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2.
J Pharm Policy Pract ; 17(1): 2344223, 2024.
Article in English | MEDLINE | ID: mdl-38798764

ABSTRACT

Introduction: Chronic kidney disease (CKD) is a major public health concern in Saudi Arabia. it is pertinent to mention that in the Southwestern region of Saudi Arabia. Hypertension and diabetes mellites are considered the major drivers of CKD. Research has documented worldwide the inappropriate dose adjustments in patients, ranging from 25% to 77%, of drugs requiring dose modifications. Pharmacists are pivotal members of the healthcare team, tasked with addressing issues pertaining to medications. This study aims to unveil pharmacist perspectives on renal dose adjustment in Saudi Arabia an important step in gauging their involvement in promoting healthy behaviours. Method: A cross-sectional study design was conducted from December 2023 to January 2024 among pharmacists working in diverse healthcare settings, including clinical and hospital pharmacies, retail, and community pharmacies who had direct encounters with patients diagnosed with CKD. A validated questionnaire, the Renal Dose Adjustment-13 (RDQ-13) was used for this study. For comparing the knowledge, attitude, and perception scores of pharmacists statistical tests like One-Way ANOVA, and independent t-test; while for factors influencing the knowledge, attitude, and perception scores a multivariate linear regression was performed. The statistical significance level was set at 0.05. Results: A total of 379 pharmacists completed the questionnaire, the knowledge score of pharmacists was 22.06 ± 2.81, while the attitude score was 8.56 ± 2.62 and the practice score was 5.75 ± 2.25. The findings of multivariate linear regression analysis indicated a statistically significant positive association between knowledge score and pharmacist's age while for practice score the findings revealed a statistically negative association between working setting and designation of pharmacists. Conclusion: The pharmacist in Saudi Arabia exhibited a proficient knowledge score of drug dosage adjustment pertinent to renal function while the attitude and practice score was less as compared to the knowledge score.

3.
Nutr Metab Cardiovasc Dis ; 34(6): 1371-1380, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38503618

ABSTRACT

BACKGROUND AND AIMS: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR). METHODS AND RESULTS: In this retrospective, single-center study, 1071 adult patients who underwent an MVR between 2004 and 2018 were stratified into five BMI groups (<20, 20-24.9, 25-29.9, 30-34.9, >35). Cox proportional hazard regression models were used to determine the association between BMI and all-cause mortality. Patients who were underweight had significantly higher all-cause mortality rates at the longest follow-up (median 8.2 years) than patients with normal weight (p = 0.01). Patients who were in the obese group had significantly higher readmission rates due to myocardial infarction (MI) at the longest follow-up (p = 0.017). Subgroup analysis revealed a significant increase in long-term all-cause mortality for female patients who were underweight. Significant changes in left atrial size, mitral valve peak and mean gradients were seen in all BMI groups. CONCLUSIONS: For patients undergoing mitral valve replacement, BMI is unrelated to operative outcomes except for patients who are underweight.


Subject(s)
Body Mass Index , Heart Valve Prosthesis Implantation , Mitral Valve , Obesity , Ventricular Remodeling , Humans , Female , Male , Retrospective Studies , Middle Aged , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Heart Valve Prosthesis Implantation/instrumentation , Time Factors , Mitral Valve/surgery , Mitral Valve/physiopathology , Risk Factors , Treatment Outcome , Aged , Obesity/mortality , Obesity/physiopathology , Obesity/surgery , Obesity/complications , Obesity/diagnosis , Risk Assessment , Adult , Heart Valve Diseases/surgery , Heart Valve Diseases/mortality , Heart Valve Diseases/physiopathology , Cause of Death , Patient Readmission
4.
Obstet Gynecol Sci ; 67(1): 76-85, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37985950

