Iranian Biomedical Journal
Volume:16 Issue: 2, Apr 2012

A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential. An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations. Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 µg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma. The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.

Wound healing of burned skin remains a major goal in public health. Previous reports showed that the bone marrow stem cells were potent in keratinization and vascularization of full thickness skin wounds. In this study, mesenchymal stem cells were derived from rat adipose tissues and characterized by flowcytometry. Staining methods were used to evaluate their differentiation ability. A collagen-chitosan scaffold was prepared by freeze-drying method and crosslinked by carbodiimide-based crosslinker. The results of immunecytochemistry and PCR experiments confirmed the adipose-derived stem cells (ASC) in differentiation to the keratinocytes under the treatment of keratinocyte growth factor. The isolated ASC were seeded on the scaffolds and implanted at the prepared wounds. The scaffolds without cells were considered as a control and implanted on the other side of the rat. Histopathological analyses confirmed the formation of new tissue on the scaffold-cell side after 14 days with the formation of dermis and epidermis. These results indicated the capacity of ASC in differentiation to keratinocytes and also wound healing in vivo.

Cryptorchidism has been proved to cause apoptosis in germ cells in respond to changes in the stimulation levels of specific physiological events. The purpose of this study was to determine whether treatment of bilateral cryptorchidism was associated with alterations in testicular gene expression. To induce bilateral cryptorchid model, immature mice were anesthetized and a small incision was made in the abdominal skin and peritoneum, then fat pad at the upper end of testis was sutured to the peritoneum. Transcript level of Bax, Bcl-2 proper, p53 and survivin mRNA and protein were determined after performing the two treatment surgical return of testis into scrotum (Exp1) and transplantation of spermatogonial stem cells with later orchidopexy (Exp2), performed 2 and 3 months after heat exposure, respectively. RT-PCR data showed decreased levels of p53 and Bax expression as well as decreased levels of Bcl-2 mRNA in treatment groups especially after transplantation compared with control group. The expression of survivin 140 was increased significantly after treatment, whereas that of survivin 40 was lower especially in the orchidopexy group. Immunohistochemistry staining showed that the intensity of Bax expression mainly was decreased in treated cryptorchid testis and rates of Bcl-2 were increased significantly, but expression of p53 and survivin proteins did not changed significantly after treatment. These observations suggest that cell-type-specific and many apoptotic systems control germ cell apoptosis after treatment of cryptorchidism.

Neuroinflammation, as a major outcome of microglia activation, is an important factor for progression of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. Microglial cells, as the first-line defense in the central nervous system, act as a source of neurotoxic factors such as nitric oxide (NO), a free radical which is involved in neuronal cell death. The aim of this study was to inhibit production of NO in activated microglial cells in order to decrease neurological damages that threat the central nervous system. An in vitro model of a newborn rat brain cell culture was used to examine the effect of betaine on the release of NO induced by lipopolysaccharide (LPS). Briefly, primary microglial cells were stimulated by LPS and after 2 minutes, they were treated by different concentrations of betaine. The production of NO was assessed by the Griess assay while cell viability was determined by the MTT assay. Our investigations indicated that LPS-induced NO release was attenuated by betaine, suggesting that this compound might inhibit NO release. The effects of betaine on NO production in activated microglial cells after 24 h were "dose-dependent". It means that microglial cells which were treated with higher concentrations of betaine, released lowers amount of NO. Also our observations showed that betaine compound has no toxic effect on microglial cells. Betaine has an inhibitory effect on NO release in activated microglial cells and may be an effective therapeutic component to control neurological disorders.

The primary phase of traumatic spinal cord injury (SCI) starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid (VPA) is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes. In this study, rats were randomly assigned to five experimental groups (laminectomy, untreated, and three VPA-treated groups). For SCI, severe contusion was used. In treated groups, VPA was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. To compare locomotor improvement among experimental groups, behavioral assessments were performed by the Basso, Beattie and Bresnahan (BBB) rating scale. The expression of neurotrophins was evaluated by RT-PCR and real-time PCR. VPA administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mRNA levels. Local inflammation and the expression of the lysosomal marker ED1 by activated macrophages/microglial cells were reduced by VPA and immunoreactivity of acetylated histone and microtubule-associated protein were increased. The results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test (BBB scale) with rapid recovery.

