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1.
Proc Natl Acad Sci U S A ; 121(27): e2406946121, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38917015

ABSTRACT

Progerin, the protein that causes Hutchinson-Gilford progeria syndrome, triggers nuclear membrane (NM) ruptures and blebs, but the mechanisms are unclear. We suspected that the expression of progerin changes the overall structure of the nuclear lamina. High-resolution microscopy of smooth muscle cells (SMCs) revealed that lamin A and lamin B1 form independent meshworks with uniformly spaced openings (~0.085 µm2). The expression of progerin in SMCs resulted in the formation of an irregular meshwork with clusters of large openings (up to 1.4 µm2). The expression of progerin acted in a dominant-negative fashion to disrupt the morphology of the endogenous lamin B1 meshwork, triggering irregularities and large openings that closely resembled the irregularities and openings in the progerin meshwork. These abnormal meshworks were strongly associated with NM ruptures and blebs. Of note, the progerin meshwork was markedly abnormal in nuclear blebs that were deficient in lamin B1 (~50% of all blebs). That observation suggested that higher levels of lamin B1 expression might normalize the progerin meshwork and prevent NM ruptures and blebs. Indeed, increased lamin B1 expression reversed the morphological abnormalities in the progerin meshwork and markedly reduced the frequency of NM ruptures and blebs. Thus, progerin expression disrupts the overall structure of the nuclear lamina, but that effect-along with NM ruptures and blebs-can be abrogated by increased lamin B1 expression.


Subject(s)
Lamin Type A , Lamin Type B , Nuclear Lamina , Nuclear Lamina/metabolism , Lamin Type A/metabolism , Lamin Type A/genetics , Lamin Type B/metabolism , Lamin Type B/genetics , Humans , Progeria/metabolism , Progeria/genetics , Progeria/pathology , Animals , Protein Precursors/metabolism , Protein Precursors/genetics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Mice
2.
Front Vet Sci ; 11: 1346313, 2024.
Article in English | MEDLINE | ID: mdl-38716232

ABSTRACT

Introduction: Canine bacterial keratitis is a corneal infection that causes various symptoms, including visual impairment, and necessitates eye removal in severe cases. Staphylococcus pseudintermedius is a pathogen that causes significant bacterial keratitis in canine patients. Moreover, multi-drug resistant Staphylococcus pseudintermedius (MDRSP) has been reported in both humans and animals. Regarding treatment failure against multi-drug resistant (MDR) pathogens with classic antibiotics, antimicrobial compounds derived from probiotics have been suggested as an alternative approach. Methods: Ligilactobacillus animalis SWLA-1 strain and its cell-free supernatant (CFS) have previously demonstrated potent antimicrobial activity against various MDR pathogenic bacteria. Based on this finding, we evaluated the anti-staphylococcal activity of CFS derived from Ligilactobacillus animalis SWLA-1 against MDRSP in a newly established ex vivo canine corneal infection model using fresh canine corneoscleral rims. Additionally, an in vitro cytotoxicity test using human keratocytes was performed. Results and Discussion: CFS significantly inhibited the growth of MDRSP in the novel ex vivo model and did not exhibit any significant toxicity against keratocytes in vitro. Based on these results, the antimicrobial compounds in CFS show potential as a novel approach for MDR staphylococcal keratitis treatment.

3.
Vasc Specialist Int ; 40: 10, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38527946

ABSTRACT

Purpose: : Endotension is a rare late complication characterized by an increase in sac size without any type of endoleak following endovascular aortic aneurysm repair (EVAR). Due to its rarity, few studies have demonstrated the mechanism behind and the management of endotension. In this study, we aimed to better understand the treatment and the long-term outcome of endotension in a single-center cohort. Materials and Methods: : This study was designed for a retrospective review of the patients diagnosed with endotension between January 2006 and December 2017. The study patients were categorized into two groups (primary versus secondary) based on the presence of any type of endoleak before the diagnosis of endotension. We collected data related to endotension treatment, intraoperative findings, and long-term outcomes. Results: : In a cohort of 15 patients diagnosed with endotension following EVAR, eight were classified into the primary endotension (PE) group without prior endoleak, and seven exhibited secondary endotension (SE). Among the eight PE patients, endovascular intervention for a preemptive purpose was conducted in six patients; however, three (50%) showed continuous sac expansion and finally received open conversion. Overall, eight patients (five in PE and three in SE) underwent open conversion, and one (12.5%) presented with an undetected endoleak during the operative findings. Postoperative morbidity was observed in three patients with no operative mortality. Conclusion: : Endotension can be managed initially through simple observation for changes on serial images, along with preemptive endovascular intervention. However, surgical intervention should be considered for patients with specific indications including continuous aneurysm sac enlargement, presence of symptoms, suspicions of migration of stent-graft with endoleak, and infection.

