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Vasonatrin peptide (VNP) is a synthetic peptide that possesses vasodilatory, natriuretic, and anti-inflammatory properties. The authors aimed to analyze the effects of VNP on fat graft survival. Twenty Sprague–Dawley rats are randomly divided into two groups of 10. Fat grafts are harvested from the right inguinal region. After preparation, fat grafts are placed to the interscapular region. The first group of rats were administered VNP after their fat injection, while the second group received tail-vein injections of an equal volume of sterile saline following their fat injection. Experiment and control groups are evaluated according to their level of degeneration of adipocytes, fat necrosis, vacuolization, cyst formation in adipocytes, fibrosis of the fat tissue, capillary density, and CD31 immunohistochemical staining. Degeneration, vacuolization, and cyst formation in adipocytes were lower in the experiment group. Increased capillary density in the experiment group was demonstrated by CD31 antibody staining and by counting capillary density under a microscope. The average percentage of change in weight of the fat grafts in the experiment group was lower than that in the control group. The results indicate that VNP has some beneficial effects on fat graft survival by multiple independent mechanisms that influence both local and systemic homeostasis.

Subnuclear vacuolization of the renal tubular epithelium refers to discrete lipid vacuoles displacing the nuclei toward the lumen. This phenomenon has been associated with conditions sharing fatal ketoacidosis as a common denominator. This retrospective study aimed to investigate renal tubular epithelial subnuclear vacuolization and other postmortem examination findings in fatal hypothermia and diabetic ketoacidosis (DKA) cases.Fourteen cases with hypothermia and 19 cases with DKA were included. More cases with DKA had focal or diffuse subnuclear vacuolization compared with hypothermia cases (89% vs 43%; P = 0.007). In 6 cases with DKA, formalin pigment was detected within subnuclear vacuoles, whereas no case with hypothermia had formalin pigment deposition. Comparative analyses of hypothermia and DKA cases revealed further differences: Vitreous beta-hydroxybutyrate was higher in the DKA group compared with the hypothermia group (P = 0.044), whereas blood ethanol concentrations were higher in the latter (P = 0.008). Hypothermia cases were older compared with the DKA cases (P = 0.022).When all cases were included in the statistical analysis, cases with subnuclear vacuolization had higher vitreous beta-hydroxybutyrate and blood ethanol concentrations (P = 0.029 and 0.023, respectively). The findings corroborate the results of previous studies suggesting a link between subnuclear vacuolization and increased levels of ketoacidosis.

Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria. ispartof: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY vol:12 ispartof: location:Switzerland status: published

We encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.

Cassia angustifolia Vahl. plant is used for many therapeutic purposes, for example, in people with constipation, skin diseases, including helminthic and parasitic infections. In our study, we demonstrated an amoebicidal activity of C. angustifolia extract against Acanthamoeba triangularis trophozoite at a micromolar level. Scanning electron microscopy (SEM) images displayed morphological changes in the Acanthamoeba trophozoite, which included the formation of pores in cell membrane and the membrane rupture. In addition to the amoebicidal activity, effects of the extract on surviving trophozoites were observed, which included cyst formation and vacuolization by a microscope and transcriptional expression of Acanthamoeba autophagy in response to the stress by quantitative polymerase chain reaction. Our data showed that the surviving trophozoites were not transformed into cysts and the trophozoite number with enlarged vacuole was not significantly different from that of untreated control. Molecular analysis data demonstrated that the mRNA expression of AcATG genes was slightly changed. Interestingly, AcATG16 decreased significantly at 12 h post treatment, which may indicate a transcriptional regulation by the extract or a balance of intracellular signalling pathways in response to the stress, whereas AcATG3 and AcATG8b remained unchanged. Altogether, these data reveal the anti-Acanthamoeba activity of C. angustifolia extract and the autophagic response in the surviving trophozoites under the plant extract pressure, along with data on the formation of cysts. These represent a promising plant for future drug development. However, further isolation and purification of an active compound and cytotoxicity against human cells are needed, including a study on the autophagic response at the protein level.

The ability of the new coronavirus SARS‐CoV‐2 to spread and contaminate is one of the determinants of the COVID‐19 pandemic status. SARS‐CoV‐2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound‐guided postmortem biopsies in COVID‐19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT‐qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS‐CoV‐2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8–83 years). RT‐qPCR for SARS‐CoV‐2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70–100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti‐SARS‐CoV‐2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS‐CoV‐2 by immunohistochemistry. Salivary glands are a reservoir for SARS‐CoV‐2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID‐19 and highlight this biological fluid's role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Plastic debris is ubiquitous in the marine environment and many of this is polyethylene based plastic bags. Its potential effect on marine organisms is still understudied. Hence, this study determined the histological changes induced in the intestine and liver of the juvenile rabbit fish, Siganus guttatus. S. guttatus (N = 150) were sub chronically exposed to plastic bag debris suspensions (0, 0.01, 0.1, 1.0 and 10 mg L−1) for 10 days. In addition to histological changes, the condition factor (CF) index of the fishes were assessed. Results showed that there was no significant difference in the CF index of the fishes exposed to varying concentrations of plastic suspensions, there was however histological changes in fishes exposed to 10 mg L−1. The histological changes in the intestine were hyperemia, necrosis, goblet cells hyperplasia, and shortening of the villi. Histological changes in the liver were hyperemic blood vessels and vacuolization. Fishes exposed to 10 mg L−1 exhibited a higher proximal, distal, liver and total organ index as compared to those unexposed (p

The toxicity of metal to living organisms, including human beings, was discovered a long time ago. In the present time, aluminum exposure is widely used for wrapping food to keep it taste and smell. However it will affect to human health security, specially the brain. This study aimed to investigate the changes of histological Structure on the cerebral cortex caused by aluminum chloride. The mice were injected intraperitoneally with AlCl3 200 mg/kg body weight, once every 3 days, totalizing 10 administrations. Control only was administration distilled water. Histological observations were carried out using the paraffin method. The results of this study show that aluminum chloride cause disorganization of the laminated cerebral cortex, vacuolization, karyolysis, congestion, and hemorrhage. The mice of one and two-months of age group were more susceptible to aluminum chloride than the mice of the three-months of age group. This research can apply for an assessment of the exposure risk to heavy metal. Increasing Al contamination can occur naturally or by anthropogenic activities. The accumulation of the heavy metal in the organism can occur by biomagnification, by which heavy metal is passed from one trophic level to the next within a food web. Therefore communities that live in urban areas potentially exposed to metals aluminum and should be more concerned related to understanding health risks. Further studies are needed to examine the above matters. We recommend calculating the Provisional Tolerable Weekly Intake of aluminum and implication on local people

