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19 avril 2011 2 19 /04 /avril /2011 15:05

Mucosal Immunology (2011) 4, 252–260; doi:10.1038/mi.2011.13; published online 23 March 2011

Role of innate cytokines in mycobacterial infection

A M Cooper1, K D Mayer-Barber2 and A Sher2

  1. 1Trudeau Institute, Saranac Lake, New York, USA
  2. 2Laboratory of Parasitic Diseases, Immunobiology Section, NIAID, NIH, Bethesda, Maryland, USA

Correspondence: AM Cooper, (acooper@trudeauinstitute.org); A Sher, (asher@niaid.nih.gov)

Received 12 January 2011; Accepted 11 February 2011; Published online 23 March 2011.stract

Cells of the innate immune system produce cytokines and lipid mediators that strongly influence the outcome of mycobacterial infection. In the case of Mycobacterium tuberculosis, the lung is a critical site for this interaction.

 

Here, we review current information on the role of the major innate cytokine pathways both in controlling initial infection as well as in promoting and maintaining adaptive T-cell responses that mediate host resistance or immunopathology.

 

Understanding this important feature of the host–pathogen interaction can provide major insights into the mechanisms of virulence and can lead to new approaches for immunological intervention in tuberculosis and other mycobacterial diseases.

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19 avril 2011 2 19 /04 /avril /2011 15:02

Mucosal Immunology(2011) 4, 246–251; doi:10.1038/mi.2011.11; published online 16 March 2011

The impact of mucosal infections on acquisition and progression of tuberculosis

S Perry1, R Hussain2 and J Parsonnet1

.                1Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA

.                2Department of Molecular Biology, Aga Khan University, Karachi, Pakistan

Correspondence: S Perry, (shnperry@stanford.edu)

 

More than one-third of the world's population, or over 2 billion people, are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis in humans.

 

Why only 10% of those infected develop active disease while the remainder harbor latent infection remains one of the greatest scientific and public health mysteries.

 

Bacterial persistence is characterized by a dynamic state of immunological tolerance between pathogen and host.

 

The critical role of CD4+ T cells in defense against intracellular pathogens became evident during epidemiological studies of HIV-1 infection, which showed a clear inverse relationship between CD4+ T-cell count in peripheral blood and increased risk of infection with M. tuberculosis, pneumocystis and Toxoplasma gondii.

 

There is also growing evidence of a common mucosal immune system, whereby immune cells activated at one mucosal site may disseminate to remote effector sites.

 

In this commentary, we review emerging evidence from human studies that the outcome of M. tuberculosis infection is influenced by concurrent mucosal infections, using Helicobacter pylori and geohelminths as examples.

 

Understanding how the complexity of microbial exposures influences host immunity may have important implications for vaccine development and therapeutic interventions.

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18 avril 2011 1 18 /04 /avril /2011 12:15

Acta Med Indones. 2010 Jul;42(3):130-4.

Efficacy of Nigella sativa on serum free testosterone and metabolic disturbances in central obese male.

Datau EA, Wardhana, Surachmanto EE, Pandelaki K, Langi JA, Fias.

Department of Internal Medicine, Sam Ratulangi University School of Medicine - Prof. Dr. RD Kandou General Hospital, Jl. Raya Tanawangko, Manado, North Sulawesi, Indonesia.

 

 

AIM: to study the efficacy of Nigella sativa in central obese men on serum free testosterone, body weight, waist circumference, blood sugar, lipid, uric acid, adiponectin, hs-CRP, and side effects in the treatment group compare to control.

 

METHODS: an experimental, clinical test, double blinded with placebo control, pre-test and post-test design. Subjects are 30-45 years old, divided into the treatment and control groups, and evaluated weekly for 3 months.

Data obtained were subjective complaints, body weight, waist circumference, and blood pressure, serum free testosterone, fasting blood sugar, triglyceride, HDL-Cholesterol, uric acid, creatinin, SGOT and SGPT, adiponectin, and hs-CRP. Data collected from March 2007 to June 2007 at Prof.Dr.RD Kandou General Hospital, Manado, North Sulawesi, Indonesia.

Statistical analysis was performed using descriptive for subjects characteristic and drug's side effect, t independent to compare between two parametric independent variables, Mann-Whitney U to compare between two non-parametric independent variables, and Wilcoxon Signed Ranks test to compare between two non-parametric dependent variables.

