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1.
PLoS Biol ; 21(7): e3002168, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37410722

ABSTRACT

We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we first tracked whisker tips in anesthetized rats under low (0.5 m/s) and high (1.5 m/s) airflow. Whisker tips showed increasing movement from low to high airflow conditions, with all whisker tips moving during high airflow. Low airflow conditions-most similar to naturally occurring wind stimuli-engaged whisker tips differentially. Most whiskers moved little, but the long supra-orbital (lSO) whisker showed maximal displacement, followed by the α, ß, and A1 whiskers. The lSO whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted lSO whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography (micro-CT) revealed that the ring-wulst-the follicle structure receiving the most sensitive afferents-was more complete/closed in the lSO, and other wind-sensitive whiskers, than in non-wind-sensitive whiskers, suggesting specialization of the supra-orbital for omni-directional sensing. We localized and targeted the cortical supra-orbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supra-orbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supra-orbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supra-orbital whiskers act as wind antennae.


Subject(s)
Somatosensory Cortex , Vibrissae , Rats , Animals , Vibrissae/physiology , X-Ray Microtomography , Somatosensory Cortex/physiology , Physical Stimulation , Movement/physiology , Mammals
2.
Biotechnol Bioeng ; 121(6): 1961-1972, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38555480

ABSTRACT

Oxygen is essential for tissue regeneration, playing a crucial role in several processes, including cell metabolism and immune response. Therefore, the delivery of oxygen to wounds is an active field of research, and recent studies have highlighted the potential use of photosynthetic biomaterials as alternative oxygenation approach. However, while plants have traditionally been used to enhance tissue regeneration, their potential to produce and deliver local oxygen to wounds has not yet been explored. Hence, in this work we studied the oxygen-releasing capacity of Marchantia polymorpha explants, showing their capacity to release oxygen under different illumination settings and temperatures. Moreover, co-culture experiments revealed that the presence of these explants had no adverse effects on the viability and morphology of fibroblasts in vitro, nor on the viability of zebrafish larvae in vivo. Furthermore, oxygraphy assays demonstrate that these explants could fulfill the oxygen metabolic requirements of zebrafish larvae and freshly isolated skin biopsies ex vivo. Finally, the biocompatibility of explants was confirmed through a human skin irritation test conducted in healthy volunteers following the ISO-10993-10-2010. This proof-of-concept study provides valuable scientific insights, proposing the potential use of freshly isolated plants as biocompatible low-cost oxygen delivery systems for wound healing and tissue regeneration.


Subject(s)
Bandages , Oxygen , Photosynthesis , Zebrafish , Animals , Oxygen/metabolism , Proof of Concept Study , Humans , Wound Healing/drug effects , Skin/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism
3.
Phys Chem Chem Phys ; 26(17): 13489-13496, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38651219

ABSTRACT

The photoinduced cycloreversion of oxetane derivatives is of considerable biological interest since these compounds are involved in the photochemical formation and repair of the highly mutagenic pyrimidine (6-4) pyrimidone DNA photoproducts ((6-4)PPs). Previous reports have dealt with the photoreactivity of heterodimeric oxetanes composed mainly of benzophenone (BP) and thymine (Thy) or uracil (Ura) derivatives. However, these models are far from the non-isolable Thy〈ºã€‰Thy dimers, which are the real precursors of (6-4)PPs. Thus, we have synthesized two chemically stable homodimeric oxetanes through the Paternò-Büchi reaction between two identical enone units, i.e. 1,4-benzoquinone (BQ) and 1,4-naphthoquinone (NQ), that led to formation of BQ-Ox and NQ-Ox, respectively. Their photoreactivity has been studied by means of steady-state photolysis and transient absorption spectroscopy from the femtosecond to the microsecond time scale. Thus, photolysis of BQ-Ox and NQ-Ox led to formation of the monomeric BQ or NQ, respectively, through ring opening in a "non-adiabatic" process. Accordingly, the transient absorption spectra of the triplet excited quinones (3BQ* and 3NQ*) were not observed as a result of direct photolysis of the quinone-derived oxetanes. In the case of NQ-Ox, a minor signal corresponding to 3NQ* was detected; its formation was ascribed to minor photodegradation of the oxetane during acquisitions of the spectra during the laser experiments. These results are supported by computational analyses based on density functional theory and multiconfigurational quantum chemistry (CASSCF/CASPT2); here, an accessible conical intersection between the ground and excited singlet states has been characterized as the main structure leading to deactivation of excited BQ-Ox or NQ-Ox. This behavior contrasts with those previously observed for heterodimeric thymine-derived oxetanes, where a certain degree of ring opening into the excited triplet state is observed.

