Adenovirus-Mediated Gene Transfer in Olfactory Epithelium and Olfactory Bulb: A Long-Term Study

2005 ◽  
Vol 114 (8) ◽  
pp. 629-633 ◽  
Author(s):  
Kiyoshi Doi ◽  
Ken-Ichi Nibu ◽  
Haruhiko Ishida ◽  
Haruo Okado ◽  
Toshio Terashima
Keyword(s):  
Gene Transfer ◽  
Olfactory Epithelium ◽  
Adenoviral Vector ◽  
Olfactory Nerve ◽  
Lacz Gene ◽  
Long Term Effects ◽  
Olfactory Bulbs ◽  
Long Term Study ◽  
Receptor Neurons

Objectives: We sought to study the spatiotemporal gene expression mediated by adenoviral vector in the olfactory pathways. Methods: The replication-defective adenoviral vector AxCALacZ, which encodes the enzyme Escherichia coli β-galactosidase, was applied to mouse olfactory epithelium by intranasal instillation. Results: The LacZ gene product, β-galactosidase, was expressed not only in the olfactory receptor neurons and their axons, but also in the olfactory bulbs. The first evidence of anterograde labeling was observed at postinfection day (PID) 2. At PID 3, β-galactosidase was strongly expressed in olfactory nerve axons, as well as their terminal glomeruli, in the olfactory bulbs. β-Galactosidase expression persisted up to PID 90, and there was a significant decrease in the number of labeled neurons at PID 30. Conclusions: These results suggest possible long-term effects of adenovirus-mediated gene transfer on the olfactory neurons, as well as the olfactory bulbs.

scholarly journals Assessing the Beneficial Effects of the Immunomodulatory Glycan LNFPIII on Gut Microbiota and Health in a Mouse Model of Gulf War Illness

2020 ◽  
Vol 17 (19) ◽  
pp. 7081
Author(s):  
Ryan S. Mote ◽  
Jessica M. Carpenter ◽  
Rachel L. Dockman ◽  
Andrew J. Steinberger ◽  
Garret Suen ◽  
...  
Keyword(s):  
Global Scale ◽  
Gulf War ◽  
Lipocalin 2 ◽  
Gut Health ◽  
Long Term Effects ◽  
Gulf War Illness ◽  
Term Study ◽  
Long Term Study ◽  
Short And Long Term

The microbiota’s influence on host (patho) physiology has gained interest in the context of Gulf War Illness (GWI), a chronic disorder featuring dysregulation of the gut–brain–immune axis. This study examined short- and long-term effects of GWI-related chemicals on gut health and fecal microbiota and the potential benefits of Lacto-N-fucopentaose-III (LNFPIII) treatment in a GWI model. Male C57BL/6J mice were administered pyridostigmine bromide (PB; 0.7 mg/kg) and permethrin (PM; 200 mg/kg) for 10 days with concurrent LNFPIII treatment (35 μg/mouse) in a short-term study (12 days total) and delayed LNFPIII treatment (2×/week) beginning 4 months after 10 days of PB/PM exposure in a long-term study (9 months total). Fecal 16S rRNA sequencing was performed on all samples post-LNFPIII treatment to assess microbiota effects of GWI chemicals and acute/delayed LNFPIII administration. Although PB/PM did not affect species composition on a global scale, it affected specific taxa in both short- and long-term settings. PB/PM elicited more prominent long-term effects, notably, on the abundances of bacteria belonging to Lachnospiraceae and Ruminococcaceae families and the genus Allobaculum. LNFPIII improved a marker of gut health (i.e., decreased lipocalin-2) independent of GWI and, importantly, increased butyrate producers (e.g., Butyricoccus, Ruminococcous) in PB/PM-treated mice, indicating a positive selection pressure for these bacteria. Multiple operational taxonomic units correlated with aberrant behavior and lipocalin-2 in PB/PM samples; LNFPIII was modulatory. Overall, significant and lasting GWI effects occurred on specific microbiota and LNFPIII treatment was beneficial.

LONG-TERM EFFECTS OF LIME ADDITIONS ON SUGARCANE YIELD AND SOIL CHEMICAL PROPERTIES IN NORTH QUEENSLAND

2000 ◽  
Vol 36 (3) ◽  
pp. 397-413 ◽  
Author(s):  
A. D. NOBLE ◽  
A. P. HURNEY
Keyword(s):  
Acid Soil ◽  
Ion Pairs ◽  
Chemical Properties ◽  
Exchange Capacity ◽  
Cane Yield ◽  
Long Term Effects ◽  
Exchangeable Acidity ◽  
Long Term Study ◽  
Highly Weathered Soils

