Anatomical Considerations for the Injection of Botulinum Neurotoxin in Shoulder and Arm Contouring.

The utilization of botulinum neurotoxin in the field of body contouring is on the rise. Body contouring procedures typically focus on specific muscle groups such as the superior trapezius, deltoid, and lateral head of the triceps brachii. The authors propose identifying optimal injection sites for botulinum neurotoxin to achieve desired aesthetic contouring of the shoulders and arms. The authors conducted a modified Sihler's staining method on specimens of the superior trapezius, deltoid, and lateral head of the triceps brachii muscles, totaling 16, 14, and 16 specimens, respectively. The neural distribution exhibited the most extensive branching patterns within the horizontal section (between 1/5 and 2/5) and the vertical section (between 2/4 and 4/4) of the superior trapezius muscle. In the deltoid muscle, the areas between the anterior and posterior deltoid bellies, specifically within the range of the horizontal 1/3 to 2/3 lines, showed significant intramuscular arborization. Furthermore, the middle deltoid muscle displayed arborization patterns between 2/3 and the axillary line. Regarding the triceps brachii muscle, the lateral heads demonstrated arborization between 4/10 and 7/10. The authors recommend targeting these regions, where maximum arborization occurs, as the optimal and safest points for injecting botulinum toxin.

Chaperone-mediated autophagy dysregulation during aging impairs hepatic fatty acid oxidation via accumulation of NCoR1.

OBJECTIVE: Alterations in lipid metabolism are associated with aging and age-related diseases. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process involved in specific protein degradation. Heat shock cognate 71 kDa protein (Hsc70) recognizes cytosolic proteins with KFERQ motif and allows them to enter the lysosome via lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A). CMA deficiency is associated with dysregulated lipid metabolism in the liver. In this study, we examined the effect of CMA on lipid metabolism in the aged liver. METHODS: 12-week-old and 88-week-old mice were employed to assess the effect of aging on hepatic CMA activity. We generated CMA-deficient mouse primary hepatocytes using siRNA for Lamp2a and liver-specific LAMP2A knockdown mice via adeno-associated viruses expressing short hairpin RNAs to investigate the influence of CMA on lipid metabolism. RESULTS: We noted aging-induced progression toward fatty liver and a decrease in LAMP2A levels in total protein and lysosomes. The expression of genes associated with fatty acid oxidation was markedly downregulated in the aged liver, as verified in CMA-deficient mouse primary hepatocytes. In addition, the aged liver accumulated nuclear receptor corepressor 1 (NCoR1), a negative regulator of peroxisome proliferator-activated receptor α (PPARα). We found that Hsc70 binds to NCoR1 via the KFERQ motif. Lamp2a siRNA treatment accumulated NCoR1 and decreased the fatty acid oxidation rate. Pharmacological activation of CMA by AR7 treatment increased LAMP2A expression, leading to NCoR1 degradation. A liver-specific LAMP2A knockdown via adeno-associated viruses expressing short hairpin RNAs caused NCoR1 accumulation, inactivated PPARα, downregulated the expression of fatty acid oxidation-related genes and significantly increased liver triglyceride levels. CONCLUSIONS: Our results elucidated a novel PPARα regulatory mechanism involving CMA-mediated NCoR1 degradation during aging. These findings demonstrate that CMA dysregulation is crucial for the progression of aging-related fatty liver diseases.

A Nationwide Survey on Gastrointestinal Endoscopy Practice Patterns among Pediatric Endoscopists in South Korea.

Purpose: Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. Methods: Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. Results: The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. Conclusion: While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.

New anatomical insights of the superficial branch of the zygomaticotemporal nerve for treating temporal migraines: An anatomical study.

