scholarly journals Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

2001 ◽  
Vol 69 (9) ◽  
pp. 5352-5362 ◽  
Author(s):  
Matthias Eberl ◽  
Jan A. M. Langermans ◽  
Patrice A. Frost ◽  
Richard A. Vervenne ◽  
Govert J. van Dam ◽  
...  

ABSTRACT The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.

2019 ◽  
Vol 56 (3) ◽  
pp. 529-533
Author(s):  
Mihaela Pantea ◽  
Diana Andreea Ighigeanu ◽  
Alexandra Totan ◽  
Maria Greabu ◽  
Daniela Miricescu ◽  
...  

This in vitro study analyses the biochemical interaction between saliva and three types of dental composite resins (a direct resin, an indirect resin and a dual-cure resin used for cementation of indirect dental restorations). The resin samples were obtained following a specific protocol and in line with the producers� recommendations; the resin samples were incubated with saliva samples collected from 19 healthy volunteers. The obtained results showed that the tested composite resins did not produce significant changes in oxidative stress parameters that were analysed (albumin, uric acid, GGT / gamma glutamyl transferase, OXSR-1 / oxidative stress responsive kinase 1) and do not influence the inflammatory salivary status reflected by the levels of IL-6 - an inflammatory marker.


2020 ◽  
Vol 11 (1) ◽  
pp. 25-38
Author(s):  
Nadia I. Zakhary ◽  
Emad E.H. El Gemeie ◽  
Adel K. Youssef ◽  
Marwa Abdel-salam Ibrahim Metwaly

Erucaria pinnata (Viv.) is a wild annual plant growing in North-Western Coastal Region in Egypt. This study reports for the first time the cytotoxic activity of different extracts of Erucaria pinnata plant against HEP-G2 cell line. The 70% methanolic extract (E1) recorded the best potent cytotoxic activity (IC50=13.6 µg/ml), so we analysis the flavonoids constituent of this extract using HPLC, which show that our extract is rich with important flavonoids compounds (rutin, quercetin, leutolin, etc.). We evaluated its antitumor activity against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) (200mg/Kg. b.wt., i.p, single dose) after two weeks, animals received carbontetrachloride (CCl4) (3ml/Kg. b.wt., SC, once a week for 6 weeks) and the experiment continued for 44 weeks in rats. After the experimental period, the administration of DEN/CCl4 showed significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyl transferase (γGT) and significant decrease in the levels of total proteins and albumin content in the serum with reduction in the liver antioxidants, including superoxide dismutase (SOD) and catalase (CAT). This was accompanied by increases in serum specific tumor markers (AFP). The 70% methanolic plant extract (E1) was orally administrated (400mg/kg/day respectively) for the whole study period, and it showed a significant improvement at the different biological liver functions, remodeled the antioxidant enzymes activity and down-regulated the serum AFP. All these findings were confirmed by histopathological studies of the liver samples obtained from all groups. In addition, we evaluated its antiangeogenic activity by docking study against VEGFR-2 tyrosine kinase after it showed an ability to inhibit the VEGFR-2 expression in vitro and inhibit the concentration of VEGF-A in vivo. The hepatoprotective effect of our extract was attributed to its antioxidant and antiangeogenic activity.


2019 ◽  
Vol 44 (6) ◽  
pp. 606-618 ◽  
Author(s):  
Khaled Bellassoued ◽  
Ferdaws Ghrab ◽  
Houda Hamed ◽  
Rim Kallel ◽  
Jos van Pelt ◽  
...  

The inner bark of cinnamon (Cinnamomum verum) is widely used as a spice. Cinnamon plants are also a valuable source of essential oil used for medicinal purposes. The present study aimed to investigate the composition and in vitro antioxidant activity of essential oil of C. verum bark (CvEO) and its protective effects in vivo on CCl4-induced hepatic and renal toxicity in rats. Groups of animals were pretreated for 7 days with CvEO (70 or 100 mg/kg body weight) or received no treatment and on day 7 a single dose of CCl4 was used to induce oxidative stress. Twenty-four hours after CCl4 administration, the animals were euthanized. In the untreated group, CCl4 induced an increase in serum biochemical parameters and triggered oxidative stress in both liver and kidneys. CvEO (100 mg/kg) caused significant reductions in CCl4-elevated levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein, urea, and creatinine and increased the level of high-density lipoprotein compared with the untreated group. Moreover, pretreatment with CvEO at doses of 70 and 100 mg/kg before administration of CCl4 produced significant reductions in thiobarbituric acid reactive substances and protein carbonyl levels in liver and kidney tissues compared with the untreated group. The formation of pathological hepatic and kidney lesions induced by the administration of CCl4 was strongly prevented by CvEO at a dose of 100 mg/kg. Overall, this study suggests that administration of CvEO has high potential to quench free radicals and alleviate CCl4-induced hepatorenal toxicity in rats.


2021 ◽  
Author(s):  
Maria Amélia Agnes Weiller ◽  
Evandro Schmoeller ◽  
Antônio Amaral Barbosa ◽  
Adriane Dalla Costa de Matos ◽  
Marcio Nunes Correa ◽  
...  

