Design of gelatin cryogel scaffolds with the ability to release simvastatin for potential bone tissue engineering applications.

Tissue engineering aims to improve or restore damaged tissues by using scaffolds, cells and bioactive agents. In tissue engineering, one of the most important concepts is the scaffold because it has a key role in keeping up and promoting the growth of the cells. It is also desirable to be able to load these scaffolds with drugs that induce tissue regeneration/formation. Based on this, in our study, gelatin cryogel scaffolds were developed for potential bone tissue engineering applications and simvastatin loading and release studies were performed. Simvastatin is lipoliphic in nature and this form is called inactive simvastatin (SV). It is modified to be in hydrophilic form and converted to the active form (SVA). For our study's drug loading and release process, simvastatin was used in both inactive and active forms. The blank cryogels and drug-loaded cryogels were prepared at different glutaraldehyde concentrations (1, 2, and 3%). The effect of the crosslinking agent and the amount of drug loaded were discussed with morphological and physicochemical analysis. As the glutaraldehyde concentration increased gradually, the pores size of the cryogels decreased and the swelling ratio decreased. For the release profile of simvastatin in both forms, we can say that it depended on the form (lipophilic and hydrophilic) of the loaded simvastatin.

Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron.

BACKGROUND: Cyclophosphamide (CP) is an alkylating chemotherapeutic drug used in the treatment of many types of cancer. However, as with other chemotherapeutic drugs, the use of CP is limited by the damage to healthy tissues such as testes, bladder and liver as well as cancerous tissue. Boron (B) is a trace element with many biological properties such as antioxidant, anti-apoptotic and anti-lipid per oxidation. METHODS: This current study aims to determine protective effects of B on CP induced testicular toxicity. The rats were divided into 4 groups (control, CP, B and B plus CP groups). The testes of experimental animals were taken for histological, apoptotic markers and biochemical analysis. RESULTS: The damage to some seminifer tubules, loss of typical appearance, thinning of seminifer epithelium and relative enlargement of the tubule lumen were watched in testis of the group that administrated CP. Moreover, Bcl-2, TAC and GSH levels decreased while TOC, OSI, MDA, Bax and Caspase-3 levels increased. On the other hand, pretreatment limited to B in the B plus CP group, testicular tissue improved. In addition, Bcl-2, GSH, TAC levels increased, Bax, MDA, TOC, OSI and caspase-3 levels decreased. CONCLUSION: B significantly reduced testicular lipid per-oxidation and strengthened antioxidant defenses. Our results showed that pre-treatment B can protect rat testis against CP-induced testicular damage owing to its anti-lipid per oxidation, anti-oxidant and anti-apoptotic properties.

Morphometric measurements of MRI findings in patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common degenerative neurological disorders among elderly people, and is associated with progressive cerebral atrophy. AD is characterized by deterioration of the memory, difficulties with language, alterations in behavior and dysfunction in daily activities. OBJECTIVES: The purpose of the present study was to measure the total volumes of different parts of the brain of AD patients and healthy gender-matched controls using Cavalieri's volume estimate method, and to establish some brain ratios. Moreover, the authors wanted to test this method in measuring the volumes of various parts of the brain from MRI scans. MATERIAL AND METHODS: In this study, the MRI scans of 15 right-handed individuals with probable AD and 10 healthy controls were assessed. Cavalieri's volume estimate method was applied to the brain MRI scans to calculate the volumes of various parts of the brain. RESULTS: While the measurements showed a marked increase in the volume of cerebral ventricles and sulci in AD patients in comparison to the gender-matched controls, the volumes of cortical gray matter and cerebral hemispheric brain matter were reduced considerably. However, no significant differences were detected in the volume of the cerebellum + brainstem or intracranium in AD patients. There were also no major variations between male and female values of the two groups. CONCLUSIONS: Overall, cerebral hemisphere and cortical gray matter atrophies were the most remarkable findings among AD patients in the present study; consequently, expansions of both the ventricles and subarachnoid space were formed. Cavalieri's volume estimate method was very efficient in calculating the volumes of different parts of brain from the MRI scans of both groups.

