Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.

A quantitative analysis of surgical smoke-derived particulate matter and formaldehyde exposure during spine surgery: a possible occupational hazard.

OBJECTIVE: Since its introduction, electrocautery has served as a valuable surgical tool, enabling precise tissue cutting and effective hemostasis in spine surgery. While there have been numerous efforts to elucidate the possible hazardous effects of surgical smoke in various surgical fields, there has been very little discussion in the context of spine surgery. The objective of this study was to measure and conduct a quantitative analysis of the particulate matter (PM) of different sizes and of formaldehyde (HCHO) generated by smoke during spine surgeries. METHODS: This study included a consecutive series of patients who underwent 1- or 2-level lumbar spinal fusion surgery between June and November 2021. Particle counts were measured using a particle counter, specifically focusing on six different sizes of PM (0.3, 0.5, 1, 2.5, 5, and 10 µm). Additionally, measurements were taken for HCHO in parts per million (ppm). Monopolar cautery was used in the surgical setting. Systematic measurements were conducted at specific time points during the surgical procedures to assess the levels of PM and HCHO. Furthermore, the efficacy of surgical smoke suction was evaluated by comparing the PM levels with and without adjacent placement of suction. RESULTS: This study involved 35 patients, with measurements of both PM and HCHO taken in 27 cases. The remaining 8 cases had measurements only for PM. In this study, statistically significant quantitative changes in various PM sizes were observed when electrocautery was used during spine surgery (12.3 ± 1.7 vs 1975.7 ± 422.8, 3.4 ± 0.5 vs 250.1 ± 45.7, and 1.9 ± 0.2 vs 78.1 ± 13.3, respectively, for 2.5-, 5-, and 10-µm PM; p < 0.05). The level of HCHO was also significantly higher (0.085 ± 0.006 vs 0.131 ± 0.014 ppm, p < 0.05) with electrocautery use. Utilization of adjacent suction of surgical smoke during electrocautery demonstrated a statistically significant reduction in PM levels. CONCLUSIONS: The findings of this study highlight the potential surgical smoke-related hazards that spine surgeons may be exposed to in the operating room. Implementing simple interventions, such as utilizing nearby suction, can effectively minimize the amount of toxic surgical smoke and mitigate these risks.

Determining Average Linear Dimension and Volume of Korean Lungs for Lung Phantom Construction.

ABSTRACT: The purpose of this study was to determine the average size and volume of lungs and to simulate the morphology of internal organs for the development of a Korean adult lung phantom. The body-size data of 2,195 males and 2,293 females aged between 20 and 60 y were included to calculate the average physical dimensions. Two hundred datasets of computed tomography corresponding to the average physique range were collected to measure the average linear dimensions (the length of x, y, and z-axis) of lungs. One set of lung CT images was finally obtained and converted to three-dimensional (3D) format. To confirm the validity of the new lung model, physical lung phantoms were constructed using International Commission on Radiation Units and Measurements (ICRU) density and similar density to what was obtained from the human CT image and then compared with the Lawrence Livermore National Laboratory (LLNL) phantom. The mean size of the chest width and thickness was 31.8 ± 2.8 and 21.4 ± 1.9 cm for males and 28.0 ± 1.6 cm and 19.4 ± 2.0 cm for females, respectively. The standard deviation of the lung dimension in this group was ± 3.0 cm in length, ± 0.8 cm in width, and ± 2.27 cm in depth. The two modified lung phantoms showed highly accurate geometry and linear attenuation coefficient vs. those of the LLNL phantom. The difference in CT number was ± 2% HU for the LLNL phantom and ± 4% HU for the human CT image based on a CT examination conducted using the chest CT protocol. Moreover, both lungs weighed 734 g to 1,246 g, within the range of the reference value of the ICRU report. These results demonstrate that a new lung model based on average linear dimension measurement in a group with average physique simulated the features and physical properties of real human lungs and facilitated further studies for phantom construction.

Associations of Metabolic Syndrome with Total Testosterone and Homocysteine Levels in Male Korean Workers.

