Investigation of the Efficacy of Bevacizumab Treatment in An Experimental Rat Model of Chronic Subdural Hematoma.

INTRODUCTION: Chronic subdural hematoma (cSDH), a condition that develops over time, is characterized by inflammation, angiogenesis, and membrane development. As the population's average age increases, the incidence of cSDH is expected to grow. While surgery is the primary treatment technique, medicinal therapy options are being explored for high-risk patients. Currently, the most effective therapy combination is dexamethasone (Dex) and atorvastatin (Ato); however, it is associated with an increased risk of mortality. This study explored the effects of bevacizumab (Bev), a VEGF antagonist, on cSDH. MATERIALS AND METHODS: Ninety-five rats were divided into four groups (n = 18): sham, control hematoma, Dex-Ato, and Bev. Two separate autologous blood injections into the subdural space were used as the model. Weight was monitored for all rats to assess changes in their overall health. The control group was given i.p. saline, the Dex-Ato treatment was given by gavage, and the Bev treatment was given i.p. On 7th, 14th and 21st days six rats from each group were sacrificed and analyzed, while 23 rats were excluded from the experiment. RESULTS: The maximum immunological response to cSDH was observed on day 14. Hematoma volume decreased over time in all groups. Dex-Ato and Bev were both found effective, while Dex-Ato caused weight loss. CONCLUSION: Bev had similar effects to the Dex-Ato group and was well tolerated by rats. Given that cSDH is a disease of the elderly and vulnerable populations, Bev may be a viable alternative that can shed light on the disease's etiology for future research.

Histopathological Evaluation of Bipolar and Microneedle Radiofrequency Energy on the Skin and Fat of the Abdominal Region of the Rat.

BACKGROUND: Radiofrequency (RF)-based devices are frequently used in plastic surgeries. In the current literature, no comparative experimental study has demonstrated the histological and immunological effects of these devices that are frequently used in the facial area. In this study, we investigated the histological and immunological effects of Bipolar RF (BodyTite) and Microneedle RF (Morpheus 8) devices in the rat abdominal region. METHODS: 24 rats were used in this study. The rats were divided into four groups: group I: Control. In group II, BodyTite was applied to the abdominal region. Group III: Morpheus 8 was applied to the abdominal region. Group IV: Both Morpheus 8 and BodyTite were applied to the abdominal region. The histological and immunological features of the tissues in the groups were examined using light microscopy, and collagen formation and desmosome structures were examined using light microscopy. RESULTS: Collagens in Group II were thinner than those in the other groups. In addition, there were fewer vessels in Group III. The collagen scores were as follows: Group II:1.5; Group III:2; and Group IV:3. The VEGF scores were II:2.5, group III:2, and IV:3, respectively. The collagen score in group II and VEGF score in group III were significantly lower than those in the other groups. In addition, the bonds between desmosomes in group III were found to be looser using electron microscopy. Collagen morphology in groups III and IV was found to be similar to that in group I. CONCLUSIONS: The conclusion of comparison RF-based devices increased tissue regeneration and healing. CLINICAL RELEVANCE STATEMENT: The use of radiofrequency devices has increased in plastic surgery practice over the past two decades, particularly emerging as a unique alternative for non-surgical candidates. There is a lack of experimental studies concerning these commonly used devices in clinical practice.

Intramuscular nerve distribution of the sternocleidomastoid muscle for the botulinum toxin injection.

PURPOSE: The aim of this study is to define the intramuscular nerve distribution of the sternocleidomastoid muscle (SCM) and the innervation zones (IZ) to describe the optimal botulinum toxin injection sites. METHODS: The cricoid cartilage (CC), laryngeal prominence (LP) and hyoid bone (HB) and angle of mandible (AM) were determined as landmarks. The length of the muscles were measured between the sternoclavicular joint and tip of the mastoid process. SCM was evaluated in two parts as anterior and posterior divided by the line where the length of the muscle was measured. Measurements were made to define the relationships of the SCM with common carotid artery, internal and external jugular veins. IZ were described according to these vessels. Afterwards, Modified Sihler's staining technique was applied to expose the intramuscular nerve distribution. RESULTS: The average length of SCM was 160,1 mm. Motor entry point of the accessory nerve fibers were between the AM-HB lines, in the range of 30-40% of the muscle length, and in the posterior part of the muscles. IZ were between the HB-CC lines in the anterior and posterior part. When this interval was examined according to the vessels, the optimal injection sites were between the LP-CC lines. CONCLUSIONS: This study shows the position of the intramuscular nerve fibers endings of the SCM according to the chosen landmarks and the relationship of the IZ with the vessels to prevent complications. These results can be used as a guide for safe and effective botulinum toxin injections with optimal quantities.

