Mononuclear Cellular Infiltration Research Articles

Insight into didecyl dimethyl ammonium bromide toxicity following acute exposure in pullets (Gallus gallusdomesticus).

Didecyl dimethyl ammonium bromide (DDAB) is a quaternary ammonium compound used for the sanitation of drinking water of poultry and water pipelines in farms. There is scarcity of information on the toxicology of DDAB in poultry. This study set out to profile the acute toxicity of DDAB in poultry. Issa brown pullets (n = 34) as experimental birds were orally administered varying doses of DDAB, using a syringe, after 12h fasting, and observed for toxicity over 14 days. Control birds (n = 10) were similarly given normal saline orally. Toxic signs in the experimental birds were depression, anorexia, adipsia, vocalization with foamy salivation, later emaciation and death. The LD50 was calculated as 458.00mg/kg. Birds given 2151mg/kg DDAB died within 24h, while those treated with 516mg/kg succumbed on Day 14. At necropsy, grossly, there were necrosis and sloughing of the oesophagus and intestines, pale and friable liver, congested and necrotic lungs, friable popped out kidneys and emaciated carcasses. Microscopically, desquamation and necrosis of the oesophagus, crop, proventriculus and intestines and disruption of the koilin membrane of the gizzard were observed. The lungs, liver and kidneys were congested with mononuclear cellular infiltration plus loss of architecture in the lungs and liver. In conclusion, at high doses, DDAB caused significant toxicity in chickens and these findings provide new information which could serve as a guide in the diagnosis of quaternary ammonium toxicity in chicken. The results could be extrapolated to other quaternary ammonium toxicities in related avian species.

Effect of Consumption of Caffeinated Energy Drinks on the Myocardium of the Adult Male Albino Rat (A Histological and Morphometric Study)

Abstract Background Energy drinks are non-alcoholic beverages containing mainly caffeine. Chronic consumption of energy drinks may be associated with increased blood pressure, and cardiac work load, as well as, increased heart rate. Energy drinks consumption has been related to myocardial infarction in healthy young adult. Aim of the Work The aim of the present work was to study the harmful effect of energy drinks histologically and morphometrically, on the myocardium of the adult male albino rats. Material and Methods 20 Adult male albino rats aging 4-6 moths were divided randomly into two groups; Group I (Control group) which consisted of 10 male albino rats with free access to food (rat chew) and water and Group II (Experimental group): 10 male albino rats which received 3.75 ml/kg body weight red bull through oral gavage daily for 4 weeks with free access to food (rat chew) and water. At the end of experiment, rats werescarificed, and cardiac muscle was extracted and processed into paraffin blocks for light microscopic examination. Morphometric study and statistical analysis were done. Results The present work demonstrated that Red Bull induced several histopathological changes of the cardiac muscle. The results showed the cardiac muscle of rats with irregularities in the arrangement of fibers and wide spaces in between. Some cardiomyocytes showed areas of pale stained sarcoplasm, partial loss of the cross striations and ill-defined intercalated discs. Localized areas of hyaline degeneration and areas of tissue disruption were also noticed with less frequently localized coalesced cytoplasmic vacuoles. The nuclei of the cardiomyocytes appeared small, darkly stained, and pyknotic. Others were flattened and deeply stained. Congested, and thick walled blood vessels were also observed, with mononuclear cellular infiltrations. In Masson’s Trichrome sections, relative increase in collagen deposition between the cardiac muscle fibers was observed which was associated with focal fibrous degeneration. Examination of the semithin sections showed partial disruption of the cardiomyocytes. The nuclei of the cardiomyocytes were small, darkly stained with perinuclear degeneration. Some nuclei were eccentric, or with an irregular outline, and peripheral chromatin condensation. The characteristic finding was the presence of longitudinal wavy cardiac muscle fibers with relatively wide spaces in between and localized areas of partially lost cross striations and intercalated discs. Dilated, thick walled blood vessels was noticed between the bundles of cardiac muscle. Mononuclear inflammatory cellular infiltrations were also detected. Conclusion The present study demonstrated the degenerative and cardiotoxic effects of Red Bull as an example of energy drinks on the histological structure of the cardiac muscle.

The Potential Role of Bone Marrow Mesenchymal Stem Cells Derived Exosomes on Experimentally Induced Osteoarthritis of Knee Joint in Male Albino Rats. Histological and Immunohistochemical Study

