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Current Problems in Cardiology Jun 2024Individuals afflicted with heart failure (HF) with preserved ejection fraction (HFpEF) often exhibit obesity, a condition that is frequently associated with a pronounced... (Review)
Review
Individuals afflicted with heart failure (HF) with preserved ejection fraction (HFpEF) often exhibit obesity, a condition that is frequently associated with a pronounced prevalence of symptoms and physical constraints related to HF, alongside detrimental hemodynamic profiles and an elevated susceptibility to adverse cardiac events. The amelioration of health status is a pivotal objective in the management of HF, with extant research suggesting that a considerable number of patients with this condition place equal emphasis on the enhancement of these health dimensions as they do on the prolongation of life. The administration of a weekly subcutaneous dose of 2.4 mg Semaglutide has been observed to yield significant amelioration in symptomatology, physical limitations, and exercise capacity, alongside a reduction in inflammatory markers and a more pronounced reduction in body weight when compared to a placebo in the study's obese HFpEF cohort. Nevertheless, the extent to which these therapeutic benefits of Semaglutide manifest differentially in relation to the baseline severity of health status impairment remains to be elucidated. Additionally, a more nuanced comprehension of the impact of Semaglutide on the comprehensive spectrum of health status parameters, encompassing symptomatology, physical limitations, life quality, and social impediments, is warranted. This includes an assessment of the proportion of patients experiencing deterioration, as well as those attaining minimal, moderate, substantial, and marked improvements within these respective domains.
PubMed: 38944224
DOI: 10.1016/j.cpcardiol.2024.102736 -
European Journal of Pharmaceutics and... Jun 2024Monoclonal antibodies (mAbs) are an essential class of therapeutic proteins for the treatment of cancer, autoimmune and rare diseases. During their production, storage,...
Monoclonal antibodies (mAbs) are an essential class of therapeutic proteins for the treatment of cancer, autoimmune and rare diseases. During their production, storage, and administration processes, these proteins encounter various stressors such as temperature fluctuations, vibrations, and light exposure, able to induce chemico-physical modifications to their structure. Viral inactivation is a key step in downstream processes, and it is achieved by titration of the mAb at low pH, followed by neutralization. The changes of the pH pose a significant risk of unfolding and subsequent aggregation to proteins, thereby affecting their manufacturing. This study aims to investigate whether a combined exposure to light during the viral inactivation process can further affect the structural integrity of Ipilimumab, a mAb primarily used in the treatment of metastatic melanoma. The biophysical and biochemical characterization of Ipilimumab revealed that pH variation is a considerable risk for its stability with irreversible unfolding at pH 2. The threshold for Ipilimumab denaturation lies between pH 2 and 3 and is correlated with the loss of the protein structural cooperativity, which is the most critical factor determining the protein refolding. Light has demonstrated to exacerbate some local and global effects making pH-induced exposed regions more vulnerable to structural and chemical changes. Therefore, specific precautions to real-life exposure to ambient light during the sterilization process of mAbs should be considered to avoid loss of the therapeutic activity and to increase the yield of production. Our findings underscore the critical role of pH optimization in preserving the structural integrity and therapeutic efficacy of mAbs. Moreover, a detailed conformational study on the structural modifications of Ipilimumab may improve the chemico-physical knowledge of this effective drug and suggest new production strategies for more stable products under some kind of stress conditions.
PubMed: 38944210
DOI: 10.1016/j.ejpb.2024.114387 -
International Journal of Pharmaceutics Jun 2024Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone... (Review)
Review
Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancreatic β-cells. Insulin is highly sensitive to environmental stresses and readily undergoes structural changes, being also able to unfold and aggregate in physiological conditions. Even; small changes altering the structural integrity of insulin may have significant impacts on its biological efficacy to its physiological and pharmacological activities. Insulin analogs have been engineered to achieve modified properties, such as improved stability, solubility, and pharmacokinetics, while preserving the molecular pharmacology of insulin. The casually or purposively strategies of chemical modifications of insulin occurred to improve its therapeutic and pharmaceutical properties. Knowing the effects of chemical modification, formation of aggregates, and nanoparticles on protein can be a new look at the production of protein analogues drugs and its application in living system. The project focused on effects of chemical modifications and nanoparticles on the structure, stability, aggregation and their results in effective drug delivery system, biological activity, and pharmacological properties of insulin. The future challenge in biotechnology and pharmacokinetic arises from the complexity of biopharmaceuticals, which are often molecular structures that require formulation and delivery strategies to ensure their efficacy and safety.
PubMed: 38944170
DOI: 10.1016/j.ijpharm.2024.124399 -
International Journal of Pharmaceutics Jun 2024Ulcerative colitis (UC) is a chronic bowel inflammatory disease affecting the colorectum. Epidermal growth factor (EGF) has been demonstrated to be effective to...