The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.

Evaluation of graphene oxide-doped poly-lactic-co-glycolic acid (GO-PLGA) nanofiber absorbable plates and titanium plates for bone stability and healing in mandibular corpus fractures: An experimental study.

BACKGROUND: Open reduction with internal fixation is the preferred treatment option for displaced facial bone fractures. The superior mechanical properties of metallic plates have made them the most widely used material in existing bone fixation systems. However, after the healing period, these permanent plates can cause various problems. Alternative bioresorbable materials are being investigated to reduce these potential problems. This study compares bone stability and viability by using graphene oxide (GO)-doped poly-lactic-co-glycolic acid (PLGA) nanofiber plates and titanium plates for rats with fractured mandibles. MATERIALS AND METHODS: The study included 20 male Sprague-Dawley rats, divided into four groups: a control group (Group I), a mandibular fracture group with no additional application (Group II), a mandibular fracture group repaired with titanium plates (Group III), and a mandibular fracture group repaired with GO-PLGA plates (Group IV). After 2 months, all of the rats were euthanized. A bone compression test was performed to assess bone stability, and a histological examination was performed to evaluate bone healing. RESULTS: The osteocyte lacunae, Haversian ducts, canaliculi, and vascular structures of Group IV were found to be higher. In the compression test, vertical compression was applied to the bone axis, and Group IV had a higher maximum load and maximum stretch. GO-PLGA plates were found to be statistically superior to titanium plates in terms of both bone stability and bone healing (p < 0.05). CONCLUSIONS: The present study found that GO-PLGA plates are more effective than titanium plates for the treatment of mandibular corpus fractures.

Effects of ozone treatment to the levels of neurodegeneration biomarkers after rotenone induced rat model of Parkinson's disease.

The study investigated the effects of ozone treatment on the neurodegeneration of stereotaxic rotenone-induced parkinson's disease (PD) model. The model was confirmed using the apomorphine rotation test. α-synuclein, amyloid-ß, Tau, phosphorylated Tau, as well as tyrosine hydroxylase(+), nNOS(+), and glial cell counts were used to evaluate neurodegeneration in the substantia nigra pars compacta and ventral tegmental area. The experiment involved 48 Sprague-Dawley rats divided into four groups: dimethyl sulfoxide (DMSO), DMSO with ozone (O), DMSO/rotenone (R), and D/R/O. Ozone treatment significantly improved tissue α-synuclein level and TH+, nNOS+, and glial cell counts compared to the rotenone-only group. The study suggests that ozone treatment may have beneficial effects on PD biomarkers in the rotenone model. Further studies on ozone dosage, duration, and administration methods in humans could provide more evidence for its potential use in Parkinson's disease treatment.

Histological and Immunological Evaluation of the Osteogenic Effects of Compact Bone-Delivered Stem Cell on Spongiosis Bone in the Rat Zygomatic Arch Defect Model.