Seleno L-methionine acts on cyclophosphamide-induced kidney toxicity.

The anticancer drug cyclophosphamide (CP) has nephrotoxic effects besides its urotoxicity, which both in turn limit its clinical utility. The nephrotoxicity of CP is less common compared to its urotoxicity, and not much importance has been given for the study of mechanism of CP-induced nephrotoxicity so far. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the kidney injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the nephrotoxicity of CP and the possible protective effects of seleno L-methionine (SLM) on rat kidneys were investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats each. The control group received saline, and other rats were injected with CP (100 mg/kg), SLM (0.5 or 1 mg/kg), or CP + SLM intraperitoneally. Malondialdehyde (MDA) and glutathione (GSH) levels in kidney homogenates of rats were measured, and kidney tissues were examined under the microscope. CP-treated rats showed a depletion of renal GSH levels (28% of control), while CP + SLM-injected rats had GSH values close to the control group. MDA levels increased 36% of control following CP administration, which were significantly decreased after SLM treatment. Furthermore, these biochemical results were supported by microscopical observations. In conclusion, the present study not only points to the therapeutic potential of SLM in CP-induced kidney toxicity but also indicates a significant role for ROS and their relation to kidney dysfunction.

Protective effect of seleno-L-methionine on cyclophosphamide-induced urinary bladder toxicity in rats.

Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. Its urotoxicity may cause dose-limiting side effects like hemorrhagic cystitis. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the urothelial injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the urotoxicity of CP and the possible protective effects of seleno-L: -methionine (SLM) on urinary bladder of rats were investigated. Intraperitoneal (i.p.) administration of 50, 100, or 150 mg/kg CP induced cystitis, in a dose-dependent manner, as manifested by marked congestion, edema and extravasation in rat urinary bladder, a marked desquamative damage to the urothelium, severe inflammation in the lamina propria, focal erosions, and polymorphonuclear (PMN) leukocytes associated with occasional lymphocyte infiltration determined by macroscopic and histopathological examination. In rat urinary bladder tissue, a significant decrease in the endogenous antioxidant compound glutathione, and elevation of lipid peroxidation were also noted. Pretreatment with SLM (0.5 or 1 mg/kg) produced a significant decrease in the bladder edema and caused a marked decrease in vascular congestion and hemorrhage and a profound improvement in the histological structure. Moreover, SLM pretreatment decreased lipid peroxide significantly in urinary bladder tissue, and glutathione content was greatly restored. These results suggest that SLM offers protective effects against CP-induced urinary bladder toxicity and could be used as a protective agent against the drug toxicity.

Hematoprotective effect of seleno-L-methionine on cyclophosphamide toxicity in rats.

Cyclophosphamide (CP) is a widely used antineoplastic drug that causes toxicity in the normal cell due to its metabolites. The major drawback of this drug is an undesirable myelosuppression. Selenium (Se) is a potent nutritional antioxidant that carries out biological effects by its incorporation into selenoproteins, such as glutathione peroxidase (GPx). The possible protective effects of seleno-L-methionine (SLM) against CP-related toxicity of blood cells and bone marrow of rats were investigated in this study. Intraperitoneal (i.p) administration of 50, 100, or 150 mg/kg of CP caused, in a dose-dependent manner, reductions in the number of leukocytes (78, 89, and 92%, respectively), thrombocytes (22, 33, and 52%, respectively), and bone marrow-nucleated cells (72, 90, and 94%, respectively). The groups that had CP treatment alone were killed 3 days after the CP injection. For the groups having CP+SLM, SLM (0.4 or 0.8 mg/kg i.p) administration was started 3 days earlier than the CP administration and continued to the end of the experiment (6 days). On day 4, the animals were weighed again, relative doses of CP were estimated, and CP+SLM was administered together. On day 7, blood samples were collected and bone marrow of animals were resected under anesthesia. The results indicated that treatment of rats within a select dose range of SLM could reduce CP-induced toxicity on blood cells and bone marrow.