The zygomaticotemporal nerve is known to contribute to temporal migraines; however, its precise anatomy remains unknown. The potential accessory branches of the zygomaticotemporal nerve may be considered a cause of continued temporal migraines after surgical procedures. In this study, we defined the novel superficial branch of the zygomaticotemporal nerve (sZTN) and investigated its anatomical course, distribution, and clinical implications. Twenty-two hemifaces from 11 fixed Korean cadavers (six males, five females; mean age, 78.3 years) were used in this study. The piercing points of the sZTN through the deep and superficial layers of the deep temporal fascia, and the superficial temporal fascia were defined as P1, P2, and P3, respectively. The distance of each point from the zygomatic tubercle was measured using an image analysis software. The sZTN ascended between the bone and the temporalis after emerging from the zygomaticotemporal foramen. It then pierced the deep temporal fascia without penetrating the temporalis. After then, it pierced the superficial layer of the deep temporal fascia and turned superiorly toward the upper posterior temple. When the sZTN passed through the superficial temporal fascia, it intersected with the superficial temporal artery in every case. The novel findings of the sZTN may help in the treatment of intractable temporal migraines refractory to injection or surgical procedure. Based on our findings, targeting the sZTN may be applied as an alternative treatment strategy for patients who do not show significant improvement with treatment targeted to trigger sites.

Mitochondrial H2O2 Is a Central Mediator of Diclofenac-Induced Hepatocellular Injury.

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with adverse consequences, including hepatic injury. The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS). The primary ROS responsible for inducing diclofenac-related hepatocellular toxicity and the principal antioxidant that mitigates these ROS remain unknown. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-eliminating enzyme in the mitochondria of mammalian cells. Here, we investigated the role of mitochondrial H2O2 and the protective function of PrxIII in diclofenac-induced mitochondrial dysfunction and apoptosis in hepatocytes. Mitochondrial H2O2 levels were differentiated from other types of ROS using a fluorescent H2O2 indicator. Upon diclofenac treatment, PrxIII-knockdown HepG2 human hepatoma cells showed higher levels of mitochondrial H2O2 than PrxIII-expressing controls. PrxIII-depleted cells exhibited higher mitochondrial dysfunction as measured by a lower oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, and caspase activation, and were more sensitive to apoptosis. Ectopic expression of mitochondrially targeted catalase in PrxIII-knockdown HepG2 cells or in primary hepatocytes derived from PrxIII-knockout mice suppressed the diclofenac-induced accumulation of mitochondrial H2O2 and decreased apoptosis. Thus, we demonstrated that mitochondrial H2O2 is a key mediator of diclofenac-induced hepatocellular damage driven by mitochondrial dysfunction and apoptosis. We showed that PrxIII loss results in the critical accumulation of mitochondrial H2O2 and increases the harmful effects of diclofenac. PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.

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.

Ultrasonography Analysis of Vessels Around the Forehead Midline.

BACKGROUND: Filler injection into the glabella is well known to be a highly dangerous procedure due to the high risk of embolism and intravascular injection. Although it is conventional practice to insert the cannula into the middle of the forehead to perform injections into the glabella or radix, vascular structures can be observed in this region during anatomic dissection procedures. OBJECTIVES: The aim of this study was to characterize the blood vessels around the forehead midline in order to provide crucial anatomic information for ensuring the safety of noninvasive procedures involving the forehead and glabella. METHODS: Ultrasonography image scanning was performed at the following 4 points on the forehead midline: trichion (P1), metopion (P2), halfway point between metopion and glabella (P3), and glabella (P4). The courses and locations of vessels were identified and classified according to their proximity to the forehead midline. RESULTS: Vessels coursing within 0.75 cm either side of the forehead midline were found in 34% to 50% of individuals. Arteries running near the forehead midline tended to be dominant on the right side of the forehead except in the P4 area. About half of the individuals had vessels in the P4 area, of which 96.7% were veins. CONCLUSIONS: The present results indicate that there are superficial vessels running close to the midline of the forehead. This anatomic information can explain the higher incidence of vascular complications during conventional aesthetic procedures. To ensure safety, the cannula entry point or needle puncture point for glabella augmentation should be reconsidered.

Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in Mice.