4.
Neurol Sci ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472552

ABSTRACT

Neurolymphomatosis (NL) describes an infiltration of cranial and peripheral nerves by lymphoma cells, most frequently in non-Hodgkin B-cell lymphoma. This clinical entity is rare and poses a challenging diagnosis. We describe a case of a 64-year-old female patient with NL associated with extra-nodal NK/T-cell lymphoma (ENKTL), nasal type, presenting as a painful progressive mononeuropathy multiplex with an oral cavity lesion. ENKTL is usually associated with Epstein-Barr virus (EBV) infection and rarely affects the central and peripheral nervous system. Lumbar puncture, magnetic resonance imaging (MRI), nerve biopsy, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) help to establish the diagnosis. Thereby, NL should be considered in the differential diagnosis of painful progressive multiple neuropathies, even in patients without previous history of cancer.

5.
Int J Clin Oncol ; 29(6): 780-789, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38528295

ABSTRACT

PURPOSE: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US). METHODS: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported. RESULTS: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50-66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8-13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0-9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively. CONCLUSION: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.


Subject(s)
Ado-Trastuzumab Emtansine , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Aged , United States , Trastuzumab/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ado-Trastuzumab Emtansine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Neoplasm Metastasis , Progression-Free Survival , Treatment Outcome , Camptothecin/analogs & derivatives , Immunoconjugates
6.
Euro Surveill ; 29(14)2024 Apr.
Article in English | MEDLINE | ID: mdl-38577804

ABSTRACT

In February 2023, German public health authorities reported two dengue cases (one confirmed, one probable) and four possible cases who travelled to Ibiza, Spain, in late summer/autumn 2022; the infection was probably acquired through mosquito bites. Case 1 visited Ibiza over 1 week in late August with two familial companions; all three developed symptoms the day after returning home. Only Case 1 was tested; dengue virus (DENV) infection was confirmed by presence of NS1 antigen and IgM antibodies. Case 2 travelled to Ibiza with two familial companions for 1 week in early October, and stayed in the same town as Case 1. Case 2 showed symptoms on the day of return, and the familial companions 1 day before and 3 days after return; Case 2 tested positive for DENV IgM. The most probable source case had symptom onset in mid-August, and travelled to a dengue-endemic country prior to a stay in the same municipality of Ibiza for 20 days, until the end of August. Dengue diagnosis was probable based on positive DENV IgM. Aedes albopictus, a competent vector for dengue, has been present in Ibiza since 2014. This is the first report of a local dengue transmission event on Ibiza.


Subject(s)
Aedes , Dengue Virus , Dengue , Animals , Humans , Dengue/diagnosis , Dengue/epidemiology , Dengue Virus/genetics , Spain/epidemiology , Mosquito Vectors , Disease Outbreaks , Immunoglobulin M
7.
J Neurosci ; 42(44): 8252-8261, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36113990

ABSTRACT

The identity and location of vocalization pattern generating (VPG) circuits in mammals is debated. Based on physiological experiments, investigators suggested anterior brainstem circuits in the reticular formation, and anatomic evidence suggested the nucleus retroambiguus (NRA) in the posterior brainstem, or combinations of these sites as the putative mammalian VPG. Additionally, vocalization loudness is a critical factor in acoustic communication. However, many of the underlying neuronal mechanisms are still unknown. Here, we evoked calls by stimulation of the periaqueductal gray in anesthetized male rats, performed a large-scale mapping of vocalization-related activity using the activity marker c-fos, and high-density recordings of brainstem circuits using Neuropixels probes. Both c-fos expression and recording of vocalization-related activity point to a participation of the NRA in vocalization. More important, among our recorded structures, we found that the NRA is the only brainstem area showing a strong correlation between unit activity and call intensity. In addition, we observed functionally diverse patterns of vocalization-related activity in a set of regions around NRA. Dorsal to NRA, we observed activity specific to the beginning and end of vocalizations in the posterior level of the medullary reticular nucleus, dorsal part, whereas medial and lateral to the NRA, we observed activity related to call initiation. No clear vocalization-related activity was observed at anterior brainstem sites. Our findings suggest a set of functionally heterogeneous regions around the NRA contribute to vocal pattern generation in rats.SIGNIFICANCE STATEMENT Vocalization patterns are shaped in the mammalian brainstem, but the identity and location of the circuits involved is debated. Additionally, the neuronal mechanisms of vocal intensity control are still unknown. This study consisted of a large-scale mapping of brainstem vocalization circuits based on the activity marker c-fos and high-density recordings with Neuropixels probes. The results confirm the role of nucleus retroambiguus in call production and point to a key role of neurons in this nucleus in loudness control. Dorsal to the nucleus retroambiguus and in the posterior medulla, the authors identify neurons with activity specific to the beginning and end of vocalizations. The results point to specific neural dials for various aspects of rat vocalization control in the posterior brainstem.