 

RESULTS:

 

In the treatment group, complaints related to central obesity disappear in first week, very significant reduction of body weight, waist circumference, and systolic blood pressure, insignificant reduction in serum free testosterone, diastolic blood pressure, fasting blood sugar, triglyceride and cholesterol-HDL, uric acid, hs-CRP, and insignificant increase of adiponectin.

 

On comparison between both groups, we found a very significant reduction on body weight and waist circumference, but the insignificant reduction on serum free testosterone, systolic and diastolic blood pressure, and the unsignificant increase of adiponectin, meanwhile the reduction of serum free testosterone in the treatment group was smaller than the control group, that means Nigella sativa could inhibit the decreasing of serum free testosterone.

No side effects were detected in the treatment group.

 

CONCLUSION: Although the other variables in the treatment group were not significantly different, we found them better than the control group, which can be a good sign for metabolic restoration in COM.

It is suggested that larger dose and longer duration of NS consumption will give better results.

 

PMID: 20724766 [PubMed - indexed for MEDLINE]

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18 avril 2011 1 18 /04 /avril /2011 11:59

Am J Otolaryngol. 2010 Oct 12. [Epub ahead of print]

Herbal treatment of allergic rhinitis: the use of Nigella sativa.

Nikakhlagh SRahim FAryani FHSyahpoush ABrougerdnya MGSaki N.

Departments of ENT, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

BACKGROUND AND AIMS: 

 Allergic rhinitis is the most common chronic and allergic disease, especially in children.

This study aimed to investigate the anti-inflammatory effects of Nigella sativa and its effects on inflammatory factors in patients with allergic rhinitis symptoms and the process their clinical study charges.


SETTING: The present study is a clinical trial that conducted as prospective and double blind with descriptive analytic.


MATERIALS AND METHODS: The sample included 66 patients (case and placebo) with allergic rhinitis exposed to N. sativa oil.

Individual characteristics, including age and sex, and characteristics of the disease, including nasal congestion, runny nose, itchy nose, and sneezing attacks, were evaluated.

From the start of the study, that is, day 0, up to the end of the study, that is, day 30, an observer completed the symptoms severity questionnaire.


STATISTICAL ANALYSIS: Data were presented as means ± SEM. Comparisons between groups were performed by using paired Student t test. Differences were considered significant if P values are less than .05 and .01.


RESULTS: In the present study, 66 patients with allergic rhinitis, including 22 males (33.3%) and 44 females (66.7%) with a mean age of 47.19 years, were included. Immunoglobulin E total of more than 100 was reported in 38 patients before treatment. Immunoglobulin E in nasal wash from 7 patients was observed and was not measurable in 59 cases. Only 6.1% of the study population had nasal mucosal eosinophil.


CONCLUSION: The results show that N. sativa could reduce the presence of the nasal mucosal congestion, nasal itching, runny nose, sneezing attacks, turbinate hypertrophy, and mucosal pallor during the first 2 weeks (day 15).

The present findings are consistent with evidence that the antiallergic effects of N. sativa components could be attributed to allergic rhinitis.

Moreover, N. sativa should be considered for treating allergic rhinitis when the effects of other antiallergic drugs need to be avoided.

PMID: 20947211 [PubMed - as supplied by publisher]

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18 avril 2011 1 18 /04 /avril /2011 11:51

Epilepsy Res. 2011 Jan;93(1):39-43. Epub 2010 Nov 26.

The effect of thymoquinone on intractable pediatric seizures (pilot study).

Akhondian JKianifar HRaoofziaee MMoayedpour AToosi MBKhajedaluee M.

Mashhad University of Medical Sciences, Department of pediatric neurology, Ghaem Hospital, Mashhad, Khorasan, Iran. Akhondian@mums.ac.ir

INTRODUCTION: despite administration of numerous combinations of epileptic drugs, nearly 15% of childhood seizures are resistant to treatment and it is still a problem in pediatric practice. In traditional medicine, Nigella sativa was known to have anticonvulsant effects.

Recent studies also have shown its anticonvulsant effects.

Most of the properties of N. sativa or its extracts are mainly attributed to thymoquinone.

It has been shown that thymoquinone has several therapeutic effects and no evidence of toxicity or side effects is reported.


MATERIALS AND METHODS: 

 in this pilot, double-blinded crossover clinical trial study on children with refractory epilepsy, thymoquinone with dose of 1mg/kg was administered as an adjunctive therapy and its effects on frequency of seizures were compared with those of a placebo.