BACKGROUND: Low testosterone is associated with metabolic syndrome (MetS), and homocysteine (Hcy) is elevated in individuals with MetS. We investigated the relationships of total testosterone (TT) and serum Hcy levels with MetS in male Korean workers. METHODS: We conducted a cross-sectional study including 8,606 male workers, aged 20 to 58 years, who underwent a physical examination in 2015. MetS was diagnosed based on the criteria of the 2009 harmonized definition, while the Korean standard for waist circumference (WC) was used. Participants' biochemical parameters, including TT and serum Hcy, were measured, and participants were divided into quartiles. Multiple logistic regression models were used to estimate the association of MetS and its individual components depending on TT and serum Hcy quartiles. RESULTS: The prevalence of MetS in the study population was 16%. TT was lower in participants with MetS than in those without MetS (P<0.001). By contrast, Hcy level was similar between groups (P=0.694). In multiple logistic regression analysis, the odds ratio for the lowest TT quartile was 1.29 (95% confidence interval, 1.06 to 1.57) after adjusting for potential confounders. Participants with lower TT were more likely to have high WC, hypertriglyceridemia, and low high density lipoprotein levels. Serum Hcy levels were not significantly associated with MetS. Of the five components of MetS, only WC was significantly associated with serum Hcy. CONCLUSION: In male Korean workers, TT may be an independent predictor of MetS, and serum Hcy levels could be a marker of abdominal obesity. However, future prospective studies are needed.

What is a Right Distal Fusion Level for Prevention of Sagittal Imbalance in Multilevel Posterior Cervical Spine Surgery: C7 or T1?

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To evaluate the sagittal alignment and T1 slope after multilevel posterior cervical fusion surgery depending on the distal fusion level; C7 or T1, and find out the appropriate distal fusion level. SUMMARY OF BACKGROUND DATA: The sagittal balance of the cervical spine is known to be affected by cervical lordosis and T1 slope. However, T1 slope is not a constant parameter that can be frequently changed after the surgery. Furthermore, useful studies to help guide surgeons in decision-making as to the most appropriate distal level of fusion for cervical sagittal balance are very limited. MATERIALS AND METHODS: From 2014 to 2015, 50 patients who underwent multilevel posterior cervical fusion surgery were evaluated and followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion level was C7. Group 2 was composed of 21 patients whose distal fusion level was T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured on preoperative and the last follow-up. RESULTS: In group 1, C2-C7 SVA (23.1→30.4 mm, P=0.043) was worsened, and T1 slope (22.3→32.9 degrees, P=0.001) was increased after the surgery. In group 2, no significant change occurred in C2-C7 SVA after the surgery (25.3 →23.6 mm, P=0.648). The last follow-up T1 slope was similar with preoperative T1 slope (22.7→21.8 degrees, P=0.04) in group 2. CONCLUSIONS: This study showed that sagittal alignment became worse after the multilevel posterior cervical surgery when distal fusion level was stopped at C7, which was associated with increase of T1 slope. However, when we extended the distal fusion level to T1, T1 slope was not changed after the surgery. Therefore, sagittal alignment was maintained after the surgery. On the basis of the results of this study, we recommend distal fusion extends to T1. LEVEL OF EVIDENCE: Level III.

Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation.

Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range.

Radiologic Outcomes According to Varus Deformity in Minimally Invasive Surgery Total Knee Arthroplasty.

