Enhancement of anti-OVA IgG2c production in vivo by enalapril

Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.

Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

Early surgical complications after gastric by-pass: a literature review / Complicações cirúrgicas precoces após bypass gástrico: revisão da literatura

INTRODUCTION: Gastric bypass is today the most frequently performed bariatric procedure,but, despite of it, several complications can occur with varied morbimortality. Probably all bariatric surgeons know these complications, but, as bariatric surgery continues to spread, general surgeon must be familiarized to it and its management. Gastric bypass complications can be divided into two groups: early and late complications, taking into account the two weeks period after the surgery. This paper will focus the early ones. METHOD: Literature review was carried out using Medline/PubMed, Cochrane Library, SciELO, and additional information on institutional sites of interest crossing the headings: gastric bypass AND complications; follow-up studies AND complications; postoperative complications AND anastomosis, Roux-en-Y; obesity AND postoperative complications. Search language was English. RESULTS: There were selected 26 studies that matched the headings. Early complications included: anastomotic or staple line leaks, gastrointestinal bleeding, intestinal obstruction and incorrect Roux limb reconstruction. CONCLUSION: Knowledge on strategies on how to reduce the risk and incidence of complications must be acquired, and every surgeon must be familiar with these complications in order to achieve an earlier recognition and perform the best intervention. .

INTRODUÇÃO: O bypass gástrico é hoje o procedimento bariátrico mais realizado, mas, apesar disso, várias complicações podem ocorrer com variada morbimortalidade. Provavelmente todos os cirurgiões bariátricos conhecem essas complicações, mas como a cirurgia bariátrica continua a se espalhar, o cirurgião geral deve estar familiarizado com essas complicações e seu manuseio. As complicações do bypass gástrico podem ser divididas em dois grupos: as precoces e tardias, tendo em conta o período de duas semanas após a operação. Este artigo irá focar as precoces. MÉTODO: Foi realizada revisão da literatura utilizando as bases Medline/PubMed, Cochrane Library, SciELO, e informações adicionais sobre sites institucionais de interesse cruzando os descritores: bypass gástrico AND complicações; seguimento AND complicações; complicações pós-operatórias AND anastomose, Roux-en-Y; obesidade AND complicações pós-operatórias. A língua usada para a busca foi o inglês. RESULTADOS: Foram selecionados 26 artigos que combinavam com os descritores. As complicações imediatas foram: fístula na linha de grampeamento, sangramento gastrointestinal, obstrução intestinal e reconstrução incorreta da alça em Roux. CONCLUSÃO: O conhecimento sobre as estratégias de como reduzir o risco e incidência das complicações deve ser adquirido ao longo do tempo, e cada cirurgião deve estar familiarizado com essas complicações, a fim de reconhecê-las precocemente e realizar a melhor intervenção. .

Dietary germanium biotite supplementation enhances the induction of antibody responses to foot-and-mouth disease virus vaccine in pigs

We evaluated the potential ability of germanium biotite (GB) to stimulate the production of antibodies specific for foot-and-mouth disease virus (FMDV). To this aim, we measured the total FMDV-specific antibody responses and IgM production after vaccination against FMD both experimentally and in the field. GB supplementation with FMDV vaccination stimulated the production of anti-FMDV antibodies, and effectively increased IFN-gamma and TNF-alpha levels. These results suggest that GB may be a novel alternative feed supplement that can serve as a boosting agent and an immunostimulator for increasing the efficacy of FMDV vaccination in pigs.

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9+/-32.5 microg/mL vs 219.8+/-59.0 microg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Attenuation of the effect of lindane on immune responses and oxidative stress by Ocimum sanctum seed oil (OSSO) in rats.

Present study was done to evaluate the effect of Ocimum sanctum seed oil (OSSO) on the immunotoxicity and oxidative activity of lindane in rats. Rats were divided into four groups (n = 8) and were treated with lindane (10 mg/kg, po) and/or OSSO (1 mg/kg, po) during the study period. Humoral immunity was assessed by measuring haemagglutination titre to sheep red blood cells (SRBC) and delayed type hypersensitivity (DTH) was assessed by measuring foot pad thickness. Lindane showed significant decrease in anti-SRBC antibody titre and also decreased percentage change in foot pad thickness in DTH response as compared to control group. OSSO per se produced significant increase in anti-SRBC antibody titre, but did not produce significant change in the foot pad thickness as compared to control group. However, it significantly antagonized the effect of lindane on the anti-SRBC antibody titre and foot pad thickness parameters. Lindane produced oxidative stress as indicated by increase in the levels of MDA and decrease in GSH levels. Treatment with OSSO per se showed antioxidant activity and also reversed the oxidative stress produced by lindane. The results suggest that OSSO can attenuate the immunotoxicity and oxidative stress produced by lindane.

Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.

Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

Effect of centchroman on cellular and humoral immunity.

