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Farshid Saadat

Publications and source records attributed to Farshid Saadat.

14 recordsLinked to original sources
PubMed2005

Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine.

Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.

Animals↗
PubMed2005

Effect of pyrimethamine in experimental rheumatoid arthritis.

BACKGROUND: Recent evidence has shown that the antimalarials are useful drugs in the treatment of various rheumatic diseases. The present study was designed to test the therapeutic effect of pyrimethamine (PYR) in collagen-induced arthritis (CIA). MATERIAL/METHODS: CIA was induced in Lewis rats. The intraperitoneal administration of PYR and methotrexate (MTX) were started on day 25 post-immunization and continued until final assessment on day 35. During this period, clinical examination was performed intermittently. Anti-C II Ab and nitric oxide (NO) synthesis were measured. The paws and knees were then removed for histopathology and radiography assay. The biocompatibility of PYR and MTX were assessed using a fibrosarcoma cell line. RESULTS: Data showed that i.p. injection of pyrimethamine to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cell infiltrate in the joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following PYR therapy. Moreover, our radiography results paralleled our histological findings. Cytotoxicity analysis of PYR showed greater tolerability compared with MTX. Treatment with PYR significantly diminished nitric oxide formation in treated rats compared with untreated controls. CONCLUSIONS: Our findings shed light on the therapeutic efficacy of pyrimethamine in experimental rheumatoid arthritis compared with a choice drug (methotrexate), which may recommended it as a second-line drug in the treatment of rheumatoid arthritis.

Animals↗
PubMed2005

Apoptotic efficacy and inhibitory effect of dexamethasone on matrix metalloproteinase.

BACKGROUND: There is now accumulating evidence that matrix metalloproteinases and apoptosis may play an important role in inflammation processes. This study was undertaken to determine the effect of dexamethasone on apoptosis and matrix metalloproteinase 2 (MMP-2) activity compared with two nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and diclofenac. MATERIAL/METHODS: A fibrosarcoma (WEHI-164) cell line was used for evaluating tolerability, MMP-2 activity, and apoptosis. Dexamethasone, piroxicam, and diclofenac were used at concentrations of 10-200 microg/ml in triplicate, two-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of apoptosis, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used. RESULTS: Cytotoxicity analysis of dexamethasone showed a greater tolerability than diclofenac at concentrations of 10-100 microg/ml, whereas the cytotoxic effect of dexamethasone and piroxicam were parallel at doses of 5-80 microg/ml. The dose-dependent inhibitory effect of dexamethasone on MMP-2 activity was significantly less than that of the tested NSAIDs at concentrations of 10-80 microg/ml, while it increased at doses of >100 microg/ml compared with piroxicam. Moreover, the rate of apoptosis for dexamethasone-treated cells was 20.92%, the values for diclofenac and piroxicam being 78% and 28.15%, respectively. CONCLUSIONS: Our findings suggest that dexamethasone is able to induce apoptosis and suppress MMP-2 activity. Collectively, dexamethasone might be assumed as an agent which could be recommended for chemopreventive purposes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

A case of invasive aspergillosis in CGD patient successfully treated with Amphotericin B and INF-gamma.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absence of superoxide and hydrogen peroxide production in phagocytes predisposes patients to bacterial and fungal infections. The most common fungal infections in these patients are caused by Aspergillus species. CASE PRESENTATION: Here, we describe Aspergillus osteomyelitis of the ribs and hepatic abscess in a 5-year-old boy. The patient was successfully treated with Amphotericin B and INF-gamma. CONCLUSION: With respect to the high frequency of aspergillosis in the CGD patient, immune deficiency should be investigated in patients with invasive aspergillosis. Moreover, using antifungal drugs as prophylaxis can improve the quality of life in these patients.

Amphotericin B↗
PubMed2005

Concomitant reduction of matrix metalloproteinase-2 secretion and intracellular reactive oxygen species following anti-sense inhibition of telomerase activity in PC-3 prostate carcinoma cells.