PURPOSE: To identify the accuracy of postoperative implant alignment in minimally invasive surgery total knee arthroplasty (MIS-TKA), based on the degree of varus deformity. MATERIALS AND METHODS: The research examined 627 cases of MIS-TKA from November 2005 to December 2007. The cases were categorized according to the preoperative degree of varus deformity in the knee joint in order to compare the postoperative alignment of the implant: less than 5° varus (Group 1, 351 cases), 5° to less than 10° varus (Group 2, 189 cases), 10° to less than 15° varus (Group 3, 59 cases), and 15° varus or more (Group 4, 28 cases). RESULTS: On average, the alignment of the tibial implant was 0.2±1.4°, 0.1±1.3°, 0.1±1.6°, and 0.3±1.7° varus, and the tibiofemoral alignment was 5.2±1.9degrees, 4.7±1.9°, 4.9±1.9°, and 5.1±2.0° valgus for Groups 1, 2, 3, and 4, respectively, in the preoperative stage, indicating no difference between the groups (p>0.05). With respect to the accuracy of the tibial implant alignment, 98.1%, 97.6%, 87.5%, and 86.7% of Groups 1, 2, 3, and 4, respectively, had 0±3° varus angulation, demonstrating a reduced level of accuracy in Groups 3 and 4 (p<0.0001). There was no difference in terms of tibiofemoral alignment, with 83.9%, 82.9%, 85.4%, and 86.7% of each group, respectively, showing 6±3° valgus angulation (p>0.05). CONCLUSION: Satisfactory component alignment was achieved in minimally invasive surgery in total knee arthroplasty, regardless of the degree of varus deformity.

Impact of ENPP1 K121Q on change of insulin resistance after web-based intervention in Korean men with diabetes and impaired fasting glucose.

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose≥5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted ß=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice.

We previously determined that AKR/J mice housed in a low-dose-rate (LDR) ((137)Cs, 0.7 mGy/h, 2.1 Gy) γ-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) ((137)Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice.

Identification of radiation-sensitive expressed genes in the ICR and AKR/J mouse thymus.

We have investigated radiation-sensitive expressed genes (EGs), their signal pathways, and the effects of ionizing radiation in the thymus of ICR and AKR/J mice. Whole-body and relative thymus weights were taken and microarray analyses were done on the thymuses of high-dose-rate (HDR, (137) Cs, 0.8 Gy/min, a single dose of 4.5 Gy) and low-dose-rate (LDR, (137) Cs, 0.7 mGy/h, a cumulative dose of 1.7 Gy) irradiated ICR and AKR/J mice. Gene expression patterns were validated by quantitative polymerase chain reaction (qPCR). The effect of ionizing radiation on thymus cell apoptosis was measured terminal deoxynucleotidyl-transferase-mediated dUTP-end labeling (TUNEL). LDR-irradiation increased the mean whole-body weight, but decreased the relative thymus weight of AKR/J mice. Radiation-sensitive EGs were found by comparing HDR- and LDR-irradiated ICR and AKR/J mice. qPCR analysis showed that 12 EGs had dose and dose-rate dependent expression patterns. Gene-network analysis indicated that Ighg, Igh-VJ558, Defb6, Reg3g, and Saa2 may be involved in the immune response, leukocyte migration, and apoptosis. Our data suggest that expression of the HDR (Glut1, Glut4, and PKLR) and LDR radiation-response genes (Ighg and Igh-VJ558) can be dose or dose-rate dependent. There was an increased number of apoptotic cells in HDR-irradiated ICR mice and LDR-irradiated AKR/J mice. Thus, changes of the mean whole-body weight and relative thymus weight, EGs, signal pathways, and the effects of ionizing radiation on the thymus of ICR and AKR/J mice are described.

Reproducibility of the kinetic analysis of 3'-deoxy-3'-[(18)F]fluorothymidine positron emission tomography in mouse tumor models.

