Tehran University Medical Journal

Cutaneous leishmaniasis (CL) is an endemic parasitic disease of major health impact in many parts of the world and is caused by several species of the protozoan parasite Leishmania. Antimonial compounds (i.e glucantime and pentostam) are the first-line treatment for cutaneous leishmaniasis with emerging drug resistance as a problem. The control of Leishmania is further complicated by the emergence of drug-resistant parasites. In the clinical settings, resistance to SbV containing drugs is now well established and it was found to occur in South America, Europe, the Middle East and most notably in India. Clinical resistance to organic pentavalent antimonials, in the form of sodium stibogluconate (pentostam) or N-methylglucamine antimoniate (glucantime), has long been recognized. However, it is unknown whether the clinical failure of chemotherapy is attributable to the development of drug resistance mechanisms in the parasite or to a variety of host factors that might also contribute to low drug response. Reported rate of drug-resistance to antimonial compounds in Iran varies from 9.4% to 94.2% and there is not any comprehensive study on this issue. Indeed, in the endemic region treatment with SbV fails in more cases; thus, in general patients infected with resistant parasites are unresponsive although exceptions have been reported. This article aims to review the mechanisms of drug resistance to these compounds. The main resistance factors include genetical, enzymatic, intracellular (such as apoptosis and cytoskeleton changes) and resistance proteins. Also, mechanisms related to drug transport and intracellular activation are discussed. Various methods of drug resistance detection such as culture and molecular methods (i.e polymerase chain reaction) are reviewed. Although the exact mechanism of action glucantime is not clear, it seems that protein and gene factors involved in cellular drug entry are the main causes of drug resistance. Cross-sectional studies on meglumine antimoniate resistance in endemic areas of cutaneous leishmaniasis in Iran are highly recommended. Also, studies for evaluation of alternatives therapies for antimonial resistant cases are required.   

Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound) and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore) in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

Background: Despite advances in diagnosis and treatment, leishmaniasis is now considered a severe public health problem, particularly in developing countries, such as Iran. Leishmaniasis is among the six most important, parasitic diseases of the world affecting 88 countries in almost every continent. The disease is complex with different clinical presentations such as visceral, cutaneous and mucocutaneous forms. Cutaneous leishmaniasis (CL) is the most common form of the disease in Iran. Antimony compounds are the first line treatment of CL. The treatment of leishmaniasis in endemic areas relies on chemotherapy, and in several parts of the world the mainstay remains the pentavalent antimony (SbV)-containing drugs Pentostam (sodium stibogluconate) and Glucantime (meglumine). There is no comprehensive study on treatment failure rate of this compounds. This study was designed to evaluate treatment failure rate and possible involving factors of antimonial resistance in CL to facilitate and improve treatment strategies of this disease.
Methods: All patients with CL referred to Skin Disease and Leishmaniasis Research Center (SDLRC), from October 2011 to October 2013, treated with antimony compounds were assessed in this study. Patient characteristics (gender, age and place of residence), number, type and location of the lesions, comorbidities and type of treatment were recorded and analyzed.
Results: Rate of treatment failure with Meglusan was 4.3%. Failure rate in men and in patients with previous history of cutaneous leishmaniasis was more than women or patients without CL history (P= 0.000, 0.024 respectively). The results of this study showed that treatment failure was higher in patients with systemic treatment than intralesional (IL) or combination therapy (both IL and systemic treatment) group but this difference was not statistically significant. Also, size and number of the lesions, wound infection, the patient's age, location, education and occupation do not have a significant correlation with treatment failure.
Conclusion: Greater treatment failure rate of Meglusan compared to Glucantime (4.3% versus< 1%, respectively) is an important issue to be considered in CL therapeutic strategy.