Changes In Vital Organs Research Articles

Retrospective analysis of ferrotherapy methodology in patients with chronic heart failure and chronic kidney disease

The course of chronic non-infectious diseases is often accompanied by the development of comorbid conditions. In chronic heart failure and chronic kidney disease, special attention is drawn to iron deficiency and anemia. Intravenous iron preparations have become widely used for the prevention and treatment of anemia. Their use contributes to the progression of structural changes in vital organs. However, attempts to implement high-dose intravenous ferrotherapy as a routine strategy for compensating iron deficiency in patients with heart failure, with or without anemia, raise questions related to the search for diagnostic markers of iron deficiency states, goals, and conditions for its use. The article discusses the influences of a combination of opposing factors (inflammation, hypoxia) on the erythron system, its humoral regulators, and iron metabolism based on the author’s own research to justify the choice of strategy and tactics for ferrotherapy in patients with heart failure and chronic kidney disease.

ASSESSING THE SAFETY PROFILE OF POLYMERS IN TRANSDERMAL MICRONEEDLE PATCH FABRICATION: INSIGHTS FROM AN ACUTE TOXICITY STUDY

The acute toxicity study is a crucial component of preclinical toxicology assessments conducted to evaluate the potential adverse effects of a substance or compound on albino rabbits. This study provides key findings and implications of an acute toxicity study of natural and synthetic polymers that are used in the preparation of transdermal microneedle patches (TMNPs) for sustained delivery of doxazocin mesylate. In this study, we divided the albino rabbits into three equal groups (n = 6). Group-I was labeled as a control group and group-II was treated with TMNPs-1 (HPMC, maltose) and group-III was treated with TMNPs-2 (PLGA, polyvinyl acetate). The results obtained from feed consumption, hematology profile, biochemical studies, vital organ weight, and histopathological changes in vital organs were compared with the control group, and proved the safety profile of the polymers involved in the fabrication of microneedle patches. Mechanical strength and dermal safety study established the facts about the safety of microneedle patches and potential risks to health as a carrier system for the delivery of drugs into the systemic circulation directly.

A Comprehensive Pathophysiologic, Histologic, and Biochemical Analysis of Buthus paris (C. L. Koch, 1839) Venom.

Buthus species, including B paris, are classified as one of the most dangerous scorpion genera in Morocco, implicated in several cases of human death. Our objective is to characterize, for the first time, the toxicity and histopathologic and biochemical impacts of B paris venom. We investigated the experimental pathophysiology of B paris venom by examining histologic changes in vital organs (heart, kidneys, liver, and lungs) and assessing biochemical enzymatic markers (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase, urea, and creatinine) in mice injected subcutaneously with 2 doses of 400 and 450 mg·kg-1. Our results showed that the subcutaneous median lethal dose of B paris venom was around 0.52 mg·kg-1. Histologic findings revealed significant tissue damage in the previously mentioned vital organs, confirmed through biochemical analysis indicating impaired heart and liver functions. Additionally, an increase in urea, creatinine, and glucose levels occurred following B paris venom injection. Our findings show that B paris venom exhibits a high level of experimental toxicity. These results highlight the potentially lethal nature of this venom and emphasize the potential medical importance of this species.

Guardians of Liver Health: Unveiling the Resilient Shield of Antioxidant Vitamins (C, E) Against Glyphosate-Induced Havoc in Experimental Rats

Glyphosate, a widely used herbicide, has gained popularity due to its broad-spectrum effects and use in genetically modified, glyphosate-resistant crops. Recent data, however, points to possible adverse effects of glyphosate and herbicides based on glyphosate, such as genotoxic and cytotoxic effects, elevated stress levels, disturbance of the hormones such as estrogen pathway and possible associations with specific cancer types. This has raised concerns about the widespread use of glyphosate and its impact on human health and the environment. The objective of this study was to determine whether antioxidants vitamin C and E could shield experimental rats' livers from the damaging effects of glyphosate. Animals were grouped as Group I-control, 30 days of oral glyphosate-treated rats as Group II, and Rats that received simultaneous glyphosate treatment and oral administration of vitamins C and E were for 30 days as Group III. We used the user's manual to figure out the fasting blood glucose (FBG) levels, the histomorphology of liver tissue using H&E staining, and the liver and kidney function tests using Diatek Greiner kits. The study revealed that prolonged exposure to glyphosate can alter the SREBPI and HNF1 pathways, leading to diabetes. As an herbicide, glyphosate can cause harmful changes in vital organs, leading to diabetes and other disorders.

