ASES Function Research Articles

Improved patient reported outcomes with knotless double-row rotator cuff repair with and without lateral row biceps tenodesis at 2- and 5-years

BackgroundThe purpose of this study is to report outcomes of an arthroscopic knotless double-row (DR) rotator cuff repair (RCR) technique at 2- and 5- years postoperatively, and to compare clinical outcomes in patients undergoing knotless DR RCR with incorporated lateral row biceps tenodesis vs. those without lateral row biceps tenodesis. MethodsAll primary RCR surgeries were performed by a single surgeon at a single institution using a knotless transosseous equivalent (TOE) technique. The postoperative rehabilitation protocol was standardized for all patients. The primary outcomes collected included ASES Function, ASES Index, SANE, SST, VR-12 physical and mental, and VAS scores. ResultsThree hundred forty-two patients met inclusion criteria, of which 262 patients underwent isolated RCR and 61 underwent RCR with a concomitant lateral row biceps tenodesis, 15 underwent RCR with concomitant tenotomy and 4 had RCR with débridement of the biceps. Significant improvements in VAS, ASES, SANE, SST, and VR-12 scores were observed at all time points in all patient groups. No statistically significant differences in outcomes were noted in patients undergoing RCR with a lateral row tenodesis vs. those undergoing RCR alone. Similarly, no differences were seen when stratified by age, sex, BMI, Worker’s Compensation (WC) status, smoking, and diabetes mellitus (DM). Based on ASES, 81% of patients met minimum clinically important difference (MCID), and 64% met maximum outcome improvement (MOI) at 1-year postoperatively. ConclusionKnotless DR TOE arthroscopic RCR significantly improves patient-reported clinical outcomes at 1-, 2- and 5-year follow-ups. These results are reflected in clinical practice because 80% achieve MCID postoperatively. Patient-related factors, including BMI, age, sex, WC, and DM do not significantly affect patient-reported outcomes in the first 5 years after surgery. Smokers have worse baseline scores which persist at 2-year follow-up. Lastly, adding an arthroscopic lateral row biceps tenodesis in knotless DR TOE arthroscopic RCR provides similar clinical outcomes to knotless DR TOE arthroscopic RCR without biceps tenodesis.

Do preoperative scapular fractures affect long-term outcomes after reverse shoulder arthroplasty?

Postoperative scapular stress fractures (SSFs) are a formidable problem after reverse shoulder arthroplasty (RSA). Less is known about patients who have these fractures preoperatively. The primary aim of this study was to examine postoperative satisfaction in patients undergoing primary RSA who have preoperative SSF and compared to a matched cohort without preoperative fracture. The secondary aim was to examine the differences in patient-reported outcomes between and within study cohorts. A retrospective chart review of primary RSAs performed by a single surgeon from 2000 to 2020 was conducted. Patients diagnosed with cuff tear arthropathy (CTA), massive cuff tear (MCT), or rheumatoid arthritis (RA) were included. Five hundred twenty-five shoulders met inclusion criteria. Fractures identified on preoperative computed tomography scans were divided into 3 groups: (1) os acromiale, (2) multifragments (MFs), and (3) Levy types. Seventy-two shoulders had an occurrence of SSF. The remaining 453 shoulders were separated into a nonfractured cohort. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) and visual analog scale (VAS) scores were compared pre- and postoperatively in the total fracture group and the nonfractured group cohort. The multifragment subgroup was also compared to the pooled Os/Levy subgroup. The total incidence of SSF in all shoulders was 13.7%. There was a difference in satisfaction scores at all time points between the nonfracture (7.9±2.8) and total fracture group (5.4±3.6, P <.001, at last visit). There was also a greater ASES total score in the nonfractured group vs the total fracture group at the final visit (69.4±23.4 and 62.1±24.2; P=.02). The MF group had worse ASES functional or VAS functional scores than the Os/Levy group at all time points: at 1 year, ASES function: MF 24.2±14.5 and Os/Levy 30.7±14.2 (P=.045); at 2 years, ASES function: MF 21.4±14.4 and Os/Levy 35.5±10.6 (P <.001); and at last follow-up, VAS function: MF 4.8±2.8 and Os/Levy 6.4±3.2 (P=.023). Scapular fractures were proportionally most common in patients diagnosed with CTA (16.3%) compared with a 9.2% and 8.6% incidence in patients diagnosed with MCT and RA, respectively. Patients with preoperative SSF still see an improvement in ASES scores after RSA but do have lower satisfaction scores compared with the nonfractured cohort. The multifragment fracture group has lower functional and satisfaction scores at all postoperative time points compared with both the nonfracture and the Os/Levy fracture group.