Abstract The aim of this study was to determine zootechnical and health performance of Girolando calves born with high or low birth weight, and compare metabolic parameters between groups. The study was carried out on a commercial dairy farm located in Passos, Minas Gerais, Brazil. In this sense, a hundred Girolando calves were divided into 2 groups: Control, which consisted of calves that were born weighing ≤ 35 kg; and HBW, calves that were born weighing > 35 kg. Calves were monitored for zootechnical parameters; epidemiological indexes such as morbidity, mortality, recurrence of diarrhea, pneumonia; as well as serum concentrations of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, cholesterol, triglycerides, paraoxonase1, albumin, urea and globulin). Calves from the HBW group had a higher mortality rate as well as a tendency to more cases of pneumonia, but no effect on zootechnical performance was seen. The reasons for the differences in mortality need to be clarified since our study found no changes in biochemical parameters between the groups. The results allow us to conclude that Girolando calves from in vitro fertilization that are born heavier have a greater chance of clinical complications and a higher mortality rate, but the birth weight does not influence the zootechnical performance.


2010 ◽  
Vol 57 (2) ◽  
Author(s):  
Ana Cipak ◽  
Suzana Borovic ◽  
Morana Jaganjac ◽  
Nikolaus Bresgen ◽  
Iva Kirac ◽  
...  

Liver is a unique mammalian organ with a great capacity of regeneration related to its function. After surgical resection or injury, hepatic cells, especially hepatocytes, can proliferate rapidly to repair the damage and to regenerate the structure without affecting the function of the liver. Loss of catalase activity during regeneration indicates that oxidative stress is present in the liver not only in pathological conditions but also as a 'physiological' factor during regeneration. As we have shown in our previous work, liver stem cell-like cells treated with 4-hydroxynonenal (HNE), a cytotoxic and growth regulating lipid peroxidation product, recover in the presence of spleen cells. In the current study we characterized this novel cell line as liver-derived progenitor/oval-like cells, (LDP/OCs), i.e. functional liver stem-like cells. We showed that LDP/OC were OV6 positive, with abundant glycogen content in the cytoplasm and expressed alpha-fetoprotein, albumin, biliverdin reductase and gamma-glutamyl transferase. Also, we compared their growth in vitro with the growth of cultured primary hepatocytes stressed with HNE and co-cultured with autologous spleen cells. The influence of spleen cells on HNE-treated primary hepatocytes and on LDP/OCs showed that spleen cells support in a similar manner the recovery of both types of liver cells indicating their important role in regeneration. Hence, LDP/OC cells may provide a valuable tool to study cell interactions and the role on HNE in liver regeneration.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Nor Aziyah Mat-Rahim ◽  
Tong-Hye Lim ◽  
Nur-Asyura Nor-Amdan ◽  
Sazaly AbuBakar

Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.


2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Neylisa Dario Lazaro ◽  
Flavia Barbieri Bacha ◽  
Rayane Chitolina Pupin ◽  
Juliana Paniago Lordello de Paula ◽  
Paula Velozo Leal ◽  
...  

Background: Stryphnodendron fissuratum is a tree from the Brazilian Cerrado. Its fruit is toxic to cattle and can cause clinical digestive signs, hepatogenous photosensitization, and abortion. Cases of poisoning in cattle, goats and guinea pigs have been experimentally reproduced; however, photosensitization could not be reproduced. The aim of this work was to describe an outbreak of natural poisoning and experimental reproduction in cattle, both with hepatogenous photosensitization.Materials, Methods & Results: Its described and natural outbreak and an experimental poisoning. In the outbreak, three bovines in the acute phase and three in the chronic phase were examined. Blood samples were collected from all of these animals in order to measure serum levels of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), urea, and creatinine. The first three animals underwent necropsy and histopathological evaluation. The experiment was conducted with two nine-month-old calves that received an oral paste made with crushed S. fissuratum fruits mixed with water. These fruits were collected at a farm at which cattle poisoning cases had occurred. Blood samples were collected in order to measure serum levels of AST, GGT, urea, and creatinine, before plant administration and then daily during the experimental period. Skin biopsies were taken before plant administration and new one after the first signs of skin lesions. The natural outbreak affected 52 of 160 bovine (31 calves and 21 cows) in the lot. Two calves and 14 cows died. Clinical signs consisted of depression, ataxia, incoordination, behavioral changes, decubitus, and death. One animal that died and 36 others that recovered had photodermatitis. Necropsy findings in the animals consisted of bad corporal condition, pale kidneys, evidence of liver lobular pattern, dry rumen contents, and full bladder. In two animals, fruit seeds were found in the rumen, and one animal had ulcers and transmural edema in the abomasum. Microscopically, mild to moderate renal tubular distension, accumulation of proteinaceous material in lumen with mild to moderate swelling, and epithelial necrosis. In the liver, swelling of hepatocytes and moderate bile stasis was detected. Enzymes values in all evaluated bovines were higher than those considered normal for the species. Experimentally, both calves became ill and one died. The clinical signs were apathy, inappetence, wobbling, weight loss, and goosebumps. One of them had jaundice, tearing, photophobia, ear skin detachment, and ulcers at the muzzle, nostrils and ventral face of the tongue. This animal was euthanized in extremis, and the necropsy findings showed generalized jaundice, evidence of increased liver lobular pattern, thick bile, pale kidneys, and esophageal, tongue, and epiglottal ulcers. Microscopically, the lesions were similar to those described during the natural outbreak. The skin biopsy from the calf that recovered showed perivascular edema and mild eosinophilia.Discussion: The diagnosis was made based on clinical signs, necropsy findings, histopathological lesions, and epidemiological analysis. Experimentally, the plant was toxic at the administered doses. Photosensitization was the most common clinical sign during the natural outbreak and until now, has never been experimentally reproduced. Based on histopathological lesions observed in this study, we can consider that is from hepatogenous origin. The results showed that the kidney lesions have an important role during the pathogenesis caused by this poisoning and during disease evolution.


