bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic E‐Cigarette Usage on Blood Glucose
Authors: Hoskinson Hannah Nicole , Breit Matthew , Pitzer Christopher , Wu Zhong X , Olfert I M , Bryner Randy 
Published: November 2023

IntroductionTraditional cigarette usage has been linked to a number of nefarious metabolic effects, including insulin resistance, however the effects of electronic cigarettes (E‐cigs) are not currently known. Advertised as a safe alternative for traditional tobacco cigarettes, long‐term studies investigating the metabolic effects of E‐cigs are lacking. The purpose of this study was to gain a better understanding of the possible metabolic consequences of E‐cig usage. We hypothesize E‐cig usage will induce insulin resistance in mice.MethodsC57BL/6 mice were divided between E‐cig (n=13) and control (n=13) groups and exposed to either vaporized cappuccino flavored E‐cig liquid (18 mg/mL nicotine) or filtered air for 4h/d, 5 d/wk for 6 months. Fasting blood glucose (FBG) and glucose tolerance (GTT) were assessed following an overnight fast. A glucose bolus was administered via gelatin pellet (3g glucose/kg) which was ingested within 2 min. Blood was collected by tail nick and glucose measured using Bayer Contour glucometer and test strips.ResultsAfter 6 months exposure, total body mass (28.1 ±3.2g vs 27.3 ±3.1g) and lean body mass (18.71 ±0.25g vs 18.38 ±0.27g) were similar between E‐cig and air exposed groups, respectively. Likewise, E‐cig exposure did not result in significant difference in FBG (128. ±35mg/dL vs 120 ±33mg/dL), GTT0‐120, and peak glucose response (174 ±6mg/dL vs 159 ±6mg/dL, p=0.08). However for GTT0‐30 there was a significant interaction for glucose response between the groups (p=0.05).ConclusionThese results suggest there may be some initial differences in glucose response in animals exposed to E‐cigs when compared to controls, however FBG and overall glucose handling was not significantly different between the groups. Future studies are needed to determine if greater levels of nicotine exposure via E‐cigs contribute to impairment of glucose metabolism.Support or Funding InformationNIH Grant P20GM103434 (West Virginia IDeA Network for Biomedical Research Excellence) and Marshall‐WVU Health Initiative Award
Lhx1 is Required for Beta Cell Function Via Regulation of Glp1 Receptor (Glp1R)
Authors: Bethea Maigen M , Liu Yanping , Wade Alexa K , Habegger Kirk M , Hunter Chad S 
Published: November 2023

Diabetes mellitus is a disease by which functional insulin producing beta cells are lost. Understanding the transcription factor and co‐regulator complexes that govern beta cell development and function is essential for the generation of novel therapeutics and or cell replacement strategies to treat this disease. Our lab previously showed that the LIM‐homeodomain (LIM‐HD) transcription factor Islet‐1 (Isl1) interacts with the LIM domain binding protein 1 co‐regulator (Ldb1) to regulate key beta cell genes (e.g. Glp1R and MafA). However, recent mRNA analysis and immunofluorescence studies revealed the presence of another LIM‐HD transcription factor in the pancreas, LIM homeobox 1 (Lhx1). Through co‐immunoprecipitation experiments in beta cell nuclear extracts, we found that Lhx1 also interacts with Ldb1 and surprisingly, Isl1. This suggests that a novel Lhx1‐Ldb1‐Isl1 complex exists in beta cells. We therefore hypothesized that Lhx1 regulates similar target genes as Ldb1 and Isl1. To test this, we employed siRNA‐mediated Lhx1 knockdown along with chromatin immunoprecipitation experiments. We discovered that, Lhx1 knockdown in beta cell lines resulted in significantly reduced Glp1R transcripts. Additionally, we revealed that Lhx1 occupied a regulatory domain of Glp1R. Together, these data suggest that Lhx1 directly regulates Glp1R. Glucagon‐like peptide‐1 (Glp1) is an incretin hormone secreted from the L‐cells in the gut that acts through a receptor (Glp1R) on pancreatic beta