Search results for: rats and histology

Authors: Sadaf Kalhori

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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

Procedia PDF Downloads 137

Authors: Sasan Khademnematolahi, Kevine Kamga Silihe, Katarína Pružinská, Martina Chrastina, Elisabeth Louise Ndjengue Mindang, František Dráfi, Katarína Bauerová

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Background: In ethnomedicine, plant parts and compounds are traditionally utilized to treat many disorders. Azadirachta indica, known as Neem, has been traditionally used in medicinal practices. Due to the presence of bioactive substances such as nimbolide, azadirachtin, and gedunin, Neem offers a variety of medicinal properties, including anti-inflammatory and antioxidant properties. Through its effect on pathological inflammatory processes, supplementation with it could alleviate the symptoms of rheumatoid arthritis (RA). Methods: This research aimed to assess Neem seed oil's impact on rats with adjuvant arthritis. Three doses in monotherapy and two in combination with methotrexate (MTX) have been studied, and their effect was compared. Neem p.o. doses of 100, 200, and 300 mg/kg and MTX p.o. doses of 0.3 mg/kg were examined. After clinical parameters assessment, biochemical analysis was performed in plasma. Results: During the acute phase of the experimental arthritis (Day21), levels of MMP-9, MCP-1, and cytokines IL-1beta and IL-17A were measured. The positive results of inflammatory mediators evaluation in plasma encourage additional analysis also in related tissues to prove if Neem seed oil can be used as an adjuvant therapy for RA. Conclusion: In this study, the combination therapy of Neem with MTX was the most effective of all therapies investigated. Acknowledgement: SAIA PROJECT of Kevine Kamga Silihe, Slovakia-Cameroon 2023: “The effect of Crocus sativus L (Saffron), Azadirachta indica (Neem) and their main bioactives compounds in combinatory treatment with methotrexate on experimental arthritis”, VEGA 2/0079/24, VEGA 2/0136/20, VEGA 2/0126/23 and VEGA 2/0091/23.

Keywords: adjuvant, Neem, methotrexate, arthritis

Procedia PDF Downloads 43

Authors: Veronica Barragan, Ligia Luna, Maria Patricia Zambrano, Carlos Bulnes, Eduardo Diaz, Talima Pearson

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Leptospirosis impacts animal production and is responsible for important economic losses in the pig industry. Infection is associated with reproductive failures that lead to abortions, stillbirth, and perinatal mortality. The leptospira serogroups that have been traditionally linked to disease in pigs are Pomona, Australis, and Tarassovi. Unfortunately, knowledge about pig leptospirosis is biased towards infection in large-scale commercial farms from developed countries, where exposure is usually limited to host-specific serotypes. The aim of our study is to describe leptospirosis in pigs from rural communities located in the coast of Ecuador-South America, where leptospirosis is endemic. A particularity of these pigs is that, because they are usually raised in the backyard of their owner’s houses, exposure to other leptospira excreted by other animals is likely to occur. Therefore, we collected 420 kidney samples from pigs sacrificed at a local slaughterhouse, and Leptospira positivity was tested in all samples by amplifying the Lipl32 gen. Our results show pathogenic Leptospira positivity in 19.3% (81/420) of pigs. Microaglutination test was performed in 60 PCR positive samples with titers >1:100 in 17 pigs, titers of 1:50 in 28 pigs, and no MAT titers in 15 pigs even though Leptospira DNA was found in their kidneys. Interestingly, reacting serovars were very diverse, with 18.3% of pig sera reacting with two or more serovars. Additionally, serovar Canicola was found in 16.7% of pigs followed by Tarassovi (10%), Australis (6.7%), Pyogenes (5%), Icterohaemorrhageae (1.7%), and Grippotyphosa (1.7%). It is also important to highlight that most of the analyzed animals came from small-scale farms where pigs may be exposed to the pathogen by exposure to other domestic and peridomestic animals such as rats, dogs, horses, donkeys, and even wildlife. This would explain the finding of non-pig adapted Leptospira serovars such as Canicola, which is commonly reported in dogs.

