Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 54
Filter
1.
J Clin Transl Endocrinol ; 35: 100335, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38525377

ABSTRACT

Multiple randomized controlled trials have extensively examined the therapeutic effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors, ushering in a transformative approach to treating individuals with type 2 diabetes mellitus (DM). Notably, emerging reports have drawn attention to the potential positive impacts of SGLT2 inhibitors in nondiabetic patients. In an effort to delve into this phenomenon, a comprehensive systematic literature review spanning PubMed (NLM), Medline (Ovid), and Cochrane Library, covering publications from 2000 to 2024 was undertaken. This systematic review encompassed twenty-six randomized control trials (RCTs) involving 35,317 participants. The findings unveiled a multifaceted role for SGLT2 inhibitors, showcasing their ability to enhance metabolic control and yield cardioprotective effects through a reduction in cardiovascular death (CVD) and hospitalization related to heart failure (HF). Additionally, a renalprotective effect was observed, evidenced by a slowdown in chronic kidney disease (CKD) progression and a decrease in albuminuria. Importantly, these benefits were coupled with an acceptable safety profile. The literature also points to various biological plausibility and underlying mechanistic pathways, offering insights into the association between SGLT2 inhibitors and these positive outcomes in nondiabetic individuals. Current research trends indicate a continual exploration of additional role for SGLT2 inhibitors in. Nevertheless, further research is imperative to fully elucidate the mechanisms and long-term outcomes associated with the nondiabetic use of SGLT2 inhibitors.

2.
J Clin Med ; 13(4)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38398269

ABSTRACT

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i acts by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

3.
J Clin Med ; 12(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37834929

ABSTRACT

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone's efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors' (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease.

4.
Front Microbiol ; 14: 1222503, 2023.
Article in English | MEDLINE | ID: mdl-37529322

ABSTRACT

Background: Vulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC. Aim of work: To compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium. Methods: In total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3-5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue. Results: Both L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus. Conclusion: Through maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.

5.
Int J Biol Macromol ; 239: 124238, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37003386

ABSTRACT

Aerogels, especially bio-based ones, present a promising option for wound dressing; specifically, because of their low toxicity, high stability, bio-compatibility, and good biological performance. In this study, agar aerogel was prepared and evaluated as novel wound dressing material in an in vivo rat study. Agar hydrogel was prepared by thermal gelation, after that the water inside the gel was exchanged with ethanol, and finally the alcogel was dried by supercritical CO2. The textural and rheological properties of the prepared aerogel were characterized, showing that the prepared agar aerogels possess high porosity (97-98 %), high surface area (250-330 m2g-1) as well as good mechanical properties and easiness of removal from the wound site. The results of the in vivo experiments macroscopically demonstrate the tissue compatibility of the aerogels in dorsal interscapular injured rat tissue and a shorter wound healing time comparable to that of gauze-treated animals. The histological analysis underpins the reorganisation and healing of the tissue for the injured skin of rats treated with agar aerogel wound dressing within the studied time frame.


Subject(s)
Bandages , Wound Healing , Rats , Animals , Agar , Skin , Hydrogels/pharmacology
6.
J Clin Med ; 12(5)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36902660

ABSTRACT

Kidney failure poses an enormous burden on patients, caregivers, healthcare providers, and society as a whole [...].

7.
J Clin Med ; 12(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36615175

ABSTRACT

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI.

