Epilepsy lifetime prevalence in Iran: a large population- based national survey.

Epilepsy has garnered increased public health focus because patients who suffer from epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment and care advances. The epidemiology of epilepsy is diverse in different countries and regions. This nationwide population-based cross-sectional study was conducted to determine the life time prevalence and health related factors of epilepsy for the first time in Iran through a two-phase door-to-door survey method. In phase I, a screening for epilepsy was performed on 68,035 people. Then in phase II, after the neurological evaluation of participants and reviewing medical records, 1130 subjects with epilepsy was confirmed. The life time prevalence of epilepsy was achieved to be 16.6 per 1000 people (95% CI 15.4-17.8) with the average age onset 19.1 ± 21.1 (active prevalence 9.5 per 1000 people). Focal seizure (59.3%), generalized epilepsy (38%) and unknown types of epilepsy (2.7%) were detected among participants. The overall life time prevalence of febrile convulsion was 4.1 per 1000 people. The frequency of attacks per year and per month were 3.0 ± 1.6 and 0.5 ± 0.1, respectively. Age-specific life time prevalence was highest among the age group of 15-19 years old [32.7 per 1000 persons (95% CI 29.1-36.8)] and it was higher in male (53.8%) than female (46.2%) participants. Our results showed that the life time prevalence of epilepsy in Iran is higher than worldwide average.

Comparison of Two Validation Nutrition Tools in Hospitalized Elderly: Full Mini Nutritional Assessment and Short-form Mini Nutritional Assessment.

BACKGROUND: The aim was to determine validity, reliability, and cutoff of full-mini nutritional assessment (MNA) and MNA-short form (SF) also which one was better for the screening of malnutrition in the Iranian hospitalized elderly. METHODS: In this cross-sectional validation study, 96 hospitalized elderly ≥60 years selected from two hospitals in Tehran. Anthropometric measures (body mass index [BMI], mid-arm circumference [MAC], calf circumference [CC], abdomen, and waist skinfold thickness) and laboratory tests (albumin and hemoglobin levels, and red blood cell count were performed. Nutrition tools (full-MNA and MNA-SF), cognition tool (mini-mental state examination, depression scale (Geriatric Depression Scale15 and activities of daily living (ADL) index (Modified Barthel-ADL) were administered. RESULTS: The full-MNA scores were significantly correlated to measures of MAC, BMI, waist, and CC. The MNS-SF scores were significantly related to measures of MAC, waist, and CC. Serum albumin showed a poor correlation with both tools. At cutoff 24 in full-MNA had a sensitivity 75% and specificity 77.8% and the MNA-SF considered 62.5% sensitivity and 65.3% specificity at cutoff 10.50 to detect well-nourished from malnourished subjects. The internal consistencies of both tools were >90%. In exploratory factor analysis, six components found for full-MNA and two components for MNA-SF. Known group validity of full-MNA was reflected significant differences between geriatric patients with expected higher full-MNA scores and patients with expected lower scores (BMI ≥24 vs. BMI <24 or bed ulcer or assisted food intake). CONCLUSIONS: It seems the Persian version of full-MNA is more appropriate in comparison to MNA-SF for screening malnutrition in the Iranian hospitalized elderly patients.

Controlled release of an endostatin peptide using chitosan nanoparticles.

Whereas several anticancer peptides are in different stages of clinical development, their administration is limited by the fast elimination from the systemic circulation. Peptide loading on nano-carriers can pave the way for their future application. We have recently indicated that a disulfide loop rather than a Zn-binding loop improves the anti-angiogenic and antitumor activities of the N-terminal fragment of endostatin. In this study, chitosan nanoparticles (CS NPs) are used for the controlled release of the engineered peptide. Loading of the peptide into CS NPs using the ionic gelation method was confirmed by FTIR and resulted in final particle size, poly-dispersity index and surface charge of 186.5 ± 24.0 nm, 0.26 ± 0.02 and 20.1 ± 0.4 mV respectively. The SEM morphological analysis revealed spherical particles with an average size of 80 ± 5 nm. Peptide loading studies revealed that CS NPs are able to adsorb the peptide as ~70%. The release measurements indicated an initial burst release by 49% after 2 hr and complete release after 80 hr. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than different cancer cell lines. These results underscore the promise of CS NPs as therapeutics nanosystems and open a perspective for improving the clinical applications of peptide drugs.

Progesterone-induced transdifferentiation of bone marrow stromal cells into Schwann cells improves sciatic nerve transection outcome in a rat model.

