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1.
Article in English | MEDLINE | ID: mdl-38966517

ABSTRACT

We present an interesting and complex case of cardiac tamponade due to uremic pericarditis (UP), resolving with intensive hemodialysis (HD). HD should be considered as first line management for patients with UP and pericardial effusion. Intensification of HD should be considered based on clinical presentation and severity of presentation.

2.
J Family Med Prim Care ; 13(4): 1278-1283, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38827657

ABSTRACT

Background: According to the 2011 census in Tamil Nadu, out of a total population of 721.47 lakhs, 7.95 lakhs were scheduled tribes (STs), which constitutes about 1.1% of ST in Tamil Nadu and 0.8% of ST compared to the total ST population in India. A brief understanding of India's caste system and its evolution over time was required to determine caste-based discrimination. Hence, they are vulnerable and isolated due to this untouchability in the caste system. This study focuses on the quality of life (QOL) and caste discrimination among the tribal population of Chengalpattu district. Further, it provides suggestions to improve the QOL and to put an end to discrimination. Methodology: It is a community-based cross-sectional study, conducted among 300 participants among the tribal population in Chengalpattu district by a systematic random sampling technique. Results: The QOL scores were further converted into categorical variables by obtaining the mean score and dividing the group into those who got a score above the mean and those below the mean. They were labeled as good and poor QOL. More than half of them (52.7%) had poor QOL. Almost two-third of the workers had poor QOL in the social relationship (60.7%) and psychological (64%) domains, and nearly half in the physical (52.7%) and environmental (52.7%) domains. Out of 300 participants included in the analyses, 141 (47%) participants reported experiencing discrimination a few times a year/a few times a month. Conclusion: This study found that the tribal population in Chengalpattu district has poor social and psychological QOL compared to QOL in the environmental and physical domains. In spite of many government initiatives, a wide range of issues and problems are being faced by the tribals in India. Hence, we recommend strategies to improve the physical, social, and psychological well-being of this vulnerable population through strict legislation. The other component regarding discrimination concluded that caste but not socio-economic class is closely linked with perceived discrimination among the tribal population in Chengalpattu district and their responses to unfair treatment.

3.
J Family Med Prim Care ; 12(1): 128-132, 2023 Jan.
Article in English | MEDLINE | ID: mdl-37025227

ABSTRACT

Purpose/Background: Hence, this comparative study of risk assessment was carried out among out patients visiting urban and rural health centers. This study aimed to find out and compare the risk factors for NCDs among out-patients visiting urban and rural health centers. Methods: This cross-sectional study was carried out in Urban health centre Rukmini Nagar and Rural health centre Vantamuri. Using convenient universal sampling, 200 out-patients from urban area and 200 from rural area were selected. The data were entered into MS-EXCEL and analyzed using SPSS software. Results: In urban area, males were more common (53.7%), whereas females were more common in rural areas (53.8%). Maximum study participants were laborers in urban area (24.5%), whereas home makers were common in rural area (40.5%). Most people in urban areas (11.5%) were indulged in smoking, whereas only 5% smoked in rural area. Participants in urban area had higher waist circumference (20.5%) than those in rural area (17.5%). Physical inactivity was more in rural area (68%), as compared to urban area (47%). 29.5% of participants were found to be at risk for NCDs in urban area, whereas 30% of those were found to be at risk in rural area. Conclusions: Awareness regarding ill effects of risk factors: smoking, alcohol consumption, physical inactivity, and obesity should be created among the community through health education and behavioral change communication to prevent its progression as a disease in future.

4.
Cureus ; 14(10): e30904, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36465756

ABSTRACT

Endocarditis is a condition that is usually caused by an infection or inflammation of the endocardium. The disease is commonly seen among intravenous drug abusers, patients with intravenous catheters, and those who undergo cardiovascular and invasive dental procedures. Multiple different pathogens can cause endocarditis (bacterial, fungal, and viral) depending upon the patient's risk factors, epidemiology, and bacteria that are prevalent/endemic to the region. We present the case of a woman who had a history of polysubstance abuse, having presented to the hospital on multiple occasions with bacteremia with a previous admission for endocarditis, who developed a multi-bacterial infection at this presentation involving Pseudomonas aeruginosa and group C Streptococcus, which affected both the right and left side of the heart. In this paper, we reviewed common presentations of endocarditis caused by either bacteria, as well as recommendations for medical or surgical management of the condition.