8.
J Am Dent Assoc ; 153(12): 1154-1170.e60, 2022 12.
Article in English | MEDLINE | ID: mdl-36435528

ABSTRACT

BACKGROUND: The aim of this network meta-analysis was to assess the comparative effects of different dexamethasone (DXM) routes and doses on reducing postoperative sequelae (pain, swelling, trismus) after surgical extraction of impacted mandibular third molars. METHODS: Five databases were searched on September 22, 2021, for randomized controlled trials. Risk of bias (ROB) was assessed using the Cochrane ROB 2 tool. Study heterogeneity, publication bias, and quality of evidence were investigated. Network meta-analyses were conducted (P < .05), and the P-score was used to rank comparisons of DXM doses and routes. RESULTS: Thirty-four eligible studies were included. Eight studies had low ROB, 21 had some concerns, and 5 had high ROB. The certainty of evidence evaluated by the Confidence in Network Meta-Analysis tool indicated low to very low certainty in most comparisons. The results showed that most DXM route and dose combinations were superior to a placebo in reducing the postoperative sequelae 1 day after surgical extraction. The results also showed that a 4-mg DXM submucosal injection substantially reduces pain 3 days after extraction compared with a 4-mg twin-mix or 8-mg intramuscular injection. Overall, it appears that 4 mg DXM submucosal injection or admixed with local anesthetic is effective in reducing postoperative sequelae after surgical extraction. CONCLUSIONS: Within the limitations of this study, the administration of DXM appears to be effective in reducing the postoperative sequelae, especially in the submucosal route. However, no noteworthy differences were found between the investigated DXM route and dose comparisons. PRACTICAL IMPLICATIONS: Submucosal DXM injection effectively reduce postoperative sequelae of third-molar extractions.


Subject(s)
Molar, Third , Tooth, Impacted , Humans , Molar, Third/surgery , Network Meta-Analysis , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Randomized Controlled Trials as Topic , Tooth, Impacted/surgery , Dexamethasone/therapeutic use , Molar , Injections, Intramuscular
9.
J Clin Med ; 11(21)2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36362503

ABSTRACT

Acute kidney injury (AKI) is a serious problem, affecting multiple organs, and is associated with a high mortality. The severe consequences of AKI extend beyond hospital discharge to the outpatient setting. While a plethora of literature exists guiding the management of AKI in the hospital setting, currently, there are no guidelines for the best care of AKI patients post-hospital discharge. In this review, we address the burden of AKI on patients and the importance of optimal coordinated care of these patients post-hospital discharge. We review the care of patients with or without dialysis requirements at the time of discharge and thereafter.

10.
Wiad Lek ; 75(5 pt 2): 1305-1308, 2022.
Article in English | MEDLINE | ID: mdl-35758448

ABSTRACT

OBJECTIVE: The aim: To assess nurses' infection control knowledge at basic health care clinics and knowledge in practices nurses on infection control. PATIENTS AND METHODS: Materials and methods: This is cross-sectional study, conducted in primary health care centers within descriptive research in Al-Hilla City, from 17th May, 2021 to 2nd October, 2021. The researcher created the instruments to achieve the study's objectives through non-probability sampling: the purposive sample is made from of 140 searched, who worked in the dressing and immunization units of primary health care centers were chosen, and two study instruments [questionnaire and demographic data] were used for proper data collection. RESULTS: Results: In this study revealed that (47.1%) at age groups (35-39) ages, the current study's findings revealed that (69.8%) of Males made up the sample and (60.7%) graduated from a nursing school (50%) have Training courses and (42.1%) consume (16-20) years of experience. And The nurses' general knowledge levels about infection control were good. CONCLUSION: Conclusions: The majority of health-care personnel' knowledge, attitude, and practice regarding basic precautions were adequate, favorable, and safe by the expected standard.


Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Clinical Competence , Cross-Sectional Studies , Female , Humans , Infection Control , Iraq , Male , Primary Health Care , Surveys and Questionnaires , Young Adult
11.
Environ Sci Pollut Res Int ; 29(32): 47931-47941, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35543788

ABSTRACT

Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory.


Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Breast Neoplasms/pathology , Female , Frozen Sections , Humans , Lymphatic Metastasis/pathology , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy/methods
12.
Build Environ ; 219: 109176, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35599669

ABSTRACT

The pandemic of COVID-19 currently shadows the world; the whole earth has been on an unprecedented lockdown. Social distancing among people interrupted domestic and international air traffic, suspended industrial productions and economic activities, and had various far-reaching and undetermined implications on air quality. Improvement in air quality has been reported in many cities during the lockdown. On March 22, 2020, the Turkish government enforced strict lockdown measures to reduce coronavirus disease transmission. This lockdown had a significant impact on the movement of people within the country, which resulted in a major drop in worldwide commercial activities. During this period, university campuses were emptied due to the transition to distance education. In this study, various air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), fine particulate matter (PM2.5), total bacteria, and total fungi were measured in different indoor environments at Eskisehir Technical University Campus in Eskisehir, Turkey during COVID-19 lock down period. Also, to calculate the indoor and outdoor ratios (I/O) of the pollutants, simultaneous outdoor measurements were also carried out. The average indoor SO2, NO2, O3, and PM2.5 concentrations in different indoor environments ranged between 2.10 and 54.58, 1.36-30.89, 12.01-39.05, and 21-94 µg/m3, respectively. The total number of bacteria and fungi ranged between 21.83-514.15 and 13.10-83.36 CFU/m3, respectively. Our study intends to give a glimpse to quantify the impact of a pandemic on air quality in different indoor environments in a university campus in Eskisehir, Turkey and calls for follow-up studies. Indoor concentrations were evaluated together with outdoor concentrations. In general, it can be said that the calculated I/O ratios for SO2, NO2, O3, bacteria, and fungi were less than 1 in most indoor environments.

13.
Front Oncol ; 11: 673276, 2021.
Article in English | MEDLINE | ID: mdl-34178661

ABSTRACT

The tumor microenvironment (TME) is greatly multifaceted and immune escape is an imperative attribute of tumors fostering tumor progression and metastasis. Based on reports, the restricted achievement attained by T cell immunotherapy reflects the prominence of emerging other innovative immunotherapeutics, in particular, natural killer (NK) cells-based treatments. Human NK cells act as the foremost innate immune effector cells against tumors and are vastly heterogeneous in the TME. Currently, there exists a rapidly evolving interest in the progress of chimeric antigen receptor (CAR)-engineered NK cells for tumor immunotherapy. CAR-NK cells superiorities over CAR-T cells in terms of better safety (e.g., absence or minimal cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), engaging various mechanisms for stimulating cytotoxic function, and high feasibility for 'off-the-shelf' manufacturing. These effector cells could be modified to target various antigens, improve proliferation and persistence in vivo, upturn infiltration into tumors, and defeat resistant TME, which in turn, result in a desired anti-tumor response. More importantly, CAR-NK cells represent antigen receptors against tumor-associated antigens (TAAs), thereby redirecting the effector NK cells and supporting tumor-related immunosurveillance. In the current review, we focus on recent progress in the therapeutic competence of CAR-NK cells in solid tumors and offer a concise summary of the present hurdles affecting therapeutic outcomes of CAR-NK cell-based tumor immunotherapies.

14.
Physiol Rep ; 9(5): e14766, 2021 03.
Article in English | MEDLINE | ID: mdl-33713581

ABSTRACT

Recently we showed that homoarginine supplementation confers kidney protection in diabetic mouse models. In this study we tested whether the protective effect of homoarginine is nitric oxide synthase-3 (NOS3)-independent in diabetic nephropathy (DN). Experiments were conducted in NOS3 deficient (NOS3-/- ) mice and their wild type littermate using multiple low doses of vehicle or streptozotocin and treated with homoarginine via drinking water for 24 weeks. Homoarginine supplementation for 24 weeks in diabetic NOS3-/- mice significantly attenuated albuminuria, increased blood urea nitrogen, histopathological changes and kidney fibrosis, kidney fibrotic markers, and kidney macrophage recruitment compared with vehicle-treated diabetic NOS3-/- mice. Furthermore, homoarginine supplementation restored kidney mitochondrial function following diabetes. Importantly, there were no significant changes in kidney NOS1 or NOS2 mRNA expression between all groups. In addition, homoarginine supplementation improved cardiac function and reduced cardiac fibrosis following diabetes. These data demonstrate that the protective effect of homoarginine is independent of NOS3, which will ultimately change our understanding of the mechanism(s) by which homoarginine induce renal and cardiac protection in DN. Homoarginine protective effect in DN could be mediated via improving mitochondrial function.