Centchroman (Ormeloxifene) is a nonsteroidal selective estrogen receptor modulator that is used as once a week oral contraceptive agent. The effect of centchroman on the immune system was evaluated by using different experimental models such as carbon clearance test, cyclophosphamide induced neutropenia, neutrophil adhesion test, effect on serum immunoglobulins, mice lethality test and indirect haemagglutination test. The first three models namely carbon clearance test, cyclophosphamide induced neutropenia and neutrophil adhesion test were used to study cell mediated immunity while the latter three models were used to see the effect on humoral immunity. Centchroman was administered orally at a dose of 5 mg/kg and levamisole (2.5 mg/kg/ p.o) was used as standard drug. Centchroman significantly increased the levels of serum immunoglobulins and also prevented the mortality induced by bovine Pasteurella multocida in mice. It also increased significantly the circulating antibody litre in indirect haemagglunation test. However, it did not show any significant effect on phagocytic index in carbon clearance assay and nor did influence the adhesion of neutrophils in the neutrophil adhesion test. Centchroman was also not effective in preventing the cyclophosphamde induced neutropenia. Hence, it was concluded that centchroman increases humoral immunity with no significant effect on cell mediated immunity.

Immunotoxic effects of lambda-cyhalothrin in rabbits

The effect of Lambda-cyhalothrin on the immune response was studied in rabbits exposed to the insecticide via food at concentrations of 1373.23, 686.76 or 343.38 ppm [equivalent to 1/10[th], 1/20[th] and 1/40[th] oral LD50, respectively] for 8 weeks. The humoral immune response was measured by determination of the antibody titre against sheep red blood cells [SRBC], a T - cell dependent antigen. Moreover, the cell-mediated immune response was evaluated by the delayed - type hypersensitivity reaction to tuberculin. The chemical treatment resulted in a dose - dependent suppression of both humoral and cellmediated immune responses as evidenced by decreased serum hemolysin titres and inhibition of the delayed-type hypersensitivity reaction to tubercluin, respectively. In addition, leucopenia, lymphopenia, depletion of lymphoid cells in the white pulps of spleen, mesentric lymph nodes and Peyer's patches and severe atrophy of thymus cortex were recorded. The serum total protein, albumin, globulin [specially gamma globulin], albumin/globulin [A/G] ratio and the organ to body weight ratios for spleen and thymus were significantly decreased with increasing the insecticide dosage. Moreover, different pathological alterations in liver, and brain were also observed. In conclusion, Lambdacyhalothrin exposure suppressed both humoral and cell-meditated immune responses in rabbits at the tested concentrations in a dose - dependent manner

Effect of AC II, a herbal formulation on radiation-induced immunosuppression in mice.

A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.

Immunostimulatory effect of Tinospora cordifolia Miers leaf extract in Oreochromis mossambicus.

Immunostimulatory effect of leaf extract of T. cordifolia on (i) specific immunity (antibody response), (ii) non-specific immunity (neutrophil activity) and (iii) disease resistance against Aeromonas hydrophila was investigated in O. mossambicus. Ethanol and petroleum ether extracts of the leaves were used. Both ethanol and petroleum ether extracts administered at doses of 0.8, 8 or 80 mg/kg body weight, prolonged the peak primary antibody titres upto one to three weeks. Ethanol extract at the dose of 8 mg/kg and petroleum ether extract at the doses of 0.8 or 8 mg/kg enhanced the secondary antibody response. All the doses of ethanol extract significantly enhanced neutrophil activity. Fish injected with petroleum ether or ethanol extract at a dose of 8 mg/kg were protected against experimental infection with virulent A. hydrophila. The results indicates the potential of T. cordifolia leaf extracts for use as an immunoprophylactic to prevent diseases in finfish aquaculture.

Immunotoxicity of phosphamidon following subchronic exposure in albino rats.

Effect of subchronic doses of phosphamidon exposure on humoral and cell mediated immune (CMI) responses were studied in male albino rats using SRBC, ovalbumin and KLH as antigens. Humoral immune responses were assessed by estimating antibody titre against antigen and splenic plaque forming cells (PFC) assay. CMI responses were studied by using leucocyte migration inhibition (LMI), macrophage migration inhibition (MMI) and delayed type hypersensitivity (DTH) response. Results obtained in the present study revealed marked suppression of humoral and CMI responses in a dose dependent pattern. Hence, suppression of immune responses by phosphamidon even at subchronic doses is clearly an important aspect for its safety evaluation.

Protective effect of melatonin against propoxur-induced oxidative stress and suppression of humoral immune response in rats.

Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation.

Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts.

Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for treatment of various illnesses, but the mechanisms of action remain largely unknown. This study focused on the influence of CA and RN extracts on cell-mediated and humoral immune responses. In human peripheral blood mononuclear cells (PBMCs), CA (water extract) and RN (water and ethanol extracts) significantly increased proliferation and the production of IL-2 and TNF-alpha. In contrast, an ethanol extract of CA inhibited human PBMC mitogenesis and the production of IL-2 and TNF-alpha. BALB/c mice treated with CA extracts (100 mg/kg bw) showed higher responses to both primary and secondary antibodies against BSA when compared with non-treated group. Only the secondary antibody response was increased in RN extract-treated mice. The present study revealed immunomodulating activity of CA and RN extracts with regard to both non-specific cellular and humoral immune responses. The data available to date suggest that they may have chemopreventive or anticancer potential.