OBJECTIVES: We assessed the reproducibility of the kinetic analysis of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) in A431 human epidermoid carcinoma and murine Lewis lung carcinoma (LLC) tumor models. METHODS: We injected 7.4 MBq of FLT (n=10 for each group) and acquired 2-h dynamic PET images. A second scan was performed 1 day later. We calculated standardized uptake value (SUV), kinetic rate constants, volume of distribution of phosphorylated FLT (V(dm)), net influx constant (K(FLT-CA)) and influx constant by Patlak graphical analysis (K(FLT-PA)). The percent difference between measurements of a parameter was calculated to compare the reproducibilities of different parameters. RESULTS: FLT phosphorylation was higher in mice with A431 tumors than in mice with LLC tumors (P<.005). Differences in the standard deviations of the percent differences of parameters were statistically significant (P<.001) in each model. In mice with A431 tumors, SUV, V(dm), K(FLT-CA) and K(FLT-PA) had standard deviations of the percent difference of < or = 20%. The most reproducible parameter was K(FLT-PA), although the standard deviation (15.6%) was not statistically different from those of V(dm) (15.8%), K(FLT-CA) (17.5%) and SUV (18.9%). In mice with LLC tumors, K(1), K(1)/k(2) and k(3) had standard deviations of the percent difference of < or = 20%. No macroparameters reflecting a total FLT flux had standard deviations of < or = 20%. CONCLUSION: Our results show the reproducibility of the kinetic macroparameters of FLT PET in mouse tumors with high FLT phosphorylation.

F-18 FDG PET/CT in the management of infected abdominal aortic aneurysm due to Salmonella.

Mycotic aneurysm is a rare and life-threatening disorder. Computed tomography (CT) is considered to be the best diagnostic imaging modality that can detect an abdominal aortic aneurysm and changes in the surrounding structures. More recently, F-18 fluorodeoxyglucose (FDG) PET would seem to hold promise for the diagnosis of focal infection and during the follow-up after antibiotic treatment. We present a case of an infected abdominal aortic aneurysm due to Salmonella enteritidis. In this case, a combination of CT and FDG PET/CT provided accurate information for the diagnosis of the infected abdominal aortic aneurysm. Moreover, FDG PET/CT made an important contribution for monitoring response to antibiotic therapy.

[A case of abdominal actinomycosis presenting as mesenteric mass].

Actinomycosis is an indolent, slowly progressive infection caused by Actinomyces species and usually results in the formation of characteristic clumps called sulfur granules. Depending on the site of primary infection, it is generally classified as cervicofacial, thoracic, and abdominal type. Abdominal actinomycosis is often difficult to diagnose before operation because of its infrequent and chronic disease progression without any characteristic clinical features. In principle, diagnosis is based on histologic demonstration of sulfur granules in pus or surgically resected specimen, and the treatment consists of long-term antibiotic therapy coupled with or without surgical resection. We report a case of abdominal actinomycosis presenting as mesenteric mass adhering to small bowel confirmed by laparoscopic exploration and biopsy. Treatment with intravenous penicillin for 4 weeks followed by additional oral therapy for 11 months resulted in clinical resolution.

[18F]3'-deoxy-3'-fluorothymidine PET for the diagnosis and grading of brain tumors.

UNLABELLED: The aim of this study was to evaluate the feasibility of using [(18)F] 3'-deoxy-3'-fluorothymidine (FLT) positron emission tomography (PET) for the diagnosis and grading of brain tumors. METHODS: The patient population comprised 26 patients (15 males, 11 females) with brain tumors (n=18) or nontumorous lesions (n=8). 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) and FLT PET images were obtained using a dedicated PET scanner 1 h after the injection of 370 MBq of FDG or FLT. Uptake of FDG and FLT by the lesions was visually and semiquantitatively assessed in comparison with normal brain tissue. RESULTS: Of 26 brain lesions, four showed increased FDG uptake compared with normal gray matter (grade 5). These four lesions showed intensely increased FLT uptake and were all high-grade tumors. Twenty-two lesions with similar (grade 4) or decreased (grades 1-3) FDG uptake compared with normal gray matter showed variable pathology. Among the 18 brain tumors, FLT PET showed increased uptake in all 12 high-grade tumors but FDG uptake was variable. In 22 brain lesions with similar or decreased uptake compared with normal gray matter on FDG PET, the sensitivity and specificity of FLT PET for the diagnosis of brain tumor were 79% (11/14) and 63% (5/8), respectively. The uptake ratios of 14 brain tumors on FLT PET were significantly higher than the lesion to gray matter ratios (p=0.012) and lesion to white matter ratios (p=0.036) of FDG uptake and differed significantly between high (5.1+/-2.6) and low (2.1+/-1.1) grade tumors (p=0.029). In nine gliomas, FLT uptake was significantly correlated with the Ki-67 proliferation index (rho=0.817, p=0.007). CONCLUSION: These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors. It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET. FLT PET, however, did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions.

