Automated radiosynthesis of mGluR5 PET tracer [18F]FPEB from aryl-chloro precursor and validation for clinical application.

The radioligand [18F]FPEB, used for PET imaging of the brain's metabotropic glutamate receptor subtype 5 (mGluR5), undergoes a thorough validation process to ensure its safety, efficacy, and quality for clinical use. The process starts by optimizing the synthesis of [18F]FPEB to achieve high radiochemical yield and purity. This study focuses on optimizing the radiolabeling process using an aryl-chloro precursor and validating the GMP production for clinical applications. Fully automated radiolabeling was achieved via one-step nucleophilic substitution reaction. [18F]FPEB was produced and isolated in high radioactivity and radiochemical purity. Throughout the validation process, thorough quality control measures are implemented. Radiopharmaceutical batch release criteria are established, including testing for physical appearance, filter integrity, pH, radiochemical purity, molar activity, radiochemical identity, chemical impurity, structural identity, stability, residual solvent, sterility, and endotoxin levels. In conclusion, the validation of [18F]FPEB involved a comprehensive process of synthesis optimization, quality control, which ensure the safety, efficacy, and quality of [18F]FPEB, enabling its reliable use in clinical PET. Here, we successfully radiolabeled and validated [18F]FPEB using aryl-chloro precursor according to GMP production for clinical application.

Vertical triband flag sign for differential diagnosis of Rathke's cleft cyst.

Background: The Rathke cleft cyst (RCC) is a type of cystic growth that is benign, circular, and well-defined with an incidence rate of 4 %. This study aims to identify a useful diagnostic imaging sign that can aid in the differentiation of RCC from other cystic lesions. Methods: We retrospectively analyzed the records of 42 symptomatic RCC patients who were referred to our facility between 2016 and 2023. The data for the study were obtained from our electronic database. All magnetic resonance imaging (MRI) studies were performed using a 1.5-T superconducting magnetic scanner. All patients underwent endonasal transsphenoidal surgical resection. All MRIs were reviewed and evaluated by a neurosurgeon and a neuroradiologist. Results: There were 8 (19 %) males and 34 (81 %) females with a mean age of 37.2-years. Our study identified a distinct imaging characteristic in 38 of the cases, which we have named the "vertical triband flag sign", due to the growth of the cyst developing a specific appearance. The flag sign was mostly observed only in the T1-images (71.5 %), while in four cases the sign was spotted only in T2-images, and in four cases it appeared in both T1 and T2. In 4 cases, the flag sign was not observed in which further investigations revealed that these cases were suprasellar or small sellar RCCs. The dot sign, which is a characteristic finding in RCCs was only observed in one of our cases. Conclusion: Early diagnosis of RCCs may be facilitated by utilizing the vertical triband flag sign.

Efficacy of adoptively transferred allogeneic CIK cells on colorectal cancer: Augmentative antitumoral effects of GvHD.

OBJECTIVE: A preclinical study was designed to evaluate the effects of adoptively transferred cytokine-induced killer (CIK) cells on colorectal adenocarcinoma. METHODS: Forty NOG mice bearing HT-29 xenograft tumors were developed and equally divided into 2 groups of treatment and control. The mice in the treatment group received cumulatively 40-60 × 106 CIK cells in four divided doses. RESULTS: Median tumor doubling times for HT-29 xenograft tumors in the treatment and control groups were found to be 8.98 and 4.32 days; respectively. The treatment resulted in tumor growth delay (TGD) of 52.5 %. CIK cell-induced log cell kill (LCK) was found to be 0.67, which implies reduction of 78.6 % of neoplastic colorectal cells. Median length of survival in the treated mice was significantly longer than controls (57 (41-63) vs 41 (31-57) days, P < 0.001). Mice in the treatment group experienced graft-versus-host disease (GvHD) from median of day 13th after the cell therapy. LCK and TGD significantly increased after emergence of GvHD. After necropsy, tumors of the treatment group contained high levels of human-originated CD3+, CD4+ and CD8+ cells and showed significantly lower mitotic counts (P < 0.001) and residual tumor scores (P = 0.005) than the controls (entirely negative for the mentioned CD markers). Ninety percent of the treated mice were found to be responding. CONCLUSIONS: Adoptive transfer of allogeneic CIK cells may be an efficient antitumoral therapy for colorectal cancer. Allogeneic CIK cell-mediated GvHD may contribute to amplification of graft-versus-tumor effects of the cellular therapy.

