ZIF-8 as a pH-Responsive Nanoplatform for 5-Fluorouracil Delivery in the Chemotherapy of Oral Squamous Cell Carcinoma.

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 µg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 µg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.

Effects of Zeolite as a Drug Delivery System on Cancer Therapy: A Systematic Review.

Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer drugs. At present, there is no other systematic review that assesses the potency of zeolites/ZIFs as anticancer drug carriers. Due to the porous nature and inherent pH-sensitive properties of zeolites/ZIFs, the compounds can entrap and selectively release anticancer drugs into the acidic tumor microenvironment. Therefore, it is valuable to provide a comprehensive overview of available evidence on the topic to identify the benefits of the compound as well as potential gaps in knowledge. The purpose of this study was to evaluate the potential therapeutic applications of zeolites/ZIFs as drug delivery systems delivering doxorubicin (DOX), 5-fluorouracil (5-FU), curcumin, cisplatin, and miR-34a. Following PRISMA guidelines, an exhaustive search of PubMed, Scopus, Embase, and Web of Science was conducted. No language or time limitations were used up to 25th August 2021. Only full text articles were selected that pertained to the usage of zeolites/ZIFs in delivering anticancer drugs. Initially, 1279 studies were identified, of which 572 duplicate records were excluded. After screening for the title, abstract, and full texts, 53 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for the 53 articles. The included studies suggest that anticancer drug-incorporated zeolites/ZIFs can be used as alternative treatment options to enhance the efficacy of cancer treatment by mitigating the drawbacks of drugs under conventional treatment.

Effects of Glycogen Synthase Kinase Inhibitor on Glioblastoma Multiforme Cell Line via Apoptosis and Cell Signaling Pathways.

AIM: To investigate the apoptotic and molecular effects of glycogen synthase kinase-3 (GSK-3) in glioblastoma multiforme (GBM). MATERIAL AND METHODS: Human primary glioblastoma cell line (U-87 MG) and the human fetal glial cell line (SVGp12) were used. The cells were exposed to the different doses of GSK inhibitor for 24, 48 and 72 hours. Induction of apoptosis was assessed by DNA fragmentation (TUNEL) assay. EGFR and NF-kB expression was evaluated by immunofluorescence analyses. RESULTS: GSK-3 inhibitor IX induced cytotoxicity and apoptosis in dose-dependent manner in GBM cells. Our results indicated that GSK-3 inhibitor IX induces apoptosis, resulting in a significant decrease in the expression of NF-kB and EGF. CONCLUSION: Inhibition through GSK-3 has been found promising in creating therapeutic management of GBM cells. Proliferation, differentiation, cell cycle regulation, and apoptosis are mechanisms that must be interpreted as a whole. Components associated with EGFR, NF-kB, and apoptosis affect the mechanism solely and collectively. Our collective data suggest that GSK-3 inhibitor IX inhibited cellular proliferation and induced apoptotic events by modulating EGFR and NF-kB expression in GBM cells. GSK-3 inhibition holds promise for the development of new approaches for the therapeutic management of GBM cells.

Does Decompressive Duraplasty Have a Neuroprotective Effect on Spinal Trauma?: An Experimental Study.

BACKGROUND: Spinal cord injury (SCI) may result in neuromotor, sensory, and autonomic function damages. Edema because of spinal cord trauma can reach serious dimensions. The aim of this study was to histologically evaluate the effects of duraplasty on neural tissues. METHODS: Twenty-eight Wistar rats were randomly divided into 4 experimental groups: group 1 received laminectomy without SCI (sham); group 2 received laminectomy and SCI with the weight drop method; group 3 received laminectomy, SCI, and duraplasty within the first 6-8 hours of SCI; and group 4 received laminectomy, SCI, and duraplasty after 24 hours of SCI. The neurologic functions of the rats were tested periodically. All animals were euthanized 28 days after the surgery. Histopathologic and immunohistochemical evaluations were performed, and Kruskal-Wallis tests were used for statistical comparison of data between the groups. RESULTS: There was no significant difference in the Tarlov examination scores from different time points between the groups. The number of neurons stained with nuclear factor kappa beta was higher in group 3 than groups 1 and 4. The number of neurons stained with terminal deoxynucleotidyl transferase dUTP nick-end labeling was higher in group 2 than group 3. CONCLUSIONS: Decompressive laminectomy is a procedure frequently used in spinal trauma surgery. However, it is often unclear whether the decompression is fully adequate. Our results will aid the development of further studies regarding the reliability of duraplasty in the treatment of SCI.