BACKGROUND: In stem cell applications, apart from bone marrow and adipose tissue, compact bone is also used as an alternative. However, studies on this subject are limited. In our study, we investigated the effect of stem cell derived from compact bone on rat zygomatic arch defect. METHODS: Fifteen rats were included in the study. Five rats were killed to obtain stem cells before the experiment. The rats were divided into 2 groups with 5 rats each. In group 1, compact bone-derived stem cell was applied. In group 2, adipose tissue-derived stem cell was applied. Right zygomatic arch defect was created in rats in both groups. Zygomatic bones were decellularized by cryosurgery. Stem cells were transferred to zygomatic bones. The number of stem cells, stem cell differentiation, and superficial markers obtained from the groups were examined. Histologically, cell structure, osteocyte count and osteopontin scores, elemental composition of the groups, percentages of resemblance to intact bone, osteocytes numbers, and cells were examined by electron microscopy of the bones in the groups after killing. RESULTS: The number of stem cells administered to the groups was 5 × 107 and 3.2 × 107 for group 1 and group 2, respectively (P > 0.05). Histologically, the morphology of the cells in group 1 was found to be healthier than group 2. The number of osteocytes was 97.56 ± 15.4 and 132.93 ± 10.8 in group 1 and group 2, respectively (P < 0.05). The osteopontin score was 3.47 ± 0.73 and 65 ± 0.64 in group 1 and group 2, respectively (P < 0.05). In the electron microscope examination, the morphologies of the cells in group 1 were seen more normal. The Ca/P ratio of the groups was 1.51 and 1.59 in group 1 and group 2, respectively (P > 0.05). Osteocyte counts were 10.7 ± 2.8 and 6.1 ± 1.2 in group 1 and group 2, respectively (P < 0.05). Morphological similarity percentages to normal bone were 88.4% and 79.6% in group 1 and group 2, respectively (P > 0.05). CONCLUSION: Stem cells obtained from compact bone gave positive results in zygomatic arch defect. This method can also be used as an alternative in stem cell applications.

Evaluation of In Vivo Biological Activity Profiles of Isoindole-1,3-dione Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies.

The anticancer activity of N-benzylisoindole-1,3-dione derivatives was evaluated against adenocarcinoma (A549-Luc). First, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide activity assay studies of two isoindole-1,3-dione derivatives were performed against A549 cell lines. Both compounds showed inhibitory effects on the viability of A549 cells. Then, we explored the potential of these compounds as active ingredients by in vivo studies. Nude mice were given A549-luc lung cancer cells, and tumor growth was induced with a xenograft model. Then, nude mice were divided into three groups: the control group, compound 3 group, and compound 4 group. After application of each compound to the mice, tumor sizes, their survival, and weight were determined for 60 days. Furthermore, toxicological studies were performed to examine the effects of the drugs in mice. In addition to toxicological studies, histopathological analyses of organs taken from mice were performed, and the results were evaluated. The obtained results showed that both N-benzylisoindole derivatives are potential anticancer agents.

The BDNF-TrkB signaling pathway is partially involved in the neuroprotective effects of hydrogen sulfide in Parkinson's disease.

Recent studies have demonstrated that hydrogen sulfide (H2S) has a neuroprotective effect in neurodegenerative diseases. It is possible that this effect is supported by brain-derived neurotrophic factor (BDNF). Our aim is to examine the effects of H2S on neural damage in Parkinson's disease (PD) and to reveal the role of the BDNF-TrkB pathway in its possible effect. PD model was created with 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 breed male mice were randomly divided into six groups: control, K252a, MPTP, MPTP + K252a, MPTP + NaHS, and MPTP + NaHS + K252a. TrkB receptor antagonist K252a and sodium hydrosulfide (NaHS) as a H2S donor were administered intraperitoneally. An increase was observed in the motor behavior tests in MPTP group, but NaHS treatment shortened the time spent on the balance beam and pole tests. It was also noticed that the BDNF-pathway played a role in the shortening of this period. Mice that received NaHS were found to have less MPTP-induced cellular damage. A positive effect of BDNF was also detected in the protection of these neurons. BDNF levels in the SN were significantly increased in MPTP group, compared to control group. Tissue CBS levels decreased in the groups that received K252a, compared to MPTP group. The findings of the present study display that the BDNF-TrkB pathway partially plays a role in the protective effect of H2S in the experimental mouse model of PD. This effect is probably due to changes in intracellular signaling pathways, rather than TrkB receptor expression.

Effects of vitrification solution supplemented with platelet-rich plasma in rat ovarian tissue cryopreservation.

