Mononuclear Leukocyte Infiltration Research Articles

Purified L-glutaminase effects against multidrug-resistant Pseudomonas aeruginosa in experimental vaginosis model: An immunological and histopathological observation

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin −12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use.

Antidiabetic and Liver Histological and Ultrastructural Effects of Cynara scolymus Leaf and Flower Head Hydroethanolic Extracts in Nicotinamide/Streptozotocin-Induced Diabetic Rats.

This study aims to investigate the effect of hydroethanolic extracts of Cynara scolymus (C. scolymus) leaf (CLHE) and C. scolymus flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C-peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor-α in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ-induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill-defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, via suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.

Low doses and short duration of prednisolone administration in guinea pigs experimentally infected with Schistosoma haematobium: Histopathology of liver and lungs

In our previous study, administration of 5 mg prednisolone for five days pre-Schistosoma haematobium infection in guinea pigs increased susceptibility and produced pathological reactions in the liver and bladder. Since corticosteroids can suppress granuloma formation, maturation, and size, this study sought to investigate if prednisolone given at low doses and short duration can produce granulomatous lesions in the tissues of guinea pigs experimentally infected with S. haematobium. Guinea pigs were shared into six groups: group I and II were the immunosuppressed-infected guinea pigs (I0.5 and I1.5- 20 animals each), group III was the unimmunosuppressed-infected guinea pigs (UI- 20 animals), and group IV, V and VI were the immunosuppressed-uninfected and normal guinea pigs (D0.5, D1.5, and normal- 10 animals each). Prednisolone was given in doses of 0.5 mg/kg and 1.5 mg/kg to the different groups, a day before infection and on day 5 post-infection. The infected groups were subcutaneously injected with 250–300 S. haematobium cercariae. Screening for S. haematobium eggs in urine and fecal samples of animals, and quantitative analysis for leukocyte and red blood cell (RBC) counts in urine samples of guinea pigs began nine weeks post-infection (WPI). Guinea pigs were killed, perfused, worms recovered and sections of the liver, lungs, and bladder excised for histopathological examination at 6, 8, 11, 14 and 16 WPI. S. haematobium eggs were only seen in urine samples of I1.5 at 15 and 16WPI. Although the parasite eggs were seen in fecal samples of all infected guinea pigs from 9WPI, those of UI were sparse and took longer time to hatch. High leukocyte counts were seen in all immunosuppressed groups at 6WPI, which returned to normal levels in D1.5 and D0.5 at 16WPI. At 16WPI, significant numbers of leukocyte and RBC counts were seen in urine samples of I1.5. The immunosuppressed-infected groups had significant numbers of mature and total worm loads than UI group (p > 0.05). However, the worm burden of I1.5 was higher than I0.5 at 14WPI and 16WPI. Non-granulomatous lesions were only recorded in the liver sections of the immunosuppressed-infected animals and in lung sections of UI and I1.5 guinea pigs. Liver lesions seen were hepatocyte degeneration; necrosis; Kupffer cell involvements as hyperplasia, phagocytosis, proliferation; hyperaemia and haemorrhage, and mononuclear leukocyte infiltration. Lung lesions seen in I1.5 at 11-16WPI were hemosiderin depositions and hyperaemia, emphysema and atelectasis, and mononuclear leukocyte infiltrations while in UI, emphysema and mononuclear leukocyte infiltration were seen only at 16WPI. In the immunosuppressed-infected groups, composite liver lesion scores showed that peak lesion severity was at 8WPI and 11WPI in I1.5 and I0.5, respectively. However, there was no significant difference (p = 0.105) in composite liver lesion scores of I1.5 and I0.5. Lung lesion score of UI at 16WPI was significantly higher (p > 0.05) than that of I1.5. Findings from this study show that even at low doses and short duration of administration, corticosteroids can only increase susceptibility of guinea pigs but cannot improve its suitability as experimental models of S. haematobium infection.

