scholarly journals Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Pravesh Sharma ◽  
Jeffrey Davis ◽  
Vivekananda Rachamallu ◽  
Manish Aligeti
Keyword(s):  
African American Male ◽  
Paranoid Schizophrenia ◽  
Severe Neutropenia ◽  
Psychotic Symptoms ◽  
Rapid Decline ◽  
Dependent Manner ◽  
Gradual Decline ◽  
History Of ◽  
Leukocyte Counts ◽  
Dose Dependent

This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient’s psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient’s laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner.

Ketamine Inhibits Monoamine Transporters Expressed in Human Embryonic Kidney 293 Cells 

1998 ◽  
Vol 88 (3) ◽  
pp. 768-774 ◽  
Author(s):  
Mitsuhiro Nishimura ◽  
Kohji Sato ◽  
Tomoya Okada ◽  
Ikuto Yoshiya ◽  
Patrick Schloss ◽  
...  
Keyword(s):  
Eukaryotic Expression ◽  
Psychotic Symptoms ◽  
Kidney Cells ◽  
Dependent Manner ◽  
Monoamine Transporters ◽  
Human Embryonic Kidney ◽  
General Anesthetic ◽  
Serotonin Transporters ◽  
Human Embryonic Kidney Cells ◽  
Dose Dependent

Background Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibility that ketamine affects monoaminergic neurotransmission. To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, dopamine, and serotonin transporters and investigated the effects of ketamine on these transporters. Methods Human embryonic kidney cells were transfected using the Chen-Okayama method with the human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbital. Results Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters. Conclusions Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.

scholarly journals Loxapine in patient with clozapine-resistant psychosis

2021 ◽  
Vol 11 (4) ◽  
pp. 263-266
Author(s):  
Jennifer Erley ◽  
Sarah Goldsborough ◽  
Amy VandenBerg ◽  
Alexandra Audu
Keyword(s):  
Adverse Effects ◽  
Clinical Improvement ◽  
Receptor Binding ◽  
First Generation ◽  
Paranoid Schizophrenia ◽  
Severe Neutropenia ◽  
Drug Of Choice ◽  
Psychotropic Agents ◽  
History Of ◽  
Treatment Refractory

Abstract Clozapine is recognized as the drug of choice for treatment-refractory schizophrenia, but use may be limited because of strict monitoring requirements and adverse effects including severe neutropenia, seizures, and myocarditis. Loxapine is a first-generation antipsychotic with similarities to clozapine in both structure and receptor binding. This case describes a 57-year-old male with a history of severe paranoid schizophrenia despite treatment with clozapine and other psychotropic agents, who experienced clinical improvement after a cross titration from clozapine to loxapine. Loxapine may be a reasonable alternative in patients with treatment-refractory schizophrenia who do not tolerate or respond to clozapine.

scholarly journals The effectiveness of long-term aripiprazole injections to a patient with paranoid schizophrenia: a case report

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna Maria Szota ◽  
Aleksander Araszkiewicz
Keyword(s):  
Case Report ◽  
Negative Symptoms ◽  
Social Withdrawal ◽  
Paranoid Schizophrenia ◽  
Psychotic Symptoms ◽  
Suicidal Thoughts ◽  
Duration Of Hospitalization ◽  
History Of ◽  
Long Acting

AbstractParanoid schizophrenia is a chronic, psychotic disorder which can be treated with long-acting injectable (LAI) antipsychotic drugs. There are risperidone (Risperdal Consta®), olanzapine (Zypadhera®), paliperidone (Xepilon®) and aripiprazole (Abilify Maintena®) currently available.The aim of this study was to present a case history of the patient to whom monthly injections of aripiprazole effectively prevented both relapses of psychotic symptoms and hospitalizations.Case report: A 55-year-old male patient with a 13-year history of paranoid schizophrenia has been effectively treated with aripiprazole (LAI) (400mg, every 4 weeks). During the last 8 years of treatment his mental state has been stabilized, without any acute psychotic symptoms and without any anxiety, or violent behaviours. Moreover, there have been no psychotic symptoms, or suicidal thoughts, or tendencies recordered. Therefore, no hospitalization has been required. However, despite the treatment, negative symptoms such as blunted affect, cognitive dysfunction and social withdrawal have been sustained.Discussion: The available articles on aripiprazole (LAI) treatment indicate that it was effective in reducing the positive and negative symptoms of schizophrenia, as well as reducing the frequency and duration of hospitalization. However, the case report of a patient who has not had relapses of psychotic symptoms and suicidal thoughts and has not been hospitalized during 8 years of treatment with aripiprazole (LAI) has not yet been reported.Conclusions: Regular, long-term injections of aripiprazole (LAI) are very effective at preventing positive symptoms of schizophrenia development and preventing both suicidal thoughts and hospitalizations. Therefore, treatment with this drug in everyday practice should be increased.

