The association between infection burden in Iranian patients with acute myocardial infarction and unstable angina.

AIM: to evaluate the association of ischemic heart disease (IHD) with the number of pathogens (infection burden) among individuals with infection. METHODS: a total of 120 patients with IHD as the acute myocardial infarction (AMI; n=60) or unstable angina (UA; n=60) group and 60 healthy subjects with sex- and age-matched as control group were enrolled in this study. Serum samples of all participants were tested for the presence of antibodies to Helicobacter pylori (H. pylori), cytomegalovirus (CMV), type-1 herpes simplex virus (HSV-1) and type- 2 HSV (HSV-2) by using ELISA. RESULTS: Regarding the association of the infection burden with IHD, the prevalence ratios and 95% confidence intervals (CI) were 3.18 (CI: 1.50-6.72; P<0.001) for 3 seropositivities and 3.83 (CI: 0.84-17.43; P<0.05) for 4 seropositivities. The rate of subjects with high infection burden (3 seropositivities) was significantly higher in IHD group as compared to control group (53.4% vs 21.6%; P<0.01). Moreover, the mean number of seropositivities was also significantly higher in patients with IHD in comparison to control group (2.47 vs 1.68; P<0.01). The seroprevalence of anti-H. pylori antibodies in AMI and UA groups was significantly higher compared to control group (P<0.0001). The seroprevalence of anti-CMV antibodies in AMI and UA group was also significantly higher than those observed in control group (P<0.01). Moreover, the seroprevalence of anti-HSV-1 antibodies was significantly higher in AMI and UA groups in comparison to control group (P<0.001). The seroprevalence of anti-HSV-2 antibodies was similarly expressed in patients and healthy control group. CONCLUSION: the infection burden was significantly higher in patients with IHD, which represent that the parameter should also be considered as an independent risk factor for development of IHD. The seroprevalence of H. pylori, CMV and HSV-1 were also higher in patients with IHD.

Serum concentrations of Helicobacter pylori IgG and the virulence factor CagA in patients with ischaemic heart disease.

To compare the serum concentrations of IgG to Helicobacter pylori and its virulence factor CagA in patients with ischaemic heart disease (IHD), we recruited 120 patients with IHD [acute myocardial infarction (AMI) (n = 60); unstable angina (UA) (n = 60)] and 60 sex- and age-matched healthy controls in this study. The seroprevalence of anti-H. pylori IgG was 86.7% in AMI, 91.7% in UA patients and 58.3% in the control group with mean titres of 33.2 U/ml [standard error (SE) 4.76], 57.96 U/ml (SE 7.54) and 25.72 U/ml (SE 4.01) respectively. The seroprevalence of anti-H. pylori in the patient groups was significantly higher than the control group. The mean levels of anti-H. pylori in the AMI and UA groups were also significantly higher than in the control group. The seroprevalence and mean titre of anti-CagA IgG did not differ significantly between patient and control groups.

Cytokines in dementia of the Alzheimer's type (DAT): relevance to research and treatment.

There is indirect evidence suggesting that some cytokines may be involved in the pathophysiology of dementia of the Alzheimer type (DAT). Measurement of proinflammatory cytokines in the biologic fluids and brain tissues of DAT patients have provided some support for such a role. However, these studies are limited in scope and have included a relatively small number of patients. Future studies are needed to elucidate the role of cytokines in the pathogenesis and treatment of DAT.

Substance P and neuropsychiatric disorders: an overview.

Substance P (SP) is a naturally-occurring tachykinin peptide isolated from brain tissues and gastrointestinal tract. In the brain, substantia nigra and basal ganglia contain relatively high amounts of substance P. There is evidence suggesting that substance P functions as a neurotransmitter. It has been implicated in the pathophysiology of several neuropsychiatric disorders. Substance P may also serve as a useful tool in studying the effects of antidepressant drugs and electroconvulsive therapy. However, the contribution of substance P to the understanding of neuropsychiatric disorders is far from clear. Future studies should focus on the interactions and coexistence of substance P with other neurotransmitters and neuropeptides.

Neuropsychiatric aspects of cytokines research: an overview.

Cytokines are a group of proteins primarily synthesized by various immune cells. They have multiple functions within the immune system and have been implicated in a number of disease states. There is growing evidence that some cytokines are also synthesized in the central nervous system. Taking into consideration that some cytokines are also capable of inducing behavioral effects, it has been suggested that cytokines may play a role in some psychiatric and neurologic disorders.

S-adenosylmethionine in the treatment of depression.