ABSTRACT

OBJECTIVE: Pregnancy-associated breast cancer (PABC) is a rare cancer. This study aimed to determine the survival probabilities and prognostic factors in patients with PABC. METHODS: A retrospective cohort study was conducted in two tertiary care hospitals in Kota Bharu. We included all patients with breast cancer who were diagnosed by histopathology while pregnant or within 2 years post-partum from 2001 through 2020. We matched patients with PABC to non-pregnant patients with breast cancer by age and year of diagnosis. The data were analyzed using Cox proportional hazard regression. RESULTS: A total of 35 cases of PABC and 70 non-PABC controls were recruited. The 3-year, 5-year, and 10-year survival probabilities for patients with PABC were 58.6%, 47.54%, and 38.03%, respectively. The patients with PABC had a non-significant difference in survival probabilities compared with non-PABC patients. The significant prognostic factors of PABC were age (adjusted hazard ratio [aHR], 0.91; 95% confidence interval [CI], 0.86-0.96; P=0.001), advanced stage of cancer (aHR, 9.97; 95% CI, 3.96-25.2; P<0.001), and no surgery (aHR, 3.16; 95% CI, 1.01-9.85; P=0.047). Pregnancy was not found to be an independent factor in the prognosis of PABC (aHR, 0.72; 95% CI, 0.39-1.28; P=0.266). CONCLUSION: Women diagnosed with PABC had similar survival probabilities compared with non-PABC patients. Pregnancy was not an independent prognostic factor for breast cancer. This information can be useful when women with breast cancer are counseled and supported with the option of beginning treatment with pregnancy continuation.

6.
Cureus ; 15(10): e47376, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021861

ABSTRACT

Health security has gained significant attention at the national and global levels, "security" is not a simple term; instead, it is "essentially contested" - that is, it induces debates about what it means and how to use it. This study aimed to define three terms frequently used in health security discussions. These terms are national health security, Global Health Security, and public health. The research method was a scoping review performed in three stages. The first stage was electronic searching based on selection criteria among multiple sources at various time points during the year 2023. These sources included online literature searches, websites of non-governmental organizations (NGOs), and other governmental health agencies. The second stage involved determining the relevance of the selected papers to the study's objectives; the selected papers had moderate to high relevance to the study's objectives. The third stage was to evaluate the methodological quality of a study; we selected peer-reviewed published papers and websites recognized as trustworthy sources of information. The search yielded 143 articles; five met the inclusion criteria and were subjected to the definition of health security. Despite proposed definitions, agreement has yet to be reached on the content and scope of health security. Another main finding is that health security requires more state and international collaboration efforts to reach Global Health Security. To the best of our knowledge, no known government body or organization is responsible for governing health security in Saudi Arabia. However, the current study presents a definition of health security and differentiates it from the public health approach, in addition to emphasizing the importance of governing the related health sectors within each country in order to improve health security and have a positive impact on overall Global Health Security.

7.
Polymers (Basel) ; 15(16)2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37631435

ABSTRACT

In this study, we developed highly efficient nonwoven membranes by modifying the surface of polypropylene (PP) and poly(butylene terephthalate) (PBT) through photo-grafting polymerization. The nonwoven membrane surfaces of PP and PBT were grafted with poly(ethylene glycol) diacrylate (PEGDA) in the presence of benzophenone (BP) and metal salt. We immobilized tertiary amine groups as BP synergists on commercial nonwoven membranes to improve PP and PBT surfaces. In situ Ag, Au, and Au/Ag nanoparticle formation enhances the nonwoven membrane surface. SEM, FTIR, and EDX were used to analyze the surface. We evaluated modified nonwoven membranes for photocatalytic activity by degrading methylene blue (MB) under LED and sunlight. Additionally, we also tested modified membranes for antibacterial activity against E. coli. The results indicated that the modified membranes exhibited superior efficiency in removing MB from water. The PBT showed the highest efficiency in dye removal, and bimetallic nanoparticles were more effective than monometallic. Modified membranes exposed to sunlight had higher efficiency than those exposed to LED light, with the PBT/Au/Ag membrane showing the highest dye removal at 97% within 90 min. The modified membranes showed reuse potential, with dye removal efficiency decreasing from 97% in the first cycle to 85% in the fifth cycle.