BACKGROUND: The level of activity of the telomerase has been shown to correlate with the degree of invasiveness in several tumor types. In addition, cellular redox state is believed to regulate the secretion of matrix metalloproteinase-2 (MMP-2). AIMS: To determine the effect of anti-sense telomerase treatment of prostate cancer cells on MMP-2 activity, and the reactive oxygen and nitrogen species (two effectors of cellular redox state). METHODS: Anti-sense oligonucleotide against RNA component of human telomerase (hTR) was introduced into the cells using Fugene-6 transfection reagent. The activity of telomerase was assessed using Telomere Repeat Amplification Protocol (TRAP assay). Activity of matrix metalloproteinase-2 (MMP-2) was determined by zymography. Levels of intracellular reactive oxygen species (ROS) and nitric oxide metabolites were measured by dichlorofluorescein diacetate (DCFH-DA) staining and Griess reagent, respectively. The level of apoptosis was determined using TUNEL assay. RESULTS: TRAP assay showed more than 90% inhibition of telomerase activity after 72 h of transfection. Pro-MMP-2 activity was decreased down to 50% of the control levels. Intracellular reactive oxygen species were also significantly decreased. Neither apoptosis rate nor the level of nitric oxide metabolites was significantly different between anti-sense treated and control cells. CONCLUSIONS: Concomitant reduction of the pro-MMP-2 secretion and ROS in PC-3 cells following hTR inhibition suggests that over-activity of telomerase in cancer cells might increase the level of matrix metalloproteinase-2 and thus, be directly involved in the invasion process through enhancement of intracellular oxidative stress.

Apoptosis↗
PubMed2005

Artemether: a new therapeutic strategy in experimental rheumatoid arthritis.

The current research was designed to determine the effect of artemether in treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was induced in Lewis rats. The intramusculary administration of artemether (ART) and intraperitoneally injection of methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was taken intermittently. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m. injection of ART to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed a reduced inflammatory cell infiltrate in joints of treated rats; tissue edema, and bone erosion in the paws were markedly reduced following ART therapy. Furthermore, our radiography results paralleled our histological findings. Cytotoxicity analysis of ART showed greater tolerability compared with MTX. Treatment with ART significantly diminished NO formation in treated rats compared with nontreated controls. Our data shed light on the therapeutic efficacy of artemether in experimental rheumatoid arthritis compared with a choice drug (methotrexate), and it may be offered as a second-line drug in treatment of rheumatoid arthritis.

Animals↗
PubMed2005

Bee venom, immunostimulant or immunosuppressor? Insight into the effect on matrix metalloproteinases and interferons.

The current evidence has defined conflicting properties for bee venom. The goal of this study was to determine whether bee venom (BV) is an immunosuppressor or immunostimulant. The WEHI-164, HT-1080, and K562 cell lines were used for assaying toxicity, proliferative response, matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) activity, and interferon production. The Australian and Iranian BV (ABV and IBV) were used at concentrations of 0.025-1 microg/ml in triplicate and 2-fold dilutions. MMP-2 and -9 activities were evaluated using the zymography method. The production of interferons (IFN-alpha and IFN-beta) were assessed using enzyme-linked immunoassay procedure. Our results show no significant difference between two sources of honeybee venom (ABV and IBV) when they are added to an identified cell line, whereas the response of various cell lines against BV could be different. The increasing amounts of ABV and/or IBV (between doses 0.025-0.5 microg/ml) to human monocyte cell line (K562) exhibit a significant increase in proliferative response. Our data show that the immunomodulatory effect of ABV and/or IBV on MMP-2 and MMP-9 activity in both cell culture media, WEHI-164 and K562, is similar. The stimulatory effect of BV on MMP-2 and -9 activities is occurred between doses 0-0.05 microg/ ml. In contrast, the inhibitory effect of BV on these two MMPs is seen at concentrations of >0.05 microg/ml. The ABV and/or IBV has no influence on IFN-alpha production in cell culture media, whereas adding the BV to K562 cell line could significantly increase the production level of IFN-beta only on day 8 posttreatment. We conclude that time- and dose-dependent response as well as the type of treated cell line could determine the immunosuppressive and/or immunostimulant property of bee venom that could be effective in future therapeutic strategies.