scholarly journals Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

2017 ◽  
Vol 76 (11) ◽  
pp. 1845-1852 ◽  
Author(s):  
Cecilia Orellana ◽  
Saedis Saevarsdottir ◽  
Lars Klareskog ◽  
Elizabeth W Karlson ◽  
Lars Alfredsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Population Based ◽  
Case Control ◽  
Residential Area ◽  
Dependent Manner ◽  
Epidemiological Investigation ◽  
Long Duration ◽  
History Of ◽  
Dose Dependent ◽  
Anticitrullinated Protein Antibodies

ObjectivesTo study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA.MethodsWomen aged ≥18 years, participants in the population-based case–control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction.ResultsCompared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14–0.42)) on the risk of ACPA-positive RA. No interactions were found for BF.ConclusionsOC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.

scholarly journals Reduction of Pulmonary Toxicity ofStachybotrys chartarum Spores by Methanol Extraction of Mycotoxins

2000 ◽  
Vol 66 (7) ◽  
pp. 2817-2821 ◽  
Author(s):  
Carol Y. Rao ◽  
Joseph D. Brain ◽  
Harriet A. Burge
Keyword(s):  
Bronchoalveolar Lavage ◽  
Pulmonary Inflammation ◽  
Lactic Dehydrogenase ◽  
Lavage Fluid ◽  
Dose Effect ◽  
Dependent Manner ◽  
Methanol Extraction ◽  
Leukocyte Counts ◽  
Dose Dependent

ABSTRACT The fungus Stachybotrys chartarum has been implicated in cases of nonspecific indoor air quality complaints in adults and in cases of pulmonary hemorrhaging in infants. The effects that have been described have been attributed to mycotoxins. Previous dose-effect studies focused on exposure to a single mycotoxin in a solvent, a strategy which is unlikely to accurately characterize the effects of inhaled spores. In this study we examined the role of mycotoxins in the pulmonary effects caused by S. chartarum spores and the dose dependency of these effects. S. chartarum spores were extracted in methanol to reduce the mycotoxin content of the spores. Then either untreated (toxin-containing) or methanol-extracted S. chartarum spores were intratracheally instilled into male 10-week-old Charles River-Dawley rats. After 24 h, the lungs were lavaged, and the bronchoalveolar lavage fluid was analyzed to determine differences in lactic dehydrogenase, albumin, hemoglobin, myeloperoxidase, and leukocyte differential counts. Weight change was also monitored. Our data show that methanol extraction dramatically reduced the toxicity of S. chartarum spores. No statistically significant effects were observed in the bronchoalveolar lavage fluids of the animals that were treated with methanol-extracted spores at any dose. Conversely, dose-dependent effects of the toxin-containing spores were observed when we examined the lactic dehydrogenase, albumin, and hemoglobin concentrations, the polymorphonuclear leukocyte counts, and weight loss. Our findings show that a single, intense exposure to toxin-containing S. chartarum spores results in pulmonary inflammation and injury in a dose-dependent manner. Importantly, the effects are related to methanol-soluble toxins in the spores.

scholarly journals Herbicide injury induces DNA methylome alterations in Arabidopsis

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3560 ◽  
Author(s):  
Gunjune Kim ◽  
Christopher R. Clarke ◽  
Hailey Larose ◽  
Hong T. Tran ◽  
David C. Haak ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Evolutionary Mechanisms ◽  
Herbicide Resistant ◽  
Modern Agriculture ◽  
Adaptive Mechanisms ◽  
History Of ◽  
Mock Treatment ◽  
Methylation Patterns ◽  
Dose Dependent ◽  
Herbicide Glyphosate

