Modulation of human lymphocyte function by C3a and C3a(70-77).

Human C3a and the synthetic octapeptide C3a (70-77), which retains the activities of an anaphylatoxin, inhibit in a concentration-dependent manner the generation of leukocyte inhibitory factor (LIF) activity by human mononuclear leukocytes and T lymphocytes cultured with the mitogens phytohemagglutinin (PHA) or concanavalin A (Con A) or the antigen streptokinase-streptodornase (SK-SD). The generation of LIF activity was inhibited by 50% by 10(-8) M C3a or C3a(70-77) with PHA or Con A as the stimulus, whereas a more than 10-fold higher concentration of C3a(70-77) than C3a was required to achieve the same level of suppression with SK-SD as the stimulus. Similar concentrations of C3a(70-77) inhibited to the same extent the migration of T lymphocytes stimulated by alpha-thioglycerol of Con A. Neither C3a nor C3a(70-77) altered significantly the uptake of [3H]thymidine by human mononuclear cells exposed to PHA, Con A, or SK-SD. The capacity of C3a(70-77)-Sepharose,m but not Sepharose alone, to adsorb or inactivate mononuclear leukocytes required for the generation of LIF activity established a direct interaction. Analysis of the lymphocytes in the effluent from C3a(70-77)-Sepharose columns, using monoclonal antibodies to surface antigens, showed a selective depletion of the helper/inducer population of lymphocytes. C3a might represent an important mediator of the functionally selective regulation of human T lymphocyte activities by the complement system

Mycoplasma hominis brain abscess following uterus curettage: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Mycoplasma hominis </it>is mostly known for causing urogenital infections. However, it has rarely been described as an agent of brain abscess.</p> <p>Case presentation</p> <p>We describe a case of <it>M. hominis </it>brain abscess in a 41-year-old Caucasian woman following uterus curettage. The diagnosis was obtained by 16S rDNA amplification, cloning and sequencing from the abscess pus, and confirmed by a specifically designed real-time polymerase chain reaction assay.</p> <p>Conclusions</p> <p>Findings from our patient's case suggest that <it>M. hominis </it>should be considered as a potential agent of brain abscess, especially following uterine manipulation.</p

Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review

BACKGROUND: Considerable interest exists in the potential therapeutic value of dietary supplementation with the omega-3 fatty acids. Given the interplay between pro-inflammatory omega-6 fatty acids, and the less pro-inflammatory omega-3 fatty acids, it has been thought that the latter could play a key role in treating or preventing asthma. The purpose was to systematically review the scientific-medical literature in order to identify, appraise, and synthesize the evidence for possible treatment effects of omega-3 fatty acids in asthma. METHODS: Medline, Premedline, Embase, Cochrane Central Register of Controlled Trials, CAB Health, and, Dissertation Abstracts were searched to April 2003. We included randomized controlled trials (RCT's) of subjects of any age that used any foods or extracts containing omega-3 fatty acids as treatment or prevention for asthma. Data included all asthma related outcomes, potential covariates, characteristics of the study, design, population, intervention/exposure, comparators, and co interventions. RESULTS: Ten RCT's were found pertinent to the present report. CONCLUSION: Given the largely inconsistent picture within and across respiratory outcomes, it is impossible to determine whether or not omega-3 fatty acids are an efficacious adjuvant or monotherapy for children or adults. Based on this systematic review we recommend a large randomized controlled study of the effects of high-dose encapsulated omega-3 fatty acids on ventilatory and inflammatory measures of asthma controlling diet and other asthma risk factors. This review was limited because Meta-analysis was considered inappropriate due to missing data; poorly or heterogeneously defined populations, interventions, intervention-comparator combinations, and outcomes. In addition, small sample sizes made it impossible to meaningfully assess the impact on clinical outcomes of co-variables. Last, few significant effects were found

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ(17–40/42)). The presence of N-terminally truncated Aβ(17–40) and Aβ(17–42) in the control brains was confirmed by Western blotting and the identity of Aβ(17–40) was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ(17–42) immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism

Food Use and Health Effects of Soybean and Sunflower Oils

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oil