The management of the Neotropical brown stinkbug Euschistus heros (Hemiptera: Pentatomidae) in soybean fields has been heavily dependent on the application of neonicotinoid insecticides. Neonicotinoids act primarily by impairing the function of the nicotinic acetylcholine receptors of the nervous system. These compounds also target specific organs (e.g., salivary glands), which may potentiate their insecticidal efficacy. Here, we evaluated whether the exposure to the neonicotinoid imidacloprid would cause cytomorphological changes in the salivary glands of E. heros. First, we determined the lethal concentrations (LCs) of imidacloprid through contact and ingestion. Subsequently, the cytomorphology of the salivary glands were evaluated in insect groups that survived exposure to the LC5 (3.75 mg a.i./L), LC50 (112.5 mg a.i./L), or LC75 (375.0 mg a.i./L, equivalent to the recommended field rate) doses. Imidacloprid induced apoptosis and necrosis in the salivary gland cells according to the insecticide concentration and salivary gland region. All concentrations increased apoptosis and injured cells (e.g., vacuolization, chromatin condensation, swelling of organelles, and plasma membrane rupture) in the principal and accessory salivary glands. Individuals that survived exposure to the highest concentrations (i.e., LC5 and LC50) were more affected, and exhibited several necrotic cells on their main principal salivary glands. Collectively, our results indicate that imidacloprid exerts toxic effects on the non-target organs, such as the salivary glands, which increases the efficacy of this compound in the management of stink bug infestations.

Fibrosarcoma is a malignant neoplasm of fibroblast that commonly found in middle-aged or older dogs. Breed and sex do not influence the incidence of fibrosarcoma. A 10 years old grey female mix Pomeranian with a bodyweight of 9.2 kg showed a semi-solid mass, with meat-like consistency that felt integrated with the tissue underneath. A mass with a diameter of ± 5 cm had been found in the left thigh near the anus. The other two unusual masses with smaller size (diameter ±1 cm) were also found at lateral sinister near extremities cranial of the body. A serial of diagnostic check-ups, such as physical and clinical check-up, USG, haematology, cytology, and histopathology tests was run to examine the dog condition. The USG result showed hypoechoic masses with slightly anechoic appearances. The haematology analysis showed a decrease in lymphocyte, MCV and hematocrit, meanwhile the granulocyte, MCHC and MHC showed an increasing trend. The cytology test revealed a fat-like vacuolization. Furthermore, the histology examination indicating the presence of large hyperchromic oval cells. The histopathology examination also found fibroblast cells that suspected as tumour cells with mitotic and infiltrated oval cores. Thus, the dog was diagnosed with fibrosarcoma and the prognosis was dubious. The surgery was done to remove the tumour masses.

Patients with atypical hemolytic uremic syndrome (aHUS) associated with a C3 p.Ile1157Thr mutation show a relatively high renal survival and low mortality rates, but renal histopathological findings after recurrence have been rarely reported. A 30-year-old man with a C3 p.Ile1157Thr mutation experienced a third recurrence of thrombotic microangiopathies with neurological and gastrointestinal disorders. A renal biopsy performed during the recovery phase of acute kidney injury revealed collapsed glomeruli and arteriolar vacuolization. Approximately 10% of glomeruli were globally sclerotic, despite the absence of arterio-/arteriolo-sclerosis. These findings suggest substantial progression of irreversible injuries in multiple organs, including kidneys, which occurs in aHUS patients with repeated thrombotic microangiopathies.

Chromium (Cr) compounds are markedly toxic and carcinogenic. Previously, we found that Cr (VI) induced autophagy in A549 cells. Here, the effect of mitochondrial dysfunction and endoplasmic reticulum (ER) stress on inducing mitophagy was investigated in both A549 and H1299 cells. Exposure to Cr (VI) for 6 h significantly enhanced reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (MMP). Transmission electron microscopy showed that Cr (VI) induced mitochondrial morphological changes, such as, mitochondrial swelling and vacuolization. The elevated expression of GRP78 and p-PERK suggested that Cr (VI) resulted in ER stress. Both mitochondrial dysfunction and ER stress played an important role in Cr (VI)-induced mitophagy, as the mitochondrial function inhibitor, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) induced PINK1 and PARK2 and increased the expression of GRP78 and p-PERK while the levels of Cr (VI)-induced PINK1, PARK2, LC3-II were reduced after ER stress inhibitor, phenylbutyric acid (4PBA) pretreatment. When A549 cells were treated with CCCP and 4-PBA simultaneously, CCCP-induced expressions of PINK1, PARK2 and LC3-II decreased significantly compared with that of only CCCP-treated cells, indicating that there was a crosstalk between mitochondria and ER in inducing mitophagy. Additionally, the crosstalk between mitochondrial dysfunction and ER stress modulated the expression of Cr (VI)-induced ATF4, which resulted in mitophagy. Collectively, our data demonstrated that Cr (VI)-induced mitophagy mediated by ATF4 via the crosstalk between ER stress and mitochondrial dysfunction.

This study analyzes the histological peculiarities of the internal organs of the lake form of Mongolian grayling Thymallus brevirostris (Kessler, 1879) caught in the cold-water mountain Lake Hindiktig-Khol (Tuva Republic, Russia) in the summer. The maturation of the females starts at 4+ years; the peak of their spawning activity is observed at 5+. Males mature 1 year earlier than females. In summer, in the ovaries of mature females, the older generation of germ cells is represented by oocytes at the phase of the cytoplasm vacuolization; the younger generation of cells is represented by numerous previtellogenous oocytes. The peak of spermatogenesis is observed in the testes. Significant pathomorphological changes are revealed in the gill epithelium which inhibit the respiratory function. Weakly expressed liver congestion and moderate basophilia of hepatocytes both indicate normal conditions in this lake.

Quantifying lymphocyte vacuolization in peripheral blood smears (PBSs) serves as a measure for disease severity in CLN3 disease—a lysosomal storage disorder of childhood‐onset. However, thus far quantification methods are based on labor‐intensive manual assessment of PBSs. As machine learning techniques like convolutional neural networks (CNNs) have been deployed quite successfully in detecting pathological features in PBSs, we explored whether these techniques could be utilized to automate quantification of lymphocyte vacuolization. Here, we present and validate a deep learning pipeline that automates quantification of lymphocyte vacuolization. By using two CNNs in succession, trained for cytoplasm‐segmentation and vacuolization‐detection, respectively, we obtained an excellent correlation with manual quantification of lymphocyte vacuolization (r = 0.98, n = 40). These results show that CNNs can be utilized to automate the otherwise cumbersome task of manually quantifying lymphocyte vacuolization, thereby aiding prompt clinical decisions in relation to CLN3 disease, and potentially beyond.

