Excretory Organs Research Articles

Histology, serum biochemistry and haematological profiles of Clarias gariepinus fed diets containing Luffa cylindrica seedmeal

Abstract. A 56-day feeding trial was conducted to evaluate the effect of processing time, inclusion level and/or their interactions on serum biochemistry, haematology and histology of the liver and kidney of Clarias gariepinus fed diets containing Luffa cylindrica seedmeal. The five formulated diets were designated as control (CTR) and tested, replaced at 15 and 30% by 5- and 10-min toasted Luffa cylindrica seedmeal (D515T, D530T, D1015T and D1030T). The experimental design followed a 2×2 factorial experiment in a completely randomised design; the processing time of 5- and 10-min toasting and inclusion level of 15 and 30% serves as factors. Triplicate groups of each treatment were made. Blood sampling, harvesting of organs, serum biochemistry, histology and haematological studies followed standard procedures. The results of the study showed that the effect of processing time, inclusion level and their interactions had significant impact (p<0.05) on Clarias gariepinus. A decrease in RBC, PCV and Hb was observed when compared with control for inclusion level, processing time and/or their interaction. Total protein, albumin and globulin of the blood of fish fed diet CTR was not significantly different (p>0.05) from that of the blood of the fish fed D1015T. Mild to moderate vacuolation of the hepatocytes were recorded among the livers of fish fed control and test dietary treatments except those fed D1030T that recorded very severe vacuolation of the hepatocytes. The kidney, being the excretory organ, was also affected. However, normal cell architecture was recorded in fish fed CTR, D530T and D1030T.

Evaluation of Renal Anionic Secretion Following Living-donor and Deceased-donor Renal Transplantation: A Clinical Pharmacokinetic Study of Cefoxitin Microdosing.

Background.Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs).Methods.The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation.Results.No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls.Conclusions.These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.

Protective Effect of Diosgenin on Streptozotocin Induced Diabetic Nephropathy in Experimental Rats

Diabetes mellitus is a multifactorial metabolic disorder associated with the diabetes related vascular diseases. Oxidative stress along with inflammation is the Key factor leading to diabetic complications. Present study was designed to investigate the protective role of diosgenin, a steroidal saponin, in diabetes induced early kidney injury and oxidative stress markers and histopathological changes in kidney of diabetic rats, induced by single intra-peritoneal injection of streptozotocin (55 mg/kg weight (b.w.). After 72 hrs, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for four weeks. At the end of the experiment, diabetic rats showed a significant increase in the levels of plasma glucose, glycosylated hemoglobin with a significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione, and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in kidney tissues of diabetic rats. Oral administration of diosgenin to diabetic rats considerably shrivelled the plasma glucose and exaggerated the endocrine level supported a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings recommend that diosgenin may have a helpful role against excretory organ harm evoked by aerobic stress within the diabetic state.

Multiomics Evaluation of Gastrointestinal and Other Clinical Characteristics of COVID-19

Since December 2019, coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced a worldwide panic. Beyond the principal human-to-human transmission method by droplet and contact, there is still limited knowledge about possible alternate transmission methods to guide clinical care. Recent clinical studies have observed digestive symptoms in patients with COVID-19,1 possibly because of the enrichment and infection of SARS-CoV-2 in the gastrointestinal tract, mediated by virus receptor of angiotensin converting enzyme 2 (ACE2),2 which suggests the potential for a fecal-oral route of SARS-CoV-2 transmission.3,4 However, there is still a large gap in the biological knowledge of COVID-19. In this study, via a bulk-to-cell strategy focusing on ACE2, we performed an integrated omics analysis at the genome, transcriptome, and proteome levels in bulk tissues and single cells across species to decipher the potential routes for SARS-CoV-2 infection in depth.

The Obstacles to Using Milk Composition as Management Tool in Dairy Cattle Farms

The main objective of this discussion highlights the use of milk composition data as a management tool. Milk composition, and in particular, milk fat content, milk protein content and the ratio of milk fat/protein may be significantly altered due to a variety of factors. The development of milk production in the world in the last 10 years reflects the enormous performance potential of the herds and the farms. However, there is a concomitant worsening of fertility and an increase in the number of animals that leave the herd due to metabolic disorders, infertility, hoof disease and mastitis. In order to reduce such losses, indicators are required that indicate a disease or the risk of a disease at an early stage. In addition to the kidney, the mammary gland is the most important excretory organ of the intermediately converted nutrients. for a range of nutrients, milk reflects the quality and/or quantity of these transformation processes, and thus milk is a medium with which we can prove the success of our feeding and recognize some important feeding and management errors. But this tool can never replace close monitoring of a herd by the farmer and appropriate veterinary care but may be used as an efficient alert system for preventing health disorders in cows. Further research based on larger data set even entire population of animals is necessary to confirm the results obtained in this study.