MRI-negative Cushing's Disease: Management Strategy and Outcomes in 15 Cases Utilizing a Pure Endoscopic Endonasal Approach.

BACKGROUND: Cushing's disease (CD) is among the most common etiologies of hypercortisolism. Magnetic resonance imaging (MRI) is often utilized in the diagnosis of CD, however, up to 64% of adrenocorticotropic hormone (ACTH)-producing pituitary microadenomas are undetectable on MRI. We report 15 cases of MRI negative CD who underwent surgical resection utilizing a purely endoscopic endonasal approach. METHODS: Endoscopic endonasal transsphenoidal surgery (EETS) was performed on 134 CD cases by a single surgeon. Fifteen cases met inclusion criteria: no conclusive MRI studies and no previous surgical treatment. Data collected included signs/symptoms, pre- and post-operative hormone levels, and complications resulting from surgical or medical management. Data regarding tumor diameter, location, and tumor residue/recurrence was obtained from both pre- and post-operative MRI. Immunohistochemistry was performed to assess for tumor hormone secretion. RESULTS: Aside from a statistically significant difference (P = 0.001) in histopathological results between patients with negative and positive MRI, there were no statistically significant difference between these two groups in any other demographic or clinical data point. Inferior petrosal sinus sampling (IPSS) with desmopressin (DDAVP®) administration was performed on the 15 patients with inconclusive MRIs to identify the origin of ACTH hypersecretion via a central/peripheral (C/P) ratio. IPSS in seven, five and three patients showed right, left, and central side lateralization, respectively. With a mean follow-up of 5.5 years, among MRI-negative patients, 14 (93%) and 12 patients (80%) achieved early and long-term remission, respectively. In the MRI-positive cohort, over a mean follow-up of 4.8 years, 113 patients (94.9%) and 102 patients (85.7%) achieved initial and long-term remission, respectively. CONCLUSIONS: Surgical management of MRI-negative/inconclusive Cushing's disease is challenging scenario requiring a multidisciplinary approach. An experienced neurosurgeon, in collaboration with a dedicated endocrinologist, should identify the most likely location of the adenoma utilizing IPSS findings, followed by careful surgical exploration of the pituitary to identify the adenoma.

Spontaneous xenogeneic GvHD in Wilms' tumor Patient-Derived xenograft models and potential solutions.

Severely immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Sug (NOG) mice are among the ideal animal recipients for generation of human cancer models. Transplantation of human solid tumors having abundant tumor-infiltrating lymphocytes (TILs) can induce xenogeneic graft-versus-host disease (xGvHD) following engraftment and expansion of the TILs inside the animal body. Wilms' tumor (WT) has not been recognized as a lymphocyte-predominant tumor. However, 3 consecutive generations of NOG mice bearing WT patient-derived xenografts (PDX) xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention. In the initial generation, dermatitis, auto-amputation of digits, weight loss, lymphadenopathy, hepatitis, and interstitial pneumonitis were observed. Despite antibiotic treatment, no response was noticed, and thus the animals were prematurely euthanized (day 47 posttransplantation). Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor, whereas no microbial infection or lymphoproliferative disorder was found. Mice of the next generation that lived longer (91 days) developed sclerotic skin changes and more severe pneumonitis. Cutaneous symptoms were milder in the last generation. The xenografts of the last 2 generations also contained TILs, and lacked lymphoproliferative transformation. The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD. While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts, this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication.

Flow Cytometric Measurement of Reactive Oxygen Species to Assess the Effects of Preconditioning Total Body Irradiation on NOG Mice.