Abstract Introduction Osteoarthritis (OA) is the most common joint disorder worldwide characterized by progressive loss of articular cartilage. This study was conducted to evaluate the role of bone marrow mesenchymal stem cells (BMSCs) derived Exosomes as a promising therapy for treating osteoarthritis. Aim of the Work to study the healing potential of BMSCs derived exosomes on experimentally induced knee osteoarthritis. Materials and Methods Forty adult male albino rats, weighing 200-250 gm, were used in this study, five rats used as a source of BM-MSCs derived exosomes. The other thirty-five rats were randomly divided into three main groups Group I: The control group (20 rats) in which rats were subdivided into four subgroups. Subgroups IA and IB were sacrificed 2 and 6 weeks after the beginning of the experiment. Subgroup IC left for 2 weeks then were received intra-articular injection of 0.1ml Phosphate buffer saline (PBS) in right knee joint once weekly for 4 weeks Subgroup ID: left for 2 weeks then given intra-articular injection of purified exosome concentrate in the right knee joint once weekly for 4 weeks then the animals were sacrificed Group II:(15 rats) in which OA was induced by intra-articular injection of 2% formaldehyde solution in the right knee joints. The rats of group II were subdivided into two subgroups. Subgroups IIA and IIB were sacrificed 2 and 6 weeks after induction of OA respectively. Group III (5 rats), Osteoarthritis induced, as in group II and animals left for 2 weeks then treated by intra-articular injection of purified exosome concentrate in right knee joint once weekly for 4 weeks. The right joints from all groups were collected, decalcified and processed for histological studies. Morphometric and statistical measurements were done. Results Histological examination of the right knee joints of OA group (subgroups IIA and IIB) showed surface erosions, decrease cartilage thickness, chondrocytes with pyknotic nuclei and areas of chondrocytes loss with longitudinal clefts reaching the deep zone. Synovial membrane of group II showed increased thickness of the intima, mononuclear cellular infiltration with abundant collagen fibres deposition and dilated congested blood vessels in subintima, apparent increase in the number of iNOS positive intimal synovial cells. Meanwhile, group III showed smooth articular surface, with multiple colonies of chondrocytes and multiple cell nests, significant increase in the mean area percentage of PCNA positive chondrocytes in animals of group Ш when compared to all the other groups. Conclusion BMSCs derived exosomes improved OA induced damage of articular cartilage and synovial membrane. Therefore, it offers a cell-free treatment of OA and joint damage.

The Possible Effect of Platelet Rich Plasma on Liver and Small intestine in Adult and Aged Male Rats. A Histological and Immunohistochemical Study

Abstract Introduction There is a general modest decline in the function of different organs in the body with aging. In the small intestine, there may be alterations in the intestinal morphology, as well as a decline in the absorption of fatty acids and sugars. The aging process decreases regenerative ability which significantly delays the restoration of liver function. Platelet-rich plasma (PRP) has recently attracted interest in many medical fields. PRP might has benefit effect on aged male rats. Aim of the Work This study aims to investigate the structural changes that might occur during normal aging and the possible effect of PRP intraperitoneal injection on adult and aged male albino rats. Materias and Methods Forty-two male albino rats were classified according to age into adult group and old aged groups. Adult male rats (300 -350 g), their age range between 6-8 months. Aged male rats (570-660 g), their age range between 12-24 months. They were divided randomly into four groups: Group I (Control adult): Included 14 rats that further subdivided into 2 equal subgroups: subgroup IA: untreated rats and subgroup Ib: rats were injected by sterile saline intraperitoneally (0.5 mL/kg by intraperitoneal injection 3 times/week). Group II (Control Aged): Included 14 rat that further subdivided into 2 similar subgroups as group I, Group III (Adult treated): Included 7 rats that received intraperitoneal injection of PRP (0.5 mL/kg by intraperitoneal injection 3 times/week), Group IV (Aged treated): Included 7 rats that received intraperitoneal injection of PRP as group III. Animals were kept under observation and the treated groups received intraperitoneal injections for 21 days. At the end of the experiment, Liver and small intestine specimens were processed for histological and immunohistochemical examination. Morphometric and statistical analysis was also done. Results Group II showed decrease in height of intestinal villi with disruption of their epithelium surface, increase spacing between enterocytes and abundant mononuclear cellular infiltration. Changes in the liver comprised nuclear and cytoplasmic changes that included an increase in nuclei number in hepatocytes with droplets fat infiltration. Treated Groups showed decreasing mononuclear cellular infiltration with decreasing collagen fibres and congested blood vessels. Conclusion Aging process enhanced the vulnerability to injury and inflammation in both the liver and small intestine. PRP had ameliorating effects on these changes.

Histological Evaluation of the Protective Role of β-glucan Against Cisplatin-Induced Hepatotoxicity

Cisplatin is a commonly used chemotherapeutic agent in the treatment of many cancers. The most important dose-limiting side effect is hepatotoxicity. Some studies have shown that antioxidant treatment with cisplatin reduces the toxic effect. In the present study, we were aimed to investigate the protective effects of antioxidant β-glucan on histological injury caused by cisplatin treatment in the liver. Wistar rats were randomly divided into three groups according to time of sacrifice, 7th day and 14th day (n=20 rats each). Both groups were then divided into four sub-groups Control, Cisplatin (10 mg/kg bw), β-glucan (100 mg/kg bw) and cisplatin+β-glucan (n=5 in each group). The rats were sacrificed at the 7th day and 14th day after the last injection. The liver sections were evaluated under a light microscope after the histological procedure. Histological injury caused by cisplatin in different days were evaluated as as sinusoidal congestion, hydropic degeneration, disorganization of hepatic cords, and mononuclear cellular infiltration in liver. When β-glucan was administered with cisplatin, it was determined that cellular damage caused by cisplatin decreased considerably in the liver in the different days groups. The light microscopic examination showed that the antioxidant beta-glucan protects against hepatotoxicity caused by cisplatin with its free radical scavenging effect. In conclusion, β-glucan may improve patients' quality of life by reducing cisplatin's toxicity on the liver.