5.
Article in English | MEDLINE | ID: mdl-36262902

ABSTRACT

Heparin Induced Thrombocytopenia (HIT) is a life threatening condition which is caused due to antibody formation following exposure to heparin or heparin products. It occurs due to the formation of Platelet Factor 4 antibodies (PF4). HIT is classified into 3 categories based on the duration between heparin exposure and onset of drop in platelet counts. A less common form of HIT is delayed onset HIT which occurs more than 9 days after exposure to heparin or heparin products. In this report we would like to present a rare case of delayed onset HIT which occurred in our patient who presented with rhabdomyolysis and Non ST elevation myocardial infraction (NSTEMI); which resulted in limb ischemia which needed to be treated by amputation of the affected area. We also highlight further management of patients who have thrombotic disease in the setting of HIT and review literature of how heparin or heparin products can be reintroduced in such patient who cannot be managed by other anticoagulation.

6.
Food Funct ; 13(15): 8283-8303, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35834215

ABSTRACT

Colon cancer is the most prevalent cause of death from cancer across the globe. Although chemotherapy drugs are predominantly used, their toxicity always remains a cause of concern. As an alternative to synthetic drugs, natural compounds or nutraceuticals are comparatively less toxic. Honey is widely used across different cultures as an alternative form of medicine. It represents a prominent source of plant-phenolic compounds and there is demonstrable evidence of its anti-oxidant and anti-microbial activities. The aim of the present work was to investigate the anti-proliferative effect of some Indian honeys and analyze their mechanism of action in colon cancer. In order to establish the composition-activity relationship, we evaluated the bioactive components present in selected honey samples by GC-MS and HPLC analysis. Indian honey samples showed a significant inhibitory impact on cell growth by restricting cell proliferation, causing apoptosis, and restricting the cell cycle in the G2/M phase specifically for colon cancer cells. The apoptotic activities, as imparted by the honey samples, were established by Annexin V/PI staining, real-time PCR, and immunoblot analyses. The treated cells showed increased expressions of p53 and caspases 3, 8, and 9, thus indicating the involvement of both extrinsic and intrinsic apoptotic pathways. The honey samples were also found to inhibit the ß-catenin/Wnt pathway. In the next phase of the study, the efficacy of these honey samples was evaluated in colon carcinoma induced SD-rats. Overall, these findings demonstrated that selected Indian honeys could be established as effective nutraceuticals for the prevention as well as cure of colon cancer.


Subject(s)
Colonic Neoplasms , Honey , Animals , Apoptosis , Cell Proliferation , Colonic Neoplasms/drug therapy , Honey/analysis , Rats , Wnt Signaling Pathway , beta Catenin
7.
J Surg Case Rep ; 2022(6): rjac211, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35685294

ABSTRACT

Spontaneous splenic rupture is a rare and life-threatening phenomenon, usually associated with an underlying infectious, inflammatory, hematological, neoplastic or rheumatologic condition. Indeterminate cell tumor is a rare neoplastic dendritic cell disorder that is poorly understood but shares immunophenotypic markers for Langerhans cells without Birbeck granules. A 73-year-old man presented with upper abdominal pain after an unwitnessed fall. Computed tomography angiography showed splenomegaly and a large ruptured splenic subcapsular hematoma. Intraoperative findings from an emergency laparotomy revealed a large hemoperitoneum and a ruptured spleen. Microscopic sections identified numerous, mostly poorly formed, small nodules classified as a proliferation of indeterminate dendritic cell tumors.

8.
Article in English | MEDLINE | ID: mdl-35712688

ABSTRACT

Spontaneous coronary artery dissection (SCAD) is a rare but life-threatening condition which occurs due to non-traumatic separation of the coronary artery wall. It is more common in women, with an unclear, non-atherosclerotic mechanism. We report a unique case of spontaneous coronary artery dissection presenting as ST-elevation myocardial infarction (STEMI). A 54-year-old woman presented with fever and recurrent abscess. On presentation, she was tachycardic, tachypneic and hypoxic, requiring nasal cannula. Physical exam was notable for healing a wound on the right lower back, status post incision and drainage, with no erythema, edema, ecchymosis or purulent drainage. Laboratory investigations were remarkable for anemia. EKG showed sinus tachycardia with no ST-segment changes. Her hospital course was complicated by septic shock, renal failure, and acute hypoxic respiratory failure requiring intubation. Following extubation, she complained of sudden-onset, severe chest pain. EKG showed ST-elevations in the lateral and inferior leads, with an elevated high-sensitivity troponin level. Cardiac catheterization revealed SCAD involving the mid to distal right posterior descending artery (RPDA) with TIMI-3 flow in the distal RPDA. Given vessel tortuosity and poor target for stenting, was medically managed with dual antiplatelet therapy, a beta-blocker and an eptifibatide infusion for 12 h post-procedure. Extensive rheumatological workup negative. She remained hemodynamically stable with no new ST changes on subsequent EKGs. This is an uncommon medical emergency requiring prompt recognition, appropriate management and early intervention to prevent unfavorable patient outcomes.

