Fluorescence turn-off detection of myoglobin as a cardiac biomarker using water-stable L-glutamic acid functionalized cesium lead bromide perovskite quantum dots.

Water dispersible L-glutamic acid (Glu) functionalized cesium lead bromide perovskite quantum dots (CsPbBr3 PQDs), namely CsPbBr3@Glu PQDs were synthesized and used for the fluorescence "turn-off" detection of myoglobin (Myo). The as-prepared CsPbBr3@Glu PQDs exhibited an exceptional photoluminescence quantum yield of 25% and displayed emission peak at 520 nm when excited at 380 nm. Interestingly, the fluorescence "turn-off" analytical approach was designed to detect Myo using CsPbBr3@Glu PQDs as a simple optical probe. The developed probe exhibited a wide linear range (0.1-25 µM) and a detection limit of 42.42 nM for Myo sensing. The CsPbBr3@Glu PQDs-based optical probe provides high ability to determine Myo in serum and plasma samples.

Hypertensive Emergency During Dialysis: A Paradoxical Physiologic Response.

Most end-stage renal disease patients experience a reduction in blood pressure during their hemodialysis session compared to predialysis. Surprisingly, a small subset of patients will experience an unusual physiological response to dialysis that results in a paradoxical increase in blood pressure. We discuss a case that involved an exaggerated elevation in blood pressure, ultimately requiring immediate cessation of dialysis and admission to the intensive care unit for intravenous treatment of a hypertensive emergency. This case serves as a framework to introduce the infrequently discussed concept of intradialytic hypertension. The underlying pathogenesis is poorly understood with multiple theoretical etiologies including activation of the renin-angiotensin-aldosterone system, imbalances in circulating levels of endothelium-derived mediators, clearance of antihypertensive medications, increased cardiac output, and changes in arterial thickness. It is important to be cognizant of this phenomenon as emerging evidence suggests that patients with any elevation in blood pressure during hemodialysis have increased rates of both short-term and long-term mortality.

Synthesis of multicolor silver nanostructures for colorimetric sensing of metal ions (Cr3+, Hg2+ and K+) in industrial water and urine samples with different spectral characteristics.

In this work, we have synthesized four different color (yellow, orange, green, and blue (multicolor)) silver nanostructures (AgNSs) by chemical reduction method where silver nitrate, sodium borohydride and hydrogen peroxide were used as reagents. The as-synthesized multicolor AgNSs were successfully functionalized with bovine serum albumin (BSA) and applied as a colorimetric sensor for the assaying of metal cations (Cr3+, Hg2+, and K+). The addition of metal ions (Cr3+, Hg2+, and K+) into BSA functionalized AgNSs (BSA-AgNSs) causes the aggregation of BSA-AgNSs, and are accompanied by visual color changes with red or blue shift in the surface plasmon resonance (SPR) band of BSA-AgNSs. The BSA-AgNSs show different SPR characteristic for each metal ions (Cr3+, Hg2+, and K+) with exhibiting different spectral shift and color change. The yellow color BSA-AgNSs (Y-BSA-AgNSs) act as a probe for sensing Cr3+, orange color BSA-AgNSs (O-BSA-AgNSs) act as probe for Hg2+ ion assay, green color BSA-AgNSs (G-BSA-AgNSs) act as a probe for the assaying of both K+ and Hg2+, and blue color BSA-AgNSs (B-BSA-AgNSs) act as a sensor for colorimetric detection of K+ ion. The detection limits were found to be 0.26 µM for Cr3+ (Y-BSA-AgNSs), 0.14 µM for Hg2+ (O-BSA-AgNSs), 0.05 µM for K+ (G-BSA-AgNSs), 0.17 µM for Hg2+ (G-BSA-AgNSs), and 0.08 µM for K+ (B-BSA-AgNSs), respectively. Furthermore, multicolor BSA-AgNSs were also applied for assaying of Cr3+, and Hg2+ in industrial water samples and K+ in urine sample.

An Exciting Case of Acute on Chronic Hypercalcemia in the Setting of Chronic Primary Hyperparathyroidism: A Case Report and Diagnostic Approach.