Ulcerative colitis (UC) is a chronic bowel inflammatory disease affecting the colorectum. Epidermal growth factor (EGF) has been demonstrated to be effective to counteract UC. However, there exists the gastrointestinal challenges such as stomach acid, enzyme and bile salts for oral delivery of EGF. Herein, calcium alginate microsphere was prepared by the microfluidic technique to encapsulate EGF. The morphology of EGF-loaded microsphere (MS-EGF) was spherical and its average particle size was 80 ± 23 μm. The encapsulation efficiency of EGF was reaching to 93.8 % ± 1.6 %. In vitro release experiments showed that MS-EGF presented the good pH-sensitive properties, that was, it could effectively resist the gastric acid and small intestinal fluids, and undergone the rapid dissolution in the artificial colon fluid. In vitro cellular experiments demonstrated that the bioactivity of EGF was well preserved by microsphere. Moreover, in vivo murine colitis model showed that MS-EGF presented the obvious colitis alleviation. Furthermore, the colonic morphology of colitis mice was effectively recovered and the tight junction between the gut epithelium was obviously repaired. In conclusion, calcium alginate microsphere might be a promising vehicle of EGF for UC treatment.
PubMed: 38944169
DOI: 10.1016/j.ijpharm.2024.124394 -
The Journal of Heart and Lung... Jun 2024Real-time lung weight (LW) measurement is a simple and non-invasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We...
BACKGROUND
Real-time lung weight (LW) measurement is a simple and non-invasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We investigated the feasibility of real-time LW measurement in clinical EVLP as a predictor of transplant suitability and post-transplant outcomes.
METHODS
In our clinical acellular EVLP protocol, real-time LW was measured in 117 EVLP cases from June 2019 to June 2022. The estimated LW gain at each timepoint was calculated using a scale placed under the organ chamber. The lungs were classified into four categories based on LW adjusted for height and compared between suitable and unsuitable cases. The relationship between estimated LW gain and primary graft dysfunction was also investigated.
RESULTS
The estimated LW gain during the EVLP significantly correlated with the LW gain (post EVLP LW - pre EVLP LW) measured on the back table (R=0.61, P<0.01). In the adjusted LW categories 2-4, the estimated LW gain at 0-1 h after EVLP was significantly higher in unsuitable cases than in suitable cases. The area under the curve for the estimated LW gain was ≥0.80. Primary graft dysfunction grade 0-1 had a significantly lower estimated LW gain at 60 min than grades 2-3 (-43 vs. 1 g, P<0.01).
CONCLUSIONS
Real-time lung measurements can predict transplant suitability and post-transplant outcomes by the early detection of extravascular lung water during the initial 1 h of EVLP.
PubMed: 38944131
DOI: 10.1016/j.healun.2024.06.013 -
Food Chemistry Jun 2024Some wheat-based foods require different doses of oil to moderate quality of dough during processing and the influence mechanisms remain unclear. Therefore, the effect...
Some wheat-based foods require different doses of oil to moderate quality of dough during processing and the influence mechanisms remain unclear. Therefore, the effect of rapeseed oil addition on physicochemical characteristics and fine structure of dough and underlying mechanism were elucidated by rheometer, scanning microscope and molecular spectroscopic method. Results showed that compared with native dough (without exogenous rapeseed oil), the addition of rapeseed oil changed the fine structure, improved extensibility, but reduced viscoelasticity of the dough. Moreover, high addition especially 20 wt% oil (based on wheat flour) significantly changed gelatinization and retrogradation behaviors of the dough, whilst disrupted gluten network and increased random coil content (32.1%) of dough except that decreased its α-helix (21.2%), β-sheet (23.1%), disulfide bond (7.9 μmol/g) compared with native dough which were 16.3%, 29.2%, 33.1%, 11.0 μmol/g, respectively. Results in the study could provide a certain understanding for application of vegetable oils in wheat-based products.
PubMed: 38943950
DOI: 10.1016/j.foodchem.2024.140227 -
International Journal of Surgery Case... May 2024Congenital gangrene of the limb in a newborn child is an extremely rare pathology with polyetiological causes that has not been fully studied. Therefore, each case of...
INTRODUCTION AND IMPORTANCE
Congenital gangrene of the limb in a newborn child is an extremely rare pathology with polyetiological causes that has not been fully studied. Therefore, each case of this pathology has its own characteristics of manifestations and allows you to get closer to solving this problem.
CASE PRESENTATION
We present a clinical case of congenital gangrene of the right upper limb in a newborn child. Analysis of the newborn baby's medical history indicated gestational hypertension and pyelonephritis during pregnancy in the mother, hemostasis disorders in the newborn. Computed tomography (CT) of the vessels of the right upper limb and thoracic segment confirmed brachial artery thrombosis. At the initial stage, conservative treatment was carried out, which included preventive antibacterial therapy and local care of the affected area. Only after a clear delineation of the dead tissue, the amputation of the segment of the right upper limb was performed. Amputation was performed with preservation of the proximal growth zone in order to provide an adequate stump for subsequent prosthetics.