Prediction, Synthesis and Evaluation of a Synthetic Peptide as an Enzyme-Linked Immunosorbent Assay (ELISA) Candidate for Screening of Bovine Antibodies against Theileria annulata.

Tick-borne diseases (TBDs) of livestock are endemic across various parts of tropical countries. Theileriosis is one such economically important TBD, caused by the Theileriidae family of organisms, which is transmitted by ticks. Theileria annulata, the causative agent of tropical theileriosis, contributes a significant loss to the dairy sector by causing anorexia, high fever, anemia, inflammatory changes in vital organs and icterus, thus, a loss in milk yield. Though vaccines are available, their protective efficacy is not absolute, and treatment is limited to early diagnosis of the causative agent. Routinely, microscopic identification of piroplasms in the erythrocytes (Giemsa-stained) of infected animals or schizonts in lymph node biopsies are practiced for diagnosis. PCR-based techniques (multiplex, uniplex, nested and real-time) have been reported to perform well in diagnosing active infection. Several attempts have been made using serological assays like Dot blot, ELISA and ICT, but the results were of variable sensitivity and specificity. Recombinant proteins like the Theileria annulata merozoite surface antigen (Tams1) and Theileria annulata surface protein (TaSP) have been explored as antigenic candidates for these assays. In the present study, we predicted an immunogenic peptide, i.e., TaSP-34, from the TaSP using various computational tools. The predicted peptide was custom synthesized. The diagnostic potential of the peptide was assessed by indirect plate ELISA to detect the bovine-IgM against Theileria annulata. Alongside, a recombinant truncated TaSP (rTaSP(tr)) was expressed and purified, which was used to compare the performance of the peptide as a diagnostic candidate. The IgM-based peptide ELISA was 100% sensitive and 92.77% specific as compared to PCR (Tams1 targeting), while 98.04% sensitivity and 97.44% specificity were observed in comparison with rTaSP(tr) ELISA. Almost perfect agreement between peptide ELISA and Tams1 PCR was observed with a Cohen's kappa coefficient (κ-value) of 0.901 and agreement of 95.31%. Further, the κ-value between the peptide ELISA and rTaSP(tr) ELISA was found to be 0.95, and the agreement was 97.65%, which shows a good correlation between the two tests. The findings suggest that the TaSP-34 peptide can be an efficient and new-generation diagnostic candidate for the diagnosis of T. annulata. Furthermore, the peptide can be synthesized commercially at a larger scale and can be a cost-effective alternative for the protein-based diagnostic candidates for T. annulata.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosinstaining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-β1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-β1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

Marine toxin C17-SAMT causes major structural damage to vital organs in mice following subchronic toxicity trials

C17-sphinganine analog mycotoxin (C17-SAMT) has been characterized as the contaminant responsible for the atypical toxicity reported in mussels from the Bizerte lagoon (northern Tunisia) over the past decade. C17-SAMT exhibited common symptoms of toxicity in mice, including flaccid paralysis and severe respiratory distress, followed by rapid death. To determine the potential health risks of this neurotoxin, we assessed its subchronic toxicity according to the recommendations of OCDE n° 407. The body weight and the structural changes of vital organs were recorded. Biochemical and hematological parameters were also quantified. Macroscopic observations showed that mice treated with 0.9, 9, and 90 µg/kg C17-SAMT had significantly reduced stomach weights, swollen and fragile intestines, and signs of nephritis with renal abscesses. Transaminase assays pointed out that exposure to C17-SAMT can lead to transaminitis. Above-average lactate dehydrogenase values were recorded in both the treated and satellite groups. Hematology data showed a significant reduction in red blood cell counts in high-dose-treated group. Reductions in hemoglobin and hematocrit were also recorded. Mean leukocyte counts were significantly elevated in the high-, mid-dose treated and satellite groups. At the microscopic level, we noted myocardial atrophy and hyperemia. In the lungs, we noted necrosis associated with macrophages perivascular infiltration and congestion. The kidneys showed mild inflammation and glomerular atrophy. The stomach exhibited mucosal atrophy, while a thin colon and distended small intestine were observed in high-dose-treated group. The liver was affected by vascular congestion, inflammatory infiltration, and lobular necrosis that evolved into acute hepatitis. Lesions, such as inflammatory infiltration and mild necrosis of the liver, cortical abscess with central necrosis in the kidney, and mild congestion of cardiac tissue were recorded in the satellite group.

Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma

The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy.