BACKGROUND: Studies have suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase (SULT1E1, or EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but studies on the role of SULT1E1 in AKI are lacking. METHODS: We used the renal ischemia-reperfusion model to investigate the role of SULT1E1 in AKI. We subjected wild-type mice, Sult1e1 knockout mice, and Sult1e1 knockout mice with liver-specific reconstitution of SULT1E1 expression to bilateral renal ischemia-reperfusion or sham surgery, either in the absence or presence of gonadectomy. We assessed relevant biochemical, histologic, and gene expression markers of kidney injury. We also used wild-type mice treated with the SULT1E1 inhibitor triclosan to determine the effect of pharmacologic inhibition of SULT1E1 on AKI. RESULTS: AKI induced the expression of Sult1e1 in a tissue-specific and sex-specific manner. It induced expression of Sult1e1 in the liver in both male and female mice, but Sult1e1 induction in the kidney occurred only in male mice. Genetic knockout or pharmacologic inhibition of Sult1e1 protected mice of both sexes from AKI, independent of the presence of sex hormones. Instead, a gene profiling analysis indicated that the renoprotective effect was associated with increased vitamin D receptor signaling. Liver-specific transgenic reconstitution of SULT1E1 in Sult1e1 knockout mice abolished the protection in male mice but not in female mice, indicating that Sult1e1's effect on AKI was also tissue-specific and sex-specific. CONCLUSIONS: SULT1E1 appears to have a novel function in the pathogenesis of AKI. Our findings suggest that inhibitors of SULT1E1 might have therapeutic utility in the clinical management of AKI.

The Nasolabial Fold: A Micro-Computed Tomography Study.

BACKGROUND: The nasolabial fold is known to be a challenging midface feature for aesthetic physicians. However, the steric conformation of the structures related to the nasolabial fold has remained undefined because the composition and topography of this region are highly intricate. Therefore, this study aimed to clarify the three-dimensional structures of the nasolabial fold using micro-computed tomography and verify their detailed composition by means of histologic observation. METHODS: Twenty-four specimens were collected from the area beside the alae nasi to the area above the oral angle of 12 cadavers (mean age, 80.3 years) bilaterally. Twelve specimens were evaluated by means of phosphotungstic acid contrast staining, and the rest were evaluated by means of histologic staining. All specimens were divided into three regions and analyzed comprehensively. RESULTS: The medial region of the nasolabial fold had dense irregular connective tissue intermingled with muscle fibers; the lateral region of the nasolabial fold had numerous fibrous septa with abundant adipose tissue. The levator labii alaeque nasi and the zygomaticus minor were attached to the medial part of the nasolabial fold, and the fascial septa were intermittently tethered to the dermis, lateral to the nasolabial fold. The extension of the adipose tissue within the fascial septa was limited by the lateral border of the muscle attachment. CONCLUSIONS: Dimensional and distributional alterations of the adipose tissues with senescence could render the nasolabial fold deeper by increasing the depth of the subcutaneous layer, lateral to the fold. Thus, to ameliorate the fold, the adipose tissue, lateral to the fold, or the muscle traction, medial to the fold, should be altered.

The Paradox of Smoking & Perceived Stress: Do Graphic Health Warnings Influence Smokers under High Stress in Adverse Ways?

The positive effects of graphic health warnings (GHWs) on quitting smoking have been widely demonstrated in the literature on cigarette warning. However, recent findings of smoker reactance to GHWs demand investigations of factors that may constrain the effects of GHWs. The current study sought to identify conditions in which GHWs do not have a positive impact on smokers' desire to quit with a focus on smokers' perceived stress. Two hundred and forty-four smokers in South Korea were exposed to either a text-only or a GHW cigarette pack in a between-subjects experiment. Results from this study suggest that the GHW condition is effective in increasing attention to the GHW, enhancing perceived usefulness of information, and desire to quit only among those with low (vs. high) perceived stress. In addition, an interaction effect between warning type and perceived stress on the desire to quit was sequentially mediated by attention and perceived information effectiveness. Based on the results, we suggest that GHWs were less effective for smokers with high levels of perceived stress because their stress appeared to exhaust the cognitive resources necessary to process the information.

