Disruptive behavior disorders and substance use disorders in adolescents

Disruptive behaviors disorders in the form of conduct disorder, oppositional defiant disorder and/or attention-deficit hyperactivity disorder are found in a majority of adolescents with substance use disorders These disorders influence the risk for and the course of substance use disorders in adolescents and potentially provide important targets for intervention. Interventions such as family therapy and multisystemic therapy can focus on important environmental factors that help to produce and sustain substance use, related problems and disruptive/deviant social behavior. Researchers and clinicians are increasingly utilizing multimodal approaches that use several psychosocial approaches in addition to medication, if indicated. This article reviews our current understanding of the relationship between disruptive behavior disorders and substance use disorders in adolescents and the importance of this understanding in the prevention, assessment and treatment of adolescents with substance use disorders.     

Clindamycin and taste disorders

What is already known about this subject.

• The antibiotic clindamycin has a bitter taste when it is used orally.

What this study adds

• A case series on oral as well as i.v. use of clindamycin associated with taste disorders is presented.
• After corrections in a case-by-case analysis for several possible confounders such as indication, clindamycin is disproportionally associated with taste disorders.
• Serum and hence saliva and sputum clindamycin levels seem to be responsible for this reversible adverse drug reaction.

Aims

Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin-induced taste disorders and to analyse the factors involved.

Methods

The adverse drug reaction database of the Netherlands Pharmacovigilance Centre was searched for reports concerning taste disorders with antibiotics. Clinical review of the cases and statistical analysis with logistic regression were performed. Characteristics of patients who reported taste disorders were compared for age, gender and formulation in clindamycin vs. other antibiotic users.

Results

Taste disorders were reported in seven (18%) of the clindamycin cases. In five reports an oral formulation was involved, in one report intravenous (i.v.) administration and in one report both formulations were used. Latency was <1 day after start and in one case taste disorders were present repeatedly at 10 min after every i.v. application. The adjusted reporting odds ratio was 7.0 (95% confidence interval 2.8, 17.3) and supports a possible causal relationship.

Conclusions

The association of clindamycin and taste disorders is supported by disproportionality analysis and seems to be independent of possible confounders such as age, gender and infections. The case reports suggest a role for clindamycin concentrations excreted in body fluids like saliva.     

烟碱和大脑功能障碍(英文)

During the last decade, brain nicotinic acetylcholine receptors were extensively characterized from electrophys-iological and pharmacological points of view. These receptors play important roles in memory and cognition and participate in the pathogenesis of several brain disorders (Parkinson's and Alzheimer's diseases, Tourette's syndrome, schizophrenia, depression, attention deficit disorder) . In the same diseases, clinical studies showed that nicotine had beneficial effects, both as therapeutic and prophylactic agent. This review presents recent data concerning the structure and properties of neuronal nicotinic receptors, their involvement in the pathogenesis of various brain disorders and the beneficial effects of nicotine as therapeutic agent.     

Tachykinins and neuropsychiatric disorders

The classical tachykinins, substance P, neurokinin A and neurokinin B are predominantly found in the nervous system where they act as neurotransmitters and neuromodulators. Their respective preferred receptors are NK1, NK2, and NK3 receptors. The presence of substance P in nociceptive primary afferent neurons, electrophysiological studies showing that it activated neurons in the dorsal horn of the spinal cord, and behavioral studies in animals, supported the concept that substance P was an important transmitter in the nociceptive pathway. It was therefore surprising that non-peptide NK1 receptor antagonists were ineffective as analgesics in clinical pain conditions. Nevertheless, the discovery that NK1 receptor antagonists had antidepressant activity led to renewed interest in these antagonists. It is disappointing that clinical trials of MK869 (aprepitant) for depression were suspended. The future of NK1 receptor antagonists as antidepressant drugs will depend on the outcome of clinical trials with other NK1 receptor antagonists. NK1 receptor antagonists were also found to be effective antiemetics, and aprepitant has recently become available for the treatment of chemotherapy induced emesis. Although less is known of the potential of NK2 and NK3 receptor antagonists, recent trials of NK3 receptor antagonists have shown efficacy in schizophrenia. The discovery of a new family of tachykinins, the hemokinins and endokinins, which acts on NK1 receptors and has potent effects on immune cells, has implications for the clinical use of NK1 receptor antagonists. Thus specific therapeutic strategies may be required to enable NK1 receptor antagonists to be introduced for treatment of neuropsychiatric disorders.     

Immunophilins and thrombotic disorders

The immunophilin family includes a large group of proteins with peptidyl prolyl-isomerase activity (PPI-ase). Immunophilins chaperone activity has been documented to be crucial for the correct folding and activation of many proteins. Thus, they have been subjected of intense investigation since they were firstly described in the last decades of the past century. Many of these studies have been focused on leukocyte constitutively expressed immunophilins, due to their relevance in the correct folding, and subsequently, sensitization and activation of the glycoprotein receptor (RGBs) of lymphocyte T CD4+ and Treg, hence regulating immunological responses against pathogen insults. Several clinical trials have been completed in the last decade reporting that administration of immunophilin-binding drugs, derived from macrolide lactones, like cyclosporine A (CsA) and tacrolimus (FK506), induced successful results in preventing organ rejection. By contrast, the expression of immunophilins and their physiological function remain poorly investigated in others cell types, such as platelets, where a reduced number of studies presenting evidences of immunophilins expression and their physiological contribution have been published, despite a number of clinical trials have noticed side effects of these drugs in thrombosis and platelet count, thus suggesting a possible regulatory function of immunophilins in human platelets, which is reviewed here.     

