Recent developments in the pharmacological treatment and prevention of corneal graft rejection

At present, given the high initial success rate of corneal transplantation (although late survival is poor), immunosuppression is often reserved for 'high-risk' patients. Despite immune privilege, corneal graft rejection remains the leading cause of corneal allograft failure. Interpreting the limited and also restricted design of most trials, immunosuppressive therapy has not enjoyed the success seen in solid organ grafts. This review discusses the limited data available whilst proposing newer therapies that have developed as a result of our increased understanding of the immunobiology of corneal graft rejection.     

Recent developments in the pharmacological treatment and prevention of corneal graft rejection

At present, given the high initial success rate of corneal transplantation (although late survival is poor), immunosuppression is often reserved for ‘high-risk’ patients. Despite immune privilege, corneal graft rejection remains the leading cause of corneal allograft failure. Interpreting the limited and also restricted design of most trials, immunosuppressive therapy has not enjoyed the success seen in solid organ grafts. This review discusses the limited data available whilst proposing newer therapies that have developed as a result of our increased understanding of the immunobiology of corneal graft rejection.     

Recent developments in the treatment of sepsis

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.     

Recent developments in the treatment of tuberculosis

The history of chemotherapy of tuberculosis commenced in 1944 with the discovery of streptomycin. Currently, short-course chemotherapy comprising rifampicin, isoniazid, pyrazinamide and ethambutol/streptomycin administered under directly observed settings for 6 months (initially all four drugs followed by the former two drugs), constitutes the cornerstone treatment for pulmonary tuberculosis. Multi-drug resistant tuberculosis requires alternative chemotherapy, ideally in the form of individualised regimens, for management. To improve on the duration of chemotherapy for drug-susceptible tuberculosis and to achieve better treatment for multi-drug resistant tuberculosis as well as latent tuberculosis infection, there arises a genuine need for new drugs. The quest for new agents is, however, impeded by obstacles. Hopefully, tackling these through collaborative public-private partnerships on an international scale will lead to a fruitful outcome.     

Recent developments in the treatment of tuberculosis

The history of chemotherapy of tuberculosis commenced in 1944 with the discovery of streptomycin. Currently, short-course chemotherapy comprising rifampicin, isoniazid, pyrazinamide and ethambutol/streptomycin administered under directly observed settings for 6 months (initially all four drugs followed by the former two drugs), constitutes the cornerstone treatment for pulmonary tuberculosis. Multi-drug resistant tuberculosis requires alternative chemotherapy, ideally in the form of individualised regimens, for management. To improve on the duration of chemotherapy for drug-susceptible tuberculosis and to achieve better treatment for multi-drug resistant tuberculosis as well as latent tuberculosis infection, there arises a genuine need for new drugs. The quest for new agents is, however, impeded by obstacles. Hopefully, tackling these through collaborative public-private partnerships on an international scale will lead to a fruitful outcome.     

Recent developments in the treatment of sepsis

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-α, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.     

Recent developments in the treatment of bipolar disorders

Recently, many new therapeutic options have become available for the treatment of bipolar disorder. Most of these options are agents originally developed to treat other conditions, such as anticonvulsants and antipsychotics. Some older agents have also been rediscovered or reformulated. New drug combinations and treatment strategies have enabled a more comprehensive treatment of the spectrum of bipolar symptoms, as well as bipolar disorder complicated by a range of comorbidities, to be targeted. A growing range of novel therapeutic options for the treatment of bipolar disorder is under investigation. This paper summarises some of the data regarding these potential therapeutic options.     

Recent developments in the treatment of bipolar disorders

Recently, many new therapeutic options have become available for the treatment of bipolar disorder. Most of these options are agents originally developed to treat other conditions, such as anticonvulsants and antipsychotics. Some older agents have also been rediscovered or reformulated. New drug combinations and treatment strategies have enabled a more comprehensive treatment of the spectrum of bipolar symptoms, as well as bipolar disorder complicated by a range of comorbidities, to be targeted. A growing range of novel therapeutic options for the treatment of bipolar disorder is under investigation. This paper summarises some of the data regarding these potential therapeutic options.     

