The impact of letrozole on oocyte quality in assisted reproductive technology (ART); a randomized double-blind clinical trial.

OBJECTIVE: To examine the effect of letrozole on oocyte quality and pregnancy outcome in assisted reproductive technology (ART). METHODS: This double blind placebo controlled clinical trial was conducted in Vali-Asr Infertility Center. Infertile women candidate for IVF that underwent antagonist protocol were selected. Eligible women randomly allocated into treatment (letrozole/Let group) and control (placebo) group. Participants received letrozole 5 mg/day or placebo at the time of gonadotropin start until trigger day in the same manner. Number of oocyte retrieved, metaphase II oocyte number, high grade oocyte number (G1), high quality embryo, Chemical and clinical pregnancy rate and OHSS (ovarian hyperstimulation syndrome) rate was recorded. 216 infertile women (104 in letrozole and 112 in the control group) were evaluated. RESULTS: In the Let group estradiol level was significantly lower (p_value < .001) and testosterone significantly higher than in the control group (p_value = .02). The number of retrieved oocytes, MII oocytes, G1 oocytes, and 2PN was significantly lower in the Let group (p < .05). No significant difference was found in the day of stimulation, total gonadotropin dose, OHSS rate, and clinical pregnancy rate between the two groups (p > 0.05). CONCLUSIONS: According to the results, letrozole may reduce oocyte quality and cause poor IVF outcomes as well.

Fabrication and study of curcumin loaded nanoparticles based on folate-chitosan for breast cancer therapy application.

Purpose of this article is developing novel, inexpensive curcumin loaded chitosan nanoparticles with targeting ability. Curcumin loaded folate-modified-chitosan-nanoparticles (NPs) have been synthesized and fabricated via self-assembling process. Chemical structures of modified chains, nanoparticle size in dry and wet state, zeta potential, morphology of NPs, physical state of curcumin in NPs, drug release profile and cytotoxicity of NPs were investigated by FTIR, FE-SEM, DLS and XRD, UV-vis spectrophotometer, and MTT assay against L929 and MCF7 cell lines, respectively. Results show nanoparticle size in dry state varied in range of 119-127nm and curcumin was loaded into nanoparticles with 96.47% efficacy. Drug release studies showed by decreasing pH of release medium from 7.4 to 5, release rate of curcumin from NPs increased, which shows pH responsive capacity of folate-modified chitosan nanoparticles. Cell viability studies confirmed that curcumin loaded NPs have good potential as a drug delivery system for breast cancer therapy.

The healing effect of silicone gel on sciatic nerve injuries in experimental rat.

BACKGROUND: Peripheral nerve repair is often complicated by fibroblastic scar formation, nerve dysfunction, and traumatic neuroma formation. Use of silicone may improve outcomes of these repairs. In this study, we tried to evaluate effectiveness of silicone gel on rats' sciatic nerve repair, axon regeneration and scar formation around and in the nervous tissues. METHODS: This experimental study was performed on 18 rats. They underwent bilateral sciatic nerve dissection. Then, right and left damaged sciatic nerves were sutured. In left side, silicone gel was applied. Two months later, both sides were evaluated regarding to myelin fiber diameter (µm), total fascicular area (mm(2)), axon diameter (µm), myelin thickness (µm), G- ratio (axon diameter/myelin thickness), connective tissue area, ratio of connective tissue area/fascicular area, neuroma and foreign body formation in liver and lungs and spleen reaction. Results of right and left sides were compared. RESULTS: Silicone was significantly more effective in increasing myelin thickness in the side that silicone was applied) than the control side. It was not associated with inflammation, scar formation, granuloma, and neuroma formation. No foreign body reaction occurred in liver, spleen and lungs after silicone application; but axonal regeneration did not improve with after its use. CONCLUSION: According to our findings, it seems that silicone application in the cases with significant complications or in the cases that nerve graft is not possible would be an ideal option.

Injectable scaffold as minimally invasive technique for cartilage tissue engineering: in vitro and in vivo preliminary study.

