Histological Aspects Research Articles

Myl-4 mutation induces atrial inflammation and fibrosis associated with increased Atrial Fibrillation vulnerability

Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia. The genet mutation Myl4-pE11k affecting the atrial cardiomyocyte contractile machinery, via a myosin light chain abnormality, is associated with familial AF. The underlying pathophysiological mechanisms governing the through which the Myl-4 mutation causes AF remains poorly understood. To elucidate the arrhythmogenic atrial remodeling induced by the Myl4-p.E11 K mutation associated with AF in rats. A Knock-In (KI) model using male Wistar rats was generated to study the impact of the Myl-4 mutation on atrial structure and function. Different age groups (embryo, neonate, 15 days, 1 month, 3 months, and 6 months) were used to identify whether the mutation is associated with age-dependant arrhythmogenic remodeling. The functional consequences of this mutation were assessed by electrocardiogram, transoesophageal pacing and optical mapping. Morphometric and histologic aspects of Myl4-mutation-induced atrial changes were determined by immunohistochemistry. Atrial expression levels of genes and proteins involved in fibrosis, inflammation and cellular necrosis were studied by qPCR, Western blot and Multiplex assays. Compared to control rats, a significant decrease in P-wave amplitude and duration was reported in transgenic rats. In vivo transoesophageal tachypacing induced AF and/or atrial flutter in 80% KI rats compared to control animals. The mutation was associated with early development of atrial fibrosis (observed from embryonic ages) and increased expression of fibrosis biomarkers. Atrial tissue from KI rats showed increased infiltration of proinflammatory macrophages associated with increased gene and protein expression of inflammation-associated genes. Pronecrotic genes were also upregulated under KI conditions. These parameters were aggravated as the KI animals aged, reaching a plateau between 15 days and 1 months post-birth for atrial fibrosis and inflammation. This study demonstrates that Myl-4 mutation provokes the development of an arrhythmogenic substrate and cardiac remodelling characterised by atrial fibrosis, inflammation and cell death in an age-dependant manner.

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming

BackgroundCholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA.MethodsCholangiocarcinogenesis was induced in rats (TAA) and mice (JnkΔhepa + CCl4 + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRASG12D cells. Cell signaling, growth, gene regulation and [U-13C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model.ResultsPathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRASG12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRASG12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRASG12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression.ConclusionsIn CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA.

Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects

Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70–98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects.

Heterogeneous genetic landscape of congenital neutropenia in Korean patients revealed by whole exome sequencing: genetic, phenotypic and histologic correlations

Congenital neutropenia (CN) is a hematological disease heterogeneous in its genetic, phenotypic and histologic aspects. We aimed to identify the genetic etiology of Korean CN patients in the context of bone marrow (BM) histology and clinical phenotype. Whole-exome sequencing (WES) or targeted sequencing was performed on the BM or peripheral blood specimens of 16 patients diagnosed with CN based on BM exam from 2009 to 2018. Absolute count of myeloperoxidase (MPO)-positive cells was calculated using ImageJ software. Semi-quantitation of MPO-positive cells in BM sections was performed by MPO grading (grades 0–3). Comprehensive retrospective review on real-world data of 345 pediatric patients with neutropenia including 16 patients in this study during the same period was performed. Seven disease-causing variants were identified in ELANE, G6PC3 and CXCR4 in 7 patients. A novel homozygous G6PC3 variant (K72fs) of which the mechanism was copy-neutral loss of heterozygosity was detected in two brothers. A low myeloid-to-erythroid ratio (0.5–1.5) was consistently observed in patients with ELANE mutations, while MPO-positive cells (40%–50%) with MPO grade 1 or 2 were detected in myelokathexis caused by G6PC3 and CXCR4 mutations. Meanwhile, disease-causing variants were detected in ELANE, TAZ and SLC37A4 in 5 patients by retrospective review of medical records. Our results suggest that following the immunological study and BM exam, WES or an expanded next generation sequencing panel that covers genes related to immunodeficiency and other inherited bone marrow failures as well as CN is recommended for neutropenia patient diagnosis.

