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Pharmacological interventions for acute pancreatitis.

BACKGROUND: In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care … mes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin …

Targeted prevention of renal accumulation and toxicity of gentamicin by aminoglycoside binding receptor antagonists.

Receptor-mediated endocytosis plays an important role in accumulation of aminoglycosides in renal proximal tubule. To prevent aminoglycoside-induced nephrotoxicity following concentrated accumulation of gentamicin in the kidney, effect of cationic proteins and their peptide fragments, which could inhibit gentamicin binding to its binding receptor(s), was investigated. Among several substrates for megalin, an endocytic receptor responsible for renal accumulation of aminoglycosides, cytochrome c potently inhibited gentamicin accumulation in renal cortex. Concentration-dependent inhibition by cyt

Delayed gastric emptying in critical illness: is enhanced enterogastric inhibition with cholecystokinin and peptide YY involved?

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… Aprotinin is a naturally occurring bovine serine protease inhibitor that acts on plasma serine proteases such as plasmin, kallikrein, trypsin, and some coagulation proteins. … Aprotinin has been shown to reduce blood loss in patients undergoing cardiopulmonary bypass surgery 145 by inhibiting fibrinolysis and preventing platelet damage. …

Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.

BACKGROUND: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study h

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… prepare nuclear extracts, gastrocnemius (100 mg) was homogenized in ice‐cold 10 mm 4‐(2‐Hydroxyethyl)piperazine‐1‐ethanesulfonic acid (HEPES), pH 7.5, containing 10 mM MgCl 2 , 5 mM KCl, 0.1 mM EDTA pH 8.0, 0.1% Triton X‐100, 0.1 mM phenylmethanesulfonyl fluoride, 1 mM DL‐Dithiothreitol (DTT), 2 µg/ml aprotinin … Samples were centrifuged (5 min, 3000 g ), pellets resuspended in ice‐cold 20 mM HEPES, pH 7.9, containing 25% glycerol, 500 mM NaCl, 1.5 mM MgCl 2 , 0.2 mM EDTA, pH 8.0, 0.2 mM phenylmethanesulfonyl fluoride, 0.5 mM DTT, 2 µg/ml aprotinin, 2 µg/ml leupeptin, and incubated on ice for 30 min. …

Pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic and long bone fractures.

BACKGROUND: Pelvic, hip, and long bone fractures can result in significant bleeding at the time of injury, with further blood loss if they a … been prospectively registered. Eligible interventions included: antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants, and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. W …

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias.

Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95%

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… summary, cells were labeled with 35 S-methionine and cysteine, lysed in 0.5 M NaCl, 2 mM ethylenediaminetetraacetic acid (EDTA), 50 mM Tris (pH 7.5), 0.3% octylphenyl polyethylene glycol (IGEPAL CA-630) buffer containing 0.5 mM phenylmethylsulfonyl fluoride, and 0.3 trypsin inhibitory units (TIU)/mL of aprotinin …

Mechanisms of IFNalpha-1a-Induced Apoptosis in a Laryngeal Cancer Cell Line.

BACKGROUND Interferon alpha (IFNalpha) exerts its anti-proliferative effect on many human cancers. Among the 13 subtypes of human IFNalpha, IFNalpha-1 subtype has 2 variants, named IFNalpha-1a and IFNalpha-1b, that differ from each other in only 1 amino acid, at residue 114. However, the mechanism by which IFNalpha-1a mediates growth inhibition is still unclear. MATERIAL AND METHODS Human laryngeal carcinoma HEp2 cells were treated with IFNalpha-1a by either transient transfection or exogenous delivery. Western blot and RT-PCR analysis were carried out to assess apoptotic pathways active in IF

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… Western blot analysis The transiently transfected or IFNalpha-1a-treated HEp-2 cells were lysed with ice-cold lysis buffer (1% NP-40, 50 mM Tris-HCl (pH 7.5), 120 mM NaCl, 200 μM NaVO4, 1 μg/mL leupeptin, 1 μg/mL aprotinin, and 1 μM PMSF) for 30 min at 4°C. …

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viabi

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… Louis, MO, USA) (10 µg/ml leupeptin, 10 µg/mL aprotinin, 1 µg/mL pepstatin A, 1 mM sodium fluoride, and 2 mM Na 3 VO 4 ). The measurement of total protein was performed using the Bradford method. 4.4. …

Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells.

Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expressio

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… Western blotting The cells were collected and lysed in a lysis buffer (pH=7.4, containing 0.1% SDS, 100 mM NaCl, 1% Triton-X 100, 10 mM Tris, 1 mM NaF, 2 mM Na3VO4, 20 mM Na4P2O7, 1 mM EGTA, 1 mM EDTA, 0.5% sodium deoxycholate, 1 mM PMSF, 60 μg/mL aprotinin, 10 μg/mL leupeptin, and 1 μg/mL pepstatin …

Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro.

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic dea

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… were washed twice with ice-cold PBS/BSA, scraped and centrifuged for 30 min at 4°C in 1 ml of lysis buffer (1% Triton, 0.5% sodium deoxycholate, 0.1N NaCl, 1 m M EDTA, pH 7.5, 10 m M Na 2 HPO 4 , pH 7.4, 10 m M phenylmethylsulphonyl fluoride (PMSF), 25 m M benzamidin, 1 m M leupeptin, 0.025 U ml −1 aprotinin …

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats.

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Tra

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… The bladder samples were homogenized with a pre-chilled mortar and pestle in extraction buffer (10 mM Tris-HCl (pH 7.6), 140 mM NaCl, 1 mM PMSF, 1% NP-40, 0.5% deoxycholate, 2% β-mercaptoethanol, 10 μg/mL pepstatin A, and 10 μg/mL aprotinin). …

In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma.

Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later

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… For cell extract preparation, cells were washed twice with ice-cold PBS/BSA, scraped and centrifuged for 30 min at 4°C in 1 ml of lysis buffer (1% Triton, 0.5% sodium deoxycholate, 0.1 M NaCl, 1 mM EDTA, pH 7.5, 10 mM Na 2 HPO 4 , pH 7.4, 10 mM PMSF, 25 mM benzamidin, 1 mM leupeptin, 0.025 U/ml aprotinin …

Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma.

Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium channel Kv1.3 in their mitochondria. The mitochondrial Kv1.3 inhibitors PAPTP and PCARBTP are efficient against two tested human multiple myeloma cell lines (L-363 and RPMI-8226) and against ex vivo cultured, patient-derived myeloma cells, while healthy b

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… The resulting pellet was resuspended in RIPA-Buffer (50 mM Tris-HCl (pH7.4), 150 mM NaCl, 1 mM PMSF, 1 mM EDTA, 5 µg/mL aprotinin, 5 µg/mL leupeptin, 1% Triton x-100, 1% sodium deoxycholate, 0.1% SDS). …

CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

BackgroundHistone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib.MethodsThe anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate

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… Cells were lysed on ice for 20 min using lysis buffer (50 mM Tris-HCl, pH 7.4; 1% Nonidet P-40, 0.25% sodium deoxycholate; 150 mM NaCl; 1 mmol/L EDTA; 1 mM phenylmethylsulfonyl-fluoride; 1 mM Na3VO4; 1 mM NaF; and 1 mg/mL each of aprotinin, pepstatin, and leupeptin) and centrifuged at 14,000× g for 10 …

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest. Tumor xenogra

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… Cells were homogenized in RIPA buffer (50 mM Tris-HCl, pH 7.4; 150 mM NaCl; 1% Nonidet P-40; 0.5% sodium deoxycholate; 0.1% SDS; 1 mM EDTA; 1 mM PMSF; 1 mg/ml Aprotinin), and proteins quantified using the bicinchoninic acid (BCA) protein assay kit (Pierce, IL, USA). …

Acute Pancreatitis: Genetic Risk and Clinical Implications.