Diabetes mellitus is an alarming life style disease in the modern world. Exploitation of the anti-diabetic drugs for the amelioration of diabetes and associated life style diseases has become an imperative concern. In this milieu, this study was designed to explore the plausible effects of metformin intervention on hepatic and renal functions in a rat model of alcoholic liver disease. Thirty rats were divided into five groups (n = 6): ethanol control, ethanol water and also low, moderate and high doses of metformin. Ethanol 20% v/v (1 ml/100 g) was administered by oral gavage (p.o.) to all five groups for 21 days. Blood and tissue samples were collected for the assessment of lipid profile, hepatic and renal functions. After 21 days, the levels of hepatic function and lipid parameters were maintained at normalcy, especially in the high-dose metformin treated alcoholic rats as compared to the levels at day 1. Despite this, the renal biomarkers did not display any significant variation due to ethanolic exposure in any group. The histopathological score portrayed that the noxious effect of ethanol is prevented in the liver of moderate- and high-dose metformin, whereas the renal histological scores were unchanged in all the groups including ethanol control. These results suggest that the dose of ethanol required to induce hepatic dysfunction does not influence renal functions. In addition, high-dose metformin offers maximal hepatoprotection and spares kidney from per se toxicity, thereby advocating the beneficial intervention of the anti-diabetic drug, metformin, in alcoholic liver dysfunction.

Initial studies have shown that low-energy ultrasound stimulates living tissue cells to reduce regeneration or speed up their recovery. The purpose of this study was to examine the effects of various ultrasound parameters on the speed of recovery in injured sciatic nerves.

NMRI mice (n = 200) with injured left paw, caused by crushing their sciatic nerves, were randomly selected. The animals were exposed to ultrasound radiation with various frequencies, intensities, and exposure time. They were allocated into 20 groups (19 treatment and 1 control groups). Sciatic functional index (SFI) test was used to evaluate the difference between the groups with respect to functional efficiency of the sciatic nerve and its recovery.

The results of SFI test obtained from the 14th day showed a significant difference among the groups (P<0.05). On the 14th day after treatment, one of the groups (US11) recovered up to 90%.

Altered ultrasound exposure parameters had more favorable outcomes compared with our previous work.

Zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major is increasing in many parts of Iran. This disease originally is a disease found in gerbils. Leishmania parasites are transmitted by sandflies that live and breed in gerbil burrows. Nested PCR amplified Leishmania ITS1-5.8S rRNA gene in both main reservoir host “Rhombomys opimus” and in the “Phlebotomus papatasi” main vector of ZCL, in Iran. Population differentiation and seasonal variation of sandflies were analyzed at a microgeographical level in order to identify any isolation by distance, habitat or seasons. Populations of sandflies were sampled from the edges of villages in Natanz, Isfahan province, Iran, using the Centers for Disease Control traps and sticky papers. Individual sandflies were identified based on external and internal morphological characters. Nested PCR protocols were used to amplify Leishmania ITS1-5.8S rRNA gene, which were shown to be species-specific via DNA sequence. A total of 4500 sandflies were collected and identified. P. papatasi, Phlebotomus sergenti and Phlebotomus jacusieli from genus Phlebotomus and Sergentomyia sintoni and Sergentomyia clydei from genus Sergentomyia were identified in this region. P. papatasi was the most abundant sandfly in the collections. Ten out of 549 female P. papatasi and four out of 19 R. opimus were found to be infected with L. major. Seasonal activity of sandflies starts in June and ends in November. Abundance of P. papatasi was in September. Finding and molecular typing of L. major in P. papatasi and R. opimus confirmed the main vector and reservoir in this region.