scholarly journals Translational modeling of non-traumatic raised intracranial pressure in rodents; the impact of diet-induced obesity on cephalic hypersensitivity and retinal degeneration

2021 ◽  
Author(s):  
Connar Stanley James Westgate ◽  
Snorre Malm Hagen ◽  
Ida Marchen Egerod Israelsen ◽  
Steffen Ellitsgaard Hamann ◽  
Rigmor Jensen ◽  
...  

Elevated intracranial pressure (ICP) is a feature of critical cerebral disorders. Obesity has been linked to raised ICP, and especially to disorders such as idiopathic intracranial pressure (IIH). We aimed to explore the impact of diet-induced obesity (DIO) on ICP, cephalic sensitivity and structural retinal changes with the dual goal of developing a disease model for non-traumatic raised ICP and IIH. Rats were fed high-fat diet or matched control diet. To assess pain sensitivity, Von Frey and light/dark box testing were performed. Dual energy x-ray absorptiometry scanning was used to measure body composition. Optic nerve head and retinal structures were evaluated using optical coherence tomography. Intraocular pressure was assessed. Rats were then implanted with telemetric device for continuous ICP recording. At the end, eye histology and molecular analysis on choroid plexus (CP) and trigeminal ganglion (TG) were performed. The DIO rats had double the abdominal fat mass. ICP was 55% higher in obese rats (p=0.003). Altered pain thresholds were found in DIO rats as denoted by a lower periorbital threshold (p=0.0002). Expression of Calca and Trpv1 was elevated in TG. Furthermore, a peripapillary retinal nerve fiber layer swelling (p=0.0026) with subsequent neuroretinal degeneration p=0.02) was detected in DIO rats. There was a trend to increased expression of AQP1 and NKCC1 at CP. This study demonstrates for the first time that DIO leads to raised ICP, with clinically relevant sequalae. Our novel model for non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP and IIH.

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
O. Merino ◽  
R. Sánchez ◽  
B. M. Gregorio ◽  
F. J. Sampaio ◽  
J. Risopatrón

Obesity has adverse effects on male fertility and usually is diagnosed with a prevalence of vitamin D deficiency (VD-). Discussion on the impact of obesity/VD- on sperm function has been limited. This study analyzed the effects of diet-induced obesity/VD- on viability and plasma membrane integrity (PMI), superoxide anion (O2-) level, and DNA fragmentation (DNAfrag) in sperm Sprague-Dawley rats. The males were randomized into four groups and fed for a period of 12 weeks: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+), and G4: high-fat diet without vitamin D (HF/VD-). Sperm function parameters were analyzed by flow cytometry. PMI percentages and O2- levels were not affected by any of the diets. DNA fragmentation was increasing significantly (p<0.05) in the spermatozoa of animals with diets vitamin D deficient (G2) and diet-induced obesity (G4). Our results allow us to point out that diet-induced obesity and VD- produce greater damage in DNA sperm of rats. The use of nutraceuticals containing vitamin D could be reducing the risk of fragmentation of DNA in spermatozoa.


2017 ◽  
Vol 9 (2) ◽  
pp. 223-231 ◽  
Author(s):  
E. S. Dorey ◽  
C. L. Cullen ◽  
D. Lucia ◽  
K. M. Mah ◽  
M.-L. Roy Manchadi ◽  
...  

Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine active transporter (Slc6a3). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Matthew Pierce ◽  
Melissa Totten ◽  
Keith Erikson