The noncanonical small heat shock protein HSP-17 from Caenorhabditis elegans is a selective protein aggregase

Small heat shock proteins (sHsps) are conserved, ubiquitous members of the proteostasis network. Canonically, they act as "holdases" and buffer unfolded or misfolded proteins against aggregation in an ATP-independent manner. Whereas bacteria and yeast each have only two sHsps in their genomes, this number is higher in metazoan genomes, suggesting a spatiotemporal and functional specialization in higher eukaryotes. Here, using recombinantly expressed and purified proteins, static light-scattering analysis, and disaggregation assays, we report that the noncanonical sHsp HSP-17 of Caenorhabditis elegans facilitates aggregation of model substrates, such as malate dehydrogenase (MDH), and inhibits disaggregation of luciferase in vitro Experiments with fluorescently tagged HSP-17 under the control of its endogenous promoter revealed that HSP-17 is expressed in the digestive and excretory organs, where its overexpression promotes the aggregation of polyQ proteins and of the endogenous kinase KIN-19. Systemic depletion of hsp-17 shortens C. elegans lifespan and severely reduces fecundity and survival upon prolonged heat stress. HSP-17 is an abundant protein exhibiting opposing chaperone activities on different substrates, indicating that it is a selective protein aggregase with physiological roles in development, digestion, and osmoregulation.

Do hair follicles operate as primitive, multifocal kidney-like excretory (mini-) organs?

Besides their many other functions, hair shafts (HS) also are a repository for potentially noxious compounds. These are neutralized by their deposition within terminally differentiated, avital epithelial cells (trichocytes) that also facilitate the interaction of potential toxins with melanin, a toxin-adsorbent biopolymer. Trichocytes are completely extruded via HS shedding during exogen, an actively controlled process. This underappreciated functional property of the human hair follicle (HF) makes it a bona fide excretory (mini-) organ. Here, we ask whether the ca. 2 million HFs of the human integument operate in part as primitive, spatially dispersed kidney-like excretory organs. Despite the many obvious differences between kidneys and HFs, this provocative hypothesis is also supported by other underappreciated renal-follicular similarities such as anatomical parallels between Bowman's capsule and the anagen hair bulb, renal podocytes and HF winged cells ["Fuegelzellen"], and hypoxia-dependent production of erythropoietin and extensive prostaglandin synthesis by human scalp HFs-just as in the kidney. The proposed kidney-like excretory function of HFs may have constituted a major selection advantage of mammals during evolution and could be clinically relevant. We explain how the many open questions (eg, how are molecules destined to be excreted by hair shaft entrapment recognized, taken up and deposited into hair matrix cells?) can be tested experimentally. Finally, we explore how the therapeutic targeting of kidney-like excretory HF functions may usefully complement classical nephrological therapy (dialysis) and ask whether stimulation of intrafollicular erythropoietin synthesis might become exploitable for the benefit of patients with renal anaemia.

Comparison between Apicystis cryptica sp. n. and Apicystis bombi (Arthrogregarida, Apicomplexa): Gregarine parasites that cause fat body hypertrophism in bees

The molecular divergence, morphology and pathology of a cryptic gregarine that is related to the bee parasite Apicystis bombi Lipa and Triggiani, 1996 is described. The 18S ribosomal DNA gene sequence of the new gregarine was equally dissimilar to that of A. bombi and the closest related genus Mattesia Naville, 1930, although phylogenetic analysis supported a closer relation to A. bombi. Pronounced divergence with A. bombi was found in the ITS1 sequence (69.6% similarity) and seven protein-coding genes (nucleotide 78.05% and protein 90.2% similarity). The new gregarine was isolated from a Bombus pascuorum Scopoli, 1763 female and caused heavy hypertrophism of the fat body tissue in its host. In addition, infected cells of the hypopharyngeal gland tissue, an important excretory organ of the host, were observed. Mature oocysts were navicular in shape and contained four sporozoites, similar to A. bombi oocysts. Given these characteristics, we proposed the name Apicystis cryptica sp. n. Detections so far indicated that distribution and host species occupation of Apicystis spp. overlap at least in Europe, and that historical detections could not discriminate between them. Specific molecular assays were developed that can be implemented in future pathogen screens that aim to discriminate Apicystis spp. in bees.