In many highly weathered soils of the humid tropics, crop exploitation of the subsoil environment is limited through acid soil infertility. Since the use of mechanical profile modification is often prohibitive, surface incorporation of soil amendments is often the only means available to rectify this problem. A field trial was established with sugarcane on a strongly Acidic Dystrophic Brown Dermosol (Oxic Humitropept) in 1978 to evaluate the effects of surface incorporated lime additions on yield and performance of sugarcane. Eighteen years after the establishment of this trial, significant responses in cane yield were still evident following a single application of 5 t lime ha−1 made in 1978, as well as repeated applications of 5 t ha−1 on three occasions over the past 18 years. Progressive reductions in exchangeable acidity were accompanied by increases in subsoil Ca2+ and Mg2+. Soil pH increased significantly to a depth of 100 cm, this being attributed to the formation of ion pairs with NO3 in the surface soil, the subsequent leaching of these complexes and the differential uptake of NO3 at depth by roots. The results from this long-term study indicate that surface incorporation of lime is an economically viable approach to the remediation of subsoil acidity on soils such as those studied, namely, those with a low inherent cation exchange capacity and anion exchange capacity.

scholarly journals Long-Term Effects of AAV1/SERCA2a Gene Transfer in Patients With Severe Heart Failure

2014 ◽  
Vol 114 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Krisztina Zsebo ◽  
Alex Yaroshinsky ◽  
Jeffrey J. Rudy ◽  
Kim Wagner ◽  
Barry Greenberg ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Transfer ◽  
Severe Heart Failure ◽  
Long Term Effects

scholarly journals In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs

2000 ◽  
Vol 355 (1401) ◽  
pp. 1219-1223 ◽  
Author(s):  
Hans Peter Zippel
Keyword(s):  
Amino Acid ◽  
Olfactory Epithelium ◽  
Functional Recovery ◽  
Olfactory System ◽  
Olfactory Nerve ◽  
Sensory Cells ◽  
Similar Concentration ◽  
Olfactory Bulbs ◽  
Discriminative Ability ◽  
Bilateral Lesions

Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (107 -6 M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery, i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in ‘incorrect’ position (i) and (iii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii).

Neurogenesis in olfactory epithelium: loss and recovery of transepithelial voltage transients following olfactory nerve section

1981 ◽  
Vol 45 (3) ◽  
pp. 516-528 ◽  
Author(s):  
P. A. Simmons ◽  
T. V. Getchell
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Epithelium ◽  
Olfactory Receptor ◽  
Time Course ◽  
Olfactory Nerve ◽  
Nerve Section ◽  
Retrograde Degeneration ◽  
Transepithelial Voltage ◽  
Receptor Neurons ◽  
Voltage Transients

1. Unilateral olfactory nerve section was performed on the salamander, Ambystoma tigrinum. Physiological recordings and macroscopic observations were made to investigate the physiological correlates of functional recovery in the olfactory epithelium. 2. Slow transepithelial voltage transients, Veog, evoked by several odorous stimuli systematically decreased in amplitude during the initial 7 days and were not recorded at 10 days following nerve section, suggesting retrograde degeneration of receptor neurons. This was true for negative Veog(-), and positive, Veog(+), response components. Responses obtained from the untreated contralateral side of each animal remained similar to nonaxotomized controls. 3. Progressive recovery of the voltage transients was studied at 24, 45, 80, and 100 days following nerve section. At all stages of recovery, the wave form and time course of the responses were characteristic for each stimulus. This suggested that the response properties of the newly differentiated neuronal population were similar to those of the mature population. 4. At 100 days, response amplitudes evoked by all stimuli were similar to control values at all recording sites on the epithelial surface. The simultaneous loss and recovery of positive and negative components of the Veog indicated that the sources of both are dependent on the presence of functionally mature olfactory receptor neurons. 5. Visual inspection indicated that the olfactory nerve was reconstituted and reconnected to the olfactory bulb between 30-60 days following transection. The fact that physiological activity was recorded in the epithelium prior to this event suggests that molecular recognition and sensory transduction are not dependent on connectivity with the olfactory bulb. 6. It is concluded that physiological recovery of the olfactory receptor cell population occurs following axotomy. The time course of recovery was consistent with morphological evidence (see Ref. 57), indicating that newly differentiated receptor neurons are derived from cells in the basal region of the epithelium and replace the population lost through retrograde degeneration.

scholarly journals Impacts of Prepubertal Rearing Intensity and Calf Health on First-Lactation Yield and Lifetime Performance

2019 ◽  
Vol 19 (1) ◽  
pp. 201-214
Author(s):  
Nina Volkmann ◽  
Nicole Kemper ◽  
Anke Römer
Keyword(s):  
Body Weight ◽  
Milk Yield ◽  
Average Daily Gain ◽  
Long Term Effects ◽  
Duration Of Treatment ◽  
Feeding Intensity ◽  
Long Term Study ◽  
Lifetime Performance ◽  
Daily Gain

