Perrin and Förster unified: dual-laser triple-polarization FRET (3polFRET) for interactions at the Förster-distance and beyond

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Béta-laktámokhoz vezető dominó reakció: átmenetifém-katalizált ketén képződés és cikloaddíció szintetikus és elméleti vizsgálata = Domino transition metal-catalysed ketene formation — cycloaddition reactions leading to beta-lactams. Synthetic and theoretical aspects.

Reakciókinetikai, spektroszkópiai és elméleti kémiai számítási módszerekkel tisztáztuk a kobalt-katalizált etil-diazoacetát karbonilezés mechanizmusát. Kvantumkémiai számításokkal vizsgáltuk diazometán és etil-diazoacetát reakcióját nikkel-tetrakarbonil és Ni(CO)3(PH3) komplexekkel. Vizsgáltuk a HM(CO)2Cp komplexek szerkezetét (M=Mo, W) és trimetilszilil-diazometánnal történő reakcióját. A foszfántartalmú kobalt-komplex heterogenizálásával aktív és többször felhasználható katalizátort fejlesztettünk ki. Az etil-diazoacetát alkil-szubsztituált iminek jelenlétében megvalósítható karbonilezésével egyreakcióedényes ? -laktám szintézist dolgoztunk ki. Ferrocéntartalmú iminek reakciójában a ? -laktám képződés mellett vagy helyett gyűrűnyitást tapasztaltunk. Ily módon új 2-(1-ferrocenil-metilidén)-malonsav- vagy tetrahidro-4(1H)-pirimidinon származékokat állítottunk elő jó hozammal. Javaslatot tettünk a reakciók mechanizmusára. Megállapítottuk, hogy 2-szubsztituált ferrocénszármazékok alkalmazásával a gyűrűnyitás megakadályozható. Az oldalláncban ?-laktámot tartalmazó szteroidokat állítottunk elő palládium-katalizált karbonilezés alkalmazásával. Változatos szerkezetű egyéb heterociklusos szteroidokat és ferrocénszármazékokat is szintetizáltunk homogén katalitikus reakciók felhasználásával. Egyes szteránvázas kiindulási vegyületek szintézise kapcsán vizsgáltuk epoxi-szteroidok gyűrűnyitását ionfolyadékokban és a vizsgálatokat kiterjesztettük többféle nukleofil reakciópartnerre. | Mechanism of cobalt-catalysed carbonylation of ethyl diazoacetate has been clarified by detailed kinetic and spectroscopic investigations and quantum chemical calculations. Reactions of diazomethane and ethyl diazoacetate with Ni(CO)4 or Ni(CO)3(PH3) were investigated by means of DFT calculations. Structure of a HM(CO)2Cp (M=Mo, W) complexes and their reactions with trimethylsilyl-diazomethane were investigated. By the heterogenization of a phosphane containing cobalt complex, a supported, reusable catalyst was obtained and used succesfully in the domino reaction.. A one-pot reaction was developed for the synthesis of ? –lactams. In case of ferrocene-substituted compounds, lactam ring-opening was observed and 2-(1-ferrocenyl-methylidene)-malonic acid derivatives or tetrahidro-4(1H)-pirimidinones were obtained in good yields. The reaction mechanisms were clarified by experimental and theoretical investigations. It was proved that ring-opening can be hindered by the use of 2-substituted ferrocene derivatives. New steroid-?-lactam hibrids have been obtained by palladium-catalysed carbonylation. Various other new steroids and ferrocene derivatives with heterocyclic moieties have been synthesised by homogeneous catalytic reactions. Related to the synthesis of some of the steroidal substrates, ring-opening of steroidal epoxides in ionic liquids, in the presence of various nucleophilic reagents, was investigated

Obesity-induced cognitive impairment in older adults: a microvascular perspective

Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed

A sugárkezelés okozta cardiotoxicitas kockázatának csökkentése bal oldali emlőtumoros betegek kezelése során

Bevezetés: Az emlődaganat a nőket érintő egyik leggyakoribb rosszindulatú daganatos megbetegedés. A kezelés során alkalmazott gyógyszeres és sugárterápiás eljárások növelik a késői cardiovascularis megbetegedések előfordulását. Ezért különösen fontos a szív sugárterheléssel szembeni védelme. Módszer: 45 bal oldali emlődaganatos beteg besugárzási tervét készítettük el mély belégzéses és normál légzéses technika alkalmazásával. Az elkészült terveket összehasonlítottuk, elemeztük. A besugárzási tervek a Philips Pinnacle v. 16 tervezőrendszerben készültek. Eredmények: Azonos céltérfogat-lefedettség mellett a mély belégzéses technika alkalmazása a szív és a bal elülső leszálló coronariaág dózisterhelésének csökkenéséhez vezet, mérsékelve így a késői cardiovascularis szövődmények előfordulását. Megbeszélés: A kapott eredmények azt mutatják, hogy a mély belégzéses technika alkalmazása bal oldali emlődaganatos betegek adjuváns sugárkezelése során kedvezően hat a szív sugárterhelésére. Eredményeink jól illeszkednek a hazai centrumok hasonló adataihoz. A céltérfogat lefedettségét nemcsak, hogy meg tudtuk őrizni, hanem még 1%-os javulást is sikerült elérni. Szignifikáns különbség a szívet és a coronariát ért dózisban van. Mély belégzéses technikával közel a felére sikerült csökkenteni az átlagszívdózist (mély belégzés: 2,87 Gy, normállégzés: 5,4 Gy). A coronaria sugárterhelését 19,5 Gy-ről 10,98 Gy-re redukáltuk. Következtetés: A kezelés pontossága légzéskapuzó rendszerrel, felületvezérelt sugárterápiás rendszerrel tovább javítható. A mély belégzéses technika sikeres alkalmazásához szükséges a kezelőszemélyzet szakmai felkészültsége, a beteg jó kooperációja. Kevésbé eszközigényes, mint a légzésvezérelt rendszer. A mély belégzéses technika már nem számít a legkorszerűbb módszernek a légzéskapuzás korában, mégis érdemesnek tartottuk ismertetni az osztályunkon szerzett tapasztalatokat onkokardiológiai aktualitásuk miatt

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI)

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice

Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI)

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient’s activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm(2)/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens)