing) drugs (piracetam, phenotropil, noopept, semax, pantogam, nooglutil) have been evaluated using the exploratory cross-maze test. It was found that BALB/c mice in comparison to C57BL/6 mice are characterized by greater anxiety and lower efficiency of exploratory behavior in the previously unfamiliar environment. All tested drugs clearly improved the exploratory behavior in BALB/c mice only. In BALB/c mice, piracetam, phenotropil, noopept, and semax also reduced anxiety, while phenotropil additionally increased locomotor activity. Thus, the nootropic drugs displayed clear positive modulation of spontaneous orientation in the mice strain with initially low exploratory efficiency (BALB/c) in the cross-maze test. Some drugs (pantogam, nooglutil) exhibited only nootropic properties, while the other drugs exhibited both nootropic effects on the exploratory activity and produced modulation of the anxiety level (piracetam, fenotropil, noopept, semax) and locomotor activity (fenotropil).

Low bone mineral density and vitamin D deficiency in patients with benign positional paroxysmal vertigo.

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Talaat, Hossam Sanyelbhaa; Abuhadied, Ghada; Talaat, Ahmed Sanyelbhaa; Abdelaal, Mohamed Samer S

2015-09-01

Several studies indicated the association between benign paroxysmal positional vertigo (BPPV) with osteoporosis and vitamin D deficiency implying that abnormal calcium metabolism may underlie BPPV. The aim of the present study is to confirm the correlation between BPPV and both decrease in bone mineral density (BMD) and vitamin D deficiency. The study group included 80 patients with idiopathic BPPV (52 females, 28 males), with age range 31-71 years (47.6 ± 9.1). The patients were divided into two groups; recurrent BPPV group including 36 subjects and non-recurrent group including 44 subjects. The control group included 100 healthy volunteers with age and gender distribution similar to the study group. All the subjects in the study were examined using Dual-energy X-ray absorptiometry to assess BMD, and serum 25-hydroxyvitamin D for vitamin D assessment. The accepted normal levels were T-score > -1, and 25-hydroxyvitamin D > 30 ng/ml. Twenty-six (26 %) subjects showed abnormal T-score in the control group; 26 (59 %) in the non-recurrent BPPV and 22 (61 %) in the recurrent BPPV group. Chi square test showed significant difference between the control group and both BPPV groups. The control group had significantly higher 25-hydroxyvitamin D levels than the BPPV subgroups (p disorders in cases with recurrent BPPV.

Unilateral posterior canal-plugging surgery for intractable bilateral posterior canal-type benign paroxysmal positional vertigo.

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Hotta, Sayaka; Imai, Takao; Higashi-Shingai, Kayoko; Okazaki, Suzuyo; Okumura, Tomoko; Uno, Atsuhiko; Ohta, Yumi; Morihana, Tetsuo; Sato, Takashi; Inohara, Hidenori

2017-10-01

To investigate the effectiveness of unilateral posterior semicircular canal (PSCC)-plugging surgery for patients with intractable bilateral PSCC-type benign paroxysmal positional vertigo (P-BPPV). From July 2011 to December 2015, we diagnosed 136 patients with P-BPPV. Of these, 3 patients had bilateral P-BPPV, and in 2 of the 3, the condition had been refractory to conservative treatment for more than 1 year. We planned a staged PSCC-plugging surgery for these 2 patients; initially one side was treated, and the contralateral side was treated 6 months later. After the first surgery, both patients experienced improvement in symptoms of vertigo and nystagmus on the operated side and no change on the non-operated side. Patients underwent the Epley maneuver for the non-operated side. In one case, the non-operated side was cured. In the other case, although the P-BPPV was not completely resolved, the patient was satisfied with the result of unilateral surgery because he was now able to turn in bed to the operated side without vertigo. Before surgery, he had experienced vertigo when turning even slightly in bed. We propose that even unilateral PSCC-plugging surgery is effective for some patients with intractable bilateral P-BPPV. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

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Marcos A.S. Leal

2017-12-01

Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

Peptide YY induces characteristic meal patterns of aged mice.

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Mogami, Sachiko; Yamada, Chihiro; Fujitsuka, Naoki; Hattori, Tomohisa

2017-11-01

Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device. Plasma peptide YY (PYY) levels were assessed under the several feeding status or after treatment of PYY. PYY and its receptor (NPY Y2 receptor, Y2R) antagonist were intraperitoneally administered 30min before the monitoring. Although the basal 24-h meal amounts did not differ by age, the total meal time and frequency of minimum feeding activity (bout) were significantly increased and the average bout size and time per bout were significantly decreased in aged mice. PYY dynamics were abnormal and the temporal reduction in food intake by exogenous PYY was more prominent in aged mice than in young mice. PYY administration to young mice induced aged-like meal patterns, and Y2R antagonist administration to aged mice induced young-like meal patterns. Aged mice exhibited characteristic meal patterns probably due to PYY metabolism dysfunction and/or enhanced PYY-Y2R signaling, suggesting a novel method for assessing eating difficulties in aged animals and a potential target for the remedy. Copyright © 2017 Elsevier Inc. All rights reserved.

Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

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Tesemma Sileshi

2014-03-01

Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo.

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Jeong, Seong-Hae; Kim, Ji-Soo; Shin, Jong Wook; Kim, Sungbo; Lee, Hajeong; Lee, Ae Young; Kim, Jae-Moon; Jo, Hyunjin; Song, Junghan; Ghim, Yuna

2013-03-01

Previous studies have demonstrated an association of osteopenia/osteoporosis with idiopathic benign paroxysmal positional vertigo (BPPV). Since vitamin D takes part in the regulation of calcium and phosphorus found in the body and plays an important role in maintaining proper bone structure, decreased bone mineral density in patients with BPPV may be related to decreased serum vitamin D. We measured the serum levels of 25-hydroxyvitamin D in 100 patients (63 women and 37 men, mean age ± SD = 61.8 ± 11.6) with idiopathic BPPV and compared the data with those of 192 controls (101 women and 91 men, mean age ± SD = 60.3 ± 11.3) who had lived in the same community without dizziness or imbalance during the preceding year. The selection of the controls and acquisition of clinical information were done using the data from the Fourth Korean National Health and Nutrition Examination Survey, 2008. The serum level of 25-hydroxyvitamin D was lower in the patients with BPPV than in the controls (mean ± SD = 14.4 ± 8.4 versus 19.1 ± 6.8 ng/ml, p = 0.001). Furthermore, patients with BPPV showed a higher prevalence of decreased serum vitamin D (diabetes, proteinuria, regular exercise and the existence of decreased bone mineral density demonstrated that vitamin D insufficiency (10-20 ng/ml) and deficiency (<10 ng/ml) were associated with BPPV with the odds ratios of 3.8 (95 % confidence interval = 1.51-9.38, p = 0.004) and 23.0 (95 % confidence interval = 6.88-77.05, p < 0.001). Our study demonstrated an association between idiopathic BPPV and decreased serum vitamin D. Decreased serum vitamin D may be a risk factor of BPPV.

Hyperandrogenemia Induced by Letrozole Treatment of Pubertal Female Mice Results in Hyperinsulinemia Prior to Weight Gain and Insulin Resistance.

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Skarra, Danalea V; Hernández-Carretero, Angelina; Rivera, Alissa J; Anvar, Arya R; Thackray, Varykina G

2017-09-01

Women with polycystic ovary syndrome (PCOS) diagnosed with hyperandrogenism and ovulatory dysfunction have an increased risk of developing metabolic disorders, including type 2 diabetes and cardiovascular disease. We previously developed a model that uses letrozole to elevate endogenous testosterone levels in female mice. This model has hallmarks of PCOS, including hyperandrogenism, anovulation, and polycystic ovaries, as well as increased abdominal adiposity and glucose intolerance. In the current study, we further characterized the metabolic dysfunction that occurs after letrozole treatment to determine whether this model represents a PCOS-like metabolic phenotype. We focused on whether letrozole treatment results in altered pancreatic or liver function as well as insulin resistance. We also investigated whether hyperinsulinemia occurs secondary to weight gain and insulin resistance in this model or if it can occur independently. Our study demonstrated that letrozole-treated mice developed hyperinsulinemia after 1 week of treatment and without evidence of insulin resistance. After 2 weeks of letrozole treatment, mice became significantly heavier than placebo mice, demonstrating that weight gain was not required to develop hyperinsulinemia. After 5 weeks of letrozole treatment, mice exhibited blunted glucose-stimulated insulin secretion, insulin resistance, and impaired insulin-induced phosphorylation of AKT in skeletal muscle. Moreover, letrozole-treated mice exhibited dyslipidemia after 5 weeks of treatment but no evidence of hepatic disease. Our study demonstrated that the letrozole-induced PCOS mouse model exhibits multiple features of the metabolic dysregulation observed in obese, hyperandrogenic women with PCOS. This model will be useful for mechanistic studies investigating how hyperandrogenemia affects metabolism in females. Copyright © 2017 Endocrine Society.

Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

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Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

2015-01-01

Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

Anticonvulsant Activity of Argyreia speciosa in Mice.

