Immunomodulatory Effect of Ganoderma Lucidum Polysaccharides (GLP) on Long-Term Heavy-Load Exercising Mice

2012 ◽  
Vol 82 (6) ◽  
pp. 383-390 ◽  
Author(s):  
Yali Shi ◽  
Dehua Cai ◽  
Xiaojie Wang ◽  
Xinshen Liu
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Ganoderma Lucidum ◽  
Phagocytic Index ◽  
High Dose ◽  
Heavy Load ◽  
Ganoderma Lucidum Polysaccharides ◽  
High Doses ◽  
Serum Agglutination

Long-term heavy-load exercise can lead to a decrease in the organism’s immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

scholarly journals Phosphorus Inactivation in Lake Sediments Using Calcite Materials and Controlled Resuspension—Mechanism and Efficiency

Minerals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 223
Author(s):  
Agnieszka Bańkowska-Sobczak ◽  
Aurelia Blazejczyk ◽  
Elisabeth Eiche ◽  
Uwe Fischer ◽  
Zbigniew Popek
Keyword(s):  
Adsorption Capacity ◽  
Soluble Reactive Phosphorus ◽  
High Dose ◽  
Eutrophic Lakes ◽  
Precipitated Calcium Carbonate ◽  
Anoxic Conditions ◽  
P Fraction ◽  
Reactive Phosphorus ◽  
High Doses

The efficiency and mechanism of orthophosphate—soluble reactive phosphorus (SRP)—inactivation in eutrophic lakes using controlled resuspension and calcite application into the sediment were investigated in this study. Two calcite materials, industrially produced precipitated calcium carbonate (PCC) and natural ground limestone (GCC), were tested in short-term batch experiments and long-term sediment incubations under oxic and anoxic conditions. Maximum SRP adsorption capacity calculated using Langmuir model for PCC (3.11 mg PO43− g−1) was 6 times higher than of GCC (0.43 mg PO43− g−1), reflecting substantial difference in the surface area of calcite materials (12.36 and 1.72 m2 g−1, respectively). PCC applied into the sediment during controlled resuspension reduced SRP release by 95% (oxic) and 78% (anoxic incubation) at medium dose (0.75 kg m−2) and suppressed it completely at high dose (1.5 kg m−2) for at least 3 months, irrespectively of incubation conditions. The maximum achieved reduction of SRP release using GCC was also meaningful: 78% under oxic and 56% under anoxic conditions, but this required very high doses of this material (6 kg m−2). Mechanisms of SRP inactivation by calcites were: (1) adsorption of SRP during application into the resuspended sediment and (2) precipitation of calcium-phosphate compounds (Ca-PO4) during subsequent incubation, which was reflected in a substantial increase in the HCl-P fraction (phosphorus extractable in 0.5 M HCl) in sediments enriched with calcite, irrespectively of oxygen presence. However, anoxia strongly promoted the formation of this fraction: the rise of HCl-P was 2–6 times higher in anoxic than in oxic conditions, depending on the dose and form of calcite applied. The results showed that SRP inactivation using the controlled resuspension method is only successful if highly efficient reactive materials are used, due to large amount of SRP being released from sediment during resuspension. Thus, calcite materials exhibiting high adsorption capacity should be used in this lakes’ restoration technology to ensure fast and sufficient SRP inactivation. The rise in the HCl-P fraction in sediment suggests SRP inactivation through precipitation of relatively stable Ca-PO4 minerals, which makes calcite a suitable agent for sustainable, long term SRP inactivation. As anoxic conditions promoted formation of these compounds, calcite seems to be a promising SRP inactivation agent in highly reductive sediments.

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

1995 ◽  
Vol 73 (9) ◽  
pp. 1609-1619 ◽  
Author(s):  
S. L. Monfort ◽  
J. L. Brown ◽  
T. C. Wood ◽  
M. Bush ◽  
L. R. Williamson ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Fertile Period ◽  
Nonbreeding Season ◽  
Testosterone Secretion ◽  
High Doses ◽  
Seasonal Decline ◽  
Seasonally Breeding

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

Fluconazole-Induced Symptomatic Phenytoin Toxicity

1994 ◽  
Vol 28 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Richard M. Cadle ◽  
Golden J. Zenon ◽  
Maria C. Rodriguez-Barradas ◽  
Richard J. Hamill
Keyword(s):  
Continuous Monitoring ◽  
Case Reports ◽  
Review Literature ◽  
High Dose ◽  
Data Synthesis ◽  
High Doses ◽  
Phenytoin Toxicity ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

