anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
1,268,316. 2-Allyl-3-hydroxy-1,4-naphthoquinone derivatives. PFIZER Inc. 5 May, 1970 [2 March, 1970], No. 21669/70. Heading C2C. Novel 2-allyl-3-hydroxy-1,4-naphthoquinone derivatives of the general formula wherein each R is a halogen atom or a trifluoromethyl group or the two Rs together form a C 3-6  carbocyclic ring, which have antitumour activity, are prepared by reaction of a 2- hydroxy-1,4-naphthoquinone salt of the general formula with an allyl halide of the general formula XCH 2 CH=C(R) 2  orCH 2 =CH-CX(R) 2 , wherein X is a chlorine, bromine or iodine atom, in the presence of a metal iodide and a solvent. 3,3-Bis-(trifluoromethyl)-allyl iodide is prepared by reaction of vinyl magnesium chloride with hexafluoroacetone in tetrahydrofuran with external cooling, treatment of the resulting complex with saturated ammonium chloride solution, reaction of the resulting 1,1,1-trifluoro- 2-trifluoromethyl-3-buten-2-ol with p-bromobenzenesulphonyl chloride in the presence of sodium hydride and reaction of the resulting 1,1-bis- (trifluoromethyl)-allyl p-bromobenzenesulphonate with potassium iodide.
The invention discloses a polypeptide composition for external use on skin and application thereof. The skin external polypeptide composition comprises the following components in parts by mole: 3 to 10 parts carnosine, 3 to 6 parts tripeptide GHK, 2 to 5 parts copper peptide, and 6 to 8 parts palmitoyl tetrapeptide. The invention verifies through repeated experiments that 4 polypeptides are screened from more than 20 polypeptides which effectively act on the skin and are quantitatively combined. Experiments prove that the traditional Chinese medicine composition can relieve inflammatory response after hormone use is stopped, shorten the course of disease and has small recurrence risk for glucocorticoid-dependent symptoms. The skin external application agent containing Chang' e composite soothing polypeptide provided by the invention is screened from more than 20 polypeptides which effectively act on the skin and quantitatively combined. Experiments prove that the traditional Chinese medicine composition can relieve inflammatory response after hormone use is stopped, shorten the course of disease and has small recurrence risk for glucocorticoid-dependent symptoms.
PURPOSE:To obtain the title solid agent having low viscosity in coating, capable of readily producing and capable of preserving Bifidobacterium over a long period in active state and surely sending Bifidobacterium to the intestine in a state of living bacterium by applying enteric coating film to solid agent having low water content. CONSTITUTION:The aimed solid agent obtained by applying an enteric coating film to a solid agent having low water content. As the enteric coating film, a material having low viscosity and insoluble in stomach and capable of sending Bifidobacterium-containing solid agent to intestine in a state of living bacterium, e.g. a blend of a copolymer of methacrylic acid and ethyl acrylate capable of dissolving at pH>=5.0 and copolymer of methacrylic acid and methyl acrylate is used. The blend is preferably carried out at a weight ratio of 1:1. The content of the enteric coating film in coating liquid composition is preferably 5-8%. Furthermore, anhydrous calcium hydrogen phosphate which is a moisture absorbing agent may be blended therewith as a diluting agent in an amount of 5-50wt.% based on one tablet.
RAD001 is an orally administered cell cycle inhibitor with antitumor activity. RAD001, like Rapamycin, binds with high affinity to an intracellular immunophilin, FKBP12 and this complex specifically interacts with the mammalian target of rapamycin (mTOR) protein kinase, inhibiting downstream events such as the initiation of mRNA translation. RAD001 inhibits the growth of a wide range of histologically diverse tumor cells. RAD001 is being developed as a cytostatic agent to delay the time to tumor recurrence/progression or to increase survival in patients with various malignancies. The compound has good tolerability, a partially discovered mechanism of action. RAD001 has the ability to arrest cells in the G1 phase, and the ability to induce apoptosis. RAD001 is being investigated as an anticancer agent based on its potential to act directly on the tumor cells by inhibiting tumor cell growth and proliferation through possible inhibition of the PI3/AKT/MTOR pathway.