How Safe is the Use of Intrathecal Fluorescein? An Experimental Study.

AIM: To investigate the effects of fluorescein-sodium on neural tissues. MATERIAL AND METHODS: Twenty-one Wistar rats were randomly divided into three experimental groups: control (group 1) and fluorescein-sodium groups with different doses (groups 2 and 3). In the control group, craniectomy following with durotomy was performed with the help of a loupe microscope, and a dry sponge was overlayed to the brain tissue. In the study groups, the open dura was covered with a sponge soaked with 0.02 mg (group 2) and with 0.2 mg (group 3) fluorescein sodium following craniectomy. Three weeks postoperatively, rats were sacrificed for the histopathologic evaluations. RESULTS: Fluorescein-induced apoptosis occurs in a dose-dependent manner in rats' neurons. It was determined that neuron and neuroglial cell TUNEL staining was statistically different among the three groups (p < 0.001). Our results indicated that fluorescein induces apoptosis, resulting in increased nuclear factor kappa beta (NF-kß) expression in a dose-dependent manner. CONCLUSION: Fluorescein sodium is used frequently during surgery for CSF fistulas. However, information in the literature about its safety is insufficient. Our study holds promise for the development of new studies on the reliability of this agent.

Superficial Siderosis of the Central Nervous System Due to Recurrent Surgeries of the Thoracic Spine: A Rare Case.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare condition caused by hemosiderin deposition in the subpial layers of the brain and spinal cord. Surgical complications are the primary factor for occurrence of secondary SS. We present a case of SS with an identified bleeding origin in the thoracic spine. CASE DESCRIPTION: A 58-year-old female patient experienced 9 months of continuous progressive dizziness, difficulty with mobilization, drop attacks, and lack of hearing. The patient also had an extensive history of thoracic spinal surgeries. She came to the hospital with gait imbalance. Gradient echo (GE) magnetic resonance imaging (MRI) confirmed hemosiderin deposition along the cerebellar folia and vermis. GE sequences are preferable in this diagnosis, because of higher sensitivity, and for detecting characteristic T2 hypointensity. The dural defect was repaired with an artificial dural patch in thoracal operation area. Clinical findings, imaging studies, intraoperative findings, and literature information are presented. CONCLUSIONS: Performance of an open neurosurgical procedure to repair a dural defect in the presence of MRI confirmed that superficial siderosis is an optimal method and a crucial step to ensure the safe resolution of the condition and to break the circle of emergency admissions of a patient with a dural defect and a history of multiple spinal surgeries.

Recurrent Osteoma Overlying a Methylmethacrylate Bone Cement Cranioplasty: A Rare Case.

Osteomas are generally benign tumors of the skull that affect all age groups and are diagnosed in the fourth or fifth decade of life, and are rare in childhood. Surgical resection is curative and malignant transformation is very rare. A 12-yearboy who had undergone a craniotomy for resection of a parietal osteoma four years ago, followed by a cranioplasty with methylmethacrylate bone cement, presented to our clinic with an expanding mass overlying the cranioplasty. Upon reoperation, the mass was totally excised, and the parietal cranial defect was repaired using methylmethacrylate bone cement. On histologic examination, the mass was found to be a recurrent osteoma overlying the methylmethacrylate bone cement. In this report, we discuss the etiologies of recurrence of osteoma and treatment options of these rare cases. We believe that this recurrence resulted from contamination of the surgical area and cranioplasty materials with osteoma material. Extensive washing of the cranioplasty materials and perioperative area may prevent recurrence of such tumors.

Neurological recovery after traumatic Cauda Equina syndrome due to glass fragments: An unusual case.

Penetrating spinal injuries with foreign bodies are exceedingly rare. To date, pathological problems due to glass fragments in the spinal canal have rarely been reported. In this report, the case presenting with a back laceration, leg pain, and leg weakness was found to have glass frag-ments in the spinal canal at the L2-L3 level by lumbar computed tomography and magnetic resonance imaging. After L2 total laminectomy and retrieval of the glass fragments, the dura was re-paired. The patient was discharged from the hospital after complete neurological recovery. In cases of spinal canal injuries due to foreign bodies, early operative decompression of the neural elements is the treatment of choice. Patients with Cauda Equina syndrome due to glass fragments have a good prognosis for functional recovery.

