The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model.

INTRODUCTION: This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB). MATERIALS AND METHODS: BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay. RESULTS: Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h. CONCLUSION: In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

OBJECTIVE: This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. METHODS: In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. RESULTS: According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. SIGNIFICANCE: It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Effects of 405-, 532-, 650-, and 940-nm wavelengths of low-level laser therapies on orthodontic tooth movement in rats.

BACKGROUND: Investigating the effects of 405-nm, 532-nm, 650-nm, and 950-nm wavelengths of LLLTs (low-level laser therapies) on the orthodontic tooth movement in rats by using histological and immunohistochemical methods. Forty-five Wistar albino rats were randomly divided into 5 groups: control group (positive control: the left maxillary 1st molar side; negative control: the right maxillary 1st molar side), 405 nm LLLT group (Realpoo), 532 nm LLLT group (Realpoo), 650 nm LLLT group (Realpoo), and 940 nm LLLT group (Biolase). The left maxillary 1st molar teeth of all rats were applied mesially 50-g force. Starting from the 1st day, 48 h intervals, LLLT was applied in continuous wave mode and in contact with the tissue. The application area was approximately 1 cm2. The lasers were performed for 3 min on each surface (buccal, palatal, mesial), totally 9 min (total dose 54 J/cm2). The amount of the molar mesialization, the bone area between the roots, PDL (periodontal ligament) measurements, TRAP (tartrate-resistant acid phosphatase), and ALP (alkaline phosphatase) immunoreactivity intensity were calculated. RESULTS: The amount of the molar mesialization was significantly higher in the 650 nm LLLT group (mean 0.878 ± 0.201 mm; 95% CI (confidence interval) 0.724 and 1.032) than in the groups of positive control (mean 0.467 ± 0.357 mm; 95% CI 0.192 and 0.741) and 405 nm LLLT (mean 0.644 ± 0.261 mm; 95% CI 0.443 and 0.845) (p < 0.001). There were significant differences in the PDL-mesial (p = 0.042) and PDL-distal (p = 0.007) regions between the groups. The immunoreactivity intensity for TRAP-mesial was significantly higher in the positive control group (mean 109,420.33 ± 8769.17; 95% CI 100,217.65 and 118,623.02) than in the 405 nm (mean 91,678.83 ± 7313.39; 95% CI 84,003.9 and 99,353.77) and the 650 nm LLLT (mean 87,169.17 ± 4934.65; 95% CI 81,990.56 and 92,347.77) groups (p = 0.002). There was no statistically significant difference between the groups on immunoreactivity intensity with ALP staining. CONCLUSIONS: The results of this study show that LLLT with 650-nm wavelength increases orthodontic tooth movement more than 405-nm, 532-nm, and 940-nm LLLTs. The 940-nm and 650-nm LLLTs also increase the bone area between the roots by more than 405-nm and 532-nm wavelengths.

The protective role of melatonin against the effects of different doses of caffeine on the fetus.

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated.  Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples.  TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method.  The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P<0,001). No significant difference in samples of the LDC group (P>0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.

Cherry laurel fruit extract counters dimethoate-induced reproductive impairment and testicular apoptosis.

Dimethoate is an organophosphorus pesticide used against agricultural insects, which causes oxidative stress and damage in many organs, including the reproductive ones. Cherry laurel (Laurocerasus officinalis Roem.) fruit is rich in vitamins and phenolic compounds with antioxidant effect. The aim of this study was to investigate how effective its extract would be against dimethoate-induced testis and sperm damage in rats. Sixty animals were divided in six groups of 10. Group 1 (control) received only 1 mL of saline (0.9 % NaCl). Group 2 received 7 mg/kg of dimethoate in 1 mL of saline. Group 3 received 4 mg/kg of extract in 1 mL of saline. Group 4 received the extract 30 min before dimethoate administration. Group 5 received vitamin C (positive control, 100 mg/kg in 1 mL of saline) 30 min before dimethoate administration. Group 6 received only dimethoate for the first four weeks and then a combination of dimethoate and extract for another four weeks. All doses were administered daily by oral gavage. After eight weeks of treatment, the rats were euthanised and their reproductive organs removed. We took their body and reproductive organ weights and evaluated testicular oxidative stress, semen characteristics, sperm DNA damage, testicular apoptosis, and histopathological changes. Dimethoate significantly decreased body and reproductive organ weights, sperm motility and concentration, testicular superoxide dismutase, and glutathione-peroxidase activities and significantly increased lipid peroxidation, abnormal sperm rate, sperm DNA damage, testicular apoptosis, and caused histopathological lesions. Cherry laurel extract significantly countered many dimethoate-induced adverse effects, both as pre- and post-treatment, including reproductive organ weight, semen parameters, oxidant-antioxidant balance, sperm DNA integrity, testicular apoptosis, and histological structure. Our findings clearly suggest that the beneficial effects of the extract are associated with countering oxidative stress, lipid peroxidation in particular.

The effects of gilaburu (Viburnum opulus) juice on experimentally induced Ehrlich ascites tumor in mice.

OBJECTIVE: The aim of study was to investigate anticancer effect of Viburnum opulus (VO) on Ehrlich ascites carcinoma (EAC) bearing mice that treated with different concentrations of VO. MATERIALS AND METHODS: For tumor transplantation; mice were inoculated with 1 × 106 EAC cells intraperitoneally and than divided into five groups (n = 9). Two hours after inoculation; experimental groups were treated daily with VO extract at doses of 1000 mg/kg, 2000 mg/kg, 4000 mg/kg. RESULTS: Extracts obtained from gilaburu juice can have hinder effect on tumor cell growth. CONCLUSION: As far as we known, this is the first study about in vivo antitumoral activity of VOon Ehrlich ascites tumor model, and consequently VO extract exhibited anticancer activity against EAC-bearing mice.