Clinicopathologic Associations in a Large International Cohort of Patients With Giant Cell Arteritis

In addition to aiding in diagnosis, histopathologic findings from temporal artery biopsy (TAB) specimens in giant cell arteritis (GCA) may be valuable for their associations with clinical features of the disease. This study was undertaken to compare histopathologic findings on TAB with biopsy interpretation and demographic, clinical, and imaging features at time of diagnosis. Patients with a clinical diagnosis of GCA who had a TAB were selected from an international, multicenter observational cohort of vasculitis. Associations between demographic, clinical, radiographic, and histopathologic features were identified using bivariate testing and multivariate regression modeling. Of 705 patients with GCA who underwent TAB, 69% had histopathologic evidence of definite vasculitis. Specific histopathologic findings included the presence of giant cells (51%), fragmentation of the internal elastic lamina (41%), intimal thickening (33%), and predominantly mononuclear leukocyte infiltration (32%). Histopathologic interpretation of definite vasculitis was independently associated with giant cells (odds ratio [OR] 151.8 [95% confidence interval (95% CI) 60.2-551.6]), predominantly mononuclear leukocyte infiltration (OR 11.8 [95% CI 5.9-24.9]), and fragmentation of the internal elastic lamina (OR 3.7 [95% CI 1.9-7.4]). A halo sign on temporal artery ultrasound and luminal damage of large arteries on angiography were significantly associated with presence of giant cells (OR 2.6 [95% CI 1.1-6.5] and OR 2.4 [95% CI 1.1-5.2], respectively). Specific histopathologic findings were associated with older age, but no associations were identified with vision loss or other clinical features. Histopathologic findings in GCA are strongly associated with the clinical diagnosis of GCA but have a limited role in identifying patterns of disease.

Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats.

Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, antimetabolic, and immunosuppressive agents with substantial risks such as oxidative lesions to the liver. This study examined the effect of grape seed extract (GSE; gervital) in attenuating hepatotoxicity caused by MTX or AZA treatment. Rats were divided into six groups (six rats per group): Group I, normal control group; Group II, GSE (150mg/kg/day); Group III, MTX (8mg/kg/week); Group IV, AZA (15mg/kg/day); Group V, GSE (150mg/kg/day) + MTX (8mg/kg/week); and Group VI, GSE (150mg/kg/day) + AZA (15mg/kg/day). After 35-day experimental period, all rats were sacrificed and blood was collected for biochemical study and hemoglobin (Hb) assessment. The liver was weighed and triaged for histological, ultrastructural, and biochemical studies. MTX and AZA treatment decreased Hb levels, increased relative liver weight, increased the activity of glutamate pyruvate transaminase (ALT) and glutamate oxaloacetate transaminase (AST) aminotransferase (ALT) and aspartate aminotransferase (AST) values, and displayed histopathological and ultrastructural alterations. These changes included the disorganization of hepatocytes, pyknosis, karyolysis of some nuclei, and mononuclear leukocytic infiltration. The liver with significant oxidative stress (OS) showed decreased reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and increased malondialdehyde (MDA) levels. In contrast, GSE administration ameliorated ALT, AST, and all histopathological and ultrastructural changes. GSE treatment also reduced MDA levels but increased the antioxidant parameters. In conclusion, it was concluded that GSE supplementation could be considered as a promising antioxidant in reducing OS, histopathological and ultrastructural alterations induced by MTX and AZA.

Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms

Ethnopharmacological relevancePeptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. Aim of the studyHere, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. Material and methodsRats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. ResultsOral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1β levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. ConclusionsThe gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Otitis Media and Internal with Brainstem Extension in a French Bulldog

