Therapeutic manipulation of the renin-angiotensin-aldosterone system (RAAS) is an important strategy for improving hypertension, diabetes, cardiovascular disease, and chronic kidney disease. Development of hyperkalemia after the administration of RAAS inhibitors is of particular concern because patients at highest risk for this complication are often the same patients who derive the greatest cardiovascular or renoprotective benefit. Based on an overview of the incidence of hyperkalemia during treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers alone and in combination, this review suggests approaches for monitoring, detecting, and managing hyperkalemia in patients treated with RAAS inhibitors. Although the incidence of hyperkalemia with RAAS inhibitors is generally low, hyperkalemia can be associated with increased mortality. When using RAAS inhibitors, it is important to monitor on-treatment electrolyte levels and renal function parameters in patients with a high risk for hyperkalemia.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Cardiovascular Diseases ; Humans ; Hyperkalemia ; Hypertension ; Incidence ; Organothiophosphorus Compounds ; Peptidyl-Dipeptidase A ; Renal Insufficiency, Chronic ; Renin-Angiotensin System

Urate is produced in the liver by the degradation of purines from the diet and nucleotide turnover and excreted by the kidney and gut. The kidney is the major route of urate removal and has a pivotal role in the regulation of urate homeostasis. Approximately 10% of the glomerular filtered urate is excreted in the urine, and the remainder is reabsorbed by the proximal tubule. However, the transport of urate in the proximal tubule is bidirectional: reabsorption and secretion. Thus, an increase in reabsorption or a decrease in secretion may induce hyperuricemia.In contrast, a decrease in reabsorption or an increase in secretion may result in hyperuricosuria. In the proximal tubule, urate reabsorption is mainly mediated by apical URAT1 (SLC22A12) and basolateral GLUT9 (SLC2A9) transporter. OAT4 (SLC22A11) also acts in urate reabsorption in the apical membrane, and its polymorphism is associated with the risk of hyperuricemia. Renal hypouricemia is caused by SLC22A12 or SLC2A9 loss-of-function mutations, and it may be complicated by exercise-induced acute kidney injury. URAT1 and GLUT9 are also drug targets for uricosuric agents. Sodium-glucose cotransporter inhibitors may induce hyperuricosuria by inhibiting GLUT9b located in the apical plasma membrane. Urate secretion is mediated by basolateral OAT1 (SLC22A6) and OAT3 (SLC22A8) and apical ATP-binding cassette super-family G member 2 (>ABCG2), NPT1 (SLC17A1), and NPT4 (SLC17A3) transporter in the proximal tubule. NPT1 and NPT4 may be key players in renal urate secretion in humans, and deletion of SLC22A6 and SLC22A8 in mice leads to decreased urate excretion. Dysfunctional variants of >ABCG2 inhibit urate secretion from the gut and kidney and may cause gout. In summary, the net result of urate transport in the proximal tubule is determined by the dominance of transporters between reabsorption (URAT1, OAT4, and GLUT9) and secretion (ABCG2, NPT1, NPT4, OAT1, and OAT3).

We retrospectively reviewed the results of nine children who were less than sixteen years old and in whom partial or total arthroscopic meniscectomy was performed for symptomatic discoid meniscus in eleven knees between March 1991 and February 1997. On arthroscopic findings, there were two complete and eight incomplete type of lateral discoid menisci and one medial discoid meniscus. Among eleven cases, partial meniscectomy was performed in seven and total meniscectomy in four. The average duration of follow-up was two and a half years (range, one to five years). In this study, arthroscopic total meniscectomy was superior to partial meniscectomy for a symptomatic discoid meniscus including pain, click and locking in children. Therefore, arthroscopic meniscectomy may offer the best prognosis following accurate diagnosis in children.
Child* ; Diagnosis ; Follow-Up Studies ; Humans ; Knee ; Prognosis ; Retrospective Studies

