A Khamesipour

Publications of A Khamesipour

• Leishmanicidal Activity of Films Containing Paromomycin and Gentamicin Sulfate both In Vitro and In Vivo.

  Authors: S Tolouei, Sj Hasheminia, M Narimani, A Khamesipour, Ma Shatalebi, Sh Hejazi

  Iranian journal of parasitology. 08/2011; 6(3):60-5.

  Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomycin and gentamicin wasBased on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomycin and gentamicin was prepared and anti-Leishmania activities of the prepared films were assessed in vitro and in vivo. METHODS : Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellulose and HPMC (Hydroxyl Propyl Methyl Cellulose). In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overlay liquid layer. Therapeutic effects of the films were evaluated using Balb/c mice model. The mice were inoculated with 2×10(6)L. major promastigotes (MRHO/IR/75/ER) and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated. Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to reduce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study. It seems that the prepared films might be further used in human clinical trials.

• Cloning, expression and dynamic simulation of TRYP6 from Leishmania major (MRHO/IR/75/ER).

  Authors: G Eslami, F Frikha, R Salehi, A Khamesipour, H Hejazi, M A Nilforoushzadeh

  Molecular biology reports. 12/2010; 38(6):3765-76.

  Leishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules, such as reactive oxygen species and reactive nitrogenLeishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules, such as reactive oxygen species and reactive nitrogen species is crucial for Leishmania to survive and replicate in the host cells. Tryparedoxin peroxidase, a member of peroxiredoxins family, is vital for parasite survival in the presence of antioxidant, hence it is one of the most important molecules in Leishmania viability and then, it may be an appropriate goal for challenging against leishmaniasis. After cloning and sub-cloning of TRYP6 from Leishmania major (MRHO/IR/75/ER), homology modeling of the LmTRYP6 was proposed to predict some functional property of this protein. The refined model showed that the core structure consists of a seven β stranded β-sheet and five α helices which are organized as a central 7-stranded β2-β1-β5-β4-β3-β6-β7 surrounded by 2-stranded β-hairpin, α helices A and D on one side, and α helices B, C and E on the other side. The peroxidatic active site is located in a pocket formed by the residue Pro45, Met46, Thr49, Val51, Cys52, Arg128, Met147 and Pro 148. The catalytic Cys52, located in the first turn of helix αB, is in van der Waals with a Pro45, a Thr49 and an Arg128 that are absolutely conserved in all known Prx sequences. In this study, an attractive molecular target was studied. These results might be used in designing of drugs to fight an important human pathogen.

• Immunization against leishmaniasis by PLGA nanospheres loaded with an experimental autoclaved Leishmania major (ALM) and Quillaja saponins.

  Authors: M Tafaghodi, M Eskandari, M Kharazizadeh, A Khamesipour, M R Jaafari

  Tropical biomedicine. 12/2010; 27(3):639-50.

  Immune responses against the Leishmania antigens are not sufficient to protect against a leishmania challenge. Therefore these antigens need to be potentiated by various adjuvants and deliveryImmune responses against the Leishmania antigens are not sufficient to protect against a leishmania challenge. Therefore these antigens need to be potentiated by various adjuvants and delivery systems. In this study, Poly (d,l-lactide-co-glycolide (PLGA) nanospheres as antigen delivery system and Quillaja saponins (QS) as immunoadjuvant have been used to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter for nanospheres loaded with ALM+QS was 294 ± 106 nm. BALB/c mice were immunized three times in 3-weeks intervals using ALM plus QS loaded nanospheres [(ALM+QS)PLGA], ALM encapsulated with PLGA nanospheres [(ALM)PLGA], (ALM)PLGA + QS, ALM + QS, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P < 0.05) smaller footpad, were observed in mice immunized with (ALM)PLGA. The (ALM+QS)PLGA group showed the least protection and highest swelling, while the (ALM)PLGA+QS, ALM+QS and ALM showed an intermediate protection with no significant difference. The mice immunized with ALM and ALM+QS showed the highest IgG2a/IgG1 ratio (P < 0.01), followed by (ALM)PLGA+QS. The highest IFN-γ and lowest IL-4 production was seen in (ALM)PLGA+QS, ALM+QS groups. The highest parasite burden was observed in (ALM)PLGA+QS and (ALM+QS)PLGA groups. It is concluded that PLGA nanospheres as a vaccine delivery system could increase the protective immune responses, but QS adjuvant has a reverse effect on protective immune responses and the least protective responses were seen in the presence of this adjuvant.