Z-ligustilide and n-Butylidenephthalide Isolated from the Aerial Parts of Angelica tenuissima Inhibit Lipid Accumulation In Vitro and In Vivo.

Abnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of Angelica tenuissima Nakai (ATX) inhibited high-fat diet-induced hepatic steatosis in mice as well as oleic acid-induced neutral lipid accumulation in HepG2 cells. ATX decreased the mRNA and protein levels of CD36 and diglyceride acyltransferase 2 (DGAT2), the maturation of sterol regulatory element-binding proteins (SREBP), and the expression of the lipogenic target genes fasn and scd1. The ATX components, Z-ligustilide and n-butylidenephthalide, inhibited the expression of FATP5 and DGAT2 and thus oleic acid-induced lipid accumulation in HepG2 cells. These results suggest that ATX and its active components Z-ligustilide and n-butylidenephthalide inhibit fatty acid uptake and esterification in mice and have potential as therapeutics for NAFLD.

Hepatic upregulation of fetuin-A mediates acetaminophen-induced liver injury through activation of TLR4 in mice.

Acetaminophen (APAP)-induced liver injury (AILI) is initiated by the generation of a reactive metabolite and ultimately leads to hepatocyte necrosis. Necrotic cells secrete damage-associated molecular patterns that activate hepatic nonparenchymal cells and induce an inflammatory response. Fetuin-A is a hepatokine with reported involvement in low-grade inflammation in many diseases, due to acting as an endogenous ligand for TLR4. However, little is known about the role of fetuin-A in AILI. In this study, we showed that fetuin-A is involved in the aggravation of hepatotoxicity during the initial phase of AILI progression. Treatment with APAP increased the expression and serum levels of fetuin-A in mice. Fetuin-A upregulated transcription of pro-inflammatory cytokines and chemokines through activation of TLR4 and also increased monocyte infiltration into the liver, leading to necroinflammatory reactions in AILI. However, these reactions were attenuated with the silencing of fetuin-A using adenoviral shRNA. As a result, mice with silenced fetuin-A exhibited less centrilobular necrosis and liver injury compared to controls in response to APAP. In conclusion, our results suggest that fetuin-A is an important hepatokine that mediates the hepatotoxicity of APAP through production of chemokines and thus regulates the infiltration of monocytes into the liver, a critical event in the inflammatory response during the initial phase of AILI. Our results indicate that a strategy based on the antagonism of fetuin-A may be a novel therapeutic approach to the treatment of acetaminophen-induced acute liver failure.

Activation of SIRT1 by L-serine increases fatty acid oxidation and reverses insulin resistance in C2C12 myotubes.

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and the function is linked to cellular metabolism including mitochondrial biogenesis. Hepatic L-serine concentration is decreased significantly in fatty liver disease. We reported that the supplementation of the amino acid ameliorated the alcoholic fatty liver by enhancing L-serine-dependent homocysteine metabolism. In this study, we hypothesized that the metabolic production of NAD+ from L-serine and thus activation of SIRT1 contribute to the action of L-serine. To this end, we evaluated the effects of L-serine on SIRT1 activity and mitochondria biogenesis in C2C12 myotubes. L-Serine increased intracellular NAD+ content and led to the activation of SIRT1 as determined by p53 luciferase assay and western blot analysis of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) acetylation. L-Serine treatment increased the expression of the genes associated with mitochondrial biogenesis and enhanced mitochondrial mass and function. In addition, L-serine reversed cellular insulin resistance determined by insulin-induced phosphorylation of Akt and GLUT4 expression and membrane translocation. L-Serine-induced mitochondrial gene expression, fatty acid oxidation, and insulin sensitization were mediated by enhanced SIRT1 activity, which was verified by selective SIRT1 inhibitor (Ex-527) and siRNA directed to SIRT1. L-Serine effect on cellular NAD+ level is dependent on the L-serine metabolism to pyruvate that is subsequently converted to lactate by lactate dehydrogenase. In summary, these data suggest that L-serine increases cellular NAD+ level and thus SIRT1 activity in C2C12 myotubes.

