جستجوی مقالات مرتبط با کلیدواژه « imiquimod » در نشریات گروه « پزشکی »

Psoriasis is a chronic, untreatable and disabling disease. In this research, we investigated the pharmacological properties of Euphorbia milii petroleum ether and ethyl acetate in a psoriasis mouse model. 

Thirty-one albino mice were used in this study. They were divided into five groups: group I, healthy animals; group II, inducer group with imiquimod 12.5 mg (5% cream); and groups III, IV and V were imiquimod-induced and then treated with clobetasol 0.05% in group III, E. milii petroleum ether fraction in group IV and E. milii ethyl acetate fraction in group V. Immunohistochemistry for interleukin-17 (IL-17), vascular endothelial growth factor and transforming growth factor-beta, as well as histopathology were done on the mice skin.

E. milii petroleum ether group showed a significant decrease in skin immunohistochemistry of IL-17, transforming growth factor-beta, and other histopathology parameters, while ethyl acetate fraction showed a significant reduction in vascular endothelial growth factor and other histopathology parameters

E. milii petroleum ether and ethyl acetate fractions may have a role in psoriasis treatment in a mice model.

Psoriasis is a chronic inflammatory autoimmune disease. The effectiveness of noscapine has been employed as a helpful treatment for various disorders and subjected to recent theoretical breakthroughs. Psoriasis-like lesions were induced by topical application of 5% imiquimod (IMQ) (10 mg/cm2 of skin) in male Balb/c mice and then medicated with a single oral dose of methotrexate (MET) as a positive control or daily oral treatment of noscapine (5, 15 and 45 mg/kg). In this way, skin inflammation intensity, psoriatic itchiness, psoriasis area severity index (PASI) score, ear length, thickness, and organ weight were daily measured. At the end of the study, histological and immunohistochemical and enzyme-linked immunosorbent assays (ELISA, for pro-/anti-inflammatory factors) were performed in each ear. IMQ caused psoriasis-like lesions. Noscapine markedly alleviated macroscopic parameters, namely ear thickness, ear length, skin inflammation, itching, and organ weight, as well as microscopic parameters including, pathology and Ki67 and p53, and tissue immunological mediators, such as tumour necrosis factor (TNF-α), interleukin (IL)-10, transforming growth factor (TGF-β), interferon-g (IFN-g), IL-6, IL-17, and IL-23p19 in the psoriatic skin in a concentration manner (p<0.05-<0.001). Therefore, noscapine with good pharmacological properties has considerable effects on psoriasis inflammation.

This study was performed to evaluate in vitro and in vivo Leishmanicidal potential of morphine (Mph), imiquimod (IQ), and their combination.

Leishmania infantum promastigote and amastigote assays were performed at the presence of 0.015–150µM Mph, 0.04–416µM IQ, and their combination. The inhibition effects of these drugs on promastigotes were evaluated after 24, 48, and 72h. The cytotoxic effects of the drugs were evaluated by MTT as well as flow cytometry after 72h. We explored the therapeutic effects of Mph and IQ in BALB/c mice at the end of the treatment using parasite load de termination and cytokine assay. One group of mice received Mph for three weeks before infection.

The results of promastigote and amastigote assays showed the cytotoxic effects of the drugs at low concentra tions. The cytotoxic effects were higher on promastigotes than amastigotes (p< 0.05). There was a negative correlation between drug concentration and amastigote/promastigote viability. Imiquimod alone or combined with Mph showed remarkable cytotoxic effects at all concentrations (p< 0.05). Flow cytometry results revealed apoptosis in the parasite following exposure to the drug combinations. Accordingly, the reduction of parasite loads in the spleen and liver was observed (p< 0.05) with simultaneous increases in IFN-γ and IL-4. We believe that the in vivo leishmanicidal effect was mediated by Mph through IL-4 and by IQ through both IL-4 and IFN-γ.

Results pointed out the promising effects of Mph and IQ at low concentrations, especially when combined.

Toxoplasma gondii, an obligate intracellular protozoan parasite, is widespread across the world. It causes congenital disease and abortion in humans and domestic animals. One of the major concerns in parasitology, thus, is an effective vaccine development to control Toxoplasmosis.

In the present research, a nano-liposomal vaccine containing soluble antigens (SA) was designed to evaluate the immunity and protective efficacy against T. gondii infection in BALB/c mice. Soluble antigens (SA) were achieved from tachyzoites, encapsulated in the liposome, and investigated via scanning electron microscope. Three times with 2-week intervals, BALB/c mice were immunized subcutaneously with different formulations. The level of protection against infection was assessed through the percent survival survey of BALB/c mice after challenge with tachyzoites of T. gondii RH strain; also, the type of generated immune response was determined by evaluating the generation of cytokine (IFN-γ, IL-4) and titration of IgG isotypes.