BACKGROUND: Preclinical development of new drugs for cancer immunotherapy requires preconditioning total body irradiation (TBI) of mice to be humanized via hematopoietic stem cell transplantation. To assess the effect of preconditioning TBI, we detected the reactive oxygen species (ROS), Annexin V, propidium iodide (PI) level in bone marrow samples by flow cytometer. METHODS: We divided all NOG mice between irradiated (n = 20) and control groups (n = 10) for two time points. Irradiated mice were exposed to 3.5 Gy of radiation. After sacrificing BM samples were collected, the flow cytometric percentage of ROS, Annexin V, and PI markers were investigated on days 2 and 14 after exposure. RESULTS: At the first time point, the level of ROS was higher in the irradiated group than in the control group, and this difference was statistically significant (P < 0.05). Also, at the second time point, the mean differences of all markers in the irradiated group were significantly compared to the control group (P < 0.05). CONCLUSION: Thus, in NOG mice, the measurement of ROS level is helpful to the assessment of preconditioning TBI.

Multimodal Intraoperative Image-Driven Surgery for Skull Base Chordomas and Chondrosarcomas.

Given the difficulty and importance of achieving maximal resection in chordomas and chondrosarcomas, all available tools offered by modern neurosurgery are to be deployed for planning and resection of these complex lesions. As demonstrated by the review of our series of skull base chordoma and chondrosarcoma resections in the Advanced Multimodality Image-Guided Operating (AMIGO) suite, as well as by the recently published literature, we describe the use of advanced multimodality intraoperative imaging and neuronavigation as pivotal to successful radical resection of these skull base lesions while preventing and managing eventual complications.

The utility of SYNTAX score predictability by electrocardiogram parameters in patients with unstable angina.

BACKGROUND: SYNTAX score is one of the risk assessment systems to predict cardiac events in acute coronary syndrome patients. Despite the large number of SYNTAX score benefits, invasive methods such as coronary angiography are necessary to perform the scoring. We hypothesized that ECG parameters could predict the SYNTAX score in unstable angina patients. METHODS: During the retrospective cohort study, a total number of 876 patients were diagnosed with unstable angina. After applying the exclusion criteria, 600 patients were divided into tertiles based on the SYNTAX scores as low (0-22), intermediate (23-32), and high (≥ 33). The association between ECG parameters and SYNTAX score was investigated. RESULTS: The study included 65% men and 35% women with a mean age of 62.4 ± 9.97 years. The delayed transition zone of QRS complex, ST-depression in inferior-lateral territories or/and in all three territories, and T-wave inversion in lateral territory were significant (p < 0.05) independent predictors of intermediate SYNTAX score. High SYNTAX score was predicted by the presence of prolonged P wave duration, ST-depression in lateral territory or/and anterior-lateral territories, ST-elevation in aVR-III leads or/and aVR-III-V1 leads. Among those, all three territories ST-depression (AUC: 0.611, sensitivity: 75%, specificity: 51%) and aVR + III ST-elevation (AUC: 0.672, sensitivity: 50.12%, specificity: 80.50%) were the most accurate parameters to predict intermediate and high SYNTAX scores, respectively. CONCLUSION: The present study demonstrates that accompanying the STE in the right side leads (aVR, III, V1) with ST-depression in other leads indicates the patients with high SYNTAX score; meanwhile, diffuse ST-depression without ST-elevation is a marker for intermediate SYNTAX score in unstable angina patients and can be applied for early risk stratification and intervention.

Indigenous production, characterization and evaluation of polyclonal antibody against Camelus dromedarius immunoglobulin.

No diagnostic kits and reagents are available in the market to detect and evaluate camel immune responses to different pathogens. This study aimed to produce sheep anti-camel (Camelus dromedarius) polyclonal antibodies (pAbs) and to determine the specificity with other species immunoglobulin. Immunoglobulins (Igs) from camel serum samples were purified using ammonium sulfate precipitation (40.00% saturated ammonium sulfate). Purity of the camel Igs was tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis. PAbs against (Camelus dromedarius) immunoglobulins were generated by immunizing sheep with purified Igs. Anti- camel Ig polyclonal antibodies titer and specificity were determined using ELISA and Western blot techniques. Polyclonal antibodies specific to camel Igs were significantly high in immunized sheep which confirmed the immunization procedure. PAbs reacted specifically with camel serum immunoglobulin and did not react with other species immunoglobulin of horse and chickens. Polyclonal antibodies produced in this study can be regarded as a valuable tool to be used for immune-diagnostic purposes in camel population world-wide.

