High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia

Author(s):  
Takahiro Sannohe ◽  
Tohru Ohnuma ◽  
Masayoshi Takeuchi ◽  
Eriko Tani ◽  
Yasue Miki ◽  
...  
Keyword(s):  
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4913-4913
Author(s):  
Lilach Lifshitz ◽  
Assaf Berger ◽  
Maayan Avneon ◽  
Moshe Mittelman ◽  
Drorit Neumann

Abstract Erythropoietin (EPO) is an important component in the treatment of cancer patients for improvement of cancer related anemia. EPO treatment for cancer related anemia is usually combined with chemotherapy. Cyclophosphamide (CP) is a known cytotoxic alkylating agent widely used in cancer chemotherapy. While at high doses it functions as an immunosuppressive agent, the anti-neoplastic activities of CP at low doses are attributed to enhancement of cellular and humoral immunity e.g. (Berd et al., Cancer Res; 1984). We have previously shown that EPO displays anti-neoplastic activities (Mittelman, 2001, 2004) and that EPO treatment is associated with enhancement of both the humoral and cellular immune responses (Prutchi-Sagiv 2006, Katz 2007). Here we focused on a murine model of DNP-KLH-injection, used to assess the humoral response in mice. Recently we demonstrated that administration of high doses of EPO (180U×3) to DNP-KLH-injected C57BL mice resulted in an increase in anti-DNP immunoglobulin G1 (IgG1) production. The present study was designed to examine the effect of combining low dose CP (12.5mg/kg ×2) used to achieve an anti-neoplastic activity, with a lower dose of recombinant human EPO (rHuEPO; 90U×3) on the humoral immune response of the DNP-KLH-injected mice, thus simulating the conditions of patient care. Hence, we compared anti-DNP Ig serum levels in DNP-KLH-injected C57BL mice that were treated with either EPO or CP alone, or the combination of CP and EPO (CP-EPO). CP treatment alone resulted in increased levels of serum anti-DNP IgG1 (O.D.(CP) = 0.38±0.06 vs O.D.(Non treated) = 0.18±0.064). In contrast, EPO treatment alone enhanced serum levels of IgG2 (O.D.(EPO) = 0.47±0.09 vs O.D.(Non treated) = 0.18±0.069). CP or EPO alone did not affect the total levels of anti-DNP total Ig (O.D.(EPO) = 0.37±0.07 vs O.D.(Non treated) = 0.28±0.04). Yet, the combined CP-EPO treatment resulted in increased levels of anti-DNP total Ig (O.D.(EPO+CP) = 0.48±0.05 vs O.D.(EPO or CP) = 0.37±0.04), maintaining the higher levels of IgG1 (O.D.(EPO+CP) = 0.38±0.06) and IgG2 (O.D.(EPO+CP) = 0.49±0.1). In summary, the combined CP-EPO treatment additively improved immunoglobulin production, compared to treatment with CP or EPO alone. We thus demonstrate that in context of chemotherapy treatment as usually administered in the clinic, EPO can enhance humoral immunity alongside its erythropoietic activities. Our findings emphasize the role of EPO as an immunomodulator, particularly when given as treatment in a combined therapeutic panel


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Anastasios Anyfantakis ◽  
Dimitrios Anyfantakis ◽  
Irene Vourliotaki

Resistance to thyroid hormone (RTH) is an extremely rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormone (TH). Most patients with RTH have mutations in the gene that encodes theβisoform of the receptor of thyroid hormone (THR-βgene). Mutant receptors are unable to activate or repress target genes. The majority of them are asymptomatic or rarely have hypo- or hyperthyroidism. RTH is suspected by the finding of persistent elevation of serum levels of free T3 (FT3) and free T4 (FT4) and nonsuppressed TSH. We present two cases of RTH diagnosed after total thyroidectomy. The first patient was initially diagnosed with primary hyperthyroidism due to toxic multinodular goiter. The second patient had undergone thyroidectomy for multinodular goiter 16 years before diagnosis of RTH. After thyroidectomy, although on relatively high doses of levothyroxine, both of them presented with the laboratory findings of RTH. Genetic analysis revealed RTH.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4001-4001
Author(s):  
Jaime Garcia Chavez ◽  
Moises L. Mendoza-Torres ◽  
Jorge Vela-Ojeda ◽  
Eduardo E. Reynoso