Candida species are opportunistic fungi that can cause mucosal or invasive infections. Especially in biofilm-related infections, resistance is very high to anifungals; therefore more effective treatment strategies are needed. Farnesol(3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) is the quorum sensing (QS) signal molecule and can interact with Candida species both as a QS molecule and as an exogenous agent. The aim of this study was to investigate the effects of farnesol on both the planktonic and biofilm forms of Candida species by colorimetric, microbiological, and electron microscopic methods. Obtained results demonstrated the inhibitory effect of farnesol on the planktonic and biofilm forms of Candida. Farnesol showed a biofilm-enhancing effect at lower concentrations. TEM findings showed the membrane and wall damage, vacuolization, or granulation in cells. SEM images confirmed biofilm reduction in pre-/post-biofilm applications as a result of farnesol treatment. In conclusion, farnesol can be used as an alternative agent to reduce the Candida biofilms, with future studies.

Effect of geraniin extracted from sugar maple (Acer saccharum) leaves on the viability of the phytopathogen Xanthomonas campestris pv. vitians was evaluated with the SYTOX Green nucleic acid stain, penetrating only compromised membranes, and plate counts. In parallel, structural changes of treated bacteria were examined in transmission electron microscopy (TEM). Based on SYTOX Green and plate counts, geraniin at the minimum bactericidal concentration (3.125 mg/ml) increased mortality after 45 min by 37% and 62%, respectively, when compared with controls. According to observations in TEM, geraniin caused morphological alterations of these rod-shaped bacteria, including degradation of their envelopes, as also suggested by the incorporation of SYTOX. These alterations were often accompanied by cytoplasm leakage and the formation of more pronounced whitish areas in the cytoplasm similar to vacuolization. Moreover, multi-membranous and/or –wall systems were at times formed in the treated bacteria. The presence of some extracellular electron-dense material was frequently noted around the treated bacteria. The matrix surrounding control bacteria tended to disappear after geraniin treatment. This study highlights for the first time the effect of geraniin on bacterial ultrastructure, thus contributing to a better understanding of the mechanism by which this molecule exerts antibacterial activity.

Outbred white female rats were exposed to an aerosol of lead oxide nanoparticles in a nose-only inhalation setup at an average concentration of 1.30 ± 0.10 mg / m3 during 5 days for 4 hours a day. In parallel, the control group of rats was subjected to sham exposure under similar conditions. The deposition of nanoparticles in the lungs and in the olfactory region of the brain was detected using transmission electron microscopy. Some disorders of the body state were detected in the exposed group, some of which can be considered as the result of a lead-specific toxic effect (an increase in the proportion of reticulocytes and in urinary excretion of δ-aminolevulinic acid), and others - the result of nanoparticles circumventing the blood-brain barrier (axon demyelination, vacuolization of the neurons’ cytoplasm).

Green synthesis of nanoparticles (NPs) had shown the positive effects on various parameters of human health. However, this can vary depending on plant category, NPs nature, doses of green synthesized NPs and type of cell or tissue taken for experiment. The aim of this study is to evaluate the effects of Allium cepa (A. cepa)-mediated zinc oxide ZnO NPs on male reproductive tissues and aberrations in sperm structure of albino mice. The green-synthesized NPs were synthesized with A. cepa and further characterized through ultraviolet–visible spectroscopy, scanning electron microscopy (SEM), zeta potential and FTIR analysis. Various doses (75 mg, 150 mg, 225 mg and 300 mg/kg) were given orally to adult albino mice by keeping them in various groups for 28 days. Epididymis and testis were removed for assessment of spermatogenesis and histopathological analysis of testicular tissues was performed. The synthesized NPs showed absorption at 330 nm and size ranging from 50 to 90 nm through SEM. Dose-dependent significant decrease (P

The current study investigates the toxic effects of acute dose of an endocrine disruptor atrazine on Grass carp (Ctenepharyngodon idella) using histopathological changes as biomarkers. Histopathology is promising field for research in aquatic toxicology, in this manner vital organs; brain, gills, and liver tissues were inspected histological after exposing to sublethal groupings of atrazine 0.025 and 0.03 μl/L for 3, 6, 9, 12 and 15 days individually with equal untreated control group. Against various doses, rapid movements, gulping of air and jumping of fish to scat from toxic medium were noticed. Various severe (+++) morphological modifications in tissue were documented in comparison with control group comprised of degenerated neurons, vacuolization, inflammatory cells infiltration and neural necrosis in brain tissue. The most well-known gills tissue alteration at all concentrations of atrazine was epithelial hyperplasia, desquamation, epithelial lifting and smaller aneurism while hepatic injuries were described by overcast expanding of hepatocytes esteemed as cloudy swelling of hepatocytes followed by karyolysis, karyohexis and dilation of sinusoids which shows that atrazine introduction upgraded the toxicosis impacts with the increase concentration, influenced the strength of the fish, inferable from histological inconsistencies.

Extensive usage of silver in several applications may contaminate the freshwater compartment and affects the health status of aquatic organisms. In the present investigation, fingerlings of Indian major carp Labeo rohita were exposed (35 days) to sublethal concentrations of silver nitrate (AgNO3) and bioaccumulation pattern, biochemical and histological alterations were evaluated. Initially, the median lethal concentration (LC 50) of silver nitrate to the fish Labeo rohita for 96 h was calculated and it was found to be 0.035 mg L−1. To assess the toxicity of ionic silver two sublethal concentrations (0.0035 mg L−1: 1/10th of LC 50 and 0.007 mg L−1; 1/5th of LC 50) were selected and the experiment was conducted for a period of 35 days. A considerable quantity of AgNO3 was accumulated in the gill, liver and kidney tissues of Labeo rohita. Accumulation of AgNO3 was high in liver tissue compared to other organs/tissue. Membrane-bound enzyme (Na+/K+/-ATPase) activity was inhibited in both the concentrations when compared with the control group. Likewise, plasma electrolytes (Na+, K+ and Cl−) level were significantly decreased when compared with untreated groups. On the other hand, a noticeably increased level of glucose was observed in fish exposed to 0.0035 and 0.007 mg L−1 of AgNO3. Moreover, declining protein level was assessed during the initial days (7 and 14 days), and the level was increased in the rest of the exposure period. Extensive histopathological abnormalities were noticed in gill (hyperplasia, epithelial lifting, curling of lamellae) and liver (degeneration of hepatic nucleus, vacuolization, hepatic necrosis) of fish treated with silver nitrate when compared to control groups. The results obtained in the present study revealed that the bioaccumulation pattern, alterations in membrane-bound gill-ATPase activity, plasma electrolytes, biochemical and histological parameters of fish can be useful for biomonitoring the changes in the environment and health condition of fish in freshwater ecosystem contaminated with silver. Highlights •The fingerlings of Labeo rohita were exposed to sublethal concentrations of AgNO3 for 35 days.

