Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin and quercetin

Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with antiinflammatory, antiischemic, vasodilating and chemoprotective properties. In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubicin-induced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes. After preincubation of cardiomyocytes with the test compounds for 1 h the cardiomyocytes were treated with the toxic agent, doxorubicin (100 micro M for 8 h). Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production. Cytoprotection was concentration dependent for baicalein > luteolin congruent with apigenin > quercetin > kaempferol. All test compounds had signi fi cantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy. In microsomes/mitochondria the IC(50) values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/73.1 +/- 6.4 mM, respectively. The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E(p/2)). Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds.     

Early pregnancy losses in in vitro fertilization and oocyte donation

Objective: To evaluate prospectively the incidence of early pregnancy losses (before menstruation occurs) in IVF and ovum donation cycles.

Design: Prospective case-control study.

Setting: Tertiary care, university-associated center.

Patient(s): One hundred forty-five patients undergoing IVF and 92 undergoing oocyte donation were recruited. The control group for IVF consisted of 15 ovum donors who had no ET and were instructed to avoid intercourse. The control group for oocyte donation included 10 women undergoing a mock cycle of steroid replacement.

Intervention(s): Starting on day 6 after ET, the women were instructed to collect the first urine sample of the day every 2 days. Each patient collected six different specimens of urine (days 6, 8, 10, 12, 14, and 16 after ET for cases or the same days without ET for controls.

Main Outcome Measure(s): β-HCG was measured with a standardized microparticle enzyme immunoassay, and IVF reproductive outcome was assessed.

Result(s): For IVF, positive implantation was registered in 88 of 145 cycles of embryo replacement (60.7%). Only 30 (20.7%) resulted in viable pregnancies, whereas the remaining 58 miscarried. Forty-two of these miscarriages (72.4%) were early pregnancy losses and 13 (22.4%) were classified as clinical abortions. In ovum donation, positive implantation was recorded in 64 of 92 cycles of ET (69.6%). A total of 30 (32.6%) ended in viable pregnancies, whereas the remaining 34 (37.0%) were miscarriages. Early pregnancy loss accounted for 70.6% of pregnancy losses, whereas biochemical pregnancies and clinical abortions accounted for 11.8% and 17.6%, respectively.

Conclusion(s): Our results demonstrate that patients undergoing assisted reproductive technology have an increased rate of early pregnancy loss compared with fertile patients. In addition, these data indicate that implantation is more frequently impaired in IVF than in oocyte donation cycles, resulting in a high incidence of early pregnancy loss. This suggests that implantation may be subjected to abnormal conditions in assisted reproduction.     

Enhancing the Buccal Mucosal Delivery of Peptide and Protein Therapeutics

Pharmaceutical Research - With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and...     

Comparison of the AMPA Antagonist Action of New 2,3-Benzodiazepines in Vitro and Their Neuroprotective Effects in Vivo

PURPOSE: AMPA receptor-mediated excitotoxicity is thought to be a critical process in diseases accompanied by neuronal cell loss following a hypoxic/anoxic state of the central nervous system. It has been suggested that blockade of AMPA receptors might result in significant protection of neurons against cellular damage. For testing the hypothesis, in vitro efficacy and in vivo neuroprotective action of new 2,3-benzodiazepine (2,3BDZ) AMPA antagonists have been compared. METHODS: 2.3BDZs were tested on kainate-evoked whole-cell currents in cultured neurons as well as on population spikes (PS) in rat hippocampal slices. Data were correlated with those obtained from the spreading depression (SD) experiments in chicken retina. Compounds were also examined in the gerbil bilateral carotid occlusion model (BCO), where percentage decrease of ischemia-related hypermotility (HM), impaired spatial memory (SA), and hypoxia-induced hippocampal CA1 neuronal cell death (CA1) were evaluated. RESULTS: Certain structural modifications of classical 2,3BDZs resulted in increased in vitro activity and improved in vivo efficacy. In particular, the halogen-substituted compounds EGIS-9879 and EGIS-9883 showed the highest neuroprotective efficacy (84% and 47% protection in CA1, 71% and 82% decrease in HM, respectively; 4 x 5 mg/kg i.p.) in BCO. PS and SD were correlated to the decrease of neuronal loss in the CA1 area. Lack of significant correlation was found between PS and CA1 (r = 0.437, p = 0.079) or SD and CA1 (r = 0.380, p = 0.146). CONCLUSIONS: Several new 2.3BDZ AMPA receptor antagonists have been synthesized at EGIS Pharmaceuticals characterized by remarkable in vitro and corresponding in vivo neuroprotective properties.     

