Penile length and circumference: are they related to nose size?

Background: We investigated the relationship between the size of the penis and that of the nose. Methods: We retrospectively analyzed 1,160 patients whose nose and penis sizes were measured. These participants were selected from a subset of 1,531 patients who visited the Dr. JOMULJU Urology Clinic between March and October 2022. Patients aged <20 years and those who underwent surgery for the nose and penis were excluded. Nose size was determined by measuring the length, width, and height of the nose, which were used to calculate the volume of the triangular pyramid. Stretched penile length (SPL) and penile circumference before erection were measured. The participants' height, weight, foot size, and serum testosterone levels were measured. Testicular size was measured using ultrasonography. Predictors of penile length and circumference were assessed using linear regression analysis. Results: The participants' average age was 35.5 years, mean SPL was 11.2 cm, and mean penile circumference was 6.8 cm. Univariate analysis revealed that body weight, body mass index (BMI), the serum testosterone level, and nose size were associated with SPL. Multivariable analysis revealed that BMI (P=0.001) and nose size (P=0.023) were significant predictors of SPL. Univariate analysis revealed that penile circumference was related to an individual's height, weight, BMI, nose size, and foot size. Multivariable analysis revealed that body weight (P=0.008) and testicular size (P=0.002) were significant predictors of penile circumference. Conclusions: Nose size was a significant predictor of penile size. The sizes of the penis and nose increased with a decrease in BMI. This interesting study confirms the truth of an erstwhile myth about penis size.

Three-Dimensional Evaluation of the Depressor Anguli Oris and Depressor Labii Inferioris for Botulinum Toxin Injections.

BACKGROUND: Botulinum toxin type A (BoNT-A) injection administered at an inappropriate site or depth can produce an unwanted change in facial animation because the depressor anguli oris (DAO) and depressor labii inferioris (DLI) muscles are partially overlapped. Therefore, simple BoNT-A injection guidelines, based on 3-dimensional (3D) facial anatomic references and landmarks, would be very useful. OBJECTIVES: The aim of this study was to establish novel BoNT-A injection guidelines that include the soft tissue thickness at the lower perioral region. Data were acquired with a 3D scanning system combined with dissections in order to obtain accurate injection sites and depths for the DAO and DLI. METHODS: 3D scans of the facial skin, superficial fat, and facial muscle surface were performed in 45 embalmed cadavers. The thicknesses of the skin and subcutaneous layer were calculated automatically from superimposed images at each of 5 reference points (P) in the perioral region. RESULTS: In every case (100%), P3 and P5 were located in the DLI and DAO areas, respectively (45/45). Therefore, we defined P3 as the "DLI point" and P5 as the "DAO point." The soft tissue thicknesses at the DLI and DAO points were 6.4 [1.7] mm and 6.7 [1.8] mm, respectively. CONCLUSIONS: The P3 and P5 described in this study are effective guidelines that only target the DLI and DAO. Clinicians, specifically, can easily use facial landmarks, such as the cheilion and pupil, to assign the DLI and DAO points without any measurement or palpation of the modiolus.

DDIAS promotes STAT3 activation by preventing STAT3 recruitment to PTPRM in lung cancer cells.

DNA damage-induced apoptosis suppressor (DDIAS) regulates cancer cell survival. Here we investigated the involvement of DDIAS in IL-6-mediated signaling to understand the mechanism underlying the role of DDIAS in lung cancer malignancy. We showed that DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in malignant cancers. Interestingly, siRNA protein tyrosine phosphatase (PTP) library screening revealed protein tyrosine phosphatase receptor mu (PTPRM) as a novel STAT3 PTP. PTPRM knockdown rescued the DDIAS-knockdown-mediated decrease in STAT3 Y705 phosphorylation in the presence of IL-6. However, PTPRM overexpression decreased STAT3 Y705 phosphorylation. Moreover, endogenous PTPRM interacted with endogenous STAT3 for dephosphorylation at Y705 following IL-6 treatment. As expected, PTPRM bound to wild-type STAT3 but not the STAT3 Y705F mutant. PTPRM dephosphorylated STAT3 in the absence of DDIAS, suggesting that DDIAS hampers PTPRM/STAT3 interaction. In fact, DDIAS bound to the STAT3 transactivation domain (TAD), which competes with PTPRM to recruit STAT3 for dephosphorylation. Thus we show that DDIAS prevents PTPRM/STAT3 binding and blocks STAT3 Y705 dephosphorylation, thereby sustaining STAT3 activation in lung cancer. DDIAS expression strongly correlates with STAT3 phosphorylation in human lung cancer cell lines and tissues. Thus DDIAS may be considered as a potential biomarker and therapeutic target in malignant lung cancer cells with aberrant STAT3 activation.