Twenty-two patients entered in the study. They were assigned in two groups and received either thymoquinone or placebo for a period of four weeks, and then during the two weeks of wash out period, they received only their pre-existing anti-epileptic drugs; then, after cross-overing, they received thymoquinone or placebo for a period of four weeks again.

During these periods their effects on seizure frequency were investigated.


RESULTS: the reduction of frequency of seizures at the end of first period in comparison with the same period before the study demonstrated a significant difference between two groups (thymoquinone and placebo) (P=0.04).

Also reduction of frequency of seizure has shown significant difference between two groups at the end of second period in comparison with end of first period (P=0.02).

The parental satisfaction showed significant difference between the two groups at the end of the first period (P=0.03).


CONCLUSION: it can be concluded that thymoquinone has anti-epileptic effects in children with refractory seizures.


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18 avril 2011 1 18 /04 /avril /2011 11:48

Exp Biol Med (Maywood). 2010 Dec;235(12):1425-31.

Thymoquinone inhibits matrix metalloproteinase expression in rabbit chondrocytes and cartilage in experimental osteoarthritis.

 

Chen WPTang JLBao JPWu LD.

Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88#, 310009 Hangzhou, People's Republic of China.

 

Thymoquinone (TQ) is the main constituent of Nigella sativa oil, which has been traditionally used against arthritis in the Middle East.

 

In this study, we investigated the effect of TQ against matrix metalloproteinase (MMP) expression in both rabbit chondrocytes and animal mode of osteoarthritis (OA) induced by anterior cruciate ligament transection and tested whether or not nuclear factor kappa B (NF-κB) was involved in this process. TQ down-regulated MMP-1, MMP-3 and MMP-13 expression and up-regulated tissue inhibitors of metalloproteinase-1 expression as assessed by quantitative realtime polymerase chain reaction.

 

In addition, NF-κB p65 protein level as well as its translocation induced by interleukin-1β were inhibited by TQ.

 

Our findings suggest the potential of TQ in the treatment of OA.

PMID: 21127340 [PubMed - indexed for MEDLINE]

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18 avril 2011 1 18 /04 /avril /2011 11:45

Plant Physiol Biochem. 2011 Feb;49(2):131-7. Epub 2010 Nov 18.

Novel antifungal defensins from Nigella sativa L. seeds.

Rogozhin EAOshchepkova YIOdintsova TIKhadeeva NVVeshkurova ONEgorov TAGrishin EVSalikhov SI.

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16/10, 117997 Moscow, Russian Federation. rea21@list.ru

From seeds of Nigella sativa L. (Ranunculaceae), an endemic plant of Uzbekistan, two novel defensins named Ns-D1 and Ns-D2, were isolated and sequenced.

The peptides differ by a single amino acid residue and show high sequence similarity to Raphanus sativus L. defensins Rs-AFP1 and Rs-AFP2.


The Ns-D1 and Ns-D2 defensins display strong although divergent antifungal activity towards a number of phytopathogenic fungi.

 

High antifungal activity of N. sativa defensins makes them promising candidates for engineering pathogen-resistant plants.

PMID: 21144761 [PubMed - in process]

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18 avril 2011 1 18 /04 /avril /2011 11:42

Int Immunopharmacol. 2011 Feb;11(2):250-4. Epub 2010 Dec 9.

The protective effect of thymoquinone against sepsis syndrome morbidity and mortality in mice.

Alkharfy KMAl-Daghri NMAl-Attas OSAlokail MS.

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. alkharfy@ksu.edu.sa

 

Sepsis and septic shock are life threatening complications and most common cause of death in intensive care units.

Thymoquinone, a constituent of Nigella sativa (black seed), holds exceptional promise as an anti-cancer and anti-inflammatory agent.

 

No evidence has been published, however, whether this compound has a protective effect from sepsis-related morbidity, mortality and associated organ dysfunction.


To examine this, two sets of mice (n=12 per group), with parallel control groups, were acutely treated with thymoquinone intraperitoneal injections of 1.0 and 2.0mg/kg body weight, and were subsequently challenged with endotoxin Gram-negative bacteria (LPS O111:B4).

 

In another set of experiments, thymoquinone was administered at doses of 0.75 and 1.0mg/kg/day for three consecutive days prior to sepsis induction with live Escherichia coli.