Humeral Loosening in Reverse Shoulder Arthroplasty: An Analysis of 2,000 Cases.

Humeral loosening is a rare complication in reverse shoulder arthroplasty (RSA) representing approximately 1% of total complications. The purpose of this study is to identify patients who underwent RSA and were revised due to loosening of the humeral component, identify patients who are at increased risk, and report on their surgical outcomes. A retrospective review of all patients who received a primary RSA or revision RSA (rRSA) by a single surgeon from 2002-2021 identified a total of 1,591 primary RSA and 751 rRSA procedures. These procedures were then organized based on indication for surgery. Further analysis was performed to identify RSAs that were subsequently revised due to aseptic loosening of the humeral component. A total of 41 surgeries met inclusion criteria for the study, which was any RSA or rRSA that was revised due to loosening of the humeral component. Exclusion criteria was revision for a reason other than humeral loosening, neurogenic arthritis, or revision for loosening that was not originally implanted by the senior author (9 surgeries). Ultimately, 32 surgeries met criteria for further analysis. These 32 surgeries were organized by indication for preceding RSA or rRSA and were assessed for an association between indication for RSA/rRSA and eventual revision for humeral loosening. Additionally, these procedures were compared to a "control cohort" of procedures that were not revised and that had minimum 2-years follow-up. To assess outcomes for these patients, pre- and postoperative SST, ASES, and ranges of motion were compared. Twenty procedures had sufficient data for outcomes analysis and were followed for an average of 54 months (range: 24-132 months). In primary RSAs, procedures performed for fracture or fracture sequelae were associated with revision for humeral-sided loosening (p = 0.009). In rRSAs, procedures performed for failed hemiarthroplasty for CTA were associated with re-revision for humeral-sided loosening (p = 0.009). Nine percent of patients revised for humeral loosening required re-revision for recurrent humeral loosening. Analysis of patients with 2-year clinical follow-up for humeral-sided loosening showed improvement in ASES pain (p = 0.014), ASES function (p = 0.042), and total ASES scores (p = 0.007). Humeral loosening is rare in RSA. In our cohort, 0.7% of primary RSAs performed and 2.8% of rRSAs performed were eventually revised for humeral loosening. Revisions of RSA for humeral loosening yield modest clinical improvements. Re-revision for humeral loosening was 6.3% of patients in our cohort.

Mechanism of life-long maintenance of neuron identity despite molecular fluctuations.

Cell fate is maintained over long timescales, yet molecular fluctuations can lead to spontaneous loss of this differentiated state. Our simulations identified a possible mechanism that explains life-long maintenance of ASE neuron fate in Caenorhabditis elegans by the terminal selector transcription factor CHE-1. Here, fluctuations in CHE-1 level are buffered by the reservoir of CHE-1 bound at its target promoters, which ensures continued che-1 expression by preferentially binding the che-1 promoter. We provide experimental evidence for this mechanism by showing that che-1 expression was resilient to induced transient CHE-1 depletion, while both expression of CHE-1 targets and ASE function were lost. We identified a 130 bp che-1 promoter fragment responsible for this resilience, with deletion of a homeodomain binding site in this fragment causing stochastic loss of ASE identity long after its determination. Because network architectures that support this mechanism are highly conserved in cell differentiation, it may explain stable cell fate maintenance in many systems.

The Reliability of Remote Patient-Reported Outcome Measures via Mobile Apps to Replace Outpatient Visits After Rotator Cuff Repair Surgery: Repetitive Test-Retest Comparison Study for 1-Year Follow-up.

