Heteropterys tomentosa (A. Juss.) infusion counteracts Cyclosporin a side effects on the ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controlling mechanical undesirable side effects with a tooth indicated for extraction: free anchorage

This manuscript describes the use of a tooth indicated for extraction due
to orthodontic reasons as an anchorage aid to receive undesirable side effects caused by orthodontic uprighting of a contralateral molar tooth. The mandibular right second molar was mesially tipped as a result of loss of the adjacent first molar. Since the treatment plan involved extraction of the mandibular left first premolar, undesirable side effects associated with the molar uprighting movement were transferred to this tooth. Once the second molar was vertical, the premolar was extracted and the treatment continued. The results suggest that treatment time can be reduced if undesirable orthodontic mechanical side effects can be directed to a tooth whose extraction is indicated.

Taste alteration, mouth dryness and teeth staining as side effects of medications taken by elderly

Elderly patients generally use several types of medication, some of which may cause oral side effects. Aim: To investigate the oral side effects caused by medication in an elderly sample. Methods: Three hundred patients were interviewed about their use of medication and were divided in two groups: institutionalized (n=150) and community-dwelling (n=150) elderly. Results: The most used drugs were antihypertensives (53%) for community-dwelling elders and antiulceratives (76%) for the institutionalized ones. The more prevalent side effects were taste alterations that occurred in 19%, dry mouth in 17% and teeth staining in 2%. Conclusions: A high prevalence of oral side effects from medications used by the elderly was found in this study. The health professionals should be aware of the possible side effects caused by prescribed medications.

SIDE EFFECTS OF PERSISTENT TOXICANTS

As you can see from the general tenor of the printed program for this seminar, I am in the unenviable position of trying to discourage you from certain types of chemical control; but my assigned topic "Side Effects of Persistent Toxicants," implies that mission. However, my remarks may be somewhat anticlimax at this time, because it is now generally conceded that we need to reevaluate certain chemicals in control work and to restrict or severely curtail use of those that per¬sist for long periods in the environment. So let me detail my reasons for a somewhat negative attitude toward the use of the persistent hydrocarbons from my experience with the effects of these materials on birds. But first a few words of caution about control work in general, which so often disrupts natural processes and leads to new and unforseen difficulties. As an example, I think of the irruption of mice in the Klamath valley in northern California and southern Oregon in the late '50's. Intensive predator control, particularly of coyotes, but also of hawks and owls, was followed by a severe outbreak of mice in the spring of 1958. To combat the plague of mice, poisoned bait (1080 and zinc phosphide) was widely distributed in an area used by 500,000 waterfowl each spring. More than 3,000 geese were poisoned, so driv¬ing parties were organized to keep the geese off the treated fields. Here it seems conceivable that the whole chain of costly events--cost of the original and probably unnecessary predator control, economic loss to crops from the mouse outbreak, another poisoning campaign to combat the mice, loss of valuable waterfowl resources, and man-hours involved in flushing geese from the fields--might have been averted by a policy of not interfering with the original predator-prey relationship. This points to a dilemma we always face. (We create deplorable situations by clumsy interference with natural processes, then seek artificial cures to correct our mistakes.) For example, we spend millions of dollars in seeking cures for cancer, but do little or nothing about restricting the use of known or suspected carcinogens such as nicotine and DDT.

Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Insights into cardiovascular side-effects of modern anticancer therapeutics

Modern anticancer therapeutics can be associated with significant cardiovascular side-effects. Detection, risk assessment, and treatment of these unwanted effects are an important task for treating physicians. The purpose of this review is to focus on approved novel cancer therapeutics and discuss the most important cardiovascular side-effects, prognosis, and potential treatment. We will contrast these effects to those of conventional cardiotoxic chemotherapeutics.

The complex clinical picture of side effects to biologicals

Biologicals are proteins used as drugs. Biologicals target clearly defined molecular structures, being part of established pathogenetic pathways. Therefore, their focused mode of action seems to render them superior to classic small molecular drugs regarding "off-target" adverse drug reactions (ADR). Nevertheless, the increasing use of biologicals for the treatment of different diseases has revealed partially unexpected adverse reactions. The often direct interaction of a biological with the immune system provides a clue to most side effects, which have consequently been subclassified, based on pathogenetic principles, into 5 subtypes named alpha, beta, gamma, delta, and epsilon, reflecting overstimulation (high cytokine values, type alpha), hypersensitivity (type beta), immune deviation (including immunodeficiency, type gamma), cross-reactivity (type delta), and nonimmune mediated side effects (type epsilon). This article presents typical clinical manifestations of these subtypes of ADR to biologicals, proposes general rules for treating them, and provides a scheme for a thorough allergological workup. This approach should help in future handling of these often very efficient drugs.