Surface characteristics of bioactive Ti fabricated by chemical treatment for cartilaginous-integration.

Artificial hip joints are generally expected to fail due to wear after approximately 15years and then have to be replaced by revision surgery. If articular cartilage can be integrated onto the articular surfaces of artificial joints in the same way as osseo-integration of titanium dental implants, the wear of joint implants may be reduced or prevented. However, very few studies have focused on the relationship between Ti surface and cartilage. To explore the possibility of cartilaginous-integration, we fabricated chemically treated Ti surfaces with H2O2/HCl, collagen type II and SBF, respectively. Then, we evaluated surface characteristics of the prepared Ti samples and assessed the cartilage formation by culturing chondrocytes on the Ti samples. When oxidized Ti was immersed in SBF for 7days, apatite was formed on the Ti surface. The surface characteristics of Ti indicated that the wettability was increased by all chemical treatments compared to untreated Ti, and that H2O2/HCl treated surface had significantly higher roughness compared to the other three groups. Chondrocytes produced significantly more cartilage matrix on all chemically treated Ti surfaces compared to untreated Ti. Thus, to realize cartilaginous-integration and to prevent wear of the implants in joints, application of bioactive Ti formed by chemical treatment would be a promising and effective strategy to improve durability of joint replacement.

Primary spinal epidural Hodgkin's lymphoma.

Primary spinal epidural Hodgkin's lymphoma is very rare. We will discuss the clinical features and treatment of primary spinal epidural Hodgkin's lymphoma. In this paper, a 30-year-old male patient who presented with spinal epidural tumor at the T9-11 level is reported. Subtotal resection of the tumor was performed and the histological examination of the tumor specimen revealed Hodgkin's lymphoma. All other examinations were negative for an occult disease. Six courses of chemotheraphy containing adriamycin, bleomycin, vinblastine and dacarbazine were given to the patient. Surgery is the first therapeutic approach in malignancies compressing the spinal cord. Hodgkin's lymphoma is a very chemo- and radio-sensitive tumor. The indications for surgery were reduced and limited to laminectomy or even biopsy only, leaving the major role to chemo- and radiotheraphy.

Neurotoxic effect of povidone-iodine on the rat spine using a laminectomy-durotomy model.

OBJECTIVE: The efficacy and safety of povidone-iodine in wound dressing and irrigation of some operative cavities were established by many in vitro and in vivo experimental reports and clinical series. However, its use in defective tissue in neural structures has not been confirmed yet. The aim of the present study was to histopathologically investigate its effect on neural tissues when applied on the upper side of defective dura. METHODS: Wistar rats were randomly divided into two experimental groups: control and povidone-iodine groups. In the control group, durotomy was performed following laminectomy, and the spinal cord was covered with a dry sponge. In the study group, the same procedure was performed, but open duras were covered with a sponge that had been wetted with 0.1 % povidone-iodine solution. Three weeks after surgery, all experimental animals were sacrificed, and histopathological evaluations were conducted. RESULTS: Myelin changes were absent or minimal in all cases of the control group but were present as markedly increased myelin degeneration in nearly all cases in the study group. Axonal degeneration and hypoxic neuronal damage were absent in the control group, whereas they were marked in half of the study group. No statistically significant differences were established in Schwann cell proliferation, venous congestion, and lymphocytic proliferation between the two groups. CONCLUSIONS: Based on the present study, 0.1 % povidone-iodine solution cannot be recommended for wound dressing for neural structures such as myelomeningocele cases because of possible damage to underlying neural tissues.

Effects of Levetiracetam on neural tube development and closure of the chick embryos in ovo.