Lymphoproliferative disorders and chemokines

Chemokines are low molecular weight cytokines specialized in leukocyte recruitment. Recent studies have shown that tumor cells of hematopoietic and non hematopoietic origin express different chemokine receptors that may be involved in neoplastic cell growth, metastasis and angiogenesis. Human lymphoproliferative disorders arise from the malignant transformation of normal lymphoid cells frozen at discrete maturational stages. Studies performed with acute or chronic lymphoproliferative disorders have shown that CXCR4, the unique receptor for CXCL12, is up-regulated in many B and T cells malignancies and may be involved in metastatic localization of the neoplastic elements. Additional chemokine receptors are expressed in the individual lymphoproliferative disorders, but some of these are often non functional. Here we shall review the state of the art on chemokine receptor expression and function in human lymphoproliferative disorders, stressing the potential value of chemokines receptors as novel therapeutic targets. In this respect, small antagonistic peptides are being produced by pharmaceutical companies and hold great promise for clinical application.     

Fluoroquinolones and tendon disorders

Fluoroquinolones are the most potent oral antibiotics in clinical use today. Increasingly, these drugs are being prescribed for relatively benign infections and for new categories of patients, including paediatric patients. As their use becomes more frequent, so will the adverse events. This review focuses on a rare but debilitating adverse reaction, the fluoroquinolone-associated tendinopathy. Despite many published case reports and approximately 3500 cases reported to the World Health Organization Collaborating Centre for Drug Monitoring, little is known about the mechanisms behind this fluoroquinolone-specific toxicity. Data on chemical properties, mode of action, pharmacokinetic features, clinical presentation and risk factors in relation to tendon toxicity are discussed and the literature reviewed. As long as the musculoskeletal toxicity cannot be predicted by in vitro or in vivo models and this class of antibiotics is one of the most commonly linked to selection of resistant bacteria, a more prudent use of fluoroquinolones is warranted.     

糖尿病与焦虑障碍

糖尿病已是公认的心身疾病，尤其是2型糖尿病。现代医学研究表明：心理因素可通过大脑边缘系统和交感神经影响胰岛素的分泌，当人处于紧张、焦虑、恐惧或受惊吓等应激状态时，交感神经兴奋，使肾上腺素的分泌增加，间接抑制胰岛素的分泌和释放，使血糖升高；糖代谢紊乱可直接使患者产生抑郁、焦虑；稳定的情绪可以使糖尿病病情缓解，而忧郁、紧张和悲愤等情绪常导致病情加剧或恶化。     

Neurological disorders and travel

Travel is associated with a number of neurological disorders that can be divided into two categories: (1) Neurological infections including encephalitides, neurotuberculosis, neurobrucellosis, cysticercosis and trichinosis. Some of these disorders can be prevented by vaccinations, such as Japanese B encephalitis and rabies, some by the use of insect repellents and some by avoiding raw milk products and undercooked meat. (2) Non-infective neurological disorders, such as acute mountain sickness and high altitude cerebral oedema, problems occurring during air travel such as syncope, seizures, strokes, nerve compression, barotrauma and vertigo, motion sickness and foodborne neurotoxic disorders such as ciguatera, shellfish poisoning and intoxication by cassava. This group of diseases and disorders could be prevented if the traveller knows about them, applies simple physiological rules, takes some specific medications and knows how to avoid intoxications in certain geographical areas. Meningococcal meningitis, malaria and jet lag syndrome are extensively discussed in other articles of this issue. The discussion in this paper will be limited to the other disorders.     

Anxiety disorders among patients with co-occurring bipolar and substance use disorders

Bipolar and substance use disorders are known to co-occur frequently, but limited attention has been paid to anxiety disorders that may accompany this dual diagnosis. Therefore, we examined the prevalence and nature of anxiety disorders among treatment-seeking patients diagnosed with current bipolar and substance use disorders, and investigated the association between anxiety disorders and substance use. Among 90 participants diagnosed with bipolar disorder I (n = 75, 78%) or II (n = 15, 22%), 43 (48%) had a lifetime anxiety disorder, with post-traumatic stress disorder (PTSD) occurring most frequently (n = 21, 23%). We found that those with PTSD, but not with the other anxiety disorders assessed, began using drugs at an earlier age and had more lifetime substance use disorders, particularly cocaine and amphetamine use disorders, than those without PTSD. Further examination revealed that (1) most participants with PTSD were women, (2) sexual abuse was the most frequently reported index trauma, and (3) the mean age of the earliest index trauma occurred before the mean age of initiation of drug use. Our findings point to the importance of further investigating the ramifications of a trauma history among those who are dually diagnosed with bipolar and substance use disorders.     

