Sodium R-lipoate and enzymatically-modified isoquercitrin suppressed IgE-independent anaphylactic reactions and stress-induced gastric ulceration in mice.

Anaphylaxis is a life-threatening allergic reaction, for which the worldwide prevalence is rapidly increasing. The currently used synthetic antiallergic drugs have a high tendency to cause adverse effects, like gastric ulcers, in long-term use. Therefore, a great deal of attention has been given to develop new safer and more effective antiallergic agents from natural compounds that are chemically/enzymatically-modified. Here, we evaluated/compared the efficacy of two different doses (50 and 100 mg/kg body weight "b.w", given orally) of sodium R-lipoate (NaRLA) and enzymatically-modified isoquercitrin (EMIQ) in alleviating both local/systemic non-immunological anaphylactic reactions and stress-induced gastric ulceration in mice, in comparison with sulfasalazine (SSZ) as a reference drug. The results indicated that the pre-treatment of animals with NaRLA or EMIQ (especially at 100 mg/kg b.w) completely succeeded, as SSZ, in alleviating the hind paw edema induced by either histamine or compound 48/80 (Cpd 48/80). Furthermore, NaRLA and EMIQ prevented the mast cell degranulation and anaphylactic shock caused by Cpd 48/80 (in a dose-dependent manner) and reduced significantly (P < 0.001) the histamine release from the mouse peritoneal mast cells, like SSZ. Moreover, their use was associated with alleviating both gastric histopathological and biochemical alterations in the water-restraint stress (WRS) mice model towards the control values. They also decreased the percentage of degranulated mesenteric mast cells in the WRS mice model. In conclusion, our findings provide possibility that both NaRLA and EMIQ may serve as an effective therapeutic agents for mast cells-dependent anaphylactic reactions without risks of inducing gastric ulcers.

Dietary supplementation of Sargassum latifolium modulates thermo-respiratory response, inflammation, and oxidative stress in bacterial endotoxin-challenged male Barki sheep.

Endotoxemia is mainly caused by translocation of bacterial lipopolysaccharides (LPS) into the bloodstream. This in turn enhances systemic inflammation and inappropriate production of reactive oxygen species, leading to oxidative injury of vital internal organs and other dangerous effects that can be life-threatening. Here, we evaluated/compared the modulatory effects of consuming two different doses (2% and 4% of the diet) of brown seaweeds (Sargassum latifolium) for 40 consecutive days on thermo-respiratory response, inflammation, and oxidative stress in Barki male sheep (Ovis aries) challenged twice with bacterial LPS (1.25 µg/kg body weight, injected intravenously on days 28 and 35 of the experimental period). The results showed that the diet containing Sargassum latifolium (especially at 4%) modulated significantly (P < 0.05-0.001) the increase in the thermo-respiratory response (skin and rectal temperatures, and respiration rate) and the obtained systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations) in the LPS-challenged sheep. In addition, it improved significantly (P < 0.001, especially at 4%) the total antioxidant capacity of the blood of LPS-challenged sheep by increasing the catalase and superoxide dismutase activities. Moreover, it decreased the blood markers of tissue damage (malondialdehyde concentration and the activities of alanine aminotransferase and lactate dehydrogenase) in the LPS-challenged sheep. In conclusion, the diet containing 4% Sargassum latifolium may have potential impact in protecting the ruminant livestock from the serious effects of endotoxemia through improving the animals' antioxidant defense system and regulating their inflammatory and thermo-respiratory responses.

Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries).