The demodex: the non-incriminated suspect of chronic blepharitis

We report the case of a 55-year-old patient, followed in ophthalmology for recurrent chronic blepharitis for 5 years. The ophthalmological examination found a 20/20 visual acuity in both eyes, conjunctival hyperemia, instability of the tear film with a BUT less than 5 seconds, as well as the presence of a crusting anterior blepharitis, mainly located at the level of the upper eyelid, with microscopic evidence of cylindrical dandruff at the base of the eyelashes, corresponding to demodex. The patient was treated for blepharitis, including multiday palpebral hygiene, based on palpebral massage by hot compresses and combinations of eye-drops and ointments based on antibiotics and corticosteroids, all associated with an additional treatment with artificial tears. Eye demodex is a common condition, but clinically under-diagnosed; demodex mites have been incriminated in the physiopathology of anterior blepharitis (D.folliculorum) and posterior blepharitis (D.Brevis). The folliculorum finds its main habitat at the base of the eyelash follicle, where it feeds on epithelial cells, causing direct mechanical damage. Since demodex does not have excretory organs, the undigested residues are regurgitated, and then combine with epithelial cells, keratin and eggs to form the cylindrical deposits of the eyelashes, characteristic of the presence of demodex. D.brevis was associated with dysfunction of the Meibomus glands, where it causes a primary mechanical blockage of the glandular orifice.

Taxonomic diversity of Biomphalaria (Planorbidae) in São Paulo state, Brazil

Abstract: Morphological and molecular identifications were carried out for Biomphalaria occidentalis, Biomphalaria oligoza, Biomphalaria peregrina, Biomphalaria schrammi, Biomphalaria straminea and Biomphalaria tenagophila collected from 55 sites located along the upper basin of Tietê River in the Southeast Region of Brazil. Morphological analysis considered aspects of the shell, mantle, excretory organs and reproductive system. Molecular data included 122 sequences of Cytochrome C Oxidase I gene (COI). Our results showed that some shell characters, as well as other characters related to the mantle and the reproductive system, are fundamental for the identification of the six Biomphalaria species included in this study. The use of DNA barcoding together with morphological taxonomy generated more reliable results, proving to be a very useful approach, even for malacological surveillance services.

A guide to crystal-related and nano- or microparticle-related tissue responses.

Crystals and nano- and microparticles form inside the human body from intrinsic proteins, minerals, or metabolites or enter the body as particulate matter from occupational and environmental sources. Associated tissue injuries and diseases mostly develop from cellular responses to such crystal deposits and include inflammation, cell necrosis, granuloma formation, tissue fibrosis, and stone-related obstruction of excretory organs. But how do crystals and nano- and microparticles trigger these biological processes? Which pathomechanisms are identical across different particle types, sizes, and shapes? In addition, which mechanisms are specific to the atomic or molecular structure of crystals or to specific sizes or shapes? Do specific cellular or molecular mechanisms qualify as target for therapeutic interventions? Here, we provide a guide to approach this diverse and multidisciplinary research domain. We give an overview about the clinical spectrum of crystallopathies, about shared and specific pathomechanisms as a conceptual overview before digging deeper into the specialty field of interest.

English

In view of World Health Organization (WHO) recommendation on the use of medicinal plants for the management of diabetes mellitus, this study evaluated the effect of ethanolic leaf extract of Vinca major L. on biochemical parameters and glucose level of alloxan induced diabetic rats as objective. Sixty-four male Wistar albino rats were induced with diabetes by a single intraperitoneal injection and were separated into four groups (1-4) of sixteen rats each. Group 1 served as the control while groups 2 to 4 served as the test groups. Apart from the control, the test groups were treated with different concentrations of the leaf extract, and four rats from each group were sacrificed every seven days for assessment. The treatment period lasted for 28 days. Haemoglobin (Hb) levels in groups 3 and 4 rats significantly increased (p<0.05) against the control throughout the number of days of the study. Red blood cell (RBC) levels in groups 2 and 4 increased significantly (p<0.05) against the control on the 14th day, while all the test group rats had significantly increased (p<0.05) RBC levels on the 21st and 28th days of the study. The observed trend followed by electrolyte ions, urea and creatinine in test rats against the control in the present study, may be attributed to V. major leaf extract trying to salvage the excretory organs of alloxan battered diabetic rats. Glucose level, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) liver enzymes reduced significantly (p<0.05) in test rats against the control. Diabetic rats treated with V. major leaf extract in this study, showed significant improvements on those associate problems of diabetes which include anaemia, dyslipidaemia, and hepatic necrosis and inflammation. Rats treated with the leaf extract also showed reduced glucose level (Hypoglycemia). From the observations of this study, extract from leaf of V. major may be effective against diabetes and some of its associate problems. Key words: diabetes, biochemical parameters, Vinca major, leaf extract, Wistar rats.