Background: Otitis is a frequent condition in dogs, with a multifactorial etiology covering primary causes, predisposing and perpetuating factors. It is characterized by an inflammatory process of structures that make up the auditory system, with prevalence data ranging from 15 to 20%, which can occur in any age group and without sex predisposition. According to the location, it can be classified as uni or bilateral, affecting the outer, middle and / or inner ear, the latter two being associated with neurological changes such as vestibulopathy, facial nerve paresis and Horner's syndrome. The morbidity and mortality of otitis media and internal may increase with delay in diagnosis, resulting in delay in the correct treatment, and the extension to brainstem is described in felines and considered rare in dogs. The present study aims to report an atypical case of otitis media and internal, with extension to the brain parenchyma in a brachycephalic dog.Case: A 3-year-old bitch French Bulldog canine was seen, weighing 12 kg, with a history of vomiting, apathy, nystagmus, ataxia and acute evolution hemiparesis. As a result of adoption, it was not known about the animal's morbid past. On special physical and clinical examination, depressed mental status, changes in postural reactions, nostril stenosis with unilateral mucopurulent nasal discharge, corneal ulcer, palpebral and labial ptosis, absence of eyelid reflex and spontaneous strabismus were observed, all of these findings observed on the left side of the face. No signs of otitis external to otoscopy were found. The clinical signs found characterize left facial nerve paresis and peripheral and central vestibulopathy. Otitis media / internal and meningoencephalitis were suspected. Hemogram, serum biochemistry (glucose, urea, creatinine, alanine aminotransferase, total proteins, albumin, globulin, alkaline phosphatase, gamma glutamyltransferase, phosphorus, total bilirubin, cholesterol and total calcium), urinalysis, rapid tests for erlichiosis, anaplasms , borreliosis, heartworm, distemper and leishmaniasis, CSF analysis, neurological panel performed by PCR (Polymerase Chain Reaction) that tested the animal for Bartonellosis, Lyme Disease (Borrelia burgdorferi), Blastomyces dermatitidis, Cryptococcus sp., Virus West Nile, Distemper, Toxoplasmosis, Neosporose and Coccidioides sp. using conjunctival swab, whole blood, urine and CSF samples. The samples were negative for all of these tests. As an image exam, brain magnetic resonance was performed. In the latter, otitis media and left internal was observed with extension of the lesion to the brain parenchyma. CSF analysis showed cytological changes compatible with a non-suppurative inflammatory process, mild pleocytosis with predominantly mononuclear leukocyte infiltrate. As a form of treatment, antibiotic therapy and total ablation of the auditory canal with lateral bulectomy were performed, showing good results with reduced clinical symptoms.Discussion: It is concluded that although the diagnosis of otitis media and internal with extension to brainstem is more common in cats, it should be included as a differential for central vestibular disorders in dogs, and that the diagnosis together with early and effective treatment are important, since that the evolution of the infection to the central nervous system represents a risk to the patient.Keywords: vestibulopathy, meningoencephalitis, brachycephalic.Descritores: vestibulopatia, meningoencefalite, braquicefálico.Título: Otite média e interna com extensão para tronco encefálico em cão buldogue francês

Histological, ultrastructural, and biochemical study on the possible role of Panax ginseng in ameliorating liver injury induced by Lambda cyhalotherin

BackgroundLambda-cyhalotherin (LCT) is a pyrithroid type 2 pesticide that is broadly utilized in pest control in public health, animal health, and agriculture. Although claiming that LCT has a low mammalian toxicity, several investigations reported its mammalian hepatotoxicity by mediating oxidative stress causes severe hepatotoxicity and liver damage.ResultsLCT significantly decreased catalase (CAT), superoxide dismutase (SOD), and total thiol (T. thiol) and increased lipid peroxidation (LPO). mRNA and protein expression levels of p53 were upregulated, whereas Bcl-2 mRNA and protein expression levels were downregulated in LCT-intoxicated animals. Also, light microscopic and ultrastructure studies for liver tissues of LCT-intoxicated animals showed mononuclear leukocytic infiltration in the parenchyma, congested portal vein with thickened wall, and proliferation of bile duct and hepatocytes with cytoplasmic vacuolations, fatty changes, and collagen fibers. Panax ginseng co-treatment attenuated oxidative stress biomarkers. Both tested doses of Panax ginseng (100 and 200 mg /kg b. wt./day) significantly decreased p53 and elevate Bcl-2 mRNA and protein expression levels and reveals significant amelioration and restoration of normal histology and ultrastructure of liver, but 200 mg/kg b. wt. of Panax ginseng seems to be more potent.ConclusionPanax ginseng exhibited ameliorative effect against hepatic oxidative stress, apoptosis, histopathological, and ultrastructural changes induced by LCT.

Enhancement of Anti-allergic Effect of Diethylcarbamazine Citrate in Asthmatic Mouse Model: Testing of Anti-drug Antibodies and Quercetin.

