scholarly journals Whole blood metabolomics of dementia patients reveal classes of disease-linked metabolites

2021 ◽  
Author(s):  
Takayuki Teruya ◽  
Yung-Ju Chen ◽  
Hiroshi Kondoh ◽  
Yasuhide Fukuji ◽  
Mitsuhiro Yanagida

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using non-targeted liquid chromatography-mass spectroscopy (LC-MS). Thirty-three metabolites, classified into 5 groups (A-E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven Group A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (Groups B-E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six Group B metabolites, normally enriched in red blood cells (RBCs) of healthy subjects, all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent anti-oxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. Group C compounds, also include some oxidoreductants and are normally abundant in RBCs (NADP+, glutathione, ATP, pantothenate, S-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Groups D (12) contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven Group D compounds have been identified previously as dementia markers. Group B-E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish so significantly in dementia remain to be determined.

2021 ◽  
Vol 118 (37) ◽  
pp. e2022857118
Author(s):  
Takayuki Teruya ◽  
Yung-Ju Chen ◽  
Hiroshi Kondoh ◽  
Yasuhide Fukuji ◽  
Mitsuhiro Yanagida

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography–mass spectroscopy (LC-MS). Thirty-three metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (B to E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six B metabolites, normally enriched in red blood cells (RBCs), all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds that have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent antioxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. C compounds also include some oxidoreductants and are normally abundant in RBCs (NADP+, glutathione, adenosine triphosphate, pantothenate, S-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Twelve D metabolites contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, and 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven D compounds have been identified previously as dementia markers. B to E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish significantly in dementia remain to be determined.


1998 ◽  
Vol 42 (6) ◽  
pp. 1433-1436 ◽  
Author(s):  
Osamu Kozawa ◽  
Toshihiko Uematsu ◽  
Hiroyuki Matsuno ◽  
Masayuki Niwa ◽  
Yoshiharu Takiguchi ◽  
...  

ABSTRACT The pharmacokinetics and tolerability of a new parenteral carbapenem antibiotic, biapenem (L-627), were studied in healthy elderly volunteers aged 65 to 74 years (71.6 ± 2.7 years [mean ± standard deviation], n = 5; group B) and ≥75 years (77.8 ± 1.9 years, n = 5; group C), following single intravenous doses (300 and 600 mg), and compared with those of healthy young male volunteers aged 20 to 29 years (23.0 ± 3.5 years, n = 5; group A). The agent was well tolerated in all three age groups. Serial blood and urine samples were analyzed for biapenem to obtain key pharmacokinetic parameters by both two-compartment model-dependent and -independent methods. The maximum plasma concentration and area under plasma concentration-versus-time curve (AUC) increased in proportion to the dose in all three groups. Statistically significant age-related effects for AUC, total body clearance, and renal clearance (CLR) were found, while elimination half-life (t 1/2β) and percent cumulative recovery from urine of unchanged drug (% UR) remained unaltered (t 1/2β, 1.51 ± 0.42 [300 mg] and 2.19 ± 0.64 [600 mg] h [group A], 1.82 ± 1.14 and 1.45 ± 0.36 h [group B], and 1.75 ± 0.23 and 1.59 ± 0.18 h [group C]; %UR, 52.6% ± 3.0% [300 mg] and 53.1% ± 5.1% [600 mg] [group A], 46.7% ± 7.4% and 53.0% ± 4.8% [group B], and 50.1% ± 5.2% and 47.1% ± 7.6% [group C]). A significant linear correlation was observed between the CLR of biapenem and creatinine clearance at the dose of 300 mg but not at 600 mg. The steady-state volume of distribution tended to be decreased with age, although not significantly. Therefore, the age-related changes in parameters of biapenem described above were attributable to the combination of decreased lean body mass and lowered renal function of the elderly subjects. However, the magnitude of those changes does not necessitate dosage adjustment in elderly patients with normal renal function for their age.