Repeatedly deposition of anthropogenic chemicals such as chlorpyrifos led to the risk of its associated unwanted toxicity to the non-targeted organisms. The present project was designed to assess the toxicity of chlorpyrifos, an organophosphorus insecticide, at different dose level and duration of exposure to elucidate its cellular and nuclear anomalies in erythrocytes and histopathological effect on brain and liver tissues of the fresh water fish (Ctenopharyngodon idella). The chlorpyrifos was used at 0.01 and 0.015 μL/L for a duration of 3, 6, 9, 12, and 15 days respectively. Alteration in functional markers such as cellular anomalies associated with exposed dosage was reported as swollen cells, swollen or enlarged cells, and hemolyzed cells followed by nuclear abnormalities stated as micronucleus, deformed nucleus and nuclear shift. The result indicated alterations observed in brain and liver tissues were categorized as necrosis, vacuolization, degeneration of neurons and hepatic necrosis, hepatolysis and hepatic vacuolization that were further scored on the basis of severity from 0 (normal) to 3 (severe). These effects significantly increased with the increase in dose level of chlorpyrifos and duration of exposure (p < 0.05). The present findings contributed that extended exposure of such chemicals to the aquatic ecosystems led to behavioral and histopathological alterations that may result in loss of normal functioning of the organs.

This study aimed to understand the role played by haemocytes of Schistocerca gregaria adults in response to injection with Bacillus thuringiensis israelensis (Bti) into the hemocoel. Light microscopy recognized four types of haemocytes namely: prohaemocytes (PRs), plsamatocytes (PLs), granular cells (GRs) and coagulocytes (COs). Different responses were observed in the haemocyte populations at different time intervals (6, 12 24 and 48 h) following injection with a sublethal dose of bacteria; (1) Pathological consequences in the haemocytes including variation in the cell volume, vacuolization in the cytoplasm, distortion of the cell membrane and pycnosis in the nuclei, (2) Various changes in the differential haemocyte counts (DHCs), the most important is a decrease in the numbers of GRs and COs accompanied with an increase in PLs and PRs, (3) A marked decrease in the total haemocyte counts (THCs) at most time periods. (4) Phagocytosis was shown during all periods post-injection with peak at 6 h, and PLs were the essential phagocytic cell type. (5) A significant increase in nodule counts at all time intervals post-injection was observed above controls, with the peak was at 12 h post-injection.

In this study, hemocytes and fat body changes were investigated after activation the immuneresponse of the third instar larvae of Sarcophaga argyrostoma by injecting the larvaewith MDA-MB-231cancer cell lines. To investigate the changes in hemolymph and fat bodytissue, light and transmission electron microscopy (TEM) were used. Apoptosis demonstrationin the larval flesh fly after injection was immunohistochemically tracked using a markerof caspase initiator activity; namely caspase-3 antibody.The results showed remarkable changesin morphology, viability and the spreading ability of immunocompetent hemocytes andfat body cells between normal and immunized S. argyrostoma larvae. In hemocytes, multicellularaggregates were formed to entrap invading cancer cells, in addition to membrane blebbing,cytoplasm vacuolization, cell and organelle swelling, and chromatin condensation.Meanwhile, in fat body cells of injected larvae, depletion of lipid droplets, changes in the appearanceof protein granules and degrade of basement membrane overlying the fat body wereobserved. These features are typical for apoptotic and autophagal cell death which were confirmedby detection of apoptotic fat body cells after cancer cell injection using activatedcaspase-3 immunostaining.

Objective To characterize ovarian tissue from pediatric patients by evaluating development and vascularization in follicle populations and comparing it with adult tissue after xenografting. Design Prospective experimental study. Setting Academic research center. Patient(s) Five children (median age 3 years) and seven women (median age 28 years). Intervention(s) Hematoxylin and eosin staining, immunofluorescence, and transmission electron microscopy (TEM) evaluation before and after grafting. Main Outcome Measure(s) Follicle density, morphology, classification, and size, ovarian tissue vascularization, follicle ultrastructure. Result(s) Frozen-thawed ovarian tissue was divided into three fragments: nongrafted controls, TEM, and xenografting for 20 weeks. Follicle density was statistically significantly higher in pediatric than adult patients; even though it decreased in both groups after transplantation, it remained higher in pediatric patients. In the pediatric group, quiescent-stage follicles were the majority of the follicle pool before and after grafting, while growing follicles statistically significantly increased in both groups after grafting. Abnormal and atretic follicles were also observed in pediatric tissue and declined with age and after grafting. Pediatric ovarian tissue contained more and larger immature vessels, while mature vessels were larger in adults. The TEM analysis of abnormal pediatric follicles showed loss of shape and vacuolization of the cytoplasm without organelle damage. Conclusion(s) Statistically significant differences in follicle density were observed between pediatric and adult patients, but the follicle proportions were similar before and after grafting, with the exception of atretic and abnormal follicles. Pediatric tissue contains more and larger immature vessels than adult tissue, and the posttransplantation revascularization process is accelerated in this group.

Acute toxicity (96 h LC50) of phenol was analyzed in the cat fish Mystus vittatus in static bio-assay over a 96-h exposure period using probit method. The 24, 48, 72, and 96 h LC50 values (with 95% confidence limits) of phenol for fingerling catfish were found out as 13.98, 13.17, 12.62, and 12.21 mg/l respectively. Investigations pertaining to the histopathological sections have shown high degree of pathological lesions observed in various parts like gill, liver intestine, and kidney of the fish species. Analysis of gill section revealed observable changes in the experimental species such as fusion, malformation at the tip of secondary lamellae, vacuolation, hyperplasia, and epithelial damage. Exposure of phenol showed cytoplasmic vacuolation, tissue damage, and loss of hepatic cell wall in the liver of experimental organism. Lesions of tissue damage at the epithelial site, inflammation, and clumping of adjacent villi made of columnar epithelium have been observed in the intestine of fish, and also the excretory part of the fish kidney revealed various changes like glomerular atrophy, damage of Bowman's capsule, vacuolization, and degeneration of renal epithelium. The current study on histological changes observed in the experimental organisms has thrown light on the current scenario which poses threat and danger to the whole aquatic ecosystem, and this study plays a vital role in assessing the aquatic pollution.

Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose exposure. The systemic dysfunction appears partly due to acetylcholinesterase inhibition, exhibiting a primary toxic effect on the endocrine system but also on the liver and kidneys, which are responsible for products metabolization and elimination. Prolonged OP exposure can be responsible for histopathological (HP) changes that can either evolve or worsen pre-existing conditions. We conducted an experimental study including six male Wistar rats divided into two groups (four rats in the study group and two in the control group). The subjects in the first group were administered 100 mg∕kg Chlorpyrifos half median lethal dose (LD50) at baseline and at 48 hours, under general anesthesia. Organ harvesting was achieved after one week. HP modifications were discovered in all kidney samples, with dystrophic changes and vacuolization of mesangial cells, dilation of renal tubules and epithelial atrophy. Congestion of vascular structures also occurred. The liver samples showed severe alteration in both vessels and hepatocytes. Adrenal gland impairment was confirmed through an increase in vacuole number in all areas, while a decrease in colloid content was noted in the thyroid gland simultaneously with a modified foamy aspect. This study is the first to certify the extent of organ injury induced by OP exposure, describing both glomerular and tubular involvement in the kidneys, liver necrosis and endocrine disturbances.

