Biochemical and ultrastructural evidences for toxicity of lead through free radicals in rat brain

Studies suggest that some lead-induced toxic effects may occur through free radical production and oxidative stress. This study examined the relationship between brain histopathological alterations and oxidative stress in subchronic lead exposure. Male Albino rats received lead acetate at 0.01%, 0.05% and 0.1% w/v in their drinking water for 30 days. Animals given sodium acetate (0.1% w/v) served as control in the same period. At the end of exposure, blood-lead levels, blood catalase (CAT) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content (in blood and brain) were measured. The brain tissue samples were prepared and analysed by light and scanning electron microscopy. The results show that, the blood-lead levels in treated animals were higher in comparison with control. CAT and SOD activities in animals treated with 0.01% and 0.05% w/v did not increase in comparison with control (P > 0.05) but these values were higher in animals treated with 0.1% w/v lead acetate (P < 0.01). MDA content in blood and brain of animals treated with lead acetate 0.1% w/v, increased significantly (P <0.01), but these values were not significantly increased in other treated animals. No major histopathological alterations were detected in the brains of animals treated with lead acetate at 0.01% and 0.05% w/v. In animals treated with lead acetate 0.1% w/v, demyelinization and collagenous scar formation with neuronal atrophy in hippocampus region was observed. It is concluded that lead acetate induce oxidative stress which has an important role in brain damage in rats.     

Production and characterization of monoclonal antibodies with specificity for human HLA-G isoforms

Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical importance. In the present study, monoclonal antibodies were prepared which recognize different membrane bound and soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic peptide. Use of this peptide (23 residues), which is present in the alpha1 domain of HLA-G, was previously demonstrated to provide antibodies useful for recognition of HLA-G isoforms in human placenta. Antibody-producing hybridomas were screened by an indirect one-step ELISA method. A clone designated 5E6H7, secreted antibodies useful in immunostaining studies involving both surface HLA-G of placental tissues and soluble forms of this antigen in human sera. In addition, unreactivity of this antibody with human lymphocytes and sections of normal human skin was observed by immunofluorescence microscopy, thus demonstrating its specificity for HLA-G.     

Pycnogenol((R)) in the Management of Asthma

Asthma is characterized as a chronic inflammatory process. Pycnogenol((R)), a bioflavonoid mixture extracted from Pinus maritima, is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties. The objective of this study was to evaluate the efficiency of this agent in a randomized, double-blinded, placebo-controlled, crossover study in patients with varying asthma severity. Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study. Medical history, physical examination, blood sample analyses, and spirometric values were obtained at baseline, 4 weeks, and 8 weeks. The patients were randomly assigned to receive either 1 mg/lb/day (maximum 200 mg/day) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks. No adverse effects were observed related to the study drug. Within the contingent of 22 patients who completed the study, almost all responded favorably to Pycnogenol in contrast to placebo. Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo. The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma. We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy.     

Protection against experimental autoimmune encephalomyelitis by a proteasome modulator

The capacity of interferon beta to alter the course of multiple sclerosis has promoted a new therapeutic concept, based upon the modulation of the immune response rather than its suppression. As the proteasome plays a crucial role in the control of the inflammatory process and immune cell survival, targeting the proteasome appears as a novel approach for the prevention and treatment of inflammatory autoimmune diseases. We have previously shown that ritonavir, an HIV-1 protease inhibitor used in AIDS therapy, can modulate the proteasome function by inhibiting the chymotrypsin-like activity and enhancing the trypsin-like activity. We have, therefore, explored its therapeutic potential on experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis, in Lewis rats and SJL mice. Daily administration of ritonavir during autoimmune antigen stimulation prevented clinical symptoms of EAE in a dose- and time-dependent manner. This protection was accompanied by an inhibition of the mononuclear cell infiltration into the central nervous system usually observed in EAE. Despite a complete absence of clinical symptoms during first EAE induction, ritonavir-treated animals became resistant to further induction of EAE, suggesting an immune mechanism of protection. These results suggest that proteasome modulation using ritonavir or analogues may be of interest for patients with multiple sclerosis.     

Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial

OBJECTIVE: Clonidine-based therapies have been utilized as the main protocol for opiate detoxification for several years. However, detoxification with clonidine has its limitations, including lack of efficacy for mental symptoms. Accumulating evidence shows the efficacy of Passiflora incarnata extract in the management of anxiety. In our continuing study of traditional medicines, which have neurotropic effects, this plant had an anxiolytic effect, which may be used as an adjuvant agent in the detoxification of opiates by clonidine. We present the results of a double-blind randomized controlled trial of clonidine plus passiflora extract vs. clonidine plus placebo in the outpatient detoxification of 65 opiates addicts. METHODS: A total of 65 opiates addicts were assigned randomly to treatment with passiflora extract plus clonidine tablet or clonidine tablet plus placebo drop during a 14-day double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. The fixed daily dose was 60 drops of passiflora extract and a maximum daily dose of 0.8 mg of clonidine administered in three divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). CONCLUSION: Both protocols were equally effective in treating the physical symptoms of withdrawal syndromes. However, the passiflora plus clonidine group showed a significant superiority over clonidine alone in the management of mental symptoms. These results suggested that passiflora extract may be an effective adjuvant agent in the management of opiate withdrawal. However, a larger study to confirm our results is warranted.     

Standardized percentile curves of body mass index of Iranian children compared to the US population reference.

OBJECTIVE: To present standardized percentile curves of body mass index (BMI) for Iranian children, and compare these to the US population reference. SUBJECTS: 1599 boys and 1702 girls aged 2-18 y living in urban Tehran as a part of a random cluster sample survey of 1 in 1000 families throughout Iran. MEASUREMENTS: Heights (cm) and weights (kg) were collected by trained health staff. RESULTS: Standardized BMI reference curves for Iranian boys and girls were constructed. The curves are shown to fit the data well. The development pattern of BMI for boys and girls are compared. CONCLUSIONS: The major differences observed between Iranian and the US BMI charts underline the need for population-specific reference data. For children over six years the 5th and 95th percentiles of our data may be used provisionally as cut-off points for defining thinness and obesity for Iranian children and adolescents.     

The polymorphism of human leucocyte antigen-G gene in a healthy population of Iran

Human leucocyte antigen-G (HLA-G) is a non-classical HLA class I molecule that unlike the classical HLA, has low polymorphism. This molecule, initially, found on invasive trophoblast cells and is postulated to have mediatory role in maternal–fetal interface. So far 43 alleles of HLA-G gene have been found. Studies on alleles of HLA-G gene could be useful in understanding the genetic variants of HLA-G alleles in Iranian population. The goal of this research was to determine the polymorphism of HLA-G gene in a healthy population of Iran. Genomic DNA was isolated from the whole blood of 102 randomly selected, healthy, unrelated Iranian individuals using salting-out technique followed by polymerase chain reaction (PCR) amplification of the exons 2 and 3 of HLA-G gene. For the performance of PCR–restriction fragment length polymorphism method, the PCR products were digested with several restriction enzymes and the resulted fragments were analysed using gel electrophoresis. The obtained results indicated nine alleles of HLA-G in Iranian individuals including G*01011 (4%), G*01012 (29.86%), G*01013 (10.8%), G*01015 (1.47%), G*01017 (1.96%), G*01018 (2.45%), G*01041 (29.4%), G*01043 (1.96%) and the null allele G* 0105N (18.1%). According to this study, in the Iranian subjects the most incident alleles were G*01012 and G*01041. The results for the frequency of G*01012 showed some similarity with Caucasians (36.3%).     

Disturbed grip function in women with rheumatoid arthritis.

OBJECTIVE: Hand dysfunction is a frequent cause of disability in rheumatoid arthritis (RA). In patients with RA, we studied the precision grip-lift sequence in relation to pain, stiffness, and observer assessed hand function and their relation to patients' experience of clumsiness and tendency to drop objects. METHODS: Performance of the precision grip-lift sequence was studied in 23 women with RA and 7 age and sex matched controls. The results were correlated to self-estimation of pain and stiffness of hands and to observer assessed measurements of hand function. RESULTS: A prolongation of the preload and loading phases and of the acceleration part of the transition phase as well as a disturbance of the safety margin (SM) during precision grip-lift were noted. Patients with good hand function (low Grip Ability Test score; GAT) displayed normal or increased SM compared to the healthy controls, whereas patients with more pronounced disease exhibited a lower SM. Disturbances seen in the precision grip-lift performance were related to stiffness, range of motion, and GAT score. In RA patients with decreased hand function the SM was correlated to feeling of clumsiness, but did not explain the frequency of object dropping. CONCLUSION: A disturbance in the precision grip-lift performance was noted in patients with RA. These grip performance changes need further investigation to determine possible mechanisms.