Marked Pathological Changes Research Articles

Diagnosis and hormonal treatment of cystic ovaries associated with uterine disorders in Egyptian buffaloes: ultrasonography, histopathological and serological investigations

Cystic ovarian disease (COD) with uterine abnormalities is a postpartum reproductive pathology in Egyptian buffaloes causing significant economic losses. In this study, we aimed to employ various diagnostic methods for detecting cystic ovarian disease (COD) in Egyptian buffaloes. tour study assessed the effectiveness of the GnRH/PGF2α protocol as a treatment strategy. Our goal was to determine if this protocol could effectively reduce economic losses associated with cystic ovarian disease and improve herd fertility in Egyptian buffaloes. Eighty Egyptian buffalo cows were included in this study. They were identified to have follicular cysts through rectal examination, which was confirmed by ultrasonography. These buffaloes were then divided into two main groups: the COD Control (untreated) (GA) (n = 40) and COD group (GB) (n = 40) treated with GnRH/PGF2α. According to our immunological studies, buffaloes in the COD-treated group (GB) exhibited significantly lower serum levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) compared to the control group. This observation was consistent with the decline in E2 levels and the increase in P4 levels (p < 0.01–0.001) observed in the treated animals compared to the untreated group. Furthermore, serum cortisol and glucose concentrations decreased in COD-treated buffaloes. Histopathological examination of ovaries and uterine tissue from slaughtered COD buffaloes has revealed significant structural alterations. These include the presence of ovarian cysts of varying sizes with vacuolar degeneration. Additionally, lymphoplasmacytic endometritis was observed in the uterine tissue of affected animals, featuring degeneration and desquamation of the endometrial lining accompanied by infiltration of mononuclear inflammatory cells. Severe and prolonged cases of COD, which did not respond to treatment, exhibited marked adverse pathological changes upon histopathological assessment of the genital tract. In conclusion, hormonal treatment with GnRH/PGF2α appears to be effective in treating COD-affected animals. The study provides valuable insights into the immunological, biochemical, and histopathological aspects of cystic ovaries associated with uterine disorders in Egyptian buffaloes, while also evaluating hormonal treatment for cystic ovarian disease as a means to minimize economic losses and improve herd fertility in this species.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis

BackgroundPancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR−/−) to examine the evolution of pancreatic disease through gestation.Methods Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry.ResultsTranscriptomic evidence from bulk RNA-seq showed alterations in the CFTR−/− pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR−/− animals at 80- and 120-days gestation, as are stellate cells at term.ConclusionThe transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

An assessment of the thickness of the retinal nerve fiber layer around the optic disc using spectral domain optical coherence tomography in myopia patients at an industrial hospital in India

Myopia is rising as a silent epidemic across the globe with marked ocular morbidity and pathological changes. The retinal nerve fiber layer (RNFL) thinning is indicative of glaucomatous damage; it remains uncertain whether RNFL thickness would vary with the refractive status of the eye. It is therefore important to investigate whether any correlation exists between RNFL measurements and axial length/refractive error in myopia. Purpose. To assess the peripapillary RNFL thickness by spectral domain optical coherence tomography (SD-OCT) and to determine the correlation between axial length and peripapillary RNFL thickness in myopia patients. Material and methods. A total of 100 patients (200 eyes) with low, moderate and high myopia (ave -3.58 ± 2.45 D) aged 15 to 40 years were examined to assess the peripapillary RNFL thickness by SD-OCT and to determine the correlation between axial length (AL) and peripapillary RNFL thickness myopia patients. Results. Average 360-degree RNFL thickness (mean ± SD) was 92.25 ± 10.04 μm. In the low myopic group this parameter was 98.82 ± 6.67 μm, in the moderate myopic group — 89.28±5.23 μm, and in the high myopic group — 78.54 ± 7.32 μm. The average 360-degree mean RNFL thickness in patients with AL &lt; 24 mm was 100.06 ± 5.92 μm, in patients with AL between 24–26 mm — 89.48 ± 4.59 μm, and in patients with AL &gt; 26 mm — 78.2 ± 6.77 μm. There was significant association between thinning of the average 360-degree RNFL thickness with increasing degree of myopia and AL (p &lt; 0.0001). Conclusion. The study shows RNFL thickness decreases with increase in refractive error and increase in axial length of myopic eyes. The degree of myopia may affect the RNFL thickness differently.