Characterizing the Binding of Angiotensin Converting Enzyme I Inhibitory Peptide to Human Hemoglobin: Influence of Electromagnetic Fields.

BACKGROUND: Drug-protein complexes is one of the crucial factors when analyzing the pharmacokinetics and pharmacodynamics of a drug because they can affect the excretion, distribution, metabolism and interaction with target tissues. OBJECTIVES: The aim of this study was to investigate the interaction of human hemoglobin (Hb) and angiotensin I converting enzyme inhibitory peptide (ACEIP) in the absence and presence of different- frequency electromagnetic fields (EMF). METHODS: Various spectroscopic methods like fluorescence spectroscopy, ultraviolet, circular dichroism and conductometry techniques were applied to investigate Hb-ACEIP interaction in the absence and presence of EMF. RESULT: The presented spectroscopic studies indicated that EMF changed the interaction between Hb and ACEIP. The a-helix content of Hb decreased upon binding to ACEIP and conductivity of the solution enhanced upon binding. Based on Stern-Volmer equations, it could be stated that the Hb-ACEIP affinity was higher in the presence of EMF. CONCLUSION: It can be concluded that for patients who use the drug to control blood pressure, a low-frequency electromagnetic field would have a positive effect on the uptake of the drug.

Effects of partial internal biliary diversion on long-term outcomes in patients with progressive familial intrahepatic cholestasis: experience in 44 patients.

PURPOSE: Progressive familial intrahepatic cholestasis (PFIC) is a hereditary disease characterized by cholestasis, which may cause jaundice, severe pruritus, and cirrhosis in the later stages. By the invention of biliary diversion methods, these patients were prevented from undergoing liver transplant. Using biliary diversion techniques, the entero-hepatic cycle was interrupted. This lowers the bile acid pool and resolves the pruritus. Herein, we report 44 cases of PFIC who underwent partial internal biliary diversion (PIBD) and long-term follow-up of these children. This comprises the largest case series of PIBD. METHODS: All patients were diagnosed by liver biopsy as PFIC before the operation. All underwent cholecysto colic bypass by jejunal interposition due to severe pruritus unresponsive to medication. Laboratory blood tests, sonography, and physical exam were done before and after the operation once every 3 months. Besides, a questionnaire was designed to ask the patients about the symptoms after the operation, and a pruritus score was measured using the 5D-itch scale. RESULTS: 44 children (25 boys, 19 girls), between 1.75 and 27.5 years (at the time of this study) were followed for a median period of 54 months. Age at operation ranged from 2 months to 18 years, with a median of 29 months. Of these children, 14 were lost to follow up. Results showed a significant decrease in pruritus and sleep disturbance after the surgery (p < 0.001). Also, jaundice decreased from 82.1 before to 7.1% following the surgery. 50% of the patients became medication-free at follow-up. CONCLUSION: PIBD is a safe procedure which helps non-cirrhotic children preserve their liver function. Therefore, PIBD prevents them from undergoing liver transplant. Effective results were achieved in terms of severe pruritus and jaundice, and children were able to regain their sleep patterns. It also avoided external stoma, which is more convenient from the patient's point of view.

Comparative evaluation of Enterococcus faecalis counts in different tapers of rotary system and irrigation fluids: An ex vivo study.

