共查询到20条相似文献,搜索用时 15 毫秒
1.
Many genetic studies have focussed on dopamine receptors and their relationship to neuropsychiatric disease. Schizophrenia, bipolar disorder, and substance abuse have been the most studied, but no conclusive linkage or association has been found. The possible influence of dopamine receptor variants on drug response has not received as much attention. While there is some evidence that polymorphisms and mutations in dopamine receptors can alter functional activity and pharmacological profiles, no conclusive data link these gene variants to drug response or disease. The lack of unequivocal findings may be related, in part, to the subtle changes in receptor pharmacology that these polymorphisms and mutations mediate. These subtle effects may be obscured by the influence of genes controlling drug metabolism and kinetics. Further insight into the pharmacogenetics of dopamine receptors may require not just more studies, but novel approaches to the study of complex genetic traits and diseases. 相似文献
2.
Dijendra Nath Roy Ritobrata Goswami Ayantika Pal 《Xenobiotica; the fate of foreign compounds in biological systems》2017,47(7):632-643
1.?In the last few years, a substantial scientific work is focused to identify the potential toxicity of nanomaterials by studying the cellular pathways under in vitro and in vivo conditions. Owing to high surface area to volume ratio nanoparticles (NPs) can pass through cell membranes which might be responsible for creating adverse interactions in biological systems. Simultaneously, researchers are also interested to assess the fate of NP inside the living system, which may lead to altered protein expression as well as protein corona formation.2.?According to published reports, NP-mediated toxicity involves altered cellular system including cell morphology, cell differentiation, cell metabolism, cell mobility, cellular immunity, which is derived from the side effects of nanoformulation and leading to apoptosis and necrosis. These results indicate the existence of potential toxic effect of these particles to human health.3.?The advent of proteomics with sophisticated technical improvement coupled with advanced bioinformatics has led to identify altered proteins due to nanomaterial exposure that could provide a new avenue to biomarker discovery.4.?This review aims to provide the current status of safe production and use of nanomaterials. 相似文献
3.
Laura E. O'Dell 《Pharmacology, biochemistry, and behavior》2009,91(4):481-488
Tobacco products are widely abused in humans, and it is assumed that nicotine is the key substrate in these products that produces addiction. Based on this assumption, several pre-clinical studies have utilized animal models to measure various aspects of nicotine addiction. Most of this work has focused on behavioral measures of nicotine and how other variables contribute to these effects. Here we discuss the most commonly used animal models including, self-administration (SA), place conditioning (PC), and the intracranial self-stimulation (ICSS) paradigms in rodents. The strengths, limitations and procedural variables of these models are reviewed, followed by a discussion of how the animal models have been used to study factors such as age, sex, stress, and the effects of tobacco products other than nicotine. These factors are discussed in light of their influences on human tobacco abuse. The rodent models are evaluated in the context of face, predictive, and construct validity, and we propose that inclusion of factors such as age, sex, stress and other constituents of tobacco aside from nicotine can increase the utility of these animal models by more closely mimicking human tobacco abuse. 相似文献
4.
5.
Mueller A 《British journal of pharmacology》2007,152(8):1145-1146
Chemokine receptors play an important role in trafficking leukocytes within the body, a process that depends on expression of the receptors on the cell surface. Expression levels are regulated by the rate of internalizing receptor compared to the rate of recycling/recovering receptor. Internalization is commonly induced by binding of agonists to their receptors that in turn use clathrin-coated pits or caveolae to internalize. Joplin and colleagues describe a novel usage of internalization assays to determine pharmacokinetic/pharmacodynamic relationships of an antagonist on CXCR3 in a murine system. Intriguingly their results show that internalization assays give robust data about the pharmacokinetics/pharmacodynamics of different agonists and antagonists in an in vivo model. This kind of assay will allow investigations of the pharmacological properties of agonists and antagonists in a completely different setting and also give new insight into the regulation of cell surface expression of chemokine receptors and other G protein-coupled receptors, which can lead to potential novel therapeutic targets. 相似文献
6.
Couteau C Couteau O Alami-El Boury S Coiffard LJ 《International journal of pharmaceutics》2011,415(1-2):181-184
Whereas for fifty or so years acquiring a tan has been the trend for aesthetic reasons relating to current beauty criteria, the health authorities are now advocating vigilance in this area, prompted by the knowledge of the harmful effects of the sun, especially from its ultra-violet rays. In the European Union, sunscreen products are considered cosmetics and tests on their effectiveness can be performed in vivo or in vitro to determine four effectiveness indicators: the SPF (Sun Protection Factor), the PF-UVA (UVA Protection Factor), the SPF/PF-UVA ratio and the critical wave length. It is the erythemal SPF which is measured in the vast majority of cases: it can therefore be confirmed that sunscreen products protect us from sunburn under good conditions of use. We thought it would be interesting to calculate other indicators to assess protection against non-melanoma skin cancers (NMSC) and to quantify the effectiveness of the product against UVA1 or UVA2. To characterize the products tested, we have determined in vitro different SPF and PF-UVA values, by using not just the erythemal weighting factor but also the weighting factor relating to the non-melanocytic skin cancer (SPF(cnm) and PF-UVA(cnm)), by getting away from any weighting factor (SPF(m) and PF-UVA(m)) and lastly, by varying the integration limits to quantify the effectiveness of the tested product in the UVB (290-320 nm), UVA1 (340-400 nm) and UVA2 320-340 nm) fields. In this way, and using these new indicators, we have been able to qualify eleven commercial products-ten cosmetic products and one medical device. It can be interesting to take into account the non-melanocytic skin cancer protection in order to qualify the sunscreen products. 相似文献
7.