CLINICAL DISCUSSION
Adverse factors during pregnancy can cause increased thrombosis. Through fetal communications, blood clots from the right atrium can enter the left atrium, the left ventricle and further into the large circulatory circle and cause thrombosis of the artery of the right upper limb. Another factor of increased thrombosis is congenital intrauterine infection of the newborn. Conservative treatment is carried out after diagnosis until the final determination of the boundaries of gangrene. When performing amputation, it is important to preserve the proximal bone growth zone in order to form an adequate stump for prosthetics.
CONCLUSION
Congenital gangrene of the limb in a newborn child is an extremely rare pathology. Irreversible changes in the upper limb in the child were caused by a combination of two factors: gestational hypertension and pyelonephritis in a pregnant woman and hemostasis disorders in a newborn due to intrauterine infection. Therefore, the preparation of women for pregnancy, examination for intrauterine infection and treatment of extragenital pathology are important in the prevention of this disease.
PubMed: 38943943
DOI: 10.1016/j.ijscr.2024.109738 -
International Journal of Surgery Case... Jun 2024Esophageal varices are dilated distal submucosal esophageal veins that connect the portal and systemic circulations. They are formed due to portal hypertension, which...
INTRODUCTION
Esophageal varices are dilated distal submucosal esophageal veins that connect the portal and systemic circulations. They are formed due to portal hypertension, which commonly resulted from cirrhosis. We presented an 8-year-old girl with esophageal varices without signs of cirrhosis. This case report aims to describe non-cirrhotic portal hypertension causing esophageal varices in a school-age girl.
PRESENTATION OF CASE
An 8-year-old girl presented with one month of progressive hematemesis. The patient had been diagnosed with esophageal varices since she was 6 years old. Liver function test was within normal limits, complete blood count revealed bicytopenia.
DISCUSSION
Due to well-preserved liver function, the patient underwent distal splenorenal shunt (DSRS). After the surgical procedure, the patient's clinical condition generally improved.
CONCLUSION
NCPH (non-cirrhotic portal hypertension) is treated similarly with cirrhotic portal hypertension. DSRS could be the treatment of choice for refractory esophageal varices.
PubMed: 38943932
DOI: 10.1016/j.ijscr.2024.109941 -
Ultrasonics Sonochemistry Jun 2024Meat is highly susceptible to contamination with harmful microorganisms throughout the production, processing, and storage chain, posing a significant public health... (Review)
Review
Meat is highly susceptible to contamination with harmful microorganisms throughout the production, processing, and storage chain, posing a significant public health risk. Traditional decontamination methods like chemical sanitizers and heat treatments often compromise meat quality, generate harmful residues, and require high energy inputs. This necessitates the exploration of alternative non-ionizing technologies for ensuring meat safety and quality. This review provides a comprehensive analysis of the latest advancements, limitations, and future prospects of non-ionizing technologies for meat decontamination, with a specific focus on ultrasonication. It further investigates the comparative advantages and disadvantages of ultrasonication against other prominent non-ionizing technologies such as microwaves, ultraviolet (UV) light, and pulsed light. Additionally, it explores the potential of integrating these technologies within a multi-hurdle strategy to achieve enhanced decontamination across the meat surface and within the matrix. While non-ionizing technologies have demonstrated promising results in reducing microbial populations while preserving meat quality attributes, challenges remain. These include optimizing processing parameters, addressing regulatory considerations, and ensuring cost-effectiveness for large-scale adoption. Combining these technologies with other methods like antimicrobial agents, packaging, and hurdle technology holds promise for further enhancing pathogen elimination while safeguarding meat quality.
PubMed: 38943850
DOI: 10.1016/j.ultsonch.2024.106962 -
Inorganic Chemistry Jun 2024The manuscript focuses on an original method of preparation of metatitanic acid when only environmentally safe base substances are used in the synthesis process. The...
The manuscript focuses on an original method of preparation of metatitanic acid when only environmentally safe base substances are used in the synthesis process. The synthesis is based on the reaction of solid titanyl sulfate in an aqueous solution of sodium hydroxide. This method allows for (i) a full preservation of the morphology of the starting titanyl sulfate and (ii) a preparation of metatitanic acid substances with specific parameters. This can be achieved via a precise control of the alkali metal/titanyl sulfate ratio resulting in substances with varying contents of alkali metals or even sulfate anions. The prepared metatitanic acid then also contains very small weakly crystalline particles (2-3 nm) and forms pseudomorphic aggregates whose shape and dimensions correspond to those of the starting titanyl sulfate. These aggregates exhibit regular nanoporosity with a high surface area of up to 500 m·g, have no tendency to form colloids, and are mechanically highly resistant even by high-energy ultrasound. The characterization of the resulting products is done via their chemical composition and methods of structural analysis, as well as by electron microscopy and local analysis. The mechanism of product formation is discussed based on the structure of the precursor, including the so far unknown structure of metatitanic acid.
PubMed: 38943595
DOI: 10.1021/acs.inorgchem.4c00369