• Immune response of BALB/c mice against an experimental vaccine of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with BCG or Mycobacterium vaccae.

  Authors: M Nateghi Rostami, H Keshavarz, A Khamesipour

  Tropical biomedicine. 04/2010; 27(1):89-102.

  Immune response in BALB/c mice immunized 3 times with different doses (50 μg or 200 μg of protein) of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with either BCG (1x10(7); CFU) orImmune response in BALB/c mice immunized 3 times with different doses (50 μg or 200 μg of protein) of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with either BCG (1x10(7); CFU) or different doses of killed Mycobacterium vaccae (1x10(6), 1x10(7)) was assessed. Mice immunized with low dose of Alum-ALM mixed with either BCG or low M. vaccae showed a significantly higher IFN-gamma production and a lower IL-4 level and a significantly lower parasite burden compared to the control PBS injected group. It seems that immunization with a low dose of Alum-ALM mixed with an adjuvant induces a Th1 type of immune response in susceptible BALB/c mice.

• Dynamics of Leishmania infection rates in Rhombomys opimus (Rodentia: Gerbillinae) population of an endemic focus of zoonotic cutaneous leishmaniasis in Iran.

  Authors: A A Akhavan, M R Yaghoobi-Ershadi, A Khamesipour, H Mirhendi, M H Alimohammadian, Y Rassi, M H Arandian, R Jafari, H Abdoli, N Shareghi, M Ghanei, N Jalali-zand

  Bulletin de la Société de pathologie exotique (1990). 04/2010; 103(2):84-9.

  Zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major is a great public health problem in the Old World. Leishmania major is widely distributed in populations of rodents in arid and savannahZoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major is a great public health problem in the Old World. Leishmania major is widely distributed in populations of rodents in arid and savannah regions. In this study, seasonal variation of natural infection with Leishmania parasites in Rhombomys opimus (Rodentia: Gerbillinae) population of an endemic focus of ZCL in Iran was monitored. The study was conducted from October 2007 to October 2008 in the central part of the country. Nested polymerase chain reaction (PCR) assay was used for the detection and identification of Leishmania parasites, and the results were confirmed by PCR-restriction fragment length polymorphism (RFLP). The results showed that Leishmania infection rate was 55.8% (29 out of 52 gerbils) using nested PCR. The highest and lowest Leishmania infection rates were observed in fall and summer, respectively. Gerbils that were found to be infected only with L. major were 5.8%, and that with Leishmania turanica were 23.1%. A mixed natural infection was seen in the rodents with L. major and L. turanica (21.2%), with L. major and L. gerbilli (1.9%), and with all the three species (3.9%). Leishmania major infection alone was seen in fall and winter whereas mixed infection of L. major and L. turanica was observed in all seasons except in summer. Leishmania turanica infection was observed throughout the year. It is concluded that L. major, L. gerbilli, and L. turanica circulate in the population of R. opimus in central part of Iran. Leishmania major infection is usually accompanied by L. turanica in naturally infected gerbils with the highest rate in fall. It is recommended that the role of L. turanica in the epidemiology and transmission of ZCL should be reconsidered.

• The Role of Liposomal CpG ODN on the Course of L. major Infection in BALB/C Mice.

  Authors: H Hejazi, M Tasbihi, Mr Jaafari, A Badiee, N Pestechian, A Javadi, A Khamesipour

  Iranian journal of parasitology. 03/2010; 5(1):47-54.