Agriculture ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 557
Author(s):  
Roberta Barrasso ◽  
Vincenzo Tufarelli ◽  
Edmondo Ceci ◽  
Francesco Luposella ◽  
Giancarlo Bozzo

The aim of this study was to evaluate the persistence of two signs of consciousness (rhythmic breathing and corneal reflex) in lambs slaughtered according to the traditional method and Halal ritual rite. A total of 240 lambs were examined and divided into two equal groups (n = 120 each). Lambs of group A were subjected to the stunning phase by the action of an electric current on the brain, while lambs of group B were slaughtered according to the religious Halal method without prior stunning. Rhythmic breathing (RB) and corneal reflex (CR) were used as indicators of prolonged brain function, and their evaluation was carried out by the operators in three subsequent steps at 15 s, 30 s, and 90 s post-bleeding, respectively. The stunning of the lambs reduced the animal’s state of consciousness and, consequently, reduced suffering, pain, and distress. Indeed, the lambs of group B showed longer duration consciousness than the animals stunned by electrodes. The permanence of the reflexes in Halal slaughter could be reduced by introducing a reversible stunning method to make the animal temporarily unconscious. Moreover, given that our results revealed consciousness also after 90 s post-cut, the assessment of the animal’s state of consciousness in wider time intervals than those commonly used is recommended.


1989 ◽  
Vol 257 (3) ◽  
pp. H785-H790
Author(s):  
T. Sakamoto ◽  
W. W. Monafo

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.


2010 ◽  
Vol 8 (3) ◽  
pp. 281-284
Author(s):  
Mariana Varkala Lanuez ◽  
Fernanda Varkala Lanuez ◽  
Eduardo Gunther Montero ◽  
Wilson Jacob Filho

ABSTRACT Objectives: To assess the effect of exercise on gait using two different programs: a group of aerobic exercises (Group A, n = 18) and a group of flexibility and balance exercises (Group B, n = 19). Methods: A casualized controlled study, in which each sample controlled itself, was undertaken. The sample comprised 37 male and female subjects, aged from 60 to 90 years, from the outpatient clinic of the Geriatrics Unit of Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo; the patients were sedentary and had not exercised regularly during the past six months. Results: Improvement of gait was seen mainly in the group that did specific exercises. Conclusion: The results of this study underline the importance of physical exercises in sedentary elderly subjects, but show the need for programming the exercises towards specific goals, which can optimize the results of this tool of health promotion for the elderly.


2015 ◽  
Vol 23 (2) ◽  
pp. 211-214
Author(s):  
Halima Afroz ◽  
Abu Sadat Mohammad Nurunnabi ◽  
Mushfika Rahman ◽  
Nurun Nahar ◽  
Shamim Ara

Context: The pineal gland has been described as an endocrine or neuroendocrine gland; however, its functions in humans are still to be defined. Different shapes of the human pineal gland have been identified. Due to its small size and different shapes recognition of this gland is much critical. Besides, due to its cellularity it may be mistaken for a neoplasm. Hence, a sound knowledge on different shapes of the pineal gland is essential for neurosurgeons, radiologists and pathologists for better diagnosis and management of pineal disorders.Methods: A descriptive study was done in the Department of Anatomy, Dhaka Medical College, Dhaka, from July 2009 to June 2010, to see the morphological shape of the human pineal gland. The present study was performed on 60 human pineal glands collected from whole human brains of unclaimed dead bodies that were under postmortem examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The pineal gland was collected from the brain by meticulous dissection. Then, the shape of the pineal gland was observed under the magnifying glass.Results: In the present study, pea-shaped pineal glands were found 60% in group A, 30% in group B, 5% in both group C and D, while pine cone shaped were found 25% in group A, 37.5% in group B, 25% in group C and 12.5% in group D. Besides, fusiform shaped glands were found 18.2% in group A, 63.6% in group B, 9.1% in both group C and D, where as piriform shaped found 66.7% in group B, and 16.7% in both group C and D. Moreover, cone-shaped glands were found 28.6% in group B, 57.1% in group C and 14.3% in group D.J Dhaka Medical College, Vol. 23, No.2, October, 2014, Page 211-214


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
A. Mustillo ◽  
J. P. Ayoub ◽  
D. Charpentier ◽  
L. Yelle ◽  
M. Florescu

