scholarly journals Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Malin Wennström ◽  
Shorena Janelidze ◽  
K. Peter R. Nilsson ◽  
Geidy E. Serrano ◽  
Thomas G. Beach ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Cellular Localization ◽  
Amyloid Plaques ◽  
Area Fraction ◽  
Granulovacuolar Degeneration ◽  
Plasma Biomarker ◽  
Age Related ◽  
Plaque Load ◽  
The Mean ◽  
Granulovacuolar Degeneration Bodies

AbstractRecent studies highlight phosphorylated tau (p-tau) at threonine tau 217 (p-tau217) as a new promising plasma biomarker for pathological changes implicated in Alzheimer’s disease (AD), but the specific brain pathological events related to the alteration in p-tau217 plasma levels are still largely unknown. Using immunostaining techniques of postmortem AD brain tissue, we show that p-tau217 is found in neurofibrillary tangles (NFTs) and neuropil threads that are also positive for p-tau181, 202, 202/205, 231, and 369/404. The p-tau217, but not the other five p-tau variants, was also prominently seen in vesicles structure positive for markers of granulovacuolar degeneration bodies and multi-vesicular bodies. Further, individuals with a high likelihood of AD showed significantly higher p-tau217 area fraction in 4 different brain areas (entorhinal cortex, inferior temporal gyrus, and superior frontal gyrus) compared to those with Primary age related tauopathy or other non-AD tauopathies. The p-tau217 area fraction correlated strongly with total amyloid-beta (Aβ) and NFT brain load when the whole group was analyzed. Finally, the mean p-tau217 area fraction correlated significantly with p-tau217 concentrations in antemortem collected plasma specifically in individuals with amyloid plaques and not in those without amyloid plaques. These studies highlight differences in cellular localization of different p-tau variants and suggest that plasma levels of p-tau217 reflect an accumulation of p-tau217 in presence of Aβ plaque load.

Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Half Life ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Primary Source ◽  
Positive Correlation ◽  
Activation Marker ◽  
Fibrin Degradation Products ◽  
The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

Age related volume of cadaver-prostates in Bangladesh

1970 ◽  
Vol 4 (2) ◽  
pp. 74-77
Author(s):  
Rukshana Ahmed ◽  
Shamim Ara
Keyword(s):  
Prostate Gland ◽  
Age Groups ◽  
Clinical Settings ◽  
Cross Sectional ◽  
Medical College ◽  
Age Related ◽  
Group A ◽  
Key Words Prostate ◽  
The Mean ◽  
Group B

Pathological changes in the prostate gland occur commonly with advancing age including inflammation, atrophy, hyperplasia and carcinoma and a change in volume is also evident. Estimation of volume of prostate may be useful in a variety of clinical settings. A cross-sectional descriptive study was designed to see the changes in volume of the prostate with advancing age and done in the Department of Anatomy, Dhaka Medical College, Dhaka from August 2006 to June 2007. The study was performed on 70 post-mortem human prostates collected from the unclaimed dead bodies that were under examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The samples were divided into three age groups; group A (10-20 years), group B (21-40 years) and group C (41-70 years). Volume of the sample was measured by using the ellipsoid formula. The mean ± SD volume of prostate was 7.68 ± 3.64 cm3 in group A, 10.61 ± 3.99 cm3 in group B and 15.40 ± 6.31 cm3 in group C. Mean difference in volume between group A and group C, group B and group C were statistically significant (p<0.001). Statistically significant positive correlation was found between age and volume of prostate (r = + 0.579, p < 0.001). Key Words: Prostate; volume; Bangladeshi. DOI: 10.3329/imcj.v4i2.6501Ibrahim Med. Coll. J. 2010; 4(2): 74-77

EFFECT OF OESTRONE-PELLET IMPLANTATION ON PLASMA LEVELS OF PROLACTIN

1970 ◽  
Vol 64 (2) ◽  
pp. 265-272 ◽  
Author(s):  
A. A. van der Gugten ◽  
M. Sala ◽  
H. G. Kwa
Keyword(s):  
Plasma Levels ◽  
Male Rats ◽  
Mean Values ◽  
The Mean ◽  
Dose Levels ◽  
Higher Doses ◽  
Primary Break