  Historically, leishmanization is the most effective protective measure against Cutaneous Leishmaniasis (CL), CL lesion induced by leishmanization sometimes takes a long time to heal. Manipulation ofHistorically, leishmanization is the most effective protective measure against Cutaneous Leishmaniasis (CL), CL lesion induced by leishmanization sometimes takes a long time to heal. Manipulation of leishmanization inoculums needed to induce a mild and acceptable CL lesion. The aim of this study was to explore if liposomal form of CpG ODN (Cytosin phosphate Guanin Oligodeoxynucleotides) mixed with Leishmania major would induce a milder lesion size in Balb/c mice. This study was performed in Biotechnology Research Center, Mashhad, and Center for Research and Training in Skin Diseases and Leprosy, Tehran, Iran during 2008-2009. Different groups of BALB/c mice were subcutaneously (SC) inoculated with L. major mixed with liposomal form of CpG ODN, or L. major plus free CpG ODN, or L. major mixed with empty liposomes or L. major in PBS. The lesion onset and the size of lesion were recorded; the death rate was also monitored. Footpad thickness was significantly (P<0.01) smaller, death rate was also significantly (P<0.05) lower in the mice received L. major mixed with liposomal CpG ODN or free CpG ODN than control groups received L. major in PBS or L. major plus liposomes, also mice which received L. major mixed with CpG ODN in soluble form showed a significantly (P<0.001) smaller lesion size than control groups. CpG ODN seems to be an appropriate immunopotentiator mixed with Leishmania stabilate in leishmanization.

• Differential in vitro CD4+/CD8+ T-cell response to live vs. killed Leishmania major.

  Authors: M Nateghi Rostami, H Keshavarz Valian, S E Eskandari, A Miramin Mohammadi, S T Shahrestani, A Sarraf-Nejad, A Khamesipour

  Parasite immunology. 02/2010; 32(2):101-10.

  Clinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is notClinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is not known and in vivo studies on T-cell function may provide valuable information. Nevertheless, there are limited studies on the nature of the stimulatory effects of live vs. killed parasites on human T cells in vitro. A total of nine Leishmanin Skin Test+ volunteers with a history of self-healing CL (HCL) and seven healthy volunteers were included in this study. 5,6-carboxyfluroescein diacetate succinimidyl ester-labelled CD4(+)/CD8(+) lymphocytes were cultured with killed Leishmania Lysate (Killed LL) or live Leishmania major (Live LM) and analysed for proliferation using flow cytometry. Culture supernatants were used for cytokine titration. In HCL volunteers, upon stimulation with killed LL, the number of proliferated CD4(+)/CD8(+) cells was significantly more than that of unstimulated (P < 0.001) or live LM stimulated (P < 0.05) cells, or cells from controls (CD4(+)/CD8(+): P < 0.05/P < 0.001). Stimulation of CD4(+) cells with Live LM (P < 0.001) or Killed LL (P < 0.05) induced a significantly higher IFN-gamma production compared with that of controls, but Live LM induced significantly (P < 0.05) more IFN-gamma than Killed LL. A significantly (P < 0.05) higher IFN-gamma production was observed when CD8(+) cells were stimulated with Live LM. Cells from HCL volunteers showed significantly more IL-10 production to Live LM stimulation compared with that of controls (CD4(+): P < 0.05 /CD8(+): P < 0.001) or cells stimulated with Killed LL (CD4(+)/CD8(+): P < 0.001/P < 0.0005). Whereas Killed LL induced more proliferation response in purified T cells, Live LM induced cytokine production without significant induction of proliferation. The results from healed CL volunteers in this study could be implicated in further studies on T-cell response in vaccinated individuals.

• Plasma sCD26 and sCD30 levels in cutaneous leishmaniasis.

  Authors: R Jafari-Shakib, M A Shokrgozar, M Nassiri-Kashani, B Malakafzali, B Nikbin, A Khamesipour

  Acta tropica. 11/2008;

  CD26 and CD30 are surface molecules expressed on activated Th1 and Th2 cells, respectively. It is, therefore assumed that plasma levels of CD26 and CD30 (sCD26 and sCD30) correlate with Th1 and Th2CD26 and CD30 are surface molecules expressed on activated Th1 and Th2 cells, respectively. It is, therefore assumed that plasma levels of CD26 and CD30 (sCD26 and sCD30) correlate with Th1 and Th2 response, respectively. In this study, plasma levels of sCD26 and sCD30 in patients with non-healing form of cutaneous leishmaniasis (CL) were measured and compared with the levels of sCD26 and sCD30 in patients with healing form of CL and healthy control volunteers. The results indicate that the plasma levels of sCD26 and sCD30 are significantly (p<0.05) higher in patients with non-healing form of CL than patients with healing form of CL or healthy control. No significant difference is seen in the levels of sCD26 and sCD30 in patients with healing form of CL in comparison with healthy control group. It is concluded that sCD30 might be used as an indicator of a Th2 response in patients with non-healing form of CL.