Neoadjuvant Chemo-Immunotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Review of the Literature.

Non-small cell lung cancer accounts for approximately 80–85% of all lung cancers and at present represents the main cause of cancer death among both men and women. To date, surgery represents the cornerstone; nevertheless, around 40% of completely resected patients develop disease recurrence. Therefore, combining neoadjuvant chemo-immunotherapy and surgery might lead to improved survival. Immunotherapy is normally well tolerated, although significant adverse reactions have been reported in certain patients treated with inhibitors of immune checkpoints. In this review, we explore the current literature on the use of neoadjuvant chemo-immunotherapy followed by surgery for treatment of locally advanced non-small-cell lung cancer, with particular attention to the histological aspects, ongoing trials, and the most common surgical approaches. In conclusion, neoadjuvant immunotherapy whether combined or not with chemotherapy reveals a promising survival benefit for patients with advanced non-small-cell lung cancer; nevertheless, more data remain necessary to identify the best candidates for neoadjuvant regimens.

MO028: Kidney biopsy in females with Fabry disease is an important tool to establish the indication for Fabry-specific therapy

Abstract BACKGROUND AND AIMS Fabry disease (FD) is a rare lysosomal storage disease causing progressive kidney, nervous system and heart disorders. Specific therapy may stop or mitigate disease progression, but is very expensive and results depend significantly on early initiation of treatment. Thus, clear criteria for treatment options are necessary. Kidney biopsy in FD has important diagnostic, prognostic and therapeutically implications. Some countries already decided to include as a criterion for reimbursement of FD-specific therapy in presence of renal biopsy evidence related to FD. National criteria for starting FD specific therapy according to renal involvement include eGFR &amp;lt;80 mL/min/1.73 m2 and/or proteinuria &amp;gt;300 mg/day. METHOD The aim of our retrospective study is to evaluate clinical and histological aspects of renal involvement in untreated female patients diagnosed with FD by genetic test between 2015 and 2021 in our center. Biological renal manifestations using serum creatinine, albumin creatinine ratio and proteinuria. Also, presence of neurological involvement was assessed by clinical exam, electroneurographic exam and brain magnetic resonance, and heart manifestations were assessed by echocardiography, electrocardiogram (ECG), ECG Holter and cardiac magnetic resonance. Kidney biopsy specimens were analyzed by light and electron microscopy. Specific renal FD lesions, as well as general lesions of progression, were evaluated according to the International Study Group of Fabry Nephropathy Score Sheet. RESULTS From a total of 25 female patients, we enrolled 11 female patients in which kidney biopsy was performed. The mean age at diagnosis was 47.7 ± 12 years (range 30–65 years), although mean age of symptoms onset was 36.1 years. The mean eGFR was 72.7 ± 19.8 mL/min/1.72 m2 while mean proteinuria was 0.72 ± 1.3 mg/day. Average Mainz score was 16.6 ± 11.5. Heart involvement was found in five patients (45.5%), and neurological manifestations were present in five patients. Co-morbidities were as follows: arterial hypertension in six patients, diabetes mellitus in one patient and obesity in two patients. All kidney biopsies showed lysosomal accumulation in the podocytes, in the parietal cells of the Bowman capsule and in the tubules, while vascular inclusions were found in nine cases. Also, we observed segmental glomerular sclerosis in four cases and global glomerular sclerosis in three cases, interstitial fibrosis in six cases, tubular atrophy in five cases, arteriosclerosis in four cases and arteriolar hyalinosis in five cases. Considering national criteria for initiation of FD therapy, five patients (54.6%) fulfilled the renal criteria, three patients (27.3%) presented criteria for other organs involvement, while three patients (mean age 37.7 years) did not fulfill any criteria. We emphasize that, even in our six patients without renal criteria for FD therapy, kidney biopsy showed FD-specific lesions (lysosomal accumulation) in all cases, associated with segmental glomerular sclerosis in one case, interstitial fibrosis in four cases, tubular atrophy in three cases, arteriosclerosis in one case and arteriolar hyalinosis in three cases. Thus, in our three patients without clinical, biological and imaging criteria for FD therapy, evidence of specific FD lesions in kidney biopsy supported our recommendation to initiate FD treatment. CONCLUSION The data from our small cohort of females with Fabry disease underline the importance of kidney biopsy for detection of early kidney involvement and provide additional support to the consideration of early initiation of FD-specific therapy, potentially improving long-term outcome. Thus, proof of specific FD renal lesions as revealed by kidney biopsy could become a distinct criterion for initiation of FD therapy, in the absence of other criteria according to current guidelines. Future studies are necessary in order to specify the role of renal histology in the establishment of the proper timing to start the FD treatment, especially in young patients.