4.
Ann Transplant ; 29: e942763, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38319291

ABSTRACT

BACKGROUND Simultaneous liver-kidney transplantation (SLKT) and kidney transplantation (KT) after liver transplantation (LT) provide potential treatment options for patients with end-stage liver and kidney disease. There is increasing attention being given to liver-kidney transplantation (LTKT), particularly regarding the immune-protective effects of the liver graft. This retrospective, single-center, observational study aimed to evaluate the clinical outcomes of KT in LTKT patients - either SLKT or KT after LT (KALT) - compared to KT alone (KTA). MATERIAL AND METHODS We included patients who underwent KT between January 2005 and December 2020, comprising a total of 4312 patients divided into KTA (n=4268) and LTKT (n=44) groups. The LTKT group included 11 SLKT and 33 KALT patients. To balance the difference in sample sizes between the 2 groups, we performed 3: 1 propensity score matching (PSM). RESULTS There was no significant difference in graft survival between the groups. However, the LTKT group exhibited significantly superior rejection-free survival compared to the KTA group (P.


Subject(s)
Kidney Transplantation , Humans , Retrospective Studies , Transplantation, Homologous , Liver , Allografts
5.
Exp Eye Res ; 240: 109782, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38199260

ABSTRACT

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.


Subject(s)
Cytokines , Dry Eye Syndromes , Rabbits , Humans , Animals , Cytokines/genetics , Cytokines/metabolism , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/metabolism , Interleukin-10/adverse effects , Interleukin-10/metabolism , Mucin-4/metabolism , Tumor Necrosis Factor-alpha/metabolism , CA-125 Antigen , Phylogeny , Dry Eye Syndromes/metabolism , Tears/metabolism , Benzalkonium Compounds , RNA, Messenger/genetics , RNA, Messenger/metabolism , Mammals
6.
Eur J Nucl Med Mol Imaging ; 51(4): 978-990, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38049658

ABSTRACT

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Fibronectin Type III Domain , Fluorine Radioisotopes , Lung Neoplasms , Recombinant Proteins , Humans , Mice , Animals , B7-H1 Antigen/metabolism , Ligands , Macaca fascicularis/metabolism , Positron-Emission Tomography/methods , Peptides/chemistry
7.
Vet Med Sci ; 10(1): e1334, 2024 01.
Article in English | MEDLINE | ID: mdl-38100149

ABSTRACT

OBJECTIVE: The tear clearance rate (TCR), determined using anterior segment optical coherence tomography (AS-OCT) images, and its correlation with ocular surface parameters, including blink rate, Schirmer tear test-1 (STT-1) and tear film breakup time (TFBUT), were evaluated. ANIMALS STUDIED: Left eyes of 20 client-owned dogs with no ocular disease symptoms. PROCEDURES: The tear meniscus height (TMH) was evaluated using AS-OCT images before the instillation of 5 µL saline (TMHbase ), immediately post-instillation (TMH0 ), 30-s post-instillation (TMH0.5 ) and at 1 min intervals for 5 min post-instillation (TMH1 , TMH2 , TMH3 , TMH4 and TMH5 ). The TCR was calculated using the formula [(TMH0  - TMH0.5 )/TMH0 ]×100 (%). The eyes were classified into two groups with the median: 'High TMHbase ' (n = 10) and 'Low TMHbase ' (n = 10). Eyes with STT-1 values ≥15 mm/min and TFBUT ≥ 12 s were assigned to the 'Satisfied' subgroup, whereas eyes not satisfying these criteria were assigned to the 'Not satisfied' subgroup. RESULTS: TMH0 was higher than TMH0.5 (p = 0.02), wherein TMH0.5 to TMH5 did not differ significantly. The TCR and blink rate were negatively correlated (p = 0.02). The 'Not satisfied' subgroup in the low TMHbase group had a lower TCR (p = 0.02) and higher blink rate (p = 0.04) than the 'Satisfied' subgroup. CONCLUSIONS: TCR can be evaluated using AS-OCT in dogs. Eyes with a lower TCR blink more frequently. TMH merits studying to understand ocular surface health.