Subject(s)
Brain Stem , Vocalization, Animal , Rats , Male , Animals , Vocalization, Animal/physiology , Brain Stem/physiology , Medulla Oblongata/physiology , Periaqueductal Gray/physiology , Reticular Formation , Mammals
8.
Opt Lett ; 48(20): 5431-5434, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37831885

ABSTRACT

We propose a single-shot, high-repetition rate measurement scheme of the carrier-envelope phase offset of ultrashort laser pulses. The spectral fringes resulting from f-2f nonlinear interferometry, encoding the carrier-envelope-phase, are evaluated completely optically via an optical Fourier transform. For demonstration, the carrier-envelope-phase of a 200 kHz, few-cycle optical parametric chirped-pulse amplification (OPCPA) laser system was measured employing an interferometer as a periodic optical filter. The proposed method shows excellent agreement with simultaneous measurement of the spectral fringes by a fast line-scan camera.

9.
J Org Chem ; 88(14): 10111-10121, 2023 07 21.
Article in English | MEDLINE | ID: mdl-37437138

ABSTRACT

The quest for simple systems achieving the photoreductive splitting of four-membered ring compounds is a matter of interest not only in organic chemistry but also in biochemistry to mimic the activity of DNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidatively generated lesion of guanine, has been shown to act as an intrinsic photoreductant by transferring an electron to bipyrimidine lesions and provoking their cycloreversion. But, in spite of appropriate photoredox properties, the capacity of guanine to repair cyclobutane pyrimidine dimer is not clearly established. Here, dyads containing the cyclobutane thymine dimer and guanine or 8-oxoguanine are synthesized, and their photoreactivities are compared. In both cases, the splitting of the ring takes place, leading to the formation of thymine, with a quantum yield 3.5 times lower than that for the guanine derivative. This result is in agreement with the more favored thermodynamics determined for the oxidized lesion. In addition, quantum chemistry calculations and molecular dynamics simulations are carried out to rationalize the crucial aspects of the overall cyclobutane thymine dimer photoreductive repair triggered by the nucleobase and its main lesion.


Subject(s)
Cyclobutanes , Pyrimidine Dimers , Pyrimidine Dimers/chemistry , Thymine/chemistry , DNA/chemistry , Guanine
10.
Phys Chem Chem Phys ; 25(23): 16148-16156, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37279011

ABSTRACT

The interaction dynamics between flurbiprofen (FBP) and tryptophan (Trp) has been studied in covalently linked dyads and within human serum albumin (HSA) by means of fluorescence and ultrafast transient absorption spectroscopy. The dyads have proven to be excellent models to investigate photoinduced processes such as energy and/or electron transfer that may occur in proteins and other biological media. Since the relative spatial arrangement of the interacting units may affect the yield and kinetics of the photoinduced processes, two spacers consisting of amino and carboxylic groups separated by a cyclic or a long linear hydrocarbon chain (1 and 2, respectively) have been used to link the (S)- or (R)-FBP with the (S)-Trp moieties. The main feature observed in the dyads was a strong intramolecular quenching of the fluorescence, which was more important for the (S,S)- than for the (R,S)- diastereomer in dyads 1, whereas the reverse was true for dyads 2. This was consistent with the results obtained by simple molecular modelling (PM3). The observed stereodifferentiation in (S,S)-1 and (R,S)-1 arises from the deactivation of 1Trp*, while in (S,S)-2 and (R,S)-2 it is associated with 1FBP*. The mechanistic nature of 1FBP* quenching is ascribed to energy transfer, while for 1Trp* it is attributed to electron transfer and/or exciplex formation. These results are consistent with those obtained by ultrafast transient absorption spectroscopy, where 1FBP* was detected as a band with a maximum at ca. 425 nm and a shoulder at ∼375 nm, whereas Trp did not give rise to any noticeable transient. Interestingly, similar photoprocesses were observed in the dyads and in the supramolecular FBP@HSA complexes. Overall, these results may aid to gain a deeper understanding of the photoinduced processes occurring in protein-bound drugs, which may shed light on the mechanistic pathways involved in photobiological damage.