Background Brain metastasis from breast cancer (bca) in young women is doubly devastating because both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged, survival is expected to increase for these young women.Methods Using the oacis and sardo patient databases, we identified 121 patients diagnosed with bca and brain metastasis between 2006 and 2016 at the University of Montreal Hospital Centre. Those patients were divided into Group A, patients who developed brain metastasis during the evolution of metastatic bca, and Group B, patients whose first metastasis was to the brain. For each group, we compared young patients (<40 years of age) with older patients (≥40 years of age).Results Among the 121 patients with brain metastasis, median overall survival (mos) was significantly longer for those less than 40 years of age than for those 40 or more years of age (18 months vs. 4 months, p < 0.001). With respect to the timing of brain metastasis, survival was significantly longer in Group B than in Group A (7 months vs. 4 months, p = 0.032). In Group A, mos was significantly longer for patients less than 40 years of age than for patients 40 or more years of age (18 months vs. 3 months, p = 0.0089). In Group B, the 2-year overall survival rate was 57% for patients less than 40 years of age and 12% for those 40 or more years of age (mos: not reached vs. 7 months; p = 0.259).Conclusions In our single-centre retrospective cohort of women with brain metastasis from bca, prognosis was better for young women (<40 years) than for older women (≥40 years). Survival was also longer for patients whose initial metastasis was to the brain than for patients whose brain metastasis developed later in the disease course. In patients who received systemic treatment, median survival remained significantly higher in women less than 40 years of age. Further studies are needed to validate those results.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 899-899
Author(s):  
Jin Zhou ◽  
Ran Meng ◽  
Limin Li ◽  
Jie Yu ◽  
Baofeng Yang

Abstract Background Arsenic trioxide provides significant benefits in newly diagnosed and relapsed acute promyelocytic leukemia (APL) respectively. However, the high relapsed rate is still threatened the life of APL patients. Which regimen should be used to overcome or reduce the relapse in consolidated treatment is a key problem at present. We performed a pilot study about that. Objective To Compare the effectiveness and security of cocktail therapy with single arsenic trioxide therapy in APL consolidated treatment. Methods Sixty-Five APL patients, who once received arsenic trioxide treatment and obtained complete remission, were enrolled in this study. Patients were divided into two groups according to the different consolidated regimens. After reinforced treated with DA (daunomycin and cytarabine) or HOAP (harringtonine, vincristin, cytarabine and prednisone) for two course, Group A involved twenty cases received single arsenic trioxide consolidated, Group B included forty-five cases treated with the cocktail therapy, alternatively treated with arsenic trioxide, all trans-retinoic acid and chemotherapy (DA or HOAP). The relapse rates, the survival rates and the central nervous system infiltration rates in 3 years followed up were compared. Results The relapsed rate of Group A was 55%, which was higher than that of Group B(17.8%). The re-remission rate after the first relapse in Group A was 22%, which was lower than that of Group B(42.8%). The central nervous system infiltration rate of Group A was 28%, which was higher than that of Group B(6%). The average survival time of Group A was 10.5±4.2months, which was shorter than that of Group B (22.5±5.5 months). The three-year survival rate of Group A was 15%, which was less than that of Group B (65.8%). Conclusions Cocktail therapy —alternatively treated with arsenic trioxide, all trans-retinoic acid and chemotherapy will be the reasonable regimen for APL consolidated treatment. Which provided benefited on inhibiting relapse and central nervous system infiltration of APL.


1988 ◽  
Vol 117 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Ramón Cacabelos ◽  
Hisayoshi Niigawa ◽  
Yoshiaki Ikemura ◽  
Yuji Yanagi ◽  
Shigemi Tanaka ◽  
...  

Abstract. To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1–44)NH2 (100 μg) elicited a marked plasma GH response with a maximum peak (709.54 ± 259.0 pmol/l; P < 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 ± 0.15 Hz) and increasing amplitude (8.25 ± 4.5 μV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6285
Author(s):  
Peerasak Lerttrakarnnon ◽  
Winthana Kusirisin ◽  
Pimpisid Koonyosying ◽  
Ben Flemming ◽  
Niramon Utama-ang ◽  
...  

Iron fortifications are used for the treatment of iron-deficiency anemia; however, iron dosing may cause oxidative damage to the gut lumen. Thai Sinlek rice is abundant in iron and contains phytochemicals. We aimed at evaluating the effect of an iron-rice (IR) hydrolysate drink (100 mL/serving) on neurological function, red cell indices and iron status in elders. Healthy elderly subjects were divided into three non-anemic groups and one anemic group. The non-anemic groups consumed one WR (2 mg iron/serving) and two IR drinks (15 and 27 mg iron/serving) (groups A, B and D, respectively), while the anemic group consumed one IR drink (15 mg iron serving) (group C) every day for 30 days. There were no significant differences in the MMSE Thai 2002 and PHQ9 test scores for members of all groups, while the nutrition scores and body weight values of group D subjects were significantly increased. Hemoglobin (Hb) and mean corpuscular hemoglobin concentrations increased significantly only in group C. Serum iron and transferrin saturation levels tended to increase in group A, while these levels were decreased in members of group C. Serum antioxidant activity levels were increased in all groups, and were highest in group C. Thus, consumption of an IR drink for 15 days functioned to increase Hb and antioxidant capacity levels in anemic elders.


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