Cartilage is a tissue with limited repair capacity and also sparse population of cells entrapped within a dense extracellular matrix, therefore, delivery of the cells to site of damaged cartilage can improve its healing potential. Synthetic biomaterials such as poly (d,l-lactide-co-glycolide) (PLGA) have been used as both preformed or injectable scaffolds in tissue engineering in order to carry and keep cells in the site of injury with minimal side effects. The injectable biocompatible polymeric scaffolds can reach to effected area via minimally invasive injection without need to open the joint, less painful approach and also having possibility to fill complicated shape defects. In this study, it was hypothesized that PLGA solved in n-methyl pyrrolidine (NMP) may act as a proper carrier for cell delivery to the site of the damage and also supports their growth. The results of in vitro assays including both live/dead (AO/PI) and MTT showed the majority of the cells were remained alive between 3 up to 21 days, respectively. The amount of resealed GAG from the mesenchymal stem cells (MSCs) which were in contact with both PLGA and alginate constructs (used as control) indicated that for day 7 MSCs in contact with alginate secreted more GAG (3.45 ± 0.453 µg/mL for alginate and 2.36 ± 0.422 µg/mL for PLGA matrices), but at longer times (21 days) cells in contact with PLGA elicited more GAG (6.26 ± 0.968 µg/mL for alginate and 8.47 ± 0.871 µg/mL for the PLGA matrices). Sol-gel systems comprising PLGA, NMP, and cells as well as alginate/cells were subcutaneously injected into four nude mice (each mouse had three injection sites). PLGA/NMP was solidify immediately and formed an interconnecting 3-D porous structure that allowed body fluid to penetrate through them. In vivo evaluation showed that PLGA/NMP scaffolds could support injected cells as a fibrocartilage tissue was formed after 6 months of injection. We found that PLGA/NMP system might be a proper minimally invasive therapeutics option for cartilage repair.

A novel approach for repairing of intestinal fistula using chitosan hydrogel.

Intestinal fistula is associated with high morbidity and difficult to manage. Many fistulas require surgical treatment, which usually consists of segmental resection. In this study, using a rat model, the effectiveness of chitosan hydrogel as an intestinal fistula repair agent was investigated. Twenty rats underwent laparotomy under general anesthesia. The antimesentric portion of the cecum was incised (1 cm) and sutured to the abdominal wall. Chitosan hydrogel was applied daily to the fistula until it was completely closed. Blood samples taken from all animals were analyzed. After sacrifice, the cecum was removed and histopathologic investigation was performed. Spontaneous closure of the intestinal fistula was observed in all animals for both the control and chitosan hydrogel groups. Healing in the chitosan hydrogel group healing was faster than that in the control group. Blood analysis revealed significant differences between the chitosan hydrogel and control groups with regard to the total protein, albumin, total cholesterol and HDL before the surgery versus that on the day of sacrifice. Pathologic investigation also showed greater healing in the chitosan hydrogel group than the control group. This preliminary study showed the potential of chitosan hydrogel for repair of intestinal fistula. However further studies must be performed before we can approve testing chitosan hydrogel for intestinal fistula repair in humans.

ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap.

Ischemic preconditioning (IPC) and pharmacologic preconditioning by morphine and adenosine may significantly decrease the amount of necrosis in rat random pattern skin flaps. We examined the role of ATP-sensitive potassium channels (K(ATP) channels) in mediating these protective phenomenon by using glibenclamide a nonspecific blocker of these channels. We also investigated whether administration of diazoxide an opener of the K(ATP) channels could mimic the same protective effect. Ninety male Sprague-Dawley rats were randomly divided into either control or treatment groups (n = 6 each). Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, 1 mL of morphine (5 mg/flap), adenosine (0.5 mg/flap), or different doses of diazoxide (0.5, 1, 5, and 15 mg/flap) were administered locally in the cranial half of the flap, respectively. One milliliter of saline was locally injected in the control group. In the IPC group, 1 hour after local saline injection the cranial pedicle was clamped for 20 minutes, and then 40 minutes' reperfusion was performed. In another experiment, 0.3 mg/kg of glibenclamide was injected intraperitoneally 30 minutes before local administration of saline or drug in ischemic or pharmacologic preconditioning groups. Regardless of the group, all flaps were cut at the cranial side 2 hours after elevation and were sutured back. Flap survival area was evaluated on the seventh postoperative day. IPC and pharmacologic preconditioning with morphine, adenosine, and diazoxide (in higher doses; 1, 5, and 15 mg/flap) improved survival area compared with the control group. Glibenclamide abolished their protective effect. K(ATP) channels may have a key role in anti-ischemic properties of IPC and pharmacologic preconditioning.