Heat Stress and Histopathological Changes of Vital Organs: A Novel Approach to Assess Climate Resilience in Farm Animals

Heat stress causes functional and metabolic alterations in different cells and tissues. There are several pathomorphological changes and biomarkers associated with head load in adaptive and productive organs of livestock. Heat stress-induced histopathological alterations in livestock were categorized as degenerative changes (fatty degeneration, steatosis, hydropic degeneration), necrosis (pyknosis, fibrosis), circulatory disturbances (hyperemia, edema, hemorrhage, congestion, thrombosis, ischemia), growth disturbances (hyperplasia, atrophy) and focal/diffuse inflammation (vascular changes, exudation). Upon immunohistochemical analysis, the biomarkers identified in growth-related organs were HSP70, HSP60, GABA, GABAAR, GABABR, HSP90, GnRH, LH, FSH, m6A, Nrf2, and C/EBPβ. The biomarkers in the reproductive organs were HSP70, Bax, Bcl-2, GABA, GABAAR, GABABR, Caspase-3, HSP90, HSPB9, HSPB10, HSF1, HSP40, T, E2, Cyt-C, CAT, BCL2L1, and VEGF. The identified biomarkers in the immune organs were CD3+ T cells, CD4+ T cells, CD8+ T cells, HSP70, and Bcl-2. All these biomarkers could serve as reliable variables in heat stress assessment in livestock. Further, HSP70, HSP90, HSP60, NPY, HSP27, Bcl-2, NF-κB, AQP2, Insulin, CD3+ T cells, CD4+ T cells, CD172a, EGF, AQP1, AQP3, AQP4, AQP5, CRYAB, GHR, 5-HT, CCK, and GLP-1 are heat stress-related biomarkers in adaptive organs that help in assessing the climate resilience of a livestock species and improving understanding about adaptive mechanisms. Among these biomarkers, HSP70 was established to be the ideal cellular biomarker for scaling heat response in livestock. Thus, examining heat-stressed organ histopathology and identifying cellular markers by immunohistochemistry may lay the foundation for screening climate-resilient livestock breeds in the challenging climatic scenario. Further, such an approach could help in developing concepts to combat the detrimental consequences of heat stress to ensure sustainability in livestock production.

Neutrophil membrane-coated nanoparticles exhibit increased antimicrobial activities in an anti-microbial resistant K. pneumonia infection model

ObjectiveTo investigate the efficacy and safety of neutrophil membrane-coated nanoparticles mediated KLA peptides (KLAKLAKKLAKLAK) and gentamicin in the targeted therapy of anti-microbial resistant Klebsiella pneumoniae (K. pneumonia) lung infection. MethodsThe characteristics of KLA-neutrophils nanoparticles (NNPs) are identified via dynamic light scattering (DLS), transmission electron microscope (TEM), SDS-PAGE, Western blot, quantitative flow cytometry (QFCM) and confocal microscopy. The safety of KLA-NNPs both in vitro and in vivo is evaluated by hemolysis test, platelet α granule membrane protein concentration, protein adsorption capacity, in vitro macrophage phagocytosis, weight change, liver function indicators, blood biochemical indicators, and pathological changes of vital organs in mice. The efficacy of KLA-NNPs is determined by time-kill assay, fluorescent label test, intracellular bacterial content, caspase-1 activity, survival rate, and HE staining both in vitro and in vivo. ResultsThe prepared KLA-NNPs have a typical “core-shell” structure, uniform nanometer size, and retain the membrane proteins on the neutrophil membrane that achieve functional effects. In vitro safety analysis showed that KLA-NNPs have good blood compatibility and can inhibit macrophage phagocytosis in vitro. KLA-NNPs can effectively release KLA and significantly reduce intracellular bacteria and caspase-1 activity. In vivo safety analysis and efficacy analysis revealed that KLA-NNPs have good biocompatibility and could effectively improve the survival rate of mice. ConclusionThe prepared KLA-NNPs have good nano-medicine chemical and physical properties and safety. It can evade immune system clearance, achieve high-efficiency targeted aggregation and drug delivery to bacterial infection sites, and effectively inhibit the development of pneumonia induced by drug-resistant K. pneumonia.

Morphophysiological alterations in fruit-eating bats after oral exposure to deltamethrin.

Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore theobjective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats.

A narrative review on the role of carbon nanoparticles in oncology.