BackgroundWith the development of health care–related mobile apps, attempts have been made to implement remote patient-reported outcome measures (PROMs). In order for remote PROMs to be widely used by mobile apps, the results should not be different depending on the location; that is, remote PROM results performed in locations other than hospitals should be able to obtain reliable results equivalent to those performed in hospitals, and this is very important. However, to our knowledge, there are no studies that have assessed the reliability of PROMs using mobile apps according to the location by comparing the results performed remotely from the hospital and performed at the outpatient visits.ObjectiveThe purpose of this study was to evaluate the reliability of remote PROMs using mobile apps compared to PROMs performed during outpatient follow-up visits after arthroscopic shoulder surgery.MethodsA total of 174 patients who underwent arthroscopic rotator cuff repair completed questionnaires 2 days before visiting the clinic for the 1-, 2-, 3-, 6-, and 12-month follow-ups (test A). The patients completed the questionnaires at the clinic (test B) using the same mobile app and device for the 1-, 2-, 3-, 6-, and 12-month follow-ups. Test-retest comparisons were performed to analyze the differences and reliability of the PROMs according to the period.ResultsComparisons of tests A and B showed statistically significant differences at 1, 2, and 3 months (all Ps<.05 except for the ASES function scale at 3-months) but not 6 or 12 months after surgery (all Ps>.05). The intraclass correlation values between the two groups were relatively low at the 1-, 2-, and 3-month follow-ups but were within the reliable range at 6 and 12 months after surgery. The rate of completion of tests A and B using the mobile app was significantly lower in the group older than 70 years than in the other groups for all postoperative periods (P<.001).ConclusionsPROMs using mobile apps with different locations differed soon after surgery but were reliably similar after 6 months. The remote PROMs using mobile apps could be used reliably for the patient more than 6 months after surgery. However, it is to be expected that the use of mobile app–based questionnaires is not as useful in the group older than 70 years as in other age groups.

Grip and shoulder strength correlation with validated outcome instruments in patients with rotator cuff tears

The ability to better define preoperatively the extent of rotator cuff (RC) dysfunction is desired. The study's purpose was to prospectively examine the relationships between absolute and percentage loss (affected compared to unaffected) of grip and shoulder strength, and RC dysfunction. Forty-seven consecutive patients with proven RC tears participated in this study. Prior to surgery, bilateral strengths of grip, shoulder abduction, and shoulder external rotation (ER) were measured with a handheld dynamometer, and subjective outcome measures were gathered. RCtear size was determined via arthroscopy. Patient-reported outcomes were gathered on the day of the examination or via e-mail following initial evaluation. Descriptive statistics, difference analysis, and correlation coefficients (reported as either direct or negative) were used to analyze data. Grip, abduction and ER strengths, and percentage loss of grip, abduction, and ER strengths (percentage loss affected vs. unaffected), and tear size were analyzed in relation to all of the scores on selected subjective outcome measurement tools. The P value was set at .05. Fair direct correlations were found between grip strength and the Veterans RAND 12-Item Health Survey (VR-12) mental health scores, ER strength and Simple Shoulder Test (SST), abduction strength, and both the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) function score and SST score. Abduction and ER strengths were also found to possess a fair direct correlation. Fair negative correlations were found between the ASES function score and each of the following: percentage loss of abduction strength, percentage loss of ER strength, and tear size in centimeters. Another fair negative correlation was found between the Single Assessment Numerical Evaluation (SANE) score and tear size in centimeters. Our findings suggest that as shoulder strength decreases, ipsilateral shoulder RC dysfunction increases. Grip strength was not related to shoulder RC dysfunction. Grip strength was not found to correlate with RC tears. Those with decreased abduction and ER strengths and low ASES scores should be considered more likely to have an RC tear.

Effect of biceps tenodesis on speed of recovery after arthroscopic rotator cuff repair

BackgroundConcomitant biceps tendon pathology is often present in patients undergoing rotator cuff repair (RCR). Management of biceps pathology has been reported to influence outcomes of RCR; however, the impact on the pace of recovery remains unclear. The purpose of this study was to analyze the effects of simultaneous RCR with biceps tenodesis (RCR-BT) on time to achieve maximum improvement and recovery speed for pain and function.MethodsA retrospective review of 535 patients who underwent primary RCR for full-thickness tears. Patients treated with simultaneous RCR-BT were compared with RCR-only. Outcome measures and motion were recorded at preoperative routine postoperative intervals. Plateau in maximal improvement and recovery speed were analyzed for both pain and functional recovery.ResultsBaseline American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) function was significantly lower for the RCR-BT cohort (20.5) compared with RCR-only (23.9; P = .008). For visual analog scale (VAS) pain and measured motion, the plateau in maximal improvement occurred at 6 months for RCR-BT compared with 12 months for the RCR-only group. The remainder of the patient-reported outcome measures took 12 months to achieve a plateau in maximal improvement. At 3 months, 79% of improvement in pain and 42%-49% of functional improvement was achieved in the RCR-BT cohort. Similarly, at 3 months, the RCR-only cohort achieved 73% of pain improvement and 36%-57% of functional improvement at 3 months.ConclusionPatients requiring RCR with simultaneous biceps tenodesis have lower baseline ASES function and earlier postoperative plateaus in pain relief and motion improvement following surgery. Nonetheless, the speed of recovery was not influenced by the biceps tenodesis.