Brazilian Green Propolis Modulates Cholesterol Homeostasis in a Preclinical Guinea Pig Model

This study investigates the effect of the hydroalcoholic extract of Brazilian green propolis on lipid metabolism in hypercholesterolemic guinea pigs. This product has been considered an important source of bioactive compounds with potential health benefits. Thirty‐six guinea pigs, Cavia porcellus (male), 90 days old, weight of 400 g, were divided into six groups of six animals each and fed a standard AIN‐93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet + hydroalcoholic extract (75 mg/kg body weight [HEtOH1]; 150 mg/kg body weight [HEtOH2], and 300 mg/kg body weight [HEtOH3]), or hypercholesterolemic diet + simvastatin (1.5 mg/kg body weight) (HS) for 10 weeks. The group‐specific diet and water were provided ad libitum throughout the experimental period. Blood and liver tissue samples were collected for biochemical analysis and histopathology. Statistical analysis was performed using GraphPad Prism software version 5.0. The experimental protocol for the use of animals was approved by the Ethics Committee on Animal Use of the University of São Paulo (N°18.1.999.60.0). Animals in the H groups had a lower food intake than in the C group. Fecal excretion was regulated by the administration of extracts, being higher in these groups when compared to H and HS groups. Liver weights were influenced by the diet and administration of the hydroalcoholic extract of green propolis. Hypercholesterolemic diets determined an increase of about 2 times in the relative weight of this organ when compared to the C group, being more expressive in the groups of animals that received the hydroalcoholic extract. A significant increase in serum levels of total and non‐HDL cholesterol was observed in H group, concomitant with a reduction in the concentration of cholesterol‐HDL when compared to group C. However, these high levels of total cholesterol were reduced when simvastatin and extracts were administered with the hypercholesterolemic diet. The same was observed for the non‐HDL cholesterol fraction, where administration with simvastatin and extracts significantly reduced the concentration of these fractions, especially in HS and HEtOH3 groups when compared to group H. Analysis of the HDL fraction demonstrates that the animals submitted to the hypercholesterolemic diet had the lowest levels for this parameter when compared to the groups that received the control diet and/or extracts and simvastatin. There was a significant reduction in serum triacylglycerol levels in the HEtOH2 and HEtOH3 groups. However, a change in liver metabolism was observed, favoring the deposition of lipids in the liver, a different profile from what was observed when administering simvastatin. C group presented a histological aspect compatible with the normality of the organ. The H and HS groups presented moderate to severe fat degeneration, with a slight degeneration in the HS group when compared to the H group. A profile similar to that of the HS group was observed in the HEtOH2 group. Our results suggest that the Brazilian green propolis extract induces positive effects on dyslipidemia.