The lymphatic system is the first site of metastasis for most tumors and is a common reason for the failure of cancer therapy. The lymphatic system's anatomical properties make it difficult to deliver chemotherapy agents at therapeutic concentrations while avoiding systemic toxicity. Carbon nanoparticles offer a promising alternative for identifying and transporting therapeutic molecules. The larger diameter of lymphatic vessels compared to the diameter of blood vessels, allows carbon nanoparticles to selectively enter the lymphatic system once administered subcutaneously. Carbon nanoparticles stain tumor-draining lymph nodes black following intratumoral injection, making them useful in sentinel lymph node mapping. Drug-loaded carbon nanoparticles allow higher concentrations of chemotherapeutics to accumulate in regional lymph nodes while decreasing plasma drug accumulation. The use of carbon nanoparticles for chemotherapy delivery has been associated with lower mortality, fewer histopathology changes in vital organs, and lower serum concentrations of hepatocellular enzymes. This review will focus on the ability of carbon nanoparticles to target the lymphatics as well as their current and potential applications in sentinel lymph node mapping and oncology treatment regimens. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.

Neurological Manifestations of Fabry Disease: Literature Review

BACKGROUND: Fabry disease (FD) or Anderson FD is a hereditary disease belonging to the group of lysosomal storage diseases caused by decreased or absent activity of the enzyme α-galactosidase A. Enzyme deficiency leads to accumulation of glycospholipids in the lysosomes of cells of various organs, including the heart, kidneys, nervous system, and vascular endothelium. The complexity of the diagnosis of FD is due to the variety of its symptoms, the simultaneous involvement of many organs and systems. At present, possible pathogenetic treatment of the disease is enzyme replacement therapy, but its effectiveness is reduced in the later stages of the disease, when there are irreversible abnormal changes in vital organs and systems. In this regard, an urgent task is the early diagnosis of FD. AIM: Determination of neurological manifestations of FD as well as clinical criteria for screening for FD. MATERIALS AND METHODS: We analyzed cohort studies, randomized controlled trials, systematic reviews and meta-analyses, case-control studies, and case series from scientific medical databases: PubMed, Web of Science, Google Scholar in Russian, and English languages. CONCLUSION: The authors found that lesions of the nervous system in FD are detected in more than 80% of patients and can manifest as isolated or combined lesions of both the central and peripheral and autonomic nervous systems.

Структурно-функциональное исследование почек рыб при экологическом мониторинге и в аквакультуре

The intense anthropological impact on the ecosystems makes it necessary to monitor the state of populations of different fish species from different points of view. Health of aquatic animals, including fish, is an informative indicator of the quality of the environment, since physical and chemical changes in water, if they go beyond the optimum, cause definite reactions in the fish body. There are summarized the results of studying the kidneys of cyprinid fish species from the natural habitats of the lower reaches of the Volga and Kigach rivers and the Northern Caspian, as well as those cultivated in pond farms. The detected violations of mesonephros were described depending on localization of the pathological process. It has been shown that pathological changes are found in all structures of the kidney: in the interstitial, renal corpuscle, convoluted muscles. A change in the rheological properties of blood, glomerular changes up to atrophy of capillary loops, dystrophic changes in the tubular epithelium were found. An original system for assessing the condition of fish kidneys is proposed. Reactions in the body of hydrobionts are a consequence of the combined effects of environmental factors and natural physiological processes. The changes detected in the organ structure make it possible to assess the environmental impact on fish. Histopathological changes in vital organs, in particular, in mesonephros, are valuable indicators for assessing the consequences of negative environmental influences. Using not only qualitative, but also quantitative characteristics of mesonephros can contribute to introduce the quantitative methods in ecological and morphological studies of fish.

Soil degradation kinetics of oxybenzone (Benzophenone-3) and toxicopathological assessment in the earthworm, Eisenia fetida

A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxybenzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7–28.9 days, respectively.

In Vivo Treatment Efficacy of Essential Oil Isolated from Seeds of Momordica charantia in Streptozotocin-Induced Diabetes Mellitus.

