Short-Term Exposure to Low-Dose Ritonavir Impairs Clearance and Enhances Adverse Effects of Trazodone

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 μg per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte proliferation after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group, and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of(MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.

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Mental Health and Cognition in Older Cannabis Users: a Review

Canadian Geriatrics Journal ◽

10.5770/cgj.23.399 ◽

2020 ◽

Vol 23 (3) ◽

pp. 237-244

Author(s):

Blanca E. Vacaflor ◽

Olivier Beauchet ◽

G. Eric Jarvis ◽

Alessandra Schiavetto ◽

Soham Rej

Keyword(s):

Mental Health ◽

Older Adults ◽

Adverse Effects ◽

Low Dose ◽

Community Dwelling ◽

Cannabis Use ◽

Cognitive Effects ◽

Medical Cannabis ◽

Short Term ◽

The Impact

Background The impact of cannabis use on mental health and cognition in older adults remains unclear. With the recent legalization of cannabis in Canada, physicians will need up-to-date information about the mental and cognitive effects of cannabis use in this specific population. Method A narrative review was conducted to summarize the literature on mental health and cognitive effects of cannabis use in older adults using Medline (OvidSP). Results A total of 16 studies were identified, including nine cross-sectional studies on mental health comorbidities reported by older cannabis users. The self-reported prevalence of mental and substance use disorders is approximately two to three times higher in older adults who report past-year cannabis use, compared to older adults who report using more than one year ago or never using. The remaining seven clinical trials found that short-term, low-dose medical cannabis was generally well-tolerated in older adults without prior serious mental illness. However, mental/cognitive adverse effects were not systematically assessed. Conclusion Although preliminary findings suggests that low-dose, short-term medical cannabis does not carry significant risk of serious mental health and cognitive adverse effects in older adults without prior psychiatric history, epidemiological studies find a correlation between past-year cannabis use and poor mental health outcomes in community-dwelling older adults. These findings may indicate that longer term cannabis use in this population is detrimental to their mental health, although a direct causal link has not been established. Larger, longitudinal studies on the safety of medical cannabis in older adults are needed.

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Hormone-Like Effects of 4-Vinylcyclohexene Diepoxide on Follicular Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.00587 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Lian Bao Cao ◽

Hong Bin Liu ◽

Gang Lu ◽

Yue Lv ◽

Chi Kwan Leung ◽

...

Keyword(s):

Ovarian Reserve ◽

Low Dose ◽

Follicular Development ◽

Primordial Follicle ◽

High Dose ◽

Short Term ◽

Primary Follicle ◽

Vinylcyclohexene Diepoxide ◽

Short Term Exposure

Background4-vinylcyclohexene diepoxide (VCD) has long been considered a hazardous occupational chemical that promotes ovarian failure. However, VCD is also used as a research compound to chemically induce animal models of premature ovarian insufficiency (POI), and in related work we unexpectedly found that VCD apparently exhibits both dose- and duration-dependent opposing, hormone-like effects on the maintenance of the primordial follicle pool, follicle development, and ovulation induction.ResultsWe conducted experiments with cultured murine ovaries and performed transplantation experiments using postnatal day (PD) 2 and PD12 mice and found that low-dose, short-term exposure to VCD (VCDlow) actually protects the primordial/primary follicle pool and improves the functional ovarian reserve (FOR) by disrupting follicular atresia. VCDlow inhibits follicular apoptosis and regulates the Pten-PI3K-Foxo3a pathway. Short-term VCD exposure in vivo (80 mg/kg, 5 days) significantly increases the number of superovulated metaphase II oocytes, preovulatory follicles, and corpus luteum in middle-aged mice with diminished ovarian reserve (DOR). We demonstrate that low-dose but not high-dose VCD promotes aromatase levels in granulosa cells (GCs), thereby enhancing the levels of estradiol secretion.ConclusionOur study illustrates a previously unappreciated, hormone-like action for the occupational “ovotoxin” molecule VCD and strongly suggests that VCDlow should be explored for its potential utility for treating human ovarian follicular development disorders, including subfertility in perimenopausal women.

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Short-term exposure to tricyclic antidepressants delays righting time in marine and freshwater snails with evidence for low-dose stimulation of righting speed by imipramine

Environmental Science and Pollution Research ◽

10.1007/s11356-019-04269-0 ◽

2019 ◽

Vol 26 (8) ◽

pp. 7840-7846 ◽

Cited By ~ 1

Author(s):

Peter P. Fong ◽

Kelsey E. DiPenta ◽

Sarahrose M. Jonik ◽

Courtney D. Ward

Keyword(s):

Tricyclic Antidepressants ◽

Low Dose ◽

Freshwater Snails ◽

Short Term ◽

Short Term Exposure ◽

Stimulation Of

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Deoxynivalenol Impairs Weight Gain and Affects Markers of Gut Health after Low-Dose, Short-Term Exposure of Growing Pigs

Toxins ◽

10.3390/toxins7062071 ◽

2015 ◽

Vol 7 (6) ◽

pp. 2071-2095 ◽

Cited By ~ 56

Author(s):

Arash Alizadeh ◽

Saskia Braber ◽

Peyman Akbari ◽

Johan Garssen ◽

Johanna Fink-Gremmels

Keyword(s):

Weight Gain ◽

Low Dose ◽

Growing Pigs ◽

Gut Health ◽

Short Term ◽

Short Term Exposure

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Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.5.1469-1487.2004 ◽

2004 ◽

Vol 48 (5) ◽

pp. 1469-1487 ◽

Cited By ~ 97

Author(s):

Koen K. A. Van Rompay ◽

Laurie L. Brignolo ◽

Dennis J. Meyer ◽

Christopher Jerome ◽

Ross Tarara ◽

...

Keyword(s):

Adverse Effects ◽

Low Dose ◽

Biological Effects ◽

Daily Administration ◽

Time Range ◽

High Dose ◽

Short Term ◽

Therapeutic Benefits ◽

Short Period ◽

Renal Tubular Disorder

ABSTRACT The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.

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DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure

Archives of Toxicology ◽

10.1007/s00204-004-0639-z ◽

2005 ◽

Vol 79 (6) ◽

pp. 355-362 ◽

Cited By ~ 6

Author(s):

B. Marczynski ◽

R. Merget ◽

T. Mensing ◽

S. Rabstein ◽

M. Kappler ◽

...

Keyword(s):

Individual Differences ◽

Low Dose ◽

Dna Strand Breaks ◽

Short Term ◽

Strand Breaks ◽

Short Term Exposure ◽

Dna Strand

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Severe Tracheobronchitis from Inhalation of an Isobutyl Nitrite Preparation

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808101500110 ◽

1981 ◽

Vol 15 (1) ◽

pp. 51-52 ◽

Cited By ~ 7

Author(s):

John R. Covalla ◽

C. Vaughn Strimlan ◽

John G. Lech

Keyword(s):

United States ◽

Adverse Effects ◽

The United States ◽

Short Term ◽

Short Term Exposure ◽

Illicit Use

Isobutyl nitrite has recently become a popularly abused drug in the United States. Although many adverse effects, including headache, hypotension, and methemoglobinemia, are known to occur following exposure to this class of drugs, little has been written concerning the effects of illicit use of isobutyl nitrite. In this case, severe tracheobronchitis developed following short-term exposure by inhalation of this drug.

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