Heat stress (HS) is the most potent environmental stressors for livestock in tropical and subtropical regions. HS induced splanchnic tissue hypoxia and intestinal oxidative damage, leading to endotoxemia and systemic inflammation. The present study evaluated and compared the modulatory effects of feeding Barki male sheep (Ovis aries) on a standard concentrated diet containing 2% or 4% of the brown seaweed (Sargassum latifolium) followed by roughage for 40 consecutive days on the toxicity-induced by exposure to severe environmental HS (temperature-humidity index = 28.55 ± 1.62). The present study showed that the diet containing Sargassum latifolium (especially 4%) modulated significantly (P < 0.05-0.001) almost all changes shown in the HS-exposed sheep including the increase in the thermo-respiratory responses (skin and rectal temperatures, and respiration rate) and the resulted dyslipidemia, anemia, and systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations). In addition, Sargassum latifolium improved significantly (P < 0.05-0.001) the body-weight gain, kidney functions (especially at the high dose), and blood antioxidant defense system (total antioxidant capacity, and the activities of catalase and superoxide dismutase) in the HS-exposed sheep, as well as protected the animals from oxidative tissue damage and the risk of atherosclerosis. In conclusion, feeding sheep with the diet containing 4% of Sargassum latifolium was safe and suitable for animal nutrition, as well as efficiently alleviated the harmful effects of the environmental HS in Barki sheep through improving the animal antioxidant defense system, and regulating the thermo-respiratory and inflammatory responses.

Antihepatocarcinogenic activity of whey protein concentrate and lactoferrin in diethylnitrosamine-treated male albino mice.

Hepatocellular carcinoma is considered one of the most prevalent and lethal malignancies worldwide. Chemotherapy with cytotoxic agents showed a low response rate with possible toxic effects. Recently, some emphases have been placed on the anticancer properties of bovine whey protein and its components, especially lactoferrin. The present study aimed to evaluate and compare the antihepatocarcinogenic activity of bovine whey protein concentrate (WPC, 300 and 600 mg/kg body weight) and lactoferrin (30 and 60 mg/kg body weight), orally and daily for 14 weeks, in the mice model of diethylnitrosamine (DEN)-induced hepatocarcinogenesis. The results showed that both WPC and lactoferrin (in a dose-dependent manner) alleviated significantly (P < .001) the elevation in serum markers of liver carcinoma and inflammation in the DEN-treated mice. Also, they exhibited a great amelioration in the livers' histological structure of the DEN-treated mice by 37.0% to 66.7%. In addition, they decreased significantly (P < .001) the hepatic DNA fragmentation in the DEN-treated mice by 23.1% to 32.7%. Only, the high doses of WPC and lactoferrin completely modulated the decrease in the activity of liver enzymic antioxidant defense system (catalase, glutathione peroxidase, and superoxide dismutase) and improved significantly (P < .01-.001) the concentration of hepatic reduced glutathione of the DEN-treated mice. Moreover, the high doses of WPC and lactoferrin reduced significantly (P < .05-.001) the elevation in the concentrations of hepatic active caspases 3, 8, and 9 of the DEN-treated mice. In conclusion, both WPC and lactoferrin were effective in inhibiting the hepatocarcinogenic activity of DEN in mice model through their ability to alleviate the hepatic inflammation and apoptosis.

Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats.

Nowadays, medicinal plants have been widely used everywhere to provide essential care for many disorders including diabetes. Recent reports assumed that the antidiabetic activities of pomegranate aril juice (PAJ) may be ascribed to its punicalagin (PCG). Therefore, the present study evaluated and compared the antidiabetic activities of PAJ and its PCG, and monitored some mechanisms of their actions in streptozotocin-nicotinamide (STZ-NA) type 2 diabetic rats. STZ-NA diabetic rats were given, orally/daily, PAJ (100 or 300 mg/kg body weight, containing 2.6 and 7.8 mg of PCG/kg body weight, respectively), pure PCG (2.6 or 7.8 mg/kg body weight), or distilled water (vehicle) for 6 weeks. PAJ (especially at the high dose) alleviated significantly (P < 0.05-0.001) most signs of type 2 diabetes including body-weight loss, insulin resistance (IR) and hyperglycemia through decreasing serum tumor necrosis factor-α concentration and the expression of hepatic c-Jun N-terminal kinase, and increasing the skeletal muscle weight and the expression of hepatic insulin receptor substrate-1 in STZ-NA diabetic rats. Also, it decreased significantly (P < 0.001) the oxidative liver injury in STZ-NA diabetic rats through decreasing the hepatic lipid peroxidation and nitric oxide production, and improving the hepatic antioxidant defense system. Although the low dose of PCG induced some modulation in STZ-NA diabetic rats, the high dose of PCG did not show any valuable antidiabetic activity, but induced many side effects. In conclusion, PAJ was safer and more effective than pure PCG in alleviating IR and oxidative liver injury in STZ-NA diabetic rats.

Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis.

AIM: Recently, there has been an increasing interest in tea (Camellia sinensis) as a protective agent against inflammatory diseases. Here, we evaluated/compared the anti-inflammatory activity of two different doses (0.5 and 1.0 g/kg body weight) of green tea aqueous extract (GTE, rich in catechins) and black tea aqueous extract (BTE, rich in theaflavins and thearubigins) in rat adjuvant-induced arthritis (AIA). METHODS: Adjuvant-induced arthritis rat model received orally/daily distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14 consecutive days starting from day 0 or 14 of arthritis induction, respectively). RESULTS: The present study showed that only the high dose of GTE (from day 0) significantly alleviated (P < 0.05-0.001) all complications shown in arthritic rats, including synovial joint inflammation, elevation in erythrocyte sedimentation rate, blood leukocytosis (due to lymphocytosis and neutrocytosis), and changes in weight/cellularity of lymphoid organs. The anti-arthritic activity of the high dose of GTE (from day 0) was comparable (P > 0.05) with that of indomethacin (12.9-53.8 vs. 9.5-48.4%, respectively) and mediated by significantly decreasing and down-regulating (P < 0.001) the systemic production of pro-inflammatory cytokines and the expression of chemokine receptor-5 in synovial tissues, respectively. Moreover, the anti-arthritic activity of tea aqueous extracts was in the following order: high dose of GTE > low dose of GTE ≥ high dose of BTE > low dose of BTE. CONCLUSION: The present study proved the anti-inflammatory activity of GTE over BTE and equal to that of indomethacin in AIA rat model.

Aged garlic extract ameliorates immunotoxicity, hematotoxicity and impaired burn-healing in malathion- and carbaryl-treated male albino rats.

Malathion and carbaryl are the most widely used organophosphate and carbamate insecticides, respectively, especially in developing countries; they pose a potential health hazard for both humans and animals. Here, we evaluated the protective effects of an odorless (free from allicin) Kyolic aged garlic extract (AGE, containing 0.1% S-allylcysteine; 200 mg/kg body weight) on the toxicity induced by 0.1 LD50 of malathion (89.5 mg/kg body weight) and/or carbaryl (33.9 mg/kg body weight) in male Wistar rats. Doses were orally administered to animals for four consecutive weeks. The present study showed that AGE completely modulated most adverse effects induced by malathion and/or carbaryl in rats including the normocytic normochromic anemia, immunosuppression, and the delay in the skin-burning healing process through normalizing the count of blood cells (erythrocytes, leucocytes and platelets), hemoglobin content, hematocrit value, blood glucose-6-phosphodehydrogenase activity, weights and cellularity of lymphoid organs, serum γ-globulin concentration, and the delayed type of hypersensitivity response to the control values, and accelerating the inflammatory and proliferative phases of burn-healing. In addition, AGE completely modulated the decrease in serum reduced glutathione (GSH) concentration and the increase in clotting time in malathion alone and carbaryl alone treated rats. Moreover, AGE induced a significant increase (P < 0.001) in serum GSH concentration (above the normal value) and accelerating burn-healing process in healthy rats. In conclusion, AGE was effective in modulating most adverse effects induced in rats by malathion and carbaryl, and hence may be useful as a dietary adjunct for alleviating the toxicity in highly vulnerable people to insecticides intoxication. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 789-798, 2017.