Keywords: Leptospira, Lipl32, peridomestic, pig, serovar

Procedia PDF Downloads 137

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

Procedia PDF Downloads 182

Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

Procedia PDF Downloads 153

Authors: M. E. Kolpakova, A. A. Jakovleva, L. S. Poliakova, H. El Amghari, S. Soliman, D. R. Faizullina, V. V. Sharoyko

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Brain neuroplasticity is associated with blood-brain barrier vascular endothelial proteoglycans and post-stroke microglial activation. The study of the mechanisms of reperfusion injury limitation by remote ischemic postconditioning (RC) is of interest due to the effects on functional recovery after cerebral ischemia. The goal of the study is the assessment of the role of syndecan-1 (SDC-1) in restriction of ischemic-reperfusion injury on middle cerebral artery model in rats using RC protocol. Randomized controlled trials were conducted. Ischemia was performed by middle cerebral artery occlusion by Belayev L. (1996) on the Wistar rat-males (n= 87) weighting 250 ± 50 g. under general anesthesia (Zoletil 100 и Xylazine 2%). Syndecan-1 (SDC-1) concentration difference in plasma samples of false operated animals and animals with brain ischemia was 30% (30 min. МСАо: 41.4 * ± 1.3 ng/ml). SDC-1 concentration in animal plasma samples with ischemia + RC protocol was 112% (30 min МСАо+ RC): 67.8**± 5.8 ng/ml). Calculation of infarction volume in the ischemia group revealed brain injury in 31.97 ± 2.5%; the volume of infarction was 13.6 ± 1.3% in 30 min. МCАо + RC group. Swelling of tissue in the group 30 min. МCАо + RC was 16 ± 2.1%; it was 47 ± 3.3%. in 30 min. МCАо group. Correlation analysis showed a high direct correlation relationship between infarct area and muscle strength in the right forelimb (КК=0.72) in the 30 min. МCАо + RC group. Correlation analysis showed very high inverse correlation between infarct area and capillary blood flow in the 30 min. МCАо + RC group (p <0.01; r = -0.98). We believe the SDC-1 molecule in blood plasma may play role of potential messenger of ischemic-reperfusion injury restriction mechanisms. This leads to infarct-limiting effect of remote ischemic postconditioning and early functioning recovery.