Acute worsening of hypercalcemia in patients with chronic primary hyperparathyroidism can be challenging, and availability bias may mislead physicians to diagnose worsening primary hyperparathyroidism, especially if the parathyroid hormone is also trending higher. We report a case of stage-IV non-Hodgkin's lymphoma which presented as acute worsening of hypercalcemia in a patient with chronic primary hyperparathyroidism.

Linezolid Induced Lactic Acidosis: The Side Effect, Clinician Should Be Aware of.

Linezolid is a synthetic antibiotic that functions through the inhibition of bacterial protein synthesis by binding to ribosomal ribonucleic acid (rRNA). Deliverable in both intravenous and oral form, with a low level of resistance amongst Methicillin-resistant Staphylococcus aureus (MRSA) strains, it is recommended for a wide range of gram-positive infections. We present a case of a male patient who underwent endovascular abdominal aortic aneurysm repair complicated by abdominal sepsis due to bowel ischemia; several days after linezolid therapy was initiated, he presented with signs of lactic acidosis. After excluding other sources such as metabolic, hypoxia, or organ damage, the resulting lactic acidosis was determined to be a side effect of linezolid.

Rhabdomyolysis-Induced Acute Kidney Injury in Diabetic Emergency: Underdiagnosed and an Important Association to Be Aware of.

Rhabdomyolysis is a potentially life-threatening clinical syndrome associated with muscle injury which can cause a leakage of intracellular contents, manifested from the range of being asymptomatic to a life-threatening condition causing acute kidney injury and severe electrolyte abnormalities. Rhabdomyolysis has been associated with both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome, though there is an increased association with rhabdomyolysis and acute kidney injury with hyperosmolar nonketonic state compared with patients with diabetic ketoacidosis. Common clinical manifestations are muscle pain, dark urine, and generalized weakness. The causes of rhabdomyolysis are broadly categorized into three groups: traumatic, nontraumatic exertional, and nontraumatic nonexertional. Here, we present a case of rhabdomyolysis-induced acute kidney injury in a patient with hyperosmolar hyperglycemic state. The patient was discharged on insulin and needed intermittent dialysis for two months. Our case highlights the importance of the rare association of rhabdomyolysis causing acute kidney injury in a diabetic emergency.

Dabigatran-Induced Acute Interstitial Nephritis: An Important Complication of Newer Oral Anticoagulation Agents.

Acute kidney injury (AKI) due to an acute interstitial nephritis (AIN) is common and can lead to increased morbidity and mortality. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPI) and rifampin are common offending agents. Anticoagulant-associated AIN is more frequently reported with the use of warfarin; however, only few case reports have reported an association with the use of novel oral anticoagulants (NOACs). Herein, we report the case of a 59-year-old male who developed AKI after initiating dabigatran for the treatment of atrial fibrillation. Laboratory data demonstrated elevated blood urea nitrogen (BUN) of 115 mg/dL (baseline = 35 mg/dL) and serum creatinine (Cr) of 5.06 mg/dL (baseline = 1.3 mg/dL). Urinalysis revealed eosinophiluria. Renal biopsy disclosed diffuse tubulointerstitial nephritis and eosinophils and confirmed the diagnosis of AIN. At 1 week, renal function improved (BUN/Cr = 53/2.73 mg/dL) with steroid therapy and discontinuation of dabigatran. With an increasing use of NOACs, it is important to monitor renal function to diagnose AIN in a timely fashion. Early diagnosis and prompt treatment can mitigate serious renal damage induced by dabigatran.

Methimazole-Induced Pauci-Immune Glomerulonephritis and Anti-Phospholipid Syndrome: An Important Association to Be Aware of.