Subject(s)
Flurbiprofen , Humans , Flurbiprofen/chemistry , Flurbiprofen/metabolism , Tryptophan/chemistry , Serum Albumin, Human , Models, Molecular
11.
Med Vet Entomol ; 37(4): 871-877, 2023 12.
Article in English | MEDLINE | ID: mdl-37458405

ABSTRACT

Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of pathogens that affect wildlife and livestock. Understanding the composition and distribution of vector species is crucial for implementing control strategies and preventing the spread of infectious diseases. This study provides a morphological and molecular characterisation of Culicoides caucoliberensis, which represents the first record for Spain, increasing the number of Culicoides species in the country to 85. A total of 213 specimens were collected using Onderstepoort-ultraviolet down-draught light traps on a rocky coastline in the Balearic Islands during two sampling periods in 2022. Phylogenetic analysis showed that C. caucoliberensis forms a monophyletic cluster within the Maritimus group. Host preferences were determined for the first time and showed propensity to feed on the European shag (Phalacrocorax aristotelis). The vector role of C. caucoliberensis for haemosporidian transmission remains unclear since molecular detection of Haemosporidians (Haemoproteus and Plasmodium) was negative for all the pools of parous and engorged females analysed. This study emphasises the importance of conducting entomofauna studies in lesser-known Mediterranean islet landscapes and highlights the need for research on vectors within the One Health framework.


Subject(s)
Ceratopogonidae , Haemosporida , Parasites , Female , Animals , Phylogeny , Spain , Insect Vectors/parasitology , Birds/parasitology , Feeding Behavior
12.
Bull Entomol Res ; 113(3): 402-411, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36908249

ABSTRACT

Culicoides biting midges (Diptera: Ceratopogonidae) are the main vectors of livestock diseases such as bluetongue (BT) which mainly affect sheep and cattle. In Spain, bluetongue virus (BTV) is transmitted by several Culicoides taxa, including Culicoides imicola, Obsoletus complex, Culicoides newsteadi and Culicoides pulicaris that vary in seasonality and distribution, affecting the distribution and dynamics of BT outbreaks. Path analysis is useful for separating direct and indirect, biotic and abiotic determinants of species' population performance and is ideal for understanding the sensitivity of adult Culicoides dynamics to multiple environmental drivers. Start, end of season and length of overwintering of adult Culicoides were analysed across 329 sites in Spain sampled from 2005 to 2010 during the National Entomosurveillance Program for BTV with path analysis, to determine the direct and indirect effects of land use, climate and host factor variables. Culicoides taxa had species-specific responses to environmental variables. While the seasonality of adult C. imicola was strongly affected by topography, temperature, cover of agro-forestry and sclerophyllous vegetation, rainfall, livestock density, photoperiod in autumn and the abundance of Culicoides females, Obsoletus complex species seasonality was affected by land-use variables such as cover of natural grassland and broad-leaved forest. Culicoides female abundance was the most explanatory variable for the seasonality of C. newsteadi, while C. pulicaris showed that temperature during winter and the photoperiod in November had a strong effect on the start of the season and the length of overwinter period of this species. These results indicate that the seasonal vector-free period (SVFP) in Spain will vary between competent vector taxa and geographic locations, dependent on the different responses of each taxa to environmental conditions.