Keywords: ischemia, МСАо, remote ischemic postconditioning, syndecan-1

Procedia PDF Downloads 59

Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

Procedia PDF Downloads 146

Authors: Chee Wai Ku, Pui See Chin

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As an emerging alternative to hysterectomy, uterine artery embolization (UAE) has been widely used in the management of fibroids and in controlling postpartum hemorrhage (PPH) unresponsive to other therapies. Research has shown UAE to be a safe, minimally invasive procedure with few complications and minimal effects on future fertility. We present two cases highlighting the use of UAE in preventing PPH in a patient with a large fibroid at the time of cesarean section and in the treatment of secondary PPH refractory to other therapies in another patient. We present a 36-year primiparous woman who booked at 18+6 weeks gestation with a 13.7 cm subserosal fibroid at the lower anterior wall of the uterus near the cervix and a 10.8 cm subserosal fibroid in the left wall. Prophylactic internal iliac artery occlusion balloons were placed prior to the planned classical midline cesarean section. The balloons were inflated once the baby was delivered. Bilateral uterine arteries were embolized subsequently. The estimated blood loss (EBL) was 400 mls and hemoglobin (Hb) remained stable at 10 g/DL. Ultrasound scan 2 years postnatally showed stable uterine fibroids 10.4 and 7.1 cm, which was significantly smaller than before. We present the second case of a 40-year-old G2P1 with a previous cesarean section for failure to progress. There were no antenatal problems, and the placenta was not previa. She presented with term labour and underwent an emergency cesarean section for failed vaginal birth after cesarean. Intraoperatively extensive adhesions were noted with bladder drawn high, and EBL was 300 mls. Postpartum recovery was uneventful. She presented with secondary PPH 3 weeks later complicated by hypovolemic shock. She underwent an emergency examination under anesthesia and evacuation of the uterus, with EBL 2500mls. Histology showed decidua with chronic inflammation. She was discharged well with no further PPH. She subsequently returned one week later for secondary PPH. Bedside ultrasound showed that the endometrium was thin with no evidence of retained products of conception. Uterotonics were administered, and examination under anesthesia was performed, with uterine Bakri balloon and vaginal pack insertion after. EBL was 1000 mls. There was no definite cause of PPH with no uterine atony or products of conception. To evaluate a potential cause, pelvic angiogram and super selective left uterine arteriogram was performed which showed profuse contrast extravasation and acute bleeding from the left uterine artery. Superselective embolization of the left uterine artery was performed. No gross contrast extravasation from the right uterine artery was seen. These two cases demonstrated the superior efficacy of UAE. Firstly, the prophylactic use of intra-arterial balloon catheters in pregnant patients with large fibroids, and secondly, in the diagnosis and management of secondary PPH refractory to uterotonics and uterine tamponade. In both cases, the need for laparotomy hysterectomy was avoided, resulting in the preservation of future fertility. UAE should be a consideration for hemodynamically stable patients in centres with access to interventional radiology.

Keywords: fertility preservation, secondary postpartum hemorrhage, uterine embolization, uterine fibroids

Procedia PDF Downloads 185

Authors: Namekong Fokeng Armand

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Background: Zoonoses are nowadays a serious public health problem in both developing and developed countries. They contribute to increase the economic burden. In case of emergence, rural populations are the most affected, hence the need to investigate risk practices in rural households of Penka-Michel (West Cameroon). Methods: This cross-sectional study was conducted from October to November 2021 among 200 heads of households living in the Penka-Michel health district (West Cameroon). It was done using a pre-tested and validated questionnaire, allowing to obtain socio-demographic, economic data, and data on zoonotic risk practices. Results: The participants [women (56%), men (44%)] worked mainly in the informal private sector (53%) and practiced agriculture secondarily (90%). Their highest level of education, for the most part, was a secondary school (50%); the average household size was 06 persons with a monthly income > 36270 FCFA (72%). 74% of household heads thought that animals can transmit diseases, and 17% had heard about zoonotic diseases through the media (65%). Rats caught in households (60%) were consumed there (74%), as was bush meat (61%) or dog meat (18%). For family food (90%), animals were slaughtered within the household (97%), rarely preceded by a veterinary inspection (6%). 87% of households practiced traditional rites with animal blood, 65% shared the same habitat as their animals, 41% did not systematically wash their hands after handling animals. More than 50% of households owned one or more dogs, usually strays (41%) and 48% of which were vaccinated (rabies). Many households had at least one: poultry (98%); pig (50%); dog (57%), cat (52%). 25% of households slaughtered sick animals for consumption, and 27% ate dead animals. Conclusion: This study identified numerous zoonotic risk practices in households in the Penka-Michel health district (West Cameroon). Concerted, multisectoral communication / awareness-raising actions are needed to break with these practices.

Keywords: zoonoses, risky practices, rural households, penka-michel, cameroon

Procedia PDF Downloads 169

Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: Discrete, non aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula, showed a significant reduction of blood glucose level over 24 h. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