Animals↗
PubMed2005

Chemoprevention by pyrimethamine.

The goal of the current research was to investigate the chemopreventive potency of an antimalaria drug, pyrimethamine, in in vitro conditions. The fibrosarcoma (WEHI-164) cell line was used for evaluating cytotoxicity, matrix metalloproteinase 2 (MMP-2) activity, and apoptosis. Pyrimethamine and methotrexate were used at concentrations of 0-8 microg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymoanalysis method. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. Cytotoxicity analysis of pyrimethamine showed a greater tolerability than methotrexate at concentrations of 1-8 microg/ml. The dose-dependent inhibitory effect of pyrimethamine on MMP-2 activity was significantly less than that of methotrexate at concentrations of 1-8 microg/ml. Moreover, the rate of apoptosis for pyrimethamine-treated cells at different doses (0.1, 1, and 10 microg/ml) was 3.30%, 9.42%, and 11.32%, respectively. Our data suggest that pyrimethamine enables suppression of MMP-2 activity and induces apoptosis that could be assumed for chemoprevention therapy.

Animals↗
PubMed2005

Determination of gelatinase A using a modified indirect hemagglutination assay in human prostate cancer screening and assessment of its correlation with prostate-specific antigen parameters.

BACKGROUND: Prostate cancer is the most common malignancy affecting men and is a major cause of cancer death. There are increasing data on novel tumor markers, such as gelatinase A, which play a key role in tissue invasion and metastasis. OBJECTIVES: We designed a study to evaluate total gelatinase A content using a simple and applicable Indirect hemagglutination (IHA) test in harmony with gelatinase A activity in serum samples as compared with prostate-specifc antigen (PSA) parameters. METHODS: In this study, we analysed the circulating form of gelatinase A (MMP-2) in patients suffering from either benign prostate hyperplasia (n=54) or prostate cancer (n=26) versus normal individuals as control (n=26). The gelatinolytic activity was determined by zymography and total MMP-2 content was measured by a novel IHA method. Total PSA and free PSA were quantified using a standard ELISA technique. RESULTS: Correlation of densitometric analysis of gelatinase A activity and IHA titer is significant at the 0.01 level (P<0.01, rho=0.916). Correlation of PSA and IHA titer is significant at the 0.01 level (P<0.01, rho=0.746). Correlation of free PSA and IHA titer is significant at the 0.01 level (P<0.01, rho=0.749). Borderline of IHA titer in patients with prostate cancer was 512+/-1 tube titer, in benign prostate hyperplasia patients was 128+/-1 tube titer and the titer in normal individuals was 8+/-1 tube titer. CONCLUSIONS: These results demonstrate that assessment of gelatinase A might be a promising procedure for monitoring and screening patients with prostate cancer.

Adenocarcinoma↗
PubMed2004

Chemopreventive effect of M2000, a new anti-inflammatory agent.