2016 ◽  
Vol 94 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Hayam Ateyya ◽  
Hala Yosef ◽  
Manar A. Nader

This study was designed to evaluate the protective effects of trimetazidine (TMZ) against cisplatin (CP) induced liver damage in rats. Animals were distributed among 4 groups as follows: control group; TMZ group (20 mg/kg body mass, per oral), which was treated for 10 days; CP group (6 mg/kg, by intraperitoneal injection), which received a single injection; and the CP + TMZ group (20 mg/kg, per oral), which received TMZ 4 days before and 6 days after CP injection. The extent of hepatic damage was studied by assessing biochemical parameters and histopathological evaluation of the extracted liver tissue. The results revealed that liver enzymes were markedly elevated after injection of CP, as evident from significant increases in the serum levels of alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GT), and lactate dehydrogenase (LDH), as well as marked changes to the liver architecture, with a significant decrease in serum levels of albumin. There were also marked changes to the antioxidant defense system, as indicated by significant decreases in total antioxidants and hepatic levels of reduced glutathione (GSH) and superoxide dismutase (SOD), together with a significant increase in lipid peroxidation. However, there was a significant increase in the activity of hepatic nuclear factor kappa B (NF-κB) as well as hepatic Bax protein expression. We conclude that TMZ protects against CP-induced liver damage through scavenging free radicals and anti-inflammatory and antiapoptotic effects, as well as through reducing NF-κB activation.


2003 ◽  
Vol 71 (10) ◽  
pp. 5714-5723 ◽  
Author(s):  
Terje E. Michaelsen ◽  
Øistein Ihle ◽  
Karen Johanne Beckstrøm ◽  
Tove K. Herstad ◽  
Jan Kolberg ◽  
...  

ABSTRACT We studied the in vitro protective activities of human immunoglobulin G1 (IgG1), IgG3, and IgM antibodies against group B meningococci by constructing sets of chimeric mouse-human antibodies (chIgG1, chIgG3, and chIgM, respectively) with identical binding regions against the P1.7 and P1.16 epitopes on PorA. This was done by cloning the V genes of three mouse hybridoma antibodies and subsequently transfecting vectors containing the homologous heavy- and light-chain genes into NSO cells. Cell clones secreting intact human chIgG1, chIgG3, or chIgM antibodies originating from three parent mouse antibodies were isolated. The functional affinities appeared to be similar for all human isotypes and surprisingly also for the pentameric chIgM antibody. chIgG1 exhibited greater serum bactericidal activity (SBA) than chIgG3, while chIgG3 was more efficient in inducing a respiratory burst (RB) associated with opsonophagocytosis than chIgG1 was. On the other hand, chIgM exhibited SBA similar to that of chIgG1, but it exhibited much higher RB activity than chIgG3 and chIgG1 exhibited. The antibodies against the P1.16 epitope were more efficient in terms of SBA than the antibodies against the P1.7 epitope were; thus, 10- to 40-fold-lower concentrations of antibodies against P1.16 than of antibodies against P1.7 were needed to induce SBA. On the other hand, antibodies against these epitopes were equally effective in inducing RB. Our results revealed differences in the functional activities of human chIgG1, chIgG3, and chIgM antibodies against meningococci, which might influence their protective effects against meningococcal disease.


2014 ◽  
Vol 92 (8) ◽  
pp. 640-644 ◽  
Author(s):  
Ghada M. Suddek

One of the major reasons for terminating a clinical trial is the liver toxicity induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy may cause hepatic injury. The seeds of Nigella sativa, which contain the active ingredient thymoquinone (TQ), have been used in folk medicine for diverse ailments. TQ is reported to possess anticancer and hepatoprotective effects. In this study, the protective effects of TQ against TAM-induced hepatotoxicity in female rats were evaluated. Four groups of rats were used: control; TAM; TQ; TAM+TQ. TAM (45 mg·(kg body mass)–1·day–1, by intraperitoneal injection (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as depletion of reduced glutathione in the liver and accumulation of lipid peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide dismutase. Further, it raised the levels of tumor necrosis factor alpha in the liver and induced histopathological changes. Pretreatment with TQ (50 mg·(kg body mass)–1·day–1; orally, for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, TQ protects against TAM-induced hepatotoxicity.


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