Procedia PDF Downloads 292

Authors: Noor Ul Huda, Mushtaq Ahmed, Nadia Mushtaq, Naila Sher, Rahmat Ali Khan

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Purpose: The green synthesis of AgNPs has been favored over chemical synthesis due to their distinctive properties such as high dispersion, surface-to-volume ratio, low toxicity, and easy preparation. In the present work, the biosynthesis of AgNPs (KE-AgNPs) was carried out in one step by using the traditionally used plant Kickxia elatine (KE) extract and then investigated its enzyme inhibiting activity against rat’s brain acetylcholinesterase (AChE) in vitro. Methods: KE-AgNPs were synthesized from 1mM AgNO₃ using KE extract and characterized by UV–spectroscopy, SEM, EDX, XRD, and FTIR analysis. Rat’s brain acetylcholinesterase (AChE) inhibition activity was evaluated by the standard protocol. Results: UV–spectrum at 416 nm confirmed the formation of KE-AgNPs. X-ray diffraction (XRD) pattern presented 2θ values corresponding to the crystalline nature of KE-AgNPs with an average size of 42.47nm. The scanning electron microscope (SEM) analysis confirmed the presence of spherical-shaped and huge density KE-AgNPs with a size of 50nm. Fourier transform infrared spectroscopy (FT-IR) suggested that the functional groups present in KE extract and on the surface of KE-AgNPs are responsible for the stability of biosynthesized NPs. Energy dispersive X-ray (EDX) displayed an intense sharp peak at 3.2 keV, presenting that Ag was the chief element with 61.67%. Both KE extract and KE-AgNPs showed good and potent anti-AChE activity, with higher inhibition potential at a concentration of 175 µg/ml. Statistical analysis showed that both KEE and AgNPs exhibited non-competitive type inhibition against AChE, i.e., Vmax decreased (34.17-68.64% and 22.29- 62.10%) in the concentration-dependent mode for KEE and KE-AgNPs respectively and while Km values remained constant. Conclusions: KEE and KE-AgNPs can be considered an inhibitor of rats’ brain AChE, and the synthesis of KE-AgNPs-based drugs can be used as a cheaper and alternative option against diseases such as Alzheimer’s disease.

Keywords: Kickxia elatine, AgNPs, brain homogenate, acetylcholinesterase, kinetics

Procedia PDF Downloads 119

Authors: Hichem Sebai, Mohamed Amine Jabri, Kais Rtibi, Haifa Tounsi, Lamjed Marzouki

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Artemisia campestris has been widely used in Tunisian traditional medicine for its health beneficial effects. However, the present study aims at evaluating the antiulcer effects of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. In this respect, male Wistar rats were divided into seven groups: control, aspirin (ASPR), ASPR + various doses of ACAE (100, 200 and 400 mg/kg, b.w.), ASPR+ famotidine and ASPR+ caffeic acid. Animals were pre-treated with ACAE extract during 10 days. We firstly showed that aspirin administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level, a decrease of sulfhydryl -(SH) groups content and depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H₂O₂), free iron and calcium levels while the ACAE pre-treatment reversed all aspirin-induced intracellular mediators disturbance. The results of the present study clearly indicated that AEAC gastroprotection might be related, at least in part, to its antioxidant properties as well as to various gastric mucosal defense mechanisms, including the protection of gastric sulfhydryls and an opposite effect on some intracellular mediators such as free iron, hydrogen peroxide, and calcium. However, our data confirm the use of Artemisia campestris extracts in the Tunisian traditional folk medicine for the treatment of gastrointestinal diseases.

Keywords: gastric ulcer, Artemisia campestris, oxidative stress, sulfhydryl groups, Fenton reaction, rat

Procedia PDF Downloads 143

Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

Procedia PDF Downloads 133

Authors: Tamer Shehata

Abstract:

Recently, nanotechnology acquired a great interest in the field of pharmaceutical production. Several pharmaceutical equipment were introduced into the research field for production of nanoparticles, among them, BÜCHI’ fourth generation nano-spray dryer B-90. B-90 is specialized with single step of production and drying of nano and microparticles. Currently, our research group is investigating several pharmaceutical formulations utilizing BÜCHI Nano-Spray Dryer B-90 technology. One of our projects is the formulation and evaluation of metformin hydrochloride mucoadhesive microparticles for treatment of type 2-diabetis. Several polymers were investigated, among them, gelatin and sodium alginate. The previous polymers are natural polymers with mucoadhesive properties. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension were performed. Postformulation characters such as particle size, flowability, surface scan and dissolution profile were evaluated. Finally, the pharmacological activity of certain selected formula was evaluated in streptozotocin-induced diabetic rats. B-90’spray head was 7 µm hole heated to 120 with air flow rate 3.5 mL/min. The viscosity of the solution was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Successfully, discrete, non-aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and Sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, mucoadhesive metformin hydrochloride microparticles obtained from B-90 could offer a convenient dosage form with enhanced hypoglycemic activity.

Keywords: mucoadhesive, microparticles, metformin hydrochloride, nano-spray dryer

Procedia PDF Downloads 309

Authors: Muhammad Shahzad Hussain

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Two major problems are facing generally by conventional poultry farming that is disease outbreaks and poor performance, which results due to improper management. To enhance the growth performance and efficiency of feed and reduce disease outbreaks, antibiotic growth promoters (AGPs) which are antibiotics at sub-therapeutic levels, are extensively used in the poultry industry. European Union has banned the use of antibiotics due to their presence in poultry products, development of antibiotic-resistant pathogens, and disturbance of normal gut microbial ecology. These residues cause serious health concerns and produce antibiotic resistance in pathogenic microbes in human beings. These issues strengthen the need for the withdrawal of AGPs from poultry feed. Nowadays, global warming is a major issue, and it is more critical in tropical areas like Pakistan, where heat stress is already a major problem. Heat stress leads to poor production performance, high mortality, immuno-suppression, and concomitant diseases outbreak. The poultry feed industry in Pakistan, like other countries of the world, has been facing shortages and high prices of local as well as imported feed ingredients. Prebiotics are potential replacer for AGP as prebiotics has properties to enhance the production potential and reduce the growth of harmful bacteria as well as stimulate the growth/activity of beneficial bacteria. The most commonly used prebiotics in poultry includes mannan oligosaccharide (MOS). MOS is an essential component of the yeast cell wall (YCW) (Saccharomyces cerevisiae); therefore, the YCW wall possesses prebiotic properties. The use of distillery yeast wall (YCW) has the potential to replace conventional AGPs and to reduce mortality due to heat stress as well as to bind toxins in the feed. The dietary addition of YCW has not only positive effects on production performance in poultry during normal conditions but during stressful conditions. A total of 168-day-old broilers were divided into 6 groups, each of which has 28 birds with 4 replicates (n=7).Yeast cell wall (YCW) supplementation @ 0%, 1%, 1.5%, 2%, 2.5%, 3% from day 0 to 35. Heat stress was exposed from day 21 to 35 at 30±1.1ᵒC with relative humidity 65±5%. Zootechnical parameters like body weight, FCR, Organ development, and histomorphometric parameters were studied. A significant weight gain was observed at group C supplemented @ 1.5% YCW during the fifth week. Significant organ weight gain of Gizzard, spleen, small intestine, and cecum was observed at group C supplemented @ 1.5% YCW. According to morphometric indices Duodenum, Jejunum, and Ileum has significant villus height, while Jejunum and Ileum have also significant villus surface area in the group supplemented with 1.5% YCW. IEL count was only decreased in 1.5% YCW-fed group in jejunum and ileum, not in duodenum, that was less in 2% YCW-supplemented group. Dietary yeast cell wall of saccharomyces cerevisiae partially reduced the effects of high ambient temperature in terms of better growth and modified gut histology and components of mucosal immune response to better withstand heat stress in broilers.