Актуальність. Двоетапний метод з використанням проникаючого кріопротектору гліцерину є рутинним для кріоконсервування сперматозоїдів чоловіків з нормальним сперматогенезом. Однак застосування даного способу заморожування у випадку олігоастенотератозоосперміі (ОАТ) призводить до виникнення додаткових ушкоджень клітин і виникає необхідність у пошуку нових ефективних способах кріоконсервування. Вакуолізація сперматозоїдів, притаманна чоловічим гаметам, відіграє негативну роль, знижуючи здатність до запліднення клітин. Мета. Оцінка ступеня вакуолизації, індукованої в ОАТ сперматозоїдах людини після кріоконсервування двохетапним методом з використанням гліцерину та полівінілпіролідону (ПВП), молекулярною масою 360000. Методи. Виділену фракцію сперматозоїдів поділяли на 3 групи: група I – нативні сперматозоїди, II – сперматозоїди, кріоконсервовані з 10% розчином гліцерину, група III – кріоконсервовані з 10% ПВП. Результати. В групі I близько 5% сперматозоїдів містили вакуолі. У групі II кількості сперматозоїдів з однією дрібною вакуоллю збільшилася до (19,68 ± 2,27)%. А в групі III кількість клітин без вакуолей було порівняно з нативними сперматозоїдами: 95,59 ± 1,59 і (96,09 ± 2,02)% відповідно. Підсумок. Таким чином, використання проникаючого кріопротектори гліцерину в концентрації 10% для двоетапного кріоконсервування сперматозоїдів людини ініціює утворення вакуолей, в той час як застосування непроникаючої ПВП дозволяє запобігти вакуалізації., Background. The two–step method using penetrating cryoprotectant glycerol is a routine for cryopreservation of spermatozoa from men with normal spermatogenesis. However, the use of this freezing method in the case of oligoasthenoteratozoospermia (OAT) leads to additional cells damage and there is a need to search for new effective cryopreservation method. The sperm vacuolization inherent in male gametes plays a negative role, reducing the fertilizing ability of cells. Objective. The aim of the study was to assess the degree of vacuolization induced in human OAT sperm after cryopreservation by a two–stage method using glycerol and polyvinylpyrrolidone (PVP), molecular mass 360000. Methods. The isolated sperm fraction was divided into 3 groups: group I – native spermatozoa, II – spermatozoa cryopreserved by the two–stage method with 10% glycerol, group III – spermatozoa cryopreserved by the two–stage method with 10% PVP. Results. About 5% of spermatozoa contained vacuoles in group I. The number of spermatozoa with one small vacuole increased to (19.68 ± 2.27)% in group II. And in group III the number of cells without vacuoles was comparable with native spermatozoa: 95.59 ± 1.59 and (96.09 ± 2.02)%, respectively. Conclusion. Thus, the use of a penetrating cryoprotectant of glycerol at 10% concentration for two–stage method cryopreservation of human spermatozoa initiates the vacuoles formation while the use of non–penetrating PVP can prevent vacuolization., Актуальность. Двухэтапный метод с использованием проникающего криопротектора глицерина является рутинным для криоконсервирования сперматозоидов мужчин с нормальным сперматогенезом. Однако применение данного способа замораживания в случае олигоастенотератозооспермии (ОАТ) приводит к возникновению дополнительных повреждений клеток и возникает необходимость в поиске новых эффективных способах криоконсервирования. Вакуолизация сперматозоидов, присущая мужским гаметам, играет отрицательную роль, снижая оплодотворяющую способность клеток. Цель. Оценка степени вакуолизации, индуцируемой в ОАТ сперматозоидах человека после криоконсервирования двухэтапным методом с использованием глицерина и поливинилпирролидона (ПВП), молекулярной массой 360000. Методы. Выделенную фракцию сперматозоидов разделяли на 3 группы: группа I – нативные сперматозоиды, II – сперматозоиды, криоконсервированные с 10% раствором глицерина, группа III – криоконсервированные с 10% ПВП. Результаты. В группе I около 5% сперматозоидов содержали вакуоли. В группе II количества сперматозоидов с одной мелкой вакуолью увеличилось до (19,68±2,27)%. А в группе III количество клеток без вакуолей было сравнимо с нативными сперматозоидами: 95,59±1,59 и (96,09±2,02)% соответственно. Заключение. Таким образом, использование проникающего криопротектора глицерина в концентрации 10% для двухэтапного криоконсервирования сперматозоидов человека инициирует образование вакуолей, в то время как применение непроникающего ПВП позволяет предотвратить вакуализацию.

Bacillus thuringiensisis gaining worldwide importance in the control of pests in agriculture and public health. Characterization of new isolated strains with original, higher and broader spectrum of activity is an ever developing field. Parasporal inclusions from BLB427, a newB. thuringiensisstrain isolated from Tunisian soil, contained 2 major Cry proteins having molecular weights of about 130-135 kDa and 65-70 kDa corresponding tocry1-type andcry2-type genes, respectively. These toxins exhibited high toxicities toEphestia kuehniellaandSpodoptera littoralislarvae, with LC50values of about 81.91 µg/cm2(+/- 15.30) and 79.70 µg/cm2(+/- 36.73), respectively. BLB427 supernatant showed a promising activity against Lepidopteran pests due to the presence ofvip3-type gene in this strain. The high toxicity of BLB427 supernatant compared to that of BUPM95, used as control, was due in part to the high copy number ofvip3gene of BLB427 compared to that ofvip3Aa16of BUPM95, as demonstrated by Real-time PCR. This gene was cloned, sequenced and the comparison with the most knownvip3genes in databases, demonstrated thatvip3(427) gene and the corresponding protein showed differences that can influence the efficiency of the Vip3(427) toxin against Lepidoptera. After overexpression of Vip3(427) protein inEsherichia coliand its purification using His-Trap column, the toxin showed a promising toxicity against the lepidopteran pestS. littoraliswith extremely damages in the larvae midgut traduced by the vacuolization of the apical cells, the damage of microvilli and the disruption of epithelial cells. The results described in the present study proved thatB. thuringiensisBLB427 strain could be of a great interest for lepidopteran biocontrol by using its d-endotoxins and/or Vip3 toxins in bioinsecticides formulations.

