USE OF INHALANT ANESTHETICS IN THREE SNAKE SPECIES

Different snake species respond differently to various anesthetic agents. Hence, an anesthetic procedure developed for one species cannot necessarily be safely transferred to another species. The goal of this paper is to summarize our experience using inhalant anesthetics on three snake species, including both procedures that were successful and those we found to be less satisfactory. We found isoflurane delivered with a precision vaporizer to be the best agent to anesthetize black rat snakes (Elaphe o. obsoleta). Sex and mass did not seem to affect induction times in black rat snakes, but larger female rat snakes recovered faster from anesthesia than smaller females. Halothane delivered in the open method provided consistent anesthesia in northern water snakes (Nerodia s. sipedon), although it caused some mortality and should not be used on debilitated patients. Halothane delivered with a precision vaporizer may be used to anesthetize eastern massasauga rattlesnakes (Sistrurus c. catenatus). However, care must be taken to prevent mortality resulting from anesthetic overdose. Sex and mass had no effect on induction and recovery times in the rattlesnakes, but stressed animals require longer induction and recovery times

Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist

Several reports have provided evidence that body size early in life is positively correlated with risk of subsequent breast cancer, but the biological basis for this relationship is unclear. We examined tumour incidence in transgenic mice expressing a growth hormone (GH) antagonist and in non-transgenic littermates following exposure to dimethylbenz[a]anthracene (DMBA), a well characterized murine mammary gland carcinogen. The transgenic animals had lower IGF-I levels, were smaller in terms of body size and weight, and exhibited decreased tumour incidence relative to controls. The demonstration that both body size early in life and breast cancer incidence are influenced by experimental perturbation of the GH–IGF-I axis in a transgenic model provides evidence that variability between individuals with respect to these hormones underlies the relationship between body size early in life and breast cancer risk observed in epidemiological studies. © 2001 Cancer Research Campaign http://www.bjcancer.co

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction.

The neurochemical changes underlying human emotions and social behaviour are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala. We show that hypocretin-1 levels are maximal during positive emotion, social interaction and anger, behaviours that induce cataplexy in human narcoleptics. In contrast, melanin-concentrating hormone levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. Melanin-concentrating hormone levels increase at sleep onset, consistent with a role in sleep induction, whereas hypocretin-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized

Vestibular contributions to lateral stabilization are bilaterally dependent during split belt walking

Vestibular information is critical for maintaining balance during locomotion, and is known to be attenuated with increasing locomotor velocity and cadence. This attenuation is muscle and phase dependent, and is thought to reflect the functional contribution of each muscle to balance control during each stride of the gait cycle. Bilaterally, the vestibular coupling is mirrored relative to the gait cycle as each leg undergoes similar modulation with variation in phase, velocity and cadence. Here, we asked whether the modulation of the vestibular contribution to each limb is bilaterally dependent. By using a split-belt treadmill with asymmetric belt speeds, we can control the locomotion properties of each leg and compare the vestibular modulation to symmetric conditions. We hypothesized that bilaterally symmetric vestibular modulation would indicate leg independent vestibular influence while bilaterally asymmetric vestibular modulation would indicate leg dependent vestibular influence. Subjects were exposed to binaural bipolar stochastic vestibular stimulation (0-25 Hz) during symmetric and asymmetric walking conditions. Symmetric trials were performed at belt speeds of 0.4 and 0.8 m/s and for 10 min. The asymmetric trial was performed at belt speeds of 0.4 and 0.8 m/s for 16 min. Subjects walked with a cadence of 78 steps/min which was easily maintained in both limbs. EMG of the bilateral medial gastrocnemii and three-dimensional ground reaction force and torques were collected. Only the last 340 strides (~ 9 min of data) were used in the analysis to avoid the adaptation that typically occurs within the first 250 strides (~ 6 min) of asymmetric walking. Significant muscle activity and lateral ground reaction forces (P < 0.01) were correlated to the input stimuli in all trials. Stimulus-EMG and -lateral ground reaction force correlations decreased at higher belt speeds during symmetric walking, as previously reported. During the split belt condition, the magnitude of correlations stimulus-EMG and -force were bilaterally asymmetric and different from their symmetric counterparts. During the asymmetric condition correlations decreased for the slow leg, but more closely resembled the responses observed during slow symmetric walking, and increased for the fast leg, but more closely resembled the responses observed during fast symmetric walking. These results indicate that the modulation of vestibular reflexes is dependent upon the specific kinematics of each leg but bilaterally linked to respond to the properties of the locomotion pattern

