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Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians 下载免费PDF全文
Adriana Foster Zixuan Wang Manzoor Usman Edna Stirewalt Peter Buckley 《Neuropsychiatric Disease and Treatment》2007,3(6):965-973
There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders. 相似文献
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Alessander Danna-Dos-Santos Adriana M Degani Mark L Latash 《Clinical neurophysiology》2007,118(8):1802-1814
OBJECTIVE: We tested a hypothesis on two patterns of anticipatory postural adjustments (APAs) in neck muscles, reciprocal and co-activation, that may be used in a task-specific way. We also explored possible relation of APAs in leg and trunk muscles to head stabilization. METHODS: Load perturbations (loading and unloading) were applied to the head, trunk, and head and trunk simultaneously using similar hand actions by standing persons. Electromyographic signals (EMGs) from 10 muscles were recorded. Shifts of the center of pressure and EMG indices were computed over typical time intervals for APA. RESULTS: Time-shifted (reciprocal) activation of neck flexor and extensor muscles during APAs was seen when perturbations were applied directly to the head. Simultaneous activation dominated when the perturbations were applied to the trunk. Minimal APAs were seen in the leg/trunk muscles during head perturbation tests. APAs during trunk perturbation were not different from those during trunk and head perturbation. CONCLUSIONS: The results confirm the existence of two different patterns of APAs in neck muscles. A time-shifted (reciprocal) pattern is more likely to be used in anticipation of a perturbation acting directly on the head. A simultaneous activation (co-activation) pattern is used when direction of head perturbation cannot be predicted with certainty. Leg/trunk APAs are unlikely to help stabilize head posture. SIGNIFICANCE: These results are important for better understanding of feed-forward mechanisms of the control of head posture with possible implications for neurological patients who suffer from impaired feed-forward postural control. 相似文献
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Scheila R Schaffazick Adriana R Pohlmann Teresa Dalla-Costa Sílvia S Guterres 《European journal of pharmaceutics and biopharmaceutics》2003,56(3):501-505
Different polymeric nanoparticles were freeze-dried and the powders compared to determine the influence of the lipophilic core (Miglyol 810) or benzyl benzoate) and polymeric material (poly(epsilon-caprolactone) or Eudragit S90) on their drug content and morphology. Diclofenac, a non-steroidal anti-inflammatory drug, was used as a model. To characterize the products, a biological experiment based on the evaluation of the mucosal toxicity of diclofenac was conducted. Nanocapsule and nanosphere suspensions were prepared by nanoprecipitation and freeze-dried after the addition of colloidal silicon dioxide. The powders were examined under scanning electron microscopy (SEM) and gastrointestinal tolerance of products was evaluated in rats. Powders presented drug contents between 90.2+/-5.5 and 101.1+/-1.9% (HPLC). SEM analyzes showed non-spherical microparticles and, at higher magnifications, the micro-powder surface presented a homogeneous nanocovering. Regarding the gastrointestinal tolerance, with the exception of benzyl benzoate-loaded formulations, powders presented lesional indexes lower than the diclofenac salt solution. In contrast to the literature, nanocapsules can be dried by freeze-drying without leakage of drug or breaking the capsule wall. 相似文献
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Paola Sarchielli Andrea Alberti Beatrice Gallai Francesca Coppola Antonio Baldi Ardesio Floridi Virgilio Gallai 《The journal of headache and pain》2002,3(3):129-135
Little has been done to investigate the biochemical basis of chronic daily headache (CDH). Our group has recently demonstrated
an increase in the cerebrospinal fluid (CSF) levels of nerve growth factor (NGF) in CDH patients, supporting the involvement
of this growth factor in the abnormal processing of head pain in this pathological condition. Other members of the neurotrophin
family, especially brain-derived neurotrophic factor (BDNF), have been hypothesized as being involved in the development of
chronic head pain in patients affected by CDH, but so far no data are available on this subject. BDNF, NGF and glutamate levels
were determined in the CSF of 25 patients affected by CDH with a previous history of migraine. These levels were compared
with those of a group of 20 control subjects, for whom the CSF examination and other instrumental investigations excluded
diseases of the central and peripheral nervous systems. Significantly higher levels of BDNF, NGF and glutamate were found
in CDH patients compared with control subjects (p<0.0001, p<0.0002 and p<0.001, respectively). A significant positive correlation emerged between CSF values of BDNF and those of NGF (r=0.61, p<0.001) and glutamate (r=0.44, p<0.025) in CDH patients. No significant differences were detected in BDNF, NGF and glutamate levels between CDH patients with
analgesic overuse and those without. These results support the involvement of BDNF in CDH through the potentiation of glutamatergic
transmission involved in the processing of head pain. The significant correlation between BDNF and NGF levels suggests that
NGF-mediated up-regulation of BDNF in central sites involved in long-term sensitization plays a key role in persistent head
pain in CDH patients.