Keywords: antibiotics, AGPs, broilers, MOS, prebiotics, YCW

Procedia PDF Downloads 93

Authors: H. Sebai, M. A. Jabria, D. Wannes, H. Tounsi, L. Marzouki

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We aimed in the present study to investigate the protective effects of Tunisian Rosa canina aqueous extract (RCAE) against ethanol-induced gastric ulceration and oxidative stress in a rat model. In this respect, adult male Wistar rats were used and divided into six groups of ten each: control, EtOH, EtOH plus various doses of RCAE, EtOH plus famotidine and EtOH + gallic acid. Phytochemical and biochemical analysis were performed using colorimetric methods. We found that RCAE is rich in total polyphenols, total flavonoids, and condensed tannins, and exhibited an importance in vitro antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In vivo, the results showed that oral administration of EtOH caused macroscopic and histological changes in gastric mucosa. These injuries are accompanied by an oxidative stress status as assessed by an increase of lipid peroxidation as well as a decrease of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Alcohol intoxication also induced intracellular mediators deregulation as assessed by an increase of hydrogen peroxide (H2O2), calcium and free iron levels in gastric mucosa. More, importantly, RCAE pretreatment reversed all macroscopic, histological and biochemical changes induced by EtOH administration. In conclusion, we suggest that RCAE has potent protective effects on acute ethanol-induced gastric ulceration related in part in part its antioxidant properties and its opposite effect on intracellular mediators. Indeed, Rosa canina can be offered as a food additive to protect against alcohol consumption-induced gastric and oxidative damage.

Keywords: alcohol, antioxidant properties, food additive, gastric ulceration, rat model, Rosa canina

Procedia PDF Downloads 196

Authors: M. P. Dandekar, A. P. Bharne, P. T. Borkar, D. M. Kokare, N. K. Subhedar

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Ethanol ingestion by the mother ensue adverse consequences for her offspring. Herein, we examine the behavioral phenotype and neural substrate of the offspring of the mother on ethanol. Female rats were fed with ethanol-containing liquid diet from 8 days prior of conception and continued till 25 days post-parturition to coincide with weaning. Behavioral changes associated with anxiety, depression and learning and memory were assessed in the offspring, after they attained adulthood (day 85), using elevated plus maze (EPM), forced swim (FST) and novel object recognition tests (NORT), respectively. The offspring of the alcoholic mother, compared to those of the pair-fed mother, spent significantly more time in closed arms of EPM and showed more immobility time in FST. Offspring at the age of 25 and 85 days failed to discriminate between novel versus familiar object in NORT, thus reflecting anxiogenic, depressive and amnesic phenotypes. Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CART) is known to be involved in central effects of ethanol and hence selected for the current study. Twenty-five days old pups of the alcoholic mother showed significant augmentation in CART-immunoreactivity in the cells of Edinger-Westphal (EW) nucleus and lateral hypothalamus. However, a significant decrease in CART-immunoreactivity was seen in nucleus accumbens shell (AcbSh), lateral part of bed nucleus of the stria terminalis (BNSTl), locus coeruleus (LC), hippocampus (CA1, CA2 and CA3), and arcuate nucleus (ARC) of the pups and/or adults offspring. While no change in the CART-immunoreactive fibers of AcbSh and BNSTl, CA2 and CA3 was noticed in the 25 days old pups, the CART-immunoreactive cells in EW and paraventricular nucleus (PVN), and fibers in the central nucleus of amygdala of 85 days old offspring remained unaffected. We suggest that the endogenous CART system in these discrete areas, among other factors, may be a causal to the abnormalities in the next generation of an alcoholic mother.

Keywords: anxiety, depression, CART, ethanol, immunocytochemistry

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Authors: Jihoon Yang, Jeong II Choi

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Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

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Authors: Wen-Ting Wang, Wei-An Tsai, Rong-Hong Hsieh

