Neuronal Lipopigment: A Marker for Cognitive Impairment and Long-Term Effects of Psychotropic Drugs

1989 ◽  
Vol 155 (1) ◽  
pp. 1-11 ◽  
Author(s):  
J. H. Dowson
Keyword(s):  
Free Radicals ◽  
Chronic Administration ◽  
Long Term Effects ◽  
Neuronal Function ◽  
Alzheimer Dementia ◽  
Cellular Debris ◽  
Normal Ageing ◽  
Prophylactic Use ◽  
Long Term Studies

Lipopigment, identifiable in the fluorescence microscope, is thought to be cellular debris partly derived from free-radical-induced peroxidation of cellular constituents. The volume of neuronal lipopigment has been positively correlated with advancing age, Alzheimer dementia, and the neuronal ceroidoses, while various changes in neuronal lipopigment have been reported in association with the chronic administration of dihydroergotoxine, ethanol, phenytoin, centrophenoxine, and chlorpromazine. An increase in the volume of neuronal lipopigment may indicate increased functional activity of the cell, impaired removal of pigment or anoxia. Chronic administration of agents which can be correlated with decreased neuronal lipopigment in animal models might protect neuronal function against any adverse effects associated with (but not necessarily resulting from) lipopigment accumulation in normal ageing, anoxia, or certain degenerative diseases. Long-term studies of the prophylactic use of such agents, or of drugs which neutralise free radicals, may be indicated. Other clinical applications of such drugs may include protection against the effects of free radicals formed during periods of oxygen deprivation.

scholarly journals Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

2021 ◽  
Vol 22 (16) ◽  
pp. 8899
Author(s):  
Marina Gabaglio ◽  
Erica Zamberletti ◽  
Cristina Manenti ◽  
Daniela Parolaro ◽  
Tiziana Rubino
Keyword(s):  
Adverse Effects ◽  
Chronic Administration ◽  
Female Rats ◽  
Acid Decarboxylase ◽  
Long Term Effects ◽  
Gabaergic Neurotransmission ◽  
Long Term Consequences ◽  
Adolescent Exposure ◽  
Long Term Adverse Effects

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.

scholarly journals Thyrotoxicosis Associated with Ustekinumab Treatment for Psoriasis

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Bayanne Olabi ◽  
Shanti Ayob
Keyword(s):  
Decision Making ◽  
Monoclonal Antibody ◽  
Adverse Effects ◽  
Interleukin 12 ◽  
Long Term Effects ◽  
Thyroid Status ◽  
Large Populations ◽  
Nature Awareness ◽  
Long Term Studies

Biologic treatments have revolutionised the management of psoriasis in recent years; however, data on their safety profile in large populations and long-term effects are being gathered on an ongoing basis. Ustekinumab is a monoclonal antibody that targets interleukin-12/23 used in the treatment of moderate-to-severe psoriasis. Here, we report the case of a 32-year-old Caucasian gentleman who developed thyrotoxicosis following the commencement of ustekinumab treatment. Following control of thyroid status by the Endocrinology team, this recurred after recommencement of ustekinumab on two further occasions over a 5-year period. This is the second known reported association of this nature. Awareness of these possible adverse effects is imperative in managing patients and informing decision-making, and further long-term studies will help elucidate the precise safety profiles of biologic treatments.

Long-Term Effects of In Vivo Administration of An Anti-VLA-4 Antibody (natalizumab) on Mobilization of Committed and Primitive Hematopoietic Progenitor Cells In Humans

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2264-2264
Author(s):  
Jorge Domenech ◽  
Julien Goustille ◽  
Maud Pallix ◽  
Zakia Bekhechi ◽  
Elfi Ducrocq ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Chronic Administration ◽  
Long Term Effects ◽  
Hematopoietic Stem ◽  
One Year ◽  
In Vivo Administration

Abstract Abstract 2264 The alpha4 beta1 integrin (VLA-4) exert a critical role on hematopoiesis by confining hematopoietic stem cells (HSC) and progenitor cells (HPC) within the niche. Previous preclinical studies have pointed out this role showing that HPCs can be mobilized by in vivo administration of a blocking anti-VLA-4 antibody (Ab) (Papayannopoulou et al, 1993). Very recently, two papers (Bonig et al, 2008; Zohren et al, 2008) have shown that such Ab exhibits a similar effect in humans for one month after treatment by natalizumab. In the present study, we have investigated long-term hematopoietic effects (up to 23 months) of repeated infusions of natalizumab in patients treated for multiple sclerosis (n=22). Seven patients have been explored sequentially (every month for one year) and 15 have been studied punctually (6 before and 9 after one year of treatment). We found that peripheral blood leukocytosis was consistently increased for one year in relation to lymphocytes, particularly to B lineage (by 3-fold). In parallel, an increase of circulating HPCs (CD34+ cells and total CFU) was observed and appeared more pronounced with levels above baseline values in all the patients studied (by 6-fold) while no increase of circulating mesenchymal stromal cells (CFU-F) was found. The increase was noted for both lymphoid (T and B lineages) and myeloid (granulo-monocyte, erythroid, and megakaryocyte) committed progenitor cells but also for primitive HPC (CD34+CD38- cells and CAFC). This effect was still found at long-term (up to two years of treatment) for both committed and primitive HPC. In conclusion, the HPC mobilizing effect of chronic administration of anti-VLA-4 Ab in humans involves all types of HPCs (lymphoid and myeloid, committed and primitive ones) and is not exhausted with time. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hysterectomy and bilateral salpingoophorectomy in female-to-male transsexual: does testosterone induce anatomopatological changes? A retrospective study