PURPOSE: Effects of Levetiracetam (LEV) within its therapeutic range at a 50 mg/kg dose for the chick embryo in ovo has been studied in order to demonstrate whether LEV would effect neural tube closure at the macroscopic morphology or LEV administered embryos still encounter neuroglial detrimental effects at the histological level. METHODS: Embryos were randomly seperated into control (n = 20) and study (n = 20) groups. The eggshell was windowed at specifically 24 h of incubation, and area underlying the membrane was excised to allow injection with 4.5 µl LEV in the study group, while physiologic saline (0.045 ml) were injected in the control group and each egg were re-incubated for 48 h more. Then, histological and immunohistochemical evaluation of the subjects were done. RESULTS: Macroscopic evaluation revealed immaturity of the placental vessel network in number and width for the study group in comparison to the controls. Defects of migration, decrease in the crista neuralis content, delay of the basal plates structures in the formation of the usual configuration, and delay in the cellular proliferation and the delay of development for the central nervous system were determined in the LEV-exposed group. Immunostaining of S100 proteins in this study has clearly demonstrated increased expression patterns of both neuroglial and neuronal cell populations. Toluidine blue stainings revealed mostly bipolar, differentiating neurons and crista neuralis cells which is concordant with active migration and differentiation. CONCLUSIONS: LEV found that delay in the closure of the neural tube and microcephalic fetuses disturb further morphological, biochemical, and functional development.

Paraganglioma of the cauda equina: a highly vascular tumour.

Paragangliomas uncommonly occur in the cauda equina region. This type of tumour may be misdiagnosed pre-operatively as a neurinoma or an ependymoma. Paragangliomas are highly vascular tumours. We report three patients with paraganglioma of the cauda equina. The first patient had many dilated vessels resembling an arteriovenous malformation, which were seen during surgery. The second patient had a post-operative haemorrhage without any residual tumour. The third patient had a selective angiogram with dense tumour staining.

Atypic geniculate neuralgia: atypic anatomic correlation of cranial nerve roots and AICA.

Geniculate neuralgia is a rare cause of craniofacial pains. The anterior inferior cerebellar artery is the offending vessel which compress nervus intermedius in the patients with typical geniculate neuralgia. We report a patient whose pain was atypical for either geniculate neuralgia and trigeminal neuralgia. At operation the anterior inferior cerebellar artery was coursing with the nerves and was separated. After the decompression the pain resolved immediately.

Bond strengths of three different dentin adhesive systems to sclerotic dentin.

The two-fold aims of this study were: (1) to evaluate the microtensile bond strengths of different adhesive systems to sclerotic and sound palatal dentin; and (2) to observe the respective resin-dentin interfaces. Thirty extracted human incisor teeth were divided into two groups. Group I comprised sclerotic defects in the palatal zone. Group II comprised sound palatal dentin surfaces as control. Each group (n=15) was divided into three subgroups according to dentin adhesive systems: self-etch (Clearfil SE Bond), total-etch (Scotchbond Multi-Purpose Plus), and glass ionomer (Reactmer Bond) adhesive systems. The specimens were subjected to tensile forces. Obtained data were analyzed by two-way ANOVA and post hoc Duncan's test. Fracture sites and resin-dentin interfaces were observed using a light microscope and SEM. With sound dentin, Clearfil SE Bond showed a significantly higher bond strength than the other adhesives (p < 0.05). With sclerotic dentin, although there were no significant differences in bond strength among the adhesives groups (p > 0.05), the bond strength values of Clearfil SE Bond and Scotchbond Multi-Purpose Plus were significantly decreased. On resin-dentin interface observation, different images were presented by different bonding systems.

A rare embryologic variation: anterior communicating artery aneurysm associated with carotid-anterior cerebral artery anastomosis or infraoptic course of the anterior cerebral artery.

Aneurysms of the complex of the anterior cerebral artery are frequently associated with anatomic variations of the circle of Willis. We describe a case of aneurysmal rupture of the anterior communicating artery, a variant of the anterior cerebral artery. The aneurysm appeared to be situated on this vessel proximal to the infered site of the AcoA. Surgery was performed at the 6th day after hemorrhage. The anterior communicating artery aneurysm was clipped. The post operative course was unventful, with complete recovery. In our case, an extremely rare variation of the proximal tract of the anterior cerebral artery, i.e. an infraoptic course of the proximal precommunicating tract under the optic nerve, with the distal A1 tract anterior to the chiasm and positioned between the optic nerves, is presented.

Multiple cerebral hydatid cysts. Report of a case with 24 pieces.

A case of 19 years old female patient with 24 large primary cerebral hydatid cysts, in different localisations is presented. Cysts were removed unruptured by five separate operations in 6 months. The patient was observed to be in good health 1 year after the last operation. This case is the first case presented that contains such high number of cysts to our knowledge. The importance of MRI examination in localizing the cysts and designing the operative plan is emphasized. Interestingly, albendazole, which is an antiparasitic drug, was reported to be ineffective by infectious disease department of our hospital, because of large diameter of the cysts, in this case.