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Long term taking high fat diet can lead to over production of energy, result in accumulation of body fat, dyslipidemia and increased lipid metabolism in the body. Over metabolism of lipid results in excessive reactive oxygen species and oxidative stress, may also cause mitochondrial dysfunction and cell death. Krill oil, fish oil and linseed oil are good sources of n-3 polyunsaturated fatty acids (PUFA). The present study investigated the effect of high fat diet and various oil rich of n-3 fatty acids on mitochondrial function and cell membrane composition. Six-weeks old male Spraque-Dawley rats were randomly divided into 8 groups including: control group, high fat diet group, low dosage and high dosage krill oil group, low dosage and high dosage fish oil group, and low dosage and high dosage linseed oil group. After 12 weeks of experimental period, the low dosage krill oil, fish oil group and linseed oil group with different dosage prevented mitochondrial dysfunction caused by high fat diet. The supplementation of different oils increased plasma, erythrocyte and mitochondrial n-3/n-6 ratio and further increased the proportion of PUFA in erythrocyte and mitochondrial membrane. It also decreased serum triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) concentration. However, there was no significant change in serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), biomarker of liver function, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and plasma malonadialdehyde (MDA) concentration when compared with high fat diet group. The supplementation of different sources of n-3 PUFA can maintain mitochondrial function and modulate cell membrane fatty acid composition in high fat diet conditions, and there is a positive relationship between mitochondrial function and mitochondrial membrane composition.

Keywords: fish oil, linseed oil, mitochondria, n-3 PUFA

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

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Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

Abstract:

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

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Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

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Authors: Sam Yurdakul, Nick Baverstock, Jim Mills

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TDT 064 (FLEXISEQ®) is a drug-free gel used to treat osteoarthritis (OA)-associated pain and joint stiffness. It contains ultra-deformable phospholipid Sequessome™ vesicles, which can pass through the skin barrier intact. In six randomized OA studies, topical TDT 064 was well tolerated and improved joint pain, physical function and stiffness. In the largest study, these TDT 064-mediated effects were statistically significantly greater than oral placebo and equivalent to celecoxib. To understand the therapeutic effects of TDT 064, we investigated the localisation of the drug-free vesicles within rat synovial joints. TDT 064 containing DiO-labelled Sequessome™ vesicles was applied to the knees of four 6-week-old CD® hairless rats (10 mg/kg/ joint), 2–3 times/day, for 3 days (representing the recommended clinical dose). Eighteen hours later, the animals and one untreated control were sacrificed, and the knee joints isolated, flash frozen and embedded in Acrytol Mounting Media™. Approximately 15 sections (10 µm) from each joint were analysed by fluorescence microscopy. To investigate whether the localisation of DiO fluorescence was associated with intact vesicles, an anti-PEG monoclonal antibody (mAb) was used to detect Tween, a constituent of Sequessome™ vesicles. Sections were visualized at 484 nm (DiO) and 647 nm (anti-PEG mAb) and analysed using inForm 1.4 (Perkin Elmer, Inc.). Significant fluorescence was observed at 484 nm in sections from TDT 064-treated animals. No non-specific fluorescence was observed in control sections. Fluorescence was detected as discrete vesicles on the cartilage surfaces, inside the cartilaginous matrix and within the synovial space. The number of DiO-labelled vesicles in multiple fields of view was consistent and >100 in sections from four different treated knees. DiO and anti-PEG mAb co-localised within the collagenous tissues in four different joint sections. Under higher magnification (40x), vesicles were seen in the intercellular spaces of the synovial joint tissue, but no fluorescence was seen inside cells. These data suggest that the phospholipid vesicles in TDT 064 localize at the surface of the joint cartilage; these vesicles may therefore be supplementing the phospholipid deficiency reported in OA and acting as a biolubricant within the synovial joint.

