Search results for: histological

Authors: Saboor Saeed, Chunming Jiang

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Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extra pulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. Generally, EGPA will develop in three stages: a) The allergic phase is commonly associated with asthma, allergic rhinitis, and sinusitis, b) the eosinophilic phase, in which the main pathology is related to the infiltration of eosinophilic organs, i.e., lung, heart, and gastrointestinal system, c) vasculitis phase involved purpura, peripheral neuropathy, and some constitutional symptoms. The key to the treatment of EGPA lies in the early diagnosis of the disease. Early application of glucocorticoids and immunosuppressants can improve symptoms and the overall prognosis of EGPA. Case Description: We presented a case of an 8-year-old boy with a history of short asthma, marked eosinophilia, and multi-organ involvement. The extremely high eosinophil level in the blood (72.50%) prompted the examination of eosinophilic leukemia before EGPA diagnosis was made. Subsequently, this disease was successfully treated. This case report shows a typical case of CSS in childhood because of the extreme eosinophilia. It emphasizes the importance of EGPA is a life-threatening cause of children's eosinophilia. Conclusion: EGPA in children has unique clinical, imaging, and histological characteristics different from those of adults. In pediatric patients, the development and diagnosis of systemic symptoms are often delayed, mainly occurring in the eosinophilic phase, which will lead to specific manifestations. At the same time, we cannot detect a genetic relationship related to EGPA.

Keywords: Churg Strauss syndrome, asthma, vasculitis, hypereosinophilia, eosinophilic granulomatosis polyangiitis

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Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

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Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Ticijana Prijon, Branko Ermenc

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Background: Blunt aortic trauma (BAT) includes various morphological changes that occur during deceleration, acceleration and/or body compression in traffic accidents. The various forms of BAT, from limited laceration of the intima to complete transection of the aorta, depends on the force acting on the vessel wall and the tolerance of the aorta to injury. The force depends on the change in velocity, the dynamics of the accident and of the seating position in the car. Tolerance to aortic injury depends on the anatomy, histological structure and pathomorphological alterations due to aging or disease of the aortic wall.An overview of the literature and medical documentation reveals that different terms are used to describe certain forms of BAT, which can lead to misinterpretation of findings or diagnoses. We therefore, propose a classification that would enable uniform systematic screening of all forms of BAT. We have classified BAT into three morphologycal types: TYPE I (intramural), TYPE II (transmural) and TYPE III (multiple) aortic ruptures with appropriate subtypes. Methods: All car accident casualties examined at the Institute of Forensic Medicine from 2001 to 2009 were included in this retrospective study. Autopsy reports were used to determine the occurrence of each morphological type of BAT in deceased drivers, front seat passengers and other passengers in cars and to define the morphology of BAT in relation to the accident dynamics and the age of the fatalities. Results: A total of 391 fatalities in car accidents were included in the study. TYPE I, TYPE II and TYPE III BAT were observed in 10,9%, 55,6% and 33,5%, respectively. The incidence of BAT in drivers, front seat and other passengers was 36,7%, 43,1% and 28,6%, respectively. In frontal collisions, the incidence of BAT was 32,7%, in lateral collisions 54,2%, and in other traffic accidents 29,3%. The average age of fatalities with BAT was 42,8 years and of those without BAT 39,1 years. Conclusion: Identification and early recognition of the risk factors of BAT following a traffic accident is crucial for successful treatment of patients with BAT. Front seat passengers over 50 years of age who have been injured in a lateral collision are the most at risk of BAT.

Keywords: aorta, blunt trauma, car accidents, morphology, risk factors

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Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

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Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Malay K. Das, Bhupen Kalita

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The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: Hanaa M. M. El-Khayat, Hanan S. Gaber, Hoda Abdel-Hamid, Kadria M. A. Mahmoud, Hoda M. A. Abu Taleb