cells to increase the production and secretion of insulin. To uncover pancreatic Lhx1 roles in vivo, we generated a mouse model of pancreas‐wide Lhx1 deficiency. Mutant mice were born in expected ratios and appeared overtly normal. However, Lhx1 loss led to hyperglycemia in aged mice, plus significantly reduced Glp1R transcripts in isolated islets. Therefore, we assessed beta cell responses to Glp1 in mutant mice by employing a Glp1R agonist during an intraperitoneal glucose tolerance test. Mutant mice treated with agonist displayed a dampened ability to clear blood glucose when compared to agonist treated controls. This suggested that Lhx1‐deficient mice lack an ability to respond to Glp1. Taken together, our data reveal for the first time that Lhx1 directly regulates the beta cell Glp1R gene. Future studies will examine the role of Lhx1 in pancreas following physiological stressors (e.g. high fat diet).Support or Funding InformationWe thank our funding sources: NIH‐NIDDK DK094842 and DK105209; ADA 1‐16‐JDF‐044, UAB Endocrinology Startup, and the UAB Comprehensive Diabetes Center
Attempting to improve the health of rural Kentucky citizens through educating its youth with health integrated school work and online mentoring interactions
Authors: Cooper Richard Morris , Byrd LaShay , Ho Jenni , Wilson Jennifer , Krall Rebecca McNall , Capilouto Gilson J. , Cooper Robin L 
Published: November 2023

Kentucky consistently ranks among the top ten states nation‐wide for the highest rates of chronic, preventable diseases. High school graduates in Kentucky are only required to successfully complete one semester of health, of which the course‐work is didactic and rarely transformative. The adoption of the Next Generation Science Standards, which advocate deep understanding and application of content, and using science to make informed decisions, provides a natural opportunity to integrate the National Health Education Standards into required science classes. We are developing an educational unit around the topic of Metabolic Syndrome (MSy). We capitalize on the knowledge of the life cycle, physiology, genetics, and behavior of Drosophila melanogaster to investigate the effects of diet on development, survival, behavior, environmental stress on survival and behavior, as well as physiological functions such as heart rate and neural‐muscular function with sensory motor tasks. We have started with high school classes defining the disease of MSy and contributing factors. High school classes are now designing live models of fruit flies fed different diets and examining the health (behavior, heart function, development and survival) of the fly populations. Students are developing talking points based on what they have personally learned, design displays, and use their models to teach others. For a culminating event, students will set up their demonstrations and displays, much like they do for a school science fair/symposium, in the places where rural people congregate the most ‐ parent teacher conference night, churches, ball games, flea markets.Support or Funding InformationCollege of Health Sciences, Univ. of KY. & personal funds (RLC).
The differential roles of Ca2+/Calmodulin‐dependent protein kinase IIδ2 and δ6 (CaMKIIδ2 and δ6) in mediating remodeling of human venous smooth muscle
Authors: Ginnan Roman Gregory , Shah Ravi , Lui Yong Feng , Conti David , Singer Harold A 
Published: November 2023