RAD001 was shown to have activity in human tumor cell lines originating from lung, breast, prostate, colon, kidney, melanoma and glioblastoma. RAD001 was also shown to have activity in human pancreatic neuroendocrine cells, where induction of apoptosis was reported, as well as in acute myeloid leukemia cells, adult T-cell leukemia cells, diffuse large B cell lymphoma cells, pancreatic tumor cells, ovarian cancer cells, and hepatocellular carcinoma cells.
Tumor diseases become a huge problem when they embark on a path that advances to malignancy, such as the process of metastasis. Cancer metastasis has been thoroughly investigated from a biological perspective in the past, whereas it has still been less explored from a physical perspective. Until now, the intraluminal pathway of cancer metastasis has received the most attention, while the interaction of cancer cells with macrophages has received little attention. Apart from the biochemical characteristics, tumor treatments also rely on the tumor microenvironment, which is recognized to be immunosuppressive and, as has recently been found, mechanically stimulates cancer cells and thus alters their functions. The review article highlights the interaction of cancer cells with other cells in the vascular metastatic route and discusses the impact of this intercellular interplay on the mechanical characteristics and subsequently on the functionality of cancer cells. For instance, macrophages can guide cancer cells on their intravascular route of cancer metastasis, whereby they can help to circumvent the adverse conditions within blood or lymphatic vessels. Macrophages induce microchannel tunneling that can possibly avoid mechanical forces during extra- and intravasation and reduce the forces within the vascular lumen due to vascular flow. The review article highlights the vascular route of cancer metastasis and discusses the key players in this traditional route. Moreover, the effects of flows during the process of metastasis are presented, and the effects of the microenvironment, such as mechanical influences, are characterized. Finally, the increased knowledge of cancer metastasis opens up new perspectives for cancer treatment.
The present invention involves a novel tripyrrole dimethine-derived "expanded porphyrin" (texaphyrin), the synthesis of such compounds, their analogs or derivatives and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus potentially for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus and tumor cells as well. A variety of texaphyrin derivatives have been produced and many more are readily obtainable. Various metal (e.g , transition, main group, and lanthanide) complexes with the texaphyrin and texaphyrin derivatives of the present invention have unusual water solubility and stability which render them particularly useful. These metallotexaphyrin complexes have optical properties making them unique as compared to existing porphyrin-like or other macrocycles. For example, they absorb light strongly in a physiologically important region (i.e. 690-880 nm). These complexes also form long-lived triplet states in high yield and act as efficient photosensitizers for the formation of singlet oxygen. These properties, coupled with their high chemical stability and appreciable solubility in polar media such as water, add to their usefulness.
Following a 10 minute intravenous infusion of 300 mcg clonidine HCl to five male volunteers, plasma clonidine levels showed an initial rapid distribution phase (mean±SD t1⁄2=11±9 minutes) followed by a slower elimination phase (t1⁄2=9±2 hours) over 24 hours. Clonidine’s total body clearance (CL) was 219±92 mL/min.

Following a 700 mcg clonidine HCl epidural dose given over five minutes to four male and five female volunteers, peak clonidine plasma levels (4.4±1.4 ng/mL) were obtained in 19±27 minutes. The plasma elimination half-life was determined to be 22±15 hours following sample collection for 24 hours. CL was 190±70 mL/min. In cerebral spinal fluid (CSF), peak clonidine levels (418±255 ng/mL) were achieved in 26±11 minutes. The clonidine CSF elimination half-life was 1.3±0.5 hours when samples were collected for 6 hours. Compared to men, women had a lower mean plasma clearance, longer mean plasma half-life, and higher mean peak level of clonidine in both plasma and CSF.

In cancer patients who received 14 days of clonidine HCl epidural infusion (rate=30 mcg/hr) plus morphine by patient-controlled analgesia (PCA), steady state clonidine plasma concentrations of 2.2±1.1 and 2.4±1.4 ng/mL were obtained on dosing days 7 and 14, respectively. CL was 279±184 and 272±163 mL/min on these days. CSF concentrations were not determined in these patients.
The safety and effectiveness of ENTRESTO in pediatric heart failure patients 1 to < 18 years old are supported by the reduction from baseline to 12 weeks in NT-proBNP in a randomized, double-blind clinical study [see Clinical Studies (14.2)]. The analysis of NT-proBNP included 90 patients age 6 to 18 years and 20 patients age 1 to 6 years. 

Safety and effectiveness have not been established in pediatric patients less than 1 year of age.

Animal Data

Sacubitril given orally to juvenile rats from postnatal day (PND) 7 to PND 35 or PND 70 (an age approximately equivalent to neonatal through pre-pubertal development or adulthood in humans) at doses ≥ 400 mg/kg/day (approximately 2-fold the AUC exposure to the active metabolite of sacubitril, LBQ657, at an ENTRESTO pediatric clinical dose of 3.1 mg/kg twice daily) resulted in decreases in body weight, bone length, and bone mass. The decrease in body weight was transient from PND 10 to PND 20 and the effects for most bone parameters were reversible after treatment stopped. Exposure at the No-Observed-Adverse-Effect-Level (NOAEL) of 100 mg/kg/day was approximately 0.5-fold the AUC exposure to LBQ657 at the 3.1 mg/kg twice daily dose of ENTRESTO. The mechanism underlying bone effects in rats and the translatability to pediatric patients are unknown.