Survival of various groups was computed, and renal, hepatic and sepsis markers were quantified. Thymoquinone reduced mortality by 80-90% and improved both renal and hepatic biomarker profiles.

 

The concentrations of IL-1α with 0.75 mg/kg thymoquinone dose was 310.8 ± 70.93 and 428.3 ± 71.32 pg/ml in the 1mg/kg group as opposed to controls (1187.0 ± 278.64 pg/ ml; P<0.05).

Likewise, IL-10 levels decreased significantly with 0.75 mg/kg thymoquinone treatment compared to controls (2885.0 ± 553.98 vs. 5505.2 ± 333.96 pg/ml; P<0.01).

Mice treated with thymoquinone also exhibited relatively lower levels of TNF-α and IL-2 (P values=0.1817 and 0.0851, respectively).

 

This study gives strength to the potential clinical relevance of thymoquinone in sepsis-related morbidity and mortality reduction and suggests that human studies should be performed.

 

PMID: 21145996 [PubMed - in process]

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18 avril 2011 1 18 /04 /avril /2011 11:39

Parasitol Res. 2010 Dec 14. [Epub ahead of print]

Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.

Okeola VOAdaramoye OANneji CMFalade COFarombi EOAdemowo OG.

Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

The antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (MENS) were investigated against established malaria infection in vivo using Swiss albino mice.

 

The antimalarial activity of the extract against Plasmodium yoelli nigeriensis (P. yoelli) was assessed using the Rane test procedure.

 

Chloroquine (CQ)-treated group served as positive control.

The extract, at a dose of 1.25 g/kg body weight significantly (p < 0.05) suppressed P. yoelli infection in the mice by 94%, while CQ, the reference drug, produced 86% suppression when compared to the untreated group after the fifth day of treatment. P. yoelli infection caused a significant (p < 0.05) increase in the levels of

red cell and hepatic malondialdehyde (MDA), an index of lipid peroxidation (LPO) in the mice. Serum and hepatic LPO levels were increased by 71% and 113%, respectively, in the untreated infected mice.

Furthermore, P. yoelli infection caused a significant (p < 0.05) decrease in the activities of superoxide dismutase, catalase, glutathione-S-transferase and the level of reduced glutathione in tissues of the mice.

Treatment with MENS significantly (p < 0.05) attenuated the serum and hepatic MDA levels in P. yoelli-infected mice.

In addition, MENS restored the activities of red cell antioxidant enzymes in the infected mice to near normal.

Moreover, MENS was found to be more effective than CQ in parasite clearance and, in the restoration of altered biochemical indices by P. yoelli infection.

These results suggest that N. sativa seeds have strong antioxidant property and, may be a good phytotherapeutic agent against Plasmodium infection in malaria.

 

PMID: 21153838 [PubMed - as supplied by publisher]

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18 avril 2011 1 18 /04 /avril /2011 11:37

J Food Prot. 2010 Dec;73(12):2291-5.

In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels.

Halamova KKokoska LFlesar JSklenickova OSvobodova BMarsik P.

Department of Crop Sciences and Agroforestry, Institute of Tropics and Subtropics, Nutrition and Dietetics, Faculty of Agrobiology, Food and Nature Resources, Czech University of Life Sciences Prague, Kamycka 129, Prague 6-Suchdol, 165 21, Czech Republic.

The antiyeast activity of the black cumin seed (Nigella sativa) quinones dithymoquinone, thymohydroquinone (THQ), and thymoquinone (TQ) were evaluated in vitro with a broth microdilution method against six dairy spoilage yeast species.

Antifungal effects of the quinones were compared with those of preservatives commonly used in milk products (calcium propionate, natamycin, and potassium sorbate) at two pH levels (4.0 and 5.5).

THQ and TQ possessed significant antiyeast activity and affected the growth of all strains tested at both pH levels, with MICs ranging from 8 to 128 μg/ml. With the exception of the antibiotic natamycin, the inhibitory effects of all food preservatives against the yeast strains tested in this study were strongly affected by differences in pH, with MICs of ≥16 and ≥512 μg/ml at pH 4.0 and 5.5, respectively.

 

These findings suggest that HQ and TQ are effective antiyeast agents that could be used in the dairy industry as chemical preservatives of natural origin.

PMID: 21219751 [PubMed - indexed for MEDLINE]

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