Salvage Liver Transplant in the Treatment of a Child With Local Recurrence of Hepatoblastoma

Hepatoblastoma is the most common primary liver cancer of childhood, accounting for two-thirds of primary malignant hepatic neoplasms. Radical surgical removal combined with efficient chemotherapy is essential for cure. Despite a complete tumor resection, hepatoblastoma may recur as isolated local disease. Intrahepatic recurrence of hepatoblastoma after liver resection is among the indications for liver transplant. Here, we present a patient who underwent salvage liver transplant for the treatment of local recurrence of hepatoblastoma. A 13-year-old boy who was diagnosed with hepatocellular carcinoma arising from the left liver lobe and who had been treated with surgical resection was admitted to our outpatient oncology clinic for further evaluation because alpha-fetoprotein levels had started to increase after surgery. Histopathological reexamination of hemihepatectomy material showed a histological aspect of an epithelial hepatoblastoma. Magnetic resonance imaging revealed multifocal lesions in the right liver lobe compatible with local recurrence. Despite a favorable initial response to chemotherapy, the tumor showed progression with increased alpha-fetoprotein levels. The patient was deemed a viable candidate for an urgent liver transplant and underwent right lobe living donor liver transplant. He had excellent graft function without any complications or signs of malignancy in the last follow-up visit at 7 months posttransplant. Salvage liver transplant is a lifesaving and sometimes the only treatment option for patients with local recurrence of hepatoblastoma. Although transplant in the salvage setting has been associated with worse outcomes than primary transplant, recent data have indicated more favorable and acceptable outcomes. Further studies are warranted to better understand the role of salvage liver transplant in the treatment of hepatoblastoma. Early consultation with the liver transplant team is critical in children who are most likely to need extreme resection or liver transplant.

Protective role of Salvia officinalis silver nanoparticles on some physiological and histological aspect in bisphenol a treated female rat

Protective role of Salvia officinalis silver nanoparticles on some physiological and histological aspect in bisphenol a treated female rat

Chronic fibrosing interstitial lung diseases according to the register of Irkutsk (Russia)

The Interstitial lung diseases (ILD) are a wide heterogeneous group of disorders, different in many parameters, however having similar pathophysiological mechanisms. Idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), chronic hypersensitivity pneumonitis (CHP), ILD associated with autoimmune disorders (predominantly systemic sclerosis (SSc ILD) and rheumatoid arthritis (RA ILD), and other diseases may be accompanied by the formation of pulmonary fibrosis. Currently there are no generally accepted criteria for the fibrosing and progressive fibrosing ILD, and the information on the frequency of these conditions is limited.The study aims to research the structure of fibrosing ILD and the frequency of the progressive fibrosing phenotype (PFP) according to the register of patients with ILD in Irkutsk, Russia.Methods. At the first stage information letters were sent to all medical institutions of Irkutsk with recommendations on all referral patients with ILD for further examination. At the second stage, each ILD case was verified collegially (n = 270). All patients’ data were analysed in terms of clinical, functional, radiological and histological aspects. A register of ILD patients was formed based on this analysis. The follow-up period was 1 to 5 years.Results. According to the results of a comprehensive assessment, HRCT signs of pulmonary fibrosis were detected by 104 patients (38.5%). fibrosing course was observed in 100% IPF and SSc ILD, in 90.9% of CHP, 71.4% of NSIP and 60% of RA ILD. 61 patients (22.6% of all ILD cases, 58.6% of fibrosing ILD) was diagnosed with PFP. The 5-year mortality for PFP ILD was 55.5%.Conclusion. In the case of a PFP development, the evolution of ILD loses its nosological specificity, acquiring similarity with IPF. Due to the high mortality rate, it is necessary to actively identify the progressive fibrosing course of a wide range of ILD and to prescribe an antifibrotic therapy in a timely manner.