The emergence of herbicide-resistant weeds is a major threat facing modern agriculture. Over 470 weedy-plant populations have developed resistance to herbicides. Traditional evolutionary mechanisms are not always sufficient to explain the rapidity with which certain weed populations adapt in response to herbicide exposure. Stress-induced epigenetic changes, such as alterations in DNA methylation, are potential additional adaptive mechanisms for herbicide resistance. We performed methylC sequencing of Arabidopsis thaliana leaves that developed after either mock treatment or two different sub-lethal doses of the herbicide glyphosate, the most-used herbicide in the history of agriculture. The herbicide injury resulted in 9,205 differentially methylated regions (DMRs) across the genome. In total, 5,914 of these DMRs were induced in a dose-dependent manner, wherein the methylation levels were positively correlated to the severity of the herbicide injury, suggesting that plants can modulate the magnitude of methylation changes based on the severity of the stress. Of the 3,680 genes associated with glyphosate-induced DMRs, only 7% were also implicated in methylation changes following biotic or salinity stress. These results demonstrate that plants respond to herbicide stress through changes in methylation patterns that are, in general, dose-sensitive and, at least partially, stress-specific.

scholarly journals Statins Plus Metformin: a Promising Combination for Prevention and Treatment of Atherosclerosis

2016 ◽  
Vol 1 ◽  
Author(s):  
Fei Luo ◽  
Yuan Guo ◽  
Xiang-ping Li
Keyword(s):  
Women Elderly ◽  
Dependent Manner ◽  
Antidiabetic Medication ◽  
Asian Ethnicity ◽  
Statin Monotherapy ◽  
History Of ◽  
Prevention Of Atherosclerosis ◽  
Dose Dependent ◽  
New Onset

<p>Statins are the cornerstone for primary and secondary prevention of atherosclerosis. But statin monotherapy in some patients will not be sufficient to achieve an LDL-C target and increase the incidence of new-onset diabetes in a dose dependent manner, especially in women, elderly, presence of family history of type 2 diabetes and Asian ethnicity. Recently metformin, an old and effective antidiabetic medication, has been found to reduce LDL-C levels and has cardiac benefits for patients with T2D. Therefore, statins plus metformin may further reduce LDL-C levels and partly counteract statin-induced diabetes.</p>

Phase Ib Studies of Benegrastim in Chinese Women with Breast Cancer Receiving Myelotoxic Chemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4601-4601
Author(s):  
Junning Cao ◽  
Zhongyu Yuan ◽  
Cheng Huang ◽  
Dongmei Ji ◽  
Rujun Peng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Research Funding ◽  
Chinese Women ◽  
Dose Finding ◽  
Chemotherapy Cycle ◽  
Severe Neutropenia ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Dose Dependent

Abstract Neutropenia is common in patients receiving myelotoxic chemotherapy. BenegrastimTM(F-627), a recombinant human G-CSF dimer, is an once-per-cycle therapy for prophylactic neutropenia in cancer patients after chemotherapy. Two phase I dose finding studies of benegrastim were conducted in Chinese women with stage I-IV breast cancer receiving myelotoxic chemotherapy. The aims of the studies were to evaluate the safety profile and pharmacokinetics (PK) and pharmacodynamics (PD) properties of benegrastim. In the first study, a total of 18 patients were enrolled to receive 3 sequential dose levels of benegrastim at 80, 240 and 360 µg/kg (n=6). The patients received epirubicin/cyclophosphamide (EC) chemotherapy on day one. Benegrastim was administered to patients on day 3 by SC injection once per chemotherapy cycle for up to 4 cycles. In the second study, 15 patients were sequentially assigned to 240 µg/kg (n=7) and 320 µg/kg (n=8) of benegrastim. These patients received doxorubicin, docetaxel and cyclophosphamide (TAC) on day one, benegrastim was administered on day 2 by SC injection for up to 6 cycles. The PK/PD properties of benegrastim were evaluated in cycle one and cycle three. Benegrastim was well tolerated in both clinical studies. The treatment emergent adverse events related to benegrastim were back pain, arthralgia, musculoskeletal pain, and rash, commonly seen in rhG-CSF therapy. The PK/PD result in patients receiving TAC in the first chemotherapy cycle is shown in Fig 1. Dose-dependent benegrastim exposure and ANC increase were demonstrated in these two clinical trials. In breast cancer patients receiving EC or TAC, benegrastim showed a non-linear pharmacokinetics. Benegrastim shortened the duration of neutropenia post chemotherapy in a dose dependent manner. In conclusion, benegrastim may provide an alternative approach to manage neutropenia, especially, severe neutropenia in patients after chemotherapy. Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle. Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle. Disclosures Cao: Generon (Shanghai) Corporation Ltd.: Research Funding. Yuan:Generon (Shanghai) Corporation Ltd.: Research Funding. Huang:Generon (Shanghai) Corporation Ltd.: Employment. Ji:Generon (Shanghai) Corporation Ltd.: Research Funding. Peng:Generon (Shanghai) Corporation Ltd.: Research Funding. Yan:Generon (Shanghai) Corporation Ltd.: Employment. Tang:Generon (Shanghai) Corporation Ltd.: Employment.