Regional thickness of facial skin and superficial fat: Application to the minimally invasive procedures.

Various recently introduced minimally invasive treatment modalities are now widely used for enhancing the aging face. In a special, filler is used to increase the volume of tissue, and so understanding the regional thickness and distribution of the facial superficial fat is essential for optimizing minimally invasive procedures. The aim of this study was to establish the overall facial skin and superficial fat thicknesses using a three-dimensional (3D) scanning system. From 53 adult Korean and Thai embalmed adult cadavers, the undissected and serially-dissected facial specimens were scanned and reconstructed. The facial skin and superficial fat thicknesses on seven facial regions were calculated from the superimposed images. The facial skin tended to become thicker in the order of the radix and dorsum, and the temple, supraorbital, forehead, perioral, cheek, and infraorbital areas. The skin was thinnest at radix and dorsum (1.51 ± 0.55 mm), and thickest in infraorbital region (1.97 ± 0.84 mm). The facial superficial fat thickness tended to increase in the order of the radix and dorsum, supraorbital, forehead, temple, cheek, infraorbital, and perioral regions. The superficial fat was thinnest at the radix and dorsum (1.61 ± 1.07 mm), and thickest in the perioral region (5.14 ± 3.31 mm). The facial superficial fat thickness tended to increase in the order of the radix and dorsum, supraorbital, forehead, temple, cheek, infraorbital, and perioral regions. The present findings indicate that 3D scanning system can yield crucial anatomical information about depths of the facial skin and superficial fat layers for utilization in various clinical procedures. Clin. Anat. 32:1008-1018, 2019. © 2019 Wiley Periodicals, Inc.

Classification of unusual insertion of the pectoralis minor muscle.

PURPOSE: The pectoralis minor muscle (PMi) generally originates from the third, fourth, and fifth ribs and inserts on the medial and superior margins of the anterior portion of the coracoid process. Variations in the shape and attachment point of the PMi could cause discomfort in the shoulders. The aim of this study was to observe the types of morphological insertion patterns and attachment sites of the PMi. METHODS: Seventy-four sides of fresh, embalmed Korean (42 sides; mean age 78 years) and Thai (32 sides; mean age 78 years) cadavers were dissected to analyze the morphological insertion types and attachment sites of the PMi. RESULTS: Unusual insertion patterns were evident in about 23% of the samples. When the portion of the PMi tendon ran over the coracoid process, the most common attachment site was the glenohumeral joint capsule. We also confirmed the attachment of the PMi to the clavicle. Costal attachments of the PMi that extend from the second rib to the fourth rib were observed frequently as well. CONCLUSIONS: Unusual insertion patterns of the PMi are common. Some authors consider that tendon attachment to the joint capsule can cause shoulder pain. In addition, the PMi tendon could be utilized in acromioclavicular joint reconstruction. Surgeons need to be aware of the possibility of a PMi variant being found during surgery even when this is not visible in magnetic resonance or ultrasound imaging.

mTORC1 accelerates retinal development via the immunoproteasome.