Fast monocyte-derived dendritic cell-based immunotherapy.

Recent reports have described a new strategy for differentiation and maturation of monocyte (Mo)-derived dendritic cells (DC) within only 48-72 h of in vitro culture (fast-DC). Mature fast-DC are as effective as mature standard-DC (generated in 7-10 days of in vitro culture) in priming and propagation of antigen-specific T-cell responses. The use of fast-DC not only reduces labor and supply cost, as well as workload and time, but also increases the DC yield from Mo, which may facilitate DC-based immunotherapy for cancer patients. Detailed protocols for generation, pulsing with different antigen sources, and transduction with adenoviral vector of Mo-derived mature fast-DC as well as using of fast-DC for priming and propagation of antigen-specific cytotoxic T-cell effectors will be described here.

Protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis.

AIM: Besides joint destruction, extra-articular complications (outside the locomotor system) are frequent in rheumatoid arthritis (RA) patients, especially cardiovascular, hematological and metabolic disorders. Here, we evaluated and compared the protective activity of two different doses of mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA). METHODS: Arthritis was induced by a single intra-dermal injection of 0.1 mL of Complete Freund's adjuvant (containing heat-killed Mycobacterium tuberculosis) into the palmar surface of the left hind paw after the rats were subjected to light diethyl ether anesthesia. Arthritic rats received orally and daily (for 28 consecutive days) distilled water as vehicle, indomethacin (1.0 mg/kg body weight), or GTaq (200 or 400 mg/kg body weight) from the day of arthritis induction. RESULTS: The present study showed that GTaq (especially the high dose) was more effective (4.2-38.4% higher, P < 0.05-0.001) than indomethacin (a non-steroidal/anti-inflammatory drug) in alleviating the loss in body weight gain, the histopathological changes observed in ankle joints, blood leukocytosis and thrombocytosis, iron deficiency anemia, serum hypoalbuminemia and globulinemia, the impairment of kidney functions, and the risks for cardiovascular disease in arthritic rats. These protective effects of GTaq were mediated through increasing the food intake and decreasing the systemic inflammation that occur at the appearance of polyarthritis, oxidative stress and dyslipidemia. CONCLUSION: Ginger-turmeric rhizomes mixture may be effective against RA severity and complications as shown in an AIA rat model.

Preventive effects of Egyptian sweet marjoram (Origanum majorana L.) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats.

We made an attempt to evaluate/compare the cardioprotective activity of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) against isoproterenol (ISO)-induced myocardial infarcted rats (150 mg/kg body weight, twice at an interval of 24 h on days 29 and 30). The present study showed (probably for the first time) that both MLP and MLE (especially the high dose) significantly alleviated (P < 0.05-0.001) erythrocytosis, granulocytosis, thrombocytosis, shortened clotting time, the increase in relative heart weight, myocardial oxidative stress and the leakage of heart enzymes (creatine phosphokinase (CPK), CPK-MB isoenzyme, lactate dehydrogenase and aminotransferase) in ISO-treated rats through reactivating non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant defence system and inhibiting the production of nitric oxide and lipid peroxidation in heart tissues. The modulatory effects of marjoram leaves shown in the present study were dose-dependent in most cases and much higher in MLE (4.3-20.3 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, this study may have a significant impact on myocardial infarcted patients.

In vitro expansion of human γδ and CD56(+) T-cells by Aspergillus-antigen loaded fast dendritic cells in the presence of exogenous interleukin-12.

