Photodynamic therapy in oesophageal carcinoma: an overview.

Over the last five years, photodynamic therapy has become increasingly regarded as a viable option for palliative treatment of advanced oesophageal carcinoma, alongside more established modalities such as chemotherapy and radiotherapy. A large number of reports on the efficacy of photodynamic therapy as both a palliative and curative treatment for malignancy of the oesophagus have appeared in the 20 years since the first report on the use of this technique to treat oesophageal carcinoma, and this review aims to draw them all together to provide an overview of the current state of the field.     

Photodynamic antimicrobial therapy

Photodynamic antimicrobial therapy (PACT) involves the utilisation of photosensitizers activated by exposure to visible light in order to eradicate microbes (this method has already been applied in photodynamic therapy of tumours). Photodynamic effect of the particular photosensitive substance (PS) is attributed to its ability to penetrate susceptible microorganisms, to absorb the light of certain wavelength, and to generate reactive cytotoxic oxygen products. The target microorganisms for photoinactivation are bacteria, fungi, viruses and protozoa. Photodynamic antimicrobial therapy is proposed as a potentially topical, non-invasive approach suitable for treatment of locally occurring infection. The fact that bacteria are becoming increasingly resistant to antibiotics and antiseptics has lead to an increased interest in the development of new alternative eradication methods, such as PACT. Research and development of photosensitive substances are aimed at finding effective antimicrobial substances, which would have a broad-spectrum potency.     

Non-viral and hybrid vectors in human gene therapy: an update

Non-viral DNA vectors have several advantages over viral vectors. For example, virus production is expensive and there are safety concerns regarding viral manipulations. In addition, the size of the delivered plasmid is limited by the size of the viral capsid, whereas this is not a problem with non-viral vectors. The major disadvantage of using non-viral DNA delivery vectors, compared with their viral counterparts, is the low transfection efficiency. This has resulted in low levels of usage in clinical trials. Consequently, the majority of research into non-viral gene therapy has been focused on developing more efficient vectors.     

Photodynamic therapy: a mitochondrial inducer of apoptosis

Photodamage to the mitochondria of murine leukemia P388 cells resulted in immediate loss of the mitochondrial membrane potential together with the release of cytochrome c into the cytosol. This was followed by a rapid activation of caspase 3-like proteases, as indicated by a marked rise in DEVDase activity. There was no significant effect on WEHDase or VEIDase activities, suggesting that only the late-stage caspases had been effected. The apoptotic response to mitochondrial photodamage was abolished by the broad-spectrum caspase inhibitor zVAD-fmk, but this did not prevent loss of viability after mitochondrial photodamage. These studies indicate that the release of cytochrome c from photodamaged mitochondria is sufficient to directly initiate a caspase-dependent apoptotic response.     

Ivermectin: an update

Ivermecan was introduced as an antiparasitic agent in 1981. It is now registered for animal-health use in 35 countries and is being evaluated for possible use in man. This review summarises its antiparasitic efficacy and apparent mode of action. Additional information is given in previous review articles.     

Yersinia: an update

The 8th International Symposium on Yersinia was held in Turku, Finland, 4–8 September 2002.     

Clonorchiasis: an update

Clonorchis sinensis, the Chinese or oriental liver fluke, is an important human parasite and is widely distributed in southern Korea, China (including Taiwan), Japan, northern Vietnam and the far eastern part of Russia. Clonorchiasis occurs in all parts of the world where there are Asian immigrants from endemic areas. The human and animal reservoir hosts (dogs, pigs, cats and rats) acquire the infection from the ingestion of raw fish containing infectious metacercariae. The first intermediate snail hosts are mainly species of Parafossarulus and Bithynia. Numerous species of freshwater fish serve as the second intermediate hosts of C. sinensis. Extensive studies of clonorchiasis during several decades in Japan, Korea, China and other countries have shown much progress in proving its morphological features including ultrastructure, biology, pathogenesis, epidemiology, clinical manifestations and chemotherapy. The present review deals with mainly current results obtained on the epidemiological, pathological and clinical aspects, as well as control measures in endemic areas. As for the complications of clonorchiasis, formation of calculi in the intrahepatic biliary passages is one of the most characteristic pathological features. It is sometimes accompanied by suppurative cholangitis, cholecystitis, cholangiohepatitis and ultimately can cause cholangiocarcinoma. Experimental results on the relationship to the occurrence of cholangiocarcinoma are presented. Clinical diagnosis by radiological findings including cholangiography, sonography and computerized tomography as well as magnetic resonance imaging for biliary or pancreatic ducts are outlined. Current studies on immunology and molecular biology of C. sinensis were introduced. Praziquantel is the drug of choice for clonorchiasis. The most effective regimen is 25 mg kg(-1) three times daily (total dose, 75 mg kg(-1)) administered orally at 5- to 6-h intervals over a single day. Prevention and control measures are also discussed.     

Photodynamic therapy with fullerenes.

Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended pi-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases.     

Critical path in cardiac stem cell therapy: an update on cell delivery

Despite optimal medical therapy, cardiovascular disease remains a leading cause of morbidity and mortality worldwide. One emerging therapeutic approach for treatment of cardiomyopathies is stem cell therapy. Use of stem cells for regenerative medicine has quickly evolved over the last decade. On the basis of encouraging pre-clinical results, stem cell therapy has developed rapidly into a potentially promising treatment for ischemic heart disease, myocardial infarction and congestive heart failure. In this review, we summarize the current state-of-the-art of stem cell therapy and compare collective experiences gleaned from trials using intravenous, intra-coronary and intra-myocardial delivery in exacting credible benefits. We discuss implications of clinical outcomes reported in relation to the delivered stem cells as probable destiny therapy for cardiovascular repair.     

Photodynamic therapy of cancer: Search for ideal photosensitizer

Photodynamic therapy (PDT) is a minimally invasive and promising new modality to combat cancer. The method is based on selective accumulation of sensitizers in tumor cells. The high degree of selectivity offered by this modality has been applied for fluorescent diagnostics of cancer. Photosensitization of a tissue-localized sensitizer in the presence of oxygen generates cytotoxic reactive oxygen species results in the selective destruction of tumor. The PDT’s major advantages compared to traditional methods of cancer treatment are better selectivity, and low toxicity of administered drugs. This review highlights basic principles of this method, mechanisms underlying damage of tumor tissue and first and second generations of sensitizers. Future developments in PDT will include the development of new methods of treatment and diagnostics of tumor diseases.     

Deficit schizophrenia: an update

The criteria for deficit schizophrenia were designed to define a group of patients with enduring, primary (or idiopathic) negative symptoms. In 2001, a review of the literature suggested that deficit schizophrenia constitutes a disease separate from nondeficit forms of schizophrenia. Here we provide a review of new studies, not included in that paper, in which patients with deficit schizophrenia and those with nondeficit schizophrenia were compared on dimensions typically used to distinguish diseases: signs and symptoms, course of illness, pathophysiological correlates, risk and etiological factors, and treatment response. Replicated findings and new evidence of double dissociation supporting the separate disease hypothesis are highlighted. Weaknesses in research and treatment options for these patients are also emphasized.