Locational Relationship between the Lateral Border of the Frontalis Muscle and the Superior Temporal Line.

BACKGROUND: The frontalis is a representative target muscle for botulinum neurotoxin type A injections aimed at treating horizontal wrinkles in the forehead region. However, a lack of information regarding the shape and thickness of the frontalis may lead to unexpected side effects. METHODS: This study dissected hemifaces of 44 embalmed Korean and Thai cadavers and performed ultrasound examinations on 20 Korean volunteers. Two anatomical types were identified: (1) the lateral portion of the frontalis covered the superior temporal line in type I, and (2) the lateral border of the frontalis and the superior temporal line almost coincided in type II. A horizontal line was drawn laterally from the midpoint between the metopion and the glabella, and landmarks F1, F2, and F3 were defined as points where this horizontal reference line intersected with vertical lines from the midpoint of the pupil, the lateral canthus, and the lateral orbital rim, respectively. RESULTS: Type I was more common than type II [84 percent (37 of 44) versus 16 percent (seven of 44)]. When the lateral border of the frontalis ran along the border, there were no cases in which the superior temporal line was not visible. The mean minimum distance in type I was 10.53 mm. The muscle thicknesses at F1, F2, and F3 were 1.80 ± 0.44 mm (mean ± SD), 1.61 ± 0.37 mm, and 0.11 ± 0.04 mm, respectively. CONCLUSIONS: This study yielded data on the location and thickness of the lateral border of the frontalis. An anatomical study-based, ultrasound-guided injection technique can achieve reliable results when noninvasive treatment is applied to the forehead area.

Three-Dimensional Topography of the Emerging Point of the Ophthalmic Artery.

BACKGROUND: During periorbital noninvasive and surgical procedures, there is the risk of iatrogenic injury to the emerging point of the ophthalmic artery. This study aimed to determine the three-dimensional location of the emerging point of the ophthalmic artery and to provide clinicians with anatomical information that would help them to avoid associated complications. METHODS: Seventeen hemifaces of the emerging point of the ophthalmic artery from 10 Korean and seven Thai cadavers were dissected and scanned by a three-dimensional scanner. The emerging points of the ophthalmic artery of 30 healthy Korean volunteers were also detected using an ultrasound imaging system. RESULTS: The transverse distance from the medial canthus to the emerging of the ophthalmic artery was 3.8 ± 1.0 mm medially, and the vertical distance was 14.0 ± 2.9 mm superiorly. The transverse distance from the midline was 16.5 ± 1.7 mm to the emerging point of the ophthalmic artery and 20.0 ± 2.0 mm to the medial canthus. The measured depth from the skin surface to the emerging point of the ophthalmic artery was 4.8 ± 1.7 mm by means of three-dimensional scanning and 4.5 ± 1.1 mm using ultrasound detection. The vertical distance from the inferior margin of the superior orbital rim to the emerging point of the ophthalmic artery was 5.3 ± 1.4 mm. CONCLUSION: These data inform clinicians about the anatomical three-dimensional location of the emerging point of the ophthalmic artery, which will help them to avoid iatrogenic injury when they are performing periorbital clinical procedures.

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.

Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion-Induced Kidney and Liver Injury.