Chronic exposure to tris (2-chloroethyl) phosphate (TCEP) induces brain structural and functional changes in zebrafish (Danio rerio): A comparative study on the environmental and LC50 concentrations of TCEP.

Tris (2-chloroethyl) phosphate (TCEP) is a crucial organophosphorus flame retardant widely used in many industrial and commercial products. Available reports reported that TCEP could cause various toxicological effects on organisms, including humans. Unfortunately, toxicity data for TCEP (particularly on neurotoxicity) on aquatic organisms are lacking. In the present study, Danio rerio were exposed to different concentrations of TCEP for 42days (chronic exposure), and oxidative stress, neurotoxicity, sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) activity, and histopathological changes were evaluated in the brain. The results showed that TCEP (100 and 1500µg L-1) induced oxidative stress and significantly decreased the activities of antioxidant enzymes (SOD, CAT and GR) in the brain tissue of zebrafish. In contrast, the lipid peroxidation (LPO) level was increased compared to the control group. Exposure to TCEP inhibited the acetylcholinesterase (AChE) and Na+,K+-ATPase activities in the brain tissue. Brain histopathology after 42days of exposure to TCEP showed cytoplasmic vacuolation, inflammatory cell infiltration, degeneratedneurons, degenerated purkinje cellsand binucleate. Furthermore, TCEP exposure leads tosignificant changesin dopamine and 5-HT levelsin thebrainof zebrafish. The data in the present study suggest that high concentrations of TCEP might affect the fish by altering oxidative balance and inducing marked pathological changes in the brain of zebrafish. These findings indicate that chronic exposure to TCEP may cause a neurotoxic effect in zebrafish.

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats.

In drug development, assessment of non-clinical peripheral neurotoxicity is important to ensure human safety. Clarifying the pathological features and mechanisms of toxicity enables the management of safety risks in humans by estimating the degree of risk and proposing monitoring strategies. Published guidelines for peripheral neurotoxicity assessment do not provide detailed information on which endpoints should be monitored preferentially and how the results should be integrated and discussed. To identify an optimal assessment method for the characterization of peripheral neurotoxicity, we conducted pathological, biochemical (biomaterials contributing to mechanistic considerations and biomarkers), and behavioral evaluations of isoniazid-treated rats. We found a discrepancy between the days on which marked pathological changes were noted and those on which biochemical and behavioral changes were noted, suggesting the importance of combining these evaluations. Although pathological evaluation is essential for pathological characterization, the results of biochemical and behavioral assessments at the same time points as the pathological evaluation are also important for discussion. In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.

Chitosan nanoparticle encapsulation increased the prophylactic efficacy of Lactobacillus plantarum RM1 against AFM1-induced hepatorenal toxicity in rats

Aflatoxin M1 (AFM1) is a significant contaminant of food, particularly dairy products and can resist various industrial processes. Several probiotic strains like Lactobacillus plantarum are known to reduce aflatoxin availability in synthetic media and some food products. The current work investigated the possible chitosan coating prophylactic efficacy of Lactobacillus plantarum RM1 nanoemulsion (CS-RM1) against AFM1-induced hepatorenal toxicity in rats. Twenty-eight male Wistar rats were divided into four groups (n = 7) as follows: group 1 received normal saline, group 2 received CS-RM1 (1mL contains 6.7 × 1010 CFU), group 3 received AFM1 (60 µg/kg bwt), and group 4 received both CS-RM1(1 mL contains 6.7 × 1010 CFU) and AFM1 (60 µg/kg bwt). All receiving materials were given to rats daily via oral gavage for 28 days. AFM1 caused a significant elevation in serum levels of ALT, AST, ALP, uric acid, urea, and creatinine with marked alterations in protein and lipid profiles. Additionally, AFM1 caused marked pathological changes in the liver and kidneys, such as cellular necrosis, vascular congestion, and interstitial inflammation. AFM1 also increased the MDA levels and decreased several enzymatic and non-enzymatic antioxidants. Liver and kidney sections of the AFM1 group displayed strong caspase-3, TNF-α, and iNOS immunopositivity. Co-treatment of CS-RM1 with AFM1 significantly lowered the investigated toxicological parameter changes and markedly improved the microscopic appearance of liver and kidneys. In conclusion, AFM1 induces hepatorenal oxidative stress damage via ROS overgeneration, which induces mitochondrial caspase-3-dependent apoptosis and inflammation. Furthermore, CS-RM1 can reduce AFM1 toxicity in both the liver and kidneys. The study recommends adding CS-RM1 to milk and milk products for AFM1-elimination.

Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus.

Previous studies have reported involvement of Toxoplasma gondii (T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn's disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM. Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii-induced pancreatic pathological changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8+ T cells were evaluated using immunohistochemical staining. Pancreatic tissues of T. gondii-infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in β cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8+ T cells only in islets of Langerhans of mice with chronic toxoplasmosis. Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-β cells. Since damage of β cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM.

Transcriptome sequencing of the spleen of the Yangtze sturgeon (Acipenser dabryanus) under Edwardsiella tarda and poly(I:C) treatments

Acipenser dabryanus is an ancient living fossil and a flagship species of the Yangtze River. However, A. dabryanus was listed as a critically endangered species due to the dramatic decrease in its population, and disease outbreaks occurring during captive breeding have hindered the protection of this species. Here, we investigated the effect of the pathogenic bacterium Edwardsiella tarda and poly(I:C) on A. dabryanus at the histopathological and transcriptomic levels. After 48 h of infection with E. tarda, A. dabryanus exhibited marked pathological changes in the intestine and liver. We then conducted full-length transcriptome sequencing of the spleen by SMRT sequencing technology. Using the full-length transcriptome data as a reference, transcriptomic results obtained through Illumina sequencing technology revealed that a total of 894 and 963 unigenes were differentially expressed between the PBS and bacterial infection groups and between the PBS and poly(I:C) challenge groups, respectively. E3 ubiquitin ligases family members, T-cell receptor and clusters of differentiation were significantly upregulated by bacteria or poly(I:C) treatment, while the complement was significantly downregulated, suggesting that they might participate in multiple immune pathways in the response to pathogen invasion. Pathogen infection also induced changes in some key rate-limiting enzymes involved in energy metabolism. Our study can provide important information on the molecular mechanisms underlying the immune response of fish to pathogenic microbial infections and help explore the antibacterial and antiviral immunity of A. dabryanus.

Apigenin Ameliorates Lead Acetate Induced Hyperlipidemia and Hypogonadism in Male Rats

Background: Lead (Pb) is an environmental pollutant and has detrimental effects on human health. Apigenin (APG) is a flavonoid that have antioxidant, anti-inflammatory and antiallergic and cardioprotective so is used as treatment of many diseases. The aim of the present study was to evaluate the probable protective effect of APG against Pb-induced toxicity in rats. Methods: Adult male rats were given either Pb (as lead acetate; 20 mg/kg) alone or in combination with APG (20 mg/kg) daily for 4 weeks by intraperitoneally injection (i.p). At the end of the experimental period, Pb accumulation, lipid profile and testicular function alterations were assessed. In addition, histopathological changes in the testis were assessed. Result: Results revealed that Pb treatment significantly increased Pb concentrations in blood and testis of rats. Further, the blood levels of hormones related to testis were altered in Pb-treated rats. In parallel, low sperm count and sperm motility, increased sperm abnormalities and marked pathological changes in testis were observed. On the contrary, the treatment with both Pb and APG recorded amelioration of the deleterious effects of Pb, involving attenuation of changes in lipid profile and testicular hormonal levels, sperm parameters and pathological changes in Pb treated rat’s testis. In conclusion, it appears that dietary APG can ameliorate lead acetate induced hyperlipidemia and hypogonadism in male rats.

Cellular immune response of Staphylococcus aureus enterotoxin B in Balb/c mice through intranasal infection.