• Leishmania surface protein gp63 binds directly to human natural killer cells and inhibits proliferation.

  Authors: T Lieke, S Nylén, L Eidsmo, W R McMaster, A M Mohammadi, A Khamesipour, L Berg, H Akuffo

  Clinical and experimental immunology. 09/2008; 153(2):221-30.

  Natural killer (NK) cells contribute to immunity as the first line of defence in numerous infections by early cytokine secretion and cytotoxicity. In Leishmania infection, NK cells contribute withNatural killer (NK) cells contribute to immunity as the first line of defence in numerous infections by early cytokine secretion and cytotoxicity. In Leishmania infection, NK cells contribute with interferon-gamma and may assist in directing the immune response towards T helper type 1, which is essential for successful control of the parasites. Thus, NK cells may play an important role in both resistance and control of the infection. However, during Leishmania infection NK cells show signs of suppression. To explore the reason for this suppression, we exposed naive and interleukin (IL)-2 activated NK cells directly to promastigotes of Leishmania major in vitro. As a rapid consequence of contact between naive NK cells and promastigotes, expression of NK cell receptors show significant changes. We identify one of the major surface molecules of promastigotes, glycoprotein (gp) 63, as an important agent for these suppressive effects by using promastigotes of a gp63ko strain of L. major. Furthermore, proliferation of IL-2-activated purified NK cells is suppressed after exposure to the wild-type but not to gp63ko promastigotes. However, gp63ko L. major induced no NK cell proliferation when NK cells were co-cultured with peripheral blood mononuclear cells populations such as CD14(+) monocytes or T cells.

• CD26 expression on CD4+T cells in patients with cutaneous leishmaniasis.

  Authors: R Jafari-Shakib, S Ajdary, Z Mohtasham Amiri, A M Mohammadi, K Nourijelyani, H Mortazavi, M A Shokrgozar, B Nikbin, A Khamesipour

  Clinical and experimental immunology. 08/2008; 153(1):31-6.

  Surrogate marker(s) of protection in human leishmaniasis is not well defined. In this study, T helper 1 (Th1) and Th2 cytokine profiles and CD26 expression on CD4(+) T cells in peripheral bloodSurrogate marker(s) of protection in human leishmaniasis is not well defined. In this study, T helper 1 (Th1) and Th2 cytokine profiles and CD26 expression on CD4(+) T cells in peripheral blood mononuclear cells of patients with healing or non-healing forms of cutaneous leishmaniasis (CL) stimulated with Leishmania antigens were assessed. The level of interferon (IFN)-gamma production was significantly higher in patients with healing or non-healing forms of CL than in healthy controls, but it was not significantly different between the two patient groups. The level of interleukin-5 production was significantly higher in patients with the non-healing form of CL than in the two other groups. There was a significant increase in the level of CD26 expression on CD4(+) T cells in patients with healing (P < 0.001) or non-healing (P = 0.025) forms of CL compared with the control group, but no significant difference was seen between the two patient groups. A weak positive correlation was seen between IFN-gamma production and CD26 expression on CD4(+) T cells of patients with the healing form of lesion (r = 0.54, P = 0.008), but this correlation was not observed in patients with the non-healing form of CL (r = 0.53, P = 0.078). Surface CD26 is not correlated with the clinical manifestation of CL or IFN-gamma production. Therefore, CD26 is not a surrogate marker for IFN-gamma production in CL.

• Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs.

  Authors: R Hadighi, P Boucher, A Khamesipour, A R Meamar, G Roy, M Ouellette, M Mohebali

  Parasitology research. 11/2007; 101(5):1319-22.