The numbers and types of cells constituting vertebrate neural tissues are determined by cellular mechanisms that couple neurogenesis to the proliferation of neural progenitor cells. Here we identified a role of mammalian target of rapamycin complex 1 (mTORC1) in the development of neural tissue, showing that it accelerates progenitor cell cycle progression and neurogenesis in mTORC1-hyperactive tuberous sclerosis complex 1 (Tsc1)-deficient mouse retina. We also show that concomitant loss of immunoproteasome subunit Psmb9, which is induced by Stat1 (signal transducer and activator of transcription factor 1), decelerates cell cycle progression of Tsc1-deficient mouse retinal progenitor cells and normalizes retinal developmental schedule. Collectively, our results establish a developmental role for mTORC1, showing that it promotes neural development through activation of protein turnover via a mechanism involving the immunoproteasome.

Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.

Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity. We sought to address whether the decreases in PP2A methylation and its methylating enzyme, leucine carboxyl methyltransferase (LCMT-1), which are reported in AD, relate to tau pathology or to concomitant amyloid pathology by comparing them in the relatively pure tauopathy PSP. Immunohistochemical analysis of frontal cortices showed that methyl-PP2A is reduced while demethyl-PP2A is increased, with no changes in total PP2A or B55α subunit, resulting in a reduction in the methyl/demethyl PP2A ratio of 63% in PSP and 75% in AD compared to controls. Similarly, Western blot analyses showed a decrease of methyl-PP2A and an increase of demethyl-PP2A with a concomitant reduction in the methyl/demethyl PP2A ratio in both PSP (74%) and AD (76%) brains. This was associated with a decrease in LCMT-1 and an increase in the demethylating enzyme, protein phosphatase methylesterase (PME-1), in both diseases. These findings suggest that PP2A dysregulation in tauopathies may contribute to the accumulation of hyperphosphorylated tau and to neurodegeneration.

DNA damage-induced apoptosis suppressor (DDIAS), a novel target of NFATc1, is associated with cisplatin resistance in lung cancer.

In a previous study, we reported that DNA damage induced apoptosis suppressor (DDIAS; hNoxin), a human homolog of mouse Noxin, functions as an anti-apoptotic protein in response to DNA repair. Here we reveal that DDIAS is a target gene of nuclear factor of activated T cells 2 (NFATc1) and is associated with cisplatin resistance in lung cancer cells. In the DDIAS promoter analysis, we found that NFATc1 activated the transcription of DDIAS through binding to NFAT consensus sequences in the DDIAS promoter. In addition, tissue array immunostaining revealed a correlation between DDIAS and NFATc1 expression in human lung tumors. NFATc1 knockdown or treatment with the NFAT inhibitor cyclosporine A induced apoptosis and led to growth inhibition of lung cancer cells, indicating the functional relevance of both the proteins. In contrast, DDIAS overexpression overcame this NFATc1 knockdown-induced growth inhibition, supporting the cancer-specific role of DDIAS as a target gene of NFATc1. NFATc1 or DDIAS inhibition clearly enhanced apoptosis induced by cisplatin in NCI-H1703 and A549 cells. Conversely, DDIAS overexpression rescued NCI-H1703 cells from cisplatin-mediated cell death and caspase-3/7 activation. These results suggest that NFATc1-induced DDIAS expression contributes to cisplatin resistance, and targeting DDIAS or NFATc1 impairs the mechanism regulating cisplatin resistance in lung cancer cells. Taken together, DDIAS is a target of NFATc1 and is associated with cisplatin resistance in lung cancer cells.

Apoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice.

α-Synuclein is a key pathogenic protein in α-synucleinopathies including Parkinson's disease, and its overexpression and aggregation in model systems are associated with a neuroinflammatory response and increased oxidative stress. Apoptosis signal-regulating kinase 1 (ASK1) is activated upon stress signaling events such as oxidative stress and is a central player linking oxidative stress with neuroinflammation. Here, we demonstrate that overexpression of human α-synuclein activates ASK1 in both PC12 cells and in the brains of α-synuclein transgenic mice. Deleting ASK1 in mice mitigates the neuronal damage and neuroinflammation induced by α-synuclein and improves performance of the animals on the rotarod. ASK1 deletion does not impact the aggregation profile or phosphorylation state of α-synuclein in the mouse brain. These results collectively implicate ASK1 in the cascade of events triggered by α-synuclein overexpression, likely because of the inflammatory response and oxidative stress that lead to ASK1 activation. These conclusions raise the possibility that potent antioxidants and anti-inflammatory agents may ameliorate the phenotype of α-synucleinopathies.