BACKGROUND: Bacteria and their by-products are etiological factors for the failure of endodontic treatment. Reduction of root canal bacterial contamination is one of the chief aims of root canal therapy. The aim of this study was to compare the effects of different rotary file tapers and two irrigation fluids on Enterococcus faecalis counts. MATERIALS AND METHODS: In this ex vivo study Root canals of 72 human upper lateral incisors were enlarged to ISO #20 K-file. Then, the samples were sterilized and inoculated with E. faecalis for 72 h, divided into six experimental groups and prepared with #30 Flexmaster files with 0.02, 0.04, and 0.06 tapers and two different irrigation solutions such as normal saline and sodium hypochlorite. The control group (n = 10) was subdivided into two groups with or without bacterial inoculation and no mechanical instrumentation. Cleaning efficacy was evaluated in terms of the reduction of colony forming units (CFUs). T-test, ANOVA, Duncan, and Tukey tests were applied to the groups. A significant level of α = 0.05 was set for comparison between the groups. RESULTS: The canals instrumented with 0.06 taper exhibited greater significant reduction in CFUs compared to canals instrumented with 0.04 and 0.02 taper (P < 0.05); 0.04 taper also resulted in greater significant reduction in CFUs than 0.02 taper (P < 0.05). In addition, no significant differences were observed in E. faecalis counts between the two irrigation fluids (P > 0.05). CONCLUSION: Under the conditions of this study, root canal preparation with greater taper resulted in canal cleanliness and better debridement.

Chronic mycobacterial meningitis due to Mycobacterium chelonae: a case report.

We report a case of chronic meningitis due to Mycobacterium chelonae. This organism is a rapidly growing Mycobacterium (RGM) and can be found worldwide in environmental sources such as soil, dust, and water. M. chelonae is an uncommon cause of meningitis; the majority of infections caused by this organism are localized cutaneous or soft tissue infections, and rarely lung infections. The organism is indistinguishable phenotypically, so we applied PCR based on the rpoB gene sequence followed by restriction fragment length polymorphism (RFLP) for molecular identification. The subsequent sequencing of RFLP products revealed 99.7% similarity with M. chelonae.

Demographic distribution of odontogenic cysts in Isfahan (Iran) over a 23-year period (1988-2010).

BACKGROUND: Odontogenic cysts are relatively common lesions which can cause different complications. As demographic information is lacking in Iran and specially in Isfahan, the aim of this study was to determine the prevalence of odontogenic cysts according to age, gender and affected area among patients referring to the Oral Pathology Department of the Dental School of Isfahan University of Medical Sciences (Iran) over a 23-year period. MATERIALS AND METHODS: A total of 7412 diagnosed lesions recorded in the Oral Pathology Department archives of Isfahan Dental School between 1988 and 2010 were reevaluated, then odontogenic cysts were separated through reviewing microscopic slides according to the 2005 World Health Organization classification and variables such as age, gender, the infected jaw, and its specific region were obtained by SPSS Version 16.0 from the recorded database. RESULTS: 21.62% of the lesions were odontogenic cysts, of which 48.72% were inflammatory and 51.28% were developmental cysts. These cysts were more common in the mandible. The mean age of patients was 29.53 ± 16.1. Male to female ratio was 1.31:1. The four most frequent odontogenic cysts were radicular cysts (35.12%), dentigerous cysts (25.77%), odontogenic keratocysts (22.58%) and residual cysts (12.98%). CONCLUSION: Odontogenic cysts are fairly frequent jaw lesions (21.62%), of which radicular cyst was the most common cyst. The four most common lesions constituted a sum of 96.45% of the total. In general, the prevalence rates in our study are similar to the studies from other geographic parts of the world but with a lower incidence of inflammatory cysts, higher prevalence of dentigerous cysts and residual cysts and also mandibular predominance for residual cysts.

Evaluation of hardness and wear resistance of interim restorative materials.

BACKGROUND: The interim restorative materials should have certain mechanical properties to withstand in oral cavity. The aim of this study was to evaluate the hardness and wear resistance of interim restorative materials. MATERIALS AND METHODS: Fifteen identical rectangular shape specimens with dimensions of 2 mm × 10 mm × 30 mm were made from 7 interim materials (TempSpan, Protemp 3 Garant, Revotek, Unifast LC, Tempron, Duralay, and Acropars). The Vickers hardness and abrasive wear of specimens were tested in dry conditions and after 1 week storage in artificial saliva. The depth of wear was measured using surface roughness inspection device. Data were subjected to Kruskal-Wallis and Mann-Whitney tests. The Pearson correlation coefficient was used to determine the relationship between hardness and wear (α =0.05). RESULTS: TempSpan had the highest hardness. The wear resistance of TempSpan (in dry condition) and Revotek (after conditioning in artificial saliva) was significantly higher (P < 0.05). There was no statistically significant correlation between degree of wear and hardness of the materials (P = 0.281, r = -0.31). CONCLUSION: Hardness and wear resistance of interim resins are material related rather than category specified.