Abstract 2591: Nonclinical ocular toxicity of a maytansinoid payload-antibody drug conjugate: Ocular tissue distribution, lesion pathogenesis, and mitigation

Abstract Background: Antibody-drug conjugates (ADCs) have emerged as a compelling therapeutic modality in oncology with several recent regulatory approvals. However, on and off-target toxicities require further evaluation. Corneal microcyst-like epithelial changes (MECs) are a well-known off-target class effect of ADCs with microtubulin-acting payloads, with varying degrees of severity. Manifestation of MECs is generally unrelated to antibody target and occurs in the absence of corneal target expression. Methods: An ocular toxicology model in Dutch belted rabbits was established using a humanized monoclonal antibody not cross-reactive in rabbits conjugated through an SPDB linker to the maytansinoid drug, DM4. Radiolabeled ADC was administered once and tissues were collected for radioanalysis at multiple time points to evaluate the contribution of ADC exposure and ocular tissue distribution to corneal toxicity. Non-radiolabeled ADC was administered once or twice to evaluate onset and characterization of MECs using slit lamp microscopy and histopathology. Furthermore, potential prophylactic methods for reducing MECs were evaluated. Results: The drug radioactivity was measured over 14 days and was widely distributed with elimination from most ocular tissues (except cornea) similar to blood/plasma elimination (T1/2 of 4.5-7.5 days). In contrast, the corneal layers had an apparent absorption phase followed by a relatively stable concentration plateau through 14 days. Furthermore, preferential distribution to the corneal epithelium was evident by high tissue-to-plasma ratio (1.6 vs <0.5 for other ocular tissues, including other corneal layers). Generally, MECs increased in frequency (number of eyes affected) and decreased in time to onset with increasing dose. Ophthalmic observations of MECs began in the perilimbal cornea with axial migration over time and were reflected by the histopathologic findings in the corneal epithelium of single cell necrosis, increased mitosis, mononuclear cell infiltration, and/or atrophy. A topical ophthalmic vasoconstrictor (brimonidine tartrate 0.2%) delayed the onset of MECs compared to controls (8% vs. 67% of eyes at 7 days; 33% vs. 100% at 10 days) and mitigated severity of some histopathological findings (reduced or absent corneal epithelial atrophy, punctate erosion, pigment, and/or mononuclear cell infiltration). In contrast, corticosteroid administration (prednisolone acetate 1%) did not reduce MECs clinically but did reduce the histologic incidence and severity of corneal pigment and mononuclear cellular infiltration. Conclusion: Collectively, this rabbit model reproduces the MECs associated with maytansinoid ADCs, demonstrates selective long-term corneal epithelium exposure, and provides data to support clinical testing of vasoconstrictor drops as ocular prophylaxis. Citation Format: Ali Warbington, Olga Ab, Sribalaji Lakshmikanthan, Shana Dalton, Paul Miller, Edward Stevens, Patrick Zweidler-McKay, Grace Lytle. Nonclinical ocular toxicity of a maytansinoid payload-antibody drug conjugate: Ocular tissue distribution, lesion pathogenesis, and mitigation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2591.

Sage (Salvia officinalis) alleviates trazadone induced rat cardiotoxicity mediated via modulation of autophagy and oxidative stress.

The antidepressant drug trazodone (TRZ) is commonly used for treating depression, anxiety, and insomnia, however, it causes cardiotoxicity, which is one of its limitations. The objective of this work was to investigate the impact of sage (Salvia officinalis) in rats against cardiotoxicity induced by TRZ and to investigate the mechanisms involved in its cardio-protective properties through autophagy and oxidative stress. Fifty male albino rats were split randomly into five experimental groups: control group, sage oil group (100 mg/kg), TRZ group (20 mg/kg), protective group, and curative group. Cardiac function biomarkers (aspartate aminotransferase [AST], creatine kinase-MB [CK-MB], and cardiac troponin T [cTnI]) were assessed in serum. Oxidative stress and inflammatory biomarkers in cardiac tissue (total antioxidant capacity, malondialdehyde, and tumor necrosis factor-α) were evaluated. Heart tissues were subjected to histological, immunohistochemical, and ultrastructural evaluations. DNA damage also evaluated. Significant rise in the levels of AST, CK-MB, and cTnI were observed with enhanced autophagy along with marked histopathological changes in the form of interrupted muscle fibers with wide interstitial spaces with areas of hemorrhage and extravasated blood and interstitial mononuclear cellular infiltration in TRZ group. DNA damage was also significantly increased in TRZ group. However, administration of sage in both protective and curative groups show marked improvement of the cardiac alterations. In conclusion, sage ameliorated the alterations in the heart induced by trazadone through modulation of autophagy and oxidative stress.

