Чутливість рецепторів клітин ендометрію до естрогенів та прогестерону у корів хворих на субклінічний ендометрит

Pathological processes that strongly affect the uterine endometrium lead to infertility and abortion. The most common of these pathologies are clinical and subclinical endometritis. Subclinical endometritis is characterized by endometrial inflammation in the absence of clinical signs of endometritis. In this study, we used uterine samples obtained from Ukrainian black-and-white dairy cows aged 4 to 7 years to compare the histology of the uterine endometrium and changes in estrogen-α (ER-α), estrogen-β (ER-β) and progesterone (PgR) nuclear receptor sensitivity in cows with subclinical endometritis. Cows were separated based on cytological examination of the endometrium into a healthy group, or those presenting with subclinical endometritis. From these groups endometrial and epithelial tissue samples were obtained using biopsy forceps and an endoscope then analyzed using immunohistochemistry. Our results demonstrate that the sensitivity of ER-α and ER-β is lower while PgR sensitivity is elevated in cows with subclinical endometritis compared to the healthy control group. Additionally, we observed markedly altered histological changes characterized by enlargement of uterine glands, epithelial desquamation, and infiltration of leukocytes. These results suggest that there are significant changes in the endometrium linked to the sensitivity of nuclear steroid hormone receptors that may also play an immunoregulatory role in cows with subclinical endometriosis. While the interaction of steroid hormones and immunoregulation in the uterus remains to be elucidated, it may provide key insights into the uterine immune response.В основі патологічних процесів, що проходять у матці приводять до неплідності та абортів, важливу роль відіграє ендометрій. Найбільш поширеними патологіями, що проходять у матці є клінічний та субклінічний ендометрит. Субклінічний ендометрит характеризується запальним процесом у ендометрії без клінічних ознак. Метою нашої роботи було проаналізувати гістологічні зміни та зміни чутливості ендометрію матки до естроген-α (ER-α), естроген-β (ER-β) та прогестерону (PgR), що відбуваються у матці здорових корів та у корів за субклінічного ендометриту. Дослідження проводилось на двох групах корів української чорно-рябої молочної породи віком від 4 до 7 років. На основі цитологічного дослідження ендометрію, корови були поділені на дві групи. Контрольну групу (К), що включала клінічно здорових корів, та дослідну (Д), що включала корів хворих на субклінічний ендометрит. Надалі проводили забір зразків за допомогою біопсійних щипців та ендоскопу. Наші результати дають змогу більш глибоко зрозуміти процеси, що відбуваються у ендометрії корів хворих на субклінічний ендометрит. Активність рецепторів ядер ER-α, ER-β та PgR спостерігали у епітелії ендометрію, епітелії маткових залоз та стромі ендометрію. Активність рецепторів ядер ER-α та ER-β була нижчою у корів з субклінічним ендометритом, ніж у корів контрольної групи. Активність рецепторів ядер PgR була вищою у корів хворих на субклінічний ендометрит, ніж у корів контрольної групи. На основі отриманих даних встановлено, що ендометрій хворих на субклінінчий ендометрит зазнає значних змін, що характеризується появою лейкоцитів, розширенням маткових залоз та ділянками десквамації епітелію. Зміни відбуваються на основі чутливості ядер ендометрію до рецепторів ER-α, ER-β та PgR. Чутливість ендометрію до гормонів є важливою у локальному захисті матки. В перспективі подальших досліджень слід вивчити експресію стероїдних гормонів та цитокінів у корів хворих на субклінічний ендометрит

Опыт применения золадекса у больных эндометриозом и рецидивирующими гиперпластическими процессами эндометрия

ЭНДОМЕТРИОЗ /ЛЕК ТЕРЭНДОМЕТРИЯ ГИПЕРПЛАЗИЯ /ЛЕК ТЕРЗОЛАДЕК

In vitro selectivity, in vivo biodistribution and tumour uptake of annexin V radiolabelled with a positron emitting radioisotope

The availability of a noninvasive method to detect and quantify apoptosis in tumours will enable tumour response to several cancer therapies to be assessed. We have synthesised two radiotracers, annexin V and the N-succinimidyl-3-iodobenzoic acid (SIB) derivative of annexin V, labelled with radio-iodine (124I and 125I) and provided proof of the concept by assessing specific binding and biodistribution of these probes to apoptotic cells and tumours. We have also assessed the tumour uptake of [124I]annexin V in a mouse model of apoptosis. RIF-1 cells induced to undergo apoptosis in vitro showed a drug concentration-dependent increased binding of [125I]annexin V and [125I]SIB–annexin V. In the same model system, there was an increase in terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL)-positive cells and a decrease in clonogenic survival. Radiotracer binding was completely inhibited by preincubation with unlabelled annexin V. In RIF-1 tumour-bearing mice, rapid distribution of [125I]SIB–annexin V-derived radioactivity to kidneys was observed and the radiotracer accumulated in urine. The binding of [125I]SIB–annexin V to RIF-1 tumours increased by 2.3-fold at 48 h after a single intraperitoneal injection of 5-fluorouracil (165 mg kg−1 body weight), compared to a 4.4-fold increase in TUNEL-positive cells measured by immunostaining. Positron emission tomography images with both radiotracers demonstrated intense localisation in the kidneys and bladder. Unlike [124I]SIB–annexin V, [124I]annexin V also showed localisation in the thyroid region presumably due to deiodination of the radiolabel. [124I]SIB–annexin V is an attractive candidate for in vivo imaging of apoptosis by PET

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Using global team science to identify genetic parkinson's disease worldwide.