Subject(s)
Diabetic Nephropathies/drug therapy , Homoarginine/pharmacology , Nitric Oxide Synthase Type III/drug effects , Oxidative Stress/drug effects , Streptozocin/pharmacology , Albuminuria/metabolism , Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Homoarginine/metabolism , Kidney/drug effects , Kidney/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , Mice, Knockout
15.
Nat Rev Nephrol ; 17(5): 319-334, 2021 05.
Article in English | MEDLINE | ID: mdl-33547417

ABSTRACT

Diabetic kidney disease is the leading cause of kidney failure worldwide; in the USA, it accounts for over 50% of individuals entering dialysis or transplant programmes. Unlike other complications of diabetes, the prevalence of diabetic kidney disease has failed to decline over the past 30 years. Hyperglycaemia is the primary aetiological factor responsible for the development of diabetic kidney disease. Once hyperglycaemia becomes established, multiple pathophysiological disturbances, including hypertension, altered tubuloglomerular feedback, renal hypoxia, lipotoxicity, podocyte injury, inflammation, mitochondrial dysfunction, impaired autophagy and increased activity of the sodium-hydrogen exchanger, contribute to progressive glomerular sclerosis and the decline in glomerular filtration rate. The quantitative contribution of each of these abnormalities to the progression of diabetic kidney disease, as well as their role in type 1 and type 2 diabetes mellitus, remains to be determined. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a beneficial impact on many of these pathophysiological abnormalities; however, as several pathophysiological disturbances contribute to the onset and progression of diabetic kidney disease, multiple agents used in combination will likely be required to slow the progression of disease effectively.


Subject(s)
Diabetic Nephropathies/etiology , Hypoglycemic Agents/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Autophagy/drug effects , Diabetic Nephropathies/prevention & control , Endothelium, Vascular/drug effects , Glomerular Filtration Rate/drug effects , Humans , Hyperglycemia/complications , Hypertension/complications , Kidney Tubules/drug effects , Kidney Tubules/metabolism , Obesity/complications , Podocytes/pathology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
16.
Cureus ; 13(1): e12634, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33447496

ABSTRACT

Papillary fibroelastoma is a benign cardiac tumour that most commonly presents as an incidental finding on imaging but may present with an acute neurological event due to embolic phenomena. We report a 51-year-old female who presented with focal neurology of the right hand that lasted for 30 minutes. Her initial investigations including CT-brain were unremarkable, and given her low-risk profile for stroke she was discharged for routine outpatient workup of possible transient ischaemic attack. Transthoracic echo detected a large mobile mass attached to the left ventricular wall. This was mistakenly diagnosed as a left ventricular thrombus, for which she was commenced on warfarin. After three months on warfarin without reduction in the size of the mass, cardiac MRI was performed. The scan was repeated as the initial imaging failed to demonstrate the tumour. This was followed by positron emission tomography which suggested a benign mass of the left ventricle. The patient underwent surgical excision of the tumour and developed post-pericardiotomy syndrome. Histopathology confirmed papillary fibroelastoma. Though rare, cardiac neoplasm may remain a differential diagnosis for acute neurological presentations in non-classical patients.