9.
Cureus ; 14(2): e22000, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35282561

ABSTRACT

A 25-year-old man presented with symptoms of cervical myelopathy for 10 days. Imaging revealed an expansile, lytic lesion involving the C2 vertebra completely and compressing the spinal cord, suggestive of giant cell tumor (GCT). Tumor resection and posterior stabilization from C1-C4 were done. Histopathology confirmed the diagnosis of GCT. The patient was kept on adjuvant Denosumab (D-ab) for two years with no signs of recurrence. However, discontinuation of D-ab therapy led to recurrence of the tumor within three months, which was managed with repeated surgical resection and anterior instrumentation followed by radiotherapy. To the best of our knowledge, this is the first reported case of GCT involving the upper cervical spine with rapid recurrence following the stoppage of D-ab therapy.

10.
Article in English | MEDLINE | ID: mdl-34804390

ABSTRACT

COVID-19, also known as SARS-CoV-2, which originated in China in late 2019, has spread rapidly resulting in a global pandemic. COVID-19 has been linked to many different clinical manifestations, including hyponatremia. The cause of hyponatremia in acute COVID-19 infection is speculated to be multifactorial, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), thought to be a result of inflammatory cytokines (Interleukin-6) and/or related to the gastrointestinal symptoms of this infection. SIADH in the setting of COVID-19 pneumonia is an established complication of this disease. This is the case of an 81-year-old woman with a history of hypertension, on thiazide diuretic, initially presented after a fall in the setting of COVID-19 pneumonia. She was treated with remdesivir and dexamethasone and then discharged to a rehab facility with normal labwork, including a sodium of 137 mmol/L. Two weeks later, routine labwork identified hyponatremia of 111 mmol/L. Her vital signs were normal, she was euvolemic on exam and alert/oriented with no complaints. Investigations into the etiology of her hyponatremia included a urine sodium of 72 mmol/L, serum osmolality of 231 mOsm/kg, urine osmolality of 454 mOsm/kg. We diagnosed hypo-osmolar hyponatremia due to SIADH. Management included fluid restriction and then tolvaptan, which ultimately corrected the serum sodium to 134 mmol/L. As COVID-19 is a new infection, little is known regarding its impact on electrolyte imbalances. Our patient recovered from pneumonia, then later developed severe hyponatremia possibly secondary to the lasting effects of inflammation in her lungs.

11.
Article in English | MEDLINE | ID: mdl-34567472

ABSTRACT

Pneumorrhachis is an extremely rare clinical entity, involving air entrapment within the spinal canal. We present a unique case of epidural pneumorrhachis accompanying pneumomediastinum and pneumopericardium, in the setting of COVID-19 infection in a 62-year-old woman. Diagnostic testing was remarkable for elevated inflammatory markers, along with mild transaminitis and hyponatremia. CT scan of the chest revealed extensive patchy ground-glass opacities, with no evidence of pulmonary embolism. Intravenous antibiotics and steroids were initiated for management of advanced multifocal bilateral COVID-19 pneumonia. Her hospital course was complicated by rapidly worsening hypoxia accompanied by worsening inflammatory markers. Repeat chest CT showed worsening multifocal opacities, extensive pneumomediastinum, pneumopericardium, and subcutaneous emphysema extending into the lower neck soft tissues, posterior mediastinum, and supraclavicular regions. Neck CT confirmed diffuse subcutaneous emphysema from the mediastinum extending into the retropharyngeal space, neck, and anterior chest wall. Right-sided epidural air in the spinal canal spanning C6-T1 was also noted. She was evaluated by neurosurgery, continued on antibiotics for the epidural air, and transferred to the ICU for frequent monitoring of respiratory and neurological status, which remained stable. Although pneumorrhachis is an extremely rare clinical manifestation, prompt recognition can lead to appropriate early interventions and improved patient outcomes.