Subject(s)
Dog Diseases , Dry Eye Syndromes , Humans , Dogs , Animals , Tomography, Optical Coherence/veterinary , Tomography, Optical Coherence/methods , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/veterinary , Tears , Receptors, Antigen, T-Cell
8.
Mol Imaging Biol ; 26(2): 301-309, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38123744

ABSTRACT

PURPOSE: In cancer immunotherapy, the blockade of the interaction between programmed death-1 and its ligand (PD-1:PD-L1) has proven to be one of the most promising strategies. However, as mechanisms of resistance to PD-1/PD-L1 inhibition include variability in tumor cell PD-L1 expression in addition to standard tumor biopsy PD-L1 immunohistochemistry (IHC), a comprehensive and quantitative approach for measuring PD-L1 expression is required. Herein, we report the development and characterization of an 18F-PD-L1-binding macrocyclic peptide as a PET tracer for the comprehensive evaluation of tumor PD-L1 expression in cancer patients. PROCEDURES: 18F-BMS-986229 was characterized for PD-L1 expression assessment by autoradiography or PET imaging. 18F-BMS-986229 was utilized to evaluate tumor PD-L1 target engagement in competition with a macrocyclic peptide inhibitor of PD-L1 (BMS-986189) over a range of doses using PET imaging. A whole-body radiation dosimetry study of 18F-BMS-986229 in healthy non-human primates (NHPs) was performed. RESULTS: In vitro autoradiography showed an 8:1 binding ratio in L2987(PD-L1 +) vs. HT-29 (PD-L1-) tumors, more than 90% of which could be blocked with 1 nM of BMS-986189. Ex vivo autoradiography showed that 18F-BMS-986229 detection was penetrant over a series of sections spanning the entire L2987 tumor. In vivo PET imaging in mice demonstrated a 5:1 tracer uptake ratio (at 90-100 min after tracer administration) in L2987 vs. HT-29 tumors and demonstrated 83%-93% specific binding of BMS-986189 within those dose ranges. In a healthy NHP dosimetry study, the resultant whole-body effective dose was 0.025 mSv/MBq. CONCLUSION: 18F-BMS-986229 has been preclinically characterized and exhibits high target specificity, low background uptake, and a short blood half-life supportive of same day imaging in the clinic. As the PET tracer, 18F-BMS-986229 shows promise in the quantification of PD-L1 expression, and its use in monitoring longitudinal changes in patients may provide insights into PD-1:PD-L1 immuno-therapy treatment outcomes.


Subject(s)
B7-H1 Antigen , Neoplasms , Humans , Animals , Mice , B7-H1 Antigen/metabolism , Programmed Cell Death 1 Receptor , Positron-Emission Tomography/methods , Radiometry , Peptides
9.
J Clin Invest ; 133(23)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37824203

ABSTRACT

Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.


Subject(s)
Apolipoprotein A-V , Hypertriglyceridemia , Receptors, Lipoprotein , Animals , Mice , Capillaries/metabolism , Hypertriglyceridemia/genetics , Hypertriglyceridemia/metabolism , Lipoprotein Lipase/genetics , Lipoprotein Lipase/metabolism , Receptors, Lipoprotein/genetics , Receptors, Lipoprotein/metabolism , Triglycerides/blood , Apolipoprotein A-V/genetics
10.
Nucleus ; 14(1): 2262308, 2023 12.
Article in English | MEDLINE | ID: mdl-37754663

ABSTRACT

The Lmna knockout mouse (Lmna-/-) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of Lmna intron 7-exon 11 sequences and was reported to be a null allele. Later, Jahn and coworkers discovered that the mutant allele produces a 54-kDa truncated lamin A and identified, by RT-PCR, a Lmna cDNA containing exon 1-7 + exon 12 sequences. Because exon 12 encodes prelamin A's CaaX motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in Lmna-/- mouse embryonic fibroblasts (MEFs) was predominantly nucleoplasmic rather than at the nuclear rim, leading us to hypothesize that it was not farnesylated. Our study revealed that the most abundant Lmna transcripts in Lmna-/- MEFs contain exon 1-7 but not exon 12 sequences. Exon 1-7 + exon 12 transcripts were detectable by PCR but in trace amounts. We suspect that these findings explain the nucleoplasmic distribution of the truncated lamin A in Lmna-/- MEFs, and subsequent cell transduction experiments support this suspicion. A truncated lamin A containing exon 1-7 sequence was nucleoplasmic, whereas a lamin A containing exon 1-7 + exon 12 sequences was located along the nuclear rim. Our study explains the nucleoplasmic targeting of truncated lamin A in Lmna-/- MEFs and adds to our understanding of a commonly used strain of Lmna-/- mice.