Keywords: joint pain, osteoarthritis, phospholipid vesicles, TDT 064

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Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

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Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Michael Josef Schwerer, Oliver Peschel

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Background: The sense and purpose of forensic postmortem examinations are undoubtedly the same in Institutes of Legal Medicine all over the world. Cause and manner of death must be determined, persons responsible for unnatural death must be brought to justice, and accidents demand changes in the respective scenarios to avoid future mishaps. The latter particularly concerns aircraft accidents, not only regarding consequences from criminal or civil law but also in pursuance of the International Civil Aviation Authority’s regulations, which demand lessons from mishap investigations to improve flight safety. Irrespective of the distinct circumstances of a given casualty or the respective questions in subsequent death investigations, a forensic autopsy is the basis for all further casework, the clue to otherwise hidden solutions, and the crucial limitation for final success when not all possible findings have been properly collected. This also implies that the targeted work of police forces and expert witnesses strongly depends on the quality of forensic pathology practice. Deadly events in foreign countries, which lead to investigations not only abroad but also in Germany, can be challenging in this context. Frequently, second-look autopsies after the repatriation of the deceased to Germany are requested by the legal authorities to ensure proper and profound documentation of all relevant findings. Aims and Methods: To validate forensic postmortem practice abroad, a retrospective study using the findings in the corresponding second-look autopsies in the Institute of Legal Medicine Munich over the last 20 years was carried out. New findings unreported in the previous autopsy were recorded and judged for their relevance to solving the respective case. Further, the condition of the corpse at the time of the second autopsy was rated to discuss artifacts mimicking evidence or the possibility of lost findings resulting from, e.g., decomposition. Recommendations for future handling of death cases abroad and efficient autopsy practice were pursued. Results and Discussion: Our re-evaluation confirmed a high quality of autopsy practice abroad in the vast majority of cases. However, in some casework, incomplete documentation of pathology findings was revealed along with either insufficient or misconducted dissection of organs. Further, some of the bodies showed missing parts of some organs, most probably resulting from sampling for histology studies during the first postmortem. For the aeromedical evaluation of a decedent’s health status prior to an aviation mishap, particularly lost or obscured findings in the heart, lungs, and brain impeded expert testimony. Moreover, incomplete fixation of the body or body parts for repatriation was seen in several cases. This particularly involved previously dissected organs deposited back into the body cavities at the end of the first autopsy. Conclusions and Recommendations: Detailed preparation in the first forensic autopsy avoids the necessity of a second-look postmortem in the majority of cases. To limit decomposition changes during repatriation from abroad, special care must be taken to include pre-dissected organs in the chemical fixation process, particularly when they are separated from the blood vessels and just deposited back into the body cavities.

Keywords: autopsy practice, second-look autopsy, retrospective study, quality standards, decomposition changes, repatriation

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Rafay Ahmed, Condon Lau

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Bone healing is a complex and sequential process involving changes at the molecular level. Raman spectroscopy is a promising technique to study bone mineral and matrix environments simultaneously. In this study, subcritical calvarial defects are used to study bone composition during healing without discomposing the fracture. The model allowed to monitor the natural healing of bone avoiding mechanical harm to the callus. Calvarial defects were created using 1mm burr drill in the parietal bones of Sprague-Dawley rats (n=8) that served in vivo defects. After 7 days, their skulls were harvested after euthanizing. One additional defect per sample was created on the opposite parietal bone using same calvarial defect procedure to serve as control defect. Raman spectroscopy (785 nm) was established to investigate bone parameters of three different skull surfaces; in vivo defects, control defects and normal surface. Principal component analysis (PCA) was utilized for the data analysis and interpretation of Raman spectra and helped in the classification of groups. PCA was able to distinguish in vivo defects from normal surface and control defects. PC1 shows that the major variation at 958 cm⁻¹, which corresponds to ʋ1 phosphate mineral band. PC2 shows the major variation at 1448 cm⁻¹ which is the characteristic band of CH2 deformation and corresponds to collagens. Raman parameters, namely, mineral to matrix ratio and crystallinity was found significantly decreased in the in vivo defects compared to surface and controls. Scanning electron microscope and optical microscope images show the formation of newly generated matrix by means of bony bridges of collagens. Optical profiler shows that surface roughness increased by 30% from controls to in vivo defects after 7 days. These results agree with Raman assessment parameters and confirm the new collagen formation during healing.

Keywords: Raman spectroscopy, principal component analysis, calvarial defects, tissue characterization

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Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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