OBJECTIVE: To report two cases of fluconazole-induced symptomatic phenytoin toxicity and review literature related to this interaction. DATA SOURCES: Case reports and review articles identified by a computerized (MEDLINE) and manual ( Index Medicus) search. DATA SYNTHESIS: Fluconazole is a broad-spectrum triazole antifungal agent primarily eliminated by renal mechanisms, although hepatic cytochrome P-450 inhibition and hepatotoxicity have been observed. We report two cases of fluconazole-induced symptomatic phenytoin toxicity. Both patients received high doses of the drug; one patient developed phenytoin toxicity only after long-term coadministration. Previously reported cases have occurred primarily with high-dose fluconazole and short-term coadministration. CONCLUSIONS: Fluconazole can increase phenytoin serum concentrations leading to toxicity. Constant and continuous monitoring of serum phenytoin concentrations with fluconazole doses as low as 200 mg/d is warranted.

Long-term treatment with finasteride induces apoptosis and pathological changes in female mice

2019 ◽  
Vol 38 (7) ◽  
pp. 762-774 ◽  
Author(s):  
AA Alkahtane ◽  
G Albasher ◽  
NK Al-Sultan ◽  
WS Alqahtani ◽  
S Alarifi ◽  
...  
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Androgenetic Alopecia ◽  
High Dose ◽  
Histopathological Analysis ◽  
Once Daily ◽  
Female Mice ◽  
Long Term Treatment ◽  
High Doses

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

Late-onset neutropenia and neurological relapse, during long-term rituximab therapy in myelin oligodendrocyte glycoprotein-antibody spectrum disorder

2018 ◽  
Vol 24 (12) ◽  
pp. 1645-1647 ◽  
Author(s):  
Damien Biotti ◽  
Fleur Lerebours ◽  
Fabrice Bonneville ◽  
Jonathan Ciron ◽  
Michel Clanet ◽  
...  
Keyword(s):  
Blood Cell ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Late Onset ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Life Threatening ◽  
Spectrum Disorders

Late-onset neutropenia after rituximab therapy (LONART) is defined as a fall in the absolute neutrophil count below 500/mm3 at least 3 weeks after rituximab infusion, in the absence of any other explanation. LONART is rare during dysimmune conditions but can be life-threatening. We report on two patients with LONART and associated neurological relapse occurring in myelin oligodendrocyte glycoprotein (MOG)-antibody spectrum disorders. Rituximab was reintroduced in one patient, while the second patient was switched to tocilizumab. LONART can occur during anti-MOG spectrum disorders. Neurologists should be aware of this rare and treatable complication. Regular monitoring of blood cell counts is needed, and patients should be informed of the need to consult their physician if symptoms of infection appear.

Cognitive impairment following clinical or recreational use of gamma-hydroxybutyric acid (GHB). A systematic review

2021 ◽  
Vol 19 ◽  
Author(s):  
Jan Van Amsterdam ◽  
Tibor M. Brunt ◽  
Filipa Raposo Pereira ◽  
Cleo L. Crunelle ◽  
Wim Van Den Brink
Keyword(s):  
Systematic Review ◽  
Cognitive Impairments ◽  
High Dose ◽  
General Anaesthetic ◽  
Hydroxybutyric Acid ◽  
Alcohol Relapse ◽  
Animal Data ◽  
High Doses ◽  
Recreational Use

Background: GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use. Methods: PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol. Results: A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments. Conclusion: These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used, and GHB-induced comas occur.

scholarly journals Clozapine metabolism is associated with Absolute Neutrophil Count in individuals with treatment-resistant schizophrenia

2021 ◽  
Author(s):  
Isabella Willcocks ◽  
Sophie E. Legge ◽  
Mariana Nalmpanti ◽  
Lucy Mazzeo ◽  
Adrian King ◽  
...  
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Plasma Concentrations ◽  
Metabolic Ratio ◽  
Treatment Resistant ◽  
Clozapine Concentration ◽  
The Relationship

