Perspectives for the future

The pathophysiology of sepsis and septic shock is extremely complex and ultimately involves every physiological pathway. The initiating event is the entrance of endotoxin or similar substances into the blood which initiates the release of multiple mediators. These are designed to react locally and to protect the organism. Their constant release, however, sets in motion up- and down regulations, ultimately resulting in “metabolic anarchy”. Tumor necrosis factora and other cytokines trigger several systems, especially coagulation to yield DIC, and the complement system. Many treatment modalities have been developed, most recently those which substitute inhibitors of various systems. Antithrombin III concentrates and potentially protein C concentrates are designed to arrest DIC. C1-esterase inhibitor concentrates should intercept the activation of the complement system and the contact phase of coagulation and its relationship to kinin generation. Even newer approaches entail antibodies to tumor necrosis factora or endotoxin itself. The complex process of sepsis will undoubtedly require a multifaceted therapeutic approach.     

心房颤动治疗:现状和未来

心房颤动(房颤)是21世纪的心血管流行病,疾病负担日趋严重。华法林作为房颤卒中预防的有效药物,在我国房颤患者中的应用仍然不足。随着新型口服抗凝药和左心耳封堵技术应用的不断增加,房颤抗栓治疗面临着更多选择。导管消融是阵发性房颤治疗的一线选择,而持续房颤的最佳消融策略仍然存在争议。近年来,生活方式干预在房颤预防和治疗中的价值逐步受到重视。未来,房颤治疗将进入一个崭新的时代。     

Antiviral treatment of hepatitis C: present status and future prospects

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis. A substantial proportion of patients with chronic hepatitis C eventually develop hepatocellular carcinoma (HCC), which is one of the leading causes of death worldwide. Therefore, efficient antiviral treatments for HCV have long been needed. A recently developed combination therapy of pegylated interferon and ribavirin has dramatically improved the outcome of antiviral therapy for HCV infection. In genotype 1b HCV infection, 48 weeks of the combination therapy achieved eradication of the virus in 50% of patients, and in genotype 2 HCV infection, 24 weeks of the therapy resulted in viral eradication in 80%–90% of patients. By this eradication, an improvement in the hepatic fibrosis, an inhibition of HCC development, and an improvement in life expectancy were attained. Patients who did not respond to the combination therapy may be treated with long-term interferon monotherapy, which is not intended to eradicate HCV, but will lower the serum alanine aminotransferase (ALT) level. Thus, the treatment for HCV infection has progressed significantly, but therapies with new modalities, such as inhibitors of viral protease or RNA polymerase, are still being awaited.     

Pharmacotherapy for the treatment of Alzheimer's disease--the present state and the development in the future]

We can observe progressions through stages of symptoms, which are memory and cognitive loss, functional impairment and behavioral disinhibition or apathy, in patients with Alzheimer's disease (AD). Medications of acethylcholine esterase inhibitors such as donepezil offer hope for improving or stabilizing the symptoms of AD temporarily. We desire that new pharmacological interventions up the stream of amyloid cascade theory of AD will be established. Many medical challenges and researches will be tried to find the cause of AD and eternal disease stabilization, or even prevention, may be possible in the future.     

The past, present and future of antifolates in the treatment of Plasmodium falciparum infection

Chemotherapy remains the most important means of controlling malaria, one of the deadliest infectious parasitic diseases in the world. Antimalarial antifolates have been central for prophylaxis and treatment of malaria. This drug family was discovered in the 1940s, during the Second World War, and molecules that are currently in clinical use were discovered at that time. Since the 1940s, no new antimalarial antifolates have been developed that have reached Phase I/II stages. Limited work has been carried out to exploit the inhibition of the malaria folate pathway as a means of discovering new drugs. In this review, work carried out on antimalarial antifolates since the 1940s up to the present time is discussed in terms of discovery, clinical use, mode of action and mechanism of resistance. New concepts have been presented to improve antimalarial antifolate in vivo efficacy and to identify potent new antifolate agents.     