The immunization with liposome DSPC+ SA and liposome DSPC+ Imiquimod + SA induced a substantial increase in anti-Toxoplasma IgG antibody as compared to the PBS group (p <0.05). The IgG2a and IFN-γ secretion highest levels were seen with liposome DSPC+ Imiquimod + SA more than the control group (p <0.01) and (p <0.0001), respectively. After challenge with tachyzoites, less mortality was detected in the immunized mice by liposome DSPC + Imiquimod + SA that was meaningfully different (p <0.01) in comparison to other groups.

Vaccination with liposome DSPC + Imiquimod + SA showed more survival rate and cellular immune reaction against T. gondii.

Psoriasis is an autoimmune, chronic and debilitating disorder, mainly characterized by the presence of inflamed, dry and scaly patches of skin. This study aimed to investigate the possible anti-psoriasis effect of methanolic extract of Phoenix dactylifera seeds in mice.

Thirty-five Wistar albino male mice were divided randomly into 5 groups (n = 7). Group 1 represented the normal group (received the cream base only), group 2 through 5 received a single daily application of imiquimod 5% cream; while, groups 3, 4 and 5 received once daily application of clobetasol 0.05%, P. dactylifera seeds methanol extract 2% and 5%, respectively. All animals received the test substances on the shaved back for 10 consecutive days. Scoring for skin inflammation severity (scaling, erythema and thickness) was recorded on daily basis, and the animals were sacrificed on day 11. Skin and spleen samples were taken to evaluate histopathological and spleen index changes, respectively.

Imiquimod successfully induced psoriasis like lesion in mice as well as significant increase in the skin neovascularization. Topical methanol extract of P. dactylifera cream significantly reduced the signs of inflammation as well as skin neovascularization in a concentration-dependent manner, where 5% methanol extract cream showed better reduction in the inflammatory parameters than 2% methanol extract cream. These findings were supported by the results of the histopathological examination.

Results of the study suggest that methanol extract of P. dactylifera seeds possesses anti-psoriasis activity and could be used efficiently for the alleviation of psoriatic symptoms.

Attempts to produce vaccines for leishmaniasis need adjuvants to trigger the kind of immune reaction required for protection. In this study, we examined the properties of the TLR7 agonist imiquimod, a vaccine adjuvant, making use of a live model of infection where the immune reactions could be identified prior to and following the challenge of infection. The liposomes of EPC containing the imiquimod adjuvant were prepared and characterized for protein concentration, surface charge, and particle size. Vaccination was done using the soluble Leishmania antigen (SLA) as a first-generation vaccine model in the liposomal state to vaccinate BALB/c mice against the challenge of leishmania major. BALB/c mice were vaccinated subcutaneously, three times at a two-week interval. Parasite burden, footpad swelling, IgG isotype, as well as the level of IL-4 and IFN-γ were assessed as the protection criteria. The group of mice vaccinated by Lip+Imiquimod+SLA demonstrated a lower amount of footpad swelling and parasite burden than the buffer group. In addition, the highest level of IFN-γ and the lowest level of IL-4 production was noticed in the splenocytes of the mice vaccinated with the formulation of Lip+Imiquimod+SLA. These results imply that imiquimod added to the formulation of liposomes is able to modulate the immune reaction of the BALB/c mice vaccinated preferably to a Th1 reaction rather than a Th2 reaction which can also lead to partial protection against the challenge of Leishmania.

In this research, the effect of morphine on promastigotes and amastigotes of Leishmania major has been investigated in the presence of nalmefene as a blocking opioid drug and imiquimod as an opioid growth factor receptor.

This study was conducted at Tarbiat Modares University, Tehran, Iran in 2015-2018. Morphine with different concentration (0.1, 1, 10 and 100 1µg/ml) alone and with imiquimod (0.01, 0.1 and 1µg/ml) and nalmefene (0.1, 1 and 10 µg/ml) on promastigotes and amastigotes in macrophages and also the percentage of infected macrophages was investigated. For evaluation of the apoptosis, we used flow cytometry method. The effect of imiquimod and nalmefene on glucantime and amphotericin B as current drugs for treatment of leishmaniasis was evaluated too.

The effect of morphine on promastigotes and amastigotes has a reverse relationship with its concentration. The results of flow cytometry for drug-treated promastigotes revealed that apoptosis and necrosis did not increase markedly relative to the control group. A combination of morphine and imiquimod in concentrations of 0.05, 5 and 5 µg/ml had a pronounced effect on reduction and prevention of macrophage infection with amastigotes. Morphine at a concentration of 0.1 µg/ml plays the role of adjunctive treatment. In amastigote assay we found the better results in group that get glucantime 25 µg/ml+ imiquimod 0.5 µg/ml.