Arteriovenous fistulas (AVF) provide vascular access for lifesaving hemodialysis and involve the surgical bridging of the radial artery to the cephalic vein. The creation of the AVF results in the remodeling of the cephalic vein due to its exposure to arterial flow. Previous studies have demonstrated a positive role for CaMKIIδ2 in VSM cell proliferation and migration promoting arterial remodeling but little is known regarding CaMKII's role in mediating venous remodeling. Immunoblotting reveals an increase in the expression of CaMKII in remodeled human arteriovenous fistulas (AVF) as compared to controls. QPCR analysis indicates an increase in the CaMKIIδ isoform in these remodeled AVFs. Using CaMKIIδ selective antibodies we show an increase in CaMKIIδ2 and CaMKIIδ6 expression in the remodeled AVFs although PCR studies indicate that message for both CaMKIIδ isoforms is present in controls also. Immunofluorescent and biochemical analyses indicate that CaMKIIδ2 is expressed in the medial wall of control veins but is diminished in the medial wall of remodeled AVFs. Interestingly, CaMKIIδ2 expression is enriched in the neointimal lesions of remodeled AVFs. Conversely, CaMKIIδ6 is expressed in the medial wall of control veins and remodeled AVFs but not in the neointimal lesions of the remodeled AVFs. Studies in cultured VSM cells and an animal model of occlusive vascular disease indicate that overexpression of CaMKIIδ6 attenuates VSM cell migration and restenotic lesion development. Together, these studies indicate differential roles for CaMKIIδ isoforms in human vascular disease. While CaMKIIδ2's presence in the neointimal lesion and its known proliferative and promigratory functions indicate a positive role in neointimal lesion development, CaMKIIδ6's presence in the medial wall and its antimigratory function indicate a vasculoprotective role that could potentially be harnessed to ameliorate vascular disease.Support or Funding InformationRO1HL49426‐21 (H.S)DCI Paul Teschan Research Fund (H.S)
Chronic Cerebral Hypoperfusion Impairs Transient Receptor Potential Channel Vanilloid 4 (TRPV4)‐Mediated Dilation in Cerebral Parenchymal Arterioles From Normotensive, but not Hypertensive Rats
Authors: Dorrance Anne McLaren , Matin Nusrat , Fisher Courtney , Jackson William F 
Published: November 2023

Hypertension is a risk factor for cerebral small vessel disease and vascular cognitive impairment. Hypertension also increases the risk of other vascular injuries, such as carotid artery stenosis, that can place additional stress on the cerebral vasculature. To understand how hypertension affects the vascular response to reduced cerebral perfusion we studied normotensive Wistar Kyoto (WKY) rats and stroke prone spontaneously hypertensive rats (SHSRP). Rats underwent a bilateral carotid artery stenosis (BCAS) surgery or a sham surgery at 20 weeks of age, and they were studied 8 weeks later. In both cases the BCAS surgery impaired short‐term memory assessed by calculating the novel object exploration quotient (WKY: 0.6±0.04 vs 0.4±0.4, sham vs BCAS; n=11–13, p<0.05; SHRSP: 0.6±0.05 vs 0.5±0.04 sham vs BCAS; n=16, p<0.05). The effects of BCAS on the parenchymal arteriole (PA) function were assessed by pressure myography. BCAS had no effect of myogenic tone generation in either rat strain. In both WKY rats and SHRSP, BCAS caused a marked impairment in carbachol mediated endothelium‐dependent dilation (% dilation, WKY: 29.6±8.1 vs −10.2±7.4, sham vs BCAS; n=5–7, p<0.05; SHRSP: 17.5±5.3 vs −0.22±2.9, sham vs BCAS; n=5–6 p<0.05). Recent studies from our lab suggest that transient receptor potential channel vanilloid 4 (TRPV4) mediates endothelium‐dependent dilation in PAs. To assess the effects of BCAS on TRPV4‐dependent dilation, we used GSK1016790A, a potent and selective TRPV4 agonist. We found that TRPV4‐mediated dilation in the WKY rats was significantly impaired post‐BCAS (% dilation, 93.5±3.3 vs 57.7±13.3 Sham vs BCAS; n=3–4, p<0.05); this effect was not observed in the SHRSP (% dilation, 57.2±1.6 vs 51.8±6.9 sham vs BCAS; n=5–6, p<0.05). Interestingly TRPV4‐mediated dilation was impaired in the sham hypertensive rats compared to the sham WKY rats suggesting that hypertension impacts TRPV4 function. Together these data indicate that impaired TRPV4‐mediated dilation may contribute to the cognitive decline observed with BCAS in normotensive rats but not in rats with sustained hypertension.Support or Funding InformationSupported by 5P01HL070687‐12.
