فهرست مطالب hamid zarkesh esfahani

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system affecting young adults. MS attacks the myelinated axons in the CNS, destroying the myelin and the axons to varying degrees. The course of MS is highly varied and unpredictable. In most patients, the disease is characterized initially by episodes of reversible neurological deficits, which is often followed by progressive neurological deterioration over time. Twice as many women are affected as men. The disease is diagnosed on the basis of clinical findings and supporting evidence from ancillary tests, such as magnetic resonance imaging (MRI) of the brain and examination of the cerebrospinal fluid (CSF). MS typically present in adults 20 to 45 years of age; occasionally, it present in childhood or late middle age. The cause is unknown, but it appears to involve a combination of genetic susceptibility and a nongenetic trigger, such as a virus, metabolism, or environmental factors, that together result in a self-sustaining autoimmune disorder that leads to recurrent immune attacks on the CNS. Neurologists agree that patients may be grouped into four major categories based on the course of disease: Relapsing–remitting, Secondary progressive, Primary progressive and Progressive-relapsing. RRMS – the most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission. RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity over a specified period of time) or not active, as well as worsening (a confirmed increase in disability following a relapse) or not worsening. Approximately 85 percent of people with MS are initially diagnosed with RRMS. Interferon-beta (IFN-β) medications are commonly used as first-line therapy in multiple sclerosis. Interferons (IFNs) are naturally occurring cytokines possessing a wide range of anti-inflammatory properties. Recombinant forms of IFNβ are widely used as first-line treatment in relapsing forms of MS. The mechanism of action of IFNβ is complex, involving effects at multiple levels of cellular function. IFNβ appears to directly increase expression and concentration of anti-inflammatory agents while downregulating the expression of proinflammatory cytokines. Antibodies can develop during interferon-beta treatment and reduce or abrogate normal biologic and treatment effects. Anti-IFN-β antibodies can reduce both bioactivity and clinical efficacy of IFN-β. Binding antibodies (BAbs) are antibodies that bind to the drug but do not necessarily inhibit its biological action. BAbs may be detected within the first month of therapy. The rate at which they appear is dependent on the type of IFNβ used. Although BAbs do not necessarily inhibit the biological action of IFNβ, as therapy is continued, maturation of the antibody body response may result in the production of high-affinity neutralizing antibodies (NAbs). NAbs are a subset of BAbs which prevent the binding of the IFNβ to its receptor on the surface of cells. When BAbs are detectable it is likely that NAbs are also present, however their concentration and affinity generally increase as the response matures. Enzyme-linked Immunosorbent Assay (ELISA) can potentially be used to characterize the composition of the anti-IFN-beta antibody response. Currently, CinnoVex, a biosimilar product to Avonex produced by CinnaGen Company, Iran, is used to treat MS patients in Iran. The objective of this study was to measure serum anti-interferon antibodies (CinnoVex) in patients with MS and compare it between two groups of patients. The first group is patients with MS that received interferon-beta and responded to it. The second group was patients with MS that received interferon-beta and did not respond to it.

An Indirect ELISA test was used for the measurement of anti-IFN-β antibodies. Sera were studied for anti-IFN-β antibodies from 26 healthy individuals and 52 MS patients (26 patients from each group) treated with Interferon-beta and the obtained results were analyzed statistically.

Patients were considered positive for Anti-IFN-β antibodies, if they had a positive sample with an optical density of more than 0.085. Anti-IFN-β antibodies were found in 4(14%) of MS patients treated with Interferon-beta and responded to it, but in 9 (35%) of MS patients treated with Interferon-beta and did not respond to it.

In this study, we found that the percentage of anti-IFN-β antibodies in the second group was higher than in the first group, so we can conclude that one of the most important factors that caused the patients not to respond to interferon-beta, formation of anti-drug antibodies in the serum that can reduce clinical efficacy and bioavailability of drug.

Tumor development is angiogenesis dependent. There is evidence that leptin contributes to tumor growth. However, all the mechanisms by which leptin does this has not been clearly established. The objective of the present study was to test the hypothesis that leptin enhances melanoma tumor growth through inducing angiogenesis and cell proliferation.