8.
Saudi Med J ; 44(7): 674-678, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37463703

ABSTRACT

OBJECTIVES: To explore the effects of empagliflozin (25 mg) on metabolic and renal parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective observational comparative study was conducted at a military hospital in southern Saudi Arabia. All adults (aged >18 years) with T2DM who attended diabetic clinics between October 2021 to March 2022 (6 months), with or without insulin treatment, were eligible for inclusion in the study. RESULTS: Following the initiation of empagliflozin treatment, statistically significant reductions in patient weight (kg) were observed at 1, 3-5, and 6 months. In addition, low-density lipoprotein levels significantly decreased 3-5 months post-treatment initiation (p=0.011). However, serum creatinine level decreased gradually with time during the treatment with empagliflozin, from 87.45±31.78 (0.105) to 78.39±27.43 (0.033). Furthermore, after empagliflozin treatment, the urinary albumin-to-creatinine ratio significantly decreased at 3-5 and 6 months. Moreover, HbA1c levels exhibited statistically significant decreases at 3-5 months (p<0.001) and at 6 months (p<0.001) following the initiation of empagliflozin treatment. Notably, systolic and diastolic blood pressure significantly reduced 6 months after empagliflozin treatment. CONCLUSION: In the current study, empagliflozin has demonstrated efficacy in controlling blood pressure and body weight, and improving renal function, short-term dyslipidemia, and glycemic control in patients with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Retrospective Studies , Saudi Arabia , Glycated Hemoglobin , Benzhydryl Compounds/therapeutic use , Kidney/physiology , Hospitals , Hypoglycemic Agents/therapeutic use
9.
Polymers (Basel) ; 15(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36904530

ABSTRACT

The copper II complex's novel benzimidazole Schiff base ligands were manufactured and gauged as a new photoredox catalyst/photoinitiator amalgamated with triethylamine (TEA) and iodonium salt (Iod) for the polymerization of ethylene glycol diacrylate while exposed to visible light by an LED Lamp at 405 nm with an intensity of 543 mW/cm2 at 28 °C. Gold and silver nanoparticles were obtained through the reactivity of the copper II complexes with amine/Iod salt. The size of NPs was around 1-30 nm. Lastly, the high performance of copper II complexes for photopolymerization containing nanoparticles is presented and examined. Ultimately, the photochemical mechanisms were observed using cyclic voltammetry. The preparation of the polymer nanocomposite nanoparticles in situ was photogenerated during the irradiation LED at 405 nm with an intensity of 543 mW/cm2 at 28 °C process. UV-Vis, FTIR, and TEM analyses were utilized for the determination of the generation of AuNPs and AgNPs which resided within the polymer matrix.

10.
ACS Omega ; 8(3): 3207-3220, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36713746

ABSTRACT

Benzophenone derivatives were evaluated as new photoinitiators in combination with triethylamine (TEA) and iodonium salt (Iod) for very rapid and efficient formation of metal nanoparticles in an organic solvent, by which silver and gold ions were reduced under light at 419 nm (photoreactor) with an irradiation intensity of 250 microwatts/cm2. The new benzophenone derivatives combined with TEA/Iod salt showed good production of metal nanoparticles (Au0 and Ag0) and a small size of nanoparticles of around 4-13 nm. The photochemical mechanisms for the production of initiating radicals were studied using cyclic voltammetry, where a negative ΔG of around -1.96 eV was obtained, which made the process favorable. The obtained results proved the formation of amine and phenyl radicals, which led to the reduction of gold III chloride or silver ions to the gold and silver NPs. The UV-vis spectroscopy technique was used as a very beneficial tool for the surface plasmon resonance band detection of metal nanoparticles. To sum up the results, we have observed that nanoparticles (NPs) were distributed differently in different photoinitiator systems and the particle size also changed by changing the system of initiation. In comparison to the system alone, not only were the nanoparticles smaller but they were also generated within a shorter period of irradiation time for the system BP\Iod\TEA. Finally, the quenching process of benzophenone fluorescence by the gold and silver nanoparticles was investigated.