ABSTRACT Eight female and eight male rats were castrated at the age of 8 to 10 weeks. Four spayed and four orchidectomized rats received one oestrone/cholesterol pellet (200 μg oestrone) on the day of operation (day 0), a second pellet on day 11 and a third on day 23. The remaining animals received four oestrone/cholesterol pellets at these times. The fluctuations in the prolactin levels in the circulation induced by the oestrogen challenges in these animals were followed during 31 days by radioimmunoassays performed on days 3, 7, 9, 14, 15, 17, 23, 24, 25, 28 and 31. The results suggested that the homoeostatic mechanism regulating plasma levels of prolactin was capable of withstanding the three time-spaced oestrogen challenges only in the spayed animals receiving the lower doses of oestrogen, since it allowed the mean values of the prolactin levels to remain fairly constant during the first 4 weeks. The levels in this group rose to much higher levels only on day 31. The higher doses of oestrone in the spayed rats and both dose levels of oestrone in the orchidectomized animals apparently resulted in a primary break-down of the homoeostatic mechanism, since the prolactin levels in the animals of these groups rose to much higher levels either on day 7 or on day 9. This was followed by a period during which the prolactin levels appeared to be more or less under control, until a second and probably definitive failure of the homoeostatic mechanism allowed the mean levels to rise sharply again.

Pharmacodynamics of [D-Ser (t-Bu), Des-Gly]GnRH ethylamide (Buserelin®) in 6 normal volunteers.

1987 ◽  
Vol 115 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Y. Reznik ◽  
B. P. Winiger ◽  
M. L. Aubert ◽  
P. C. Sizonenko
Keyword(s):  
Urinary Excretion ◽  
Precocious Puberty ◽  
Plasma Levels ◽  
Intranasal Administration ◽  
Cross Reaction ◽  
Disappearance Rate ◽  
Gnrh Analog ◽  
Male Adolescents ◽  
Normal Volunteers ◽  
The Mean

Abstract. The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin®, HOE 766) was studied in plasma and urine after intranasal (300 μg) or sc (10 μg/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (± sem) was 0.46 ± 0.08, 0.50 ± 0.10, 0.28 ± 0.04, 0.24 ± 0.04, 0.13 ± 0.03, and 0.08 ± 0.02 μg/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 ± 1.96 μg/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 ± 3.0, 25.9 ± 0.8, 21.2 ± 0.9, 17.1 ± 0.7, 12.8 ± 1.1, 8.9 ± 0.4, and 5.9 ± 0.8 μg/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 ± 61 μg/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17β-E2and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.

Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease

2018 ◽  
Vol 15 (14) ◽  
pp. 1354-1360 ◽  
Author(s):  
Ping-Song Chou ◽  
Yi-Hui Kao ◽  
Meng-Ni Wu ◽  
Mei-Chuan Chou ◽  
Chun-Hung Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Alzheimer Disease ◽  
Rating Scale ◽  
Vital Role ◽  
Independent Effect ◽  
Cerebral White Matter ◽  
Clinical Dementia Rating ◽  
White Matter Changes ◽  
Age Related ◽  
The Mean

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Effect of High Plane of Nutrition on Blood Biochemical Profile and Onset of Puberty in Prepubertal HF X Kankrej Crossbred Heifers

2019 ◽  
Vol 15 (02) ◽  
pp. 14-17
Author(s):  
K K Hadiya ◽  
A J Dhami ◽  
D V Chaudhari ◽  
P M Lunagariya
Keyword(s):  
Body Weight ◽  
Treatment Group ◽  
Plasma Levels ◽  
Age Of Onset ◽  
The Body ◽  
Monthly Interval ◽  
Control Group ◽  
Blood Biochemical ◽  
Lower Protein ◽  
The Mean

This study was initiated on 24 prepubertal Holstein x Kankrej crossbred heifers of nearly identical age (7-9 months) and body weight (130-140 kg) at University farm to evaluate the effect of high plane of nutrition on blood biochemical and minerals profile and the age at puberty. Twelve heifers were managed under routine farm feeding (control) and the rest 12 under ideal optimum feeding regime (treatment) that included extra 1 kg concentrate, 30 g min mix and ad-lib dry fodder. The body weight and ovarian ultrasonography together with blood sampling was carried out at monthly interval from 10 to 18 months of age to study the ovarian dynamics and blood biochemical changes. High plane of nutrition to growing heifers was beneficial in reducing the age of onset of puberty (by 2-3 months) compared to routine farm fed group. The mean plasma total protein and cholesterol concentrations showed a rising trend with significant variations from 10 to 16 months of age, where it got mostly stabilized indicating adult profile. The activity of enzymes GOT and GPT also rose gradually and significantly from 10 months till 14-15 months of age, and thereafter it remained more or less static till 18 months of age. The levels of both these enzymes were higher, with lower protein and cholesterol, in control than the treatment group from 15-16 months of age onwards. The mean plasma levels of both calcium and phosphorus increased gradually and significantly with advancing age till 16-17 months of age, with little higher values in supplemented than a control group. The plasma levels of zinc, iron, copper, and cobalt also showed rising trend with significant differences between 10th and 12th-14th months of age, and from 15th to 18th months of age the levels were statistically the same in all the groups with slightly higher values in the treatment group.

Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study

2021 ◽  
pp. 112067212110057
Author(s):  
Pierre Gascon ◽  
Prithvi Ramtohul ◽  
Charles Delaporte ◽  
Sébastien Kerever ◽  
Danièle Denis ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Real Life ◽  
Age Related Macular Degeneration ◽  
Cumulative Number ◽  
Treat And Extend ◽  
Treatment Interval ◽  
Age Related ◽  
Treatment Naïve ◽  
The Mean

Purpose: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in “real-life” practice. Methods: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. Results: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. Conclusions: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.

scholarly journals Paucity of Entorhinal Cortex Pathology of the Alzheimer’s Type in SuperAgers with Superior Memory Performance

2021 ◽  
Author(s):  
Tamar Gefen ◽  
Allegra Kawles ◽  
Beth Makowski-Woidan ◽  
Janessa Engelmeyer ◽  
Ivan Ayala ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Entorhinal Cortex ◽  
Memory Performance ◽  
Amyloid Plaques ◽  
Memory Capacity ◽  
Relative Magnitude ◽  
Age Related ◽  
Increased Risk ◽  
Superior Memory ◽  
Normal Controls

Abstract Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer’s disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20–30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P &lt; 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers.

scholarly journals Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad
Keyword(s):  
Macular Degeneration ◽  
Healthy Aging ◽  
Intraclass Correlation ◽  
Age Related Macular Degeneration ◽  
Healthy Individuals ◽  
Age Related ◽  
Rod Function ◽  
The Mean ◽  
Highly Correlated ◽  
Effect Of Age

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

Ageing Changes in the Tensile Properties of Tendons: Influence of Collagen Fibril Volume Fraction

2008 ◽  
Vol 130 (2) ◽  
Author(s):  
K. L. Goh ◽  
D. F. Holmes ◽  
H.-Y. Lu ◽  
S. Richardson ◽  
K. E. Kadler ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Collagen Fibril ◽  
Volume Fraction ◽  
Area Fraction ◽  
Sectional Area ◽  
Cross Sectional ◽  
P Values ◽  
Age Related ◽  
Fibril Diameter ◽  
Age Related Changes

Connective tissues are biological composites comprising of collagen fibrils embedded in (and reinforcing) the hydrated proteoglycan-rich (PG) gel within the extracellular matrices (ECMs). Age-related changes to the mechanical properties of tissues are often associated with changes to the structure of the ECM, namely, fibril diameter. However, quantitative attempts to correlate fibril diameter to mechanical properties have yielded inconclusive evidence. Here, we described a novel approach that was based on the rule of mixtures for fiber composites to evaluate the dependence of age-related changes in tendon tensile strength (σ) and stiffness (E) on the collagen fibril cross-sectional area fraction (ρ), which is related to the fibril volume fraction. Tail tendons from C57BL6 mice from age groups 1.6–35.3months old were stretched to failure to determine σ and E. Parallel measurements of ρ as a function of age were made using transmission electron microscopy. Mathematical models (rule of mixtures) of fibrils reinforcing a PG gel in tendons were used to investigate the influence of ρ on ageing changes in σ and E. The magnitudes of σ, E, and ρ increased rapidly from 1.6monthsto4.0months (P-values <0.05) before reaching a constant (age independent) from 4.0monthsto29.0months (P-values >0.05); this trend continued for E and ρ (P-values >0.05) from 29.0monthsto35.3months, but not for σ, which decreased gradually (P-values <0.05). Linear regression analysis revealed that age-related changes in σ and E correlated positively to ρ (P-values <0.05). Collagen fibril cross-sectional area fraction ρ is a significant predictor of ageing changes in σ and E in the tail tendons of C57BL6 mice.

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