2021 ◽  
Author(s):  
Marina Martin Pereda ◽  
Maria Amores Vergara ◽  
Lorena Sabonet Morente ◽  
Ernesto Gonzalez Mesa ◽  
Pilar Espejo Reina ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Chronic Administration ◽  
Duration Of Treatment ◽  
Replacement Treatment ◽  
Pathological Result ◽  
Number Of Patients ◽  
Gender Reassignment ◽  
Secretory Type ◽  
Long Term Studies

Abstract Background Testosterone replacement treatment as part of gender reassignment therapy has repercussions on the final pathological result of the hysterectomies that are performed. The objective of this review is to analyze the surgical pieces of hysterectomies performed on FTM patients (female-to-male) and to describe possible changes related to testosterone. There are few studies and with a low number of patients where this possible repercussion is addressed. Methods A retrospective study was carried out, which included 117 patients between the ages of 21 and 56, operated on between 2010 and 2019, with at least an average duration of treatment of 5 years before gender reassignment surgery. Main outcome measure were changes in follicle stimulating hormone (FSH), luteinizin hormone (LH), testosterone (TST) and estradiol in blood, both preoperatively and postoperatively. Also the differente types of endometrium and ovaries found in histerectomy pieces. Results the pathological study revealed that 95 (80.3%) cases showed an atrophic endometrium, 7 (6%) cases an endometrium with secretory-type changes, and 15 (13.7%) cases with weakly proliferating endometrium. Conclusions Our data revealed that the most frequent histology after chronic administration of parenteral testosterone was such compatible with atrophic endometrium, coinciding with what has been published in the literature up to now. More long-term studies on the effects of parenteral testosterone are still needed.

scholarly journals How advances in epidemiology are influencing older adult psychiatry

2020 ◽  
Vol 26 (2) ◽  
pp. 104-105
Author(s):  
Natalie Shoham ◽  
Claudia Cooper
Keyword(s):  
Mendelian Randomisation ◽  
Long Term Effects ◽  
Controlled Clinical Trials ◽  
Individual Traits ◽  
Large Populations ◽  
Adult Psychiatry ◽  
Changes In Risk ◽  
Randomised Controlled ◽  
Long Term Studies

SUMMARYShortcomings of randomised controlled clinical trials include their high cost, which often precludes very long-term studies and very large populations, and ethical constraints of randomisation. Observational studies are a valuable alternative and we outline their use in epidemiological research to study very long-term effects of lifestyle and medication on dementia, to explore (using Mendelian randomisation) the association between Alzheimer's dementia and individual traits, and to evaluate population-wide health inequalities and lifespan changes in risk factors for psychiatric illness.

scholarly journals Air Pollution and Mortality: Timing Is Everything

Atmosphere ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1274
Author(s):  
Frederick W. Lipfert
Keyword(s):  
Air Pollution ◽  
Time Series ◽  
Air Quality ◽  
Indoor Air Pollution ◽  
Health Effect ◽  
Traffic Density ◽  
Long Term Effects ◽  
Short Term ◽  
Long Term Studies

This paper considers timing issues in health-effect exposure and response studies. Short-term studies must consider delayed and cumulative responses; prior exposures, disease latency, and cumulative impacts are required for long-term studies. Lacking individual data, long-term air quality describes locations, as do greenspaces and traffic density, rather than exposures of residents. Indoor air pollution can bias long-term exposures and effect estimates but short-term effects also respond to infiltrated outdoor air. Daily air quality fluctuations may affect the frail elderly and are necessarily included in long-term averages; any true long-term effects must be given by differences between annual and daily effects. I found such differences to be negligible after adjusting for insufficient lag effects in time-series studies and neglect of prior exposures in long-term studies. Aging of subjects under study implies cumulative exposures, but based on age-specific mortality, I found relative risks decreasing with age, precluding cumulative effects. A new type of time-series study found daily mortality of previously frail subjects to be associated with various pollutants without exposure thresholds, but the role of air pollution in the onset of frailty remains an unexplored issue. The importance of short-term fluctuations has been underestimated and putative effects of long-term exposures have been overestimated.

Ovarian Dysfunction in Fetally Irradiated Beagles

1977 ◽  
Vol 35 ◽  
pp. 658-659
Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Low Dose ◽  
Long Term Effects ◽  
Ovarian Dysfunction ◽  
Dose Rates ◽  
Highly Sensitive ◽  
Microscopic Evaluation ◽  
Ovarian Pathology ◽  
Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

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