This effect is strengthened with imiquimod and weakened with nalmefene. Using high dose morphine and nalmefene had reverse effects. They suppress immune system and had no controlling effect in macrophages amastigote infection and reduction of promastigotes.

Protection against leishmaniasis, in the murine model, is dependent on developing a potent CD4+ mediated Th1 type response. Liposomes can be applied as immunoadjuvants to stimulate immune responses to different antigens. In the present study, it was investigated whether DOTAP liposomes having SLA and imiquimod adjuvant, can induce a Th1 response and protect against Leishmania major challenge in BALB/c mice. Liposomes were provided applying the lipid film procedure. BALB/C mice were subcutaneously immunized, three times with 2-week intervals, with various formulations. Assessment of lesion development and parasite burden in the foot and spleen after challenge with L. major, assessment of Th1 cytokine (IFN-γ), and titration of IgG isotypes assessed the type of generated immune reaction and the protection extent. The mice immunized with Liposome DOTAP+imiquimod+SLA showed smaller footpad swelling which was meaningfully different (P<0.05) compared with other groups. The highest level of IgG2a was observed with Lip DOTAP+imiquimod+SLA more than the control (P<0.001). Mice immunized with Lip DOTAP+SLA+imiquimod demonstrated the least number of live parasites in the footpad and spleen. Cytokine assay showed that the greatest IFN- γ secretion was seen in the splenocytes of mice immunized with all formulations as compared to the control group (P<0.0001). In contrast, the lowest IL-4 production was detectable in Lip+imiquimod+SLA spleen, which was not significantly different compared with other groups. The results of this study show that liposome DOTAP+SLA+imiquimod formulation generates a cellular immune response that is protective against challenge against L. major.

The parasites of genus Leishmania are the causative agents of one of the most widespread and devastating diseases. According to follow-up data, these medications may provoke adverse drug reactions, drug resistance, relapse as well as financial burden. The mechanism of action of opioid drugs are primarily exerted via transmembrane G-protein coupled receptors. One of the potent synthetic immunomodulator agents is imiquimod with low molecular weight and unknown mechanism of action. Monocyte and macrophage are the primary site of action for imiquimod. Nalmefene is a well-known opioid antagonist agent which simultaneously inhibits these receptors and augments intracellular pathogenicity, hence providing opportunities to investigate their function. The aim of present work was evaluating the effect of morphine, imiquimod and nalmephen on the Leishmania major and investigating cytotoxic effect this drug on the uninfected macrophage and infected macrophage for detected early apoptosis, necrosis and secondry apoptosis by flowcytometry method. In this study we used morphine, imiquimod, nalmefene and Glucantime. We treated promastigotes, macrophages and infected macrophages with above drugs, and the apoptosis evaluated by flow cytometry. The results showed that in all concentration of morphine more than 98% of promastigotes remained alive that it is deduced that morphine lacks any lethal effect on L. major after 24 h, whereas in groups treated with Glucantime alone or in combination with Nalmephene and Imiquimod, 84.13%, 88.96% and86.72% of promastigotes were alive, respectively. The results of macrophage treatment with morphine, imiquimod and nalmefene demonstrated that most necrosis has occurred in nalmefene group (6.54%).

After decades of containment, pertussis disease, caused by Bordetella pertussis seems to be re-emerging and still remains a major cause of reported vaccine-preventable deaths worldwide. The current licensed whole-cell vaccines display reactogenicity while acellular vaccines are expensive and do not induce Th1-type immune responses that are required for optimum protection against the disease. Thus, there is an urgent need to develop new vaccines and the recombinant technology seems to be the method of choice for this purpose. The present study was an attempt to develop a new, simplified, cost-effective and well-defined vaccine against Bordetella pertussis, with capacity to induce a Th1 response.
A fusion DNA fragment encoding the N-terminal region of pertussis toxin S1 subunit and filamentous hemagglutinin type 1 immunodominant domain was constructed and the corresponding fusion protein (F1S1) was produced in Escherichia coli. F1S1 in conjunction with imiquimod was administered by subcutaneous (SC) and intranasal (IN) routes to BALB/c mice.
This vaccine formulation could elicit high levels of IFN-γ, serum IgG (with higher IgG2a/IgG1 ratio) and lung IgA after the SC and, to a lesser extent, following the IN administration.
Our results indicate that the above-mentioned important proteins of B. pertussis could be successfully produced in E. coli as a single fusion protein. Furthermore, this protein could induce proper systemic and mucosal immune responses after administration via SC or IN routes.