11.
Cureus ; 14(9): e29444, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36299925

ABSTRACT

Background In this study, we aimed to explore the possible association between hepatic steatosis (HS) and coronary artery disease (CAD) by calculating the patients' calcium scores and comparing clinical and laboratory parameters of patients in King Abdullah Medical City (KAMC), Makkah, Kingdom of Saudi Arabia (KSA). The role of risk factors associated with HS was also assessed. Methodology The medical records of 79 patients who underwent coronary cardiac computed tomography (CT) for calcium scoring and enhanced or non-enhanced CT scans of the abdomen and pelvis at the Department of Radiology, KAMC, Makkah, KSA, between April 2012 and April 2013 were collected and analyzed. Results The overall prevalence of HS was 32.9%. Gender, age, and body mass index were significantly associated with HS. Low-dose unenhanced CT is a promising screening test for the determination of HS. A severe grade of calcium score was significantly associated with HS, while hypertension had no significant relation with HS. Biomarkers such as blood urea nitrogen, creatinine, cholesterol, and triglycerides had a significant association with HS, while other liver function tests and lipid profile values did not have a significant association. Bilirubin was significantly higher in non-fatty liver than in fatty liver. Furthermore, higher grades of calcium score were significantly associated with fatty liver in non-hypertensive and non-diabetic patients. Conclusions CAD is closely associated with HS. Moreover, diabetes mellitus and hypertension play a critical role in the development of HS.

12.
Saudi Med J ; 43(2): 187-196, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35110344

ABSTRACT

OBJECTIVES: To estimate the prevalence of post- amputation pain among lower-limb amputees and its burden on their lives. METHODS: A retrospective patients record review of lower limb amputation surgeries was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between 2008-2019. e collected data included: patients demographics, surgical operations, chronic pain characteristics, functional impairment, and treatment. RESULTS: A total of 645 lower-limb amputations carried out on 509 patients, 104 (20.4%) patients had more than one amputation surgery carried out, and 40 (7.9%) patients having bilateral amputations. The estimated prevalence of chronic post-amputation pain among the lower-limb amputees was approximately 61.5%. Persistent postoperative neuropathic pain was the most common type of pain following amputation, followed by residual limb pain, then phantom limb pain. The most common cause of amputation was diabetes and its related complications (76%). The mean age at surgery was 57.46±12.02 years. Although diabetes was a common comorbid illness (95.6%), it had no correlation with the development of chronic post-amputation pain. However, peripheral vascular disease had a strong association (p=0.009), especially with the development of phantom limb pain (54.5%; p=0.016). The most common reason for functional impairment among the amputees was disability (52.7%), while only 6.6% said it was secondary to pain. CONCLUSION: Post-amputation pain is one of the major consequences of amputation. Pain was poorly managed among these patients. Special considerations should be obtained to manage these patients' pain and reduce their suffering.


Subject(s)
Amputees , Phantom Limb , Amputation, Surgical , Humans , Lower Extremity/surgery , Phantom Limb/epidemiology , Retrospective Studies , Saudi Arabia/epidemiology , Tertiary Care Centers
13.
Front Pharmacol ; 13: 831052, 2022.
Article in English | MEDLINE | ID: mdl-35145419

ABSTRACT

Numerous existing full-spectrum cannabis extract products have been used in clinical trials for the treatment of various diseases. Despite their efficacy, the clinical use of some of these full-spectrum cannabis extracts is limited by behavioral side effects such as cognitive dysfunction and impaired motor skills. To better understand what constitutes cannabis-induced behavioral effects, our objective was to identify a novel panel of blood-based metabolites that are predictive, diagnostic, and/or prognostic of behavioral effects. At 8 weeks of age, male rats were randomly assigned to groups and were gavage fed with full-spectrum cannabis extract (tetrahydrocannabinol/cannabidiol (THC/CBD) along with all other cannabis compounds, 15 mg/kg), broad-spectrum cannabis extract (CBD along with all other cannabis compounds, 15 mg/kg), or vehicle oil. Four hours after being gavage fed, behavioral assessments were determined using the open field test and the elevated plus maze. Following these assessments, serum was collected from all rats and the serum metabolites were identified and quantified by LC-MS/MS and 1H NMR spectroscopy. We found that only rats treated with full-spectrum cannabis extract exhibited behavioral changes. Compared to vehicle-treated and broad-spectrum extract-treated rats, full-spectrum extract-treated rats demonstrated higher serum concentrations of the amino acid phenylalanine and long-chain acylcarnitines, as well as lower serum concentrations of butyric acid and lysophosphatidylcholines. This unique metabolomic fingerprint in response to cannabis extract administration is linked to behavioral effects and may represent a biomarker profile of cannabis-induced behavioral changes. If validated, this work may allow a metabolomics-based decision tree that would aid in the rapid diagnosis of cannabis-induced behavioral changes including cognitive impairment.