12.
Cureus ; 13(8): e17057, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34522535

ABSTRACT

Background Industry payments to physicians raise concerns about conflicts of interest that have the potential to impact patient care. In this study, we explored nonresearch and nonownership payments from industry to nephrologists to identify trends in compensation. Methodology Using data from the Centers for Medicare and Medicaid Services (CMS), we explored financial relationships between industry and US nephrologists from 2014 to 2018. We analyzed payment characteristics including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Results In this retrospective study, a total of $75,174,999 was paid to nephrologists in the United States during the study period (i.e., 2014-2018). The number of board-certified nephrologists receiving payment from the industry increased from 11,642 in 2014 to 13,297 in 2018. Among board-certified nephrologists, 56% to 63% received industry payments during the study period. The total payments to nephrologists increased from $13,113,512 in 2014 to $16,467,945 in 2017, with consulting fees (24%) and compensation for services other than consulting (35%) being the highest-paid categories. The top 10% of physician beneficiaries collected 90% of the total industry payments. Conclusions A small proportion of US nephrologists consistently received the majority of industry payments, the value of which grew over the study period.

13.
Colloids Surf B Biointerfaces ; 203: 111771, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33894648

ABSTRACT

Boride, which belongs to the distinct category of ceramic materials, has attracted significant attention in tissue engineering applications. Magnesium diboride (MgB2) consists of a plane of magnesium atoms sandwiched between the layers of boron. Even though MgB2 showed its role in various applications, its effect on osteogenesis has not yet been investigated. In this study, we synthesized MgB2 nanosheets (MgB2NS), a new class of 2D-nanoscale structures, by the ultrasonication exfoliation method and incorporated them into a polymeric mixture of alginate (Alg) and polyvinyl alcohol (PVA) by the freeze-drying procedure. The synthesized scaffolds (Alg/PVA/MgB2NS) were characterized by SEM, XRD, FT-IR, protein adsorption, swelling, degradation, and biomineralization studies. These scaffolds were non-toxic to mouse mesenchymal stem cells (mMSCs). MgB2NS in the scaffolds enhanced osteoblast differentiation of mMSCs at the molecular level by the expression of Runx2 and osteoblast differentiation marker genes and at the cellular level by alkaline phosphatase, alizarin Red and von Kossa staining. Overall, our results showed that MgB2NS in Alg/PVA scaffolds have osteogenic potential, suggesting their possible use in bone tissue engineering applications.


Subject(s)
Polyvinyl Alcohol , Tissue Engineering , Alginates , Animals , Boron Compounds , Cell Differentiation , Cell Proliferation , Magnesium Compounds , Mice , Osteogenesis , Spectroscopy, Fourier Transform Infrared , Tissue Scaffolds
14.
Int J Biol Macromol ; 164: 1960-1972, 2020 Dec 01.
Article in English | MEDLINE | ID: mdl-32800960

ABSTRACT

Bone is a highly integrative and dynamic tissue of the human body that is regularly modeled and remodeled by bone cells such as osteoblasts and osteoclasts. When a fraction of a bone is damaged or deformed, stem cells and bone cells under the influence of several signaling pathways regulate bone regeneration at the particular locale, but in a dilatory manner. To overcome this problem, the field of bone tissue engineering (BTE) utilizes various bio-composite scaffolds that incorporate cells and appropriate growth factors to promote osteogenesis. Nanosheets are in two-dimensional (2D)-atomic structures, and metallic and non-metallic nanosheets play a keen role in biomedical applications, including BTE. Due to their intrinsic mechanical properties such as durability and flexibility, nanosheets strengthen the bio-composite scaffolds containing natural polymers (chitosan, gelatin, and collagen), synthetic polymers, bio-ceramics, and bio-glasses. Incorporating nanosheets into bio-composites promotes the bio-functionality of the cells, such as cell adhesion and osteoblast differentiation. Hence, this review was aimed to provide a detailed study on the nanosheets-incorporated bio-composites and their properties for BTE applications.


Subject(s)
Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Bone Regeneration/drug effects , Ceramics/chemistry , Nanostructures/chemistry , Osteogenesis/drug effects , Polymers/chemistry , Animals , Bone and Bones/drug effects , Ceramics/pharmacology , Humans , Polymers/pharmacology , Tissue Engineering/methods , Tissue Scaffolds/chemistry
15.
Bioorg Med Chem Lett ; 30(11): 127137, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32245598