Aspergillus fumigatus (Af) infection is especially prevalent after allogenic bone marrow transplantation (BMT) and causes invasive pulmonary aspergillosis. Human γδ T-cells have essential role in maintaining immune homeostasis and in the resistance of pathogens and tumors. Also, γδ T-cells may facilitate stem cells engraftment and decrease a life-threatening graft versus host disease after allogenic BMT. Moreover, expression of CD56 molecules on γδ T-cells increases their antitumor cytotoxic activity. This study reveals that Af-pulsed fast dendritic cells (fast-DCs, which generated within only 72 h) plus IL-12 and then IL-2 can propagate autologous γδ and CD56(+) T-cells in vitro and this expansion is sustained by repeating the stimulation (107.5 ± 13.9-fold and 37.6 ± 2.2-fold increase for γδ and CD56(+) T-cells, respectively, after three primings). Many of the expanded γδ and CD56(+) T-cells expressed CD8 molecules (29.6%-68.6%), while few of them expressed CD4 molecules (2.3%-17.5%). Also, ∼28% of the expanded γδ T-cells were CD56(+). On the other hand, the proliferation of γδ and CD56(+) T-cells significantly decreased (p < 0.001, <19-fold and 12-fold, respectively) in the absence of either Af-pulsed fast-DCs or IL-12 or in the presence of un-pulsed fast-DCs, indicating the importance of Af-antigens and IL-12 in inducing this expansion. The expansion of γδ and CD56(+) T-cells did not hamper the generation of Af-specific αß T-cell effectors. The methodology described in this study, utilizing autologous Af-pulsed fast-DCs and IL-12, permits the rapid generation of Af-specific αß T-cell effectors and propagation of γδ and CD56(+) T-cells in vitro.

Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs that show a high therapeutic index, despite the widespread side effects and toxicity particularly in high-dose regimens and long-term use. Here, we evaluated and compared the efficacy of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) in alleviating the genotoxicity, immunosuppression and other complications induced by CP in non-tumour-bearing albino rats. The present study showed (probably for the first time) that both MLP and MLE significantly alleviated (P < 0·05-0·001) most side effects and toxicity of CP-treated rats including the increase in chromosomal aberrations of bone marrow cells and serum malondialdehyde level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells. The modulatory effects of marjoram leaves shown in the present study were dose dependent in most cases and much higher in MLE (21-23 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, sweet marjoram leaves (especially in the form of a herbal tea) may be useful as an immunostimulant and in reducing genotoxicity in patients under chemotherapeutic interventions.

Generation of functional monocyte-derived fast dendritic cells suitable for clinical application in the absence of interleukin-6.

To develop dendritic cells (DCs)-based immunotherapy for cancer patients, it is necessary to have a standardized, reproducible, fast, and easy to use protocol for in vitro generation of fully functional DCs. Recently, a new strategy was described for differentiation and maturation of human monocyte (Mo)-derived fast-DCs with full T cell stimulatory capacity within only 48-72 h of in vitro culture. Interleukin (IL)-6 plus tumour necrosis factor (TNF)-α, IL-1ß, and prostaglandin (PG)-E(2) were used in this strategy to induce maturation of the generated DCs. The present study further modifies this strategy by excluding IL-6 from the cytokines cocktail used for DCs maturation. The results showed that maturation of fast-DCs without IL-6 did not significantly alter the morphology, phenotype and the yield of mature DCs (P > 0.05, compared with those generated with IL-6). Moreover, fast-DCs generated without IL-6 are functional antigen presenting cells, have the ability to induce tetanus toxoid-specific autologous T cell proliferation, and are suitable for gene delivery through adenoviral vector transduction as those generated with IL-6 (P > 0.05). In conclusion, the present study proves that fully mature and functional Mo-derived fast-DCs can be generated in vitro without adding IL-6, which not only reduces the number of required recombinant cytokines, but may also resemble DCs development in vivo more closely.

Anti-metabolic syndrome and immunostimulant activities of Egyptian fenugreek seeds in diabetic/obese and immunosuppressive rat models.