17.
JCI Insight ; 5(19)2020 10 02.
Article in English | MEDLINE | ID: mdl-32956070

ABSTRACT

Fibrosis is the final common pathway in the pathophysiology of most forms of chronic kidney disease (CKD). As treatment of renal fibrosis still remains largely supportive, a refined understanding of the cellular and molecular mechanisms of kidney fibrosis and the development of novel compounds are urgently needed. Whether arginases play a role in the development of fibrosis in CKD is unclear. We hypothesized that endothelial arginase-2 (Arg2) promotes the development of kidney fibrosis induced by unilateral ureteral obstruction (UUO). Arg2 expression and arginase activity significantly increased following renal fibrosis. Pharmacologic blockade or genetic deficiency of Arg2 conferred kidney protection following renal fibrosis, as reflected by a reduction in kidney interstitial fibrosis and fibrotic markers. Selective deletion of Arg2 in endothelial cells (Tie2Cre/Arg2fl/fl) reduced the level of fibrosis after UUO. In contrast, selective deletion of Arg2 specifically in proximal tubular cells (Ggt1Cre/Arg2fl/fl) failed to reduce renal fibrosis after UUO. Furthermore, arginase inhibition restored kidney nitric oxide (NO) levels, oxidative stress, and mitochondrial function following UUO. These findings indicate that endothelial Arg2 plays a major role in renal fibrosis via its action on NO and mitochondrial function. Blocking Arg2 activity or expression could be a novel therapeutic approach for prevention of CKD.


Subject(s)
Arginase/antagonists & inhibitors , Endothelial Cells/metabolism , Fibrosis/prevention & control , Kidney Diseases/prevention & control , Kidney Tubules, Proximal/metabolism , Ureteral Obstruction/complications , Animals , Arginase/physiology , Fibrosis/etiology , Fibrosis/metabolism , Fibrosis/pathology , Kidney Diseases/etiology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Mitochondria/pathology , Oxidative Stress
18.
Am J Physiol Renal Physiol ; 318(2): F509-F517, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31904280

ABSTRACT

Endothelial dysfunction, characterized by reduced bioavailability of nitric oxide and increased oxidative stress, is a hallmark characteristic in diabetes and diabetic nephropathy (DN). High levels of asymmetric dimethylarginine (ADMA) are observed in several diseases including DN and are a strong prognostic marker for cardiovascular events in patients with diabetes and end-stage renal disease. ADMA, an endogenous endothelial nitric oxide synthase (NOS3) inhibitor, is selectively metabolized by dimethylarginine dimethylaminohydrolase (DDAH). Low DDAH levels have been associated with cardiac and renal dysfunction, but its effects on DN are unknown. We hypothesized that enhanced renal DDAH-1 expression would improve DN by reducing ADMA and restoring NOS3 levels. DBA/2J mice injected with multiple low doses of vehicle or streptozotocin were subsequently injected intrarenally with adenovirus expressing DDAH-1 (Ad-h-DDAH-1) or vector control [Ad-green fluorescent protein (GFP)], and mice were followed for 6 wk. Diabetes was associated with increased kidney ADMA and reduced kidney DDAH activity and DDAH-1 expression but had no effect on kidney DDAH-2 expression. Ad-GFP-treated diabetic mice showed significant increases in albuminuria, histological changes, glomerular macrophage recruitment, inflammatory cytokine and fibrotic markers, kidney ADMA levels, and urinary thiobarbituric acid reactive substances excretion as an indicator of oxidative stress, along with a significant reduction in kidney DDAH activity and kidney NOS3 mRNA compared with normal mice. In contrast, Ad-h-DDAH-1 treatment of diabetic mice reversed these effects. These data indicate, for the first time, that DDAH-1 mediates renal tissue protection in DN via the ADMA-NOS3-interaction. Enhanced renal DDAH-1 activity could be a novel therapeutic tool for treating patients with diabetes.