14.
J Pharm Sci ; 110(11): 3605-3613, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34216578

ABSTRACT

Real time analysis of pharmaceuticals in controlled release nano and microsystems remains a challenge. It is hypothesized that fluorine 19 nuclear magnetic resonance (19F qNMR) can be used for real time quantification and in vitro release of maraviroc (MVC). The release of maraviroc was analyzed in simulated body fluids from spray dried sodium alginate microspheres (MS) using the 19F qNMR method. Calibration produced a linearity curve in concentration range (0.42 mg/ml - 15 mg/ml), and the limits of detection and quantification values were 0.97 mg/ml and 2.93 mg/ml, respectively. The method was confirmed to be specific, accurate, precise, and robust (%RSE > 2%). MVC was successfully microencapsulated (18% w/w) as evidenced by the FT-IR spectra and SEM images. The MS had an average diameter of 2.522 ± 0.15 µm, with a zeta potential of - 61.31 ± 2.1 mV. Overall, the 19F qNMR method enabled a direct and real time quantification of MVC for an efficient drug release kinetics. This approach could be potentially used to quantify fluorinated drug potency, purity, and stability, and evaluate in vitro release kinetic from different formulations.


Subject(s)
Fluorine , Drug Liberation , Magnetic Resonance Spectroscopy , Maraviroc , Spectroscopy, Fourier Transform Infrared
15.
FEBS Lett ; 595(12): 1681-1695, 2021 06.
Article in English | MEDLINE | ID: mdl-33876420

ABSTRACT

Doxorubicin (DOX) is a very effective anticancer agent that is widely used in pediatric cancer patients. Nevertheless, DOX is known to have cardiotoxic effects that may progress to cardiomyopathy later in life. We have recently shown that cotreatment of resveratrol (RES) with DOX in juvenile mice attenuates late-onset hypertension-induced cardiomyopathy. However, the molecular mechanism responsible for these changes remains unknown. Herein, we show that the cardiac NLRP3 inflammasome plays a crucial role in regulating cardiac injury in a DOX -treated juvenile mouse model and the detrimental effects of hypertension in these mice later in life. We further demonstrate that RES significantly reduces systemic inflammation to contribute to the improvements observed in DOX -induced cardiac injury in young mice and late-onset hypertension-induced cardiomyopathy.


Subject(s)
Cardiomyopathies/diet therapy , Cardiotoxicity/drug therapy , Doxorubicin/adverse effects , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Resveratrol/pharmacology , Animals , Cardiomyopathies/chemically induced , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cardiotoxicity/metabolism , Cardiotoxicity/pathology , Doxorubicin/pharmacology , Male , Mice
16.
Clin Cosmet Investig Dent ; 13: 531-539, 2021.
Article in English | MEDLINE | ID: mdl-34992465

ABSTRACT

BACKGROUND: Parental preferences and attitudes strongly influence dentists' choices for managing children's behavior in clinics. This study aimed to assess parental attitudes toward two behavior management technique (BMTs)-nitrous oxide (N2O) sedation and/or protective passive stabilization by papoose board (PB)-before and after their children received dental treatment at two referral centers in Jeddah, Saudi Arabia. METHODS: Participants were parents of healthy children who required dental treatment under N2O and/or PB over an 18-month period. Before and after dental treatment, parents answered a questionnaire on their attitudes toward BMTs used on their children. Parents were divided into three groups: Group 1 (parents of children who received N2O), Group 2 (parents of children who received PB), and Group 3 (parents of children who received both N2O and PB). RESULTS: Out of the 132 parents who answered the questionnaire, 106 (80.3%) were in Group 1, 10 (7.6%) in Group 2, and 16 (12.1%) in Group 3. More children of parents with low monthly family incomes were in Group 3 than Group 1 compared to other family-incomes. CONCLUSION: Parental attitudes toward N2O and/or PB improved after their children experienced BMTs. The future use of PB alone with their child's sibling was parents' least preferred BMT (p = 0.001).