Management of co-morbid anxiety and alcohol disorders: parallel treatment of disorders

Co-morbid alcohol-related disorders and anxiety disorders have been found to occur in alcohol treatment populations, anxiety treatment populations and the general community. People suffering from co-occurring alcohol-related and anxiety disorders are more prone to relapse to alcohol abuse, and more likely to re-enter the treatment system for either disorder than sufferers of either disorder without a co-morbid disorder. To review the current state of the management of this disorder, evidence of the prevalence of this co-morbid condition in clinical and community populations is examined, then the theoretical mechanisms that might explain this connection are reviewed. A comparison of the few treatment studies of co-morbid alcohol and anxiety disorders shows a limited number of pharmacological treatment trials and no psychotherapy outcome trials. This review shows that it is no longer sustainable to conceptualize co-morbidity of alcohol and anxiety disorders as a unitary concept, i.e. lumping alcohol-related and anxiety disorders as one global condition, but as separate distinct combinations of particular anxiety disorders, e.g. alcohol dependence and panic disorder, alcohol dependence and generalize anxiety disorder. The recommended treatment approach, supported by the evidence, is to offer separate and parallel therapy for the alcohol-related and anxiety disorder, until empirical evidence from treatment outcome studies suggest otherwise. There is an urgent need to conduct treatment outcome research for the subtypes of co-morbid alcohol and anxiety disorders.     

Affective disorders and biological rhythms

Disruptions of circadian rhythms are described in affective disorders, including unipolar and bipolar disorder, but also seasonal affective disorder. Sleep-wake and hormone circadian rhythms are among the most quoted examples. Depression could be conceptualized as a desynchronization between the endogenous circadian pacemaker and the exogenous stimuli, such as sunlight and social rhythms. Accordingly, Clock genes have been studied and the literature suggests that variants in these genes confer a higher risk of relapse, more sleep disturbances associated with depression, as well as incomplete treatment response. Most of therapeutic interventions in depression have an impact on biological rhythms. Some of them exclusively act via a biological pathway, such as sleep deprivation or light therapy. Some psychosocial interventions are specifically focusing on social rhythms, particularly in bipolar disorder, in which the promotion of stabilization is emphasized. Finally, all antidepressant medications could improve biological rhythms, but some new agents are now totally focusing this novel approach for the treatment of depression.     

Serotonin and GI clinical disorders

Serotonin is widely distributed throughout the gut within both the enteric nerves and enterochromaffin (EC) cells. EC cells are located in the gut mucosa with maximal numbers in the duodenum and rectum where they act as signal transducers, responding to pressure and luminal substances both bacterial and dietary. Activation leads to serotonin release which acts on a range of receptors on mucosal afferent and myenteric interneurones to initiate secretomotor reflexes. These cause nausea and vomiting as well as intestinal secretion, propulsion and if pronounced, diarrhoea. Inflammation in animal models acts via T lymphocytes to increase EC cell numbers and mucosal serotonin (5-HT) content while inflammatory cytokines decrease serotonin transporter (SERT) function. Inflammation due to coeliac disease and following gastrointestinal infection increases mucosal 5-HT availability by a combination of increased EC cells and depressed SERT. Irritable bowel syndrome (IBS) developing after gastrointestinal infection and IBS with diarrhoea is associated with excess 5-HT. The associated diarrhoeal symptoms respond well to 5-HT₃ receptor antagonists. These drugs also inhibit the nausea and vomiting occurring in patients undergoing chemotherapy which cause a marked increase in release of 5-HT as well as other mediators. Other conditions including IBS-C and constipation may have inadequate 5-HT release and benefit from both 5-HT₃ and 5-HT₄ receptor agonists.     

谷氨酸转运体与神经退行性疾病

谷氨酸是哺乳动物脑内最主要的兴奋性神经递质，其主要灭活方式是依赖谷氨酸转运体的摄取进入细胞，当谷氨酸转运体失表达，停止转运或反向释放谷氨酸时，引起突触间隙或胞外谷氨酸大量蓄积从而导致神经毒性反应，研究表明，谷氨酸转运体的摄取功能障碍与肌萎缩性侧索硬化症（amyo-trophic lateral sclerosis,ALS)、阿尔茨海默病（Alzhei-mer's disease,AD)、帕金森病（Parkinson's disease,PD）等许多神经退行性病变有关，这一发现对于神经退行性病变的病因学和治疗学研究均具有重要意义。     

Nicotine and inflammatory neurological disorders

Cigarette smoke is a major health risk factor which significantly increases the incidence of diseases including lung cancer and respiratory infections. However, there is increasing evidence that smokers have a lower incidence of some inflammatory and neurodegenerative diseases. Nicotine is the main irnrnunosuppressive constituent of cigarette smoke, which inhibits both the innate and adaptive immune responses. Unlike cigarette smoke, nicotine is not yet considered to be a carcinogen and may, in fact, have therapeutic potential as a neuroprotective and anti-inflammatory agent. This review provides a synopsis summarizing the effects of nicotine on the immune system and its （nicotine） influences on various neurological diseases.