Subject(s)
Bluetongue virus , Bluetongue , Cattle Diseases , Ceratopogonidae , Sheep Diseases , Cattle , Female , Sheep , Animals , Ceratopogonidae/physiology , Spain , Insect Vectors/physiology , Climate , Seasons , Bluetongue/epidemiology , Bluetongue virus/physiology , Cattle Diseases/epidemiology
13.
Proc Natl Acad Sci U S A ; 117(20): 10727-10732, 2020 May 19.
Article in English | MEDLINE | ID: mdl-32354996

ABSTRACT

When small quantum systems, atoms or molecules, absorb a high-energy photon, electrons are emitted with a well-defined energy and a highly symmetric angular distribution, ruled by energy quantization and parity conservation. These rules are based on approximations and symmetries which may break down when atoms are exposed to ultrashort and intense optical pulses. This raises the question of their universality for the simplest case of the photoelectric effect. Here we investigate photoionization of helium by a sequence of attosecond pulses in the presence of a weak infrared laser field. We continuously control the energy of the photoelectrons and introduce an asymmetry in their emission direction, at variance with the idealized rules mentioned above. This control, made possible by the extreme temporal confinement of the light-matter interaction, opens a road in attosecond science, namely, the manipulation of ultrafast processes with a tailored sequence of attosecond pulses.

14.
Int J Mol Sci ; 24(9)2023 May 07.
Article in English | MEDLINE | ID: mdl-37176111

ABSTRACT

Renal cell carcinoma (RCC) presents as metastatic disease in one third of cases. Research on circulating tumor cells (CTCs) and liquid biopsies is improving the understanding of RCC biology and metastases formation. However, a standardized, sensitive, specific, and cost-effective CTC detection technique is lacking. The use of platforms solely relying on epithelial markers is inappropriate in RCC due to the frequent epithelial-mesenchymal transition that CTCs undergo. This study aimed to test and clinically validate RUBYchip™, a microfluidic label-free CTC detection platform, in RCC patients. The average CTC capture efficiency of the device was 74.9% in spiking experiments using three different RCC cell lines. Clinical validation was performed in a cohort of 18 patients, eight non-metastatic (M0), five metastatic treatment-naïve (M1TN), and five metastatic progressing-under-treatment (M1TP). An average CTC detection rate of 77.8% was found and the average (range) total CTC count was 6.4 (0-27), 101.8 (0-255), and 3.2 (0-10), and the average mesenchymal CTC count (both single and clustered cells) was zero, 97.6 (0-255), and 0.2 (0-1) for M0, M1TN, and M1TP, respectively. CTC clusters were detected in 25% and 60% of M0 and M1TN patients, respectively. These results show that RUBYchip™ is an effective CTC detection platform in RCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplastic Cells, Circulating , Humans , Neoplastic Cells, Circulating/pathology , Microfluidics , Cell Line , Kidney Neoplasms/pathology , Biomarkers, Tumor/metabolism
15.
Opt Express ; 30(15): 27938-27950, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236952

ABSTRACT

We present an experimental method capable of capturing the complete spatio-temporal dynamics of filamenting ultrashort laser pulses. By employing spatially resolved Fourier transform spectrometry in combination with the capability to terminate the filament at any length, we can follow the nonlinear dynamics in four dimensions, i.e. the transverse domain, time and filament length. Our method thus not only enables the full characterization of the filamentation process throughout its evolution, but also allows to identify and select laser pulses with desired parameters.

16.
Opt Express ; 30(16): 29044-29062, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36299089

ABSTRACT

Temporally coherent supercontinuum sources constitute an attractive alternative to bulk crystal-based sources of few-cycle light pulses. We present a monolithic fiber-optic configuration for generating transform-limited temporally coherent supercontinuum pulses with central wavelength at 1.06 µm and duration as short as 13.0 fs (3.7 optical cycles). The supercontinuum is generated by the action of self-phase modulation and optical wave breaking when pumping an all-normal dispersion photonic crystal fiber with pulses of hundreds of fs duration produced by all-fiber chirped pulsed amplification. Avoidance of free-space propagation between stages confers unequalled robustness, efficiency and cost-effectiveness to this novel configuration. Collectively, the features of all-fiber few-cycle pulsed sources make them powerful tools for applications benefitting from the ultrabroadband spectra and ultrashort pulse durations. Here we exploit these features and the deep penetration of light in biological tissues at the spectral region of 1 µm, to demonstrate their successful performance in ultrabroadband multispectral and multimodal nonlinear microscopy.

17.
J Org Chem ; 87(17): 11433-11442, 2022 09 02.
Article in English | MEDLINE | ID: mdl-35980822

ABSTRACT

Photosensitized thymine<>thymine (Thy<>Thy) formation and repair can be mediated by carbazole (Cbz). The former occurs from the Cbz triplet excited state via energy transfer, while the latter takes place from the singlet excited state via electron transfer. Here, fundamental insight is provided into the role of the topology and excited state multiplicity, as factors governing the balance between both processes. This has been achieved upon designing and synthesizing different isomers of trifunctional systems containing one Cbz and two Thy units covalently linked to the rigid skeleton of the natural deoxycholic acid. The results shown here prove that the Cbz photosensitized dimerization is not counterbalanced by repair when the latter, instead of operating through-space, has to proceed through-bond.