  Cutaneous leishmaniasis (CL) is a major health problem in endemic areas of Iran. The pentavalent antimony (SbV) based drug Glucantime is the first line of treatment for CL in Iran, but recentlyCutaneous leishmaniasis (CL) is a major health problem in endemic areas of Iran. The pentavalent antimony (SbV) based drug Glucantime is the first line of treatment for CL in Iran, but recently SbV-resistant Leishmania tropica isolates derived from unresponsive patients were reported. We show in this study that these resistant parasites are cross-resistant to the other SbV-containing drug Pentostam and at least for one isolate also to amphotericin B. However, these resistant isolates were shown to be sensitive to miltefosine and paromomycin. The latter two drugs could thus be useful alternatives for the treatment of leishmaniasis in Iran even for SbV-resistant isolates.

• Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity.

  Authors: M Daneshpazhooh, C Chams-Davatchi, A Khamesipour, P Mansoori, A Taheri, A Firooz, H Mortazavi, N Esmaili, Y Dowlati

  Journal of the European Academy of Dermatology and Venereology : JEADV. 11/2007; 21(10):1319-24.

  BACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients alsoBACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients also have antibodies against desmoglein1 (Dsg1). The aims of this study were to evaluate the diagnostic value of Dsg enzyme-linked immunosorbent assay (ELISA) in Iranian PV patients, to assess its correlation with the clinical phenotype and severity of disease and to investigate the changes of these antibodies after treatment. METHODS: Seventy-three patients with PV (29 men, 44 women) presenting to the Pemphigus Research Unit at Razi Hospital, Tehran, Iran were enrolled. ELISAs were used to detect IgG autoantibodies reactive with the ectodomains of Dsg1 and Dsg3, and the correlation of antibodies with the clinical phenotype as well as oral and skin disease severity was assessed. In addition, the tests were repeated in 18 patients after treatment and the resulting remission. RESULTS: Anti-Dsg1 and anti-Dsg3 were detected in 56 (76.7%) and 69 (94.5%) patients, respectively. Anti-Dsg1 and anti-Dsg3 antibodies were present in 48 (94.1%) and 50 (98%) patients with mucocutaneous type, in 2 (12.5%) and 15 (93.7%) patients with mucosal type, and in 6 (100%) and 4 (66.7%) patients with cutaneous PV, respectively. The mean anti-Dsg1 index values were significantly higher in cutaneous and mucocutaneous phenotypes than mucosal PV (P < 0.001). The mean anti-Dsg3 index values were significantly lower in cutaneous and mucosal phenotypes than mucocutaneous PV (P < 0.01). The severity of skin lesions (but not oral lesions) was correlated with anti-Dsg1 antibody level (P < 0.001); on the other hand, the severity of oral lesions (P < 0.01) as well as skin lesions (P < 0.001) was significantly correlated with anti-Dsg3 antibody levels. Both anti-Dsg1 and anti-Dsg3 levels were significantly reduced after treatment and clinical remission (P < 0.001). CONCLUSION: Dsg ELISA is not only a sensitive tool for the diagnosis of PV, it can also serve as a predictive means for assessing the severity as well as for monitoring the disease activity. Although, in general, the clinical phenotype is related to the antibody profile, there are occasional cases with discordant phenotype and antibody profile. These discrepancies might be explained by genetic variations or the presence of possible minor antigens involved in the pathogenesis of pemphigus.

• A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis.

  Authors: M Nassiri-Kashani, A Firooz, A Khamesipour, F Mojtahed, M Nilforoushzadeh, H Hejazi, N Bouzari, Y Dowlati

  Journal of the European Academy of Dermatology and Venereology : JEADV. 02/2005; 19(1):80-3.

  BACKGROUND: Several modalities have been used for the treatment of cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of azole drugs onBACKGROUND: Several modalities have been used for the treatment of cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of azole drugs on Leishmania parasites. OBJECTIVES: To evaluate the efficacy and tolerability of oral itraconazole in the treatment of CL caused by L. major. METHODS: A total of 200 patients with parasitologically confirmed CL with a duration of less than 45 days from a well known L. major endemic area were included in a randomized, double-blind, placebo-controlled clinical trial. The patients received either itraconazole 200 mg daily (100 patients) or placebo (100 patients) for 8 weeks. The primary outcome measures were clinical cure (complete re-epithelization of all lesions) and parasitological cure at the end of the treatment. RESULTS: Eighty-three patients in the itraconazole and 75 patients in the placebo group completed the treatment course. After 8 weeks of treatment, clinical cure was observed in 59% and 53% and parasitological cure was observed in 83% and 76% of patients in the itraconazole and placebo groups, respectively, which were not significantly different. There was no difference in the rate of adverse events. CONCLUSIONS: An 8-week course of oral itraconazole was not more effective than placebo in the treatment of CL.