New developments in the treatment of neurological diseases

More than 8,000 researchers, clinicians and exhibitors from around the world gathered in San Francisco for the American Academy of Neurology 56th Annual Meeting, April 24 to May 1, 2004. Of the 1,300 studies at the conference, researchers presented more than 200 abstracts each on multiple sclerosis, stroke and dementia, 145 on epilepsy, 159 on Parkinson's disease, 132 on pain and about 50 each on tremor and dystonia. The use of brain imaging technology also figured strongly in the program, with 300 abstracts that mentioned magnetic resonance imaging and 50 that included positron emission tomography. Highlights included promising Parkinson's disease studies involving gene therapy and treatments using glial-cell-derived neurotrophic factor, but also new evidence of cardiac valve regurgitation associated with pergolide. Other highlights included studies on neural repair, new guidelines for the treatment of epilepsy and important studies comparing the thrombin inhibitor ximelagatran to warfarin for the prevention of stroke.     

隐孢子虫病的化学治疗研究进展

目的综述隐孢子虫病的化学治疗研究进展。方法依据国内外近期公开发表的29篇文献,对隐孢子虫病的化学治疗研究进展进行归纳与总结。结果隐孢子虫作为一种重要的呈世界性分布的机会性致病原虫,对营养不良的婴儿和AIDS患者带来致命的威胁。由于其独特的特征,体内外实验证明还没有一种药物能够非常有效地治疗隐孢子虫病。因此,化学治疗新靶点的发现对于开发治疗隐孢子虫病的药物就显得非常重要。结论 随着对隐孢子虫蛋白和基因组学的深入研究,开发新一代的药物靶点已逐步成为隐孢子虫病化学治疗研究的重要内容,呈现良好的发展势头。     

Recent developments in the pharmacological treatment of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra. The decline of dopamine leads to motor dysfunctions manifested as tremor, rigidity and bradykinesia. The pharmacological treatment of choice for the past 30 years has primarily been the dopamine precursor levodopa. Although it is the most effective treatment available, it is clear that other drugs are needed in order to sustain a therapeutic benefit and to alleviate fluctuations in mobility (i.e., motor fluctuations). Furthermore, there is some evidence that levodopa may hasten the occurrence of motor fluctuations and involuntary movements called dyskinesias. Hence, many clinicians delay the use of levodopa and employ the use of other symptomatic treatments including monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists as first-line therapy in de novo patients. Regardless of treatment, the disease continues to progress as there is still no obvious means of altering disease progression (i.e., no neuroprotective therapy), to restore loss of dopamine (i.e., no restorative therapy) or prevent the disease (i.e. preventative therapy). With disease progression, polypharmacy is common and often employs a combination of antiparkinsonian agents. There have been some key advances in treatment with the advent of MAO-B inhibitors, dopamine agonists and catechol-O-methyltransferase inhibitors; however, the arsenal of drug treatment remains limited. As the mechanism of PD is further elucidated, novel drug treatments will continue to emerge in the areas of preventative, restorative or symptomatic therapy. Despite the purpose of treatment, the ideal pharmacological drug for PD will include the presence of a safe side-effect profile, a simple dosing schedule, the ability to provide symptomatic relief and the potential to alter disease progression. The purpose of this article is to examine upcoming antiparkinsonian drugs in clinical trials based on their pharmacology, safety and efficacy.     

Recent developments in the pharmacological treatment of Crohn's disease

Therapy for Crohn's disease (CD) is rapidly evolving with the emergence of new discoveries in disease pathogenesis. Since the approval of the first biological agent, infliximab, there have been several others that have been studied and are available for use within the context of clinical trials, in CD patients who do not respond to conventional medications or whose disease cannot be maintained in remission with the use of infliximab. The number of available drugs that have focused on the inhibition of TNF is growing. To avoid the injectable route of administering biologicals, several oral agents, such as thalidomide analogues, nonabsorbable antibiotics, such as rifaximin, and specific antibiotics, such as ornidazole, are being studied and considered for patients with CD. Hormonal therapies, such as growth hormone, coherin, medroxyprogesterone acetate and dehydroepiandrosterone, are other novel therapies for CD. Immunomodulators in use in other fields of medicine, including tacrolimus, 6-thioguanine and leflunomide, are being evaluated for the treatment of patients with CD and are also discussed. Several other promising therapies, such as cyclophosphamide, extracorporeal photochemotherapy, stem cell transplantation and the use of porcine whipworm, add to the available therapeutic armamentarium of this life-long remitting and relapsing disease. The future for CD patients is promising with the ever-expanding repertoire of drugs that are being studied.     

Recent developments in the treatment of osteoarthritis with NSAIDs

Abstract

Objective:

To conduct a systematic review of evidence supporting the efficacy and safety profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) introduced in the last decade for the treatment of patients with osteoarthritis (OA), including their analgesic effects, ability to improve function, and adverse event profiles relative to current standards of care.