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This work aimed to examine Oreochromis niloticus fish from Lake Manzala in Port Said, Dakahlya and Damietta governorates, Egypt, as a bio-indicator for the lake water pollution through recording alterations in their hematological, physiological, and histopathological parameters. All fish samples showed a significant increase in levels of alkaline phosphatase (ALP), creatinine and glutathione-S-transferase (GST); only Dakahlya samples showed a significant increase (p<0.01) in aspartate aminotransferase (AST) level and most Dakahlya and Damietta samples showed reversed albumin and globulin ratio and a significant increase in γ-glutamyltransferase (GGT) level. Port-Said and Damietta samples showed a significant decrease of hemoglobin (Hb) while Dakahlya samples showed a significant decrease in white blood cell (WBC) count. Histopathological investigation for different fish organs showed that Port-Said and Dakahlya samples were more altered than Damietta. The muscle and gill followed by intestine were the most affected organs. The muscle sections showed severe edema, neoplasia, necrotic change, fat vacuoles and splitting of muscle fiber. The gill sections showed dilated blood vessels of the filaments, curling of gill lamellae, severe hyperplasia, edema and blood vessels congestion of filaments. The intestine sections revealed degeneration, atrophy, dilation in blood vessels and necrotic changes in sub-mucosa and mucosa with edema in between. The recorded significant alterations, in most of the physiological and histological parameters in O. niloticus samples from Lake Manzala, were alarming for water pollution impacts on lake fish community, which constitutes the main diet and the main source of income for the people inhabiting these areas, and were threatening their public health and economy. Also, results evaluate the use of O. niloticus fish as important bio-indicator for their habitat stressors.

Keywords: Lake Manzala, Oreochromis niloticus fish, water pollution, physiological, hematological and histopathological parameters

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

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With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

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Authors: A. O. Omonona, T. A. Jarikre

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Increase specialization in agriculture and use of pesticides may inadvertently cause ecosystem degradation and eventually loss of biodiversity. The populations of numerous wildlife species have undergone a precipitous decline. Many of these problems have been attributed directly to habitat loss and over exploitation resulting from unregulated pesticide uses. Carbendazim a broad spectrum benzimidazole fungicide and a metabolite of benomyl, is used to control plant disease in cereals and fruit. The effect of carbendazim exposure and the ameliorative effect of tocopherol (vitamin E) were assessed on African giant rat AGR. Hematological, biochemical and histological changes were used to determine the health condition of the animals exposed to pesticide. Sixteen AGR were stabilized, weighed and then divided into four experimental groups (A to D). Two groups were pretreated with vitamin. Group A was exposed to carbendazim only, B- carbendazim + vitamin, C- vitamin only, and D- blank (control). Packed cell volume PCV was estimated by the microhematocrit method, Leucocyte and Platelet counts were determined using the hemocytometric method. Cholinesterase (AchE) and markers of oxidative stress were quantified, and tissue changes examined microscopically. There were no behavioral changes observed in the animals, but there was a decrease in body weight and abortion after 23 days of exposure to carbendazim. There was significant differences in the packed cell volume, the hemoglobin concentration and the red blood cell counts (p < 0.05). The increases in malonyl aldehyde MDA was significant (p < 0.05) in the pesticide intoxicated rats compared to control. Vitamin E supplementation reduced MDA level significantly (p < 0.05). There was a sharp remarkable decrease in acetylcholinesterase levels in the pesticide intoxicated rats (p < 0.05). Vitamin E supplementation normalise the AchE levels comparable to that in control. Grossly, the vital organs appeared normal in the pesticide exposed and control groups except moderate pulmonary congestion. Microscopically, there was severe diffuse hepatocellular swelling in carbendazim exposed group. The severity of hepatocellular injury was reduced in the rats with vitamin E. This study ascertained the toxic effect of carbendazim and antioxidative properties of vitamins in the Africa giant rat.

Keywords: African giant rat, antioxidant, carbendazim, pesticides, toxicity

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Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

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Authors: Cheng-Kuang Hsu, Chih-Hsiang Chang, Chi-Chih Wang