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Vyawahare, N S; Bodhankar, S L

2009-03-01

Argyreia speciosa commonly known as Vridha daraka in Sanskrit is one of the important plants used in indigenous system of medicine. The root is regarded as an alternative tonic and useful in the diseases of nervous system. To confirm the veracity of aforementioned claim, we have evaluated the anticonvulsant effect of the extract. In this investigation, the mice were pretreated with different doses of Argyreia speciosa extract (100, 200, 400 mg/kg) for 10 days and then, they were subjected to either pentylenetetrazole (80 mg/kg) or maximal electroshock seizures (50 mA, 0.2 s) treatment. The hydroalcoholic extract of Argyreia speciosa at the dose of 200 and 400 mg/kg significantly delayed the latency to the onset of first clonus as well as onset of death in unprotected mice and exhibited protection in 16.66% and 33.33% of pentylenetetrazole treated mice respectively. Whereas in case of maximal electroshock-seizures, the dose of 200 and 400 mg/kg significantly reduced the duration of hind limb extension and both the doses were statistically found to be equipotent. The reference standards, clonazepam (0.1 mg/kg) and phenytoin (20 mg/kg) provided complete protection. Thus, present study revealed anticonvulsant effect of Argyreia speciosa against pentylenetetrazole- and maximal electroshock-induced convulsions in mice.

The impact of diabetes on mobility, balance, and recovery after repositioning maneuvers in individuals with benign paroxysmal positional vertigo.

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D'Silva, Linda J; Whitney, Susan L; Santos, Marcio; Dai, Hongying; Kluding, Patricia M

2017-06-01

The prevalence of benign paroxysmal positional vertigo (BPPV) is higher in people with type 2 diabetes (DM). The impact of DM on mobility, balance, and management of BPPV is unknown. This prospective study compared symptom severity, mobility and balance before and after the canalith repositioning maneuver (CRM) in people with posterior canal BPPV canalithiasis, with and without DM. Fifty participants, BPPV (n=34) and BPPV+DM (n=16) were examined for symptom severity (dizziness handicap inventory, DHI), mobility (functional gait assessment, FGA), and postural sway (using an accelerometer in five conditions) before and after the CRM. The number of maneuvers required for symptom resolution was recorded. At baseline, no differences in DHI or FGA scores were seen between groups, however, people with BPPV+DM had higher sway velocity in the medio-lateral direction in tandem stance (pdiabetes, as well as the influence of diabetic peripheral neuropathy on functional performance are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice.

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Sun-Kyoung Im

Full Text Available Sorting nexin 5 (Snx5 has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 are largely unknown. Here, we report that disruption of the Snx5 gene in mice (Snx5(-/- mice resulted in partial perinatal lethality; 40% of Snx5(-/- mice died shortly after birth due to cyanosis, reduced air space in the lungs, and respiratory failure. Histological analysis revealed that Snx5(-/- mice exhibited thickened alveolar walls associated with undifferentiated alveolar epithelial type I cells. In contrast, alveolar epithelial type II cells were intact, exhibiting normal surfactant synthesis and secretion. Although the expression levels of surfactant proteins and saturated phosphatidylcholine in the lungs of Snx5(-/- mice were comparable to those of Snx5(+/+ mice, the expression levels of T1α, Aqp5, and Rage, markers for distal alveolar epithelial type I cells, were significantly decreased in Snx5 (-/- mice. These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth.

Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

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Alessandro Ieraci

2016-01-01

Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

Intestinal flora imbalance promotes alcohol-induced liver fibrosis by the TGFβ/smad signaling pathway in mice.

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Zhang, Dong; Hao, Xiuxian; Xu, Lili; Cui, Jing; Xue, Li; Tian, Zibin

2017-10-01

Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut-liver axis. The present study investigated the role of intestinal flora in alcohol-induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol

An Overview of the Dynamics of the Volcanic Paroxysmal Explosive Activity, and Related Seismicity, at Andesitic and Dacitic Volcanoes (1960–2010

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Vyacheslav M. Zobin

2018-05-01

Full Text Available Understanding volcanic paroxysmal explosive activity requires the knowledge of many associated processes. An overview of the dynamics of paroxysmal explosive eruptions (PEEs at andesitic and dacitic volcanoes occurring between 1960 and 2010 is presented here. This overview is based mainly on a description of the pre-eruptive and eruptive events, as well as on the related seismic measurements. The selected eruptions are grouped according to their Volcanic Explosivity Index (VEI. A first group includes three eruptions of VEI 5-6 (Mount St. Helens, 1980; El Chichón, 1982; Pinatubo, 1991 and a second group includes three eruptions of VEI 3 (Usu volcano, 1977; Soufriere Hills Volcano (SHV, 1996, and Volcán de Colima, 2005. The PEEs of the first group have similarity in their developments that allows to propose a 5-stage scheme of their dynamics process. Between these stages are: long (more than 120 years period of quiescence (stage 1, preliminary volcano-tectonic (VT earthquake swarm (stage 2, period of phreatic explosions (stage 3 and then, PEE appearance (stage 4. It was shown also that the PEEs of this group during their Plinian stage “triggered” the earthquake sequences beneath the volcanic structures with the maximum magnitude of earthquakes proportional to the volume of ejecta of PEEs (stage 5. Three discussed PEEs of the second group with lower VEI developed in more individual styles, not keeping within any general scheme. Among these, one PEE (SHV may be considered as partly following in development to the PEEs of the first group, having stages 1, 3, and 4. The PEEs of Usu volcano and of Volcán de Colima had no preliminary long-term stages of quiescence. The PEE at Usu volcano came just at the end of the preceding short swarm of VT earthquakes. At Volcán de Colima, no preceding swarm of VT occurred. This absence of any regularity in development of lower VEI eruptions may refer, among other reasons, to different conditions of opening