Distribution of metals in tissues of captive and wild Morelet's crocodiles and the potential of metallothioneins in blood fractions as a biomarker of metal exposure.

The distribution of Hg, Cd, Cu, and Zn in keratinized tissues, blood fractions, and excretory organs, and MTs in blood fractions and excretory organs was determined in captive, semicaptive, and wild Morelet's crocodiles and they were compared to select the most useful non-destructive tissues for the monitoring of metal exposure and to assess the potential of MTs as a biomarker. Our results indicate blood plasma, claws, and caudal scutes altogether are suitable tissues for xenobiotic metals exposure, with concentrations in blood plasma being an indicator of recent exposure, whereas concentrations in claws and caudal scutes are indicators of chronic exposure. Results in keratinized tissues suggest they are an important detoxification strategy in crocodiles, and claws presented the highest concentrations of metals in both captive (Hg=0.44±0.23μgg-1, Cd=11.10±5.89μgg-1, Cu=45.98±23.18μgg-1, Zn=124.75±75.84μgg-1) and wild populations (Hg=1.31±0.32μgg-1, Cd=26.47±21.15μgg-1, Cu=191.75±165.91μgg-1, Zn=265.81±90.62μgg-1). Thus, they are an appropriate tool for assessing metal exposure in populations where scutes clipping as a marking technique is not allowed, and their collection is less complicated than with other tissues. MTs are a suitable biomarker in blood plasma, whereas in erythrocytes detoxification processes might depend on hemoglobin, rather than MTs. Future studies should consider the implementation of these tools for the monitoring of wild populations.

Development of Aedes aegypti (Diptera: Culicidae) mosquito larvae in high ammonia sewage in septic tanks causes alterations in ammonia excretion, ammonia transporter expression, and osmoregulation

Larvae of the disease vector mosquito, Aedes aegypti (L.) readily develop in ammonia rich sewage in the British Virgin Islands. To understand how the larvae survive in ammonia levels that are lethal to most animals, an examination of ammonia excretory physiology in larvae collected from septic-water and freshwater was carried out. A. aegypti larvae were found to be remarkably plastic in dealing with high external ammonia through the modulation of NH4+ excretion at the anal papillae, measured using the scanning ion-selective electrode technique (SIET), and NH4+ secretion in the primary urine by the Malpighian tubules when developing in septicwater. Ammonia transporters, Amt and Rh proteins, are expressed in ionoregulatory and excretory organs, with increases in Rh protein, Na+-K+-ATPase, and V-type-H+-ATPase expression observed in the Malpighian tubules, hindgut, and anal papillae in septic-water larvae. A comparative approach using laboratory A. aegypti larvae reared in high ammonia septic-water revealed similar responses to collected A. aegypti with regard to altered ammonia secretion and hemolymph ion composition. Results suggest that the observed alterations in excretory physiology of larvae developing in septic-water is a consequence of the high ammonia levels and that A. aegypti larvae may rely on ammonia transporting proteins coupled to active transport to survive in septic-water.

Automatic Assesment of Pathological Disorder using Color Retinal Images

Our vision reduced in eye because of the presence of retinal diseases like Exudates(diabetic Retinopathy), small aneurysms and vessel harm. This project principally concentrates on the symptoms of heart, lung, liver and excretory organ issues identification mistreatment retina body structure pictures. Our planned work shows that however optic disc elimination and follower the symptom detection. Optic disc is one among the components that encompass intersection of blood vessels and it conjointly has same characteristics of exudates like yellow color, intensity and distinction. Distinguish the optic disc and exudates is crucial one. Thus solely initial eliminate the optic disc and follower that exudates detection. This detection methodology terribly favorably with existing and promise preparation of those systems small aneurysms area unit the initial stage of exudates.