Role of Endothelin Type B Receptors in Microvascular Dysfunction Post‐partum in Women Who Have Had Preeclampsia
Authors: Stanhewicz Anna , Santhanam Lakshmi , Alexander Lacy 
Published: November 2023

Women with a history of preeclampsia have increased cardiovascular disease risk, however the mechanisms responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist post‐partum, despite the remission of the clinical symptoms of preeclampsia. One putative mechanism contributing to persistent microvessel dysfunction in these women is increased vasoconstrictor sensitivity to endothelin‐1 (ET‐1), is a reduction endothelin‐1 type B receptor‐(ETBR) mediated. We hypothesized that 1) women who have had preeclampsia (PreEC) would have a greater vasoconstrictor sensitivity to exogenous ET‐1 administration compared to control women who had a normal pregnancy (HC), and that 2) this increased sensitivity would be due to a reduction in ETBR‐mediated dilation (protocol 1). We further hypothesized that ETBR‐blockade would attenuate endothelium‐dependent dilation to the agonist acetylcholine (Ach) in HC, but not PreEC (protocol 2). Ten PreEC (31±2 yrs, 7±2 mos. post‐partum) and 10 HC (28±2 yrs, 7±2 mos. post‐partum) participated. In protocol 1, 3 intradermal microdialysis fibers were placed in the forearm skin for the graded infusion of ET‐1 (10−20 – 10−8M) alone, ET‐1 + 500nM BQ‐123 for ETAR‐blockade, or the graded infusion of sarofotoxin 6c (S6c; 10−12 – 10−5M). In protocol 2, 2 fibers were placed for the graded infusion of ACh (10−7 – 102 mM) alone, and ACh + 500nM BQ‐788 for ETBR‐blockade. In both protocols, red cell flux was measured over each site by laser‐Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC=LDF/MAP) and normalized to baseline (%CVCbase; protocol 1) or maximal (%CVCmax, 28mM SNP and local heat, 43°C; protocol 2). PreEC had augmented vasoconstrictor sensitivity to ET‐1 (PreEC −16.0±0.3 vs. HC −13.7±0.4 logEC50, P=0.01). Protocol 1: PreEC demonstrated a reduced dilation response to selective ETBR stimulation with ET‐1 (ET+BQ‐123: PreEC 130±22 vs. HC 290±77 %CVCbase; P=0.04), and reduced dilator sensitivity to the ETBR selective agonist S6c (PreEC −8.0±0.4 vs HC −8.9±0.7 logEC50; P=0.04). Protocol 2: PreEC had attenuated endothelium‐dependent dilation (PreEC 68±5 vs. HC 92±2 %CVCmax; P<0.01). ETBR inhibition attenuated the microvascular dilation response to ACh in HC (ACh alone 92±2 vs. ACh+BQ‐788 81±2 %CVCmax; P<0.01) but not in PreEC (ACh alone 68±5 vs. ACh+BQ‐788 74±3 %CVCmax; P=0.28). Women who have had preeclampsia demonstrate augmented vasoconstrictor sensitivity to ET‐1, mediated by a reduced ETBR‐dependent dilation response. Furthermore, attenuated ETBR‐mediated dilation contributes to diminished endothelial function which persists post‐partum in women who have had preeclampsia.Support or Funding InformationNIH F32 HL129677‐02 (Stanhewicz), R01 HL093238‐06 (Alexander)
Adiponectin Attenuates Hypertension‐Induced Vascular Remodeling through NHE‐1 Activity and LKB1/AMPK Signaling
Authors: Ghantous Crystal M , Radwan Zeina , Farhat Rima , Ghali Rana , Chaaya Nancy , Sabra Ramzi , Zeidan Asad 
Published: November 2023

IntroductionHypertension leads to vascular remodeling, affects circulating levels of leptin and adiponectin (APN), and is associated with increased sodium hydrogen exchanger isoform‐1 (NHE‐1) activity. The aim of this study is to investigate the vascular protective effects of APN during hypertension.HypothesisHypertension‐induced vascular smooth muscle cell (VSMC) remodeling is mediated by NHE‐1 activity, LKB1/AMPK signaling and attenuated by high APN/leptin ratio.MethodsIn order to study the effect of hypertension on VSMC remodeling, the in vivo rat model of angiotensin II (Ang II) infusion for 14 