Time dependent immunomodulatory response of exogenous melatonin to killed Pasteurella multocida (P52 strain) vaccine in albino rats.

The effect of time of administration of exogenous melatonin (M) at the rate of 100 microg/Kg BW of rat/day for 14 days on immunomodulation to killed Pasteurella multocida (P52 strain) vaccine (KPMV) was investigated in male albino rats during spring season with photoperiod of LL 13: DD 11 h and 25 +/- 2.5 degrees C air temperature and 70 +/- 4% relative humidity. The experiment was conducted at an altitude of 172 mts above mean sea level at latitude 28.20 degrees north, longitude 79.24 degrees east (Bareilly, U.P. India). The experimental animals were divided in-groups of 8 rats each, as KPMV + M at 4.00 h; KPMV + M at 16.00 h; KPMV and their controls M4, M16, PBS respectively. Humoral immune response was monitored at weekly intervals by an indirect ELISA and cellular immunity by leukocyte migration inhibition test (LMIT) and delayed type of hypersensitivity (DTH). As evinced by in-vitro assays and in-vivo protection studies, both humoral and cellular immune responses to KPMV were augmented in rats receiving exogenous melatonin at 4.00 h as compared to slightly reduced responses in rats treated with melatonin at 16.00 h. It was concluded that the circadian timings of melatonin administration modulate immune response in rats.

Humoral and cellular immunomodulation induced by propoxure in C57-w/6 mice

Propoxure [PPX] is a well-known carbamate insecticide, which has been used for several decades in the world and Iran in agriculture and public health programs. However, there is no clear investigation toward its immunotoxicity as yet. In this study, we examined the effects of subchronic i.p. exposure of PPX on humoral [PFC and HA] and cellular [DTH] responses, and also monitored T-Cell subtypes using FACS technique. Briefly, female C57b1/6 inbred mice were administered PPX [0.2, 2 and 10 mg/kg/day i.p. [5 inj/wk] for 28 days] or positive and negative controls. On the day 28, mice were examined for DTH, PFC and HA responses to SRBC. Splenocyte single cell suspension was used for measuring the spleen CD4/CD8 percentage and absolute number. In vitro lymphocyte proliferation response to non-specific antigen [PHA] was also measured using MTT method. Results showed that PPX at 10 mg/kg/day could suppress DTH response and could increase the spleen CD4-/CD8+ T-cell percentage. On the other hand, PPX at medium dose [2 mg/kg] could increase the antibody formation response against SRBC as determined by PFC and HA. Subchronic PPX at low dose [0.2 mg/kg/day] could not show any significant effects on humoral or cellular responses. It could be concluded that, subchronic PPX at high dose [10 mg/kg], possessed cellular immunosuppressive effect. However, PPX at 2 mg/kg does not change cellular response to antigen but can stimulate humoral responses. It seems that PPX has no adverse effects on mice immune system at low doses as 0.2 mg/kg, which is 10 fold greater than PPX Allowed Daily Intake limit

Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline.

The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.

Effect of minocycline and tetracycline on immunological responses in experimental animals.

In recent years, there has been an increase in the use of antibiotics, primarily tetracycline anlogues, like minocy cline to treat rheumatoid arthritis. However, the mechanism of action of these analogues is not clearly defined. The present study investigates the effects of minocycline and tetracycline on some immunological parameters in Wistar rats and Swiss albino mice. Haemagglutination (HA) titre was employed as parameter of humoral immune response and % leukocyte migration inhibition (% LMI) and footpad thickness tests were used as measures of cell mediated immune response. Both minocycline and tetracycline significantly improved humoral immune response in rats as indicated by an increase in anti-SRBC antibody titre. In the LMI test, depending on the time period of drug administration, there was an increase or a decrease in the % LMI. When drugs were administered on days 1-7 after sensitization, both the compounds caused a significant increase in % LMI. However, the % LMI was significantly decreased when the drugs were administered on days 7-13 of sensitization, indicating variable effects of these agents on the Immune mechanism depending on the time of administration in relation to the development of immune responsiveness. Both minocycline as well as tetracycline produced a significant decrease in the paw volume in the footpad-thickness test which indicates a decrease in lymphokine production/release. The present study thus shows that minocycline and tetracycline exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis.

Immunopotentiating activity of abrin, a lectin from Abrus precatorius Linn.

A non-toxic dose of abrin, (1.25 microg/kg body wt) consecutively for five days in normal mice stimulated specific humoral responses. A noticeable increase was observed in total leucocyte count, lymphocytosis, weights of spleen and thymus, circulating antibody titre, antibody forming cells, bone marrow cellularity and alpha-esterase positive bone marrow cells. The results suggest that abrin can potentiate the humoral immune response of the host.