Valsartan given orally to juvenile rats from PND 7 to PND 70 (an age approximately equivalent to neonatal through adulthood in humans) produced persistent, irreversible kidney damage at all dose levels. Exposure at the lowest tested dose of 1 mg/kg/day was approximately 0.2-fold the exposure at 3.1 mg/kg twice daily dose of ENTRESTO based on AUC. These kidney effects in neonatal rats represent expected exaggerated pharmacological effects that are observed if rats are treated during the first 13 days of life.
BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation.
RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors.
CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.
ARID1B is the most frequently mutated gene in Coffin-Siris syndrome (CSS). To date, the vast majority of causative variants reported in ARID1B are truncating, leading to nonsense-mediated mRNA decay. In the absence of experimental data, only few ARID1B amino acid substitutions have been classified as pathogenic, mainly based on clinical data and their de novo occurrence, while most others are currently interpreted as variants of unknown significance. The present study substantiates the pathogenesis of ARID1B non-truncating/NMD-escaping variants located in the SMARCA4-interacting EHD2 and DNA-binding ARID domains. Overexpression assays in cell lines revealed that the majority of EHD2 variants lead to protein misfolding and formation of cytoplasmic aggresomes surrounded by vimentin cage-like structures and co-localizing with the microtubule organisation center. ARID domain variants exhibited not only aggresomes, but also nuclear aggregates, demonstrating robust pathological effects. Protein levels were not compromised, as shown by quantitative western blot analysis. In silico structural analysis predicted the exposure of amylogenic segments in both domains due to the nearby variants, likely causing this aggregation. Genome-wide transcriptome and methylation analysis in affected individuals revealed expression and methylome patterns consistent with those of the pathogenic haploinsufficiency ARID1B alterations in CSS cases. These results further support pathogenicity and indicate two approaches for disambiguation of such variants in everyday practice. The few affected individuals harbouring EHD2 non-truncating variants described to date exhibit mild CSS clinical traits. In summary, this study paves the way for the re-evaluation of previously unclear ARID1B non-truncating variants and opens a new era in CSS genetic diagnosis.
SCD is an inherited blood disorder, and symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." ACS, characterized by fever, respiratory distress, and lung tissue damage, is the second most common cause of hospitalization and the leading cause of death among people with SCD. Most people with SCD will experience at least one episode of ACS, and repeated episodes can result in progressive lung disease. ACS can appear suddenly and often requires immediate hospitalization and treatment, which can include blood transfusions. People with elevated blood levels of sPLA2 may be at risk for developing ACS, and this enzyme is often detectable before the onset of ACS symptoms. The purpose of this study is to examine the use of sPLA2 as a predictor of ACS and to determine whether subsequent blood transfusions can be administered early enough to prevent the onset of ACS in people with SCD who are at risk for ACS. Study researchers will also assess the feasibility of conducting a larger study that would further examine the effectiveness of using sPLA2 levels and blood transfusions to prevent ACS.

This study will involve two parts. In the first part of the study, participants with SCD who are admitted to the hospital with an acute sickle cell pain event will be randomly assigned to receive either a single blood transfusion or standard care for ACS and no blood transfusion. All participants will be closely monitored while in the hospital for the development of ACS, and study researchers will review participants' medical records. All participants will undergo daily blood collections, which will include testing for sPLA2 levels, and at least two chest x-rays. Twenty-eight days after hospital discharge, all participants will attend a follow-up study visit for blood collection, again to determine sPLA2 levels.