Diethylcarbamazine citrate (DEC) is known as an effective treatment for bronchial asthma because of its ability to reduce eosinophil trafficking to the lung tissue. The current study aimed to potentiate the anti-allergic effect of the drug by passive immunization of the asthmatic model with anti-DEC antibody or prior treatment with quercetin (Qur). Eight mice groups were categorized into control, the model of lung asthma, treated with DEC, passively immunized with anti(α)-bovine serum albumin Ab, anti-DEC Ab, prior exposure to 10, 20, or 40 mg Qur/Kg. b.wt. Both eosinophil peroxidase (EPO) and eotaxin2 in the lung tissues were performed. Serum levels of cytokines, bronchoalveolar lavage fluid (BALF) IgE, rabbit anti-bovine serum albumin (anti-BSA), and DEC IgG in lung tissue homogenates were assayed by ELISA. Regarding the effect of anti-DEC Ab and Qur on DEC-induced recovery of histopathological alterations showed that the Ova group had peri-bronchial hyperplasia, mononuclear leukocyte infiltration, thickening in the wall of alveoli, and congested blood vessels. However, the reduction of inflammatory cells and thickened alveolar walls was dependent on the Qur dose. Qur40 enhanced the anti-allergic effect of DEC. Moreover, the present data revealed high levels of Th2 cytokines (IL-4 and IL-5) and IgE in the Ova group. An increased leukocyte infiltration/thickening of the alveolar wall and lung tissue EPO/eotaxin2 were also observed. Qur-40 could show an enhancement effect on DEC for the reduction of IL-4, IL-5, IgE, EPO, and eotaxin 2. Consequently, the IFN-γ/IL-4 ratio was increased. Qur at 40 mg/Kg could be recommended to enhance the DEC effect suggesting a novel approach for treatment.

Ameliorative effects of Panax ginseng on lung of Lambada cyhalotherin-intoxicated rats

Introduction: Lambada-cyhalotherin (LCT) caused severe oxidative damage in liver, lung and testis.Aim of the Study: The objective of this research was to evaluate the ameliorative activity and underlying techniques of pure Panax ginseng (G) using rat model of LCT-induced lung damage.Materials and Methods: 36 male adult laboratory rats Rattus norvegicus domestica in weights around 135±10 g were separated into 6 experimental groups: 1st control group. 2nd and 3th groups were G groups (100 and 200 mg G/kg b. wt.) LCT group was given by oral gavage LCT (61.2 mg /kg b. wt.) that is equivalent to 1/10 of LD50. The 5th and 6th groups were co-treated with two doses of G.Results: LCT significantly decreased superoxide dismutase (SOD), catalase (CAT) and total thiol (T. thiol) and increased lipid peroxidation (LPO). mRNA and protein expression levels of p53 gene (apoptotic gene) were increased, whereas, Bcl-2 gene (anti-apoptotic gene) mRNA and protein expression levels were decreased in LCT-treated animals. Also, light microscopic and ultrastructure studies for lung tissues of LCT-treated animals showed marked hyperplasia of dilated bronchioles wall, RBCs extravasation in bronchiolium lumen and mononuclear leukocytic infiltration in parenchyma. Additionally, blood vessels congested with thickened walls, alveoli appeared collapsed with compensatory expansion of adjacent alveoli divided by thickened inter-alveolar septa, besides to damage in type 1 and type 2 pneumocytes. G co-treatment attenuated oxidative stress biomarkers. Both tested doses of G significantly decreased p53 and elevate Bcl-2 mRNA and protein expression levels and revealed significant amelioration and restoration of normal histology and ultrastructure of lung.Conclusion: In summary, G has exhibited ameliorative activity against oxidative stress induced by LCT in lung, apoptosis, histopathological and ultrastructural changes in albino rats.

Lack of interleukin-33 and its receptor does not prevent calcipotriol-induced atopic dermatitis-like inflammation in mice

Current studies addressing the influence of interleukin-33 or its receptor (IL-33R/ST2) on development of atopic dermatitis-like inflammation in mice have reported conflicting results. We compared the response in single- and double-deficient IL-33−/−/ST2−/− C57BL/6J BomTac mice in the well-established calcipotriol-induced model of atopic dermatitis. All genotypes (groups of up to 14 mice) developed atopic dermatitis-like inflammation yet we observed no biologically relevant difference between groups in gross anatomy or ear thickness. Moreover, histological examination of skin revealed no differences in mononuclear leukocyte and granulocyte infiltration nor Th2 cytokine levels (IL-4 and IL-13). Finally, skin CD45+ cells and CD3+ cells were found at similar densities across all groups. Our findings indicate that lack of interleukin-33 and its receptor ST2 does not prevent the development of AD-like skin inflammation.