A positive answer to this topic was given in 1882 by prof. N. M. Popov in his dissertation: "Materials for science on acute mellitic toxic origin". He asserts that, first of all, the nerve cells (of the spinal cord) come to a state of turbid swelling and vacuolization. Both of these processes can lead them to complete destruction: the first, through the transition to a bland, spreading formation, the second, through an increase in the vacuole. Finally, in the late period, there is a pigment atrophy, which destroys all the cells, the improvement from the previous changes. The intensity of the process is determined by the greater or lesser proximity of the vessel .... In all likelihood, the author says, the brain also changes here. With the same positivity, the suffering of the peripheral nervous system is excluded in this work.

Zinc is an essential component of biological function, play a significant role in male reproductive functioning and deficiency of this trace metal has negative impact on spermatogenesis and semen quality. The purpose of the present study was to find out if high concentrations of zinc lead to the opposite and evaluate the protective effect of natural products such as the ethanolic extract of P. granatum peel against the toxicity and oxidative stress induced by zinc chloride in male rabbitsTwenty adult rabbits were divided into equally four groups; the control, the ZnCl2 (5 mg/kg bw), the P.granatum peel(4 mg/kg bw) and the combined group (ZnCl2- PGP). The ZnCl2 and the PGP were administrated daily by gavage for a period of 6 weeks, and then the reproductive organs’ weight, the plasma testosterone, and the biology of sperms were evaluated.The results showed that the number of sperms in the epididymis and the concentration of testosterone in serum were decreased with an increased dose of ZnCl2 .Testicular and epididymis histopathological lesions like detachment, atrophy and vacuolization of germ, Leydig and epithelial cells were observed. On the other hand, the study shows improvement in all parameters when treated with P. granatum peel extract. In conclusion, High concentrations of zinc chloride may lead to sterility, which can be treated with natural product such as P. granatum peel.

The escalating burden of type 2 diabetes (T2D) and its related complications, has become a major public health challenge worldwide. Substantial evidence indicates that T2D is one of the culprits for the high prevalence of Alzheimer’s disease (AD) in diabetic subjects. This study aimed to investigate the possible mitochondrial alterations in the pancreas induced by hyperglycemia in diabetes. We used a diabetic TallyHO/JngJ (TH), and non-diabetic, SWR/J mice strains. The diabetic and non-diabetic status in animals was assessed by performing intraperitoneal glucose tolerance test at four-time points i.e., 4-, 8-, 16- and 24-weeks of age. We divided 24 weeks old TH and SWR/J mice into 3 groups: Controls, diabetic TH mice, and diabetic TH mice treated with SS31 peptide. After the treatment of male TH mice with SS31, intraperitoneally, for 4 weeks, we studied mitochondrial dynamics, biogenesis, and function. The mRNA and protein expression levels of mitochondrial proteins were evaluated using qPCR and immunoblot analysis. The diabetic mice after 24 weeks of age, showed overt pancreatic injury as demonstrated by disintegration, and atrophy of β-cells with vacuolization and reduced islet size. Mitochondrial dysfunction was observed in TH mice, as evidenced by significantly elevated H(2)O(2) production, lipid peroxidation, and reduced ATP production. Furthermore, mRNA expression and immunoblot analysis of mitochondrial dynamics genes were significantly affected in diabetic mice, compared to controls. However, treatment of animals with SS31 reduced mitochondrial dysfunction and restored most of the mitochondrial functions, and mitochondrial dynamics processes to near normal in TH mice. In conclusion, mitochondrial dysfunction is established as one of the molecular events that occur in the pathophysiology of T2D. Further, SS31 treatment may confer protection against the mitochondrial alterations induced by hyperglycemia in diabetic TallyHO/JngJ mice.

Purpose. The aim of this study was to ascertain the characteristics of major salivary glands endocrine effect on spermatogenesis. Materials and methods. Mature white outbred male rats (2 months, 153 ± 18 g) consisted of the following groups (each containing 30 rats): intact, control, and group of rats subjected to multiple amputation of incisors. To achieve hypertrophy of major salivary glands multiple amputation of incisors was performed: incisors were cut to a level of 1-2 mm above the gingival margin under ether anesthesia once every 3 days within 2 weeks. Animals of the control group were anesthetized with ether at the same time. Rats were sacrificed by CO 2 asphyxia after 2, 3, 4, 6, 8 and 10 weeks after the first amputation of incisors. Fragments of the rat testes were examined on a JEM-1400 “JEOL” (Japan) transmission electron microscope. On electron microscopy images the specific vacuolization of the cytoplasm of Sertoli cells, spermatogonia, spermatocytes and spermatids (standard units) was analyzed by the point counting method. In spermatogenic cells the proportion of mitochondria (%) with morphological signs of swelling was assessed. Results. Transient ultrastructural changes of Sertoli and spermatogenic cells develop in the rats convoluted seminiferous tubules as a result of multiple amputation of the incisors, such as phagosomes and pronounced vacuolization in the Sertoli cells cytoplasm, cytoplasm vacuolization and mitochondrial swelling in spermatogenic cells. Sporadic spermatogenic cells with signs of nuclear (chromatin fragmentation, its condensation on the periphery of the nucleus) and cytoplasm (destruction of membrane organelles) destruction appeared as a result of multiple incisors’ amputation. Ultrastructural changes of Sertoli and spermatogenic cells are most pronounced at 2-3 weeks, decrease at 4 week and are completely leveled by the 6th week of the experiment. Conclusion. Hypertrophy of major salivary glands, caused by multiple amputations of incisors, has similar to sialoadenectomy effect on the spermatogenic epithelium. Multiple incisors’ amputation cause transient depression of granular convoluted cells function. Probably submandibular gland granular convoluted tubules cells endocrine factors make the greatest contribution to the regulation of spermatogenesis in rats.

The aim of this study was to evaluate the effects of the BAC-TRAT® probiotic complex applied on diet and in the rearing water of Nile tilapia, maintained at low temperatures. Three treatments were evaluated: control (absence of the probiotic: T0), probiotic applied to the water (T1) and a diet with probiotic (T2). Productive performance of Nile tilapia was not affected by the probiotic inclusion (p>0.05). The hematological parameters were influenced by treatments, with leukocytes and lymphocytes presenting lower concentrations in T2. Regarding to the whole-fish body composition, the inclusion of the probiotic in the water led to significant increases in the ether extract concentration, whilst the ash contents was higher in the treatments T1 and T2. Regarding histomorphometry parameters of the intestine, was observed that villi height and thickness of the muscle tunic were higher in T1 in comparison to T0. For the hepatic tissue, T2 determined the lowest values of perimeter, area and volume, and the qualitative evaluation revealed little and intermediate vacuolization in all treatments. It was concluded that despite contributing for the increase of intestinal villi area, the use of BAC-TRAT® probiotic complex at low temperatures does not have beneficial effects on Nile tilapia growth.