Background and Aim:Staphylococcus aureus produces various superantigen exotoxins, including staphylococcal enterotoxin B (SEB). It causes fatal anaphylactic reactions and toxic shock. This study aimed to evaluate the reaction of leukocytes and histopathological changes in the respiratory organs of Balb/c mice after intranasal infection with enterotoxigenic S. aureus (SEB).Materials and Methods:The presence of the seb gene in S. aureus was established in this study using polymerase chain reaction-specific primer. Two groups of 8-week-old male Balb-c mice consist of six mice in each group. The treated group was infected with 50 μL and 100 μL of SEB intranasal on days 1 and 14, respectively. NaCl was administered in the second group and was considered as a control group. Blood samples were collected through the retro-orbital plexus on days 1, 4, 7, 14, and 22 after infections. Total cell counts were analyzed with an independent sample t-test and compared using the statistical package for the social sciences (SPSS) version 16.0 (IBM Corp., NY, USA). The infected tissues of the respiratory organ were observed descriptively and compared to the control group.Results:The seb gene with a molecular size of 478 bp, indicating the SEB strain, is present in S. aureus used in this study. Intranasal administration of SEB showed increased leukocytes, lymphocytes, monocytes, and eosinophils on day 22 post-infection. Significant leukocytosis was seen on days 6 and 14; lymphocytosis on days 1, 4, 6, and 16; and eosinophilia on days 6, 14, and 22 compared with the control group (p > 0.05). In contrast, the neutrophil decreased after an increase of immature band cells compared to the control group, indicating a severe acute infection with SEB. The lungs and trachea of the test group had an inflammatory cell accumulation in the respiratory organ.Conclusion:Intranasal route infection of S. aureus containing seb gene significantly induced the cellular immune response and caused pathological changes in the respiratory tissues of the Balb/c mice model. The hematological changes were aligned with marked pathological changes in the respiratory tract. Balb/c mice could be an excellent experimental model to study toxic and anaphylactic shock against SEB to define the future therapeutic agents.

Simulation of Bubonic Plague in BSL-2 Laboratory

The causative agent of plague, Yersinia pestis, is classified as pathogenicity (hazard) group I agent, which means that the work with “wild type” strains should be carried out in BSL-3 facilities. Y. pestis EV NIIEG is a Δpgm strain, allowing experimental studies to be carried out in BSL-2 laboratories. However, the disease and its progression elicited by such strain do not entirely mirror the infection observed with fully virulent strains. Residual virulence of Y. pestis EV NIIEG strain for mice can be increased under in vivo iron supplementation. The aim of the study was to optimize methodological approaches to modeling experimental plague in laboratory animals following administration of attenuated Δpgm Y. pestis strains with iron dextran. Materials and methods. Simulation of plague infection in outbred mice was carried out through subcutaneous inoculation of Y. pestis EV NIIEG strain with iron dextran supplementation. The animal condition was assessed on a daily basis. In the course of the experiment, the pathological presentation and bacterial content in organs of mice were evaluated. Results and discussion. Mice inoculated subcutaneously with Y. pestis EV NIIEG strain in the presence of iron dextran developed a bubonic plague that resulted in lethal outcome with pathological changes of internal organs, characteristic of plague infection. In case of daily administration of iron, LD50 of Y. pestis EV NNIEG strain for the mice significantly exceeded the same one with a single injection. Differences in the survival rate among animals in the groups with a single and multiple administration of iron compared to the control group were statistically valid. Thus, attenuated Δpgm Y. pestis strains in the presence of iron dextran can be used to model experimental plague in mice with marked pathological changes and lethality in BSL-2 laboratories.

Immunophenotypical and pathological changes in dogs experimentally infected with Ehrlichia canis.

Canine monocytic ehrlichiosis (CME) is one of the most important tick-borne diseases worldwide, with multisystemic presentations. Immune dysregulation has been proposed as the primary mechanism involved in its pathogenesis and in tissue injury in dogs with CME. Experimental infection of German Shepherd dogs in the present study demonstrated that CME caused marked pathological changes in their lymph nodes and spleen, and also gave rise to mononuclear infiltration in organs and tissues. Immunophenotyping of cells in lymph nodes, spleen and injured tissues highlighted differences in lymphocyte subsets, local expression of immunoglobulin subclasses and MHCII molecules between infected and control dogs. These findings suggest that the immunophenotypic and immunopathological changes in dogs with acute experimental CME are related to Th1 bias and compartmentalized immune response.