Subject(s)
Fibroblasts , Lamin Type A , Animals , Mice , Cell Nucleus , Lamin Type A/genetics , Mice, Knockout
11.
Vet Ophthalmol ; 26(5): 440-445, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37565779

ABSTRACT

OBJECTIVE: To compare tear film (TF) osmolarity measured using TearLab® and I-PEN® osmometers in the same dogs without any ocular surface disease. ANIMAL STUDIED: Fifty-two dogs (98 eyes) of different breeds were evaluated. PROCEDURES: Tear film (TF) osmolarity was evaluated at 2-min intervals. The test was randomly determined, and single measurements were performed using each osmometer. Subsequently, complete ophthalmologic examinations were performed based on Schirmer tear test-1 (STT-1) analysis, tear film breakup time (TFBUT), and slit-lamp biomicroscopy. For each osmometer, the mean ± standard deviation of the TF osmolarity was calculated, and a paired Student's t-test was used to compare the values obtained. Pearson correlation analysis was performed to assess the association between osmolarity and other values such as STT-1, TFBUT, and age. RESULTS: Tear film osmolarity determined using TearLab® (340.42 ± 15.87 mOsm/L) and I-PEN® (321.58 ± 17.39 mOsm/L) were significantly different (p < .001). However, statistical significance could not be confirmed between osmolarity and other values, such as STT-1, TFBUT, and age. CONCLUSIONS: In dogs, the TF osmolarity values obtained using TearLab® tend to be higher than those obtained using I-PEN®, contrary to that observed in humans. These findings can serve as a reference for establishing normal values for each osmometer for clinical use in measuring TF osmolarity in dogs.


Subject(s)
Dog Diseases , Lacerations , Animals , Dogs , Eye , Lacerations/veterinary , Osmolar Concentration , Osmometry/veterinary , Slit Lamp Microscopy , Tears
12.
Sensors (Basel) ; 23(12)2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37420755

ABSTRACT

In recent years, the field of robotic portrait drawing has garnered considerable interest, as evidenced by the growing number of researchers focusing on either the speed or quality of the output drawing. However, the pursuit of either speed or quality alone has resulted in a trade-off between the two objectives. Therefore, in this paper, we propose a new approach that combines both objectives by leveraging advanced machine learning techniques and a variable line width Chinese calligraphy pen. Our proposed system emulates the human drawing process, which entails planning the sketch and creating it on the canvas, thus providing a realistic and high-quality output. One of the main challenges in portrait drawing is preserving the facial features, such as the eyes, mouth, nose, and hair, which are crucial for capturing the essence of a person. To overcome this challenge, we employ CycleGAN, a powerful technique that retains important facial details while transferring the visualized sketch onto the canvas. Moreover, we introduce the Drawing Motion Generation and Robot Motion Control Modules to transfer the visualized sketch onto a physical canvas. These modules enable our system to create high-quality portraits within seconds, surpassing existing methods in terms of both time efficiency and detail quality. Our proposed system was evaluated through extensive real-life experiments and showcased at the RoboWorld 2022 exhibition. During the exhibition, our system drew portraits of more than 40 visitors, yielding a survey outcome with a satisfaction rate of 95%. This result indicates the effectiveness of our approach in creating high-quality portraits that are not only visually pleasing but also accurate.