Canine visceral leishmaniasis (CVL) is not only an emerging veterinary concern but also a public health threat in endemic areas. The aim of this study was to assess the efficacy, immunogenicity and safety of two doses of aluminum hydroxide (alum) precipitated Leishmania major (Alum-ALM) mixed with BCG plus imiquimod against CVL. A total of 560 ownership dogs were serologically tested and 234 healthy dogs with no clinical signs of CVL, no anti-Leishmania antibodies and negative leish­manin skin test were selected and double-blind randomly injected intradermally either with 0.1 ml Alum-ALM (200µg protein) mixed with BCG (2 × 106 CFUs) plus imiquimod (121 dogs) or with 0.1 ml of normal saline (113 dogs). The follow-up examinations showed that there was no side effect associated with the vaccination except one case. Strong skin test conversion were seen in vac­cinated group (30.3%) compared to the control group (6.6%) at 22-24 weeks after the booster injection (p<0.001). The seroconversion was 16.3% (18/110) in vaccinated group and 26.4% (28/106) in control group after two transmission cycles but the differ­ence was not significant (P=0.095). The efficacy rate based on seroconversion was 40.4 %. Two injections of Alum-ALM mixed with BCG and imiquimod is safe, although decreases the seroconversion rate of CVL, but the overall efficacy was low.

Various adjuvants in combination with different antigens have been utilized as a vaccine candidate against leishmaniasis. However, the search for ideal adjuvants is still pursued due to the inefficiencies of current compounds. In the present study, the effect of imiquimod, as an adjuvant, is studied with soluble Leishmania antigens (SLA) in BALB/c mice. Four groups of mice were immunized with SLA, SLA plus imiquimod, SLA plus BCG, and PBS as control. Immunized mice received a boosting dose of SLA after 15 days. All groups were challenged with Leishmania major (L. major) promastigotes 2 weeks after the booster immunization. Our results showed that strong TH1 responses were induced in groups of SLA plus imiquimod as well as SLA plus BCGafter immunization. These responses included smaller footpad thickness, lower parasite load in lymph node, and higher proliferative response of lymph node cells to SLA, higher levels of interferon γ in culture supernatant of lymph node cells, and higher levels of IgG, and IgG2a in sera. The data supports the possibility of using imiquimod as a suitable adjuvant in leishmania vaccination.

Kerman Province, especially city of Bam in the southeast part of Iran, is epidemics for dry type cutaneous leishmaniasis (DTCL). This study was conducted to compare the effect of different treatments on parasite DNA load following therapies using Real-Time PCR method. Fifteen patients were divided into three groups under therapy with intralesional meglumine antimoniate, topical imiquimod and combination of both drugs. After obtaining consent from patients, punch biopsies were taken before and after treatment. To compare the amount of DNA load a relative quantitative Real-Time PCR method was designed and set up using Leishmania tropica ITS (internal transcribed spacer) gene. After doing PCR, the obtained results were analyzed using 2^-ΔΔCt method and relativity of DNA load before and after treatment were calculated. The highest falling of DNA load was for imiquimod (mean 4/7 cases), glucantime (mean 2/2 cases) and combination therapy (mean 2/4). From clinical point of view combination therapy had the best response. On the other hand, the overall IHC findings showed good response based on decreased CD1a epidermal, increased CD1a dermal, decreased CD68 macrophages and increased CD3 and CD20 of dermis. We set up a new method to compare Leishmania DNA load using the stable human gene of beta actin for normalization. We concluded that imiquimod was immune modulator and had synergistic effects on the best parasitocidal drug of glucantime for better response.

Infantile hemangioma is a congenital vascular malformation. Although almost all cases are self-limiting, treatment is sometimes necessary. According to previous studies, topical imiquimod induces resolution of lesions with an acceptable safety profile. The aim of the present study was to evaluate the effect of this topical treatment on Iranian infantile hemangioma patients. Patients under two years of age with infantile hemangioma who were not candidates for immediate systemic therapy with steroids were selected if the lesions were not ulcerated. Topical 5% imiquimod was applied on the lesions for 16 weeks. All the lesions were photographed before the commencement of the study and at the end of the treatment. Photographs were compared by two associate dermatology professors to evaluate the effect of treatment using a visual analogue scale. A total of 15 patients including five males (33.3%) and ten females (66.7%), with an age range of two to 18 months and a mean age of 9.1 (± 6.3) months, were enrolled in the study. The mean diameter of the lesions was 2.6 cm (± 1.8 cm). Nine patients (60%) had moderate response and five patients (33.3%) had good response while one patient had excellent response. Complications were mild local irritation and pruritus. It seems that topical imiquimod could be a suitable option in the treatment of some infantile hemangioma lesions not candidate for systemic treatment and/or other local measures such as laser and intra lesional steroid or when other drugs are useless or harmful..