First report of co-infections of Marek's disease virus and chicken infectious anaemia virus in poultry flocks in Nigeria

Marek's disease (MD) and chicken infectious anaemia (CIA) are viral immunosuppressive diseases of poultry caused by the MD virus (MDV) and CIA virus (CIAV) respectively. Despite vaccination against MD, the incidence of the disease in vaccinated poultry flocks in Nigeria persists. However, underlying factors like co-infection with CIAV have not been investigated in the country. This study was designed to investigate possible co-infections of MDV and CIAV in poultry flocks in Nigeria. In 2016, tumorous tissue samples were collected from suspected cases of MD at necropsy in Jos, Plateau State, Nigeria. The samples collected were fixed in formalin for histopathological examination, genomic DNA was extracted from a second part and analysed by polymerase chain reaction (PCR), targeting the meq and VP1 genes of the MDV and CIAV, respectively. The histology results revealed that the cutaneous and proventricular lymphomas were characterized by large numbers of mononuclear cellular infiltrates admixed with heterophils. The PCR results revealed that MDV was detected in 66.7% (16/24), CIAV in 45.8% (11/24), and co-infections of MDV and CIAV were detected in 45.8% (11/24) of the samples analysed. In addition, co-infections of MD and CIA were recorded in 100% (6/6) and 27.7% (5/18) of broilers and layer/pullet’ samples respectively. Phylogenetic analysis of the meq gene sequences revealed that the Nigerian MDV clusters with very virulent MDV from Egypt and Italy. While, CIAV sequences were genotype II and genotype III and clustered with CIAVs from Cameroon and China. This is the first report of co-infections of MD and CIA in Nigeria.

Gross and Histopathological Changes in Layers Experimentally Infected with Escherichia coli (APEC serotype O1KI)

Background: Avian pathogenic Escherichia coli (APEC) induces colibacillosis, an acute and systemic disease, resulting in substantial economic losses in the poultry sector. Aim: This study determined the gross and microscopic changes associated with Escherichia coli (E. coli) (APEC serotype O1KI) infection in layer chickens. Methods: A total of 10 layer chickens (20 weeks old) were acquired and assigned, at random, into two groups (infected and control) of 5 layers each. Each bird in the infected group was challenged with 0.5 ml of bacterial aliquot containing 109 colony-forming units (CFU) of the bacteria, administered intra-tracheally. The birds from both groups were humanely sacrificed on tenth day post-infection and subjected to post-mortem examination for gross and microscopic changes. Results: Gross lesions observed in the infected chickens included congested lungs, enlarged liver and kidney, hyperaemic intestine, congested ovarian follicles and yellowish fibrinous material in the infected group. While microscopic lesions observed were congested ovarian blood vessels, mononuclear cellular infiltration and generalised necrosis of the liver, kidney, and heart. Conclusion: This study revealed various lesions of congested lungs, enlarged liver, hyperaemic intestine, enlarged kidney, and congested ovarian follicles, yellowish fibrinous material, congested blood vessels of the oviduct that were typical of the natural infection and may be attributable to colisepticaemia.

Efficacy of dietary supplements of Glycyrrhiza glabra (Licorice) and maduramicin alone or in combination with Eimeria tenella infected chicks: A clinical study and molecular docking.

Coccidiosis is one of the most economically significant poultry diseases worldwide, caused by the pathogenic Eimeria species, and is characterized by decreased weight gain (WG) and failure to grow due to malabsorption, low feed conversion rate, bloody diarrhea, and dehydration. This study investigated the effectiveness of licorice root extract (LRE) in controlling cecal coccidiosis to determine whether its combination with maduramicin could help alleviate the pathological, biochemical, and histopathological effects of cecal coccidiosis in Sasso broiler chicks. A total of 125 one-day-old Sasso broiler chicks were categorized into five equal groups (n = 25), each consisting of five replicates (n = 5 per replicate). G1-LE received a basal diet supplemented with LRE (3 g/kg); G2-ME received a basal diet containing maduramycin (0.5 g/kg); and G3-LME received a basal diet containing LRE and maduramicin together with the same rates. G4-E (positive control) and G5-N (negative control) received no additives in their feed. Birds in groups (G1-4) were challenged on day 14 of the experiment by orally intercropping a 1 ml suspension of Eimeria tenella sporulated oocysts. Groups of birds fed on LRE and maduramicin separately or together appeared to be in good condition where no deaths or clinical abnormalities were observed, based on the analysis of clinicopathological examination. Compared with the G4-E positive control, the dropping scoring and oocyst shedding of groups G1-LE, G2-ME, and G3-LME along the 10th-day post-challenge (dpc), as well as macroscopic and microscopic lesions scoring at the 7th dpc, was considerably lower. The dual supplementation use of LRE and maduramicin in G3-LME's reduced the harmful effects of coccidian, which appeared only as a mononuclear cellular infiltration and a small number of oocysts invading the intestinal glands. Molecular docking revealed that LRE and maduramicin interacted with E. tenella DNA polymerase, E. tenella apical membrane antigen 1, and microneme protein binding sites resulting in reduced E. tenella replication and invasion. The inclusion of LRE and maduramicin, individually or in combination, in the diet might effectively mitigate the detrimental effects of coccidiosis.