Odontogenic tumors in Iran, Isfahan: A study of 260 cases.

BACKGROUND: The aim of this study was to record the relative frequency of odontogenic tumors (OTs), evaluate and analyze the epidemiological features of the lesions in patients referring to dental faculty of Isfahan and compare these data with previous studies. MATERIALS AND METHODS: In this study, we reviewed the records of 6,860 lesions from 1988 to 2010 archived in the oral pathology department of dental faculty of Isfahan retrospectively and using criteria for histological typification published by the WHO in 2005. Age, sex, site and extent of tumors were analyzed. RESULTS: Among recorded lesions 260 were OTs (3.79%). Of these, 259 were benign and just 1 was malignant. The most common lesions were ameloblastomas (n = 95) followed by odontomas (n = 86), odontogenic myxomas (n = 24) and others. There were a few more female patients (n = 133, 51.15%) than male and the mean age of patients was 27.8 years (range 1.5-80 years). The posterior of mandible was the most common site (n = 86, 33%). CONCLUSION: According to accumulated data, odontogenic tumors are uncommon lesions and malignant tumors are very rare.

Fracture strength of mesiobuccal roots following canal preparation with hand and rotary instrumentation: an in vitro study.

INTRODUCTION: The aim of this in vitro study was to compare the effect of hand and rotary instruments on fracture strength of tooth roots. MATERIALS AND METHODS: Thirty two teeth were randomly divided into two experimental groups of 15 each and one negative control group with two samples. In group 1, step-back technique with conventional stainless steel K-files was used, and in group 2, instrumentation was performed using rotary Ni-Ti Hero642. Samples in control group did not receive cleaning or shaping after access cavity preparation. After obturating each canal, tip of the spreader was locked within canal. The required force for root fracture was measured using Instron testing machine. Recorded data was statistically analyzed using t-test. RESULTS: The mean and standard deviation force required for vertical root fracture were 50.33±19.1 and 63.1±25.46 N for hand and rotary groups respectively. However, no significant difference was found between experimental groups. CONCLUSION: The results indicate that the manual technique did not lower fracture strength of obturated roots in comparison with the rotary preparation technique.

Comparing Coronal Discoloration Between AH26 and ZOE Sealers.

INTRODUCTION: Intrinsic tooth discolorations after endodontic treatment are principally attributed to the composition of necrotic pulp tissue, hemorrhage within the pulp cavity, endodontic medicaments and/or filling materials. Residual sealer left in pulp chamber after obturation can cause discoloration. The objective of this in vitro study was to evaluate coronal discoloration created by AH26 and ZOE sealers after four months. MATERIALS AND METHODS: Fifty intact human extracted maxillary central incisors were employed. Access cavities were prepared in all samples and root canals were instrumented; coronal orifices were then sealed using self-cure glass ionomer. The teeth were divided into two experimental groups (n=20) according to utilized sealer in pulp chambers including AH26 and Dorifill (ZOE). The remaining 10 teeth served as negative and positive controls (n=5). The access cavities were sealed with self-cure glass ionomer. Teeth were kept in incubator for four month. Preliminary digital images of the teeth were taken and then compared with those related to 4-month follow-up. The images were assessed using Photoshop software. Data was analyzed using paired t-test and independent samples t-test. RESULTS: The teeth which were filled with AH26 sealer showed significantly greater discoloration than those filled with ZOE sealer (Dorifill) (P<0.05). CONCLUSION: AH26 sealer causes greater discoloration of the crown compared to ZOE sealer. Despite the other disadvantage of AH26 sealer, it seems that Dorifill is more esthetically considerate.