ABSTRACT

In recent years, phytochemicals have been widely researched and utilized for the treatment of various medical conditions such as cancer, cardiovascular diseases, age-related problems and are also said to have bone regenerative effects. In this study, phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol), an acyclic unsaturated diterpene alcohol and a secondary metabolite derived from aromatic plants was investigated for its effect on osteogenesis. Phytol was found to be nontoxic in mouse mesenchymal stem cells (C3H10T1/2). At the cellular level, phytol-treatment promoted osteoblast differentiation, as seen by the increased calcium deposits. At the molecular level, phytol-treatment stimulated the expression of Runx2 (a bone-related transcription factor) and other osteogenic marker genes. MicroRNAs (miRNAs) play an essential role in controlling bone metabolism by targeting genes at the post-transcriptional level. Upon phytol-treatment in C3H10T1/2 cells, mir-21a and Smad7 levels were increased and decreased, respectively. It was previously reported that mir-21a targets Smad7 (an antagonist of TGF-beta1 signaling) and thus, protects Runx2 from its degradation. Thus, based on our results, we suggest that phytol-treatment promoted osteoblast differentiation in C3H10T1/2 cells via Runx2 due to downregulation of Smad7 by mir-21a. Henceforth, phytol was identified to bolster osteoblast differentiation, which in turn may be used for bone regeneration.


Subject(s)
Cell Differentiation/drug effects , Osteogenesis/drug effects , Phytol/pharmacology , Animals , Cell Survival/drug effects , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Down-Regulation/drug effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , MicroRNAs/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Smad7 Protein/genetics , Smad7 Protein/metabolism , Up-Regulation/drug effects
16.
World Neurosurg ; 128: 385-389, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31121367

ABSTRACT

BACKGROUND: Intradural lumbar disc herniation is rare, with an incidence of 0.3%-1%, but has been well reported in the literature. Transdural migration of the disc penetrating both ventral and dorsal dura is extremely rare, and there is a dearth of literature in the pathophysiology and surgical management of transdural herniation. Lack of knowledge on this type of presentation can cause intraoperative surprises and inadvertent cauda equina root injuries and lead to prolonged operative time. We report 1 such case, describe our surgical experience, and discuss the pathological mechanisms and signs. CASE DESCRIPTION: A 30-year-old woman presented to outpatient clinic with chronic cauda equina syndrome due to massive L4-L5 disc herniation. L4-L5 decompression and transforaminal lumbar interbody fusion were planned. Unexpectedly, however, surgery revealed a transdural herniation, which was effectively managed with laminectomy, extension of durotomy, discectomy, repair of both dorsal and ventral dura, and interbody fusion, but at the expense of prolonged surgical time. CONCLUSIONS: Transdural herniation of a lumbar disc is very rare presentation. It can be effectively managed with laminectomy, extension of durotomy, discectomy and repair of both dorsal and ventral dura. It can be diagnosed by magnetic resonance imaging preoperatively only if read with suspicion of such presentation.


Subject(s)
Cauda Equina Syndrome/surgery , Dura Mater/surgery , Intervertebral Disc Displacement/surgery , Adult , Cauda Equina Syndrome/etiology , Decompression, Surgical , Diskectomy , Dura Mater/diagnostic imaging , Female , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/diagnostic imaging , Laminectomy , Lumbar Vertebrae , Operative Time , Spinal Fusion
17.
Hypertension ; 71(1): 199-207, 2018 01.
Article in English | MEDLINE | ID: mdl-29133357

ABSTRACT

The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA.


Subject(s)
Blood Vessels , Cyclosporine , Hypertension , Interleukin-33/administration & dosage , Myeloid-Derived Suppressor Cells , Renal Insufficiency , Animals , Biological Factors/administration & dosage , Blood Pressure/drug effects , Blood Vessels/drug effects , Blood Vessels/metabolism , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/pharmacology , Cyclosporine/adverse effects , Cyclosporine/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Hypertension/chemically induced , Hypertension/metabolism , Hypertension/prevention & control , Kidney/drug effects , Kidney/metabolism , Mice , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/physiology , Renal Insufficiency/chemically induced , Renal Insufficiency/prevention & control
18.
Hypertension ; 70(1): 183-191, 2017 07.
Article in English | MEDLINE | ID: mdl-28584011

ABSTRACT

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4+/FoxP3+ regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice.


Subject(s)
Cyclosporine/pharmacology , Drug-Related Side Effects and Adverse Reactions , Hypertension , Interleukin-17/metabolism , Renal Insufficiency , T-Lymphocytes, Regulatory/physiology , Tacrolimus/pharmacology , Animals , Calcineurin Inhibitors/pharmacology , Drug-Related Side Effects and Adverse Reactions/metabolism , Drug-Related Side Effects and Adverse Reactions/pathology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Glomerular Mesangium/drug effects , Glomerular Mesangium/metabolism , Glomerular Mesangium/pathology , Hypertension/metabolism , Hypertension/prevention & control , Immunosuppressive Agents/pharmacology , Inflammation/metabolism , Inflammation/pathology , Mice , Renal Insufficiency/metabolism , Renal Insufficiency/prevention & control , Signal Transduction/drug effects
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