Subject(s)
Carbazoles , Thymine , Carbazoles/chemistry , Dimerization , Energy Transfer , Thymine/chemistry
18.
Neurol Sci ; 43(4): 2891-2893, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35075576

ABSTRACT

Giant cerebral aneurysms account for approximately 5% of all intracranial aneurysms, affecting morecommonly women in the 5th to 7th decade. When untreated, giant intracranial aneurysms face a poor prognosis withan estimated 2-year mortality of 68%. We present the case of an 82-year-old woman admitted at the emergencydepartment due to two focal to bilateral tonic-clonic seizures with a giant aneurysm of the supraclinoid segment ofthe right internal carotid artery on the CT scan. We discuss different management approaches for giant internalcarotid artery aneurysms, including direct surgical clipping, reconstructive endovascular procedures (coiling, balloon-/stent-assisted coiling, and flow diversion), deconstructive endovascular techniques (parent artery occlusion), andconservative management.


Subject(s)
Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Aged, 80 and over , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Female , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Treatment Outcome
19.
Molecules ; 27(4)2022 Feb 12.
Article in English | MEDLINE | ID: mdl-35209033

ABSTRACT

Mitochondria-targeting drugs and diagnostics are used in the monitoring and treatment of mitochondrial pathologies. In this respect, a great number of functional compounds have been made mitotropic by covalently attaching the active moiety onto a triphenylphosphonium (TPP) cation. Among these compounds, a number of molecular detectors for reactive oxygen species (ROS) are based on fluorescent and chemiluminescent probes. In this regard, luminol (probably the most widely known chemiluminescent molecule) has been employed for a number of biological applications, including ROS detection. Its oxidation under specific conditions triggers a cascade of reactions, ultimately leading to the excited 3-aminophthalate (3AP *), which emits light upon deactivation. Hence, the photophysical interaction between the light-emitting species 3AP * and TPP cations needs to be evaluated, as it can add valuable information on the design of novel emission-based mitotropic systems. We herein investigate the quenching effect of ethyltriphenylphosphonium cation onto substituted 3-aminophthalates. These were prepared in situ upon hydrolysis of the corresponding anhydrides, which were synthesized from 3-aminophthalimides. Steady-state fluorescence and time-resolved experiments were employed for the evaluation of a possible electron transfer quenching by phosphonium ions. Our experimental results confirmed such quenching, suggesting it is mainly dynamic in nature. A minor contribution of static quenching that was also detected is attributed to complex formation in the ground state. Accordingly, the chemiluminescence of luminol was indeed strongly reduced in the presence of phosphonium ions. Our results have to be taken into account during the design of new chemiluminescent mitotropic drugs or diagnostic agents of the luminol family.


Subject(s)
Luminescent Measurements , Luminol/chemistry , Organophosphorus Compounds/chemistry , Reactive Oxygen Species/chemistry , Mitochondria/chemistry
20.
J Org Chem ; 86(17): 11388-11398, 2021 09 03.
Article in English | MEDLINE | ID: mdl-34350754

ABSTRACT

Luminol is a prominent chemiluminescent (CL) agent, finding applications across numerous fields, including forensics, immunoassays, and imaging. Different substitution patterns on the aromatic ring can enhance or decrease its CL efficiency. We herein report a systematic study on the synthesis and photophysics of all possible 6,8-disubstituted luminol derivatives bearing H, Ph, and/or Me substituents. Their CL responses are monitored at three pH values (8, 10, and 12), thus revealing the architecture with the optimum CL efficiency. The most efficient pattern is used for the synthesis of a strongly CL luminol derivative, bearing a functional group for further, straightforward derivatization. This adduct exhibits an unprecedented increase in chemiluminescence efficiency at pH = 12, pH = 10, and especially at pH = 8 (closer to the biologically relevant conditions) compared to luminol. Complementary work on the fluorescence of the emissive species as well as quantum chemistry computations are employed for the rationalization of the observed results.


Subject(s)
Luminescent Measurements , Luminol
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