BACKGROUND: Peripheral nerve injury is a common lesion in clinical practice and transplantation is one of the most common approaches to its treatment. While nerve graft is used for restoring the defected nerve using autologous or allogenic tissues, Schwann cells are considered as an alternative source. In this study, bone marrow stromal cells (BMSCs) were induced to transdifferentiate into Schwann-like cells (SLCs) using progesterone. METHODS: The BMSCs were collected from the long bones of rats and were transdifferentiated in vitro into SLCs by preinduction with ß-mercaptoethanol and retinoic acid, followed by induction with bFGF, PDGF, forskelin and progesterone. The SLCs were then transplanted in a rat model of sciatic nerve injury with 1-cm gaps. A sciatic function index (SFI), histological, immunohistochemical and ultrastructural studies were used in evaluating the improvement in the nerves regeneration. RESULTS: The results show significant differences in the SFI between the control and the treated groups (P<0.05). The transplant was immunoreactive to S100, and the electron microscopy showed myelination in the transplanted cells. CONCLUSIONS: There were functional and structural improvements in the progesterone-induced SLCs, which were not significantly different from the heregulin-treated ones (positive control) but still significantly different from negative controls.

Enhancement of Neural Stem Cell Survival, Proliferation, Migration, and Differentiation in a Novel Self-Assembly Peptide Nanofibber Scaffold.

Considerable efforts have been made to combine biologically active molecules into the self-assembling peptide in order to improve cells growth, survival, and differentiation. In this study, a novel three-dimensional scaffold (RADA4GGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4 and IKVAV to promote the strength of the peptide. The cell adhesion, viability, proliferation, migration, and differentiation of rat embryonic neural stem cells (NSCs) in R-GSIK were investigated and compared to laminin-coated, two-dimensional, and Puramatrix cultures. The scanning electron microscopy studies of the R-GSIK showed an open porous structure and a suitable surface area available for cell interaction. R-GSIK promoted the cell adhesion, viability, proliferation, and migration compared to the other cultures. In addition, the R-GSIK enhanced NSCs differentiation into neuronal cells. The NSCs injected in R-GSIK had a lower glial differentiation rate than in the Puramatrix. The results suggest that R-GSIK holds great promise for cell therapies and neuronal tissue repair.

Improvement of spinal contusion model by cotransplanting bone marrow stromal cells and induced BMSCs into oligodendrocytes-like cells.

BACKGROUND: Demyelination is a common lesion in spinal cord injury, cell therapy is one of the approaches for replacing the lost oligodendrocytes. In this study, bone marrow stromal cells (BMSCs) have been transdifferentiated into oligodendrocyte-like cells (OLCs) and used in cytotherapy of contused spinal cords in rats. METHODS: The BMSCs were collected from the rat long bones, and cultured and characterized by different markers, then they were preinduced with dimethyl sulfoxide followed by retinoic acid, and then the preinduced cells were induced with combination of basic fibroblast growth factor, platelet-derived growth factor and heregulin, followed by triiodothyronine. The OLCs were transplanted in the contused spinal cords of the rats, combined with undifferentiated BMSCs. Specific markers were used in order to characterize the cells by immunohistochemistry and real-time polymerase chain reaction. The BMSCs showed typical immnuoreactivity to the markers, and the OLCs were immunostained with specific markers. RESULTS: There was an improvement in the Basso, Beattie and Bresnahan score with reduction in the cavitation in the contused rats treated with OLCs combined with BMSCs. The transplanted cells were detected in the contused spinal cord. CONCLUSIONS: The combination of the transdifferentiated BMSCs into OLCs with the undifferentiated BMSCs improved the contused spinal cord.

Intraspinal delivery of bone marrow stromal cell-derived neural stem cells in patients with amyotrophic lateral sclerosis: A safety and feasibility study.

BACKGROUND: Stem cells have been used in several studies with different methodologies to treat patients with ALS. METHODS: In this safety and feasibility study, 11 patients with definite or probable ALS according to El Escorial criteria were selected. 3 patients were excluded due to inadequate bone marrow or safety measures after acquisition of bone marrow. Bone marrow stromal cell-derived neural stem cells were injected in C7-T1 spinal cord under general anesthesia. Patients were followed for 12months after injection with manual muscle testing, ALSFRS-R, quality of life changes, pulmonary function test and electromyography. RESULTS: None of the patients had perioperative mortality or major morbidity. One patient had temporary deterioration in lower extremities after injection which improved after a few weeks. In the 12months post-injection, only one patient died due to pulmonary embolism. From the remaining 7 patients, all had a stable course after 4months and 5 were stable for the first 8months post-injection and deteriorated afterwards. DISCUSSION: In this study, intraspinal injection of bone marrow derived neural stem cells appears to be safe. Patients experienced a temporary stabilization for the first few months post-injection and then gradually deteriorated.

Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin.

Polyethylene glycol hydrogel (PEG) conjugated with arginyl glycyl aspartic acid (RGD) (PEG-RGD) has been considered to be a scaffold in three-dimensional (3D) culture that improves neurite outgrowth; on the other hand, tenascin C controls neural growth and differentiation. In this study, the effect of a combined RGD and tenascin C mixture in 3D culture (3D-PEG-RGD-TnC) on the survival, growth and differentiation of neural stem cells. The viability of the culture has been evaluated by live/dead assay and the results show that the viability of NSCs in 3D-PEG-RGD-TnC is significantly higher than its value in 3D-PEG-RGD. The proliferation was evaluated by MTS test and was found to be slightly improved but statistically not significant. Accordingly, the differentiation was evaluated by immunoreactivity to nestin, neurofilament 68, neurofilament 160, neurofilament 200 and GFAP; and the expression of nestin, neuro D, musashi1, ß-tubulin III, GFAP, MBP and Oct4 was studied using RT-PCR. The results showed enhancement of the differentiation of NSCs into the neuronal phenotype in 3D-PEG-RGD-TnC. The morphology of NSCs cultured in 3D-PEG-RGD-TnC showed neurite outgrowths and increase in the contact between the differentiated cells' extensions. The conclusion of this study was that NSC survival, proliferation and differentiation are enhanced when the cells are cultured in 3D-PEG-RGD-TnC.

Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold.

OBJECTIVES: In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs). MATERIALS AND METHODS: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods. In addition, we designed a new method for measurement of migration distance in 3D cultivation of hMgSCs in PuraMatrix. RESULTS: Our results revealed that hMgSCs have the ability to form spheres in stem cell culture condition. These meningioma cells expressed GFAP, CD133, vimentin, and nestin. Using the injection method, a higher proliferation rate of the hMgSCs was observed after seven days of culture. Furthermore, the novel migration assay was able to measure the migration of a single cell alone in 3D environment. CONCLUSION: The results indicate the injection method as an efficient technique for culturing hMgSCs in PuraMatrix. Furthermore, the novel migration assay enables us to evaluate the migration of hMgSCs.

The prevalence of carpal tunnel syndrome among long-term manual wheelchair users with spinal cord injury: A cross-sectional study.

CONTEXT: Use of a handrim wheelchair could force the wrist into extreme excursions and encroachment of the median nerve. OBJECTIVE: We performed a study of the prevalence of carpal tunnel syndrome in prolonged wheelchair users. DESIGN AND SETTING: A cross-sectional study was conducted for one year in an outpatient clinic of spinal cord injury. PARTICIPANTS: Patients had traumatic injury at the first thoracic level and below, with time since injury of at least 5 years. OUTCOME MEASURE: The prevalence of carpal tunnel syndrome by history taking, clinical examinations and motor and sensory nerve conduction studies of median nerve performed for both hands. RESULTS: Participants (N = 297) were all male. Mean (SD) age and duration since injury were 48 (8.5) and 23 (6.6) years, respectively. A significant difference in median duration of injury based on the severity of the syndrome (P < 0.001), and a significant trend in time since injury for the severity (P (one tailed) < 0.001) were seen. There was a significant difference in the median age among the groups (P = 0.009), and the median increased with the severity (P (one tailed) = 0.001). CONCLUSIONS: Carpal tunnel syndrome is a common side effect of the long time use of wheelchair, and its severity is associated with duration of wheelchair use and age. Alternative methods for wheelchair propulsion should be developed to diminish the likelihood of the syndrome.

Relationship between insulin resistance and subclinical atherosclerosis in individuals with and without type 2 diabetes mellitus.