Myths and reality about the effects of glutamate. Compilation of scientific data of modern world literature

The aim of our scientific work was to study the existing experimental models of glutamate effects on the body and to understand the mechanisms of this effect and its possible consequences. To achieve this goal, we have studied different sources of scientific medical literature. Results. In a healthy body, glutamic acid is secreted by brain neurons in the required amount as a neurotransmitter and participates in the main information flows of human body. Sodium glutamate, which enters the body with food in large quantities, affects the body, causing general toxic effects and has a local effect on the stomach, intestines, salivary glands and pancreas and so on. Based on the scientific literature, experimental models that study the effects of glutamate are divided into two types: models in which glutamate enters the body orally and when glutamate is administered subcutaneously and intraperitoneally in the neonatal period of life. In the first route of administration, glutamate causes a toxic effect, which is manifested in increased catalytic activity in the blood serum of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltranspeptidase in 2.5; 1.6; and 1.5 times, respectively, while the activity of alkaline phosphatase remained at control levels, indicating a pronounced hepatotoxic effect of monosodium glutamate as a dietary supplement. It causes an increase in content of total and tyrosine-containing peptides in the blood serum, increase of substances of low and medium molecular weight, as well as an increase in the values of intoxication, which indirectly indicates a violation of the detoxification of endogenous metabolites in the liver of experimental animals. Ingestion of sodium glutamate within the recommended doses has not been shown to cause marked pathological changes in the mucous, muscular and serous membranes of the gastric wall, but there is a slight fullness of the vessels of the submucosal membrane. It has been found that in high doses, sodium glutamate has a local pathogenic effect on the tissues of the stomach, which consists in thinning all layers of its wall, desquamation of the mucous membrane and its disorganization by reducing the size of gastric glands, increasing the number of vessels and their fullness with blood. One of the mechanisms of pathogenic effect of sodium glutamate is the contact local and free radical oxidizing effect on gastric tissues. In the oral route of administration of glutamate there are no phenomena of fat growth (obesity) as epidermal, which is characteristic of the abdominal form of obesity, so and pararectal, parallelic, pararenal and retroperitoneal, which is characteristic for the visceral form of obesity. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. Conclusion. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. There is no doubt in the fact, which is based on the results of numerous experimental studies and covered in professional scientific litefrature, that the abdominal form of glutamate-induced obesity is possible only with subcutaneous and intraperitoneal routes of its administration in the neonatal period of life and while intraorall way of administration does not occur.

Potential role of dietary chitosan nanoparticles against immunosuppression, inflammation, oxidative stress, and histopathological alterations induced by pendimethalin toxicity in Nile tilapia

A 21-days feeding screening period was conducted to highlight the protective efficacy of dietary chitosan nanoparticles (CSNPs) on pendimethalin (PD)-induced toxicity in Nile tilapia (Oreochromis niloticus). Hematology, non-specific immune response, the antioxidative enzymes [superoxide dismutase (SOD) and catalase (CAT), glutathione reduced (GSH), and glutathione peroxidase (GPx)] in the liver and anterior kidney, changes of pro-inflammatory cytokine genes [interleukins-8 (IL-8), interleukins-1β (IL-1β), and tumor necrosis-α (TNF-α)] in the anterior kidney and histopathological alterations were assessed. Fish (50 ± 7.5 g) were randomly assigned into four groups (Three replicates), the first group served as the negative control and fed on the control diet only, and the second group served as the positive control and fed on the control diet supplemented with CSNPs (1 g kg−1 diet). The two other groups were exposed to 1/10 96-h LC50 PD (0.5 mg L−1) in rearing water and simultaneously fed the control diet alone or supplemented with CSNPs (1 g kg−1 diet), respectively. Fish were fed on the experimental diets twice a day for 21 days. The results revealed that PD exposure caused a significant decline in the survival rate of the Nile tilapia, as well as in most of the hematological indices, respiratory burst activity, phagocytic activity, total immunoglobulin levels, lysozyme, and bactericidal activity. Additionally, PD toxicity markedly suppressed most of the antioxidative enzymatic activities in both tissues together with upregulation of immune genes (IL-8 and TNF-α); however, IL-1β expression remained unaffected. The histopathological results revealed marked pathological changes in spleen, liver and intestine with a notable decrease of intestinal goblet cells in PD-exposed groups. Conversely, CSNPs exerted protective effects through improving the above mentioned parameters. Thus, CSNPs supplementation exhibited defensive effects against PD toxicity in Nile tilapia that might provide an insight into the promising role of CSNPs as a potential immunomodulatory feed additive for tilapia in aquaculture.