While methimazole (MMI) is the first line treatment for hyperthyroidism, this medication is not devoid of adverse effects. In this article, we present a 70-year-old male who admitted the hospital with right lower extremity pain and rash. The patient was recently treated with MMI for hyperthyroidism. Imaging studies revealed bilateral renal and splenic infarcts along with thrombosis of popliteal artery. Laboratory data revealed hematuria and proteinuria with positive (MPO), anti-proteinase-3 (PR3) and anti-cardiolipin IgG antibodies. Renal biopsy revealed pauci-immune glomerulonephritis and features with anti-phospholipid antibody syndrome (APS). MMI was discontinued and the patient was treated successfully with steroid therapy and anti-coagulation with resolution of proteinuria, hematuria and normalization of laboratory parameters. While MMI-induced pauci-immune glomerulonephritis has been previously reported, its association with APS has never been described before. Our case demonstrates that this rare diagnosis can be treated by early withdrawal of MMI and initiation of steroids along with anticoagulation.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis.

Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Pregnancy and hemodialysis access: A case for patient satisfaction in favor of a tunneled dialysis catheter.

While an arteriovenous fistula is the best available access, many patients continue to rely on a tunneled hemodialysis catheter for dialysis therapy. Despite the highest risk of catheter-related bacteremia and associated morbidity and mortality, patients often prefer tunneled hemodialysis catheter to avoid pain associated with cannulation of an arteriovenous access. We report three tunneled hemodialysis catheter-dependent end-stage renal disease patients (age: 38, 35, 33 years), who became pregnant. Pregnancy was discovered at 10, 12 and 10 weeks of gestation. All three patients were switched to daily hemodialysis (six sessions/week) as soon as the pregnancy was discovered. The three patients had refused the placement of an arteriovenous access and expressed their strong preference for tunneled hemodialysis catheter. All had been educated about the risks and benefits of catheter, grafts, and fistulas. Patient preference was acknowledged and dialysis therapy was continued with tunneled hemodialysis catheter. Pregnancy was uneventful in two patients with the delivery of a healthy baby. The third patient had a miscarriage. Patient preference for tunneled hemodialysis catheter and satisfaction is important and can result in a successful outcome in pregnant patients. Nonetheless, in keeping with the National Kidney Foundation guidelines as well as the Fistula First, an arteriovenous fistula should be offered to hemodialysis patients. At the same time, patient's preference and wish should be respected and followed.

Subcutaneous defibrillators for dialysis patients.

Defibrillation can be successfully provided by the subcutaneous implantable cardioverter defibrillator (ICD) without the leads. In contrast, traditional ICDs require leads that can cause central venous stenosis, lead-induced endocarditis, and carry the risk of tricuspid regurgitation by valve adhesion, perforation, coaptation interference, or entanglement. Central venous stenosis, infection, and tricuspid regurgitation are all critically important considerations in hemodialysis patients. Recent reports are supporting the use of subcutaneous ICDs in renal patients maintained on long-term hemodialysis. This article provides the risks associated with leads of traditional defibrillators and raises awareness of the subcutaneous ICD and their benefits for hemodialysis patients.

Sphaeranthus indicus flower derived constituents exhibits synergistic effect against acetylcholinesterase and possess potential antiamnestic activity.

OBJECTIVE: The present investigation was aimed at discovery of novel acetylcholinesterase (AChE) inhibitors. METHODS: In vitro AchE inhibitory activity of various extracts of Sphaeranthus indicus flower heads was carried out. The petroleum ether fraction of S. indicus flowers (SIPE) exhibited significant activity. The fraction was found to be rich in sesquiterpene lactone content possibly responsible for in vitro AChE inhibition. In further study, the antiamnesic activities of SIPE in mice on the learning and memory impairments induced by scopolamine (1.0 mg/kg, i.p.) were examined. RESULTS: SIPE (10 mg/kg, p.o.) administration significantly reversed cognitive impairments in mice by passive avoidance test (P < 0.05). It also reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P < 0.05). These results indicated that S. indicus due to its sesquiterpene lactones have anti-cholinesterase activity. A major sesquiterpene lactone, 7-hydroxy frullanolide along with other constituents were isolated from SIPE and evaluated for AchE inhibitory activity. Negative results were obtained in case of isolated compounds. CONCLUSION: Synergistic effect between constituents of SIPE was confirmed to have anti-amnesic activities that may be useful for cognitive impairment treatment.