Abstract Objectives Iron (Fe), Copper (Cu), and Manganese (Mn) are essential trace elements that are critical for health and must be maintained in an optimal physiological range. When there is a disturbance of this regulation, such as obesity, pathologies ranging from anemia to neurotoxicity can occur. The objective of this current study is to examine strain and sex differences in the distribution of systemic trace elements due to diet-induced obesity (DIO). We hypothesize that high fat DIO causes significant systemic alterations of Fe, Cu, Mn distributions compared to low fat diet with sex and strain as contributing factors. Methods Beginning at 21 days of age, male and female C57BL/6 J (n = 36) and DBA/2 J (n = 36) mice were fed either a high-fat diet (60% Kcal from fat) or a control diet (10% Kcal from fat) for 16 weeks. Food intake and body mass were measured weekly. At the end of the 16 weeks, blood, liver, and spleen tissues were collected. Fe, Cu, and Mn concentrations were measured using graphite furnace atomic absorption spectroscopy. Results While DIO did not cause any strain or sex differences in hematocrit, differences were detected in all three metals, Mn, Cu, and Fe concentrations in the liver and spleen. Specifically, there was a statistically significant sex by diet interaction on liver Mn concentrations (P = 0.008) and strain by sex interaction on spleen Mn concentrations (P = 0.002). There was a sex by diet and strain by sex interaction on liver Cu concentrations (P = 0.01 and P = 0.006, respectively). A three-way strain, sex, and diet interaction (P = 0.003) was observed for Cu in spleen. There was a strain by sex and strain by diet interaction on liver Fe concentrations (P = 0.031 and P = 0.002, respectively). There was a statistically significant strain, sex, and diet interaction on spleen Fe concentrations (P = 0.0002). The most prominent interactive effects of sex, strain and DIO was observed with liver and spleen Fe concentrations compared to Cu or Mn. For example, male DBA and female C57 mice had greatly reduced Fe in liver and spleen but their opposite sex counterparts were largely unaffected by the impact of DIO. Conclusions Our results expand our previous data by showing strain and sex differences not only in Fe, but Cu and Mn systemic concentrations. For females, the impact of DIO on Fe was more significant in the C57 strain whereas in males the effect of DIO was more significant in the DBA strain. Funding Sources UNCG Health and Human Sciences Research Grant & UNCG Faculty First Award.


2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs


2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Rupesh Rastogi ◽  
Virendra Kumar

The first legislation in India relating to patents was the Act VI of 1856. The Indian Patents and Design Act, 1911 (Act II of 1911) replaced all the previous Acts. The Act brought patent administration under the management of Controller of Patents for the first time. After Independence, it was felt that the Indian Patents & Designs Act, 1911 was not fulfilling its objective. Various comities were constituted to recommend, framing a patent law which can fulfill the requirement of Indian Industry and people. The Indian Patent Act of 1970 was enacted to achieve the above objectives. The major provisions of the act, provided for process, not the product patents in food, medicines, chemicals with a term of 14 years and 5-7 for chemicals and drugs. The Act enabled Indian citizens to access cheapest medicines in the world and paved a way for exponential growth of Indian Pharmaceutical Industry. TRIPS agreement, which is one of the important results of the Uruguay Round, mandated strong patent protection, especially for pharmaceutical products, thereby allowing the patenting of NCEs, compounds and processes. India is thereby required to meet the minimum standards under the TRIPS Agreement in relation to patents and the pharmaceutical industry. India’s patent legislation must now include provisions for availability of patents for both pharmaceutical products and processes inventions. The present paper examines the impact of change in Indian Patent law on Pharmaceutical Industry.


2020 ◽  
Vol 26 ◽  
Author(s):  
Shabana Bibi ◽  
Ayesha Sarfraz ◽  
Ghazala Mustafa ◽  
Zeeshan Ahmed ◽  
Muhammad Aurang Zeb ◽  
...  

Background: Coronavirus Disease-2019 belongs to the family of viruses which cause a serious pneumonia along with fever, breathing issues and infection of lungs for the first time in China and later spread worldwide. Objective: Several studies and clinical trials have been conducted to identify potential drugs and vaccines for Coronavirus Disease-2019. The present study listed natural secondary metabolites identified from plant sources with antiviral properties and could be safer and tolerable treatment for Coronavirus Disease-2019. Methods: A comprehensive search on the reported studies was conducted using different search engine such as Google scholar, SciFinder, Sciencedirect, Medline PubMed, and Scopus for the collection of research articles based on plantderived secondary metabolites, herbal extracts, and traditional medicine for coronavirus infections. Results: Status of COVID-19 worldwide and information of important molecular targets involved in COVID-19 is described and through literature search, is highlighted that numerous plant species and their extracts possess antiviral properties and studied with respect to Coronavirus treatments. Chemical information, plant source, test system type with mechanism of action for each secondary metabolite is also mentioned in this review paper. Conclusion: The present review has listed plants that have presented antiviral potential in the previous coronavirus pandemics and their secondary metabolites which could be significant for the development of novel and a safer drug which could prevent and cure coronavirus infection worldwide.


Author(s):  
Elli Anagnostou ◽  
Alexia Kafkoutsou ◽  
Despina Mavrogianni ◽  
Ekaterini Domali ◽  
Evangelia Dimitroulia ◽  
...  