Functional inactivation of dorsal medial striatum alters behavioral flexibility and recognition process in mice.

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Qiao, Yanhua; Wang, Xingyue; Ma, Lian; Li, Shengguang; Liang, Jing

2017-10-01

Deficits in behavioral flexibility and recognition memory are commonly observed in mental illnesses and neurodegenerative diseases. Abnormality of the striatum has been implicated in an association with the pathology of these diseases. However, the exact roles of striatal heterogeneous structures in these cognitive functions are still unknown. In the present study, we investigated the effects of suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus accumbens core (NAcC) on reversal learning and novelty recognition in mice. In addition, the locomotor activity, anxiety-like behavior and social interaction were analyzed. Neuronal inactivation was performed by expressing lentivirus-mediated tetanus toxin (TeNT) in the target regions. The results showed that reversal learning was facilitated by neuronal inactivation in the DMStr but not the NAcC, which was attributable to accelerated extinction of acquired strategy but not to impaired memory retention. Furthermore, mice with NAcC inactivation spent more time exploring a novel object than a familiar one, comparable to control mice. In contrast, mice with DMStr inactivation exhibited no preference to a novel environment during the novel object or place recognition test. The DMStr mice also exhibited decreased anxiety level. No phenotypic effect was observed in the locomotion or social interaction in mice with either DMStr or NAcC inactivation. Altogether, these findings suggest that the DMStr but not the ventral area of the striatum plays a crucial role in learning and memory by coordinating spatial exploration as well as mediating information updating. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice.

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Liu, Jing-yu; Feng, Cui-ping; Li, Xing; Chang, Ming-chang; Meng, Jun-long; Xu, Li-jing

2016-05-01

To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF-α, IFN-γ, and IL-1β mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

Exhibiting Epistemic Objects

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Tybjerg, Karin

2017-01-01

of exhibiting epistemic objects that utilize their knowledge-generating potential and allow them to continue to stimulate curiosity and generate knowledge in the exhibition. The epistemic potential of the objects can then be made to work together with the function of the exhibition as a knowledge-generating set...

Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice as assessed in a radial-arm water maze.

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Wolff, Mathieu; Benhassine, Narimane; Costet, Pierre; Hen, Rene; Segu, Louis; Buhot, Marie-Christine

2003-01-01

Serotonin (5-HT) plays a modulatory role in mnemonic functions, especially by interacting with the cholinergic system. The 5-HT1B receptor is a key target of this interaction. The 5-HT1B receptor knockout mice were found previously to exhibit a facilitation in hippocampal-dependent spatial reference memory learning. In the present study, we submitted mice to a delayed spatial working memory task, allowing the introduction of various delays between an exposure trial and a test trial. The 5-HT1BKO and wild-type mice learned the task in a radial-arm water maze (returning to the most recent presented arm containing the escape platform), and exhibited a high level of performance at delays of 0 and 5 min. However, at the delay of 60 min, only 5-HT1BKO mice exhibited an impairment. At a delay of 90 min, all mice were impaired. Treatment by scopolamine (0.8 mg/kg) induced the same pattern of performance in wild type as did the mutation for short (5 min, no impairment) and long (60 min, impairment) delays. The 22-month-old wild-type and knockout mice exhibited an impairment at short delays (5 and 15 min). The effect of the mutation affected both young-adult and aged mice at delays of 15, 30, and 60 min. Neurobiological data show that stimulation of the 5-HT1B receptor inhibits the release of acetylcholine in the hippocampus, but stimulates this in the frontal cortex. This dual function might, at least in part, explain the opposite effect of the mutation on reference memory (facilitation) and delay-dependent working memory (impairment). These results support the idea that cholinergic-serotonergic interactions play an important role in memory processes.

The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

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Fritz, Brandon M; Boehm, Stephen L

2014-12-01

We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

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Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

2017-01-06

Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

Wound healing and longevity: lessons from long-lived αMUPA mice.