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds.

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.

Hippocampal neurotransplantation evaluated in the rat kainic acid epilepsy model.

OBJECTIVE: Neurotransplantation has focused on disorders that involve subcortical brain targets. We evaluated the concepts of epileptic focus repair and changes in animal behavior through replacement of lost hippocampal neurons. The safety of hippocampal neurotransplantation was assessed in the rat kainic acid (KA) epilepsy model. METHODS: Sixty-three rats were studied and classified into six groups: KA plus 40,000 LBS-Neurons (Layton BioScience, Sunnyvale, CA; n = 13); KA plus 80,000 cells (n = 12); KA plus media (n = 9); no-KA plus 40,000 cells (n = 12); no-KA plus 80,000 cells (n = 12); and no-KA plus media (n = 5). Clinical observation (2 h daily) and electroencephalogram recording (3 h every other week) were performed to check for seizures until Week 11 after KA injection. On Week 12, the Morris water maze test was performed to assess spatial learning and memory. RESULTS: Four rats were excluded because of intracranial hematoma or abscess. In the clinical observation of seizures, the no-KA plus media group had significantly fewer seizures than rats that received KA followed by injection of 40,000 cells, 80,000 cells, or media (P = 0.001, 0.0004, and 0.004, respectively). On electroencephalographic analysis, there was no significant difference between any of the groups. Transplanted rats with KA-induced epilepsy did not have an increased number of seizures. In the Morris water maze test, the hidden platform task showed that the KA plus 80,000 cell group had significantly longer swim latencies than groups with no-KA plus 40,000 cells (P = 0.035) or no-KA plus 80,000 cells (P = 0.015), demonstrating the behavioral deficits caused by KA injection. The probe trial showed no significant difference for the percentage of time in the target quadrant between any of the groups. Histological studies showed that 26 (59%) of 44 transplanted rats had evidence of graft survival. CONCLUSION: The safety of cortical neurotransplantation was demonstrated, even in an animal model predisposed to epilepsy. We did not find evidence for cessation of seizures or improvement in behavior using this model.

A molecular basis for the efficacy of magnesium treatment following traumatic brain injury in rats.

Magnesium ions have been shown to be a promising treatment for brain lesions caused by traumatic brain injury (TBI), as well as for the associated acute neurodegeneration and progressive functional deficits. This study investigated the effects of magnesium on the expression of the cell death/survival related proteins following TBI. Male Sprague-Dawley (SD) rats (n = 66, 280-320 g body weight) were subjected to sham surgery alone (n = 14), or to the surgery followed by a lateral fluid percussion brain injury of moderate severity (n = 52, 2.4-2.7 atm). The injured rats were randomly treated with an intravenous bolus of magnesium chloride (n = 26, 125 micromol) or saline vehicle (n = 26). The coronal brain sections were quantitatively analyzed for cell apoptosis and the expression of p53-related proteins, Bcl-2, cyclin D1 and PCNA at 1, 2, and 4 days post-injury by immunohistochemistry or in situ hybridization. Tissue damage was observed primarily in the ipsilateral cortex of the injured region with the induction of apoptosis and p53 mRNA level at 2 days after TBI. The expression of p53 and responding proteins (p21(WAF1/CIP1), Mdm2 and Bax) showed a temporal pattern similar to the apoptotic events in the time course experiments. They were induced in the early time points of days 1-2, decreasing by day 4 after TBI. In contrast, the expression of the cell survival related proteins - Bcl-2, cyclin D1, and PCNA - was most significant at day 4 post-injury, when the rate of apoptosis decreased. Magnesium treatment resulted in a reduction in apoptosis and expression of p53-related proteins. However, it had only a slight additive effect on the expression of the survival related proteins in the same time-course. These results provide a molecular basis for the efficiency of magnesium in treating TBI-induced tissue damage.