Correspondence to P. Sarchielli 相似文献
27.
Gabriela Gutiérrez Adriana Sarto Luciana Berod Teresa Gentile R.A. Margni S. Pasqualini . 《American journal of reproductive immunology (New York, N.Y. : 1989)》2002,48(3):149-149
The cytokines that predominate at the healthy maternal fetal interface are compatible with those produced by Th2/3 cells. Th1 and Th2 type immunity are mutually inhibitory and cytokine profiles are regulated in part by maternal sex steroids. The immune and endocrine equilibrium required for pregnancy success may be modified by external factors including stress, infection and altered maternal nutrition. The latter has received surprisingly little attention particularly as the effects of nutrition on immunity per se are widely documented. We have used animal models to investigate the effects of altered maternal diet on both immune and endocrine mechanisms important for pregnancy success. In rodents, maternal deficiencies in iron and vitamin A have been shown to negatively alter the expression of placental cytokines and in the case of vitamin A, increase placental apoptosis. In a highly controlled sheep model, overfeeding young growing females carrying singleton pregnancies restricts placental growth resulting in the premature delivery of low birth weight lambs. This is associated with reduced maternal concentrations of progesterone, placental lactogen, PSPB, GH and increased insulin, IGF-1, leptin and thyroid hormones (Wallace et al. Reprod 2001; 122:347–357). At day 80 of gestation (term=145) the placentae of overfed dams exhibit reduced expression of proliferation markers, predominantly in the fetal trophectoderm, and increased expression of the pro-apoptotic protein bax. These data indicate an altered balance between placental proliferation and apoptosis, possibly linked to maternal endocrine status. We conclude that maternal diet has considerable impact on immuno-endocrine mechanisms critical for pregnancy success. 相似文献
28.
Negro R Mangieri T Coppola L Presicce G Casavola EC Gismondi R Locorotondo G Caroli P Pezzarossa A Dazzi D Hassan H 《Human reproduction (Oxford, England)》2005,20(6):1529-1533
BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate. 相似文献
29.
Mario T. Philipp Gary P. Wormser Adriana R. Marques Susan Bittker Dale S. Martin John Nowakowski Leonard G. Dally 《Clinical and Vaccine Immunology : CVI》2005,12(9):1069-1074
C6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C6 negative or had a ≥4-fold decrease in C6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis. 相似文献
30.
Julio C Delgado Ahasan Hameed Juan J Yunis Kailash Bhol Adriana I Rojas Simeen B Rehman Ashfaq A Khan Manzoor Ahmad Chester A Alper A.Razzzaque Ahmed Edmond J Yunis 《Human immunology》1997,57(2):110-119
ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. We found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 ( p = 0.01), DQA1*0101 ( p = 0.02), and DQB1*0503 ( p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 ( p < 10−6), DQA1*0101 ( p < 10−5) and DQB1*0503 ( p < 10−6), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives’ families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations. 相似文献