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Black soybeans contain high amount of antioxidants including polyphenols, anthocyanins and flavones. The protective function of black soybean against CCl4 (a strong oxidant) induced acute and chronic liver damage was investigated in vivo using SD rats or ICR mouse. The evaluation of CCl4 induced oxidative stress in the liver tissues included the measurements of the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the concentration of thiobarbituric acid reactive substances (TBARS), the activities of antioxidant enzymes (superoxide dismutase SOD, catalase, and glutathione peroxidase GPx), as well as the level of histological lesion in the liver tissues. For chronic experiment, a decoction at the concentration of 100 or 1000 mg/kg of body weight, produced by baking black soybean at 130°C for 5 min and followed by immerging in 100°C hot water for 20 min, showed the inhibitory effect against CCl4 induced liver damage in SD rats. Hot-water extract (80 °C for 30 min) from un-preheated black soybean at the concentration of 200 mg/kg of body weight could not reduce ALT and AST levels in CCl4 treated SD rats, but the hot-water extract from preheated black soybean did enhance antioxidant enzymes activities, decline ALT and AST levels. Specially, the hot-water extract from the seed cost of black soybean had the highest liver protective function since it can reduce vacuolization and necrosis in the liver tissues. For acute experiment, the hot-water extracts from black soybean and the seed coat, as well as pure cyanidin-3-glucoside (C3G) could reduce ALT and AST levels of CCl4 induced ICR mouse. The decoction and hot-water extract from the seed coat of black soybean had higher total polyphenols, anthocyanins and flavones contents than those extracts from whole black soybean. Such results agreed with high liver protective function in the decoction and hot-water from the seed coat of black soybean. Black soybean showed protective function only after preheating process (baking at 130°C for 5 to 10 min) because preheating treatment damaged the cell wall and made the extraction of the antioxidants more effectively.

Keywords: black soybean, liver protective function, antioxidant, antioxidative stress

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Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

Abstract:

Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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Authors: Kristina Sakalauskiene, Renaldas Raisutis, Gintare Linkeviciute, Skaidra Valiukeviciene

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Cutaneous melanoma is a melanocytic skin tumour, which has a very poor prognosis while is highly resistant to treatment and tends to metastasize. Thickness of melanoma is one of the most important biomarker for stage of disease, prognosis and surgery planning. In this study, we hypothesized that the automatic analysis of spectrophotometric images and high-frequency ultrasonic 2D data can improve differential diagnosis of cutaneous melanoma and provide additional information about tumour penetration depth. This paper presents the novel complex automatic system for non-invasive melanocytic skin tumour differential diagnosis and penetration depth evaluation. The system is composed of region of interest segmentation in spectrophotometric images and high-frequency ultrasound data, quantitative parameter evaluation, informative feature extraction and classification with linear regression classifier. The segmentation of melanocytic skin tumour region in ultrasound image is based on parametric integrated backscattering coefficient calculation. The segmentation of optical image is based on Otsu thresholding. In total 29 quantitative tissue characterization parameters were evaluated by using ultrasound data (11 acoustical, 4 shape and 15 textural parameters) and 55 quantitative features of dermatoscopic and spectrophotometric images (using total melanin, dermal melanin, blood and collagen SIAgraphs acquired using spectrophotometric imaging device SIAscope). In total 102 melanocytic skin lesions (including 43 cutaneous melanomas) were examined by using SIAscope and ultrasound system with 22 MHz center frequency single element transducer. The diagnosis and Breslow thickness (pT) of each MST were evaluated during routine histological examination after excision and used as a reference. The results of this study have shown that automatic analysis of spectrophotometric and high frequency ultrasound data can improve non-invasive classification accuracy of early-stage cutaneous melanoma and provide supplementary information about tumour penetration depth.

Keywords: cutaneous melanoma, differential diagnosis, high-frequency ultrasound, melanocytic skin tumours, spectrophotometric imaging

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

Abstract:

Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

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Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Oday A. Al-Juhaishi, Sa`ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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The functional anatomy of the fascia in the greyhound is still poorly understood, and incompletely described. The basic knowledge of fascia stems mainly from anatomical, histological and ultrastructural analyses. In this study, twelve specimens of hindlimbs from six fresh greyhound cadavers (3 male, 3 female) were used to examine the topographical relationships of the superficial fascia with the skin and underlying tissue. The first incision was made along the dorsal midline from the level of the thoracolumbar junction caudally to the level of the mid sacrum. The second incision was begun at the level of the first incision and extended along the midline of the lateral aspect of the hindlimb distally, to just proximal to the tarsus, and, the skin margins carefully separated to observe connective tissue links between the skin and superficial fascia, attachment points of the fascia and the relationships of the fascia with blood vessels that supply the skin. A digital camera was used to record the anatomical features as they were revealed. The dissections identified fibrous septa connecting the skin with the superficial fascia and deep fascia in specific areas. The presence of the adipose tissue was found to be very rare within the superficial fascia in these specimens. On the extensor aspects of some joints, a fusion between the superficial fascia and deep fascia was observed. This fusion created a subcutaneous bursa in the following areas: a prepatellar bursa of the stifle, a tarsal bursa caudal to the calcaneus bone, and an ischiatic bursa caudal to the ischiatic tuberosity. The evaluation of blood vessels showed that the perforating vessels passed through fibrous septa in a perpendicular direction to supply the skin, with the largest branch noted in the gluteal area. The attachment points between the superficial fascia and skin were mainly found in the region of the flexor aspect of the joints, such as caudal to the stifle joint. The numerous fibrous septa between the superficial fascia and skin that have been identified in some areas, may create support for the blood vessels that penetrate fascia and into the skin, while allowing for movement between the tissue planes. The subcutaneous bursae between the skin and the superficial fascia where it is fused with the deep fascia may be useful to decrease friction between moving areas. The adhesion points may be related to the integrity and loading of the skin. The attachment points fix the skin and appear to divide the hindlimb into anatomical compartments.