Molecular characterisation of viruses from Kiwifruit

In 2003 Apple stem grooving virus was discovered in Actinidia accessions from China, being held in quarantine in Auckland. Subsequent examination of kiwifruit germplasm from the same source has detected several additional viruses, including a ~300 nm rigid rod related to Ribgrass mosaic virus (Tobamovirus), a 700-750 nm flexuous virus related to Citrus leaf blotch virus (Flexiviridae) and a novel vitivirus. Currently these viruses have not been reported from commercial kiwifruit crops in New Zealand or elsewhere. The biological properties of the viruses from kiwifruit and their phylogenetic relationships with similar viruses from other plants will be described, and the possible implications for the international movement of Actinidia germplasm are discussed

Lack of the transcription factor hypoxia-inducible factor (HIF)-1α in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas

Accepted ManuscriptThe establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1a (HIF-1a) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1a in the caseation of granulomas. The genetic ablation of HIF-1a in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1a in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1a inactivation, accelerates granuloma necrosis.Support from national funds through FCT/MEC (Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência), when applicable cofunded by FEDER funds within the partnership agreement PT2020 related to the research unit number 4293; from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN); and from HMSP-ICT/0024/2010. T.M.S. received postdoctoral grant ON2201310 from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN). M.R. received Ph.D. grant SFRH/BD/89871/2012 from FCT, Portuga

Evidence for cognitive vestibular integration impairment in idiopathic scoliosis patients

<p>Abstract</p> <p>Background</p> <p>Adolescent idiopathic scoliosis is characterized by a three-dimensional deviation of the vertebral column and its etiopathogenesis is unknown. Various factors cause idiopathic scoliosis, and among these a prominent role has been attributed to the vestibular system. While the deficits in sensorimotor transformations have been documented in idiopathic scoliosis patients, little attention has been devoted to their capacity to integrate vestibular information for cognitive processing for space perception. Seated idiopathic scoliosis patients and control subjects experienced rotations of different directions and amplitudes in the dark and produced saccades that would reproduce their perceived spatial characteristics of the rotations (vestibular condition). We also controlled for possible alteration of the oculomotor and vestibular systems by measuring the subject's accuracy in producing saccades towards memorized peripheral targets in absence of body rotation and the gain of their vestibulo-ocular reflex.</p> <p>Results</p> <p>Compared to healthy controls, the idiopathic scoliosis patients underestimated the amplitude of their rotations. Moreover, the results revealed that idiopathic scoliosis patients produced accurate saccades to memorized peripheral targets in absence of body rotation and that their vestibulo-ocular reflex gain did not differ from that of control participants.</p> <p>Conclusion</p> <p>Overall, results of the present study demonstrate that idiopathic scoliosis patients have an alteration in cognitive integration of vestibular signals. It is possible that severe spine deformity developed partly due to impaired vestibular information travelling from the cerebellum to the vestibular cortical network or alteration in the cortical mechanisms processing the vestibular signals.</p

Stem Cell Res

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of the liver metabolism due to functional deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in overproduction of oxalate which complexes with calcium to form insoluble calcium-oxalate salts in urinary tracts, ultimately leading to end-stage renal disease. Currently, the only curative treatment for PH1 is combined liver-kidney transplantation, which is limited by donor organ shortage and lifelong requirement for immunosuppression. Transplantation of genetically modified autologous hepatocytes is an attractive therapeutic option for PH1. However, the use of fresh primary hepatocytes suffers from limitations such as organ availability, insufficient cell proliferation, loss of function, and the risk of immune rejection. We developed patient-specific induced pluripotent stem cells (PH1-iPSCs) free of reprogramming factors as a source of renewable and genetically defined autologous PH1-hepatocytes. We then investigated additive gene therapy using a lentiviral vector encoding wild-type AGT under the control of the liver-specific transthyretin promoter. Genetically modified PH1-iPSCs successfully provided hepatocyte-like cells (HLCs) that exhibited significant AGT expression at both RNA and protein levels after liver-specific differentiation process. These results pave the way for cell-based therapy of PH1 by transplantation of genetically modified autologous HLCs derived from patient-specific iPSCs