Comparison of alpha- and gamma-thrombin on lung fluid balance in anesthetized sheep

1984 ◽  
Vol 57 (5) ◽  
pp. 1375-1383 ◽  
Author(s):  
R. R. Garcia-Szabo ◽  
D. F. Kern ◽  
R. Bizios ◽  
J. W. Fenton ◽  
F. L. Minnear ◽  
...  
Keyword(s):  
Fluid Balance ◽  
Active Enzyme ◽  
Base Line ◽  
Dependent Manner ◽  
Fibrin Deposition ◽  
Pulmonary Vessels ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Leukocyte Counts ◽  
Dose Dependent

We examined the effects of varying dosages of thrombin on lung fluid balance in halothane-anesthetized sheep prepared with lung lymph fistulas. A 15-min iv infusion of sublethal doses of alpha-thrombin (2.5 clotting units/micrograms), the native enzyme, at 0.6 or 1.1 nmol active enzyme/kg body wt increased the mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) two- to threefold. Neither parameter increased in a dose-dependent manner. Platelet counts decreased 50% with both dosages. Leukocyte counts decreased 35 and 75% from base line in the low- and high-dosage groups, respectively, and reached comparable levels of 50% below base line at 60-min postinfusion in both groups. Plasma fibrinogen concentrations decreased in a dose-dependent manner preceding dose-dependent increases in pulmonary lymph flow (Qlym) and lymph protein clearance (Clym). Fibrin deposition in pulmonary vessels was greater at 30 than at 180 min postinfusion. In contrast, a 15-min iv infusion of gamma-thrombin (0.002 clotting units/micrograms), which lacks the fibrinogen recognition site, at 1.2 nmol active enzyme/kg produced no significant increases in PVR, Ppa, Qlym, or Clym. The fibrinogen concentration did not change significantly, whereas platelet and leukocyte counts decreased 25% within 15 min. Fibrin microthrombi were less prominent in pulmonary vessels. Fibrin deposition associated with intravascular coagulation may be an important factor mediating thrombin-induced increases in pulmonary transvascular fluid and protein exchange.

scholarly journals Effect of methonolic extract of Vitex negundo on haloperidol induced catalepsy in albino mice

2020 ◽  
Vol 9 (4) ◽  
pp. 621
Author(s):  
Sandeep Kumar Kamlekar ◽  
Sangita Gupta
Keyword(s):  
Medicinal Plants ◽  
Methanolic Extract ◽  
Time Interval ◽  
Dependent Manner ◽  
Vitex Negundo ◽  
Polyherbal Formulation ◽  
History Of ◽  
Pheniramine Maleate ◽  
Albino Mice ◽  
Dose Dependent

Background: Plants are being used in traditional medicine since history of mankind. The knowledge of these medicinal plants has accrued in the course of many centuries leading to medicinal systems in India such as Ayurveda, Unani and Siddha. Objective: In the present study, we evaluated the anticataleptic efficacy of Vitex negundo, a polyherbal formulation in haloperidol induced catalepsy in mice.Methods: Five groups (n=6) of male albino mice were used in the study. Catalepsy was induced by i.p. administration of haloperidol (1 mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of Vitex negundo (50, 100, 200 mg/kg) with standard received Pheniramine maleate 10 mg/kg, i.p.Results: In vehicle treated animals, haloperidol (1 mg/kg. i.p.) produced the maximum catalepsy at 180 min (46.78±3.78 min). Standard treated as Pheniramine maleate 10 mg/kg, i.p. shows maximum at 120 min. 19.24±1.32. Test herb, i.p. Methanolic extract of Vitex negundo (50, 100, 200 mg/kg, i.p.) significantly potentiated haloperidol induced catalepsy at each time interval, in a dose dependent manner. At dose 50, 100 and 200mg/kg, extract of Vitex negundo (Linn.) roots showed maximum cataleptic score 12.34±0.78, 14.43±0.43 and 15.43±0.67 min, respectively at 120 minutes in haloperidol treated animals.Conclusions: The present study indicates that the methanolic extract of Vitex negundo reduces haloperidol-induced catalepsy in mice.

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