• Immune response measured in human volunteers vaccinated with autoclaved Leishmania major vaccine mixed with low dose of BCG.

  Authors: M Mahmoodi, A Khamesipour, Y Dowlati, S Rafati, A Z Momeni, M Emamjomeh, H Hejazi, F Modabber

  Clinical and experimental immunology. 12/2003; 134(2):303-8.

  The immune responses induced against Leishmania antigens in volunteers who were vaccinated in a double-blind, randomized field efficacy trial of a preparation of autoclaved Leishmania major (ALM)The immune responses induced against Leishmania antigens in volunteers who were vaccinated in a double-blind, randomized field efficacy trial of a preparation of autoclaved Leishmania major (ALM) mixed with a low dose of Bacille Calmette-Guerin vaccine (BCG) who developed either a cutaneous leishmaniasis (CL) lesion due to exposure to infected sandfly bite(s) or did not develop a lesion during the course of the trial were studied and compared with those of non-vaccinated controls. Blood samples were also assayed from different groups including volunteers with history of CL and volunteers with previous positive or negative leishmanin skin test (LST) without a history of CL. The vaccinated volunteers had received a single dose of either ALM mixed with a low dose of BCG or the same dose of BCG alone. The LST and in vitro proliferative response (stimulation index, SI), interferon gamma (IFN-gamma) production and, in a few cases, interleukin (IL)-4 production of peripheral blood mononuclear cells to soluble Leishmania antigens were measured. The results indicated that volunteers who developed CL in the vaccine arm showed a slightly higher SI than cases who received BCG alone. Volunteers with history of CL and volunteers with positive LST demonstrated the strongest proliferation indices and IFN-gamma production. The data suggest that a single dose of ALM + BCG induces a weak Th1 response in vaccinated volunteers that is far lower than that in volunteers with prior subclinical infection or volunteers with history of CL, who are presumed to be immune.

• Itraconazole pulse therapy improves the quality of life of patients with toenail onychomycosis.

  Authors: A Firooz, A Khamesipour, Y Dowlati

  The Journal of dermatological treatment. 07/2003; 14(2):95-8.

  BACKGROUND: Toenail onychomycosis is a common disease that can have serious adverse effects on the quality of life (QOL) of patients. AIM: To evaluate the impact of itraconazole pulse therapy on theBACKGROUND: Toenail onychomycosis is a common disease that can have serious adverse effects on the quality of life (QOL) of patients. AIM: To evaluate the impact of itraconazole pulse therapy on the QOL of patients with toenail onychomycosis. METHODS: A total of 20 patients with disto-lateral subungual toenail onychomycosis were treated with itraconazole 200 mg twice daily for 1 week every 4 weeks for 12 weeks. The patients were asked to complete a QOL questionnaire before treatment and on the last follow-up visit (week 48). A score of 0-4 was given according to the five possible responses to each question and these were summed to give the final score of the patient. The mean of the final scores of the patients before and after treatment were compared using the Wilcoxon matched-pairs test. RESULTS: At 48 weeks after commencing treatment, 14 patients (70%) responded to treatment (nine patients were cured with almost totally clear toenails and five patients improved), and 16 patients (80%) were mycologically cured (negative KOH smear and culture). The mean of the QOL scores of the patients before treatment was 18.0+/-7.8, which reduced to 13.1+/-11.3 after treatment (two-tailed, p=0.009). CONCLUSION: Itraconazole pulse therapy is an effective treatment and can improve the QOL of patients with toenail onychomycosis.

• Cytokine gene expression in healing and non-healing cases of cutaneous leishmaniasis in response to in vitro stimulation with recombinant gp63 using semi-quantitative RT-PCR.

  Authors: G R Habibi, A Khamesipour, W R McMaster, F Mahboudi

  Scandinavian journal of immunology. 11/2001; 54(4):414-20.

