Effect of Tacrolimus on Peripheral Nerve Regeneration in Allograft Transplantation: A Light and Electron Microscopic Study.

OBJECTIVES: Peripheral nerve injuries are common in Europe; however, the treatment techniques may lead to disabilities. This study aimed to evaluate the effect of tacrolimus use on the capacity of the epineural sheath graft to improve its regeneration quality in rat sciatic nerves as a treatment option for nerve injuries. MATERIALS AND METHODS: In the experimental process, 30 male Sprague Dawley were used as recipients and 10 Wistar rats were used as donors. Under anesthesia, all rats were operated on to resect the sciatic nerve. The nerve tissue of Wistar rats was used as allograft. In the autograft group, the resected nerve was reversed and sutured, resulting in an epineural sheath graft. For the allograft groups, rats were randomly divided into 2 groups as the tacrolimus-treated group and the nontreated group after allograft transplant. Tacrolimus was administered intramuscularly at 0.1 mg/kg daily for 12 weeks. After the treatment period, rats were killed and evaluated histomorphologically with light and electron microscopy. RESULTS: Histological examination showed no remarkable differences between different regions of the sciatic nerves (distal, middle, and proximal). The axonal density was decreased in the allograft groups compared with the autograft group (P < .001). Results showed that the number of mast cells was increased in the allograft group without tacrolimus treatment (P < .05). Similarly, there was a mild increase in mast cell count in the tacrolimus-treated allograft group. CONCLUSIONS: Our results showed that tacrolimus use in rats with implanted epineural nerve sheath supported recovery in terms of morphological and physiological regeneration of the nerve.

Acute dental pain elevates salivary oxytocin in women: a risk factor during pregnancy.

Irreversible pulpitis is an acute, brief, and painful condition. Oxytocin, cortisol, and secretory immunoglobulin A (sIgA) are released by the body in response to pain and emotional stress. The aim of this study was to investigate the expression of salivary cortisol, sIgA, and oxytocin among patients with irreversible pulpitis. This was an ethically approved case-control study comparing 90 cases of irreversible pulpitis and 40 healthy individuals. Five study groups were established: nonpregnant female pulpitis, pregnant female pulpitis, male pulpitis, healthy (nonpregnant) female control, and healthy male control. Pregnant women in the first trimester were enrolled in the study. Participants received both clinical and radiographic examinations, completed a simple questionnaire related to food intake, habits, and anxiety, and their pain levels were recorded on a visual analog scale in which 0 represented no pain and 10 represented the worst possible pain. Unstimulated saliva samples were collected to measure oxytocin, sIgA, and cortisol levels. Dental pulp specimens were obtained and stained with hematoxylin and eosin to evaluate the agreement between clinical and histologic pulpal diagnoses. The statistical analysis included analysis of variance and Tukey tests. The majority of patients (37%) recorded a score of 8 (severe pain) on the visual analog scale, while a score of 10 (worst possible pain) was recorded only by pregnant women (3%). There was no statistically significant difference among healthy subjects for all salivary samples. Oxytocin levels increased significantly in nonpregnant (P < 0.5) and pregnant (P < 0.001) women with pulpitis. Cortisol (P < 0.01) and sIgA (P < 0.001) levels were significantly elevated only in pregnant women with pulpitis. The results of the present study indicate that acute dental pain during pregnancy can be considered as a pregnancy risk factor because of the resulting elevated oxytocin and cortisol levels.

Astaxanthin alleviates oxidative damage in acute pancreatitis via direct antioxidant mechanisms.

BACKGROUND/AIMS: Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model. MATERIALS AND METHODS: The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed. RESULTS: Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically. CONCLUSION: ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.

Encapsulated melatonin in polycaprolactone (PCL) microparticles as a promising graft material.

Electrospraying assures many advantages with taking less time and costing less relatively to the other conventional particle production methods. In this research, we investigated the encapsulation of melatonin (MEL) hormone in polycaprolactone (PCL) microparticles by using electrospraying method. Morphology analysis of the produced particles completed with Scanning Electron Microscopy (SEM). SEM images demonstrated that micro-particles of 3 wt% PCL solution has the most suitable particle diameter size (2.3 ±â€¯0.64 µm) for melatonin encapsulation. According to the characterization of the particles, electrospraying parameters like optimal collecting distance, the flow rate of the solution and voltage of the system detected as 8 cm, 0.5 ml/h, and 10 kV respectively. For determining the chemical bonds of scaffold Fourier-Transform Infrared Spectroscopy (FTIR) were used and FTIR results showed that melatonin successfully loaded into PCL micro-particles. Drug release kinetics of the melatonin loaded particles indicated that melatonin released with a burst at the beginning and release behavior became sustainable over a period of 8 h with the encapsulation efficiency of about 73%. In addition, both in-vitro and in-vivo studies of the graft materials also completed. Primary human osteoblasts (HOB) cells and female Sprague Dawley rats were used in in-vitro and in-vivo studies. Test results demonstrate cell population, and bone volume of the rats grafted with composites has remarkably increased, this caused remodelling in bone structure. Overall, these findings indicate that encapsulation of melatonin in the PCL particles with electrospray method is optimum for new synthetic graft material.

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats.

The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 µg/mL/d), alendronate (70 µg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 µg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. HIGHLIGHTS: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.