Protective role of Salvia officinalis silver nanoparticles on some physiological and histological aspect in bisphenol a treated female rat

This study was planned to investigate the probable protective role of Salvia officinalis have in the nanoparticles and aqueous extracts on female rats which exposed to Bisphenol A. At the end of the experiment the blood samples were collected by heart puncture to evaluate the RBC and WBC count, Hemoglobin, Platelets as well as follicle stimulating hormone (FSH), luteinizing hormones (LH), estrogen, creatinin, urea, aspartate aminotransferase, alanine amino transferees and alkaline phosphatase were estimated furthermore after the rats were scarified Liver, Kidney, Uterus and ovary were collected for histological study. The result shows significant decrease in the RBC, PLT and Hb count in the BPA group in comparison with the control and SOSNPs and SOE groups. In addition, there is a significant increase in WBC count and estrogen level in the BPA treated rats in comparison with control, SOSNP and SOE treated rats. As well as, there is significant increase in the liver enzymes (AST, ALP and ALP) in the BPA treated rats in comparison with control and SOSNP &amp; BPA treated groups. Histological studies show presence of vacuolation with absence of radial arrangement in the hepatocytes in the liver of rats. The histological studies for the uterus of rats Beside ovarian sections BPA reveled mature follicle without oocyte with cyst like structure in the ovary in comparison with control group, these effects were relieved by the role of SOSNP and SOE in alleviating the effects of BPA on studied parameters.

The natural interaction between Myotis nigricans (Schinz, 1821) and its trematodes: A histopathological analysis.

Bats have a wide diversity of digeneans; however, even with the recent increased interest in studies of parasites on these hosts, there are no data on the microscopic alterations of this host-parasite interaction. The present work characterizes and compares the histological aspects of the liver, gallbladder, and intestine of non-parasitized and parasitized Myotis nigricans by digeneans. Ten specimens of Myotis nigricans collected in an urban area of Western Amazonia were analyzed for parasites. The digeneans were removed from the hosts and identified. Tissue samples of the liver, gallbladder, and intestines of parasitized and non-parasitized hosts were collected for histological studies. The gallbladder was observed in repletion and presents mucosa formed by simple epithelium that varies from cubic to cylindrical. The hepatic lobes do not have a classic polyhedral-hexagonal aspect. Variations in basophilia, acidophile, and cytoplasmatic granulations were observed in hepatocytes. The parasitism of the intestinal digeneans was restricted to space delimited by the extensions of villi in high association with the intestinal epithelium, not invading the region of the intestinal glands at the base of the villi. Trematodes maintained attached to the villus by the oral sucker and acetabulum, connected by a “pleat” composed of epithelium and lamina propria layers. We observed no signs of inflammatory processes and cellular defense infiltrates in host tissues. Cytochemistry alterations, size variation, and granular deposits in hepatocytes, enterocytes, and goblet cells were observed. Thus, this report is the first study of the natural parasite-host interaction in the liver, gallbladder, and intestine in M. nigricans in the neotropical region.

The influence of an analog of juvenile hormone on the silk gland of Africanized Apis mellifera larvae reared in vitro

As the larval silk glands of Africanized honey bees are well characterized in hive conditions, we compared the silk glands of larvae of Africanized honey bees from the hive (in vivo - literature information) with larvae reared under laboratory conditions according to a specific bioassay (in vitro rearing of Africanized honey bees). We also continuously exposed the larva to a juvenile hormone analog (JHA), the pyriproxyfen, in three different concentrations: 12.5 mg/L, 25 mg/L, and 50 mg/L. Concerning morphological and histochemical analyses, there were no characteristics in glands that indicated the acceleration of the cocoon spinning time and no features of cell death. The glands seemed to be in secretory activity. Pyriproxyfen-treated larvae had a slightly shorter silk synthesis period than control, although only in the 50 mg/L experimental group, the tactoids from silk were clearly visible in optical microscopy, probably due to a higher secretion activity as the response to JHA. We observed that the presence of lipids under artificial feeding was independent of the nurse bee presence. Thus, we found that pyriproxyfen alters the functioning of the silk gland, under laboratory conditions in morphological, histological, and/or morphometric aspects.