BACKGROUND: Insulin resistance is of utmost importance as an underlying mechanism for increased risk of cardiovascular disease (CVD). We assessed the association between Homeostatic Model Assessment (HOMA-IR) and two surrogate subclinical atherosclerosis markers (SCA) among individuals with and without type 2 diabetes (DM), those who did not have any clinical presentation of the CVD. METHODS: In a cross-sectional study, 208 participants (105 diabetics and 103 non-diabetics) were enrolled from referred patients with diabetes to an academic outpatient clinic and their non-diabetic relatives in-law. Fasting serum levels of insulin, blood glucose and lipid profile, were measured. Anthropometric and blood pressure were measuremented standardly. Body Mass Index (BMI) and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were calculated. Coronary Artery Calcium Score(CACS) was measured using a Multi-Detctor CT scanner. Flow mediated dilation (FMD) was measured using bimode ultrasonography (with linear transducer 13,000 MHZ). Univariate and multivariate logistic regression models were used to evaluate the association between these SCA markers and HOMA index in adjusting models. RESULTS: CACS and HOMA-IR were higher and FMD was lower in diabetic participants than non-diabetic ones (P < 0.01) In a stepwise logistic regression model, CACS and FMD were associated with HOMA-IR (odds ratio = 1.778; 95 % confidence interval (CI): 1.211-2.726 and odds ratio = 1.557; 95 % CI: 1.601-2.275, respectively) in non-diabetics but not among diabetic participants. CONCLUSIONS: CACS and FMD are related to insulin resistance among non-diabetic individuals, but we could not find this relationship among diabetic patients.

Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine.

One of the approaches for treating demyelination diseases is cytotherapy, and adult stem cells are potential sources. In this investigation, we tried to increase the yield of oligodendrocyte-like cells (OLCs) by inducing neural stem cells generated from BMSCs-derived neurospheres, which were used for deriving the neural stem cells (NSCs). The latter were induced into OLCs by heregulin, PDGF-AA, bFGF and triiodothyronine (T3). The BMSCs, NS, NSCs and OLCs were characterized by using immunocytochemistry for fibronectin, CD44, CD90, CD45, Oct-4, O4, Olig2, O1 and MBP markers. PDGF receptor α (PDGFR-α), Olig2 and MOG expression were evaluated by RT-PCR. The BMSCs expressed CD44, CD90, CD106 and Oct-4; the NSCs were immunoreactive to nestin and neurofilament 68. Incubation of the NSCs for 4 days with heregulin, PDGF-AA and bFGF resulted in their induction into oligodendrocyte progenitor-like cells (OPLCs), which immunoreacted to O4, Olig2 and O1, while Olig2 and PDGFR-α were detected by RT-PCR. Replacing heregulin, PDGF-AA and bFGF with T3 for 6 days resulted in repression of O4, O1, Olig2 and PDGFR-α. The OLCs were co-cultured with motoneurons resulted in induction of MOG and MBP, which were expressed in functional OLCs. The latter can be generated from BMSCs-derive NS with high yield.

Familial hemiplegic migraine and spreading depression.

OBJECTIVE: Familial hemiplegic migraine (FHM) is an autosomal dominantly inherited subtype of migraine with aura, characterized by transient neurological signs and symptoms. Typical hemiplegic migraine attacks start in the first or second decade of life. Some patients with FHM suffer from daily recurrent attacks since childhood. Results from extensive studies of cellular and animal models have indicated that gene mutations in FHM increase neuronal excitability and reduce the threshold for spreading depression (SD). SD is a transient wave of profound neuronal and glial depolarization that slowly propagates throughout the brain tissue and is characterized by a high amplitude negative DC shift. After induction of SD, S218L mutant mice exhibited neurological signs highly reminiscent of clinical attacks in FHM type 1 patients carrying this mutation. FHM1 with ataxia is attributable to specific mutations that differ from mutations that cause pure FHM1 and have peculiar consequences on cerebellar Cav2.1 currents that lead to profound Purkinje cell dysfunction and neuronal loss with atrophy. SD in juvenile rats produced neuronal injury and death. Hormonal factors involved in FHM affect SD initiation and propagation. The data identify SD as a possible target of treatment of FHM. In addition, FHM is a useful model to explore the mechanisms of more common types of migraine.

The course of anxiety and depression in surgical and non-surgical patients.

OBJECTIVE: The aim of this study was to compare the level of anxiety and depression in patients admitted to surgery or internal departments. METHODS: The study was carried out on 359 hospitalized patients over the age of 18 years and designed as a cross sectional survey. Participants were recruited from internal medicine and surgery departments of Khatam Ol Anbia hospital, Tehran, Iran. Information was collected using the Hospital Anxiety and Depression Scale. RESULTS: Ninety-four (26.18%) patients had no anxiety and depression, 96 (26.7%) were borderline cases of anxiety, 140 (39%) were very anxious, 89 (24.8%) were borderline cases of depression, and 106 (29.5%) had depressed mood. There was a significant correlation between anxious mood and sex and duration of background disease as well as between the level of depressive mood and age. Patients with anxiety are significantly more prone to depression. However there were no significant differences between the level of anxiety or depression between surgical or non-surgical patients. CONCLUSIONS: The prevalence of anxious and depressive moods was high in both surgical and non-surgical patients. However, non-surgical treatments were as stressful as surgical procedures for patients admitted to hospital in the first 24 h.