  Objectives of this study were to test the cytokine gene expression in peripheral blood mononuclear cells (PBMCs) from cases with nonhealing and healing cutaneous leishmaniasis (CL) in response to inObjectives of this study were to test the cytokine gene expression in peripheral blood mononuclear cells (PBMCs) from cases with nonhealing and healing cutaneous leishmaniasis (CL) in response to in vitro stimulation of recombinant gp63 (rgp63) and soluble Leishmania antigen (SLA). Healing and nonhealing cases are, respectively, defined as recovered from disease and refractory to various treatments. To evaluate the type of immunological response, mRNA transcription level for interleukin (IL)-4, IL-10, IL-12 and interferon (IFN)-gamma were determined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) technique in PBMCs of these volunteers. The results clearly demonstrated a high level of IL-4 expression in nonhealing cases of CL and a low expression level of transcripts for IFN-gamma and IL-12. In contrast, a high level of IFN-gamma and IL-12 expression and a low level of IL-4 and IL-10 expression were detected in the healing cases. These findings not only support the balance of Th1/Th2 cytokines in the inducing predominant profile in healing and nonhealing cases, but it may also show the potential of rgp63 as a proper immunogen which might induce protective responses.

• A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

  Authors: A Z Momeni, T Jalayer, M Emamjomeh, A Khamesipour, F Zicker, R L Ghassemi, Y Dowlati, I Sharifi, M Aminjavaheri, A Shafiei, M H Alimohammadian, R Hashemi-Fesharki, K Nasseri, T Godal, P G Smith, F Modabber

  Vaccine. 02/1999; 17(5):466-72.

  Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized doubleSafety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

• Insulin quantification in patients with seborrheic dermatitis.

  Authors: B Dowlati, A Firooz, A Khamesipour, M Lotfi, C A Stuart, E B Smith, B Larijani, Y Dowlati

  Archives of dermatology. 09/1998; 134(8):1043-5.

• Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran.

  Authors: I Sharifi, A R FeKri, M R Aflatonian, A Khamesipour, A Nadim, M R Mousavi, A Z Momeni, Y Dowlati, T Godal, F Zicker, P G Smith, F Modabber

  Lancet. 06/1998; 351(9115):1540-3.

  BACKGROUND: A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to humanBACKGROUND: A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to human transmission) cutaneous leishmaniasis in a randomised double-blind trial in Bam, Iran. METHODS: 3637 schoolchildren, aged 6-15 years, with no history of cutaneous leishmaniasis and no response to a leishmanin skin test, were randomly assigned to receive 1 mg ALM mixed with BCG (n = 1839), or BCG alone (n = 1798). Safety of the vaccine and the incidence of confirmed cases of cutaneous leishmaniasis were followed up for 2 years. FINDINGS: Side-effects were those usually associated with BCG vaccination, but tended to persist longer in the ALM + BCG group. After exclusion of four cases occurring within 80 days of vaccination (one in the ALM + BCG group and three in the BCG group), the 2-year incidence of cutaneous leishmaniasis did not differ significantly between vaccine and BCG groups: 2.8% vs 3.3%, respectively (total cases 112). A sex-stratified analysis showed that in boys the vaccine conferred a protective efficacy of 18% and 78% for the first and second years, respectively--a crude 2-year overall protection of 55% (95% CI 19-75%, p < 0.01). In the first 9 months after vaccination, there was a non-significant excess of cases in the ALM + BCG group (25 vs 16), whereas the incidence of cutaneous leishmaniasis thereafter was significantly reduced in the ALM + BCG group (27 vs 44, p < 0.05). INTERPRETATION: A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test. The exact reason for the apparent protective effect of the vaccine in boys is unknown, and may be a chance finding. However, since boys are more exposed to the infection, which is indicated by higher disease prevalence in boys in this study population, the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies. Booster injections or alternative adjuvants should be tried to improve the potential efficacy of this vaccine.

• Comparative safety and immunogenicity trial of two killed Leishmania major vaccines with or without BCG in human volunteers.

  Authors: K Bahar, Y Dowlati, B Shidani, M H Alimohammadian, A Khamesipour, S Ehsasi, R Hashemi-Fesharki, S Ale-Agha, F Modabber

  Clinics in dermatology. 14(5):489-95.