Background/aim: The subject of this study was to investigate the utility of platelet-rich plasma (PRP) in the cryopreservation process to reduce cryodamage and increase tissue viability. Materials and methods: Twenty-one female Wistar rats were randomly allocated to three groups. In Group 1 (G1), rats were not subjected to vitrification (n = 7). Group 2 (G2) was the vitrification group in which PRP was added to the basic vitrification solution (n = 7). Group 3 (G3) was the vitrification group in which fetal bovine serum was added to the basic vitrification solution (n = 7). Warmed tissues were evaluated with histochemical (HC) and immunohistochemical (IHC) staining, the TUNEL method, immunofluorescence (IF) staining, and biochemical analyses. Results: The percentages of IHC staining, TUNEL method positivity, and IF staining were significantly higher in G2 compared to both G1 and G3 (P < 0.05). G2 ovaries exhibited a significant increase in both malondialdehyde and catalase values in comparison to G1 (P < 0.05). In HC staining, degenerations in primary and secondary follicles and in ovarian tissue were more common in the PRP-supplemented group. The calcium used in PRP activation was suspected to have increased the degeneration and prevented the possible positive effects of PRP. Conclusion: To the best of our knowledge, PRP-supplemented vitrification solution was used for the first time in the literature in this study in whole rat ovarian tissue vitrification. If PRP is to be used as a component in vitrification solution for rat ovarian tissue, the use of lower amounts of calcium or different methods in PRP activation, or the use of nonactivated PRP, should be considered from the beginning.

An intravenous application of magnetic nanoparticles for osteomyelitis treatment: An efficient alternative.

The infection of bone and bone marrow is called osteomyelitis. Treatment is difficult since antibiotics can not reach with enough concentration to the infected area. For the first time in this study, we have developed gentamicin-loaded magnetic gelatin nanoparticles (GMGNPs) for nanocarrier-mediated and magnetically targeted osteomyelitis therapy. Gelatin, genipin, and magnetite were used for preparation of that novel carrier system due to their biodegradable and biocompatible properties. Cross-linking degree of gelatin nanoparticles, concentration of magnetite nanoparticles, and adsorbed drug amount were optimized. Furthermore, nanoparticles were characterized and the drug release profile was determined. The osteomyelitis model was constituted in the proximal tibia of rats. The therapeutic potential of GMGNPs on rats was monitored via X-Ray radiography and hematological and histopathological analyses were performed. According to the results, 110.3 ± 8.2 µg gentamicin/mg GMGNPs were used, hydrodynamic size was measured as 253.7 ± 11.8 nm, and GMGNPs have controlled drug release profile. Based on in vivo and ex vivo studies, after six doses of GMGNPs treatment, abscess began to heal and the integrity of periost and bone began to reconstruct. In conclusion, it can be suggested that GMGNPs could provide efficient therapy for osteomyelitis.

A surgical and anatomo-histological study on Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA).

BACKGROUND: The number of TOETVA surgeries has increased worldwide but the anatomical passage of trocars is not clearly defined. We aimed to define detailed surgical anatomical passage of the trocars in cadavers. The incisions in oral vestibule, anatomical pathways of trocars, affected mimetic muscles, neurovascular relations of trocars and histological correlation of surgical anatomy were investigated. METHODS: Four cadavers and 6 six patient oral vestibules were used. The locations of optimised vestibular incisions were measured photogrammetrically. Initial steps of TOETVA surgery were performed on cadavers according to those optimal incisions. TOETVA preformed cadavers dissected to determine anatomical passages of the trocars. Afterwards, flap of lower lip and chin were zoned by software appropriate to the trocars routes. Histological analyses of the zones were made in correlation with dissections. RESULTS: Mimetic muscles associated with median (MT) and lateral trocars (LT) are orbicularis oris, mentalis, depressor anguli oris, depressor labii inferioris and platysma muscles. Trocars affect mimetic muscles in the perioral, chin and submental regions in different ways. The risk of mental nerve injury by MT is low. LT pass through the DLI muscle. The transmission of LT to the subplatysmal plane in the submental regions can be in two different ways. The arterial injury risk is higher with LT than the MT. CONCLUSIONS: The surgical anatomy of the perioral, chin and submental regions for the initial TOETVA steps has been defined. Detailed surgical anatomical passages of the MT and LT were determined. Anatomical pattern to reach subplatysmal plane are presented. Mimetic muscles effected by trocars were determined. Endocrine surgeons should know the anatomical passage of TOETVA trocars.