With a developing worldwide epidemic of diabetes mellitus, the renal complications associated with diabetes have become a serious health concern. Primary therapy for treating diabetic nephropathy is a multifactorial process. Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists have been used primarily in clinical practice for the treatment of dyslipidemia and insulin resistance. Given that PPARalpha expression and regulation of metabolic pathways are involved in oxidative stress, inflammation, blood pressure regulation, and the renin-angiotensin aldosterone system, PPARalpha likely influences the development and pathogenesis of diabetic nephropathy via indirect effects on glucose and lipid homeostasis and also by direct action on the kidneys. These findings suggest that PPARalpha may become an important therapeutic target for treating diabetic renal complications.
Aldosterone ; Blood Pressure ; Diabetes Mellitus ; Diabetic Nephropathies ; Dyslipidemias ; Glucose ; Homeostasis ; Inflammation ; Insulin Resistance ; Kidney ; Metabolic Networks and Pathways ; Oxidative Stress ; Peroxisomes ; PPAR alpha

Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the best-studied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling.
Biology ; Carcinogenesis ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Genome ; Herpesviridae ; Humans*

No abstract available.

When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

Despite being a very new field, forensic imaging is rapidly being used in forensic medical practices around the world. Computed tomography images are being produced and used for many reasons. Forensic imaging is being used for preliminary examination of serious findings before a routine autopsy, as it might help to give positive proof in some cases. Some major preliminary findings, such as brain hemorrhage, cardiac tamponade, or aortic dissection, can then be substantiated with the results of the physical autopsy. Forensic imaging techniques may also provide additive evidence about the cause of death such as pneumothorax, ileus, gas embolism, and aspiration that are difficult to detect with the traditional surgical autopsy techniques. Forensic imaging is also proving useful outside the autopsy room; forensic anthropologists and odontologists are using images to help them determine the age, sex, and even lifestyle of human specimens. Finally, forensic images have also begun to function as a form of record keeping in complex cases.
Autopsy* ; Cardiac Tamponade ; Cause of Death ; Embolism, Air ; Humans ; Ileus ; Intracranial Hemorrhages ; Life Style ; Pneumothorax

B-lineage non-Hodgkin lymphoma may aberrantly coexpress T-cell markers. In general population, however, cases of diffuse large B-cell lymphomas with CD3 co-expression are rare because the CD3 marker is the most lineage specific T-cell antigen. We report a case of CD3 coexpressed diffuse large B-cell lymphoma in a 47-year-old male patient presented with dyspepsia who had transplanted a kidney 17 years ago. An esophagogastroduodenoscopy displayed an ulcerated mass in the gastric antrum. The pathology of the mass was monomorphic post-transplant lymphoproliferative disorder - specifically, CD20- and CD3-positive diffuse large B-cell lymphoma. Resection of the mass and postop chemotherapy were performed. A follow-up computerized tomography showed disapperance of tumor. No recurrence was observed until 7 month after treatment. Nevertheless, the patient's renal function gradually aggrevated and progressed to end stage renal disease. As far as we know, this is the first case of diffuse large B-cell lymphoma with CD3 coexpression after kidney transplant.
B-Lymphocytes ; Dyspepsia ; Endoscopy, Digestive System ; Follow-Up Studies ; Humans ; Kidney ; Kidney Failure, Chronic ; Lymphoma, B-Cell ; Lymphoma, Non-Hodgkin ; Lymphoproliferative Disorders ; Male ; Middle Aged ; Neoplasm Transplantation ; Pyloric Antrum ; Recurrence ; T-Lymphocytes ; Transplants ; Ulcer

This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, alpha-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-beta1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.
Animals ; Antioxidants/pharmacology/therapeutic use ; Collagen/metabolism ; Cyclic N-Oxides/*pharmacology/therapeutic use ; Fibrosis ; Forkhead Transcription Factors/*metabolism ; Hydrogen Peroxide/metabolism ; Kidney Diseases/drug therapy/metabolism/pathology ; Lipid Peroxidation ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/*metabolism ; Severity of Illness Index ; Signal Transduction/*drug effects ; Spin Labels ; Superoxide Dismutase/metabolism ; Ureteral Obstruction/complications/drug therapy/*metabolism/pathology