Patient Expectations for Outcomes of Upper Extremity Total Joint Arthroplasty: A Systematic Review

Joint arthroplasty leads to a dramatic improvement in outcomes of pain, function, and satisfaction for many patients. Patient expectations have been increasingly linked to these treatment outcomes, with positive expectations being associated with better outcomes and greater patient satisfaction. However, the majority of the literature focuses on lower, not upper, limb extremities. The purpose of this study is to identify and summarize studies that determine the extent to which preoperative expectations are predictive of postoperative outcomes in patients undergoing any arthroplasty of joints in the upper extremities. A comprehensive systematic online literature search was performed in Embase, Medline, CINAHL, PsycINFO, Cochrane Library, and Web of Science. Articles addressing joint arthroplasty in the upper extremities that measured preoperative expectations affecting postoperative treatment outcomes (pain, function, and satisfaction), as well as their relationships, were included, with an end result of eight studies reviewed. The methodological quality of the included articles ranged 53%-89%. Studies differed substantially in definitions and measurements of patient expectations. Only two reported a correlation analysis between patient expectations and outcomes. SF-12 function (p = 0.01), VAS pain (p = 0.05), and ASES function (p = 0.05) showed significant correlations with preoperative patient expectations. Findings show that research on upper limb arthroplasty is limited, unlike lower limb results. Future studies should focus on using preoperative patient education to modify expectations and on creating a framework to standardize patient expectations for arthroplasty of upper limb extremities.

Arthroscopic Superior Capsular Reconstruction for the Treatment of Massive Irreparable Rotator Cuff Tears in the Active Patient: 1-2 year Results

To report our results in the first 58 shoulders in 57 patients undergoing arthroscopic superior capsular reconstruction for the treatment of the younger active patient with irreparable rotator cuff tears and rotator cuff arthropathy. 57 consecutive patients presented with massive irreparable rotator cuff tear with retraction and atrophy (Goutallier grade 4). One patient has undergone bilateral arthroscopic superior capsular reconstruction. All had failed previous treatments including surgical and non- surgical modalities. These patients were too young and active (ages 42-67) for treatment with reverse total shoulder arthroplasty. All patients had unacceptable pain and weakness. The tears involved the supraspinatus or both supraspinatus and infraspinatus tendons. All patients were treated with arthroscopic superior capsular reconstruction with an acellular dermal allograft. Evaluation utilizing an internet based outcome tracking system, radiographic analysis and functional assessment to assess range of motion and dynamometric strength data utilized to track outcomes. At minimum of one year follow up, 56/57 shoulders are satisfied. One shoulder went on to revision to reverse total shoulder arthroplasty. Outcome data analysis demonstrated significantly improved scores in visual analog scores (3.6 to 1.3), Simple shoulder test (39 to 64), SANE Scores (31 to 65), ASES Function scores (14 to 21), and ASES Index scores (45 to 64) at minimal one year follow up. Active range of motion measurements in forward flexion and abduction as well as dynamometric strength measures have shown significant improvement as well. Radiographic analysis demonstrated significant improvement in acromiohumeral distance that was maintained over the postoperative period (1 to 2 years). Arthroscopic superior capsular reconstruction with acellular dermal allograft has been a successful procedure in decreasing pain and improving function during this early postoperative period. As this procedure “burns no bridges”, it is an attractive alternative to reverse total shoulder arthroplasty in the young active patient population.

Loss of Dynamin 2 GTPase function results in microcytic anaemia.