AbstractAIMTo investigate the relationship between clozapine concentration and neutrophils in a European cohort of long-term clozapine users.METHODSPearson’s Correlation and Linear Regression analyses were applied to a subset of the CLOZUK2 dataset (N = 208) to assess the association between Absolute Neutrophil Count (ANC) and plasma clozapine concentration. Norclozapine and the metabolic ratio between clozapine and norclozapine were also investigated, along with SNPs associated with clozapine metabolismRESULTSAssociation between ANC and plasma clozapine concentration was found to be significant in a linear regression model (β = −1.41, p = 0.009), with a decrease in ANC of approximately 141 cells/mm3 for every 0.1 mg/litre increase in clozapine concentration. This association was attenuated by the addition of the metabolic ratio, which was significantly negatively correlated with ANC (β=-0.69, p=0.021). In a further regression model, three SNPs previously associated with norclozapine plasma concentrations and clozapine/norclozapine ratio were also found to be significantly associated with ANC: rs61750900 (β=-0.410, p=0.048), rs2011425 (β=0.450, p=0.026) and rs1126545 (β=0.330, p=0.039)CONCLUSIONANC was found to be significantly negatively associated with plasma clozapine concentration. Further investigation has suggested that the relationship is mediated by the clozapine/norclozapine ratio, and potentially moderated by genetic variants with effects on clozapine metabolism

scholarly journals Evaluating the effect of Ganoderma lucidum polysaccharides on five cytochrome P450 isozymes with cocktail probe drugs in rats by LC–MS/MS

2019 ◽  
Vol 4 (1) ◽  
Keyword(s):  
Cytochrome P450 ◽  
Ganoderma Lucidum ◽  
Low Dose ◽  
Antioxidant Activities ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Positive Effects ◽  
Ganoderma Lucidum Polysaccharides ◽  
Tandem Mass Spectrometric

Ganoderma lucidum polysaccharides (GLPs) are commonly used as health-promoting medicine and dietary supplement due to the positive effects in immune modulation, antitumor and antioxidant activities. However, whether GLPs executes other uncharacterized effects is largely unclear. The rats were pre-primed with GLPs and then administrated with canonical “cocktail probes” of cytochrome P450 (CYP450) isozymes including caffeine, tolbutamide, dextromethorphan, omeprazole, and midazolam. The plasma concentrations of probes at each indicated time point were simultaneously detected using the designed high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. The results suggested that GLPs could increase the accumulated levels of caffeine, tolbutamide and midazolam in plasma as compared to control group. Besides, GLPs reduced the concentration of dextromethorphan in blood at high dose, while elevated it at low dose. GLPs could inhibit the activities of CYP1A2, and CYP3A4, additionally; GLPs at low dose suppressed the activity of CYP2D6, which demonstrated that drugs co-administrated with GLPs might require strictly evaluating the dose relation.

scholarly journals Safety and tolerability of high doses of intrathecal fentanyl for the treatment of chronic pain

2006 ◽  
Vol 2 (6) ◽  
pp. 365 ◽  
Author(s):  
Sulane Do Ouro, MD ◽  
Santiago Esteban, BS ◽  
Una Sibirceva, MD ◽  
Beverly Whittenberg, MD ◽  
Russell Portenoy, MD ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Dose Escalation ◽  
Scope Of Practice ◽  
Dose Titration ◽  
Term Therapy ◽  
High Dose ◽  
High Doses ◽  
Long Term Therapy

Fentanyl is commonly used systemically or neuraxially for the management of chronic pain. It can be administered intrathecally via implanted pump, but it is generally considered only after trials of intrathecal (IT) morphine and hydromorphone have proven ineffective. Published experience with IT fentanyl is limited, and long-term therapy at relatively high doses has not been described previously. We describe four patients who were treated with IT fentanyl after other analgesic approaches had failed and who gradually underwent dose escalation to levels as high as 20 times those previously reported. Safety and tolerability were maintained during dose titration. Our experience highlights an expanding scope of practice in the use of IT opioids in general and fentanyl specifically and suggests that high-dose fentanyl can be used safely in highly selected patients.

scholarly journals Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

2021 ◽  
Vol 15 (3) ◽  
pp. e0008970
Author(s):  
Frédérique Vernel-Pauillac ◽  
Gerald L. Murray ◽  
Ben Adler ◽  
Ivo G. Boneca ◽  
Catherine Werts
Keyword(s):  
Post Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Antibody Responses ◽  
High Dose ◽  
Specific Igg ◽  
High Doses ◽  
Rats And Mice ◽  
Renal Infection

Leptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied, which complicates the testing of vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection. Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the attenuated M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective and cross-reactive antibodies after L. interrogans infection, depending on the serovar and virulence of strains.

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