We injected 2 × 106 B16F10 melanoma cells subcutaneously to 32 C57BL6 mice. The mice were randomly divided into four groups of eight animals, on day 8. Two groups received twice daily intraperitoneal (i.p.) injections of either phosphate buffered saline or recombinant murine leptin (1 μg/g initial body weight). Two groups received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/injection every 3 consecutive days. By the end of the 2nd week, the animals were euthanized and blood samples and tumors were analyzed. Angiogenesis and proliferation were assessed by immunohistochemical staining for CD31 and Ki-67 respectively.

Tumors size, capillary density, plasma levels of vascular endothelial growth factor, and the number of Ki-67-positive stained cells were significantly more in the leptin than 9F8 and both control groups (P < 0.05).

Taken together, our findings reinforce the idea that leptin acts as an angiogenic and mitogenic factor to promote melanoma growth

In this study, nano-biocomposite composed of poly (lactide-co-glycolide) (PLGA) and chitosan (CS) were electrospun through a single nozzle by dispersing the CS nano-powders in PLGA solution. The cellular behavior of human adipose derived stem cells (h-ADSCs) on random and aligned scaffolds was then evaluated. In this experimental study, the PLGA/CS scaffolds were prepared at the different ratios of 90/10, 80/20, and 70/30 (w/w) %. Morphology, cell adhesion and proliferation rate of h-ADSCs on the scaffolds were assessed using scanning electron microscope (SEM), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and trypan blue staining respectively. H-ADSCs seeded on the matrices indicated that the PLGA/CS composite matrix with aligned nanofibres and higher content of CS nano-powders gave significantly better performance than others in terms of cell adhesion and proliferation rate (P<0.05). We found that CS enhanced cell adhesion and proliferation rate, and aligned nanofibers guided cell growth along the longitudinal axis of the nanofibers, which would provide a beneficial approach for tissue engineering.

Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system، which about 2. 5 million people around the world are suffering from it. Various factors including environmental and genetic factors are involved in the incidence of the disease. T cell immunoglobulin and mucin (TIM) gene is one of the genetic factors which recently demonstrated that has critical role in autoimmune diseases. In this study، the frequency and the association of TIM-3-1541C>T polymorphisms with multiple sclerosis disease in Isfahan، Iran، population were investigated. Blood samples were collected from 140 patients with multiple sclerosis and 138 healthy controls. After DNA extraction، the TIM-3-1541C>T polymorphism was detected via polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The results were analyzed with the SPSS16. 0 software package. The frequency of CT genotype in patients with multiple sclerosis was higher than the control group and there was a significant association between multiple sclerosis and TIM-3-1541C>T polymorphism in Isfahan population (P = 0. 009، OR = 4. 08). T cell immunoglobulin and mucin gene family (TIM) is located on human chromosome 5q33. 2 and play a critical role in regulating immune responses including allergy، transplant tolerance and autoimmunity. This study was done based on the results of previous studies about the association of TIM-3-1541C>T with rheumatoid arthritis، since the mechanisms of pathogenesis of this disease and multiple sclerosis are similar. Our results showed that TIM-3-1541C>T polymorphism is associated with multiple sclerosis in Isfahan population.

In recent years, adipose tissue, due to the stem cells contained within, has found a new special place in laboratory and clinical applications. These adipose‑derived stem cells (ADSCs) have the same characteristics of bone marrow mesenchymal stem cells (BMSCs). Although bone marrow (BM) is not easily accessible and its procurements may be painful, most patients possess excess fat which can be obtained by less invasive methods; this makes adipose tissue ubiquitous, available and an ideal large‑scale source for research on clinical applications. BMSCs and ADSCs were harvested from three healthy human and were characterized using flow‑cytometry. After they were treated for neurosphere formation using basic fibroblast growth factor, epidermal growth factor, B27; terminal differentiation was performed. In this study, we used immunocytochemistry, real time‑polymerase chain reaction and western blotting techniques for detection and comparison of Nestin, microtubule‑associated protein‑2 (MAP‑2) and glial fibrillary acidic protein (GFAP) markers in human ADSCs and BMSCs. Under appropriate conditions ADSCs can differentiate into neuron‑like cells and express neural markers the same as BMSCs, also the expression of GFAP marker in differentiated cells derived from ADSCs was significantly lower than the cells derived from BMSCs (P < 0.05). While the expression of MAP‑2 marker in both groups was the same. However, due to its advantages and according to our results based on the expression levels of GFAP and MAP‑2, adipose tissue rather than BM could represent a more appropriate stem cell source for investigating the application of these cells in understanding the pathophysiology and in treatment of neurodegenerative disorders.