A new approach to prevent ischemia/reperfusion injury in a rat model: remote ischemic conditioning.

PURPOSE: To evaluate the effect of remote ischemic conditioning (RIC) on ovarian ischemia/reperfusion injury in a rat model. METHODS: A total of 36 Wistar albino rats with a body weight of 220-250 g were used for this study. Right adnexal torsion was performed for 180 min, and at the end of the period, the adnex was released and the abdomen was reclosed for 180 min for reperfusion. Torsion and detorsion procedures were applied to all rats except group 1 (sham, control). The right lower extremity was tied to perform remote tissue ischemia in groups 3, 4, 5, and 6. The goal of the procedure, which was purplish discoloration and pulselessness of the extremity, was maintained. After 5 min of ischemia, reperfusion was achieved for 5 min. Repeating this procedure 3 times was defined as hypoxia attacks (RIC). Retrieved ovaries were examined for tissue injury with biochemical, histopathologic, and immunohistochemical analysis. RESULTS: Unlike the control group, vascular congestion, hemorrhage, edema, and inflammatory cell infiltration were observed in group 2 (only I/R [ischemia/reperfusion]). In groups 3 (I/R + RIC), 4 (I/R + RIC), 5 (I/R + RIC), and 6 (I/R + RIC), edema and inflammatory cell infiltration were not observed. However, vascular congestion and hemorrhage that were detected in these groups were higher than in group 1 (Control) and less than in group 2 (I/R). The Caspase-3 Index was found to be increased in all groups compared to group 1 (P < .001). However, the increase in the RIC-performed groups was significantly less than in group 2. The apoptotic index, which was determined by the TUNEL, was also found to be increased in all groups compared to group 1 (P < .001). When the comparison was made in relation to group 2, the decrease of AI in RIC-performed groups was statistically significant, except the decrease in group 6 (P = .29). CONCLUSIONS: It is not clinically conceivable to prepare the tissue for pre-ischemia in ovarian torsion. However, the RIC application, which will be initiated if torsion is suspected when arrangements are made for surgery, might be a simple, effective, and inexpensive approach to prevent I/R injury in the clinic.

Changes in tissue gadolinium biodistribution measured in an animal model exposed to four chelating agents.

PURPOSE: This study investigated the potential to reduce gadolinium levels in rodents after repetitive IV Gadodiamide administration using several chelating agents. MATERIALS AND METHODS: The following six groups of rats were studied. Group 1: Control; Group 2: Gadodiamide only; Group 3: Meso-2,3-Dimercaptosuccinic acid (DMSA) + Gadodiamide; Group 4: N-Acetyl-L-cysteine (NAC) + Gadodiamide; Group 5: Coriandrum sativum extract + Gadodiamide; and Group 6: Deferoxamine + Gadodiamide. Brain, kidney, and blood samples were evaluated via inductively coupled plasma mass spectrometry. The brain was also evaluated histologically. RESULTS: Kidney gadolinium levels in Groups 4 and 5 were approximately double that of Group 2 (p = 0.033 for each). There was almost no calcification in rat hippocampus for Group 4 rodents when compared with Groups 2, 3, 5 and 6. CONCLUSION: Our preliminary study shows that excretion to the kidney has a higher propensity in NAC and Coriandrum sativum groups. It may be possible to change the distribution of gadolinium by administrating several agents. NAC may lower Gadodiamide-induced mineralization in rat hippocampus.

Clinical Use and Patentability of Cord Blood.

BACKGROUND: The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. OBJECTIVE: Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and autologous usage, the most important disadvantage is that the number of cells is insufficient in adults. CONCLUSION: Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use.