Acute pancreatitis (AP) is one of the most common gastroenterological indications for emergency admittance and hospitalization. Gallstones, alcohol consumption or the presence of additional initiating factors give rise to a disease with a diverse clinical appearance and a hard-to predict course of progression. One major challenge in the treatment of AP patients is the early identification of patients at risk for the development of systemic complications and organ failure. In addition, 20%-30% of patients with a first episode of AP later experience progress to recurrent or chronic disease. Comp

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… MRC multicentre trial of glucagon and aprotinin. Lancet. 1977;2:632–635. 33. Buch S., Schafmayer C., Völzke H., Seeger M., Miquel J.F., Sookoian S.C., Egberts J.H., Arlt A., Pirola C.J., Lerch M.M., et al. …

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

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… The combination of a protease inhibitor (HTA, aprotinin, given IV) targeting the host enzyme TMPRSS2, plus oral favipiravir (DAA, polymerase inhibitor) has been tested in COVID-19 patients, but the study was too small to assess clinical efficacy ( 110 ). … Effect of Aprotinin and Avifavir ® combination therapy for moderate COVID-19 patients. Viruses 13:1253. doi: 10.3390/v13071253. 111. …

A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.

Acute leukemia is a highly heterogeneous disease; therefore, combination therapy is commonly used for patient treatment. Drug-drug interaction is a major concern of combined therapy; hence, dual/multi-target inhibitors have become a dominant approach for cancer drug development. HDACs and HSP90 are involved in the activation of various oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and RAF/MEK/ERK, which are also highly enriched in acute leukemia gene expression profiles. Therefore, we suggest that dual HDAC and HSP90 inhibitors could represent a novel therapeutic approach fo

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… Western blot analysis Cells were incubated with various concentrations of MPT0G449, harvested, washed with PBS, lysed in lysis buffer (50 mM Tris pH 7.4, 150 mM NaCl, 1% Triton X-100, 1 mM EDTA, 1 mM EGTA, 1 mM PMSF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, 1 mM sodium orthovanadate, and 1 mM NaF), and …

Lysine Methyltransferase Inhibitors Impair H4K20me2 and 53BP1 Foci in Response to DNA Damage in Sarcomas, a Synthetic Lethality Strategy.

BackgroundChromatin is dynamically remodeled to adapt to all DNA-related processes, including DNA damage responses (DDR). This adaptation requires DNA and histone epigenetic modifications, which are mediated by several types of enzymes; among them are lysine methyltransferases (KMTs).MethodsKMT inhibitors, chaetocin and tazemetostat (TZM), were used to study their role in the DDR induced by ionizing radiation or doxorubicin in two human sarcoma cells lines. The effect of these KMT inhibitors was tested by the analysis of chromatin epigenetic modifications, H4K16ac and H4K20me2. DDR was monitor

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… Histone Extraction Cells were lysed with the RIPA lysis buffer (150 mM NaCl, 1.5 mM MgCl 2 , 10 mM NaF, 4 mM EDTA, 50 mM Hepes, 1% Triton X-100, 0.1% SDS, and 10% glycerol) supplemented by phosphatases inhibitors (1 mM NaF and 1 mM sodium orthovanadate) and proteases inhibitors (1 mM PMSF, 10 μg/mL aprotinin …

Протеиновый ингибитор смягчает белку в мышах Lmx1b с дисфункциональной доменой LIM.

Мутации в коэффициенте транскрипции LMX1B были определены в качестве причины синдрома автосомали-доминантного заболевания гвозди-пареллы. Он проявляется в небольших или отсутствующих пателле и диспластике или в отсутствии пальцев и ногтей, но прогноз пациентов определяется появлением почечных симптомов из-за дисфункциональных подоцитов. Патогенетические механизмы, ведущие к повреждению подоцита, и их связь с конкретными мутациями в гене LMX1B не понимаются, что препятствует разработке конкретных терапевтических стратегий. Здесь мы идентифицируем патогенетический механизм, затрагивающий многих

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… Forty-eight hours later cells were lysed with 1x PBS pH 7.4, 1% Triton X-100 in the presence of the protease inhibitors 4-(2-Aminoethyl)benzolsulfonylfluorid (AEBSF), aprotinin and leupeptin, N-ethylmaleimide was added to inhibit deubiquitylases 47 . …