Keywords: attachment points, fibrous septa, greyhound, subcutaneous bursa, superficial fascia

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Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: N. D'Amico, E. Grossi, B. Colombo, F. Rigiroli, M. Buscema, D. Fazzini, G. Cornalba, S. Papa

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Purpose: To characterize, through a radiomic approach, the nature of nodules considered non-specific by expert radiologists, recognized in magnetic resonance mammography (MRm) with T1-weighted (T1w) sequences with paramagnetic contrast. Material and Methods: 47 cases out of 1200 undergoing MRm, in which the MRm assessment gave uncertain classification (non-specific nodules), were admitted to the study. The clinical outcome of the non-specific nodules was later found through follow-up or further exams (biopsy), finding 35 benign and 12 malignant. All MR Images were acquired at 1.5T, a first basal T1w sequence and then four T1w acquisitions after the paramagnetic contrast injection. After a manual segmentation of the lesions, done by a radiologist, and the extraction of 150 radiomic features (30 features per 5 subsequent times) a machine learning (ML) approach was used. An evolutionary algorithm (TWIST system based on KNN algorithm) was used to subdivide the dataset into training and validation test and to select features yielding the maximal amount of information. After this pre-processing, different machine learning systems were applied to develop a predictive model based on a training-testing crossover procedure. 10 cases with a benign nodule (follow-up older than 5 years) and 18 with an evident malignant tumor (clear malignant histological exam) were added to the dataset in order to allow the ML system to better learn from data. Results: NaiveBayes algorithm working on 79 features selected by a TWIST system, resulted to be the best performing ML system with a sensitivity of 96% and a specificity of 78% and a global accuracy of 87% (average values of two training-testing procedures ab-ba). The results showed that in the subset of 47 non-specific nodules, the algorithm predicted the outcome of 45 nodules which an expert radiologist could not identify. Conclusion: In this pilot study we identified a radiomic approach allowing ML systems to perform well in the diagnosis of a non-specific nodule at MR mammography. This algorithm could be a great support for the early diagnosis of malignant breast tumor, in the event the radiologist is not able to identify the kind of lesion and reduces the necessity for long follow-up. Clinical Relevance: This machine learning algorithm could be essential to support the radiologist in early diagnosis of non-specific nodules, in order to avoid strenuous follow-up and painful biopsy for the patient.