Background: Molecular biology tools, such as the detection of single nucleotide polymorphisms (SNPs), have been considered to assist to the management of the ovarian stimulation protocols. Purpose: The aim of this study was to evaluate the impact of two polymorphisms, the Asn680Ser polymorphism of the FSHR gene, and the FSH β subunit (FSHβ) gene polymorphism -211 G>T, in a Greek population of women undergoing IVF/ICSI program in our center. In addition, a control group of fertile women was studied, to verify whether there are differences in the genotype distribution between fertile and infertile population for both polymorphisms, as the FSHβ gene polymorphism -211 G>T is studied for the first time in the Greek population. Results : The FSH β-211 G>T polymorphism, studied for the first time in the Greek infertile population, appears to be quite rare. When studying the two polymorphisms separately, statistically significant differences were obtained that concerned the LH levels. Discussion: According to the combination analysis of the two polymorphisms by the number of alleles, women with 2-3 polymorphic alleles needed more days of stimulation, but there were no differences in pregnancy rates. Conclusion: This molecular genetic study helps to elucidate whether the polygenic combination of the Asn680Ser and FSH β subunit -211 G>T gene polymorphisms is of additive value in the prediction of ovarian response to exogenous gonadotropins.


Author(s):  
Talbot C. Imlay

This chapter examines the post-war efforts of European socialists to reconstitute the Socialist International. Initial efforts to cooperate culminated in an international socialist conference in Berne in February 1919 at which socialists from the two wartime camps met for the first time. In the end, however, it would take four years to reconstitute the International with the creation of the Labour and Socialist International (LSI) in 1923. That it took so long to do so is a testimony to the impact of the Great War and to the Bolshevik revolution. Together, these two seismic events compelled socialists to reconsider the meaning and purpose of socialism. The search for answers sparked prolonged debates between and within the major parties, profoundly reconfiguring the pre-war world of European socialism. One prominent stake in this lengthy process, moreover, was the nature of socialist internationalism—both its content and its functioning.


Author(s):  
Mark Blaxill ◽  
Toby Rogers ◽  
Cynthia Nevison

AbstractThe cost of ASD in the U.S. is estimated using a forecast model that for the first time accounts for the true historical increase in ASD. Model inputs include ASD prevalence, census population projections, six cost categories, ten age brackets, inflation projections, and three future prevalence scenarios. Future ASD costs increase dramatically: total base-case costs of $223 (175–271) billion/year are estimated in 2020; $589 billion/year in 2030, $1.36 trillion/year in 2040, and $5.54 (4.29–6.78) trillion/year by 2060, with substantial potential savings through ASD prevention. Rising prevalence, the shift from child to adult-dominated costs, the transfer of costs from parents onto government, and the soaring total costs raise pressing policy questions and demand an urgent focus on prevention strategies.


Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 125
Author(s):  
Mariola Jabłońska ◽  
Janusz Janeczek ◽  
Beata Smieja-Król

For the first time, it is shown that inhaled ambient air-dust particles settled in the human lower respiratory tract induce lung calcification. Chemical and mineral compositions of pulmonary calcium precipitates in the lung right lower-lobe (RLL) tissues of 12 individuals who lived in the Upper Silesia conurbation in Poland and who had died from causes not related to a lung disorder were determined by transmission and scanning electron microscopy. Whereas calcium salts in lungs are usually reported as phosphates, calcium salts precipitated in the studied RLL tissue were almost exclusively carbonates, specifically Mg-calcite and calcite. These constituted 37% of the 1652 mineral particles examined. Mg-calcite predominated in the submicrometer size range, with a MgCO3 content up to 50 mol %. Magnesium plays a significant role in lung mineralization, a fact so far overlooked. The calcium phosphate (hydroxyapatite) content in the studied RLL tissue was negligible. The predominance of carbonates is explained by the increased CO2 fugacity in the RLL. Carbonates enveloped inhaled mineral-dust particles, including uranium-bearing oxides, quartz, aluminosilicates, and metal sulfides. Three possible pathways for the carbonates precipitation on the dust particles are postulated: (1) precipitation of amorphous calcium carbonate (ACC), followed by its transformation to calcite; (2) precipitation of Mg-ACC, followed by its transformation to Mg-calcite; (3) precipitation of Mg-free ACC, causing a localized relative enrichment in Mg ions and subsequent heterogeneous nucleation and crystal growth of Mg-calcite. The actual number of inhaled dust particles may be significantly greater than was observed because of the masking effect of the carbonate coatings. There is no simple correlation between smoking habit and lung calcification.


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