Histological assessment of the efficiency of rabbit serum in healing skin wounds

Aim:This study aimed to investigate the impact of rabbit serum on skin wound healing with the help of histological examination.Materials and Methods:A total of ten indigenous rabbits were used in this study. The animals were divided into two groups: control and serum- treated. The histological assessment was done with a paraffin embedding technique and the histological sections were stained with H&E stain.Results:Severe infiltration of polymorphonuclear leukocytes with severe fibrin deposits were seen in serum treated group at 2 days post-injury; at 7 days post-injury the changes revealed moderate fibroplasia, fibrin deposit and severe infiltration of both mononuclear and polymorphonuclear leukocytes; at 14 days post-injury, there were marked epithelization and dermal deposition of collagen fibers; and at 21 days post-injury, the epidermis completed epithelization and the dermis showed neither fibroplasia nor infiltration of mononuclear and polymorphonuclear leukocytes.Conclusion:The results indicated that rabbit’s serum can prevent wound infection, accelerate epithelialization and cutaneous regeneration with less granulation.

Histological Changes in the Lung and Liver of Mice Treated with Brake Pad Particles

In the present study, the effects of brake pad particles of lung and liver histological sections were evaluated for (60) adult male mice. The animals were divided into three groups ( A,B,C) according to the periods of exposure (4, 8, and 12) weeks respectively exposed to brake pad particles in addition to the control groups (F) exposed to fresh air only. A special inhalation chamber designed locally has been used to expose the animals. The exposure to brake pad particles was (2.228) µg/m³ for 30 min/day, 5 days/week for (4,8and12) weeks respectively.
 The examination in group (A) of the histological sections of the lung showed the thickness of interalveolar septa. Also, a congestion of alveolar capillary was marked indicating pulmonary emphysema. The infiltration of alveolar macrophages showed the engulfed foreign particles (pad particles) within their cytoplasm, and peribronchial fibrosis. Group (B) showed the presence of pad particles (anthracosis), whereas the bronchial tree showed bronchitis with the bronchus-hyperplasia of mucin-producing cells (epithelial hyperplasia). Still another section showed an infiltration of mononuclear leukocytes and focal lobar necrosis. The third group (C), in turn, revealed acute interstitial bronchopneumonia with peribronchial focal necrosis and mild pulmonary edema with alveolar anthracosis.
 As regards the liver, group (A) showed mild central venous congestion. Group (B), on the other hand, gave acute hepatitis, congestion of the central vein hyaline degeneration and mitotic figure having 2-3 nuclei. Severe congestion of the central vein with vascular amyloid deposition and most of the hepatocytes revealed coagulate necrosis in group (C). These changing tissues increased with increasing the exposure periods and were clearer in group (C) which was exposed for 12 weeks.
 The continuous exposure to brake pad particles lead to damaging important body organs tissues and effect on human health, these particles can be considered as a type of pollutants added to air pollutants in different cities of Iraq.

Histological Changes in the Lung and Liver of Mice Treated with Brake Pad Particles