8.
9.
Romano MC Valdez RA Hinojosa L Gómez Y Jiménez P 《Current topics in medicinal chemistry》2008,8(5):408-418
Over the last years the biology of many parasites that infect humans and domestic animals has been intensively studied. Considerable efforts were addressed to obtain information on the parasite-host immune relationship. However, the knowledge of the endocrine physiology of parasites and the consequences of the local hormone production on the host tissues needs further investigation. We review here literature and our own studies on endocrine parasite capacities with special emphasis on cysticercosis. Besides the biological interest, these investigations may contribute to identify in the future alternative treatments for the disease. 相似文献
10.
11.
12.
Ondansetron is a relatively new drug whose optimal use is dependent on an understanding of its characteristics and role relative to traditional antiemetics. To assess perceptions and knowledge regarding ondansetron, we conducted a prospective written survey involving 56 physicians, pharmacists, and nurses at this hospital. Pharmacists claimed to be exposed to ondansetron promotion by industry more than the other groups. Apart from industry, pharmacists were considered to be the most common source of drug information. Nurses were less aware of dosage form equivalence than the other groups (p = 0.042). Physicians were more aware of twice daily dosing efficacy than other respondents (p = 0.0006). Nurses were able to better identify the relative duration of antiemetic benefit over metoclopramide (p = 0.008); however, most participants tended to be misinformed on this issue. Pharmacists were more familiar with the side effect profile while physicians were more cognizant of oral (p = 0.001) and parenteral (p = 0.018) drug costs than other groups. Overall, survey scores for physicians and pharmacists were higher than those for nurses (p = 0.007). There is an apparent difference across health care profession disciplines in the perceptions and knowledge about ondansetron. Specific misconceptions could lead to suboptimal drug use and warrant efforts to ensure a good understanding of the attributes and relative role of this agent. 相似文献
13.
《Expert opinion on drug safety》2013,12(6):743-745
Osteonecrosis of the jaw is a new disease, partly caused by bisphosphonates. It is commonly assumed that the bisphosphonates somehow cause cell death (osteocyte necrosis) within the jawbone, which makes it prone to chronic infection. In this article, an alternative pathogenetic theory is suggested, based on the normal effect of bisphosphonates. According to the new theory, the bone is alive until it is injured and infected, and the reduced resorptive ability due to bisphosphonates hinders the formation of a fresh bone surface for re-establishment of bone cell coverage. The theories are compared, based on the recent, very scarce literature. None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis. 相似文献
14.
The treatment of women of childbearing age who have epilepsy raises many questions because of the interactions between epilepsy, antiepileptic therapy and different aspects of reproductive life. Menstrual cycle disorders and reduced fertility have been partially ascribed to antiepileptic drugs (AEDs). Furthermore, most AEDs induce the cytochrome P450 (CYP) enzymatic system, altering the metabolism of sex hormones and contributing to the failure of oral contraceptives. Pregnancy represents, in this context, the most critical period because of the well known teratogenic potential of all established AEDs. For most of these drugs no specific patterns of malformations have been identified, although during the past few decades basic knowledge has been acquired, particularly concerning the mechanisms of AED-induced teratogenesis and related risk factors. These issues form the basis of the current guidelines for the management of epilepsy in pregnant women. In the past decade, several new AEDs have been introduced into clinical practice. For a number of reasons, these drugs appear to be more favourable than the older ones as treatments for epilepsy in women of childbearing age. They possess a good pharmacokinetic profile that makes them more stable during pregnancy, and they have a low potential for interaction with other drugs. They are also less likely than the older AEDs to be metabolised to compounds that are teratogenic. Furthermore, most of them do not possess antifolate properties. With the exception of topiramate and vigabatrin, the newer AEDs do not appear to be teratogenic in animals when administered in subtoxic doses. However, animal teratology may not be a reliable predictor of human teratogenicity, and there is a significant lack of information regarding the teratogenic profile of these newer agents in humans. Because clinical experience with these agents is limited, it is advisable to avoid exposure of the embryo to these drugs when pregnancy is planned. The establishment of pregnancy registries could allow for the rapid collection of data related to the administration of new AEDs in pregnancy and the outcomes of such exposure. 相似文献
15.
16.
17.
18.
This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism. Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus. Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (<6 weeks) beta-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression. In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy. 相似文献
19.
《Expert opinion on drug discovery》2013,8(12):1479-1489
Introduction: Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered: This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion: There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. 相似文献
20.
In recent years the availability of so-called legal highs over the Internet has hugely increased. Numerous online legal-high retailers market a broad variety of products which are advertised as research chemicals, bath salts, or plant food although clearly intended for human consumption as recreational drug replacements. No guidelines exist as to what is sold and in what purity. Consumers are led to believe that purchased goods are entirely legal. In this study, several legal-high products were purchased and analyzed for their content. The powdered products were screened with attenuated total reflectance-Fourier Transform Infrared (ATR-FTIR) followed by gas chromatography-mass spectrometry (GC-MS) analysis of methanol extracts. Spectra were compared to reference standards and the NIST library. Results showed that 6 out of 7 products did not contain the advertised active ingredient. Moreover, five samples contained the controlled substances benzylpiperazine and 1-[3-(trifluoromethyl)phenyl]piperazine combined with caffeine. 相似文献