All parts of Momordica charantia L. have potential hypoglycemic properties in reversing the metabolic disorder of diabetes mellitus. However, there exists a need for preparing an effective and safer formulation of active phytochemicals. We have also reviewed and analyzed certain patents on such preparatory methods for Momordica charantia L. formulations. This study aimed to isolate essential oil from the seeds of Momordica charantia L., analyze its phytochemicals, and study their anti-diabetic effects. The essential oil was isolated by the hydrodistillation method and analyzed for phytochemicals by GC-MS. Furthermore, its acute toxicity was tested in rats. Anti-diabetic effects were evaluated in Streptozotocin-induced diabetic rats with 17.5 and 55 mg/kg b.wt of essential oil by evaluating blood glucose, serum lipid profile, liver glycogen, protein, and other serum markers such as ALT, AST, ALP, urea, and creatinine. The histologic changes in the liver, pancreas, and kidney were evaluated using Haematoxylin and Eosin staining. The phytochemicals having hypoglycaemic and insulin induction potency were identified in the GC-MS analysis. A highly significant (p≤0.01; p≤0.001) reduction in blood glucose was observed from 17.5 mg/kg and 55 mg/kg essential oil treatments, respectively. Diabetes-associated metabolic alterations (p≤0.001) observed in diabetic control rats such as lipid profile, enzymes, glycogen, protein, urea, and creatinine were normalized upon treatment with essential oil. Moreover, the histologic changes in vital organs reversed in treated rats. The essential oil of Momordica charantia L. seed has promising potency to normalize the metabolic changes of type II diabetes mellitus.

Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein.

The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced in vitro dissolution. Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45–762.8±2.05 nm and -22.4±0.55–31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier (Maltodextrin) followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.

Гистопатологическая характеристика мультиорганных поражений у пациентов с COVID-19

The main cause of death in COVID-19 patients is acute respiratory distress syndrome (ARDS) and multi-organ failure, which is often caused by extrapulmonary dissemination and the direct damaging effect of SARS-COV-2 on the vital organs tissues. However, the nature of histopathological changes in vital organs and their significance in the thanatogenesis of COVID-19 remain insufficiently studied. Purpose of the research. To study the nature of histopathological changes in organs in COVID-19 patients, and to conduct a comparative analysis of the data obtained with the results of foreign countries’ studies with high mortality rates. Materials and methods. A pathologic study of 179 deceased COVID-19 patients was conducted. The median age of patients was 71 years. In 83.8% (150/179) of cases, COVID-19 was the main disease, and in 16.2% (29/179) of cases, it was concomitant. Results and discussion. Histopathological changes in COVID-19 were multi-organ in nature, which caused ARDS in 91.62%, cardiovascular insufficiency in 27.4%, brain edema – in 20.1%, pulmonary edema – in 3.9%, and pulmonary embolism – in 3.9% of cases. The morphological signs of ARDS in COVID-19 were: lung mass increase in 78.2% of cases, foci of pulmonary parenchyma compaction – 74.8%, discoloration of lung tissue – 60.3%, signs of congestion – 58.1%, the histological basis of which was diffuse alveolar damage. Conclusion. Old age and concomitant chronic diseases of vital organs are the main risk factors for death in COVID-19. Histological changes in organs can be the result of both direct exposure to the virus and hypoxic, metabolic, and ischemic damage.

Cardiovascular complications according to severity of renal artery stenosis based on Doppler ultrasound

IntroductionThe interactions between atherosclerotic renal artery stenosis, independently of severity, and cardiovascular risk, and mortality, are complex and have not been fully researched. The aim of this study was the assessment of the risk of cardiovascular events and mortality in patients with haemodynamically non-significant (NS-RAS) and significant renal artery stenosis (S-RAS) diagnosed with ultrasonography.Material and methodsThe study group consisted of all consecutive patients (n = 2059) who underwent Doppler ultrasound of the renal arteries during a 4-year period. The patients were divided, according to the renal aortic ratio (RAR), into the following groups: S-RAS (RAR ≥ 3.5), NS-RAS (1 &lt; RAR &lt; 3.5), and normal RAR (control group; RAR ≤ 1). The risk of cardiovascular events and death was estimated using Cox’s proportional hazard model, including severity of RAS, age, and gender, based on the data from the National Health Fund on causes of hospitalization, deaths, and statistics on percutaneous coronary angioplasty procedures.ResultsSignificant renal artery stenosis was found in 112 patients (5.4%), NS-RAS in 313 patients (15.2%), and 1634 patients (79.4%) were qualified to the control group. The NS-RAS group had an increased risk of stroke (7.0% vs. 3.0%, HR = 1.77, p = 0.032); S-RAS patients were at increased risk of heart failure (16.1% vs. 5.2%, HR = 2.19, p = 0.002) and death (19.6% vs. 4.3%, HR = 3.08, p &lt; 0.001).ConclusionsThe presence of haemodynamically non-significant renal artery stenosis is an indicator of systemic atherosclerotic changes in vital organs and an important cardiovascular risk factor for stroke.

Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.

Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2–induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2–induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.