Acute toxicity of diallyl sulfide derived from Allium sativum (garlic) in mice and its possible mechanisms

BackgroundDiallyl sulfide (DAS) is a garlic-derived organosulfur compound known for its chemotherapeutic properties, as a strong food additive and a potential radiomitigator. Despite its therapeutic potentials, the apparent lack of toxicity data hinders its clinical applications. PurposeThe present study investigated the pre-clinical toxicity of DAS to identify the maximum tolerable and lethal doses and understand its underlying mechanisms at toxic doses. Study designDAS was administered intraperitoneally to C57BL/6 mice at a range of concentrations (160, 1280, 1600, and 1920 mg/kg). Standard toxicological endpoints (survival, body weight changes, hematology, histopathology, and serum biochemistry) were supported with genotoxicity and molecular studies. Findings were correlated with DAS stability by HPLC. ResultsA single dose of DAS up to 1280 mg/kg was well-tolerated without significant changes in standard toxicological parameters. Death was observed at 1600 mg/kg (1/5 male) and 1920 mg/kg (2/5 female and 3/5 male) doses. DAS at 1920 mg/kg dose level also induced marked pathological changes in the lungs, liver, and reproductive organs. This dose increased hepatic enzyme activities and significantly reduced blood cell count. Inflammatory markers like CD68 and NF-κB were upregulated in the lungs. Propidium iodide stained ovarian and testicular germ cells revealed alterations in cell cycle distribution and increased cell death at 1920 mg/kg dose. At the highest dose of DAS, evidence of genotoxicity in terms of the occurrence of a few double minutes, rings, and fragments appeared. HPLC studies revealed a significant and rapid decrease in the DAS peak area following incubation with canola oil or plasma in vitro. ConclusionOur results indicated that lungs, liver, and reproductive organs are affected at higher DAS doses. Based on the findings, we conclude that excessive usage of DAS should be limited owing to the associated toxicities at higher concentrations (1600 mg/kg and above).

Detraction of Diclofenac-Associated Hepatotoxicity by Fresh Beet Root Juice in Male Albino Mice

The beet root as dietary supplement hepatoprotective ability has gained interest in recent days. The present study was designed to determine the potential hepatoprotective effect of beet root juice as anti-inflammatory and anti-oxidant agent to eliminate the hepatotoxic effect of diclofenac as wide spread analgesic agent. Male albino mice were divided randomly into 4 groups, the 1st group served as control group, the 2nd group received 8 mL/kg of freshly prepared beet root juice, the 3rd group received oral administration 20 mg/kg of diclofenac and the 4th group pre-treated with beet root before one-hour diclofenac administration for 30 days. Biochemical results revealed sharp significant raised levels of liver enzymes level (AST, ALT, ALP and GGT) in the 3rd group that received diclofenac, besides to marked pathological changes manifested by high pathological scoring system such as hepatocytes degeneration, ballooning, infiltration and fibrosis. Immunohistochemical analysis elucidated massive incidence of MDA as an indicator of oxidative stress, moreover great number of neutrophils were seen as main component of inflammation. Whereas, pre-treatment of beet root juice one hour before diclofenac resulted in significant decrease of liver enzymes, clear attenuation of pathological features, decrease of pathological score. A great reduction of MDA in liver tissue and number of neutrophils stained histochemically. It was concluded that beet root juice possessed beneficial hepatoprotective role against diclofenac, as significant anti-oxidant and anti-inflammatory effect.

Subacute toxicity of vatsanabha (aconitum ferox, ranunculaceae) collected from different regions of India and Nepal

Introduction: Aconitum ferox wall is considered as one of the most poisonous plants in the world and well known for its toxicity. The Vatsanabha (Sanskrit terminology) is mentioned as Mahavisha (most toxic) in Ayurveda literature. The aim of our study was to evaluate and compare the toxic effects of a root of Vatsanabha (A. ferox) aqueous extract on hematological, cardiac, and serum biochemical parameters and histopathological changes in the heart. Methods: A. ferox crude powder was prepared from tuber root collected from three geographical location: Naradevi root, Sikkim root and Dolpa root and dosed in three groups Naradevi root dosing Group (NRG), Sikkim root dosing group, and Dolpa root dosing group (DRG), respectively. They were orally administered on Wistar albino rat for 28 consecutive days at doses of 1/5th of the respective median lethal dose of dried crude powder per kg body weight in 20 ml of stock solution. Results: The results showed significant changes in serum glutamic-pyruvic transaminase, alkaline phosphatase, high-density lipoprotein in NRG, and serum glutamic-oxaloacetic transaminase, cardiac parameters-creatinine kinase MB, lactate dehydrogenase in DRG. Marked pathological changes were perceived in the brain, heart, lungs, and jejunum tissue. Conclusion: The marketed sample shows multiple visceral toxicity and higher altitude sample has greater toxicity on brain and cardiac tissue. This study recommends creatine phosphokinase (CPK) isoenzyme testing: CPK-BB, CPK-MB, etc., on the heart and brain to assess the exact source of the damaged tissue.