SHOCK4: Utilizing Mechanical Circulatory Support and Immunomodulation for the Management of Fulminant Lymphocytic Myocarditis: Case Series

Purpose: Five consecutive patients with biopsy-proven lymphocytic myocarditis (LM) presented to our medical center with cardiogenic shock (CS) requiring Mechanical Circulatory Support (MCS) and Immunomodulatory therapy. We present our experience and highlight the variability of presentation and management strategies. Methods: Five consecutive patients presented to our center between 3/1/2022 and 12/1/2022 with acute onset ventricular dysfunction and CS (Table). One had an out-of-hospital cardiac arrest. Due to the fulminant presentation and lack of typical risk factors, there was high clinical suspicion for myocarditis. One patient had positive influenza A testing. Results: All patients were managed acutely with VA-ECMO with or without left ventricular ventilation. All patients underwent an endomyocardial biopsy which showed virus-negative LM. Immunomodulatory therapy strategies varied among patients. Our initial approach was Methylprednisolone for 3 days and IVIG for all. Moreover, for those with a slower rate of recovery, or continued high inflammatory markers, plasmapharesis was utilized in addition to prolonged prednisone and/or azathioprine courses (Table). Of the five subjects, two had myocardial recovery, one developed chronic myocarditis, one developed chronic heart failure, and one required a durable LVAD. Conclusion: Lymphocytic myocarditis is a rare inflammatory disorder of the heart characterized by mononuclear cellular infiltrate and ventricular dysfunction. Fulminant myocarditis is characterized by CS or cardiac arrest. Prompt diagnosis is critical because the prognosis and recovery are better than with nonspecific histological findings or giant cell myocarditis (1,2). Our series and others have demonstrated MCS key role in decreasing mortality while treating the myocardial consequences of inflammatory injury (5-7). While viral infections are the most common cause found in 30-40% of cases (1,3,4), only one patient in our series had an influenza A infection, and none had positive viral testing on the biopsy. We found no consistent history of COVID-19 infection or vaccination among the patients. There is no consensus on the best strategy for immunomodulatory therapy, and more extensive studies with long-term outcomes are needed.

Potential role of dietary parsley and/or parsley nanoparticles against zinc oxide nanoparticles toxicity induced physiological, and histological alterations in Nile tilapia, Oreochromis niloticus

In the recent study, Nile tilapia, Oreochromis niloticus was exposed to sublethal concentration of Zinc Oxide nanoparticles (ZnO-NPs) (8 mg/L) to study the toxic influence on biochemical and oxidative stress biomarkers. Also, the protective role of dietary parsley leaves and parsley nanoparticles was evaluated. Fish were divided into 6 groups of 3 replicates as follows: group I: was served as control, group II: was fed free basal diet containing parsley leaves (4 g/kg of diet). group III: was fed diet containing parsley nanoparticles (4 g/kg of diet). group IV: exposed to (8 mg/L) ZnO-NPs and fed on basel diet for 6 weeks. group V: exposed to (8 mg/L) ZnO-NPs and fed on parsley leaves (4 g/kg of diet). group VI: exposed to (8 mg/L) ZnO-NPs and fed on parsley nanoparticles (4 g/kg diet) for 6 weeks. At the end of experiment, blood and liver tissues were collected for biochemical analysis and histopathological investigation. Results exhibited significant (p < 0.05) increase in the levels of urea, creatinine, total protein, albumin, globulin, glucose, cortisol, cholesterol, and IgM during ZnO-NPs exposure for 6 weeks. Concurrent with those changes, marked decrease (p < 0.05) in serum triglycerides and IgG levels were observed. On the other hand, the histopathological alterations of the examined liver of tilapia intoxicated with ZnO-NPs showed severe congestion, necrosis and apoptosis of hepatic cells, and marked activation of kupffer cells with mononuclear inflammatory cellular infiltration mainly lymphocytes were prevalent. Intake of parsley and parsley nanoparticles in groups (V & VI) after exposure to ZnO –NPs ameliorated hyperglycemia, total protein and lipid profiles, and blunted the increase in cortisol and modulated the levels of urea, creatinine, and IgM of ZnO –NPs treated fish, and enhanced the hepatic architecture of tilapia fish fed on parsley and nano parsley. The obtained results revealed that the dietary parsley leaves and parsley nanoparticles reduced the influence of ZnO-NPs toxicity on Nile tilapia which was more evidence in fish fed on parsley nanoparticles. It could be concluded that parsley has a hepatoprotective effect in tilapia fish against ZnO-NPs toxicity.