Bladder Cancer: Epidemiological, Clinical and Histological Aspects at Zinder National Hospital (HNZ) Niger

Objective: To present the epidemiological, clinical and histological aspects of bladder cancer at the National Hospital of Zinder (Niger). Materials and methods: This is a retrospective, descriptive and analytical study covering the period from January 2017 to January 2022 concerning the files of patients followed up for bladder cancer. The patients come from three regions bordering Zinder (Maradi, Agadez, Diffa). The parameters studied were epidemiology, age, sex, clinical signs, paraclinical tests, and histological results. Results: A total of 6724 patients were consulted during the period, which brings to 1.23% the incidence of bladder cancer at Zinder national hospital (HNZ). The median age of patients was 56.83 years with extremes of 24 and 77 years. The sex ratio was 7/1. A history of chronic smoking for an average of 5 pack-years was found in 8 cases (9.63%). Among the other risk factors, a history of urinary schistosomiasis in 58 cases (69.87%). The reasons for consultation were: total hematuria 63 cases (76.41%), permanent pollakiuria 8 cases (9.32%), acute urine retention 7 cases (8.33%), renal failure 3 cases (3.54%), exophytic tumor 2 cases (2.40%). Additional diagnostic tests were: ultrasound, cystoscopy, computed tomography (CT). Histology found 66 cases (79.51%) of squamous cell carcinoma, 15 cases (18.07%) of urothelial carcinoma and 2 cases (2.42%) of adenocarcinoma.

Comparative Testing of Two Ligature-Induced Periodontitis Models in Rats: A Clinical, Histological and Biochemical Study.

Simple SummaryThis study is the first study comparing the same parameters of inflammation in two periodontal disease experimental models proposed by the literature and used in the research. The importance of the method used to induce periodontitis in animals resides in the efficacy of proposed technologies and treatments used in preclinical trials. The inflammatory markers Interleukin-1 alpha(IL-1α), Tumor Necrosis Factor-alpha (TNF-α), and high sensitive C reactive protein (hsCRP), the hematological analyses, and the histological probes showed a similar and reproducible periodontal inflammation for the molar induced periodontitis model. Ligation-induced periodontitis in rats has limitations and will never reproduce all aspects of periodontal disease in humans. The findings of this study with the complex association between clinical, biochemical, and histological aspects of the two experimental models of periodontal pathology induction in rats suggest that a similar periodontal pathology to the one we find in humans is best replicated in rats with the molar induced periodontitis model.Experimental animal models for studying the mechanisms of periodontitis and its links are a better alternative to in vitro studies. The aim of this study is to compare two ligature induced periodontitis models and validate the best one for further use in research. An experimental study was performed on male Wistar rats that were divided into three groups: Test 1 (n = 10), incisor ligated, Test 2 (n = 10), molar ligated, and Control (n = 10). The animals were clinically evaluated at the beginning and at the end of the experiment by recording body weight, gingival bleeding index, tooth mobility score, changes in color, and consistency of gingival tissue. Two blood samples were obtained for each animal at baseline and at the end of the experiment. The hematological parameters Interleukin-1 alpha (IL-1 α), high sensitive C Reactive Protein (hsCRP), and Tumor Necrosis Factor-alpha (TNF-α) were measured. Seven days after the induction of periodontitis, the animals were sacrificed, and samples were prepared for histological evaluation. The results of this research demonstrated that the association between clinical, histological, and biochemical parameters initiate a periodontal pathology in the molar induced model in rats while the incisor experimental model initiates only a moderate and incomplete periodontal inflammation, mainly due to mechanical irritation.

Histological aspects of rat ovaries supplemented with bee pollen from Cocos nucifera

Bee pollen is a food supplement for its medicinal properties. It has a high concentration of vitamins, mineral salts, proteins, phenolic compounds and carbohydrates, which are beneficial to health. The objective of this work was to evaluate the effects of bee pollen supplementation on the ovarian performance of rats. Fifty pubescent rats were separated into groups maintained with a common feeding routine. Two experimental groups of 15 animals each were supplemented by intragastric administration with 50 mg of bee pollen from Cocos nucifera, for 30 and 90 days. The estrous cycle was followed in the last 12 days of treatment. In the first estrus after treatment, euthanasia was performed by intraperitoneal administration of sodium thiopental (50 mg/kg), to remove the ovaries for making histological sections. The number and types of ovarian structures present were analyzed: secondary follicle, Graafian follicle, atresic follicle and corpus luteum. In animals supplemented for 30 days there was a significant increase in the number of atresic follicles compared to controls. This increase also occurred in the supplemented 90 days compared to 30 days. It was also found a decrease in the number of corpora lutea, suggesting that the effects are time dependent.