In the late 1980s، it was shown that by using vectors in bacterial expression systems، recombinant antibody fragments with correct folding could be produced. Before that، antibody fragments were produced by proteolytic cleavage in format of Fab and F (ab'') 2. By progress in recombinant antibody technology، these antibodies were produced in bacterial systems، mammalian cells، insects، yeasts، plants and free cell systems. The basis of this technology is the ability to produce these fragments with conserved stability and specificity. By the development of recombinant technologies، monoclonal antibodies were dissected into minimal binding fragments and were rebuilt into multivalent high avidity reagents and fused with a range of molecules including enzymes for prodrug therapy، toxins for cancer treatment، viruses for gene therapy، cationic tails for DNA delivery، liposomes for improved drug delivery and biosensors for real-time detection of target molecules The following review will discuss the different types of recombinant fragments and their applications in various fields of science such as biology and medicine.

Helicobacter pylori (H. pylori) is a spiral Gram negative bacteria that can transform to the coccoid form in adverse conditions.. The aim of this study was to determine the in vitro morphological and bactericidal effects of metronidazole, amoxicillin and clarithromycin on H. pylori.. The standard strain 26695 of H. pylori was cultured on Brucella agar (BA) and the minimum inhibitory concentrations (MICs) of three antibiotics were determined by E-test method. The bacteria were exposed to antibiotics at 1/2 MIC, MIC and 2X MIC concentrations in Brucella broth (BB). Induced coccoid forms were confirmed by Gram staining and light microscopy. The viability of cells as well as the susceptibility of viable coccoids to antibiotics were examined using the flow cytometry method.. All of the three antibiotics at sub-MIC induced coccoid forms. The highest rates of coccoids (> 90%) were induced at 0.008 μg/mL concentration (1/2 MIC) of amoxicillin, 72 hours postexposure. Metronidazole and clarithromycin with 1/2 MIC (0.5 and 0.125 µg/mL respectively) induced lower rates of coccoid forms (60% and 40% respectively). Potent bactericidal effects on coccoids were observed with Metronidazole at 2X MIC and clarithromycin at MIC (0.25 µg/mL) (80 - 90%). Amoxicillin with MIC and 2X MIC had no bactericidal effect on coccoid forms.. Despite the good in vitro bactericidal effect of amoxicillin on spiral forms of H. pylori, this antibiotic has little effect on induced coccoids that may develop after the inappropriate in vivo antibacterial treatment. Hence, for successful therapy, it is essential not only to eradicate the spiral forms, but to eliminate the viable coccoids..

Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Leptin is a peptide predominantly produced by adipocytes. Obesity increases the expression of leptin. On the other hand, several recent experiments have suggested that tumor growth to be dependent on endothelial progenitor cells (EPCs) which are effective in generation of new blood vessels. Our objectives in the present study were to examine the effects of leptin on melanoma growth and circulating EPCs number. Melanoma tumors were induced by subcutaneous injections of 2 × 106 B16F10 melanoma cells to 32 C57BL6 mice. The mice were randomly divided into 4 groups of 8 on the 8th day. The first two groups received intraperitoneal (IP) injections of either phosphate-buffered saline (PBS) or recombinant murine leptin (1 μg/g initial body weight) twice daily. The other two groups received IP injections of either 9F8 (an anti leptin receptor antibody) or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week, the animals were euthanized and blood samples were saved for computation with flow cytometry. The tumors were also analyzed. The EPC numbers in leptin, PBS, 9F8, and IgG groups were 222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26 per ml of blood, respectively. Moreover, the corresponding values for tumor weights were 3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2, 1.7 ± 0.3 g. Tumors weight and size, and circulating EPC numbers were significantly more in the leptin group than 9F8 and both control groups (P < 0.05). In conclusion, our observations indicated that leptin caused melanoma growth likely through increased circulating EPC numbers and consequently vasculogenesis.