17.
J Contemp Dent Pract ; 21(7): 803-807, 2020 Jul 01.
Article in English | MEDLINE | ID: mdl-33020367

ABSTRACT

AIM: To demonstrate an exceptional result in the treatment of an avulsed tooth that had been stored in a dry environment for over 2 hours before being replanted. BACKGROUND: Sixteen percent of all traumatic injuries to the permanent dentition are avulsions. Maxillary central and lateral incisors are most commonly affected. CASE DESCRIPTION: In this report, a 7-year-old girl sustained trauma to the upper right maxillary incisor during a bicycle accident. The tooth was avulsed and remained outside the oral cavity for more than 2 hours in a dry napkin before eventual reimplantation in the emergency room. Upon presentation to the endodontic clinic at the University of Southern California, the case was assessed, and the available treatment options discussed with the patient's parents. Revascularization using BC putty was the chosen mode of treatment. At a 6-month recall appointment, the patient presented with a sinus tract. A decision was then made to perform apexification using the mineral trioxide aggregate (MTA) as an apical filling material. To date, the tooth remains intact and functional. CONCLUSION: Although both of the described treatment modalities are acceptable and commonly used in modern endodontics, apexification of a tooth following a failed attempt of a regenerative procedure has not been described. In this case, a chronic abscess formed and the ultimate goal of revascularization was not achieved. However, the performance of the revascularization procedure was not without benefit since it allowed the tooth to develop in both length, dentinal volume, and aided in the partial closure of the apical foramen. Additional studies are needed regarding the treatment of avulsed teeth. This case study may provide a viable treatment alternative in a number of clinical situations. CLINICAL SIGNIFICANCE: The procedures described in this case report may be of clinical significance in the treatment and retention of teeth, which may otherwise be considered to have a poor prognosis and extracted.


Subject(s)
Apexification , Tooth Avulsion/surgery , Tooth Avulsion/therapy , Child , Female , Humans , Incisor , Maxilla/surgery , Tooth Apex
18.
BMC Cancer ; 20(1): 751, 2020 Aug 12.
Article in English | MEDLINE | ID: mdl-32787791

ABSTRACT

BACKGROUND: The survival rates of women with breast cancer have improved significantly over the last four decades due to advances in breast cancer early diagnosis and therapy. However, breast cancer survivors have an increased risk of cardiovascular complications following chemotherapy. While this increased risk of later occurring structural cardiac remodeling and/or dysfunction has largely been attributed to the cardiotoxic effects of breast cancer therapies, the effect of the breast tumor itself on the heart prior to cancer treatment has been largely overlooked. Thus, the objectives of this study were to assess the cardiac phenotype in breast cancer patients prior to cancer chemotherapy and to determine the effects of human breast cancer cells on cardiomyocytes. METHODS: We investigated left ventricular (LV) function and structure using cardiac magnetic resonance imaging in women with breast cancer prior to systemic therapy and a control cohort of women with comparable baseline factors. In addition, we explored how breast cancer cells communicate with the cardiomyocytes using cultured human cardiac and breast cancer cells. RESULTS: Our results indicate that even prior to full cancer treatment, breast cancer patients already exhibit relative LV hypertrophy (LVH). We further demonstrate that breast cancer cells likely contribute to cardiomyocyte hypertrophy through the secretion of soluble factors and that at least one of these factors is endothelin-1. CONCLUSION: Overall, the findings of this study suggest that breast cancer cells play a greater role in inducing structural cardiac remodeling than previously appreciated and that tumor-derived endothelin-1 may play a pivotal role in this process.


Subject(s)
Breast Neoplasms/complications , Cell Communication/physiology , Endothelin-1/metabolism , Hypertrophy, Left Ventricular/etiology , Myocytes, Cardiac/physiology , Breast Neoplasms/blood , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Case-Control Studies , Cell Line, Tumor , Cells, Cultured , Culture Media, Conditioned/metabolism , Endothelin-1/blood , Female , Humans , Hypertrophy/etiology , Magnetic Resonance Imaging , Middle Aged , Myocytes, Cardiac/pathology , Paracrine Communication , Retrospective Studies , Tumor Cells, Cultured , Ventricular Remodeling
19.
Circ Heart Fail ; 13(6): e006573, 2020 06.
Article in English | MEDLINE | ID: mdl-32493060