Recombinant interferons alpha and gamma: comparative antiviral activity and synergistic interaction in encephalomyocarditis virus infection of mice

The antiviral properties of 2 recombinant DNA-produced interferons, a human hybrid interferon alpha that is active in mice and a murine interferon gamma, were examined in the treatment of mice infected with encephalomyocarditis virus. A single dose of interferon alpha induced a protective state in mice more rapidly than did interferon gamma, but the activity of the latter was more long lasting. When interferon and virus were administered 6 h apart, either intraperitoneally or intravenously, interferons alpha and gamma were equally effective. However, this was not the case when the routes of treatment and infection were different. Interferon alpha showed somewhat reduced activity when the route of administration (intravenous) was different from the route of virus challenge (intraperitoneal) while interferon gamma showed very little activity when tested in this manner. When interferons alpha and gamma were administered in combination to mice, a marked synergistic antiviral effect was observed.     

Transforming ophthalmology in the digital century—new care models with added value for patients

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2–3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.Subject terms: Scientific community, Health care     

Impacts of Asthma in Patients With Bronchiectasis: Findings From the KMBARC Registry

PurposeAlthough the coexistence of asthma and bronchiectasis is common, the impacts of asthma on bronchiectastic patients (BE) have not been well evaluated because this issue using bronchiectasis cohorts has been investigated in only a few studies.MethodsIn the present study, 598 patients who were prospectively enrolled in the Korean bronchiectasis registry were evaluated. The clinical characteristics between BE with asthma and those without asthma were compared.ResultsAsthma was found in 22.4% of BE. BE with asthma had a higher body mass index (BMI) (P = 0.020), more dyspnea (P < 0.001), larger sputum volume (P = 0.015), and lower forced expiratory volume in 1 second (FEV1) (P < 0.001) than those without asthma. BE with asthma had a higher rate of previous pneumonia (P = 0.017) or measles (P = 0.037) than those without asthma. Regarding treatment, BE with asthma used inhaled corticosteroids, long-acting muscarinic antagonists, and leukotriene receptor antagonists more frequently than those without asthma. Although intergroup differences were not observed in disease severity of bronchiectasis (P = 0.230 for Bronchiectasis Severity Index and P = 0.089 for FACED), the Bronchiectasis Health Questionnaire (BHQ) scores indicating the quality of life, were significantly lower in BE with asthma than in those without asthma (61.6 vs. 64.8, P < 0.001). In a multivariable model adjusting for age, sex, body mass index, forced expiratory volume in 1 second %predicted, sputum volume, modified Medical Research Council dyspnea scale ≥ 2, and the number of involved lobes, asthma was associated with lower BHQ scores (β-coefficient = −2.579, P = 0.014).ConclusionsBE with asthma have more respiratory symptoms, worse lung function, and poorer quality of life than those without asthma. A better understanding of the impacts of asthma in BE will guide appropriate management in this population.     

Supercritical CO2 Curing of Resource-Recycling Secondary Cement Products Containing Concrete Sludge Waste as Main Materials

This study aims to develop highly durable, mineral carbonation-based, resource-recycling, secondary cement products based on supercritical carbon dioxide (CO₂) curing as part of carbon capture utilization technology that permanently fixes captured CO₂. To investigate the basic characteristics of secondary cement products containing concrete sludge waste (CSW) as the main materials after supercritical CO₂ curing, the compressive strengths of the paste and mortar (fabricated by using CSW as the main binder), ordinary Portland cement, blast furnace slag powder, and fly ash as admixtures were evaluated to derive the optimal mixture for secondary products. The carbonation curing method that can promote the surface densification (intensive CaCO₃ formation) of the hardened body within a short period of time using supercritical CO₂ curing was defined as “Lean Carbonation”. The optimal curing conditions were derived by evaluating the compressive strength and durability improvement effects of applying Lean Carbonation to secondary product specimens. As a result of the experiment, for specimens subjected to Lean Carbonation, compressive strength increased by up to 12%, and the carbonation penetration resistance also increased by more than 50%. The optimal conditions for Lean Carbonation used to improve compressive strength and durability were found to be 35 °C, 80 bar, and 1 min.     

Differentiation of small hyperechoic renal cell carcinoma from angiomyolipoma: computer-aided tissue echo quantification.

To assess the value of computer-aided tissue echo quantification in differentiating small hyperechoic renal cell carcinomas from angiomyolipomas, we studied ultrasonographic images of 15 renal cell carcinomas and 20 angiomyolipomas. After digitizing the images, we measured the absolute gray scale values of the renal cortex, central echo complex, and mass. The relative gray scale value (%) of the mass was calculated by setting the gray scale value of the cortex as 0% and the central echo complex as 100%. The relative gray scale value of renal cell carcinomas was in the range of 12 to 73% (mean, 28%), whereas that of angiomyolipomas was 30 to 204% (mean, 130%). The differentiation between small hyperechoic renal cell carcinomas and angiomyolipomas can be facilitated by computer-aided tissue echo quantification.