Isoquinoline alkaloids from Tinospora cordifolia inhibit rat lens aldose reductase.

The inhibitory activity of Tinospora cordifolia stem-derived alkaloids was evaluated against lens aldose reductase (AR) isolated from male Wistar rats. Anticataract potential of the alkaloids of T. cordifolia was evaluated in vitro in rat lenses, considering the activity of normal rat lenses as 100%. The biologically active constituents of T. cordifolia extract were characterized as the isoquinoline alkaloids, jatrorrhizine, palmatine and magnoflorine, by spectral analysis. The inhibitory effects varied with all chemicals and concentrations used. The inhibitory concentration (IC50) values of jatrorrhizine, palmatine and magnoflorine are 3.23, 3.45 and 1.25 µg/mL respectively. The concentration of maximum activity was selected for its effect on galactose-induced polyol accumulation in vitro. The percentage inhibition of galactose-induced polyol accumulation was 62.6, 58.8 and 27.7% in the presence of jatrorrhizine, palmatine and magnoflorine, respectively. Magnoflorine may be useful as lead compounds and new agents for AR inhibition.

Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia.

The stem of Tinospora cordifolia (TC) is widely used in the therapy of diabetes in traditional folk medicine of India. In the present study, isoquinoline alkaloid rich fraction (AFTC) derived from stem of TC and three alkaloids viz., palmatine, jatrorrhizine and magnoflorine were evaluated for insulin-mimicking and insulin-releasing effect in vitro and in vivo. Their effect on hepatic gluconeogenesis was examined in rat hepatocytes. Insulin releasing effect was detected in vitro using rat pancreatic ß-cell line, RINm5F. Furthermore, effects of AFTC and isolated alkaloids on serum glucose and insulin level were studied in fasted and glucose challenged normal rats. AFTC significantly decreased gluconeogenesis in rat hepatocytes as insulin did and it increases insulin secretion in RINm5F cells similar to tolbutamide. In acute 30 min test in vitro, AFTC, palmatine, jatrorrhizine and magnoflorine stimulated insulin secretion from the RINm5F cell line. As in vivo results, administration of AFTC (50, 100, and 200 mg/kg), palmatine, jatrorrhizine and magnoflorine (10, 20 and 40 mg/kg each) orally significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal rats. In vivo study further justified their insulin secreting potential by raising the serum insulin level in glucose fed rats. These results demonstrate the alkaloid present in TC contributed for antihyperglycemic activity. AFTC may have hypoglycemic effects via mechanisms of insulin releasing and insulin-mimicking activity and thus improves postprandial hyperglycemia.

Quantification of dermal and transdermal delivery of meloxicam gels in rabbits.

BACKGROUND: This study was designed to quantify the effects of penetration enhancers on systemic bioavailability of 0.3% meloxicam (MLX) hydroxypropylcellulose gels. Cutaneous microdialysis was also performed to assess dermis availability and to better understand the penetration process. The gels tested were a 1% oleic acid gel, a 5% menthol gel, and a control gel without penetration enhancers. METHODS: To assess systemic bioavailability, three female rabbits received according to a crossover design 0.135 g/cm(2) of gel applied to a 7.5 × 7.5 cm area of their shaved back and a short (5 min) infusion of 1 mg. In each experiment, blood samples were collected serially for 36 h and analyzed by a validated HPLC method. For skin bioavailability studies, 0.135 g/cm(2) of the same gels were applied to a 1 × 2 cm area on top of a microdialysis probe previously inserted in the dermis. Dialysate samples were collected for 6 h every 30 min. RESULTS: Systemically, the 5% menthol gel delivered 3.93 ± 0.85 mg of MLX versus the 1.41 ± 0.24 mg of the oleic acid gel. Only traces of MLX were detectable from the control gel. In dermis, substantial concentrations of MLX were detected only after the application of the menthol gel, whereas skin concentration from the control gel and the 1% oleic acid gel were always below the lowest limit of quantification (LLOQ). CONCLUSIONS: The 5% menthol gel can possibly deliver therapeutically relevant amount of MLX in vivo. Dermis concentrations can be predictive of systemic plasma levels.