Keywords: breast, machine learning, MRI, radiomics

Procedia PDF Downloads 246

Authors: Anis Al-Yakhiri

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Introduction: The World Health Organization (WHO) classifies malignant epithelial thyroid tumors into four major groups (papillary, follicular, medullar and undifferentiated) . Papillary thyroid carcinoma (PTC) is the most common type, for about eight out of ten thyroid cancers belong to this histological type. Radioactive iodine (RAI) is considered effective for patients with total or nearly total thyroidectomy, but the beneficial effects of RAI are still controversial. War conditions forced us to study alternative methods of using radioactive iodine in the treatment of patients with PTC. Material and methods: Between January 2014 and June 2021, in Al-Yakhiri hospital, 57 Total Thyroidectomy with Radical BilateralNeckDissection (RBND) were performed, 50 for malignant disease,7 for false positive cytology.RBND involves surgical clearance of Levels II-VI. Mean age was 40.7 years old and 92% of the patients were female. 7(14%) patients had hypothyroidism which required preoperative thyroid hormone treatment. The Thyroid Stimulating Hormone- Suppression Therapy (TSH-ST) immediately started after RBND for mostpatients on the first day. It consisted in reducing the level of TSH< 0.1 mIU/L. Results: The Apron flap was used on most operations (40)80% and with lateral extensions had 10(20%). RBND involves surgical clearance of Levels II-VI performed in all operated patients, besides that, 4(8%) of them had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV) withclearance of Levels IB. The PTC was the most common 80.9% (38 patients from 47)by histopathological report. and 4(8%) patients of 50 had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV). The postoperative mortality rate not observed (0%). The postoperative morbidity rate was 22.8% (n =13).Seroma(8.7%),Hypocalcimia(7%), Wound infection(5.3%), Bleeding(1.8%). To suppress TSH and growth of any residual thyroid theTSH-ST (levothyroxine150 – 600mcg)was performed in all patients 57(100%) on the first day afterRBND. We tracked the results of treatment for two years in 30 patients with PTC, only 3 of them received radioactive iodine abroad. Biennial Recurrence rate for PTC appeared in one woman (2%), who had RAI postoperatively in the form of neck lymph nodes metastasis. Conclusion: For patients with PTC, thyroidectomy plus prophylacticRBND is a safe and efficient procedure and it results in lower recurrence rate. Postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH (not less than 150mcg), decreases incidence of recurrence. Total Thyroidectomy with RBND followed by TSH-ST, in our opinion, applicable optimal treatment scheme care for this patient population.

Keywords: thyroid cancer, Yemen war, absence of radioactive iodine, neck dissection, surgery results

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Authors: Hamid Abdulroof Saleh

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Background: Dioxins are one of the most widely distributed environmental pollutants. Dioxins consist of feedstock during the preparation of some industries, such as the paper industry as they can be produced in the atmosphere during the process of burning garbage and waste, especially medical waste. Dioxins can be found in the adipose tissues of animals in the food chain as well as in human breast milk. 2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) is the most toxic component of a large group of dioxins. Humans are exposed to TCDD through contaminated food items like meat, fish, milk products, eggs etc. Recently, natural formulations relating to reducing or eliminating TCDD toxicity have been in focus. Ginger rhizome (Zingiber officinale R., family: Zingiberaceae), is used worldwide as a spice. Both antioxidative and androgenic activity of Z. officinale was reported in animal models. Researchers showed that ginger oil has dominative protective effect on DNA damage and might act as a scavenger of oxygen radical and might be used as an antioxidant. Aim of the work: The present study was undertaken to evaluate the toxic effect of TCDD on the structure and histoarchitecture of the testis and the protective role of co-administration of ginger root extract to prevent this toxicity. Materials & Methods: Male adult rats of Sprague-Dawley strain were assigned to four groups, eight rats in each; control group, dioxin treated group (given TCDD at the dose of 100 ng/kg Bwt/day by gavage), ginger treated group (given 50 mg/kg Bwt/day of ginger root extract by gavage), dioxin and ginger treated group (given TCDD at the dose of 100 ng/kg Bwt/day and 50 mg/kg Bwt/day of ginger root extract by gavages). After three weeks, rats were weighed and sacrificed where testis were removed and weighted. The testes were processed for routine paraffin embedding and staining. Tissue sections were examined for different morphometric and histopathological changes. Results: Dioxin administration showed a harmful effects in the body, testis weight and other morphometric parameters of the testis. In addition, it produced varying degrees of damage to the seminiferous tubules, which were shrunken and devoid of mature spermatids. The basement membrane was disorganized with vacuolization and loss of germinal cells. The co-administration of ginger root extract showed obvious improvement in the above changes and showed reversible morphometric and histopathological changes of the seminiferous tubules. Conclusion: Ginger root extract treatment in this study was successful in reversing all morphometric and histological changes of dioxin testicular damage. Therefore, it showed a protective effect on testis against dioxin toxicity.