BACKGROUND: An emerging body of literature has recently defined a reduced risk of cancer following the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are generally able to exert an apoptotic property and inhibitory effects on the activity and/or expression of matrix metalloproteinases (MMPs). This study was undertaken to explore the role of a newly designed NSAID, M2000 (C6H10O7), as an anti-inflammatory drug in chemoprevention therapy under in vitro conditions. MATERIAL/METHODS: The influence of M2000 on a fibrosarcoma cell line (WEHI-164) was investigated using an in vitro cytotoxicity assay, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay to assess apoptosis, and gelatin zymography for evaluating the activity of matrix metalloproteinase 2 (MMP-2). RESULTS: Cytotoxicity analysis of M2000 showed a much higher tolerability than the other tested drugs (diclofenac, piroxicam, and dexamethasone) in that it showed no cytotoxic effect compared with them. The dose-dependent inhibitory effect of M2000 at concentrations of 20, 40, 80, and 200 microg/ml was significantly greater than that of dexamethasone and of piroxicam at a concentration of 200 microg/ml, whereas the inhibitory activity of M2000 paralleled diclofenac at doses of 10, 20, 40, and 200 microg/ml. Moreover, the apoptotic efficacy of M2000 was similar to that of dexamethasone. CONCLUSIONS: Based on our data, the induction of apoptosis together with MMP-2 inhibition could be indicative of a chemopreventive property of M2000. Thus this novel NSAID might be considered as a chemopreventive drug in the potential prevention and treatment of cancer and in inhibition of the angiopathogenic process.

Animals↗
PubMed2004

Study of the distribution of Malassezia species in patients with pityriasis versicolor and healthy individuals in Tehran, Iran.

BACKGROUND: Pityriasis versicolor is a superficial infection of the stratum corneum which caused by a group of yeasts formerly named pityrosporium. The taxonomy of these lipophilic yeasts has recently been modified and includes seven species referred as Malassezia. The aim of this study is to compare the distribution of Malassezia species isolated from pityriasis versicolor lesions and those isolated from healthy skins. METHODS: Differentiation of all malassezia species performed using morphological features and physiological test including catalase reaction, Tween assimilation test and splitting of esculin. RESULTS: In pityriasis versicolor lesions, the most frequently isolated species was M. globosa (53.3%), followed by M. furfur (25.3%), M. sympodialis(9.3%), M. obtusa (8.1%) and M. slooffiae (4.0%). The most frequently isolated species in the skin of healthy individuals were M. globosa, M. sympodialis, M. furfur, M. sloofiae and M. restricta which respectively made up 41.7%, 25.0%, 23.3%, 6.7% and 3.3% of the isolated species. CONCLUSIONS: According to our data, M. globosa was the most prevalent species in the skin of healthy individuals which recovered only in the yeast form. However, the Mycelial form of M. globosa was isolated as the dominant species from pityriasis versicolor lesions. Therefore, the role of predisposing factors in the conversion of this yeast to mycelium and its subsequent involvement in pityriasis versicolor pathogenicity should be considered.

Adult↗
PubMed2004

Inhibitory effect of Aspergillus fumigatus extract on matrix metalloproteinases expression.

BACKGROUND: Matrix metalloproteinases (MMPs) play a role in several physiologic and pathologic events. There are some evidence indicating the involvement of MMPs in the pathophysiology of fungal infections. METHODS: Here we study somatic extract of Aspergillus fumigatus. The influence of Aspergillus vs. two other fungal extracts on MMPs production by Fibrosarcoma cell line was investigated using an in vitro cytotoxicity assay, sodium dodecyl sulfate-polyacrylamide and gelatin zymography. RESULTS: Comparative dose-dependent inhibitory effects on MMPs were seen by A. fumigatus extract and compared with some steroidal and non-steroidal drugs. Cytotoxicity analysis of our extract revealed much lower cell death than other examined agents. CONCLUSIONS: Since inhibition of MMPs activity has been employed in modality therapy in such diseases as cancer, this extract might be promising in the preparation of anti-MMP therapeutic derivatives.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Facial demodicosis.

A 24-year-old man presented with papulopustular, rosacea-like centro- facial lesions. Many Demodex mites were found in the affected area by microscopy of smears from pustules. This observation provides further evidence that demodicosis is a condition distinct from common rosacea. Considering clinical similarities of demodicosis, rosacea and some mycotic infections, direct examination to confirm the etiological agent is highly recommended prior to treatment.

Adult↗