The antidepressant property of S-adenosylmethionine (SAMe) has been supported by several uncontrolled and controlled studies. Compared to standard antidepressant agents, SAMe has fewer side-effects and shorter lag period. Future studies to delineate SAMe-responsive depression are warranted.

Tranylcypromine lowers human platelet MAO B activity but not concentration.

Monoamine oxidase content in extracts of human blood platelets was determined independently of MAO activity measurements with a recently developed monoclonal antibody against human platelet monoamine oxidase (MAO B) in a competitive radioimmunoassay. Administration of a single oral dose of the irreversible inhibitor tranylcypromine to normal human subjects resulted in a rapid and marked inhibition of platelet MAO catalytic activity within 1 day, followed by recovery of activity to normal levels within 2 weeks. In contrast, there was no change in the net concentration of MAO protein during this time. Since recovery of MAO B activity approximated the reported half-life of blood platelets, these results suggest that recovery of platelet MAO activity after tranylcypromine treatment is due to the replacement of old platelets by new ones which contain catalytically active MAO B.

Ultrastructural immunolocalization of basic fibroblast growth factor in mast cell secretory granules. Morphological evidence for bfgf release through degranulation.

We previously reported that mast cells (MCs) serve as a source of basic fibroblast growth factor (bFGF), a potent angiogenic and mitogenic polypeptide, suggesting that bFGF may mediate MC-related neovascularization and fibroproliferation. Unlike many other growth factors, bFGF lacks a classic peptide sequence for its secretion, and the mechanism(s) for its release remains controversial. Because MCs release a wide spectrum of bioactive products via degranulation, we hypothesized that MC degranulation may be a mechanism of bFGF release and used ultrastructural immunohistochemistry to test the hypothesis. We reasoned that if bFGF is released through degranulation, it should be localized to MC secretory granules. Human tissues with chronic inflammation and rat/mouse tissues with anaphylaxis were studied. In all tissue samples examined, positive staining (or immunogold particle localization) for bFGF in MCs was predominantly in the cytoplasmic granules. Moderate bFGF immunoreactivity was also found in the nucleus, whereas the cytosol and other subcellular organelles exhibited minimal immunogold particle localization. In contrast, no immunogold particle localization for bFGF was observed in lymphocytes or plasma cells. In rat/mouse lingual tissue undergoing anaphylaxis, immunogold particle localization for bFGF was found not only in swollen cytoplasmic granules but also in the extruded granules of MCs. Three different anti-bFGF antibodies gave similar immunogold particle localization patterns, whereas all controls were negative. These results provide morphological evidence suggesting that, despite the lack of a classic secretory peptide in its structure, bFGF is localized to the secretory granules in MCs and may be released through degranulation.

Apoptosis in thymus of adult Xenopus laevis.

Thymocyte apoptosis in adult Xenopus laevis is demonstrated on agarose gels and is quantified by propidium iodide incorporation using flow cytometry. Basal apoptotic levels are increased after in vitro exposure to a glucocorticoid, dexamethasone (DEX), and to the lectin, phytohemagglutinin (PHA). To determine the role that newly introduced antigenic determinants may play in this regard, a repertoire of altered-self antigens was created by exposing thymuses in vitro to trinitrobenzene sulfonic acid (TNBS) thereby derivatizing self-cells and proteins via 2,4,6-trinitrophenyl-acetic acid conjugation. An increase in apoptosis in TNBS-treated thymuses is observed. Thus, the thymocytes of adult Xenopus laevis are susceptible to apoptosis when induced by a glucocorticoid, a lectin, and by altered self, antigen activation.

Apoptosis in the thymus of developing Xenopus laevis.

Metamorphosis in Xenopus laevis is a time when thyroxine and glucocorticoid levels rise, dramatic morphological and physiological changes take place, and tolerance is established to newly expressed adult antigens. In vitro exposure of thymocytes tested at different metamorphic stages, to the T-cell lectin, phytohemagglutinin (PHA), stimulates increased apoptosis, but incubation with the synthetic glucocorticoid, dexamethasone (DEX), fails in this regard. Altered-self antigenicity, following trinitrobenzene sulfonic acid (TNBS) treatment, increases apoptosis only in the late stages of metamorphosis. Developmentally blocked metamorphosing larvae demonstrate low thymic apoptotic rates that are also unaffected by in vitro exposure to DEX or by in vivo exposure to thyroxine, but are increased by PHA and in some individuals by TNBS. When released from blockade, their thymic apoptotic rates rise as progress through metamorphosis is renewed. Larval thymic apoptosis is glucocorticocoid- and thyroxine insensitive, but is lectin and altered-self antigen activated, particularly during postclimax stages.

