Downregulation of Carnitine Acyl-Carnitine Translocase by miRNAs 132 and 212 Amplifies Glucose-Stimulated Insulin Secretion

We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA–mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine–mediated regulation of IS.     

Biology of sepsis: Its relevance to pediatric nephrology

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.     

Percutaneous direct endoscopic pancreatic necrosectomy

Approximately 10%-20% of the cases of acute pancreatitis have acute necrotizing pancreatitis. The infection of pancreatic necrosis is typically associated with a prolonged course and poor prognosis. The multidisciplinary, minimally invasive “step-up” approach is the cornerstone of the management of infected pancreatic necrosis (IPN). Endosonography-guided transmural drainage and debridement is the preferred and minimally invasive technique for those with IPN. However, it is technically not feasible in patients with early pancreatic/peripancreatic fluid collections (PFC) (< 2-4 wk) where the wall has not formed; in PFC in paracolic gutters/pelvis; or in walled off pancreatic necrosis (WOPN) distant from the stomach/duodenum. Percutaneous drainage of these infected PFC or WOPN provides rapid infection control and patient stabilization. In a subset of patients where sepsis persists and necrosectomy is needed, the sinus drain tract between WOPN and skin-established after percutaneous drainage or surgical necrosectomy drain, can be used for percutaneous direct endoscopic necrosectomy (PDEN). There have been technical advances in PDEN over the last two decades. An esophageal fully covered self-expandable metal stent, like the lumen-apposing metal stent used in transmural direct endoscopic necrosectomy, keeps the drainage tract patent and allows easy and multiple passes of the flexible endoscope while performing PDEN. There are several advantages to the PDEN procedure. In expert hands, PDEN appears to be an effective, safe, and minimally invasive adjunct to the management of IPN and may particularly be considered when a conventional drain is in situ by virtue of previous percutaneous or surgical intervention. In this current review, we summarize the indications, techniques, advantages, and disadvantages of PDEN. In addition, we describe two cases of PDEN in distinct clinical situations, followed by a review of the most recent literature.     

Tumor like swellings arising from Hoffa's fat pad: A report of three patients

We report three rare cases of tumor-like conditions arising from Hoffa''s fat pad (HFP). Patients were having persistent knee pain, the cause of which was not diagnosed by the general physician, and then were referred to us for knee pain. Magnetic resonance imaging revealed the lesions to be arising from HFP (ganglion cysts and hemangioma), as was suggested by clinical findings. Anatomy, pathology, and radiological features of the Hoffa''s disease are described here to increase awareness in orthopedic community of this rare but interesting disease which is often misdiagnosed as meniscal pathology. These cases illustrate that increased cognizance can facilitate timely intervention which will prevent morbidity of the patient.     

Lamotrigine�Cdextran conjugates-synthesis, characterization, and biological evaluation

Synthesis of lamotrigine–dextran conjugates is done by oxidation of dextran using sodium periodate (NaIO₄), where the aldehyde groups formed were coupled with the amino (–NH₂) group of lamotrigine and reduced to secondary imine groups. Characterization of synthesized conjugates was done by using ultraviolet, infrared, nuclear magnetic resonance spectroscopy. Viscometer was used to determine molecular weight, and degree of substitution was estimated by complete hydrolysis of conjugates in borate buffer, which was found to be 8%. Buffer solutions with different pH, i.e., 1.2, 7.4, and 9.0 were used to perform the in vitro hydrolysis study and the amount of conjugates released was estimated by high performance liquid chromatography. The study showed that the rate of hydrolysis increases with increase in pH. The anticonvulsant and hepatotoxicity screening of the synthesized conjugates in different rat models showed that lamotrigine–dextran conjugates proved to be potentially safer than parent lamotrigine formulations.     

Diagnostic dilemma of antineutrophil cytoplasmic antibody seropositivity in human immunodeficiency virus infection

We present a case of a 48-year-old male who was diagnosed and treated for Wegener's granulomatosis on the basis of history, clinical features, computed tomography (CT) and antineutrophil cytoplasmic antibodies (ANCA) positivity. The patient initially improved and later on during course of the disease he was found to be human immunodeficiency virus (HIV) seropositive. The potential pitfalls of cANCA in a HIV-infected patient are discussed.     

Multiomics Analysis and Systems Biology Integration Identifies the Roles of IL-9 in Keratinocyte Metabolic Reprogramming

1. Download : Download high-res image (146KB)
2. Download : Download full-size image