Clinical, Imaging, Histological and Surgical Aspects Regarding Giant Paraovarian Cysts: A Systematic Review.

Paraovarian cysts (POCs) develop within the broad ligament of the uterus. POCs are considered to be giant when the threshold of 150 mm is exceeded. Clinical signs and symptoms occur as a consequence of the pressure effect on adjacent organs or due to complications. Abdominal ultrasonography, computed tomography or magnetic resonance imaging are useful imaging tools, but most often the exact origin of such voluminous cysts is revealed only by surgical exploration. The review aims to appraise and update the diagnostic, the histological aspects and the treatment of the giant POCs in rare cases. We carried out a systematic search in Medline-PubMed, Google Scholar and ResearchGate electronic databases. Twenty-seven papers fulfilling the selection criteria were included in the review. The data extracted included information about first author, year of publication, country, patient age, size and side of the POCs, symptoms, tumoral markers, imaging methods, preoperative diagnosis, surgical management and histopathological findings. Although not very numerous, all the studies highlighted the low incidence of giant POCs, the impossibility of establishing the origin of the cystic mass by clinical and imaging methods even with advanced technical tools and the low risk of torsion (11.1%). Despite the recognized benign nature of POCs, we found an unexpected high percent (25.9%) of borderline giant POCs. Surgical excision is the only treatment option. Ovarian-sparing surgery was performed in 85.1% of the cases, and minimally invasive techniques were applied in only 42.9% of the patients, which demonstrates the need of a high-level laparoscopic expertise. Knowledge of this pathology, its recognition as a possible etiology of an abdominopelvic cyst, and a higher awareness of the possibility of a borderline histology in giant POCs are required for the proper management of these particular cases.

Caffeine attenuates liver damage and improves neurologic signs in a rat model of hepatic encephalopathy

Introduction and aimsCirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. Materials and methodsAn experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. ResultsThe ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. ConclusionCaffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.

Ossifying Fibroma of the Maxilla in Two Cases and Review of the Literature

Ossifying fibroma is a benign tumor that rarely affects the face bones and exclusively the maxilla. We report two cases of ossifying fibroma of the maxilla treated in our department of maxillofacial surgery and stomatology at IBN SINA university hospital in Rabat. The 1st case is a 38-year-old female, with no particular history, who presented a progressive swelling of the left face since 05 months. Extraoral examination demonstrated a grade I left exophthalmos, without diplopia or limitation of eye movements. Intraoral examination revealed a vestibular expression of the tumor. The 2nd case is also a 45-year-old female, who presented a progressive swelling of the left maxilla which gradually increased in size over a period of 04 months. Intra-orally, the buccal vestibule was completely obliterated with the mass. The two patients presented radiological images of similar density, made of a heterogeneous tissue of the maxillary containing calcifications but with different extension. Surgical excision was performed in both patients and the diagnosis was confirmed by histological study of the resected specimen. The evolution of the ossifying fibroma is insidious; this pathology has a clinical polymorphism and a good prognosis. The etiopathogenesis of this tumor is still unknown, it’s more likely to develop in the mandible and very rare in the maxilla. It differs from other types of fibroma by their clinical, radiological and histological aspects. However, only the pathological examination confirms the diagnosis.

Postero-lateral arterio-venous fistula with particular histological aspects as the main cause of severe spinal thoracal stenosis

Spinal dural arteriovenous fistulas (AVFs) are rare spine vascular malformations. We report a case of AVF in the epidural space of T10 and degenerative medial osteophytes leading to clinical symptoms of severe spinal stenosis operated with good evolution.