In the present study, the effects of brake pad particles of lung and liver histological sections were evaluated for (60) adult male mice. The animals were divided into three groups ( A,B,C) according to the periods of exposure (4, 8, and 12) weeks respectively exposed to brake pad particles in addition to the control groups (F) exposed to fresh air only. A special inhalation chamber designed locally has been used to expose the animals. The exposure to brake pad particles was (2.228) µg/m³ for 30 min/day, 5 days/week for (4,8and12) weeks respectively.
 The examination in group (A) of the histological sections of the lung showed the thickness of interalveolar septa. Also, a congestion of alveolar capillary was marked indicating pulmonary emphysema. The infiltration of alveolar macrophages showed the engulfed foreign particles (pad particles) within their cytoplasm, and peribronchial fibrosis. Group (B) showed the presence of pad particles (anthracosis), whereas the bronchial tree showed bronchitis with the bronchus-hyperplasia of mucin-producing cells (epithelial hyperplasia). Still another section showed an infiltration of mononuclear leukocytes and focal lobar necrosis. The third group (C), in turn, revealed acute interstitial bronchopneumonia with peribronchial focal necrosis and mild pulmonary edema with alveolar anthracosis.
 As regards the liver, group (A) showed mild central venous congestion. Group (B), on the other hand, gave acute hepatitis, congestion of the central vein hyaline degeneration and mitotic figure having 2-3 nuclei. Severe congestion of the central vein with vascular amyloid deposition and most of the hepatocytes revealed coagulate necrosis in group (C). These changing tissues increased with increasing the exposure periods and were clearer in group (C) which was exposed for 12 weeks.
 The continuous exposure to brake pad particles lead to damaging important body organs tissues and effect on human health, these particles can be considered as a type of pollutants added to air pollutants in different cities of Iraq.

Compound K inhibits priming and mitochondria-associated activating signals of NLRP3 inflammasome in renal tubulointerstitial lesions.

Renal tubulointerstitial lesions (TILs), a key pathological hallmark for chronic kidney disease to progress to end-stage renal disease, feature renal tubular atrophy, interstitial mononuclear leukocyte infiltration and fibrosis in the kidney. Our study tested the renoprotective and therapeutic effects of compound K (CK), as described in our US patent (US7932057B2), on renal TILs using a mouse unilateral ureteral obstruction (UUO) model. Renal pathology was performed and renal draining lymph nodes were subjected to flow cytometry analysis. Mechanism-based experiments included the analysis of mitochondrial dysfunction, a model of tubular epithelial cells (TECs) under mechanically induced constant pressure (MICP) and tandem mass tags (TMT)-based proteomics analysis. Administration of CK ameliorated renal TILs by reducing urine levels of proinflammatory cytokines, and preventing mononuclear leukocyte infiltration and fibrosis in the kidney. The beneficial effects clearly correlated with its inhibition of: (i) NF-κB-associated priming and the mitochondria-associated activating signals of the NLRP3 inflammasome; (ii) STAT3 signalling, which in part prevents NLRP3 inflammasome activation; and (iii) the TGF-β-dependent Smad2/Smad3 fibrotic pathway, in renal tissues, renal TECs under MICP and/or activated macrophages, the latter as a major inflammatory player contributing to renal TILs. Meanwhile, TMT-based proteomics analysis revealed downregulated renal NLRP3 inflammasome activation-associated signalling pathways in CK-treated UUO mice. The present study, for the first time, presents the potent renoprotective and therapeutic effects of CK on renal TILs by targeting the NLRP3 inflammasome and STAT3 signalling.

A study on the concentration of heavy metals and histopathological changes in Persian jirds (Mammals; Rodentia), affected by mining activities in an iron ore mine in Iran.

Mining activity constitutes a potential source of heavy metal pollution in the environment. Long-term exposure to heavy metals (e.g., cadmium) has adverse health effects. Rodents frequently serve as bioindicators to monitor the levels of heavy metals in the environment. In the present study, concentrations of 10 heavy metals (Cd, Co, Cr, Cu, Fe, Mo, Ni, Pb, Sb, and Zn) in kidney, liver, and muscle tissue of the Persian jird (Meriones persicus) were evaluated. This is the first study to examine the histopathological changes in Persian jird tissues caused by the bioaccumulation heavy metals. The samples were taken at location that surrounded by Sangan Iron Ore Mine (SIOM) mining activities, in northeastern Iran. The results show that the highest concentrations for the metals were observed in kidney and liver, whereas lowest concentrations were found in muscle of Persian jirds. The concentration of Pb was below the limit of detection. Sex and age were two factors that could explain the different levels of heavy metal bioaccumulation, which affects the concentration of some metals. Adults had significantly higher Cu and Cd levels compared to juveniles. Males bioaccumulated more Zn in their kidneys than females, whereas females bioaccumulated more Fe in their livers. As expected, heavy metals affected various organs of the studied specimens. Hyperemia, hemorrhage, necrosis, and degenerative damage to the epithelial cells of the tubules, the presence of hyaline casts, and in one case, mononuclear leukocyte infiltration, were observed in samples of renal tissue. Hemorrhage and hepatocyte vacuolization were the most common histopathological changes found in samples of hepatic tissue. These effects and the concentrations of heavy metals in the studied specimens indicate the need for monitoring and frequent sampling to evaluate long-term persistent pollutants.