Az amerikai májmétely (Fascioloides magna) expanziója Délnyugat-Magyarországon – Előzetes közlemény

Európában a Fascioloides magna több endémiás területen fordul elő. A féreg a különböző élőhelyek között a végleges gazdák mozgásával, a köztigazdák széthurcolásával, illetve állatszállítások útján terjed. A tanulmányban a szerzők öt, Belső-Somogyban elejtett gímszarvas esetfeldolgozásával mutatják be a F. magna fertőzöttség terjedését. A parazitológiai vizsgálatok során négy állatban, eltérő intenzitással fordult elő a faj, egy esetben csak a férgek májban történő vándorlásának jellegzetes nyomait figyelték meg. A nagy amerikai májmétely 2018-ban megismert legészakibb belső-somogyi előfordulása és a jelenlegi előfordulások között a távolságok 21,0-37,8 km közé estek. Az eredmények a F. magna további dél-dunántúli terjedését támasztják alá.

Mercury and Selenium Localization in the Cerebrum, Cerebellum, Liver, and Kidney of a Minamata Disease Case.

Minamata disease is a methylmercury poisoning caused by consumption of marine food contaminated by man-made methylmercury environmental pollution, and its most prominent feature is marked pathological changes in the central nervous system. Morphological alterations are less pronounced in the liver and the kidney, although their mercury levels are higher than those of the brain. In marine mammals, methylmercury is known to be easily converted to inorganic mercury and it combines with selenium forming mercury selenide, which may counteract the toxicity of mercury. However, little is known about the formation of mercury and selenium complex in human organs. In the present study, we examined the cerebrum, cerebellum, liver, and kidney of a Minamata disease case to study the mercury and selenium localization using electron probe microanalysis. Our results indicated the mercury and selenium localization in the specified tissue of the brain, liver, and kidney such as glial cells, Kupffer cells, and renal tubules.

Lacrimal Gland Botulinum Toxin Injection Versus Simple Glandular Needling: Histopathological and Electron Microscopic Evidence and Potential Clinical Implications.

To investigate the histopathological and ultrastructural changes in the lacrimal glands (LGs) of rabbits following either botulinum toxin (BTX) injection or simple glandular needling. Twenty-four LGs of 24 eyes of 12 healthy New Zealand white rabbits were included in the study. Of these, 4 LGs of 4 eyes of 2 rabbits were used as controls. In the intervention group, all the right LG received 5 U in 0.1 ml of BTX-A (Botox, Allergan, Dublin, Ireland) and the left LG received simple glandular needling under general anesthesia. The BTX-A was injected directly into the LG via the transconjunctival route under direct visualization. For simple needling, 5 LG passes were made through a single-entry point using a 29-gauge needle mounted on an empty tuberculin syringe. The rabbits did not receive any postoperative medications other than lubricants. The rabbits were sacrificed at 8 weeks and the 20 treated and 4 control LG's were retrieved for histopathological and transmission electron microscopic (TEM) analysis as per standard protocols. In comparison to the control LG samples, both the treated groups showed pathological changes, which were more pronounced in the simple needling group. The BTX-A-treated LGs showed mild to moderate acinar atrophy, few degenerating acini and patchy chronic inflammatory infiltrates with thick hyalinized collagen within the glandular stroma. TEM analysis showed the cytosol of few acinar cells to contain vacuoles and autophagosomes with marginal chromatin condensation of the nucleus and an eccentric nucleolus. The LGs treated with simple needling showed marked pathological changes which include moderate to severe, focal, and diffuse acinar atrophy, dense stromal fibrosis, inflammatory infiltrates, and peri-vasculitis. TEM analysis showed focal disorganized acinar morphology, loss of intra-acinar and ductal architecture, and needle track zones with surrounding fibrotic areas. Histopathological and ultrastructural changes were noted in the LGs treated with BTX-A and simple glandular needling. Simple needling of the LG has the prospect to be an effective and cheaper alternative to BTX-A.