In the second part of the study, participants who are not eligible or who do not choose to participate in the first part of the study will be enrolled into an observational group. These participants will receive standard care for ACS, but will not receive a blood transfusion. They will undergo daily blood collection during their hospital stay and at least one chest x-ray. While participants are in the hospital and 28 days after discharge, study researchers will review participants' medical records.
Anionic polyelectrolyte comprises a linear, branched or crosslinked terpolymer of at least one monomer having a partially- or totally-salified free strong acid function with at least one neutral monomer, and an alkane-oxy monomer (I). Anionic polyelectrolyte comprises a linear, branched or crosslinked terpolymer of at least one monomer having a partially- or totally-salified free strong acid function with at least one neutral monomer and an alkane-oxy monomer of formula (R1-C(=CH 2)-C(=O)-O(CH 2-CH 2-O) n-R) (I). R1 : H; R : 8-16C alkyl; and n : >= 1 or = 10. An independent claim is included for a process of preparing the polyelectrolyte comprising mixing all monomers, where appropriate cross-linking agent and/or other additives in an organic solvent, preferably tert-butanol, initiating the polymerization reaction by introduction into the dispersion of a free radical initiator and receiving precipitate by evaporation of the solvent, when the polymerization is complete and then the dried is precipitated. ACTIVITY : Dermatological. MECHANISM OF ACTION : None given. No biological data given.
Recognition of the biological effects of vitamin D on cardiovascular function has been growing. The main objective of the parent trial (VITAL) is to evaluate the effects of vitamin D on cardiac events but is focused on atherothrombotic events and does not specifically address vitamin D effects on LV mass. In ambulatory individuals, LV mass is a key cardiac structural feature and increases in LV mass are frequently accompanied by diastolic dysfunction. This study leverages the existing infrastructure of the parent VITAL trial to perform cardiac imaging studies on a subset of subjects who will be randomized to vitamin D3 (n=500) or placebo (n=500). Echocardiography is a noninvasive, widely accessible tool to evaluate cardiac structure and function. Cardiac echo imaging visits will take place at baseline (pre-randomization), and then after 2 years, at the Massachusetts General Hospital (MGH). The acronym VITAL-Echo reflects the link to the parent VITAL trial and an ancillary investigation of vitamin D versus placebo on LV mass and function as measured by echocardiography. The effect of fish oil supplementation on these parameters will be evaluated as a secondary endpoint, thereby taking advantage of the factorial design of the parent trial.
PURPOSE OF REVIEW: The care of patients with complex postsurgical pain can be challenging and burdensome for the healthcare system. Transitional pain service (TPS) is a relatively new concept and has not been widely adopted in the USA. This article explores the benefits and barriers of transitional pain services and describes the development of a TPS at our institution.
RECENT FINDINGS: Evidence from a few institutions that have adopted TPS has shown decreased postsurgical opioid consumption for patients on chronic opioids and decreased incidence of chronic postsurgical opioid use for opioid-naïve patients. The development of a transitional pain service may improve outcomes for these complex patients by providing longitudinal and multidisciplinary perioperative pain care. In this article, we describe the implementation of a TPS at a tertiary medical center. Our TPS model involves a multidisciplinary team of anesthesiologists, pain psychologists, surgeons, and advanced practice providers. We provide longitudinal care, including preoperative education and optimization; perioperative multimodal analgesic care; and longitudinal follow-up for 90 days post-procedure. With our TPS service, we aim to reduce long-term opioid use and improve functional outcomes for our patients.
Epirubicin 90 mg/mq + Cyclophosphamide 600 mg/mq i.v. every 3 weeks for 3 courses, followed by Nivolumab (240 mg flat dose i.v. each 2 weeks) for 8 courses plus exemestane 25 mg (orally, continuous daily dose, to be continued until surgery). LHRH analogue (Triptorelin 3.75mg 1 fl i.m. every 28 days) started concomitantly to anthracycline based chemotherapy, to be continued until surgery.
FIELD: medicine. SUBSTANCE: method involves parenterally introducing material in particles containing matrix or membrane material and at least one component for creating contrast. The matrix or membrane material responses to a physiological parameter selected in advance so that contrasting efficiency of the mentioned component changes as response to a change in preselected parameter value. Image data of at least a part of organism are displayed where the component is available. Signal is generated as indicator of parameter value or value change in the mentioned part of the mentioned organism. EFFECT: enabled organism visualization; high accuracy in parameter measuring. 26 cl, 20 dwg, 21 tbl
Ketamine is an N-Methyl-d-aspartate-receptor-antagonist commonly used over the last decades as an anesthetic and analgesic agent for procedural sedation. The use of ketamine as a prolonged infusion was first described in 1990 and a prolonged infusion of ketamine has been described as a successful strategy for analgesia and sedation in patients with hemodynamic instability, in patients who were mechanically ventilated and poorly responsive to conventional drugs. An other indication for ketamine infusion is the presence of bronchospasm, due to its action in promoting bronchodilatation. However, existing studies on ketamine for prolonged sedation are mainly retrospective and include small sample size, suggesting that this topic needs to be further investigated. The aim of this observational single center study is to describe the use of ketamine used as adjuvant to conventional analgesic and sedative strategy (opioid and benzodiazepine in continuous infusion) as prolonged infusion (i.e. ≥ 12 hr) in pediatric patients. The investigators will evaluate ketamine indications, dosages, infusion duration, adoption of boluses, modality of weaning. Concomitant analgesic and sedative management and monitoring of level of sedation (using a validated scale) are considered measures of efficacy. Sparing of other bronchospasm drugs sedative dosage are considered measures of efficacy if ketamine is used in patients with obstructive respiratory diseases. Presence of adverse effects (including withdrawal syndrome symptoms and delirium) during infusione or 48 hours after weaning are considered measures of safety. Data were collected using a standardized data sheet. The study lasted 18 months to reach a numerosity of 55 patients. All the requested institutional approvals were collected before starting the data collection.
Control group (upper arm). If the patient is in the control group the research staff will direct the inserter to place the catheter into the upper arm vein at least 2 cm above the antecubital fossa.