Erratum - Effect of Albendazole Treatment in an Experimental Model of Neurocysticercosis-Induced Hydrocephalus

Hydrocephalus is a major concern in neurocysticercosis (NCC), and its management is more challenging than that of hydrocephalus caused by other etiologies. Even though albendazole is a well-established drug for the treatment of NCC, the death of the parasites may worsen the clinical symptoms and eventually, deteriorate the course of hydrocephalus. The aim of this study was to analyze the effects of treatment with albendazole on the course of hydrocephalus as well as on animal behavior in a rat model of NCC-induced hydrocephalus in order to verify whether the course of hydrocephalus and the animal behavior were changed. Ventricle volumes before and after treatment showed a slight but non-statistically significant difference (168.11 mm 3 versus 184.98 mm 3 , p = 0.45). The distribution and location of the cysts were unaffected. In addition, the behavioral patterns before and after the treatment were not significantly different, as assessed by the open field test. On histologic assessment, mononuclear leukocyte infiltration was present in diverse sites, such as the perivascular and peri-ependymal regions, choroid plexus, and meningeal membranes. A positive correlation was found between the degree of ventricle enlargement and tissue damage. Further studies with long-term comparisons are required.

Effect of Albendazole Treatment in an Experimental Model of Neurocysticercosis-Induced Hydrocephalus

AbstractHydrocephalus is a major concern in neurocysticercosis (NCC), and its management is more challenging than that of hydrocephalus caused by other etiologies. Even though albendazole is a well-established drug for the treatment of NCC, the death of the parasites may worsen the clinical symptoms and eventually, deteriorate the course of hydrocephalus. The aim of this study was to analyze the effects of treatment with albendazole on the course of hydrocephalus as well as on animal behavior in a rat model of NCC-induced hydrocephalus in order to verify whether the course of hydrocephalus and the animal behavior were changed. Ventricle volumes before and after treatment showed a slight but non-statistically significant difference (168.11 mm3 versus 184.98 mm3, p = 0.45). The distribution and location of the cysts were unaffected. In addition, the behavioral patterns before and after the treatment were not significantly different, as assessed by the open field test. On histologic assessment, mononuclear leukocyte infiltration was present in diverse sites, such as the perivascular and peri-ependymal regions, choroid plexus, and meningeal membranes. A positive correlation was found between the degree of ventricle enlargement and tissue damage. Further studies with long-term comparisons are required.

Overproduction of TNF-α and lung structural remodelling due to chronic exposure to volcanogenic air pollution

Volcanogenic air pollution studies and their effects on the respiratory system are still outnumbered by studies regarding the effects of anthropogenic air pollution, representing an unknown risk to human population inhabiting volcanic areas worldwide (either eruptive or non-eruptive areas). This study was carried in the archipelago of the Azores- Portugal, in two areas with active volcanism (Village of Furnas and Village of Ribeira Quente) and a reference site (Rabo de Peixe). The hydrothermal volcanism of Furnas volcanic complex is responsible for the release of 1000 t d−1 of CO2, H2S, the radioactive gas – radon, among others. Besides the gaseous emissions, particulate matter and metals (Hg, Cd, Zn, Al, Ni, etc.) are also released into the environment. We tested a hypothesis whether chronic exposure to volcanogenic air pollution causes lung structural remodelling, in the house mouse, Mus musculus, as a bioindicator species. Histopathological evaluations were performed to assess the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema, and the production of pro-inflammatory cytokine TNF-α. Also, the percentage of collagen and elastin fibers was calculated. Mice chronically exposed to volcanogenic air pollution presented an increased score in the histopathological evaluations for the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema and production of TNF-α; and also increased percentages of collagen and elastin. For the first time, we demonstrate that non-eruptive active volcanism has a high potential to cause lung structural remodelling. This study also highlights the Mus musculus as a useful bioindicator for future biomonitoring programs in these type of volcanic environments.