ABSTRACT

BACKGROUND: Previous studies have shown beneficial effects of acute infusion of the primary ketone body, ß-hydroxybutyrate, in heart failure (HF). However, whether chronic elevations in circulating ketones are beneficial remains unknown. METHODS: To chronically elevate circulating ketones in mice, we deleted the expression of the ketolytic, rate-limiting-enzyme, SCOT (succinyl-CoA:3-ketoacid-CoA transferase 1; encoded by Oxct1), in skeletal muscle. Tamoxifen-inducible skeletal muscle-specific Oxct1Muscle-/- knockout (n=32) mice and littermate controls (wild type; WT; n=35) were subjected to transverse aortic constriction (TAC) surgery to induce HF. RESULTS: Deletion of SCOT in skeletal, but not cardiac muscle resulted in elevated concentrations of fasted circulating ß-hydroxybutyrate in knockout mice compared with WT mice (P=0.030). Five weeks following TAC, WT mice progressed to HF, whereas knockout mice with elevated fasting circulating ketones were largely protected from the TAC-induced effects observed in WT mice (ejection fraction, P=0.011; mitral E/A, P=0.012). Furthermore, knockout mice with TAC had attenuated expression of markers of sterile inflammation and macrophage infiltration, which were otherwise elevated in WT mice subjected to TAC. Lastly, addition of ß-hydroxybutyrate to isolated hearts was associated with reduced NLRP3 (nucleotide-binding domain-like receptor protein 3)-inflammasome activation, which has been previously shown to play a role in contributing to HF-induced cardiac inflammation. CONCLUSIONS: These data show that chronic elevation of circulating ketones protects against the development of HF that is associated with the ability of ß-hydroxybutyrate to directly reduce inflammation. These beneficial effects of ketones were associated with reduced cardiac NLRP3 inflammasome activation, suggesting that ketones may modulate cardiac inflammation via this mechanism.


Subject(s)
3-Hydroxybutyric Acid/blood , Coenzyme A-Transferases/deficiency , Heart Failure/prevention & control , Myocarditis/prevention & control , Myocardium/enzymology , Animals , Coenzyme A-Transferases/genetics , Disease Models, Animal , Fibrosis , Heart Failure/blood , Heart Failure/enzymology , Heart Failure/physiopathology , Hypertrophy, Left Ventricular/blood , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Inflammasomes/metabolism , Isolated Heart Preparation , Male , Mice, Knockout , Myocarditis/blood , Myocarditis/enzymology , Myocarditis/physiopathology , Myocardium/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Up-Regulation , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/prevention & control , Ventricular Function, Left , Ventricular Remodeling
20.
Nanomedicine (Lond) ; 14(8): 931-954, 2019 04.
Article in English | MEDLINE | ID: mdl-30925102

ABSTRACT

AIM: The current work highlighted preparation of highly penetrating liquid crystalline nanoparticulates (LCNPs) reservoir of a solubility modified berberine oleate (Brb-OL) complex for effective psoriasis management. Materials & methods: Brb-OL-loaded LCNPs (Brb-OL-LCNPs) were prepared using hydrotrope method. RESULTS: The proposed Brb-OL-LCNPs showed a particle size of 137 ± 3.7 nm and negative ζ-potential (-38 ± -5.85 mV). Brb-OL-LCNPs showed a threefold increase in the drug accumulated within rat skin and around tenfold increase in the drug permeation compared with crude Brb. In vivo studies revealed that topical application of Brb-OL-LCNPs hydrogel significantly alleviated psoriasis symptoms and reduced the levels of psoriatic inflammatory cytokines. CONCLUSION: Formulating Brb-OL in the LCNPs controlled the release, retention and permeation of the drug across skin layers, which are of prime importance for psoriasis management.


Subject(s)
Berberine/pharmacology , Drug Carriers/chemistry , Liquid Crystals/chemistry , Nanoparticles/chemistry , Psoriasis/drug therapy , Administration, Cutaneous , Animals , Berberine/administration & dosage , Delayed-Action Preparations/chemistry , Drug Compounding/methods , Female , Humans , Hydrophobic and Hydrophilic Interactions , Mice , Oleic Acid/chemistry , Particle Size , Rats , Rats, Wistar , Skin/metabolism , Solubility , Surface Properties
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