NFATc1 regulates the transcription of DNA damage-induced apoptosis suppressor.

DNA damage induced apoptosis suppressor (DDIAS), or human Noxin (hNoxin), is strongly expressed in lung cancers. DDIAS knockdown induced apoptosis in non-small cell lung carcinoma A549 cells in response to DNA damage, indicating DDIAS as a potential therapeutic target in lung cancer. To understand the transcriptional regulation of DDIAS, we determined the transcription start site, promoter region, and transcription factor. We found that DDIAS transcription begins at nucleotide 212 upstream of the DDIAS translation start site. We cloned the DDIAS promoter region and identified NFAT2 as a major transcription factor (Im et al., 2016 [1]). We demonstrated that NFATc1 regulates DDIAS expression in both pancreatic cancer Panc-1 cells and lung cancer cells.

Age and gender are important considerations in choosing the sniffing position for laryngoscopic view.

AIMS: The sniffing position is considered to be the standard position for direct laryngoscopic viewing. This crossover study evaluated age and gender as variables in comparing the benefits of the sniffing position over simple head extension for laryngeal view during direct laryngoscopy. METHODS: Laryngoscopy with a curved blade was performed on 200 anesthetized adults (100 males, 100 females) presenting for routine elective surgery. Glottic visualization was assessed by using the percentage of glottic opening (POGO) score in both simple extension and sniffing positions without the aid of the assistant or external laryngeal manipulation. Each gender group was divided into a younger group (< 50 years) and an older group (≥ 50 years). POGO scores were compared between both positions within each group. RESULTS: Mean (SD) POGO scores increased significantly only in younger male patients from 43% (39%) in the head extension position to 76% (30%) in the sniffing position. CONCLUSION: The sniffing position seems to be advantageous for getting a better laryngeal view during laryngoscopy for tracheal intubation in adult male patients less than 50 years old.

Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells.

BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases by producing several pro-inflammatory enzymes and pro-inflammatory cytokines. Lipopolysaccharide (LPS)-induced inflammation leads to the activation of microglial cells in the central nervous system (CNS) and is associated with the pathological mechanisms of neurodegenerative diseases, including PD, AD, and ALS. Ginseng is a natural antioxidant used in herbal medicine and contains ginsenosides (Rb1, Rg1, Rg3, Re, and Rd), which have anti-neoplastic and anti-stress properties.This study demonstrates the involvement of the anti-inflammatory signaling pathway, ginsenoside-Re (G-Re), which is one of the ginsenosides mediated by LPS-induced neuroinflammation in BV2 microglial cells. METHODS: BV2 microglial cells were pretreated with 2 µg/ml G-Re and stimulated with 1 µg/ml LPS to induce neuroinflammation. To investigate the effect of G-Re on LPS-induced cell signaling, we performed western blotting and immunofluorescence using specific antibodies, such as phospho-p38, COX2, and iNOS. RESULTS: Pretreatment with 2 µg/ml G-Re was neuroprotective against 1 µg/ml LPS-treated microglial cells. The neuroprotective events induced by G-Re treatment in neuroinflammation occurred via the phospho-p38, iNOS, and COX2 signaling pathways in BV2 cells. CONCLUSION: Taken together, we suggest that G-Re exerts a beneficial effect on neuroinflammatory events in neurodegenerative diseases.

Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.