Anticoagulation: the present and the future

Because of its central role in the coagulation cascade thrombin is an attractive target for its inhibition. Many limitations of conventional anticoagulants have been eliminated by the development of the direct oral thrombin inhibitor ximelagatran. Thus, this compound may fulfil the criteria of an ideal anticoagulant. The antithrombotic efficacy and safety of this inhibitor is presently studied in a large clinical development program.     

30 years of pain treatment in Italy: past,present and future

Chronic pain is a situation that bring patients to ask for a medical intervention and can be originated from many different pathologic conditions. Nowadays, recent advancements in pain treatment have made possible to control pain in many patients, allowing them to return to daily activities. Anaesthesiologists are the modern pain specialists, and must know and define the origin of pain in every case: the comprehension of pain mechanisms gives them the possibility for a planned strategy of treatment.In this work we perform a overview about the “state of the art” of pain treatment in Italy analyzing what are the problems that require to focalize our attention.Therefore, sometimes many visits are necessary for a correct diagnosis and successful therapy. Pain management is still a young speciality, and the Italian pain specialist is often a self made expert who needs proper structures and dedicated people: the result is a different treatment not only between the hospitals but also in the same pain conditions.Although it seems that many of the new techniques used to control pain are successful, few studies and controlled trials have been done to verify long-term efficacy and potential adverse effects.     

Gene therapy for cancer treatment: past, present and future

The broad field of gene therapy promises a number of innovative treatments that are likely to become important in preventing deaths from cancer. In this review, we discuss the history, highlights and future of three different gene therapy treatment approaches: immunotherapy, oncolytic virotherapy and gene transfer. Immunotherapy uses genetically modified cells and viral particles to stimulate the immune system to destroy cancer cells. Recent clinical trials of second and third generation vaccines have shown encouraging results with a wide range of cancers, including lung cancer, pancreatic cancer, prostate cancer and malignant melanoma. Oncolytic virotherapy, which uses viral particles that replicate within the cancer cell to cause cell death, is an emerging treatment modality that shows great promise, particularly with metastatic cancers. Initial phase I trials for several vectors have generated excitement over the potential power of this technique. Gene transfer is a new treatment modality that introduces new genes into a cancerous cell or the surrounding tissue to cause cell death or slow the growth of the cancer. This treatment technique is very flexible, and a wide range of genes and vectors are being used in clinical trials with successful outcomes. As these therapies mature, they may be used alone or in combination with current treatments to help make cancer a manageable disease.     

Empiric treatment of gonorrhea and chlamydia in the ED.

A retrospective study was conducted on female patients who were screened for Chlamydia trachomatis and Neisseria gonorrhea. The purpose of the study was to determine if any factors predict empiric therapy at the index visit. Of 911 patients enrolled in the study, 100 were found to have positive DNA screens and 54 were given empiric therapy. A logistic regression was used to test the ability of age, ethnicity, DNA probe result and provider type (physician or midlevel provider), to predict empiric treatment. DNA probe result and provider type were the only 2 factors that were found to predict empiric therapy. A subsequent analysis using a Cochran-Mantel-Hanszel test to control for DNA probe result revealed that the provider type remained the only variable that predicted empiric treatment.     

Alternative methods, the present and future

Alternative methods are already widely used in fundamental biological research. Among 6,649 papers given at the FASEB 1989 meeting, nearly 60 p. 100 deal with experimental data obtained without the use of live animals. Alternative methods are less frequently utilized in industrial Toxicology. The reason of this discrepancy is discussed as well as the efforts made to reduce the numbers of animals for acute toxicity studies (LD 50) and cutaneous and eye tolerance. Present scientific developments as well as the possible agreement by regulatory agencies of the newly developed tests are presented. In spite of the increasing acceptance of alternative methods, large numbers of animals are still used. The reasons for this state of affairs are analysed, as well as the efforts which are made to encourage research for the replacement of animals in programs traditionally based on animal experimentation.