Subject(s)
Robotic Surgical Procedures , Humans , Face , Nose , Eye , Mouth
13.
Vet Ophthalmol ; 26(4): 324-330, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36840613

ABSTRACT

OBJECTIVE: We aimed to track and evaluate the association between vitreous degeneration and the development of cataracts or retinal detachments in dogs over a long period. ANIMAL STUDIED: Data on vitreous degeneration, cataracts, and retinal detachment in 102 eyes were collected from 68 dogs who underwent ocular ultrasonography at least twice between March 2017 and November 2021 at the Veterinary Medical Teaching Hospital, Konkuk University. The mean follow-up time was 515 ± 256 (mean ± standard deviation; range: 81-1196) days. PROCEDURE: Development of cataracts and retinal detachment, according to the severity of vitreous degeneration grade (VDG), was evaluated during long-term follow-up. RESULTS: In the cataract study (87 eyes, 61 dogs), the number of cataracts developed according to VDG (grade: 0-3) were as follows: VDG 0: 1 in 10 (10%) eyes, VDG 1: 15 in 35 (43%) eyes, VDG 2: 15 in 30 (50%) eyes, and VDG 3: 10 in 12 (83%) eyes. It was significantly different among grades (p = .026). In the retinal detachment study (95 eyes, 64 dogs), the number of retinal detachments developed according to each VDG were as follows: VDG 0: 0 in 11 (0%) eyes, VDG 1: 1 in 36 (3%) eyes, VDG 2: 5 in 35 (14%) eyes, and VDG 3: 4 in 13 (30%) eyes. It was also significantly different among grades (p = .019). CONCLUSIONS: During long-term follow-up, dogs with severe vitreous degeneration had an increased risk of cataract and retinal detachment development than those without or with mild vitreous degeneration.


Subject(s)
Cataract , Dog Diseases , Retinal Detachment , Dogs , Animals , Retinal Detachment/etiology , Retinal Detachment/veterinary , Eye/diagnostic imaging , Cataract/complications , Cataract/veterinary , Visual Acuity , Ultrasonography , Dog Diseases/etiology
14.
Proc Natl Acad Sci U S A ; 120(8): e2219833120, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36787365

ABSTRACT

Lipoprotein lipase (LPL) is secreted into the interstitial spaces by parenchymal cells and then transported into capillaries by GPIHBP1. LPL carries out the lipolytic processing of triglyceride (TG)-rich lipoproteins (TRLs), but the tissue-specific regulation of LPL is incompletely understood. Plasma levels of TG hydrolase activity after heparin injection are often used to draw inferences about intravascular LPL levels, but the validity of these inferences is unclear. Moreover, plasma TG hydrolase activity levels are not helpful for understanding LPL regulation in specific tissues. Here, we sought to elucidate LPL regulation under thermoneutral conditions (30 °C). To pursue this objective, we developed an antibody-based method to quantify (in a direct fashion) LPL levels inside capillaries. At 30 °C, intracapillary LPL levels fell sharply in brown adipose tissue (BAT) but not heart. The reduced intracapillary LPL levels were accompanied by reduced margination of TRLs along capillaries. ANGPTL4 expression in BAT increased fourfold at 30 °C, suggesting a potential explanation for the lower intracapillary LPL levels. Consistent with that idea, Angptl4 deficiency normalized both LPL levels and TRL margination in BAT at 30 °C. In Gpihbp1-/- mice housed at 30 °C, we observed an ANGPTL4-dependent decrease in LPL levels within the interstitial spaces of BAT, providing in vivo proof that ANGPTL4 regulates LPL levels before LPL transport into capillaries. In conclusion, our studies have illuminated intracapillary LPL regulation under thermoneutral conditions. Our approaches will be useful for defining the impact of genetic variation and metabolic disease on intracapillary LPL levels and TRL processing.


Subject(s)
Adipose Tissue, Brown , Receptors, Lipoprotein , Animals , Mice , Adipose Tissue/metabolism , Adipose Tissue, Brown/metabolism , Antibodies/metabolism , Lipoprotein Lipase/metabolism , Receptors, Lipoprotein/metabolism , Temperature , Triglycerides/metabolism
15.
Vet Med Sci ; 8(6): 2268-2272, 2022 11.
Article in English | MEDLINE | ID: mdl-36049128