Subject(s)
Adenoviridae/genetics , Amidohydrolases/biosynthesis , Arginine/analogs & derivatives , Diabetes Mellitus, Experimental/therapy , Diabetic Nephropathies/prevention & control , Genetic Therapy , Genetic Vectors , Kidney/enzymology , Albuminuria/enzymology , Albuminuria/genetics , Albuminuria/prevention & control , Amidohydrolases/genetics , Animals , Arginine/metabolism , Cytokines/genetics , Cytokines/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/genetics , Diabetic Nephropathies/enzymology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/genetics , Fibrosis , Inflammation Mediators/metabolism , Kidney/pathology , Male , Mice, Inbred DBA , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress , Signal Transduction , Thiobarbituric Acid Reactive Substances/metabolism
19.
Surg Infect (Larchmt) ; 21(2): 150-157, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31513456

ABSTRACT

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection remains a challenging threat because of limited treatment options. Ceftaroline was identified as having potent anti-MRSA activity. Aim: To evaluate the susceptibility of MRSA to gentamicin, macrolides, ciprofloxacin, vancomycin, and ceftaroline and to perform molecular characterization of different resistance genes as aminoglycoside modifying enzyme genes, ermA and ermC, and vanA and vanB genes. Patients and Methods: One hundred non-duplicate MRSA strains were isolated from different samples of hospitalized patients in Cairo University teaching hospitals from November 2015 to August 2016. Determination of antibiotic susceptibility was done using disk diffusion test and minimum inhibitory concentration followed by detection of resistance genes by multiplex polymerase chain reaction (PCR). Results: Of 100 MRSA isolates, 63 (63%) were resistant to gentamicin, erythromycin, clindamycin, and ciprofloxacin, however, all were sensitive to ceftaroline. Fifteen isolates (15%) were vancomycin intermediate resistant and were sensitive to ceftaroline as well. Conclusion: Ceftaroline was potent against MRSA, which was found to be non-susceptible to vancomycin, ciprofloxacin, erythromycin, clindamycin, and gentamicin and it may represent a successful treatment for MRSA infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/genetics , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Cephalosporins/pharmacology , Ciprofloxacin/pharmacology , Genes, Bacterial , Gentamicins/pharmacology , Humans , Macrolides/pharmacology , Microbial Sensitivity Tests , Vancomycin/pharmacology , Ceftaroline
20.
Physiol Rep ; 7(18): e14235, 2019 09.
Article in English | MEDLINE | ID: mdl-31552707

ABSTRACT

l-homoarginine is an endogenous, non-proteinogenic amino acid that has emerged as a new player in health and disease. Specifically, low l-homoarginine levels are associated with cardiovascular diseases, stroke, and reduced kidney function. However, the role of l-homoarginine in the pathogenesis of diabetic nephropathy (DN) is not known. Experiments were conducted in 6-week-old Ins2Akita mice supplemented with l-homoarginine via drinking water or mini osmotic pump for 12 weeks. Both plasma and kidney l-homoarginine levels were significantly reduced in diabetic mice compared to nondiabetic controls. Untreated Ins2Akita mice showed significant increases in urinary albumin excretion, histological changes, glomerular macrophage recruitment, the inflammatory cytokine KC-GRO/CXCL1, and urinary thiobarbituric acid reactive substances (TBARS) excretion as an indicator of oxidative stress, along with a significant reduction in kidney nitrate + nitrite levels compared to control mice at 18 weeks of age. In contrast, l-homoarginine supplementation for 12 weeks in Ins2Akita mice, via either drinking water or mini osmotic pump, significantly reduced albuminuria, renal histological changes, glomerular macrophage recruitment, KC-GRO/CXCL1 levels, urinary TBARS excretion, and largely restored kidney nitrate + nitrite levels. These data demonstrate that l-homoarginine supplementation attenuates specific features of DN in mice and could be a potential new therapeutic tool for treating diabetic patients.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetic Nephropathies/prevention & control , Dietary Supplements , Homoarginine/therapeutic use , Albuminuria/drug therapy , Animals , Chemokine CXCL1/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/metabolism , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Drug Evaluation, Preclinical/methods , Homoarginine/metabolism , Kidney/metabolism , Kidney/pathology , Kidney Glomerulus/pathology , Macrophages/pathology , Mice, Inbred DBA , Nitrates/metabolism , Nitrites/metabolism , Oxidative Stress/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...