[Immunosuppressive drugs - how they work, their side effects and interactions]

The central issue in organ transplantation remains suppression of allograft rejection. Immunosuppression can be achieved by depleting lymphocytes, diverting lymphocyte traffic, or blocking lymphocyte response pathways. Immunosuppressive drugs include small-molecule drugs, depleting and nondepleting protein drugs (polyclonal and monoclonal antibodies), fusion proteins, intravenous immune globulin, and glucocorticoids. Small-molecule immunosuppressive agents include calcineurin-inhibitors (cyclosporine, tacrolimus), Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus), inhibitors of nucleotide synthesis and azathioprine. The review covers the mode of action of these drugs with a special focus on belatacept, a new promising fusion protein. Different immuo-suppressive strategies mean also different safety profiles. Common side effects include the consequences of diminished immuno- response, i.e. infections and cancer (mainly involving the skin). Toxic side effects of immunosuppressive drugs range in a wide spectrum that involves almost every organ. The major interest of this toxic effects is the cardiovascular tolerance (with large differences from drug to drug), that are discussed seperately. The calcineurin- and mTOR-inhibitors are both metabolized by the CYP450 3A4 enzyme, which is also involved in the metabolism of many other drugs. The review discusses the most important interactions that in- or decreases the through level of these drugs.

Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA Expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying

It has been proposed that gonadotropins and/or gonadotropin releasing hormone (GnRH) could be involved in the pathophysiology of the side effects after spaying in bitches, such as urinary incontinence and an increased production of a woolly undercoat. In order to provide tools to investigate the role of these hormones in dogs we developed immunohistochemical techniques and real-time RT-PCR to study whether GnRH-, LH-, and FSH-receptors exist in canine skin and urinary bladder. Tissue samples from the skin of the flank region and the ventral midline of the urinary bladder from euthanised dogs were examined. We were able to quantify mRNA expression of GnRH-, FSH-, and LH-receptors in canine skin and bladder biopsies with a high primer efficacy. Immunohistochemical studies showed that GnRH-, FSH-, and LH-receptors are expressed in vessel walls, the epidermis, the hair follicle and in sebaceous and sweat glands in canine skin and in transitional epithelium, and smooth muscle tissue in the urinary bladder. Our data provide the fundamentals to examine the distribution of FSH-, LH-, and GnRH-receptors in canine skin and urinary bladder and to assess gene activity at the transcriptional level by real-time RT-PCR.

Adverse side-effects to biological agents

Biological agents-like cytokines, monoclonal antibodies and fusion proteins are widely used in anti-inflammatory and tumour therapy. They are highly efficient in certain diseases, but can cause a great variety of adverse side-effects. Based on the peculiar features of biological agents a new classification of these adverse side-effects of biological agents is proposed - related but clearly distinct from the classification of side-effects observed with chemicals and drugs. This classification differentiates five distinct types, namely clinical reactions because of high cytokine levels (type alpha), hypersensitivity because of an immune reaction against the biological agent (beta), immune or cytokine imbalance syndromes (gamma), symptoms because of cross-reactivity (delta) and symptoms not directly affecting the immune system (epsilon). This classification could help to better deal with the clinical features of these side-effects, to identify possible individual and general risk factors and to direct research in this novel area of medicine.

Patient satisfaction and side effects in primary care: An observational study comparing homeopathy and conventional medicine

Background This study is part of a nationwide evaluation of complementary medicine in Switzerland (Programme Evaluation of Complementary Medicine PEK) and was funded by the Swiss Federal Office of Public Health. The main objective of this study is to investigate patient satisfaction and perception of side effects in homeopathy compared with conventional care in a primary care setting. Methods We examined data from two cross-sectional studies conducted in 2002–2003. The first study was a physician questionnaire assessing structural characteristics of practices. The second study was conducted on four given days during a 12-month period in 2002/2003 using a physician and patient questionnaire at consultation and a patient questionnaire mailed to the patient one month later (including Europep questionnaire). The participating physicians were all trained and licensed in conventional medicine. An additional qualification was required for medical doctors providing homeopathy (membership in the Swiss association of homeopathic physicians SVHA). Results A total of 6778 adult patients received the questionnaire and 3126 responded (46.1%). Statistically significant differences were found with respect to health status (higher percentage of chronic and severe conditions in the homeopathic group), perception of side effects (higher percentage of reported side effects in the conventional group) and patient satisfaction (higher percentage of satisfied patients in the homeopathic group). Conclusion Overall patient satisfaction was significantly higher in homeopathic than in conventional care. Homeopathic treatments were perceived as a low-risk therapy with two to three times fewer side effects than conventional care

Test Blueprints - Exposing Side Effects in Execution Traces to Support Writing Unit Tests

Writing unit tests for legacy systems is a key maintenance task. When writing tests for object-oriented programs, objects need to be set up and the expected effects of executing the unit under test need to be verified. If developers lack internal knowledge of a system, the task of writing tests is non-trivial. To address this problem, we propose an approach that exposes side effects detected in example runs of the system and uses these side effects to guide the developer when writing tests. We introduce a visualization called Test Blueprint, through which we identify what the required fixture is and what assertions are needed to verify the correct behavior of a unit under test. The dynamic analysis technique that underlies our approach is based on both tracing method executions and on tracking the flow of objects at runtime. To demonstrate the usefulness of our approach we present results from two case studies.