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Yanai, Hagai; Toren, Dimitri; Vierlinger, Klemens; Hofner, Manuela; Nöhammer, Christa; Chilosi, Marco; Budovsky, Arie; Fraifeld, Vadim E

2015-03-01

Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage.

Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries.

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Velosky, Alexander G; Tucker, Laura B; Fu, Amanda H; Liu, Jiong; McCabe, Joseph T

2017-05-01

In contact sports, repetitive concussive brain injury (rCBI) is the prevalent form of head injury seen in athletes. The need for effective treatment is urgent as rCBI has been associated with a host of cognitive, behavioral and neurological complaints. There has been a growing trend in the use of female animals in pre-clinical research, but few studies have investigated possible sex differences following rCBI. The goal of the current study was to determine any differences between male and female C57BL/6J mice on assessments of learning and memory after repetitive concussive injury. Following rCBI by impact to the scalp, male mice exhibited longer righting reflexes during acute recovery. In both sexes, there were no evident histopathological changes observed in the underlying cerebral cortex or hippocampus. Reactive astrogliosis was elevated in the corpus callosum and optic tract, and astrogliosis was slightly less in the optic tract of female mice. rCBI mice exhibited impairment during the learning phase of the Morris water maze (MWM), but female mice, in comparison to male mice, were observed to have superior spatial memory during standard MWM probe trials. Female mice were overall more active, evidenced by greater distances traveled in the y-maze and greater swim speeds in the MWM. The results of this study demonstrate sex differences in cognitive performance following rCBI and support previous research suggesting the neuroprotective role of sex in brain injury. Published by Elsevier B.V.

Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

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Schlamp Cassandra L

2007-03-01

Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving

Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

International Nuclear Information System (INIS)

Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

2003-01-01

Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

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Becks, Lisa; Shi, Runhua; McLarty, Jerry; Pruitt, Kevin; Zhang, Songlin; Kleiner-Hancock, Heather E; Prince, Misty; Burson, Hannah; Christophe, Christopher; Broadway, Mason; Itoh, Ken; Yamamoto, Masayuki; Mathis, Michael; Orchard, Elysse

2010-01-01

Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis. Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test. All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice. We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression

Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

International Nuclear Information System (INIS)

Joo, Eun Yeon; Hong, Seung Bong; Tae, Woo Suk; Kim, Jee Hyun; Han, Sun Jung; Seo, Dae Won; Lee, Kyung-Han; Kim, Byung Tae; Kim, Myoung-Hee; Kim, Seunghwan; Lee, Mann Hyung

2005-01-01

Previous cerebral blood flow and glucose metabolism studies suggest that the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal kinesigenic choreoathetosis (PKC). However, the underlying cerebral abnormalities in idiopathic PKC have not been elucidated. To localise cerebral perfusion abnormalities in PKC, we performed interictal brain perfusion 99m Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in PKC patients and in normal controls. Sixteen patients with idiopathic PKC and 18 age- and sex-matched normal controls were included. The patients were de novo diagnosed as having PKC, or had not taken medication for at least 3 months; none of them had structural abnormalities on MRI. Patients had a history of PKC attacks of a duration not exceeding 5 min and starting either on one side or on both sides of the body. These attacks were always induced by a sudden initiation of voluntary movement. PKC attacks were recorded in a hospital after being induced by neurology staff in 13 of the 16 patients. Interictal brain perfusion 99m Tc-ECD SPECT was performed in all 16 patients and 18 normal controls. Differences between the cerebral perfusion in the PKC group and the normal control group were tested by statistical parametric mapping. Student's t test was used for inter-group comparisons. Compared with normal controls, patients with idiopathic PKC showed interictal hypoperfusion in the posterior regions of the bilateral caudate nuclei (false discovery rate-corrected P<0.001 with a small volume correction). This study showed that cerebral perfusion abnormality of bilateral caudate nuclei is present in idiopathic PKC. (orig.)

Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

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Joo, Eun Yeon; Hong, Seung Bong; Tae, Woo Suk; Kim, Jee Hyun; Han, Sun Jung; Seo, Dae Won [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center and Center for Clinical Medicine, SBRI, Seoul (Korea); Lee, Kyung-Han; Kim, Byung Tae [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center and Center for Clinical Medicine, SBRI, Seoul (Korea); Kim, Myoung-Hee [Ewha Women' s University, Department of Computer Science and Engineering, Seoul (Korea); Kim, Seunghwan [POSTECH, APCTP/NCSL, Department of Physics, Pohang (Korea); Lee, Mann Hyung [Catholic University of Daegue, College of Pharmacy, Gyongbook (Korea)