AbstractThe objective of the present study was to investigate possible long-term effects of calf and heifer feeding intensity on first-lactation milk yield and lifetime efficiency (milk per day of life). Detailed records from a total number of 2,252 female German Holstein calves from one commercial farm were obtained from birth to culling. Data regarding all information about calf’s birth, rearing time until first insemination, first calving, first-lactation yield and lifetime performance were collected over a 12-year period. This large data volume was merged, handled, checked for plausibility, classified and evaluated. Analyses revealed that body weight at an age of six months was significantly influenced by the average daily gain in the first two weeks of life (P<0.0001) and by the duration of treatment for respiratory diseases (P=0.0080). Moreover, first-lactation yield was affected by average daily gain in the whole first year of life (P=0.0013) and particularly in the period of month nine to twelve (P=0.00187). Lifetime efficiency was significantly influenced by body weight at first insemination (P=0.0051), average milk yield (P<0.0001) and reason for culling (P<0.0001). The results of this long-term study confirm that growth is important in general, but as shown by the negative correlation between average daily gain from month nine to twelve and the first lactation milk yield, nutrient intake (energy and protein) should be adapted to enable a controlled growth especially at certain periods of life. After six months of age, daily gain has to be controlled to avoid fat accumulation for a healthy and effective start of lactation. In addition, this analysis revealed that after passing first lactation, particularly health and fertility are the keys for a long efficient lifetime of dairy cows.

scholarly journals Hidden spinal dysraphism in the structure of osteoneural spine anomalies in children

2018 ◽  
pp. 33-37
Author(s):  
Y. N. Madzhidova ◽  
N. N. Ergasheva ◽  
N. N. Ergasheva
Keyword(s):  
Neurological Disorders ◽  
High Frequency ◽  
Spinal Dysraphism ◽  
Social Value ◽  
Long Term Effects ◽  
Term Study ◽  
Long Term Study ◽  
Sick Children ◽  
High Mics

Despite the long-term study of the problem of spinal dysraphism, its relevance is associated with a high frequency of children born with this disease and long-term effects that have medical-social value. In verified materials there are 144 sick children with osteoneural myelopathy assessed the frequency and characteristics of existing neurological disorders in hidden spinal dysraphism. Found that a combination of high MICs with urogenital and anorectal anomalies contribute aggravation of their flow.

Abstract 5423: rAAV-Mediated Gene Therapy with Inducible Nitric Oxide Synthase (iNOS) Affords Permanent Cardioprotection (1 Year) without Adverse Functional Consequences

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Qianhong Li ◽  
Yiru Guo ◽  
Wen-Jian Wu ◽  
Qinghui Ou ◽  
Santosh K Sanganalmath ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Viral Vector ◽  
Long Term Effects ◽  
Inos Gene ◽  
Inos Protein Expression ◽  
Functional Consequences ◽  
And Function ◽  
Oxide Synthase

The ultimate goal of prophylactic gene therapy is to confer permanent protection against ischemia. Although gene therapy with iNOS is known to protect against myocardial infarction at 3 days and up to 2 months, the long-term effects of iNOS gene therapy on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the iNOS gene (rAAV/iNOS) which enables long-lasting transgene expression. Mice received injections in anterior LV wall of rAAV/LacZ or rAAV/iNOS; 1 year later, they underwent a 30-min coronary occlusion (O) and 4 h of reperfusion (R). iNOS gene transfer resulted in elevated iNOS protein expression (+ 2.9-fold vs. LacZ group, n=6, P<0.05; Fig ) and iNOS activity (+ 3.3-fold vs. LacZ group, n=4, P<0.05) 1 year later. Infarct size (% of risk region) was dramatically reduced at 1 year after iNOS gene transfer (13.5+/−2.2%, n=12, vs. 42.9+/−2.6%, n=12, in LacZ group; Fig ). The infarct-sparing effects of iNOS gene therapy at 1 year were as powerful as those observed 24 h after ischemic PC (six 4-min O/4-min R cycles) (16.3+/−2.3%, n=8; Fig ). Importantly, compared with the LacZ group (n=11), iNOS gene transfer (n=10) had no effect on LV dimensions or function for up to 1 year (at 1 year: LVEDD 4.4+/−0.1 vs. 4.2+/−0.2 mm; LVESD 2.9+/−0.1 vs. 2.9+/−0.2 mm; FS 34+/−1.8 vs. 32+/−2.6%; EF 56+/−2.3 vs. 60+/−2.9%) (echocardiography). These data demonstrate, for the first time, that rAAV-mediated iNOS gene transfer affords long-term, probably permanent (1 year) cardioprotection without adverse functional consequences, providing a strong rationale for further preclinical testing of prophylactic gene therapy.

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