No abstract available

Towards smart online coffee roasting process control: Feasibility of real-time. prediction of coffee roast degree and brew antioxidant capacity by single-photon ionization mass spectrometric monitoring of roast gases.

Precise controlling and monitoring the status of the coffee roasting process is essential for consistent product quality and optimization toward targeted coffee properties. In small-scale roasting experiments, the chemical composition of the roasting offgas was analyzed by online single-photon ionization time-of-flight mass spectrometry (SPI-TOFMS) at 118 nm with 5 s time resolution. Subsequently, mass spectra at the drop of the coffee beans were combined with off-line measurements of roast degree, described by color value "Colorette", and the antioxidant capacity, obtained from the Folin-Ciocalteu (FC) assay, in an explanatory projection on latent structure regression model. While the roast degree gives an indication of the coffee flavor, antioxidants in brewed coffee are regarded as beneficial for human health. Colorette and FC values could be derived from the SPI mass spectra with root-mean-square errors from Monte Carlo cross-validation of 6.0 and 139 mg of gallic acid equiv L-1, respectively, and explained covariance (R-2(CV)) better than 89%. Finally, the regression models were applied to the SPI mass spectra over the entire roast to demonstrate the predictive ability for online process control in real time

Smart online coffee roasting process control: Modelling coffee roast degree and brew antioxidant capacity for real-time prediction by resonance-enhanced multi-photon ionization mass spectrometric (REMPI-TOFMS) monitoring of roast gases.

Process control with high time resolution is essential to maintain high product quality in coffee roasting. However, analytical techniques for quality assurance or measurements of desired coffee properties are often labor-intensive and can only be conducted after dropping the coffee beans. Resonance-enhanced multi-photon ionization time-of-flight mass spectrometry (REMPI-TOFMS) at 248 nm and 266 nm was applied to analyze the composition of the roast gas from small-scale Arabica coffee roasting. Coffee beans were dropped after different roasting times, ground and analyzed by Colorette to obtain the roast degree. Additionally, the antioxidant capacity of the coffee brew was determined by Folin-Ciocalteu (FC) assay. Models for the prediction of Colorette and FC values from REMPI mass spectra were constructed by partial least squares (PLS) regression. REMPI-TOFMS enables the prediction of Colorette values with a root-mean-square error in prediction (RMSEP) below 5 for both wavelengths. FC values could be predicted using REMPI at 248 nm with an RMSE(P)of 80.3 gallic acid equivalents (GA-eq) mg L-1, while REMPI at 266 nm resulted in RMSE(P)of 151 GA-eq mg L-1. Finally, the prediction of Colorette and FC value at 5 s time resolution were demonstrated with online measurements

Simultaneous on-line vacuum single- and multi-photon ionization on an orthogonal acceleration time-of-flight mass spectrometer platform.

The development of orthogonal acceleration time-of-flight (oa-tof) technology is driven forward due to higher mass accuracy and resolving power than conventional linear/reflectron tof instruments. This is achieved with a more accurate definition of starting energies and coordinates of ions by spatial separation of ion generation and orthogonal ion extraction. Consequently, the ability to cover the whole mass spectral range without scanning is not given anymore. Therefore, continuous ion sources are favored for ensuring high duty cycles and thus high temporal resolution. For pulsed ion sources, high repetition rates are mandatory for covering large m/z ranges without losing their high temporal resolution. We have combined an oa-tof with deuterium lamp single-photon ionization (SPI) as a continuous ion source together with a pulsed 2000 Hz excimer (KrF) laser for resonance enhanced multi-photon ionization (REMPI). These two ionization techniques can be used simultaneously. To the best of our knowledge, this system is the first of its kind in combining a vacuum pulsed ionization source with an oa-tof instrument without any other ion storage hardware. The combination of a soft broadband ionization for organics (SPI) in combination with a very sensitive and selective soft ionization (REMPI) can be used for covering the whole mass range or in targeted on-line monitoring cases one or several smaller mass ranges. To demonstrate the simultaneous SPI/REMPI-oa-tof technique, two applicative areas are explored: on-line monitoring of coffee roast gas emissions and e-cigarette vapor. The complementary information from SPI and REMPI signals are combined in a way to exploit the advantages of both ionization types. In a further development step, a second data acquisition card is built into the system. This modification allows the independent storage of data from both ionization methods without mixing. For demonstration, a third example with a GC measurement is provided. The last example shows the possibility of modified sensitivities for different mass regions in REMPI data acquisition without affecting the SPI channel. The newly developed system shows high robustness in terms of measurements in real industrial environments. The simultaneous measurement technique provides a higher density of information in a single measurement, saving time and resources

Position paper on requirements for toxicological studies in the specific case of radiopharmaceuticals

Abstract This is a position paper of the Radiopharmacy Committee of the EANM (European Association of Nuclear Medicine) addressing toxicology studies for application of new diagnostic and therapeutic radiopharmaceuticals (RP) that are not approved (i.e., not having a marketing authorization or a monograph in the European Pharmacopoeia), excluding endogenous and ubiquitous substances in humans. This paper discusses the requirements for clinical trials with radiopharmaceuticals for clinical research applications, not necessarily intended to aim at a marketing authorization. If marketing authorization is intended, scientific advice of the competent authorities is mandatory and cannot be replaced by this position paper. The position paper reflects the view of the Radiopharmacy Committee of the EANM and can be used as a basis for discussions with the responsible authorities