In a dominant mouse ethylnitrosurea mutagenesis screen for genes regulating erythropoiesis, we identified a pedigree with a novel microcytic hypochromia caused by a V235G missense mutation in Dynamin 2 (Dnm2). Mutations in Dnm2, a GTPase, are highly disease-specific and have been implicated in four forms of human diseases: centronuclear myopathy, Charcot-Marie Tooth neuropathy and, more recently, T-cell leukaemia and Hereditary Spastic Paraplegia, but red cell abnormalities have not been reported to date. The V235G mutation lies within a crucial GTP nucleotide-binding pocket of Dnm2, and resulted in defective GTPase activity and incompatibility with life in the homozygous state. Dnm2 is an essential mediator of clathrin-mediated endocytosis, which is required for the uptake of transferrin (Tf) into red cells for incorporation of haem. Accordingly, we observed significantly reduced Tf uptake by Dnm2+/V235G cells, which led to impaired endosome formation. Despite these deficiencies, surprisingly all iron studies were unchanged, suggesting an unexplained alternative mechanism underlies microcytic anaemia in Dnm2+/V235G mice. This study provides the first invivo evidence for the requirements of Dnm2 in normal erythropoiesis.

Correlates of gait speed in advanced knee osteoarthritis.

This study aims to evaluate correlates of gait speed, a measure of disability, in older adults with advanced knee osteoarthritis (OA) and chronic pain. Baseline data were analyzed from a clinical trial of 190 participants aged >50 with advanced knee OA (according to clinical and radiographic American College of Rheumatology criteria) and chronic pain. Data included 4-meter gait speed, quality of life (Short Form Health Survey 36 global health subscale), knee pain (Western Ontario and McMasters Universities Osteoarthritis Index [WOMAC]), depressive symptoms (Center for Epidemiologic Studies Depression Scale), coping strategies (catastrophizing subscale and Cognitive Strategies Questionnaire), self-efficacy (Athritis Self-efficacy Scale [ASES]), comorbidity (Cumulative Illness Rating Scale), analgesic use, and pain comorbidities (location, frequency, and intensity). A multivariable regression model was used to investigate these variables as they relate to gait speed. In the univariate analysis, the following variables were associated with gait speed: knee pain (per WOMAC), age, depressive symptoms, global health, catastrophizing, ASES function and other, comorbidity, and opioid use (all P values <0.05). In the fully adjusted multivariate model, controlling for knee pain, significant associations between gait speed and age (β = -0.006; P < 0.001), ASES function (β = 0.003; P < 0.001), and opioid use (β = -0.082; P = 0.009) persisted. The correlation between opioid dose and gait speed (among opioid users) was not statistically significant (r = 0.04; P = 0.81). In a cross-sectional study of older adults with advanced knee OA and chronic pain, we found that age, arthritis function self-efficacy, and opioid use (but not dose) were significantly associated with decreased gait speed.

Cellular physiology of the renal H+ATPase

Vacuolar-type H+ATPases are multisubunit macromolecules that play an essential role in renal acid-base homeostasis. Other cellular processes also rely on the proton pumping ability of H+ATPases to acidify organellar or lumenal spaces. Several diseases, including distal renal tubular acidosis, osteoporosis and wrinkly skin syndrome, are due to mutations in genes encoding alternate subunits that make up the H+ATPase. This review highlights recent key articles in this research area. Further insights into the structure, expression and regulation of H+ATPases have been elucidated, within the kidney and elsewhere. This knowledge may enhance the potential for future drug targeting. Novel findings concerning tissue-specific subunits of the H+ATPase that are important in the kidney and more general lessons of H+ATPase function and regulation are slowly emerging, though the paucity of cellular tools available has to date limited progress.

Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1

The vacuolar-type ATPase (H+ATPase) is a ubiquitously expressed multisubunit pump whose regulation is poorly understood. Its membrane-integral a-subunit is involved in proton translocation and in humans has four forms, a1–a4. This study investigated two naturally occurring point mutations in a4's COOH terminus that cause recessive distal renal tubular acidosis (dRTA), R807Q and G820R. Both lie within a domain that binds the glycolytic enzyme phosphofructokinase-1 (PFK-1). We recreated these disease mutations in yeast to investigate effects on protein expression, H+ATPase assembly, targeting and activity, and performed in vitro PFK-1 binding and activity studies of mammalian proteins. Mammalian studies revealed complete loss of binding between the COOH terminus of a4 containing the G-to-R mutant and PFK-1, without affecting PFK-1's catalytic activity. In yeast expression studies, protein levels, H+ATPase assembly, and targeting of this mutant were all preserved. However, severe (78%) loss of proton transport but less decrease in ATPase activity (36%) were observed in mutant vacuoles, suggesting a requirement for the a-subunit/PFK-1 binding to couple these two functions. This role for PFK in H+ATPase function was supported by similar functional losses and uncoupling ratio between the two proton pump domains observed in vacuoles from a PFK-null strain, which was also unable to grow at alkaline pH. In contrast, the R-to-Q mutation dramatically reduced a-subunit production, abolishing H+ATPase function completely. Thus in the context of dRTA, stability and function of the metabolon composed of H+ATPase and glycolytic components can be compromised by either loss of required PFK-1 binding (G820R) or loss of pump protein (R807Q).