Quercetin ameliorates acute lung injury in a rat model of hepatopulmonary syndrome

BackgroundCommon bile duct ligation (BDL) is a rat experimental model to induce biliary cirrhosis. Lung fibrosis and pulmonary vascular angiogenesis and congestion are the most common complications of biliary cirrhosis that is known as hepatopulmonary syndrome. The aim of the present work is to investigate the acute lung injury in a BDL model and to investigate the possible protective effect of quercetin on this injury.MethodsTwenty-four adult male albino rats of the Wister strain (weighing 150–250 g). Animals were divided into 3 groups, with 8 rats each: Group I: Sham-operated group (control). Group II: Bile duct ligation group (BDL) sacrificed after 28 days from the surgery. Group III: Quercetin-treated bile duct ligation group (Q-BDL) was given orally by gastric gavage in a dose of 50 mg/kg/day, starting from the 4th day of the operation until the 28th day. At the end of the experiment, at day 28, all rats were sacrificed. Lung specimens were processed to measure Endothelin B receptor gene expression by PCR, lung surfactant by ELISA, “eNO” s by immunohistochemistry. Histological assessment was done using; H&E, Masson’s trichrome, PAS, toluidine blue-stained semi-thin sections, transmission electron microscope. Histomorphometric and statistical studies were done.ResultsBDL group showed significant increase in lung index together with mononuclear cellular infiltration denoting lung inflammatory state. Also, the significant increase in pulmonary endothelial nitric oxide synthase ("eNO" s) area percent and endothelin B receptor (ETB) gene expression indicates enhanced angiogenesis. Pulmonary surfactant concentration was significantly decreased together with thickening of interalveolar septa denoting lung injury and fibrosis. Quercetin led to significant decrease in lung index, pulmonary "eNO" s area percent, ETB gene expression and significant increase in pulmonary surfactant concentration. Quercetin treatment improved histological changes and morphometric measurements, limited mononuclear cellular infiltration and decreased perivascular and perialveolar collagen deposition.ConclusionQuercetin ameliorates the hepatopulmonary syndrome-induced lung injury through its anti-inflammatory, antioxidative and antifibrotic effects.

Histopathological study on the protective effect of vitamin C against paracetamol-induced acute hepatic damage in rat.

Paracetamol (PCM) as analgesic drugs makes hepatotoxicity damage. Vitamin C (VC) has been recognized as an antioxidant and has shown protective effects against hepatotoxicity damage caused by paracetamol. The current investigation aims to study the possible protective effects of VC against hepatic damage induced by PCM in rats. Forty male rats were divided into five groups: The primary group as control; receiving distilled water orally, the second group; receiving 500 mg/kg of VC. The third group; receiving 500 mg/kg of PCM. The fourth group (protective group); receiving VC for 7 days, and then PCM for another 7 days, and the last group treated with a combination of VC and PCM for 14 days. The liver tissues after administration of PCM alone showed different changes such as disrupted lobular architecture with degenerating hepatocytes, dilated congested central vein, and mononuclear cellular infiltration. While the protective group preserved the general architecture and lacked evidence of major morphological. Additionally, VC with PCM showed some alterations in the liver architecture. In conclusion, the results of this study demonstrate that VC was effective in reducing the hepatic damage caused by PCM in male albino rats.

Subcutaneous nodular fasciitis in dogs: Two cases

Nodular fasciitis is a commonly diagnosed condition in humans with rare occurrences in veterinary practice, especially in dogs and cats, where it is usually associated with the ocular region. Two dogs separately had a mass on the shoulder girdle and the caudal part of the elbow of their respective right forelimbs upon presentation for clinical attention in two private veterinary clinics in Abuja, Nigeria. These solitary and well-demarcated masses were characterized by fibroblastic and vascular proliferation along with focal hemorrhage, mononuclear cellular infiltration, and fatty degenerative changes. Nevertheless, histomorphological lesions and positive immunoreactivity for vimentin, α-SMA, and desmin, as well as negative CD31, CD34, and CD117 immunoreactivity led to a definitive diagnosis of nodular fasciitis. This is a novel report of histomorphological and immunohistochemical diagnosis of subcutaneous nodular fasciitis on the right shoulder girdle and elbow regions of dogs in veterinary practice.

Tamoxifen Increased Parasite Burden and Induced a Series of Histopathological and Immunohistochemical Changes During Chronic Toxoplasmosis in Experimentally Infected Mice.