Preliminary trials have suggested possible hypoglycaemic, hypolipidaemic and immunomodulatory properties of the fenugreek plant. Here, we evaluated and compared the efficacy of Egyptian fenugreek seed powder (FSP, 0·5 and 1·0 g/kg body weight) in alleviating the experimentally induced metabolic syndrome (in type 1 diabetic and obese rat models) and experimentally induced immunosuppression and delay in burn-healing (in cyclophosphamide (CP)-treated rats). FSP significantly alleviated (P < 0·05-0·001) most signs of the metabolic syndrome resulting from experimentally induced type 1 diabetes and obesity by 40-76 and 56-78 %, respectively, including hyperglycaemia, hyperlipidaemia, elevation in atherogenic indices, impairment of liver functions, severe changes in body weight and oxidative stress. Besides, FSP (especially the high dose) completely modulated the immunosuppressive activity of CP including leucopenia (resulting from neutropenia and lymphopenia), decrease in weights and cellularity of lymphoid organs, serum γ-globulin level, delayed type of hypersensitivity response and delay in the skin-burning healing process. FSP decreased the immunosuppressive activity of CP by 57-108 %. These beneficial effects of FSP were dose dependent in most cases, and FSP doses used here were considered safe in general. FSP was more efficient in alleviating the signs of the metabolic syndrome in the obese animals (over 9 %) than in the type 1 diabetic animals. Moreover, the immunostimulant activity of fenugreek seeds exceeded their anti-metabolic syndrome activity by 15-24 %. In conclusion, fenugreek seeds may be useful not only as a dietary adjunct for the control of the metabolic syndrome in diabetic/obese patients, but also as an immunostimulant in immunocompromised patients such as those under chemotherapeutic interventions.

Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats.

Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P < 0·05-0·001) signs of the metabolic syndrome (hyperglycaemia and dyslipidaemia), the elevation in atherogenic indices and cellular toxicity in STZ-nicotinamide diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.

Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis.

Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P < 0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.

Modulatory effects of black v. green tea aqueous extract on hyperglycaemia, hyperlipidaemia and liver dysfunction in diabetic and obese rat models.

Cardiovascular complications are a major cause of morbidity and mortality in patients with diabetes, obesity and the metabolic syndrome. Recently, there has been an increasing interest in tea as a protective agent against CVD. Here, we compared the modulatory effects of two different doses (50 and 100 mg/kg body weight given orally for 28 consecutive days) of black tea aqueous extract (BTE, rich in theaflavins and thearubigins) and green tea aqueous extract (GTE, rich in catechins) on experimentally induced hyperglycaemia, hyperlipidaemia and liver dysfunction by alloxan (which destroys pancreatic beta-cells and induces type 1 diabetes) and a cholesterol-rich diet (which induces obesity and type 2 diabetes) in male Wistar albino rats. Both tea extracts significantly alleviated most signs of the metabolic syndrome including hyperglycaemia (resulting from type 1 and 2 diabetes), dyslipidaemia and impairment of liver functions induced by alloxan or the cholesterol-rich diet in the animals. Also, the tea extracts significantly modulated both the severe decrease and increase in body weight induced by alloxan and the high-cholesterol diet, respectively. The modulatory effects obtained here were partial or complete, but significant and dose dependent, and slightly more in GTE in most cases. No harmful effects were detected for tea consumption on all parameters measured, except that the high dose of both tea extracts significantly decreased the spleen weight:body weight ratio and induced lymphopenia. The present study supports the hypothesis that both black and green teas may have beneficial effects against the risks of the metabolic syndrome and CVD as shown in rat models of human obesity and diabetes.

Dendritic cells-based T-cell immune response for the variable region of immunoglobulin light chain of myeloma and lymphoma cell lines.