Shoulder and elbow function 2 years following long head triceps interposition flap transfer for massive rotator cuff tear reconstruction

Patient outcomes were determined at a minimum of 2 years following massive rotator cuff tear ( > or = 5 cm(2)) reconstruction using a triceps brachii long head interposition flap. A physiotherapist at an independent clinic performed all measurements. Of 24 total eligible patients, 19 completed pre-operative and follow-up UCLA Shoulder Scores and ASES Function Scores. Of these 19 patients, 14 who did not have co-morbidities that negatively impacted their ability to perform intense exercise underwent a comprehensive clinical examination of involved and uninvolved side shoulder and elbow active range of motion and strength (both isometric instrumented manual muscle testing and concentric isokinetic measurements). At 2 years following surgery, pre-operative UCLA Shoulder Scores improved from 10.6 +/- 3 to 27.4 +/- 5 and pre-operative ASES Function Scores improved from 20.1 +/- 10 to 43.2 +/- 5. However, isometric involved side shoulder abductor torque was decreased by 28.2% with instrumented manual muscle testing, and concentric shoulder external rotator torque was decreased by 44.6% at 60 degrees/s and by 53.8% at 120 degrees/s with isokinetic testing. Isometric involved side elbow extensor torque was decreased by 39% with instrumented manual muscle testing, and concentric elbow extensor torque was decreased by 17.7% and 19.2% at 60 and 120 degrees/s, respectively, with isokinetic testing. Including three additional patients who were contacted via telephone, the majority of patients (21 of 22, 95.4%) were satisfied with their improved shoulder function and reduced pain. Despite reduced pain and improved shoulder function, residual involved side shoulder abductor; shoulder external rotator and elbow extensor strength deficits were evident at 2 years following surgery. This suggests the need for more focused rehabilitation, particularly for involved side elbow extensor strengthening to further improve patient function and minimize disability.

Functional Pan-Universality of the Age-Related Regulatory Mechanisms of Gene Expression.

Through analyses of human factor IX (hFIX) and protein C (hPC) gene expressions in transgenic mice, we recently discovered the first molecular mechanism of age-dimension gene regulation, involving two critical genetic elements ASE and AIE required for age-related stable and increase patterns of gene expression, respectively. The next most critical issue to be tested was whether or not these elements, particularly ASE due to its possible utility, similarly functions with grossly different genes. We constructed hFIX expression vectors carrying a CMV promoter with or without ASE, and tested them in transgenic mice. Vectors with no ASE showed an age-dependent gradual decrease in hFIX expression, reaching the background levels in 3–9 months. Vectors with ASE, however, showed age-stable hFIX expression over the same time period. These findings supported the pan-universality of ASE function. As we previously reported, ASE regulates gene expression not only temporally but also spacially. With ASE, CMV-driven expression showed the highest in the heart muscle, whereas without ASE, the highest in the skeletal muscle. These results led to development of the Age Dimension Technology, a new field for exploring the unique applications of the age-related knowledge.

Design, Synthesis, and Evaluation of β‐Galactosylceramide Mimics Promoting β‐Glucocerebrosidase Activity in Keratinocytes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Design, synthesis, and evaluation of β-galactosylceramide mimics promoting β-glucocerebrosidase activity in keratinocytes

We have established an efficient synthesis of mimics of β-galactosylceramide (β-GalCer) increasing a β-glucocerebrosidase (β-GlcCer'ase) activity that associates with the skin barrier function. Among the synthetic β-GalCer analogues ( 6a–6e) described herein, compound 6e exhibited a potent effect on the activation of β-GlcCer'ase function in vitro and reduced the transepidermal water loss (TEWL) level in a UVB-induced barrier disrupted mice model. These findings indicated that compound 6e could be useful for cosmetics and medicines to improve skin barrier function.