Abstract Introduction: The inability to obtain a therapeutic value of the INR regardless of the warfarin high doses administration represents a significant problem to resolve in the oral anticoagulation therapy, this phenomena is called “Warfarin Resistance”. Based on the experience and success of Rituximab in the treatment of autoimmune diseases like Immune Thrombocytopenic Purpura, we treated 7 patients with Primary Antiphospholipid Syndrome (PAS) and Warfarin Resistance. Objective: To assess if Rituximab can revert the warfarin resistance in patients with thrombophilia associated to PAS Material and Methods: We evaluated 7 patients with PAS who were receiving 15 mg of warfarin and had persistent low INR values. Rituximab was given weekly at dose of 375 mg/m2 for 4 doses. Effectiveness and safety were registered weekly during 2 months since the start of treatment with clinical evaluation and INR, aPTT, warfarin serum levels and CD20 blood lymphocytes count determinations. Results: All patients were women with a mean of 35 years old (37– 48) and INR of 1.11 (0.79–1.50). All the patients (100%) reached the therapeutic level of INR between days 8 to 15, but the response lasted only a mean of 24 days (8 – 40). The maximum INR values were observed through the 2nd to the 3rd doses of Rituximab. The warfarin serum levels did not change during the assessment period. Conclusion: Rituximab was effective in reverting resistance to Warfarin therapy in patients with thrombosis for primary Antiphospholipid Syndrome, however it lasted a very short time and eventually all patients relapsed.


Cephalalgia ◽  
1985 ◽  
Vol 5 (2) ◽  
pp. 95-98 ◽  
Author(s):  
A Zuddas ◽  
S Mulas ◽  
M Del Zompo ◽  
GU Corsini

Over the last ten years the efficacy of lithium salts in cluster headache has been well demonstrated. Our patient, who had been suffering from cluster headache for approximately 30 years, had been in haemodialysis treatment for the last ten years for chronic renal failure. Moreover, he was affected by heart failure and peptic ulcer. The patient was currently under therapy with Digitalis, Isorbide dinitrate, and ranitidine and was dialyzed three times a week for a total of five hours each time. Neither prophylactic headache therapy nor high doses of analgesic drugs had proved effective. Although this patient was in haemodialysis, lithium treatment was indicated. The administration of lithium carbonate 300 mg during dialysis days and 150 mg during non-dialysis days improved the attacks. Complete recovery from the attacks was obtained when the serum levels of lithium reached the therapeutic range. No side effects were noted.


2017 ◽  
Vol 24 (8) ◽  
pp. 634-636 ◽  
Author(s):  
Mário L de Lemos ◽  
Jolene Guenter ◽  
Victoria Kletas

High-dose loperamide is often used for the acute management of chemotherapy-induced diarrhea, with a maximum daily dosing of up to 24 mg. Recently, the US Food and Drug Administration has issued a warning that loperamide can cause rare serious cardiac events, including QT prolongation, torsades de pointes, cardiac arrest and death. Most events were reported in patients taking very high doses for an extended period of time. Daily intake ranged from 64 mg to 1600 mg, often continuously for weeks or months. In addition, the reported serum levels of loperamide ranged from 22 ng/mL to 210 ng/mL, which is likely significantly higher than that expected from patients taking the recommended doses for chemotherapy-induced diarrhea. Overall, the incidence of serious cardiac events associated with loperamide remains low. In balance, the risk of uncontrolled complications from chemotherapy-induced diarrhea is likely greater than the rare cardiac risk associated with the chronic misuse of much higher doses of loperamide.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Khanna Arora ◽  
Prerna Batra ◽  
Tusha Sharma ◽  
Basu Dev Banerjee ◽  
Sushan Gupta