The global distribution of breast cancer and the opportunistic nature of the parasite have resulted in many patients with breast cancer becoming infected with toxoplasmosis. However, very limited information is available about the potential effects of tamoxifen on chronic toxoplasmosis and its contribution to the reactivation of the latent infection. The present study investigated the potential effects of tamoxifen on chronic toxoplasmosis in animal models (Swiss albino mice). Following induction of chronic toxoplasmosis and treatment with the drug for 14 and 28 days, the anti-parasitic effects of tamoxifen were evaluated by parasitological assessment and counting of Toxoplasma cysts. In addition, the effects of the drug on the parasite load were evaluated and quantitated using TaqMan real-time quantitative PCR followed by investigation of the major histopathological changes and immunohistochemical findings. Interestingly, tamoxifen increased the parasite burden on animals treated with the drug during 14 and 28 days as compared with the control group. The quantification of the DNA concentrations of Toxoplasma P29 gene after the treatment with the drug revealed a higher parasite load in both treated groups vs. control groups. Furthermore, treatment with tamoxifen induced a series of histopathological and immunohistochemical changes in the kidney, liver, brain, and uterus, revealing the exacerbating effect of tamoxifen against chronic toxoplasmosis. These changes were represented by the presence of multiple T. gondii tissue cysts in the lumen of proximal convoluted tubules associated with complete necrosis in their lining epithelium of the kidney section. Meanwhile, liver tissue revealed multiple T. gondii tissue cysts in hepatic parenchyma which altered the structure of hepatocytes. Moreover, clusters of intracellular tachyzoites were observed in the lining epithelium of endometrium associated with severe endometrial necrosis and appeared as diffuse nuclear pyknosis combined with sever mononuclear cellular infiltration. Brain tissues experienced the presence of hemorrhages in pia mater and multiple T. gondii tissue cysts in brain tissue. The severity of the lesions was maximized by increasing the duration of treatment. Collectively, the study concluded novel findings in relation to the potential role of tamoxifen during chronic toxoplasmosis. These findings are very important for combating the disease, particularly in immunocompromised patients which could be life-threatening.

A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of Orientia tsutsugamushi.

Orientia tsutsugamushi, the etiologic agent of the life-threatening febrile disease scrub typhus, is an obligately intracellular small coccobacillary bacterium belonging to the family Rickettsiaceae and is transmitted by the parasitic larval stage of trombiculid mites. Progress towards a vaccine for protection against scrub typhus has been impeded by characteristics of the pathogen and the infection. There are numerous strains of O. tsutsugamushi in the Asia-Pacific region with geographical overlap. In human cases immunity has been described as poor against heterologous strains of the pathogen, as well as short-lived against the homologous strain, with a mean antibody reversion rate of less than one year. Animal models of cross-protection as well as of deterioration of this cross-protection are needed to enhance understanding of transient immunity to scrub typhus. To build upon current understanding of this ineffective protection we sought to utilize our recently developed models, sublethal intradermal infection followed by challenge via ordinarily lethal hematogenous dissemination. Mice that were initially infected sublethally with O. tsutsugamushi Gilliam strain and were challenged with an ordinarily lethal dose of heterologous Karp strain were protected from death by a robust immune response at one month after the primary infection as evidenced by an abundance of mononuclear cellular infiltrates in target organs such as lung, liver, and kidney; maintenance of body weight; and low bacterial loads in the organs. Waning protection from lethal Karp strain challenge indicated by weight loss mirroring that observed in naïve mice was observed as early as 9 months after primary Gilliam strain infection, and higher bacterial loads, severe disease, and eventual death in some mice was observed after challenge with Karp strain at 14 months post-initial heterologous infection.

Histological Study on the effect of losartan in healing of an experimentally induced muscle laceration in adult male albino rat