BACKGROUND: Parry-Romberg disease is a rare condition that results in progressive hemifacial atrophy, involving the skin, dermis, subcutaneous fat, muscle, and, finally, cartilage and bone. Patients have been treated with dermofat or fat grafts or by microvascular free flap transfer. We hypothesized that adipose-derived stem cells (ASCs) may improve the results of microfat grafting through enhancing angiogenesis. We evaluated the utility of ASC in microfat grafting of patients with Parry-Romberg disease by measuring the change in the hemifacial volumes after injection of ASCs with microfat grafts or microfat grafts alone. METHODS: In April 2008, this investigation was approved by the Korean Food and Drug Administration and the institutional review board of the Asan Medical Center (Seoul, Korea) that monitor investigator-initiated trials. Between May 2008 and January 2009, 10 volunteers with Parry-Romberg disease (5 men and 5 women; mean age, 28 y) were recruited; 5 received ASC and microfat grafts and 5 received microfat grafts only. The mean follow-up period was 15 months. Adipose-derived stem cells were obtained from abdominal fat by liposuction and were cultured for 2 weeks. On day 14, patients were injected with fat grafts alone or plus (in the test group) 1 × 10 ASCs. Patients were evaluated postoperatively using a 3-dimensional camera and 3-dimensional CT scans, and grafted fat volumes were objectively calculated. RESULTS: Successful outcomes were evident in all 5 patients receiving microfat grafts and ASCs, and the survival of grafted fat was better than in patients receiving microfat grafts alone. Before surgery, the mean difference between ipsilateral and contralateral hemiface volume in patients receiving microfat grafts and ASCs was 21.71 mL decreasing to 4.47 mL after surgery. Overall resorption in this ASC group was 20.59%. The mean preoperative difference in hemiface volume in those receiving microfat grafts alone was 8.32 mL decreasing to 3.89 mL after surgery. Overall resorption in this group was 46.81%. The preoperative and postoperative volume differences between the groups was statistically significant (P = 0.002; random-effects model [SAS 9.1]). CONCLUSIONS: Adipose-derived stem cells enhance the survival of fat grafted into the face. A microfat graft with simultaneous ASC injection may be used to treat Parry-Romberg disease without the need for microvascular free flap transfer.

DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.

DJ-1, which is linked to recessively inherited Parkinson's disease when mutated, is a multi-functional protein with anti-oxidant and transcription regulatory activities. However, the mechanism(s) through which DJ-1 and the genes it regulates provide neuroprotection is not fully understood. Here, we show that wild-type DJ-1 induces the expression of thioredoxin 1 (Trx1), a protein disulfide oxidoreductase, whereas pathogenic mutant isoforms L166P and M26I cannot. Conversely, DJ-1 knockdown in SH-SY5Y cells and DJ-1 knockout in mice result in significant decrease in Trx1 protein and mRNA expression levels. The importance of Trx1 in the cytoprotective function of DJ-1 is confirmed using a pharmacological inhibitor of Trx reductase, 1-chloro-2,4-dinitrobenzene, and Trx1 siRNA. Both approaches result in partial loss of DJ-1-mediated protection. Additionally, knockdown of Trx1 significantly abrogates DJ-1-dependent, hydrogen peroxide-induced activation of the pro-survival factor AKT. Promoter analysis of the human Trx1 gene identified an antioxidant response element (ARE) that is required for DJ-1-dependent induction of Trx1 expression. The transcription factor Nuclear factor erythroid-2 related factor 2 (Nrf2), which is a critical inducer of ARE-mediated expression, is regulated by DJ-1. Overexpression of DJ-1 results in increased Nrf2 protein levels, promotes its translocation into the nucleus and enhances its recruitment onto the ARE site in the Trx1 promoter. Further, Nrf2 knockdown abolishes DJ-1-mediated Trx1 induction and cytoprotection against hydrogen peroxide, indicating the critical role of Nrf2 in carrying out the protective functions of DJ-1 against oxidative stress. These findings provide a new mechanism to support the antioxidant function of DJ-1 by increasing Trx1 expression via Nrf2-mediated transcriptional induction.

Exendin-4 protects oxidative stress-induced ß-cell apoptosis through reduced JNK and GSK3ß activity.

Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of ß-cell mass through ß-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of ß-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from ß-cell and differentiation to ß-cell from progenitor cells. Also, it probably has an antiapoptotic effect on ß-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in ß-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 µM H(2)O(2) for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of ß-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3ß activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in ß-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect ß-cell apoptosis by blocking the JNK and GSK3ß mediated apoptotic pathway.

DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex.

DJ-1 is a multifunctional protein linked to recessively inherited Parkinson's disease (PD) due to loss of function mutations. Among its activities is anti-oxidant property leading to cytoprotection under oxidative stress conditions. A key effector of oxidant-induced cell death is the MAP3 kinase apoptosis signal-regulating kinase 1 (ASK1) which is bound to and inhibited by thioredoxin 1 (Trx1) under basal conditions. Upon oxidative stimuli, however, ASK1 dissociates from this physiological inhibitor and is activated. In the present study, we investigated the role of DJ-1 in regulating Trx1/ASK1 interaction. Over-expression of DJ-1 suppressed ASK1 activation in response to H(2)O(2) in a time-dependent manner. Wild-type DJ-1, but not the PD-associated L166P mutant, prevented the dissociation of ASK1 from Trx1 in response to H(2)O(2). Among cysteine mutants of DJ-1, C46S, C53S, and C106S, only C106S failed to inhibit this dissociation implying that cysteine 106 is essential for Trx1/ASK1 regulation. Furthermore, compared to wild-type mice, DJ-1 null mouse brain homogenates and embryonic fibroblasts were more susceptible to oxidant-induced dissociation of ASK1 from Trx1, activation of the downstream kinase c-Jun N-terminal kinase, and to cell death. These findings point to yet another mechanism through which DJ-1 has anti-oxidant and cytoprotective properties by regulating the Trx1/ASK1 complex and controlling the availability of ASK1 to effect apoptosis.

SK-PC-B70M confers anti-oxidant activity and reduces Abeta levels in the brain of Tg2576 mice.

SK-PC-B70M is an oleanolic-glycoside saponin-enriched fraction derived from the root of Pulsatilla koreana. Recently, it was reported that hederacolchiside-E is an active ingredient of SK-PC-B70M that confers a neuroprotective effect against the cytotoxicity induced by Abeta(1-42) in SK-N-SH neuroblastoma cells. SK-PC-B70M improves scopolamine-induced impairments of spatial working memory in rats. In the present study, we investigated whether SK-PC-B70M has a beneficial effect on the Tg2576 murine model of Alzheimer's disease. ELISA analysis revealed that the levels of soluble and insoluble forms of Abeta(1-42) in Tg2576 mice fed SK-PC-B70M (2000 ppm) from 11 months to 16 months of age were reduced to, respectively, 66% and 79% of the control Tg2576 mice. Anti-Abeta antibody-stained brain sections of Tg2576 mice with SK-PC-B70M (2000 ppm) consistently showed a reduction in plaque formation in the brain. Western blot analyses showed altered expressions of various cellular factors, such as up-regulation of transthyretin, phospho-ERK, and phospho-CREB in the brain treated with SK-PC-B70M. SK-PC-B70M suppressed the neuronal toxicity induced by H(2)O(2) in primary cortical culture. Moreover, biochemical and immunohistochemical analyses showed that the levels of malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), oxidized by-products of lipid peroxidation, were notably reduced in the hippocampus of Tg2576 mice treated with SK-PC-B70M compared with the Tg2576 control. These results suggest that SK-PC-B70M attenuates AD-like pathology in the brain of Tg2576 mice.

Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse hippocampus.

Recent studies have shown that ethyl pyruvate (EP) acts as an anti-inflammatory molecule in several cell lines including RAW264.7 macrophages. However, the potential therapeutic value of EP for the treatment of the pathologic brain has not been investigated fully. In the present study, we examined whether EP has a beneficial effect on KA-induced neuronal cell death. Intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 mug) of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of EP significantly attenuated KA-induced neuronal cell death in these regions. Ethyl pyruvate was found to exert a protective effect when it was injected as late as 12 hr after KA-injection. Moreover, this EP-induced neuroprotection was accompanied by reduced levels of reactive gliosis and COX-2, IL-1beta, and TNF-alpha in the hippocampus. In addition, in passive avoidance tests, KA-induced memory impairment was improved markedly by EP. These results suggest that EP has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.