2005-10-01

Previous cerebral blood flow and glucose metabolism studies suggest that the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal kinesigenic choreoathetosis (PKC). However, the underlying cerebral abnormalities in idiopathic PKC have not been elucidated. To localise cerebral perfusion abnormalities in PKC, we performed interictal brain perfusion {sup 99m}Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in PKC patients and in normal controls. Sixteen patients with idiopathic PKC and 18 age- and sex-matched normal controls were included. The patients were de novo diagnosed as having PKC, or had not taken medication for at least 3 months; none of them had structural abnormalities on MRI. Patients had a history of PKC attacks of a duration not exceeding 5 min and starting either on one side or on both sides of the body. These attacks were always induced by a sudden initiation of voluntary movement. PKC attacks were recorded in a hospital after being induced by neurology staff in 13 of the 16 patients. Interictal brain perfusion {sup 99m}Tc-ECD SPECT was performed in all 16 patients and 18 normal controls. Differences between the cerebral perfusion in the PKC group and the normal control group were tested by statistical parametric mapping. Student's t test was used for inter-group comparisons. Compared with normal controls, patients with idiopathic PKC showed interictal hypoperfusion in the posterior regions of the bilateral caudate nuclei (false discovery rate-corrected P<0.001 with a small volume correction). This study showed that cerebral perfusion abnormality of bilateral caudate nuclei is present in idiopathic PKC. (orig.)

Inflammatory Macrophage Phenotype in BTBR T+tf/J Mice

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Paul eAshwood

2013-09-01

Full Text Available Although autism is a behaviorally defined disorder, many studies report an association with increased pro-inflammatory cytokine production. Recent characterization of the BTBR T+tf/J (BTBR inbred mouse strain has revealed several behavioral characteristics including social deficits, repetitive behavior, and atypical vocalizations which may be relevant to autism. We therefore hypothesized that asocial BTBR mice, which exhibit autism-like behaviors, may have an inflammatory immune profile similar to that observed in children with autism. The objectives of this study were to characterize the myeloid immune profile of BTBR mice and to explore their associations with autism-relevant behaviors. C57BL/6J (C57 mice and BTBR mice were tested for social interest and repetitive self-grooming behavior. Cytokine production was measured in bone-marrow derived macrophages incubated for 24 hours in either growth media alone, LPS, IL-4/ LPS, or IFNγ/ LPS to ascertain any M1/M2 skewing. After LPS stimulation, BTBR macrophages produced higher levels of IL-6, MCP-1, and MIP-1α and lower IL-10 (p<0.01 that C57 mice, suggesting an exaggerated inflammatory profile. After exposure to IL-4/LPS BTBR macrophages produced less IL-10 than C57 macrophages and more IL-12p40 (p<0.01 suggesting poor M2 polarization. Levels of IL-12(p70 (p<0.05 were higher in BTBR macrophages after IFNγ/LPS stimulation, suggesting enhanced M1 polarization. We further observed a positive correlation between grooming frequency, and production of IL-12(p40, IL-12p70, IL-6, and TNFα (p<0.05 after treatment with IFNγ/LPS across both strains. Collectively, these data suggest that the asocial BTBR mouse strain exhibits a more inflammatory, or M1, macrophage profile in comparison to social C57 strain. We have further demonstrated a relationship between this relative increase in inflammation and repetitive grooming behavior, which may have relevance to repetitive and stereotyped behavior of autism.

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

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Stapleton, David I.; Lau, Xianzhong; Flores, Marcelo; Trieu, Jennifer; Gehrig, Stefan M.; Chee, Annabel; Naim, Timur; Lynch, Gordon S.; Koopman, René

2014-01-01

Background Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Results Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (Pglycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (PGlycogen synthase activity was 12% higher (Pglycogen branching enzyme activity was 70% lower (Pglycogen breakdown, glycogen phosphorylase, had 62% lower activity (Pglycogen debranching enzyme expression was 50% higher (Pglycogen (Pglycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; Pglycogen but reduced amounts of liver glycogen. PMID:24626262

Compulsive Addiction-like Aggressive Behavior in Mice.

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Golden, Sam A; Heins, Conor; Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Epstein, David H; Shaham, Yavin

2017-08-15

Some people are highly motivated to seek aggressive encounters, and among those who have been incarcerated for such behavior, recidivism rates are high. These observations echo two core features of drug addiction: high motivation to seek addictive substances, despite adverse consequences, and high relapse rates. Here we used established rodent models of drug addiction to determine whether they would be sensitive to "addiction-like" features of aggression in CD-1 mice. In experiments 1 and 2, we trained older CD-1 mice to lever press for opportunities to attack younger C57BL6/J mice. We then tested them for relapse to aggression seeking after forced abstinence or punishment-induced suppression of aggression self-administration. In experiment 3, we trained a large cohort of CD-1 mice and tested them for choice-based voluntary suppression of aggression seeking, relapse to aggression seeking, progressive ratio responding, and punishment-induced suppression of aggression self-administration. We then used cluster analysis to identify patterns of individual differences in compulsive "addiction-like" aggressive behavior. In experiments 1 and 2, we observed strong motivation to acquire operant self-administration of opportunities to aggress and relapse vulnerability during abstinence. In experiment 3, cluster analysis of the aggression-related measures identified a subset of "addicted" mice (∼19%) that exhibited intense operant-reinforced attack behavior, decreased likelihood to select an alternative reinforcer over aggression, heightened relapse vulnerability and progressive ratio responding, and resilience to punishment-induced suppression of aggressive behavior. Using procedures established to model drug addiction, we showed that a subpopulation of CD-1 mice demonstrate "addiction-like" aggressive behavior, suggesting an evolutionary origin for compulsive aggression. Published by Elsevier Inc.

Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce.

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Yokoi, Fumiaki; Yang, Guang; Li, Jindong; DeAndrade, Mark P; Zhou, Tong; Li, Yuqing

2010-10-01

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder caused by mutations in DYT1 coding for torsinA with ∼30% penetrance. Most of the DYT1 dystonia patients exhibit symptoms during childhood and adolescence. On the other hand, DYT1 mutation carriers without symptoms during these periods mostly do not exhibit symptoms later in their life. Little is known about what controls the timing of the onset, a critical issue for DYT1 mutation carriers. DYT11 myoclonus-dystonia is caused by mutations in SGCE coding for ε-sarcoglycan. Two dystonia patients from a single family with double mutations in DYT1 and SGCE exhibited more severe symptoms. A recent study suggested that torsinA contributes to the quality control of ε-sarcoglycan. Here, we derived mice carrying mutations in both Dyt1 and Sgce and found that these double mutant mice showed earlier onset of motor deficits in beam-walking test. A novel monoclonal antibody against mouse ε-sarcoglycan was developed by using Sgce knock-out mice to avoid the immune tolerance. Western blot analysis suggested that functional deficits of torsinA and ε-sarcoglycan may independently cause motor deficits. Examining additional mutations in other dystonia genes may be beneficial to predict the onset in DYT1 mutation carriers.

Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

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Yuan Yan Sin

Full Text Available Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1, which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2 mice. The resulting mice (Arg-Cre die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.

Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function.

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Gaier, Eric D; Eipper, Betty A; Mains, Richard E

2014-05-01

Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. © 2014 New York Academy of Sciences.

Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough.

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Miura, Shiroh; Shibata, Hiroki; Kida, Hiroshi; Noda, Kazuhito; Tomiyasu, Katsuro; Yamamoto, Ken; Iwaki, Akiko; Ayabe, Mitsuyoshi; Aizawa, Hisamichi; Taniwaki, Takayuki; Fukumaki, Yasuyuki

2008-10-15

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of hereditary motor and sensory neuropathy with autosomal dominant inheritance.

Involvement of gut microbial fermentation in the metabolic alterations occurring in n-3 polyunsaturated fatty acids-depleted mice

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Carpentier Yvon A

2011-06-01

Full Text Available Abstract Backround Western diet is characterized by an insufficient n-3 polyunsaturated fatty acid (PUFA consumption which is known to promote the pathogenesis of several diseases. We have previously observed that mice fed with a diet poor in n-3 PUFA for two generations exhibit hepatic steatosis together with a decrease in body weight. The gut microbiota contributes to the regulation of host energy metabolism, due to symbiotic relationship with fermentable nutrients provided in the diet. In this study, we have tested the hypothesis that perturbations of the gut microbiota contribute to the metabolic alterations occurring in mice fed a diet poor in n-3 PUFA for two generations (n-3/- mice. Methods C57Bl/6J mice fed with a control or an n-3 PUFA depleted diet for two generations were supplemented with prebiotic (inulin-type Fructooligosaccharides, FOS, 0.20 g/day/mice during 24 days. Results n-3/-mice exhibited a marked drop in caecum weight, a decrease in lactobacilli and an increase in bifidobacteria in the caecal content as compared to control mice (n-3/+ mice. Dietary supplementation with FOS for 24 days was sufficient to increase caecal weight and bifidobacteria count in both n-3/+ and n-3/-mice. Moreover, FOS increased lactobacilli content in n-3/-mice, whereas it decreased their level in n-3/+ mice. Interestingly, FOS treatment promoted body weight gain in n-3/-mice by increasing energy efficiency. In addition, FOS treatment decreased fasting glycemia and lowered the higher expression of key factors involved in the fatty acid catabolism observed in the liver of n-3/-mice, without lessening steatosis. Conclusions the changes in the gut microbiota composition induced by FOS are different depending on the type of diet. We show that FOS may promote lactobacilli and counteract the catabolic status induced by n-3 PUFA depletion in mice, thereby contributing to restore efficient fat storage.