ABSTRACT

Since the removal of the NM causes KCS in dogs, it was contraindicated to remove the NM unless unavoidable such as in a malignant tumour. However, to the best of author's knowledge, there are no reports of conjunctivitis and keratitis owing to decreased tear production following removal of the NM gland. This case study demonstrates the tear production changes in a dog for a year after removal of the nictitating membrane (NM) due to suspicion of a malignant tumour. A 13-year-old spayed female English Cocker Spaniel who had suffered from severe ocular discharge, discomfort, keratoconjunctivitis sicca (KCS), and NM enlargement in the right eye was brought to our hospital. The dog could not tolerate treatment with topical 0.2% cyclosporine or corticosteroids. The dog's right eye had NM gland prolapse, severe follicular conjunctivitis and a very low Schirmer tear test-1 (STT-1) value of 3 mm/min. Furthermore, the result of fine needle aspiration of the enlarged NM gland suggested a risk of malignancy. Despite the risk of KCS, complete NM resection was performed to diagnose the tumour. Fortunately, the final histopathological evaluation revealed chronic inflammation without any evidence of malignancy. Contrary to concerns that the STT-1 value would further decrease after the removal of the NM gland, the STT-1 value remained elevated compared to that before surgery, and the clinical symptoms improved for a year. It is generally known that NM gland resection is not recommended due to the risk of developing iatrogenic KCS unless a malignant tumour is suspected. In this case, surgical removal of the inflammatory NM gland that was not responsive to medications had a positive effect on KCS. Since the inflammatory and structural disease of the NM was strengthening KCS, the outcome was thought to be different from that when the normal third eyelid was removed.


Subject(s)
Conjunctivitis , Dog Diseases , Keratoconjunctivitis Sicca , Neoplasms , Female , Dogs , Animals , Keratoconjunctivitis Sicca/surgery , Keratoconjunctivitis Sicca/veterinary , Nictitating Membrane/surgery , Neoplasms/veterinary , Conjunctivitis/diagnosis , Conjunctivitis/etiology , Conjunctivitis/veterinary , Inflammation/veterinary , Dog Diseases/diagnosis , Dog Diseases/surgery
16.
Top Companion Anim Med ; 50: 100674, 2022.
Article in English | MEDLINE | ID: mdl-35640871

ABSTRACT

Systemic arterial hypertension is a health condition causing target organ damage (TOD) in dogs. Early and effective treatment is essential to prevent hypertensive emergencies and to reduce the risk of TOD. This study investigated the diseases underlying hypertension and compared the short-term efficacy of antihypertensive drugs in dogs. We evaluated the medical records of client-owned dogs treated with antihypertensive drugs between 2017 and 2018. The study included 75 dogs diagnosed with systemic arterial hypertension (systolic blood pressure ≥150 mmHg). The dogs were classified based on treatment with the following antihypertensive drugs: calcium channel blocker amlodipine, angiotensin-converting enzyme inhibitor ramipril, and angiotensin receptor blocker telmisartan, either as monotherapy or combination therapy (telmisartan + amlodipine or ramipril + amlodipine). Systolic blood pressure was measured using an indirect Doppler method over 4 weeks. Naturally acquired hyperadrenocorticism was the most common disorder to be diagnosed in conjunction with systemic hypertension. In the telmisartan group, the systolic blood pressure decreased more rapidly for 3 weeks compared to ramipril. The combination of telmisartan and amlodipine showed the greatest decrease in systolic blood pressure throughout the 4-week treatment period. This study is meaningful as it suggests guidelines for the use of various antihypertensive drugs in dogs.


Subject(s)
Dog Diseases , Hypertension , Amlodipine/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Dog Diseases/drug therapy , Dogs , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/veterinary , Ramipril/therapeutic use , Telmisartan/therapeutic use , Treatment Outcome
17.
Opt Express ; 30(2): 1521-1533, 2022 Jan 17.
Article in English | MEDLINE | ID: mdl-35209310

ABSTRACT

The telecommunication society is paving the way toward ultra-high frequency regions, including the millimeter wave (mmWave) and sub-terahertz (sub-THz) bands. Such high-frequency electromagnetic waves induce a variety of physical constraints when they are used in wireless communications. Inevitably, the fiber-optic network is deeply embedded in the mobile network to resolve such challenges. In particular, the radio-over-fiber (RoF)-based distributed antenna system (DAS) can enhance the accessibility of next-generation mobile networks. The inherent benefits of RoF technology enhance the DAS network in terms of practicality and transmission performance by enabling it to support the 5G mmWave and 6G THz services simultaneously in a single optical transport link. Furthermore, the RoF allows the indoor network to be built based on the cascade architecture; thus, a service zone can be easily added on request. This study presents an RoF-based multi-service DAS network and experimentally investigates the feasibility of the proposed system.

18.
Vet Med Sci ; 8(2): 476-482, 2022 03.
Article in English | MEDLINE | ID: mdl-34919349

ABSTRACT

BACKGROUND: Eyelid mass removal and cryotherapy application using only local anaesthesia and restraint may benefit patients with high anaesthesia risks. OBJECTIVE: To evaluate and validate cryosurgery application using the CryoPen XL® on palpebral masses under local anaesthesia for patients not suitable for general anaesthesia. METHODS: Thirty patients underwent the procedure between November 2015 and April 2020. The procedure steps were as follows: skin preparation and local anaesthesia of the affected eyelid; debulking by resection and/or squeezing out the inspissated material; cryosurgery and post-operative care using topical medication, antibiotics and anti-inflammatory ointment. The medical records of the patients who underwent the operation were evaluated. Moreover, a telephonic survey with the pet owners was performed to determine recurrence, time to recurrence, survivability and side effects. RESULTS: Among the 30 owners, 29 responded to the survey. Ten (10/38, 26.3%) masses recurred with an average time to recurrence of 6.0 months. The estimated average depths for all, non-recurred, and recurred masses were 1.89, 1.88 and 1.90 mm, respectively. The average recurrence rate and time to recurrence were higher and earlier, respectively, than previously reported values. However, no patient presented intra- or post-operative complications. CONCLUSION: These findings suggest that local anaesthesia and cryosurgery using the CryoPen XL® can be used in patients with eyelid masses who are not suitable for general anaesthesia. Compared with the surgical eyelid mass removal and blepharoplasty procedure, the reported procedure is time- and cost-effective, with the additional benefit of not requiring general anaesthesia.


Subject(s)
Anesthesia, Local/veterinary , Cryosurgery/veterinary , Dog Diseases/surgery , Eyelid Diseases/veterinary , Animals , Cryosurgery/instrumentation , Cryosurgery/methods , Dogs , Eyelid Diseases/surgery , Eyelids/surgery , Recurrence
19.
Top Companion Anim Med ; 45: 100580, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34428574

ABSTRACT

Early diagnosis of chronic kidney disease (CKD) could facilitate timely and appropriate monitoring and therapy. Traditional biomarkers have limitations. Thus, new biomarkers are needed. The objective of the present study was to compare renal biomarkers (including symmetric dimethylarginine [SDMA], cystatin C [CysC], and urine neutrophil gelatinase-associated lipocalin [NGAL]-creatinine ration [UNCR]) and creatinine (CREA) for early detection of CKD in dogs. Nine healthy dogs and 32 dogs with CKD were included in this study. All dogs underwent physical examination, blood analysis (included CREA and SDMA), urinalysis, and imaging examinations. CysC and NGAL levels were measured in serum and urine, respectively. SDMA, CysC, and UNCR were significantly elevated in dogs with CKD and IRIS stage Ι (P < .0001) than in controls. CysC demonstrated a strong correlation with CREA (r2 = 0.6556, P < .0001). CysC (sensitivity 93.55%, specificity 100%) had the highest sensitivity for detecting CKD, followed by UNCR (sensitivity 90%, specificity 100%), SDMA (sensitivity 84.37%, specificity 100%), and CREA (sensitivity 43.75%, specificity 100%). Additionally, CysC and UNCR (sensitivity 88.89%, specificity 100%) exhibited higher sensitivity and specificity than CREA (sensitivity 88.89%, specificity 66.67%) and SDMA (sensitivity 88.89%, specificity 88.89%) in dogs with CKD International Renal Interest Society (IRIS) stage Ι. CysC as a marker of glomerular filtration rate (GFR) and urinary NGAL as a marker of tubular damage could be used to detect CKD early in dogs better than CREA and SDMA.


Subject(s)
Dog Diseases , Renal Insufficiency, Chronic , Animals , Biomarkers , Cystatin C , Dog Diseases/diagnosis , Dogs , Lipocalin-2 , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/veterinary
20.
Vet Ophthalmol ; 24(4): 391-399, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34240540

ABSTRACT

OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.


Subject(s)
Collagen/therapeutic use , Dog Diseases/drug therapy , Glaucoma Drainage Implants/veterinary , Glaucoma/veterinary , Glycosaminoglycans/therapeutic use , Animals , Collagen/adverse effects , Dog Diseases/surgery , Dogs , Female , Glaucoma/surgery , Glycosaminoglycans/adverse effects , Intraocular Pressure/drug effects , Male , Prospective Studies , Treatment Outcome
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