The current study evaluates the ameliorative action of Origanumvulgareethanolic extract against the hepatotoxic effects of experimental doxycycline overdose in rats. Forty male Sprague-Dawley rats (160–200 gm) were divided into four groups: the control group, administered distilled water (10 ml/kg b.w.); group (2) administered doxycycline (39.2 ml/kg b.w.) in distilled water; group (3) administered O. Vulgare ethanolic extract (20 mg/kg b.w.) +doxycycline (39.2 ml/kg b.w.) in distilled water and group (4) administered O. Vulgare ethanolic extract (60 mg/kg b.w.) + doxycycline (39.2 ml/kg b.w.) in distilled water. All rats were administrated once per day for 4weeks. Doxycycline administrated rats showed alteration in histological structure in the liver as vacuolization, necrosis, inflammation, and sinusoidal dilatations. Also increased Kupffer cells population and congestion and dilatation of central vain with fibrin thrombi filling their lumen were shown.Ultra structurally destructed cell membrane of hepatocyte, Pyknotic and karyolitic nuclei, losses in some cytoplasmic organelles, swollen mitochondria, fragmentation of rER and discarded lysosomes were observed. All of those improved by the ethanolic extract of Origanum vulgare.

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.

It is known that amphibians inhabiting agricultural areas are constantly exposed to chemicals such as insecticides. Deltamethrin, a type II pyrethroid insecticide, is widely used in the world. The present study aimed to investigate the toxic effects of different concentrations (0.625, 1.25, and 2.50 mg/kg body wt) of orally applied deltamethrin to marsh frog (Pelophylax ridibundus) after 96 h of treatment. The histopathological abnormalities in liver, gastrointestinal tract, and kidney tissues were evaluated with quantitative analyses. In liver, increase of melanomacrophagic aggregates, non-homogeneous hepatocyte parenchyma, sinusoidal dilatations, infiltration, vascular epithelial degeneration, central vein degeneration, and congestion were determined in exposed frogs. In gastrointestinal tract, vacuolization, hypertrophy, congestion, infiltration, necrosis, and erosion of the epithelial layer, increasing goblet secretion, degeneration in villi, epithelial disorganization, and edema were observed in high-dose groups. In all experimental groups, glomerular shrinkage, hemorrhage, degeneration, infiltration, increase in Bowman distance, and eosinophilic-stained tubular lumens were detected in kidneys. Histopathological changes were more prominent in 1.25 and 2.50 mg/kg groups than the other groups. To determine the genotoxic effects of deltamethrin, the peripheral blood samples of the frogs were used. The erythrocytic nuclear abnormalities such as micro-nucleus, double-nucleus, kidney-shaped nucleus, notched nucleus, and bud nucleus were determined in the frogs, and the genotoxicity did not show a significant increase between control and low-dose groups, statistically. However, the genotoxic effects increased in medium- and especially high-dose groups. The results of this study showed that acute deltamethrin exposure can lead to histopathologic and genotoxic effects in P. ridibundus.

Leishmaniasis is a much-neglected tropical disease, especially in developing countries. Visceral Leishmaniasis (VL) is the most severe form of this infection caused by Leishmania infantum specie. It affects the splenic and hepatic systems and, when left untreated, it is fatal in 95% of cases. There is no human vaccine available and the recommended treatment not only presents adverse effects but it enables the development of resistant strains if interrupted. Hence, the urgent search for new leishmanicidal compounds. In the present work, we evaluated the in vitro leishmanicidal action of new thiosemicarbazone and thiazolidine compounds against the evolutionary forms of L. infantum, as well as their hemolytic activity, ultrastructural alterations, cytotoxicity, and nitric oxide levels on peritoneal macrophages. The inhibitory concentration 50% (IC50) against promastigote forms varied from 8.62 to 34.36 µM. In the evaluation of cytotoxicity, values of CC50 in peritoneal macrophages varied from 31.80 to 196.38 µM. Data showed that compounds JW-16.2 and GT-14 were the most promising in the series as they displayed the highest CC50 (184.58 and 196.38 μM), SI (19 and 15), low hemolytic activity, induced NO production in uninfected and infected macrophages and reduced survival of amastigotes (24.39 and 16.51 μM). Ultrastructural alterations, such as shrinkage of the cell body, shortening of the flagellum, and vacuolization of the cytoplasm, were identified. Promastigote forms treated with compounds GT-14 showed depolarization of mitochondria. Therefore, both compounds are promising due to low cytotoxicity to mammalian cells and leishmanicidal action.

Publisher's version (útgefin grein), Background: The airway epithelium (AE) forms the first line of defence against harmful particles and pathogens. Barrier failure of the airway epithelium contributes to exacerbations of a range of lung diseases that are commonly treated with Azithromycin (AZM). In addition to its anti-bacterial function, AZM has immunomodulatory effects which are proposed to contribute to its clinical effectiveness. In vitro studies have shown the AE barrier-enhancing effects of AZM. The aim of this study was to analyze whether AE damage caused by inhalation of sulfur dioxide (SO2) in a murine model could be reduced by pre-treatment with AZM. Methods: The leakiness of the AE barrier was evaluated after SO2 exposure by measuring levels of human serum albumin (HSA) in bronchoalveolar lavage fluid (BALF). Protein composition in BALF was also assessed and lung tissues were evaluated across treatments using histology and gene expression analysis. Results: AZM pre-treatment (2 mg/kg p.o. 5 times/week for 2 weeks) resulted in reduced glutathione-S-transferases in BALF of SO2 injured mice compared to control (without AZM treatment). AZM treated mice had increased intracellular vacuolization including lamellar bodies and a reduction in epithelial shedding after injury in addition to a dampened SO2-induced inflammatory response. Conclusions: Using a mouse model of AE barrier dysfunction we provide evidence for the protective effects of AZM in vivo, possibly through stabilizing the intracellular microenvironment and reducing inflammatory responses. Our data provide insight into the mechanisms contributing to the efficacy of AZM in the treatment of airway diseases., This work was supported by the Icelandic Research Council Technical Fund (Rannís Grant numbers: 186943–0611) and EpiEndo Pharmaceuticals.