days and the in vitro model of mechanically stretching the rat portal vein (PV; with 1.2 gr weights due to the force‐length relationship normalized to the human force of stretch during hypertension and the longitudinal orientation of its VSMCs) were used. APN (10 μg/ml) and the selective NHE‐1 inhibitor cariporide (10 μM) were added to blood vessels. Activation of ERK1/2, AMPK and LKB1 in VSMCs was evaluated by Western blot. Leptin and APN expression was studied by Western blot, while ROS production was assessed by DHE staining.ResultsStretching the PV for 10 min increased p‐ERK1/2 by 2.10 ± 0.25 fold (n=5, p<0.05) in VSMCs (as compared to unstretched PVs), while cariporide and APN attenuated stretch‐induced ERK1/2 phosphorylation. Mechanical stretch for 10 min significantly decreased LKB1 and AMPK activation by 0.44 ± 0.14 and 0.34 ± 0.07 fold, respectively (n=6, p<0.05). This effect was attenuated by cariporide, while APN increased p‐LKB1 and p‐AMPK in stretched PVs to 1.0 ± 0.11 and 0.60 ± 0.04 fold respectively (n=4, p<0.05).Ang II‐infusion for 14 days increased leptin (1.48 ± 0.12 fold, n=4 p<0.05), decreased APN (0.86 ± 0.04 fold, n=6, p<0.05), and increased ROS (3.46 ± 0.07 fold, n=3, p<0.05) in PVs. Similar results were observed in the aortas of Ang II‐infused rats (leptin: 1.83 ± 0.36 fold; APN: 0.79 ± 0.06 fold; ROS: 1.54 ± 0.12 fold, n= 5, p<0.05) compared to sham‐operated rats.ConclusionAPN attenuates mechanical stretch‐induced VSMC remodeling by activating the LKB1‐AMPK axis and inhibiting ERK1/2, which are mediated by NHE‐1 activity. Moreover, hypertension‐induced vascular remodeling is associated with higher leptin synthesis, lower APN synthesis, and higher ROS production in VSMCs.Support or Funding InformationThis work was supported by Medical Practice Plan (MPP), Faculty of Medicine at AUB, to AZ.
STIM2 Contributes to the Proliferative Characteristics via Increasing Basal [Ca2+]cyt in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension
Authors: Song Shanshan , Carr Shane , Makino Ayako , Yuan Jason X.‐J. 
Published: November 2023

In pulmonary arterial hypertension (PAH), excessive cell proliferation is a key mechanism that results in an obstructive vasculopathy. An increase in basal intracellular free Ca2+ concentration ([Ca2+]cyt) has been described in pulmonary artery smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH) and explains the PASMCs proliferation. STIM2 is reported to be a feedback regulator that stabilizes basal [Ca2+]cyt. A selective up‐regulation of STIM2 has been observed in PASMCs from patients with IPAH and contributes to the transition of PASMCs from a contractile phenotype to proliferative phenotype in rats. The exact mechanism of STIM2‐mediated PASMC proliferation in PAH remains unclear. We hypothesized that the augmentation in cell proliferation can be explained in part by a STIM2‐mediated increase in basal [Ca2+]cyt. Compared with normal PASMCs, IPAH PASMCs had increased STIM2 expression and basal [Ca2+]cyt. Overexpression of STIM2 in normal PASMCs increased basal [Ca2+]cyt, phosphorylated‐Akt and mTOR levels, and enhanced the activation of CREB, STAT3 and NFATc2, which are Ca2+/calmodulin‐sensitive transcription factors, resulting in increased cell proliferation. Knockdown of STIM2 in IPAH PASMCs decreased basal [Ca2+]cyt, phosphorylated‐Akt and mTOR levels, and reduced the activation of CREB, STAT3 and NFATc2, leading to decreased cell proliferation. The generalized upregulation of STIM2 in human PAH may overload intracellular Ca2+ and be a therapeutic target and biomarker.Support or Funding InformationThis work was supported in part by the grants from the National Heart, Lung and Blood Institute of the National Institutes of Health (HL115014, HL066012 and HL125208).