Bacterial communities in digestive and excretory organs of cicadas.

Bacteriocyte-associated symbionts are essential for the health of many sap-sucking insects, such as cicadas, leafhoppers and treehoppers, etc., but little is known about the bacterial community in the gut and other related organs in these insects. We characterized the bacterial communities in the salivary glands, alimentary canal and the Malpighian tubules of two populations of the cicada Subpsaltria yangi occurring in different habitats and feeding on different hosts. A high degree of similarity of core microbiota was revealed between the two populations, both with the top three bacteria belonging to Meiothermus, Candidatus Sulcia and Halomonas. The bacterial communities in various organs clustered moderately by populations possibly reflect adaptive changes in the microbiota of related S. yangi populations, which provide a better understanding of the speciation and adaptive mechanism of this species to different diets and habitats. When compared with two phylogenetically distant cicada species, Hyalessa maculaticollis and Meimuna mongolica, the core microbiota in S. yangi was significantly different to that of these species. In addition, our results confirm that Ca. Sulcia distributes in the digestive and excretory organs besides the bacteriomes and gonads, which provide potential important information onto the trophic functions of this obligate endosymbiont to the host insects.

Evaluation of effectiveness of 45S5 bioglass doped with niobium for repairing critical-sized bone defect in in vitro and in vivo models.

Here, we investigated the biocompatibility of a bioactive sodium calcium silicate glass containing 2.6 mol% Nb2 O5 (denoted BGPN2.6) and compare the results with the archetypal 45S5 bioglass. The glass bioactivity was tested using a range of in vitro and in vivo experiments to assess its suitability for bone regeneration applications. in vitro studies consisted of assessing the cytocompatibility of the BGPN2.6 glass with bone-marrow-derived mesenchymal stem cells (BM-MSCs). Systemic biocompatibility was verified by means of the quantification of biochemical markers and histopathology of liver, kidneys, and muscles. The glass genotoxicity was assessed using the micronucleus test. The regeneration of a calvarial defect was assessed using both qualitative and quantitative analysis of three-dimensional microcomputed tomography images. The BGPN2.6 glass was not cytotoxic to BM-MSCs. It is systemically biocompatible causing no signs of damage to high metabolic and excretory organs such as the liver and kidneys. No mutagenic potential was observed in the micronucleus test. MicroCT images showed that BGPN2.6 was able to nearly fully regenerate a critical-sized calvarial defect and was far superior to standard 45S5 Bioglass. Defects filled with BGPN2.6 glass showed over 90% coverage compare to just 66% for 45S5 Bioglass. For one animal the defect was completely filled in 8 weeks. These results clearly show that Nb-containing bioactive glasses are a safe and effective biomaterial for bone replacement.

Effect of Edaravone on Gentamcin-Induced MDCK Cell Apoptosis: A Model for Kidney Toxicity

The kidney is an important excretory organ of the body, and tubule cells are the basic structural and functional unit that constitutes the kidney..

Дослідження впливу геністеїну, ресвератролу та кверцетину на показники обміну гідроген сульфіду в нирках і маркери функціонального стану нирок в умовно здорових щурів