Rheumatoid arthritis and schizophrenia: are they mutually exclusive?

The relationship between schizophrenia and rheumatoid arthritis has been explored in a number of studies. It has been claimed that the two disorders are mutually exclusive. Review of the literature indicates that the two conditions seldom coexist. The underlying mechanisms responsible for the infrequent coexistence of schizophrenia and rheumatoid arthritis are far from clear. However, various hypotheses have been proposed to explain the negative correlation between the two diseases.

Role of cytokines in psychopathology: therapeutic implications.

Cytokines can influence physiological functions such as sleep and food intake; they also interact with a number of neurotransmitters and second messengers in the brain. Cytokines are involved in a number of infectious, inflammatory, neoplastic, metabolic and degenerative illnesses. They also have been implicated in some psychiatric disorders, including 1) depressive and anxiety disorders; 2) schizophrenic disorders (chronic and acute); 3) autistic disorder; 4) eating disorders; and 5) obsessive-compulsive disorder. Alterations in cytokine peptide/receptor production or function in major psychiatric disorders are of special interest to researchers in the field. Exogenous administration of cytokines may be of therapeutic value in disorders in which the cytokine system may be disturbed. In some brain disorders of defined neuropathology, some cytokines have been found clinically useful. Such a development has yet to occur in the treatment of psychiatric disorders; however, some limited and very preliminary observations suggest that manipulation of the cytokine network may be of potential value in the treatment of some psychiatric disorders. Considering the human and economic costs of major psychiatric disorders, alteration of the cytokine network as a potential therapeutic tool is worthy of consideration and investigation.

Platelet MAO concentration and molecular activity: I. New methods using an MAO B-specific monoclonal antibody in a radioimmunoassay.

New methods for determination of specific concentration and molecular activity of monoamine oxidase (MAO) in platelets are described and evaluated in parallel with specific activity measures, performed in whole platelets and platelet extracts. Platelet MAO specific concentration is determined in platelet extracts by a radioimmunoassay, using a monoclonal antibody that recognizes human MAO B, the form that occurs in platelets, but not MAO A. All four platelet MAO measures are found to be reliable and stable, and thus are suitable for long-term comparisons of normal and clinical populations, such as those reported in Part II of this report. The new measures of enzyme concentration and molecular activity make available important information about the state of MAO B molecules in a given individual that reflects the genetic expression and control of the enzyme.

Platelet MAO concentration and molecular activity: II. Comparison of normal and schizophrenic populations.

Platelet monoamine oxidase (MAO B) in 59 normal and 57 RDC-diagnosed medicated and unmedicated schizophrenic subjects was analyzed for whole platelet and extracted activities, specific concentration, and molecular activity. A novel radioimmunoassay using a monoclonal antibody elicited to human platelet MAO was used. Female schizophrenics showed no differences from female normals in MAO measures; however, these data could not be clearly evaluated because of confounding effects of age and drugs. Male schizophrenics treated with neuroleptics expressed significantly reduced whole platelet MAO activity, compared to untreated male patients. Compared with normal males, male schizophrenics showed significantly lowered molecular activities, along with elevated specific concentrations, which did not appear to be explained solely by drug usage. Additional mechanisms explaining the diminished molecular activity in male schizophrenics may be the presence of an endogenous irreversible inhibitor or a genetically determined, possibly structural, variant of MAO B.

Rubidium in psychiatry: research implications.

A brief overview of the use of rubidium in affective disorders and schizophrenia is presented. Although antidepressant action of rubidium has not been supported by adequate number of controlled studies, its potential contribution to psychiatry warrants further investigations. Endogenous rubidium may be a useful research tool in the future psychopharmacological studies of affective disorders.

Cytokines and etiopathogenesis of pervasive developmental disorders.

Autistic disorder, also known as early infantile autism, is a developmental disorder of unknown etiology. However, there is some evidence to suggest that abnormalities of the immune system mediate the pathophysiology of autistic disorder. Cytokines, which play a pivotal role in initiating and maintaining immune responses, have been implicated in the etiopathogenesis of major neuropsychiatric disorders including autism. Cytokines are synthesized in the periphery, as well as in the central nervous system, and exert their effects by binding to their receptors in the nervous tissues. It is suggested that, in genetically predisposed individuals, overproduction or decreased synthesis of certain cytokines may result in neurodevelopmental arrest and/or neurotoxicity.