Metabolic Acidosis Inhibits Pulmonary Inflammation and Ameliorates Experimental Pulmonary Hypertension
Authors: Hudalla Hannes , Michael Zoe , Kourembanas Stella , Christou Helen 
Published: November 2023

IntroductionPulmonary inflammation contributes to the pathogenesis of pulmonary hypertension (PH). We previously reported that metabolic acidosis ameliorated experimental PH but the underlying mechanisms of protection are unknown. We hypothesized that treatment with Acetazolamide (ACTZ) or ammonium chloride (NH4Cl) may ameliorate Sugen/Hypoxia (SU/Hx)‐induced severe PH by modulating lung inflammation.MethodsMale Sprague‐Dawley rats injected with Sugen (20 mg/kg,sc) or vehicle were exposed to normoxia or hypoxia (9%O2) for 3 weeks. As an early intervention, ACTZ (1.7mg/ml) or NH4Cl (1.5%) in the drinking water was given from week 1 to 3 (2 weeks). We assessed hemodynamics and right ventricular hypertrophy (RVH) (Fulton's Index, FI). Lungs, alveolar macrophages, pulmonary arteries (PA) and blood serum were collected for RT‐qPCR and ELISA. Pulmonary artery smooth muscle cells (PASMC) were treated with TNFα (10ng/ml) and de‐differentiation and proliferation was assessed by RT‐qPCR and proliferation assay. Bone marrow‐derived macrophages (BMDM) were polarized to M1 using LPS (100ng/ml) and INF‐γ (20ng/ml) for 6 or 24h and exposed to non‐hypercapnic acidosis at different pH (7.4, 7.0, 6.8) in vitro. Statistical analysis by ANOVA and Mean ±SEM values are presented.ResultsBoth ACTZ‐ and NH4Cl‐treatment caused robust metabolic acidosis and significantly lowered RVSP and FI compared to untreated SU/Hx animals (RVSP: 42.47±2.95 vs ACTZ:27.81±2.97 or NH4Cl:28.61±1.23 mmHg, FI: 0.66±0.03 vs ACTZ:0.44±0.02 or NH4Cl:0.29±0.05). Expression of TNFα, IL‐6, and MCP‐1 of SU/Hx rats were significantly higher in whole lungs and alveolar macrophages from untreated SU/Hx rats compared to controls and serum levels of IL‐6 were also elevated. These changes were ameliorated in the two intervention groups. RT‐qPCR of pulmonary arteries revealed enhanced proliferation and de‐differentiation in untreated SU/Hx animals, and reversal in both intervention groups. In vitro we could demonstrate similar de‐differentiation and proliferation of PASMC upon TNFα treatment. In cultured BMDM, metabolic acidosis down regulated cytokine production (TNFα, IL‐6, and MCP‐1) in a pH‐dependent manner.ConclusionMetabolic acidosis induced by ACTZ or NH4Cl ameliorates PH and RVH in the SU/Hx model of severe PH and reduces the lung inflammatory response. pH dependency of cytokine production in macrophages may be a novel therapeutic approach in PH‐related inflammation.Support or Funding InformationFunding: NIH 1R01 HL 116573 (to H.C.)
Arginase 2 knockout mice are protected against hypoxia‐induced pulmonary hypertension
Authors: Xue Jianjing , Nelin Leif D , Chen Bernadette 
Published: November 2023

We have previously shown that hypoxia‐induced pulmonary artery smooth muscle cell proliferation depends on arginase 2 (arg2) induction. We hypothesized that deficiency of arginase 2 will be protective against pulmonary hypertension in a murine model of hypoxia‐induced pulmonary hypertension. Male and female heterozygous mice with a targeted mutation of Arg2 (B6.Cg‐Arg2tm1Weo/J, Arg2+/−; Jackson Laboratory, Bar Harbor, ME) were crossed. The littermate wild‐type (WT), Arg2+/+ controls and homozygous mutant Arg2−/− knockout (KO) mice (8–10 weeks‐old) were exposed to normoxia or normobaric hypoxia (10% O2) for 28 days. Consistent with previous reports, we demonstrate that WT mice exposed to 10% O2 for 28 days have right ventricular (RV) hypertrophy as evidenced by an increased RV/[left ventricle (LV)+septum (S)] ratio compared to mice exposed to 21% O2, a change of ~0.27 ± 0.04. This hypoxia‐induced increase in RV/(LV+S) is significantly blunted in Arg2 KO mice (0.15 ± 0.03, p < 0.05). Additionally, echocardiographic findings of elevated pulmonary artery pressures as evidenced by a decrease in pulmonary artery acceleration time (PAT)/pulmonary ejection time (PET) are seen in WT mice exposed to hypoxia compared to normoxia (0.213 ± 0.010 vs 0.263 ± 0.012, p < 0.01). There was no significant difference in PAT/PET in Arg2 KO mice exposed to hypoxia (0.248 ± 0.008) compared to WT (0.263 ± 0.012) or Arg2 KO mice (0.261 ± 0.008) exposed to normoxia. Our findings suggest that arginase 2 is critical in the pathogenesis of hypoxia‐induced pulmonary hypertension.Support or Funding Information5 K08 HL105677 05 BC