The present work supported and extended a previous study (used VLIg gene segment type VkappaIV) and indicated that a considerable (P<0.001) and specific autologous T-cell proliferation, proliferative index (PI) ranged from 386.0 to 399.5 at 20% dendritic cells (DCs):T-cells ratio, restricted mainly (>80%) to the major histocompatibility complex (MHC) class-I molecules can be elicited in vitro against other different VLg gene segments (VkappaI, VkappaIII and Vlambda2) of myeloma and lymphoma cell lines through a retroviral transduction of human DCs generated from CD34+ progenitor cells by phorbol ester (PMA) and under serum-free conditions. This study also showed a lesser proliferation, but significant (P<0.05), restricted to MHC class-II molecules and specific for VLIg gene segments. The obtained proliferation was almost completely blocked (approximately 95%, P<0.001) by anti-CD86 monoclonal antibodies, which confirmed the critical role of the CD86 costimulatory molecules in the activation of naive T-cells. The resulting immune responses did not significantly differ (P>0.05) among the different types of VLIg gene segments, as VLIg-transduced DCs equally coexpressed the VLIg genes and CD86 costimulatory molecules. In conclusion, the present study could provide the basis of a VLIg-based immunotherapy in plasma cell and B-cell malignancies.

Epstein-Barr virus-transformed B-cells as efficient antigen presenting cells to propagate Aspergillus-specific cytotoxic T-lymphocytes.

To overcome the cytotoxic T-lymphocytes (CTL) expansion limitations imposed by the lack of sufficient dendritic cells (DC) alternative sources of autologous antigen presenting cells (APC) such as Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (BLCL), which are easy to establish in vitro, have been considered and studied in the present work. Non-adherent peripheral blood mononuclear cells of three healthy donors were repeatedly primed with autologous Aspergillus fumigatus commercial culture-filtrate antigen-pulsed fast monocyte-derived DC (Aspf-CFA-DC) alone, Aspf-CFA-pulsed BLCL (Aspf-CFA-BLCL) alone or Aspf-CFA-BLCL after one, two, or three primings with Aspf-CFA-DC (1DC/BLCL, 2DC/BLCL or 3DCIBLCL; respectively). After 5th priming, lines generated by Aspf-CFA-BLCL only showed strong/weak lytic activity for EBV/Aspf; respectively. Aspf-specific lytic activity in all donors was increased by increasing the number of primings with Aspf-CFA-DC before switching to Aspf-CFA-BLCL (18.20 +/- 1.65% versus 35.67 +/- 1.02% and 40.03 +/- 1.41% in bulk cultures generated by 1DC/BLCL versus 2DC/BLCL and 3DC/BLCL, respectively). Bulk cultures generated by Aspf-CFA-BLCL after at least two primings with Aspf-CFA-DC showed approximately the same Aspf-specific lytic activity, effector cell phenotype, expansion level and percentage expression of IFN-gamma, CD69 and CD107a without any significant differences (p > 0.05) as standard bulk cultures generated by only Aspf-CFA-DC. Thus, this study explored the use of a combined DC/BLCL protocol to establish/propagate Aspf-specific CTL for adoptive immunotherapy to prevent or treat invasive pulmonary aspergillosis.

The proliferative response of T cells to Aspergillus antigen requires prior presentation on dendritic cells.

Dendritic cells (DC) are the most powerful antigen presenting cells that induce and maintain primary immune response. The present study confirms and extends the evidence that the proliferative response of T lymphocytes to Aspergillus antigen requires prior presentation on DC. Adherent blood monocytes (Mo) from healthy subjects were treated for 5 days with GM-CSF and IL-4 to generate immature DC and with IL-1beta, IL-6, tumor TNF-alpha and PGE2 for 2 days to generate matured DC and pulsed with Aspergillus antigen immediately prior to maturation. The Aspergillus pulsed DC demonstrated the typical morphology, cytoplasmic projections and surface markers of mature DC. Lymphocyte proliferation in response to soluble Aspergillus crude extract was compared with that presented by ex vivo generated autologous DC. The Aspergillus crude extract demonstrated marked toxic effect on peripheral blood mononuclear cells (PBMC) at concentrations started from 25 microg/ml and failed to initiate lymphocyte proliferative response. In contrast Aspergillus-specific T cell proliferation was demonstrated when cocultured with autologous Aspergillus-pulsed, Mo-derived DC and the culture supernatant showed marked IFN-gamma secretion. In conclusion, this study pointed out that the proliferative Th1 responses to Aspergillus requires prior presentation on DC.