Acute kidney injury (AKI) is associate with high mortality. Despite evidence of AKI-induced distant organ injury, a relationship between AKI and liver injury has not been clearly established. The goal of this study is to investigate whether renal ischemia-reperfusion (IR) can affect liver pathophysiology. We showed that renal IR in mice induced fatty liver and compromised liver function through the downregulation of constitutive androstane receptor (CAR; -90.4%) and inhibition of hepatic very-low-density lipoprotein triglyceride (VLDL-TG) secretion (-28.4%). Treatment of mice with the CAR agonist 1,4-bis[2-(3,5 dichloropyridyloxy)] benzene (TCPOBOP) prevented the development of AKI-induced fatty liver and liver injury, which was associated with the attenuation of AKI-induced inhibition of VLDL-TG secretion. The hepatoprotective effect of TCPOBOP was abolished in CAR-/- mice. Interestingly, alleviation of fatty liver by TCPOBOP also improved the kidney function, whereas CAR ablation sensitized mice to AKI-induced kidney injury and lethality. The serum concentrations of interleukin-6 (IL-6) were elevated by 27-fold after renal IR, but were normalized in TCPOBOP-treated AKI mice, suggesting that the increased release of IL-6 from the kidney may have mediated the AKI responsive liver injury. Taken together, our results revealed an interesting kidney-liver organ cross-talk in response to AKI. Given the importance of CAR in the pathogenesis of renal IR-induced fatty liver and impaired kidney function, fatty liver can be considered as an important risk factor for kidney injury, and a timely management of hepatic steatosis by CAR activation may help to restore kidney function in patients with AKI or kidney transplant.

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice.

Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein ß (C/EBPß) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver.

Inhibition of homocysteine-induced endoplasmic reticulum stress and endothelial cell damage by l-serine and glycine.

Hyperhomocysteinemia is an independent risk factor for several cardiovascular diseases. The use of vitamins to modulate homocysteine metabolism substantially lowers the risk by reducing plasma homocysteine levels. In this study, we evaluated the effects of l-serine and related amino acids on homocysteine-induced endoplasmic reticulum (ER) stress and endothelial cell damage using EA.hy926 human endothelial cells. Homocysteine treatment decreased cell viability and increased apoptosis, which were reversed by cotreatment with l-serine. l-Serine inhibited homocysteine-induced ER stress as verified by decreased glucose-regulated protein 78kDa (GRP78) and C/EBP homologous protein (CHOP) expression as well as X-box binding protein 1 (xbp1) mRNA splicing. The effects of l-serine on homocysteine-induced ER stress are not attributed to intracellular homocysteine metabolism, but instead to decreased homocysteine uptake. Glycine exerted effects on homocysteine-induced ER stress, apoptosis, and cell viability that were comparable to those of l-serine. Although glycine did not affect homocysteine uptake or export, coincubation of homocysteine with glycine for 24h reduced the intracellular concentration of homocysteine. Taken together, l-serine and glycine cause homocysteine-induced endothelial cell damage by reducing the level of intracellular homocysteine. l-Serine acts by competitively inhibiting homocysteine uptake in the cells. However, the mechanism(s) by which glycine lowers homocysteine levels are unclear.

Characterizing the Lateral Border of the Frontalis for Safe and Effective Injection of Botulinum Toxin.

BACKGROUND: The forehead is a common site for injection of botulinum neurotoxin type A (BoNT-A) to treat hyperactive facial muscles. Unexpected side effects of BoNT-A injection may occur because the anatomy of the forehead musculature is not fully characterized. OBJECTIVES: The authors described the lateral border of the frontalis in terms of facial landmarks and reference lines to determine the safest and most effective forehead injection sites for BoNT-A. METHODS: The hemifaces of 49 embalmed adult Korean cadavers were dissected in a morphometric analysis of the frontalis. L2 was defined in terms of FT (the most protruding point of the frontotemporal region), L0 (the line connecting the infraorbital margin with the tragus), and L1 (the line parallel to L0 and passing through FT) such that L2 was positioned 45° from L1 and passed through FT. RESULTS: The distance from FT to the superior margin of the orbicularis oculi was 12.3 ± 3.3 mm. The frontalis extended more than 5 cm along L2 in 49 of 49 cases (100%), more than 6 cm in 47 cases (95.9%), more than 7 cm in 34 cases (69.4%), more than 8 cm in 11 cases (22.4%), and more than 9 cm in 3 cases (6.1%). The lateral border of the frontalis ran parallel to and within 1 cm of the medial side of L2. CONCLUSIONS: Surface anatomy mapping can assist with predicting the lateral border of the frontalis to minimize the side effects and maximize the efficiency of BoNT-A injections into the forehead.