Сьогодні існує велика кількість лікарських засобів і біологічно активних сполук з ренотропною дією, серед яких є рослинні нефропротектори. Проте нез’ясованим є їхній вплив на метаболізм гідроген сульфіду (Н2S) у нирках і роль Н2S у реалізації їхнього нефропротекторного потенціалу. Мета дослідження – вивчити вплив флавоноїдів (кверцетину, ресвератролу) та ізофлавоноїдів (геністеїну) на систему Н2S у нирках щурів без експериментальної патології та визначити його зв’язок з маркерами роботи клубочкового та канальцевого апарату видільних органів. Досліди проведені на 40 щурах-cамцях лінії Вістар, масою 300–330 г. Тваринам дослідних груп внутрішньошлунково на 30 % розчині диметилсульфоксиду вводили геністеїн (5 мг/кг), ресвератрол (50 мг/кг) і кверцетин (20 мг/кг), контрольна група отримувала еквіоб’ємну кількість розчинника. Уміст H2S визначали спектрофотометрично за реакцією з N,N-диметил-пара-фенілендіаміном в присутності FeCl3; активність Н2S-синтезуючих ензимів – цистатіонін-гамма-ліази (ЦГЛ), цистатіонінбета-синтази (ЦБС), цистеїнамінотрансферази (ЦАТ) оцінювали за приростом сульфід-аніона. Утилізацію екзогенного H2S у нирках визначали за швидкістю зниження концентрації сульфід-аніона в інкубаційному середовищі. Уміст креатиніну в сироватці крові та сечі визначали за методом Яффе. Кліренс креатиніну та коефіцієнт реабсорбції води розраховували за відомими формулами. Уміст натрію та калію в сироватці крові та сечі визначали спектрофотометрично. Рівень білка визначали мікробіуретовим методом. Статистичну обробку проводили в програмі «STATISTICA 6.1», вірогідними вважали відмінності в разі p &lt; 0,05. Серед досліджуваних поліфенолів геністеїн і ресвератрол у інтактних тварин достовірно збільшували ензиматичну активність Н2S у нирках: ЦГЛ – на 15,1 і 11,7 %; ЦБС – на 14,4 і 13,1 %; ЦАТ – на 17,7 і 13,3 % відповідно. Кверцетин достовірно не змінював активність ЦГЛ і ЦАТ, та підвищував активність ЦБС на 17,5 %. Також усі три сполуки достовірно сповільнювали утилізацію екзогенного H2S і збільшували запаси ендогенного H2S у нирках умовно здорових щурів; посилювали діурез і фільтраційну здатність нирок; сприяли збільшенню екскреції креатиніну, натрію та калію з сечею і зниженню їхнього вмісту в крові порівняно з контролем; зменшували екскрецію білка з сечею. Найвищу ефективність показав геністеїн. Проведений кореляційний аналіз надав додаткові докази того, що ренотропні властивості всіх трьох досліджуваних поліфенолів пов’язані з впливом на систему H2S. Таким чином, усі застосовані поліфенольні сполуки мали потужний вплив на метаболізм H2S у нирках щурів без експериментальної патології. Найвиразніші нефротропні властивості та здатність стимулювати ендогенну продукцію H2S реєструвались у геністеїну, дещо менші – у ресвератролу та найменші –у кверцетину. Подальші дослідження захисної дії на нирки природних поліфенолів з точки зору їхнього впливу на систему H2S є перспективним напрямом корекції ниркових порушень.

Preclinical Evaluation of a Fluorine-18 (18F)-Labeled Phosphatidylinositol 3-Kinase Inhibitor for Breast Cancer Imaging.

Breast cancer is one of the commonest malignancies in women, especially in middle-aged and elderly women. Abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKt/mTOR) pathway has been found to be involved in breast cancer proliferation. Pictilisib (GDC-0941) is a potent inhibitor of PI3K with high affinity and is undergoing phase 2 clinical trials. In this study, we aimed to develop a noninvasive PI3K radiotracer to help determine the mechanism of the PI3K/AKt/mTOR pathway to aid in diagnosis. We designed a new 18F-radiolabeled radiotracer based on the structure of pictilisib, to evaluate noninvasively abnormal activation of the PI3K/AKT/mTOR pathway. To increase the water solubility, and to decrease hepatobiliary and gastrointestinal uptake of the tracer, pictilisib was modified with triethylene glycol di(p-toluenesulfonate) (TsO-PEG3-OTs) to obtain TsO-PEG3-GDC-0941 as the precursor for 18F labeling. A nonradiolabeled reference compound [19F]-PEG3-GDC-0941 was also prepared. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used as high- and low-expression PI3K models, respectively. PET imaging and ex vivo biodistribution assays of [18F]-PEG3-GDC-0941 in MCF-7 and MDA-MB-231 xenografts were also performed, and the results were compared. The precursor compound and reference standard compound were successfully synthesized and identified using NMR and mass spectroscopy. The 18F radiolabeling was achieved with a high yield (61 ± 1%) at a high molar activity (2100 ± 100 MBq/mg). MicroPET images and biodistribution studies showed a higher uptake of the radiotracer in MCF-7 tumors than in MDA-MB-231 tumors (7.56 ± 1.01%ID/g vs 4.07 ± 0.68%ID/g, 1 h postinjection). Additionally, the MCF-7 tumor uptake was significantly decreased when a blocking dose of GDC-0941 was coinjected, indicating high specificity. The liver was found to be the major excretory organ with 5.82 ± 0.88%ID/g at 30 min postinjection for MCF-7 mice. This radiotracer holds great potential for patient screening, diagnosis, and therapy prediction of PI3K-related diseases.