Abstract Background Skeletal muscle injuries are frequently encountered in athletes and military personnel. Incomplete functional recovery of these injuries usually occurs due to fibrosis of the skeletal muscle. Recently, oral administration of losartan antihypertensive drug was claimed to have a role in improving skeletal muscle healing, but still to be furtherly investigated. Aim of the work This work aimed to assess the healing effect of losartan on the histological structure of induced lacerated skeletal muscle fibers of adult male albino rats. Material and Methods Forty male albino rats were used in this study. They were divided into three groups: Group I: served as a control group and included 15 adult rats. Group II (muscle laceration group): consisted of 15 rats that were subjected to muscle laceration injury. They were subdivided into subgroup IIa: consisted of five rats that were sacrificed one day after injury, subgroup IIb: it included 10 rats that were left for spontaneous recovery for two weeks after injury. Group III (losartan-treated group): it consisted of 10 rats that were subjected to muscle laceration injury then they received oral losartan from day three till end of experiment. All rats, except rats of subgroup IIa, were sacrificed two weeks after injury. Right gastrocnemius muscle specimens were taken and processed for light microscopic examination by H &amp; E and Masson's trichome stains as well as morphometric and statistical analysis. Results In group II, there was almost complete affection of myofibers at site of injury after 1 day of induced laceration in the form of myofibers fragmentation, disorganization and distortion with apparent mononuclear cellular infiltration mainly neutrophils and macrophages. After 2 weeks some myofibers were seen distorted and ended abruptly into connective tissue, others were branched with unclear striations. Mononuclear cellular infiltration between myofibers and apparent dilated blood vessels at laceration site were also noticed. A significant increase in collagen fibers deposition between regenerating muscle fibers (p&amp;lt;0.05) was also demonstrated. Treatment of the muscle laceration by losartan in group III showed apparent partial improvement in the form of significant decrease in collagen fibers deposition (p&amp;lt;0.05) and apparent decrease in mononuclear cellular infiltration as compared to that of group II. Also, some of the regenerated myotubes were noticed with chains of central nuclei. Conclusion Excess collagen fibers deposition between myofibers hinders regular arrangement of generating myotubes. Losartan might enhance muscle regeneration through decreasing collagen fibers deposition. However, it needs longer duration to assure complete muscle healing.

The Potential Role of Human Derived Amniotic Membrane Graft in The Repair of Induced Tendon Tear in Adult Male Albino Rat: Histological Study

Abstract Introduction Achilles tendon tears cause severe impairment in patient mobility and productivity, causing significant reduction in the quality of life. Many complications are associated with the tendon healing process such as peritendinous adhesions and excessive fibrotic scars. Unsatisfactory results appeared with the existing medical and surgical treatments to regain full tendon structure and function. Amniotic membrane is avascular, and characterized by low immunogenicity, anti-inflammatory, antiscarring properties. These criteria render it as a natural biological substitute and a novel therapeutic alternative for tendon tears. Aim: The aim of the work was to study the effect of human amniotic membrane graft application on the repair of induced Achilles tendon tear. Material and methods Fresh human amniotic membrane (AM) grafts were prepared from harvested human full-term caesarian sections-delivered placentas. Thirty adult male albino rats were divided into 3 equal groups (n = 10); group I (control group), group II (tendon tear group) and group III (AM treated group). After anesthesia, a full thickness transverse incision was induced in the rat right Achilles tendons of group II and III. Human derived amniotic membrane graft measuring 1 cm2 was applied circumferentially on the tendon tear in group III. Rats were sacrificed after 28 days. Results After the tendon tear, the untreated group (II) showed gradual accumulation of fat cells replacing the collagen bundles in focal areas. Areas of mononuclear cellular infiltration were demonstrated. The AM-treated group showed many thick parallel regularly arranged collagen fibers with a significant increase in the collagen fibers area percentage. It also showed apparent increase in tenoblasts with regular organization and apparent decrease of mononuclear inflammatory cells. Conclusion This study demonstrated the potential therapeutic role of the application of human amniotic membrane grafts in the repair of Achilles tendon tears, suggesting a future alternative therapy for patients suffering from Achilles tendon tears.

Mortality of Clarias gariepinus caused by Aeromonas caviae and nitrite toxicity in a fish farm

In Nigeria, farming of freshwater fish, mainly that of Clarias gariepinus has gained prominence as means of improved protein supply and livelihood. Many farmers suffer untold losses in their bid to make a living from commercial fish production. Among the major causes of infectious disease outbreaks in fish farms are pathogenic bacteria of the genus Aeromonas. This is a case report of outbreak of Aeromonas caviae infection complicated by nitrite toxicity in Clarias gariepinus. Carcasses of 17 African catfish juveniles and two water samples were presented to the poultry and fish clinic of the Veterinary Teaching Hospital, University of Jos for investigation. The fishes had been on medication (Fish cure antibiotic +®) for over 5 days with cumulative mortality of 230 out of 2,500 fishes (9.2 %). Necropsy was conducted and samples were taken for microbial analysis and histopathology while water samples were subjected to chemical analysis. Gross lesions were broken barbels, cutaneous depigmentation, branchial pallor, ascites, renal and splenic congestion. Histologically, there was dissociation of hepatic cords, necrosis of hepatocytes with vacuolation and mononuclear cellular infiltrations. Also, there was renal tubular epithelial necrosis with mononuclear and heterophilic infiltration while micro abscesses were observed in the brain. Marked Zenker’s necrosis and edema were seen in the skeletal muscles. Organism isolated from livers and kidneys was identified as Aeromonas caviae and was susceptible to enrofloxacin, furaltadone and florfenicol. Nitrite in fish pond water was 1mg/L. Bath medication with enrofloxacin at 33mg/litre of water for 6 hours treatment per day was done to reduce the mortality. The farmer was advised to change the source of water for the fish pond immediately. It is recommended that to avoid losses in fish farming, farmers should check the quality of water intended for use on fish farms and ensure early health check on fingerlings purchased for rearing.