The great demand of people for consumption of natural additives resulted in producing natural vanillin. There are plant sources and chemical procedures for vanillin production but microbial bioconversions are being sought as a suitable alternative. In the present work, the ability to produce vanillin from isoeugenol was screened using growing cultures of various bacteria. Among the 56 strains of bacteria isolated from the soil environments of Iran, a Gram-negative rod designated as strain ISPC2 showed the capability of promoting the formation of high amounts of vanillin when grown in the presence of isoeugenol. On the basis of morphological and physiochemical characteristics and 16S ribosomal ribonucleic acid (rRNA) gene sequence analysis, the isolate was identified as Pseudomonas aeruginosa ISPC2. Vanillin formation was analyzed by GC/FID. In the presence of isoeugenol, a growing culture of P. aeruginosa ISPC2 produced 1.62 gL-1 vanillin (molar yield of 17.3%) after a 72 h reaction at 30°C and 200 rpm. This proposed procedure is an alternative approach to obtain vanillin in an environmentally friendly way. Further studies for standardization and optimization for higher yield of vanillin production, needs to be investigated.

S-layer is the outer protein layer in the most archaea and bacteria. S-layer protects bacteria against phagocytosis and prohibits entry of some biomolecules and some antibiotics and adhesion to matrix proteins. S-layer is a virulence agent in bacteria. β–lactamase can inactive β-lactame antibiotics. According to role of β-lactame antibiotics in the treatment of infectious diseases with Bacillus spp., increasing frequency of S-layer and β–lactamase producer Bacillus cereus strains in hospitals lead to increase antibiotic resistant nosocomial infections. In this basic study, 274 samples were evaluated with laboratory methods in Alzahra hospital and Isfahan University between 2004 and 2006. Bacterial identification was performed with microbiological methods, such as staining, chemical test, use of differential and selective Bacillus cereus selective agar media. Bacteria cultured in TSA for 16h, and then separated surface proteins, and finally electrophoresis was performed. S-layer in Bacillus cereus has 97KD molecular weight. Production of β-lactamase was evaluated by acidometric method. Of 247 isolated bacteria, frequency of Bacillus cereus strains, S-layer and β–lactamase in S-layer producer Bacillus cereus strains were 9.49%, 46.20% and 100%, respectively. Results showed high prevalence of nano structure S-layer and β-lactamase producer Bacillus cereus strains in hospital. We recommend controlling bacterial population in crowded places and health and therapeutic centers to decrease producing antibiotic resistance bacteria.

Hospital surfaces can serve as reservoirs of potential pathogen bacteria. β-lactam antibiotics are developed as wide-spectrum antibiotics, however, the emergence of bacteria encompassing β-lactamase was a major challenge for physicians. The present study was conducted to determine the frequency of β-lactamase and antibiotic sensitivity pattern in isolated pathogen bacteria from low and high hospital contact surfaces. This experimental study was conducted on 194 isolated samples in Azzahra hospital in Isfahan. Samples were collected from high and low contact surface with swab in NB (Nutrient Broth). Bacteria were identified with microbiological techniques, however, β–lactamase production was assessed with acidometric and antibiogram pattern was achieved with Kirby Bauer method. Of 194 isolated bacteria, the following organisms were detected: Staphylococcus spp. 55%, Bacillus spp. 26.3%, Enterobacteriaceae 9.8%, Pseudomonas spp. 3.9%, other gram negative bacteria 4.5% and Streptococcus spp. 0.5%. Meanwhile, 61.5% of bacteria produce β–lactamase. According to antibiogram, organisms showed the highest and lowest resistance to penicillin and gentamicin, respectively. Widely spread of β–lactamase represents high spread of bacteria in hospital surfaces. Obviously, improvement in the quality of disinfectant agents could pave the way for better management of antibiotic-resistant nosocomial infections.