Antidepressant effects of insulin in streptozotocin induced diabetic mice: Modulation of brain serotonin system.

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Gupta, Deepali; Kurhe, Yeshwant; Radhakrishnan, Mahesh

2014-04-22

Diabetes is a persistent metabolic disorder, which often leads to depression as a result of the impaired neurotransmitter function. Insulin is believed to have antidepressant effects in depression associated with diabetes; however, the mechanism underlying the postulated effect is poorly understood. In the present study, it is hypothesized that insulin mediates an antidepressant effect in streptozotocin (STZ) induced diabetes in mice through modulation of the serotonin system in the brain. Therefore, the current study investigated the antidepressant effect of insulin in STZ induced diabetes in mice and insulin mediated modulation in the brain serotonin system. In addition, the possible pathways that lead to altered serotonin levels as a result of insulin administration were examined. Experimentally, Swiss albino mice of either sex were rendered diabetic by a single intraperitoneal (i.p.) injection of STZ. After one week, diabetic mice received a single dose of either insulin or saline or escitalopram for 14days. Thereafter, behavioral studies were conducted to test the behavioral despair effects using forced swim test (FST) and tail suspension test (TST), followed by biochemical estimations of serotonin concentrations and monoamine oxidase (MAO) activity in the whole brain content. The results demonstrated that, STZ treated diabetic mice exhibited an increased duration of immobility in FST and TST as compared to non-diabetic mice, while insulin treatment significantly reversed the effect. Biochemical assays revealed that administration of insulin attenuated STZ treated diabetes induced neurochemical alterations as indicated by elevated serotonin levels and decreased MAO-A and MAO-B activities in the brain. Collectively, the data indicate that insulin exhibits antidepressant effects in depression associated with STZ induced diabetes in mice through the elevation of the brain serotonin levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet.

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Gong, Fang-Hua; Ye, Yan-Na; Li, Jin-Meng; Zhao, Hai-Yang; Li, Xiao-Kun

2017-07-01

Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin. Copyright © 2017. Published by Elsevier Taiwan.

PENGARUH FAKTOR PSIKOLOGIS TERHADAP KEPUTUSAN BERKUNJUNG WISATAWAN MICE MELALUI PT. Y&R KE BALI

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Ni Putu Masni Nistari; I Putu Sudana; I GPB. Sasrawan Mananda

2017-01-01

Tourism is a global industry sectors and potentially to be developed as a source of government income countries and regions. MICE (Meeting, Incentive, Convention and Exhibition) in Indonesia has great potential and is the flagship product of the tourism industry Indonesia. The purpose of this research is to determine the influence of psychological factors toward MICE tourists visiting decision to Bali through PT. Y&R. Sampling technique used in this research is purposive sampling. Sa...

Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

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Jeri-Anne Lyons

2010-09-01

Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

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Eva Ludvigsen

2011-01-01

Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

Mice with a targeted disruption of the Fanconi anemia homolog Fanca.

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Cheng, N C; van de Vrugt, H J; van der Valk, M A; Oostra, A B; Krimpenfort, P; de Vries, Y; Joenje, H; Berns, A; Arwert, F

2000-07-22

Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with cancer predisposition. Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients. Diagnosis of FA is based on their cellular hypersensitivity to DNA crosslinking agents and chromosome breakages. Somatic complementation experiments suggest the involvement of at least eight genes in FA. The gene for complementation group A (FANCA) is defective in the majority of FA patients. We show here that mice deficient of FANCA: are viable and have no detectable developmental abnormalities. The hematological parameters showed a slightly decreased platelet count and a slightly increased erythrocyte mean cell volume in mice at young age, but this did not progress to anemia. Consistent with the clinical phenotype of FA patients, both male and female mice showed hypogonadism and impaired fertility. Furthermore, embryonic fibroblasts of the knock-out mice exhibited spontaneous chromosomal instability and were hyper-responsive to the clastogenic effect of the crosslinker mitomycin C.

Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice

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Jin Jie; Wang Yu; Xu Yang; Chen Shilei; Wang Junping; Ran Xinze; Su Yongping; Wang Jin

2014-01-01

Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3 -/- ) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3 -/- mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3 -/- mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury. (author)

Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

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Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

2017-10-01

Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

Characteristics of gait ataxia in δ2 glutamate receptor mutant mice, ho15J.

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Eri Takeuchi

Full Text Available The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.

Increased anxiety-related behaviour in Hint1 knockout mice.

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Varadarajulu, Jeeva; Lebar, Maria; Krishnamoorthy, Gurumoorthy; Habelt, Sonja; Lu, Jia; Bernard Weinstein, I; Li, Haiyang; Holsboer, Florian; Turck, Christoph W; Touma, Chadi

2011-07-07

Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out.

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Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

2012-05-01

Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. Copyright © 2012 Elsevier B.V. All rights reserved.