Background. Organochlorine pesticides (OCP) are persistent organic pollutants that have been implicated in causing several deleterious effects in humans. These are known neurotoxins in high doses, but the role of environmentally acquired OCPs in the body to induce seizures in children has not been investigated yet. Objectives. To assess the serum levels of OCPs in children aged 2–12 with idiopathic seizure and to find out any association between the two are our objectives. Methods. It was a cross-sectional pilot study. Twenty developmentally normal children aged 2–12, presenting with idiopathic generalized seizures, were recruited. Twenty age-matched controls without any history of seizures were also taken. Their serum levels of α, β, and γ hexachlorocyclohexane (HCH); and aldrin; dieldrin; p,p-dichlorodiphenyltrichloroethane (DDT), o,p-DDT, and p,p dichlorodiphenyldichloroethylene (DDE); and α and β endosulfan were analysed using gas chromatography (GC). Mann-Whitney U test was used to compare OCP levels between the groups. Spearman correlation was used to find the correlation between individual pesticide levels with age and seizure duration. Results. Levels of β, γ, and total HCH were significantly higher among cases as compared to the control group (P≤0.05). Conclusion. There exists a possible association between idiopathic seizures and high serum levels of OCPs, especially HCH.


2019 ◽  
Vol 38 (7) ◽  
pp. 762-774 ◽  
Author(s):  
AA Alkahtane ◽  
G Albasher ◽  
NK Al-Sultan ◽  
WS Alqahtani ◽  
S Alarifi ◽  
...  

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.


1999 ◽  
Vol 18 (5) ◽  
pp. 307-316 ◽  
Author(s):  
Sharad D. Sawant ◽  
Paul G. Doucet ◽  
Wout Slob ◽  
Benny L. Blaylock ◽  
Harihara M. Mehendale

Prior administration of a moderately hemolytic dose of 2-butoxyethanol (2-BE) in rats leads to autoprotection against the lethal effects of high doses. Digavalli and Mehendale (Arch. Toxicol. 69:526–532;1995) showed that this autoprotection was due to recovery from the prior episode of hemolysis resulting in a higher proportion of young red blood cells (RBCs), which are more resilient to 2-BE. The objective of this research was to investigate the hypothesis that autoprotection can be entirely explained in terms of such changes in age composition of the RBC population. A simple simulation model was developed to provide predictions of the effect of various 2-BE dosage regimes, which were then experimentally verified. Some model predictions were confirmed by the experiments, but others were distinctly off the mark. The longer sequences (two or three successive episodes) in particular showed unexpected erythropoietic responses. This was further investigated in additional experiments, which also looked at reticulocyte counts and serum levels of erythropoietin (Epo). These showed that the release of reticulocytes following a 2-BE challenge is considerably faster than one would expect from the normal processing time in the bone marrow, and also becomes stronger at each successive challenge, resulting in remarkably high levels of reticulocytosis. It is concluded that changes in age composition of the RBCs cannot fully explain the time course of the hematocrit during consecutive administration of several doses of 2-BE, and that other mechanisms must play an important role as well. The results seem to indicate that after the hematocrit has recovered a buffer of (almost mature) reticulocytes remains available in the bone marrow for several days, which can be released almost immediately when another decrease in hematocrit is evoked.


Author(s):  
Jürgen Steinmeyer ◽  
Johannes Flechtenmacher

AbstractDifferential diagnosis of muscle pain and weakness is extensive, including neurological, vertebral, arthrogenic, vascular, traumatic, immunological, endocrine, genetic and infectious aetiologies, as well as medication or toxin-related causes. Muscles are highly sensitive to a large number of drugs, especially with high doses. Although many drug classes can cause toxic myopathy, a significant number of cases are caused by lipid-lowering drugs, long-term use of corticosteroids, and, most often, alcohol misuse. Some drug interactions, e.g. those that are metabolised via the enzyme CYP3A4, can increase the serum levels of the drugs and drug-induced toxicity. A careful history of patientʼs drug and alcohol consumption is therefore vital. Clinical symptoms depend on the drug, dosage and patientʼs sensitivity. They can vary from asymptomatic increase in serum levels of creatine kinase, mild myalgia and cramps to muscle weakness, rhabdomyolysis, kidney failure and even death. The pathogenesis is often only partially known and multifactorial. Toxic myopathy is often reversible once the drug is discontinued, alternative drug therapy is started or a different dosage regimen is chosen. Complications such as acute kidney failure must be avoided, and analgesic therapy may be indicated.


2021 ◽  
Vol 12 ◽  
Author(s):  
Vivien Hébert ◽  
Maud Maho-Vaillant ◽  
Marie-Laure Golinski ◽  
Marie Petit ◽  
Gaëtan Riou ◽  
...  

The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn’t (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone.


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