The potential of central nervous system regeneration was evaluated for the first time in the injured brain of the old world killifish Aphaniops hormuzensis. The histomorphological organization in the regeneration procedure was evaluated using the hematoxylin and eosin (H&E) staining and the bromodeoxyuridine (BrdU) immunohistochemistry technique. The histological tissue sections were sampled daily for 10 days. Based on the H&E staining, a large gliosis reaction was detected along with vacuolization and telencephalon deformation on 1-day post-lesion (dpl). The vacuolated zone declined fast and the telencephalon hemisphere recovered on 3 dpl. The symptoms of injured telencephalon nervous tissue were resolved within 7 dpl in both genders. In the BrdU test of the control group, BrdU-labeled cells were observed in the ventricular zone (VZ), pallium (Pa), and lateral pallium (LPa). On 1 dpl, the BrdU+ cells accumulated in the VZ, Pa, and LPa (located near the injury area). From 3 dpl onwards, the BrdU+ cells were reduced in the telencephalic VZ, Pa, and LPa. Based on the BrdU+ results, the adult brain in A. hormuzensis possesses a remarkable capacity for neuronal regeneration. By taking into account the high neural regeneration potency of A. hormuzensis and its relatively short lifespan, it could be concluded that besides the currently known models, the members of aphaniid fishes could probably be valuable animals to study the regeneration phenomenon in the vertebrates.

The need is critical and urgent for a real-time, highly specific, and sensitive acute kidney injury biomarker. This study sought to establish a sensitive and specific Miox-NanoLuc transgenic mouse for early detection of drug-induced nephrotoxicity. We generated Miox-NanoLuc transgenic mice with kidney-specific NanoLuc overexpression. Our data showed that Miox-NanoLuc-produced luminescence was kidney-specific and had good stability at room temperature, 4 °C, − 20 °C, and repeated freeze–thaw cycles. Serum levels of BUN and creatinine were significantly increased at day 2 or 3 in cisplatin-treated mice and at day 5 in aristolochic acid (AAI)-treated mice. Particularly, the serum and urine Miox-NanoLuc luminescence levels were significantly increased at day 1 in cisplatin-treated mice and at day 3 in AAI-treated mice. Renal pathological analysis showed that the kidney sections of cisplatin-treated mice at day 5 and AAI-treated mice at day 13 showed cytolysis and marked vacuolization of tubular cells. In conclusion, we developed a new platform to early quantify drug-induced nephrotoxicity before serum BUN and creatinine levels increased and pathological tubular cell injury occurred. This model may serve as an early detection for drug- and food-induced nephrotoxicity and as an animal model to investigate tubular cell injury.

Theileria orientalis (T. orientalis) is a bovine protozoal disease similar to malaria in humans. Although the common outcome of malaria in humans and T. orientalis infection in cattle is hepatic disorder, the mechanisms of its development remain unknown. In this study, we investigated hepatocyte injury characterized by accumulation of macrophages with ingested erythrocytes in sinusoid and extramedullary hematopoiesis in cattle and mice experimentally infected with T. orientalis (T. orientalis-infected cattle and T. orientalis-infected mice). Vacuolization of hepatic cells was frequently observed in the vicinity of the aggregated macrophages in the liver sinusoids of T. orientalis-infected mice. A significant percentage of the macrophages accumulated in the liver sinusoids of the severely infected cattle and mice (14.6% and 24.2 to 53.2%, respectively) reacted positively with interleukin-1, interleukin-6 and TNF-α antibodies. Increase in the production of these cytokines was confirmed in T. orientalis-infected cattle and mice by real-time RT-PCR. These findings strongly suggest that increased cytokine production by the macrophages that have phagocytosed T. orientalis-infected erythrocytes causes hepatic disorder in T. orientalis-infected animals.

Averrhoa bilimbi has been long thought to have biological activity. The aim of this study was to determine the activity of primary and secondary metabolites from A. bilimbi fruit extract on Aedes aegypti larvae mortality and midgut histopathology. Experiment was performed to third-instar Ae. aegypti larvae collected from Surabaya, which then exposed to A. bilimbi crude fruit extract at various concentration for 24 hours. After exposure, larvae were evaluated of its mortality and fixed in 2.5% neutral buffer formalin before processed and sectioned into histological slides and stained with hematoxylin-eosin (HE). Statistical analysis was performed using Spearman rank correlation to determine histopathological damage on midgut of Ae. aegypti larvae. Phytochemical screening of A. bilimbi crude fruit extract found that it contained saponins, tannins, and terpenoids. Minimum concentration able to induce mortality on Ae. aegypti larvae (LC50) was 977 ppm, while LC90 was at 1380 ppm. Severe alteration of larvae midgut was found after 24 hours exposure to 2000 ppm extract. Features of damage mostly found in larvae midgut were disruption of the microvilli, columnar cell vacuolization, epithelial nucleus crossed midgut lumen, and basal membrane damage. Damage caused by fruit extract in midgut of Ae. aegypti third instar larvae inhibited development of larvae. This study reported first finding of histopathological effect of A. bilimbi fruits extract on Ae. aegypti larvae midgut. Result of study was expected to contribute to better understand extract bioactivity of this plant to be applied as natural larvicide for Ae. aegypti.

The insecticidal activities of four insecticides (i.e. synthetic pyrethroid"lambdathrin"; indoxacarb "steward"; mineral oil"masrona" and emamectin benzoate "proclaim") were evaluated on the 1st instar larvae of the pink bollworm, Pectinophora gossypiella, as well as determining the biochemical changes and histological effects in 10-day treated insects after treatment with LC50s of aforementioned insecticides. Lambdathrin was the most toxic insecticides followed by proclaim, then steward whereas masrona was the least toxic one. The corresponding LC50values were 1.0097, 4.0423, 300.47, and 69917.34 ppm, respectively. Fluctuated biochemical changes were achieved. Total soluble protein content decreased insignificantly after treatment with lambdathrin, masrona, and proclaim. Otherwise, treatment with steward caused a significant increase in the protein content by 85.5% than control. For total lipids content, steward caused an insignificant decrease in the total lipids content by 44.62%. While lambdathrin and masrona caused a significant decrease by 50.78 and 72.58%, respectively. Also, it is noticeable that proclaim caused a significant increase in the total lipids content by 145.19-fold than control. For the determination of the changes in the AST and ALT activity, lambdathrin caused a significant increase in the AST activity by 99.93% and a significant decrease in the ALT activity by 57.12%. Steward activated both of the AST and ALT activities over control by 308.41 & 151.77%, respectively. Masrona didn’t affect AST activity. while it caused a significant decrease in the ALT activity by 64.49%. On the other hand, treatment with proclaimdidn’t affect both AST and ALT activity. According to histological effects, signs of intoxication have begun on the level of the mid-gut. Treated larvae showed morphologically, malformation, and destruction of the epithelial columnar cells, vacuolization, and sometimes detachment of the basement and peritrophic membranes of the epithelial cells afterlambdathrin, steward, masrona and proclaim treatments. At the level of masrona and steward, treatments exhibited obvious damage to the boundaries of epithelial cells leading to disruption and fusion in the columnar epithelium cells and necrotic epithelium in some regions. On the other hand, larvae treated with both lambdathrin and proclaim produced less damage of the epithelial columnar cells. However, in both masrona and proclaim treatments, microvilli of brush border appeared to be normal.