Keywords: dioxin, ginger, rat, testis

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Authors: Mahmoud Farrag, Alaa Elhaweet, El-Sayed Akel, Mohsen Moustafa

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The present work aimed to study the reproductive strategy of the common lesspsian puffer fish Lagocephalus sceleratus (Gmeln, 1879) from the Egyptian Mediterranean Waters. It is a famous migratory species plays an important role in the field of fisheries and ecology of aquatic ecosystem. The obtained results illustrated seven maturity stages of gonads as; I- Thread like stage: II- Immature stage (Virgin stage), III- Maturing stage (Developing Virgin and recovering spent), IV - Nearly ripe stage, V- Fully ripe; VI-Spawning stage, VII- Spent stage. Sex ratio, exhibited males had higher number than females representing 52.44 % of the total fishes with sex ratio 1: 0.91. Fish length corresponding to 50% maturation was 38.5 cm for males and 41 cm for females. The corresponding ages (age at first maturity) are equal to 2.14 and 2.27 years for male and female respectively. The gonado somatic index (GSI) increased from April for both sexes with peak in June (8.567±4.729) for males and May (6.769±4.662) for females, then the sharp decrease was observed in October showing prolong spawning season from April to September for both sexes. The hepato somatic indices (HSI) for males were lower values than those of females, it were high from December to early spawning (April & May), with the peak in April (5.217 ± 2.167) for males, and in March (5.453± 1.792) for females, then these values started to decrease towards the end of spawning period. The ova diameter ranged from 0.02 to 0.85mm, the mature ova ranged from 0.16 to 0.85mm and showed progressive increase from April towards September during spawning period introducing one peak of mature and ripe eggs. The absolute fecundity increased as the fish grew in weight and length; it was ranged from 260288 to 2372931 for fish weight and ranged from 698 to 3285 cm for length with an average of 1449522±720975. The relative fecundity ranged from 373 to 722 for fish weight with an average of 776±231, while it range from 5784 to 32957 for fish length groups ranged from 43-45 to 70-72 cm with an average of 24478 ±10011 eggs. Histological characters of gonads during the year of study indicating this fish species has prolonged spawning season from April to September where ripe oocytes were observed during this period. This species is considered totally or uni spawner with synchronous group as it contained one to two developmental stages at the same gonad and releases its ripe ova in one batch during the spawning season. These results illustrated more adaptation of this species in new habitat.

Keywords: reproductive biology, histology, Lagocephalus sceleratus, Mediterranean Sea, Egypt

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Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: Uma Krishnamoorthy, Vivienne Beavers, Janet Marshall

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Introduction: Cervical cytology showing features raising the suspicion of non cervical glandular neoplasia are reported as code 0 under the United Kingdom National Health Service Cervical screening programme ( NHSCSP). As the suspicion is regarding non cervical neoplasia, smear is reported as normal and patient informed that cervical screening result is normal. GP receives copy of results where it states further referral is indicated in small font within text of report. Background: There were several incidents of delayed diagnosis of endometrial cancer in Lancashire which prompted this Northwest Regional review to enable an understanding of underlying pathology outcome of code zero smears to raise awareness and also to review whether further action on wording of smear results was indicated to prevent such delay. Methodology: All Smears reported at the Manchester cytology centre who process cytology for Lancashire population from March 2013 to March 2014 were reviewed and histological diagnosis outcome of women in whom smear was reported as code zero was reviewed retrospectively . Results: Total smears reported by the cytology centre during this period was approximately 109400. Reports issued with result code 0 among this during this time period was 49.Results revealed that among three fourth (37) of women with code zero smear (N=49), evidence of underlying pathology of non cervical origin was confirmed. Of this, 73 % (36) were due to endometrial pathology with 49 % (24) endometrial carcinoma, 12 % (6)polyp, 4 % atypical endometrial hyperplasia (2), 6 % endometrial hyperplasia without atypia (3), and 2 % adenomyosis (1 case) and 2 % ( 1 case) due to ovarian adenocarcinoma. Conclusion: This review demonstrated that more than half (51 %) of women with a code 0 smear report were diagnosed with underlying carcinoma and 75 % had a confirmed underlying pathology contributory to code 0 smear findings. Recommendations and Action Plan: A local rapid access referral and management pathway for this group of women was implemented as a result of this in our unit. The findings and Pathway were shared with other regional units served by the cytology centre through the Pan Lancashire cervical screening board and through the Cytology centre. Locally, the smear report wording was updated to include a rubber stamp/ print in "Red Bold letters" stating that " URGENT REFERRAL TO GYNAECOLOGY IS INDICATED". Findings were also shared through the Pan Lancashire board with National cervical screening programme board, and revisions to wording of code zero smear reports to highlight the need for Urgent referral has now been agreed at National level to be implemented.

Keywords: code zero smears, endometrial cancer, non cervical glandular neoplasia, ovarian cancer

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