Microglial activation in rat experimental spinal cord injury model.

BACKGROUND: The present study was designed to evaluate the secondary microglial activation processes after spinal cord injury (SCI). METHODS: A quantitative histological study was performed to determine ED-1 positive cells, glial cell density, and cavitation size in untreated SCI rats at days 1, 2, and 4, and weeks 1, 2, 3, and 4. RESULTS: The results of glial cell quantification along the 4900-µm long injured spinal cord showed a significant increase in glial cell density percentage at day 2 as compared to other days. Whereas the highest increase in ED-1 immunoreactive cells (monocyte/phagocyte marker in rats) was observed at day 2 (23.15%) post-injury. Evaluation of cavity percentage showed a significant difference between weeks 3 and 4 post-injury groups. CONCLUSIONS: This study provides a new insight into the multiphase immune response to SCI, including cellular inflammation, macrophages/microglia activation, glial cell density, and cavitation. Better understanding of the inflammatory processes associated with acute SCI would permit the development of better therapeutic strategies.

Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

Improvement of Contused Spinal Cord in Rats by Cholinergic-like Neuron Therapy.

BACKGROUND: Disability in spinal cord injury is an important medical problem, and cell transplantation is considered as an option for the treatment. OBJECTIVES: The purpose of this study is to use bone marrow stromal cells (BMSCs) derived cholinergic neuron-like cells (CNL) in order to ameliorate the contusion model of spinal cord injury in rats. MATERIALS AND METHODS: The CNLs were produced by pre inducing BMSCs with ß-mercaptoethanol (BME) followed by inducing with nerve growth factor (NGF). The cells were immunoreactive to neurofilament 200, NeuN, synaptophysin, synapsin, microtubule associated protein-2 and choline acetyl transferase (ChAT). The CNL were transplanted in contused rats (CR), which were sacrificed after 12 weeks. RESULTS: The results showed that BBB test showed an improvement in the CR, while the quantitative analysis showed that the improvement rate was higher in the rats treated with CNL than those treated with BMSCs only or the untreated animals, similar results were noticed in the improvement index. Immunohistochemical analysis of the tissue section prepared from the CR showed that the transplanted cells were engrafted and integrated in the traumatized spinal cord. The morphometric analysis showed that the volume density of the cavity in the CNL treated rats was significantly lower than that of the untreated ones, while the spinal tissue regeneration index was significantly higher. CONCLUSIONS: The conclusion of the study is that CNL can improve the injured spinal cord.

Anxiety and depression in patients with amputated limbs suffering from phantom pain: a comparative study with non-phantom chronic pain.

BACKGROUND: Phantom limb pain (PLP) is approximately a common condition after limb amputation, which potentially affects the quality of life. We aimed to evaluate anxiety and depression in patients with amputated limbs suffering from PLP and to compare these psychological dysfunctions with that of patients with non-phantom chronic pain. METHODS: A total number of 16 male amputees with PLP and 24 male age-matched patients with non-phantom chronic pain were recruited in this study, which was performed at Khatam-Al-Anbia Pain Clinic, Tehran, Iran. A validated Persian version of the hospital anxiety and depression scale (HADS) was used to compare two psychological dysfunctions - anxiety and depression - between the two groups of study. RESULTS: The mean of total anxiety score was significantly lower in patients with PLP (8.00 ± 3.93 vs. 11.25 ± 5.23; P = 0.041) and the prevalence of anxiety caseness (HADS-A score ≥ 11) was also lower in the PLP group (25% vs. 58.3%; P = 0.112, power = 31.7%). The mean of total depression score was 7.69 ± 5.51 and 9.38 ± 6.11 in patients of PLP and chronic pain groups, respectively (P = 0.340, power = 15%). Consequently, the prevalence of depression caseness (HADS-D score ≥ 11) was lower in PLP patients (37.5% vs. 50%; P = 0.710, power = 8%). CONCLUSION: Our results indicate that depression and anxiety are not more common in PLP patients, whereas they are more prevalent in subjects with non-phantom chronic pain. These lower levels of anxiety and depression in PLP compared with chronic pain is a new finding that needs to be evaluated further, which may lead to new insights into the pathogenesis of phantom pain in further studies.

Effects of paraoxonase 1 activity and gene polymorphisms on long-term pulmonary complications of sulfur mustard-exposed veterans.

Sulfur mustard (SM) is an alkylating agent with prolonged adverse effects. The antioxidant paraoxonase 1 (PON1), an endogenous free radical scavenger, plays a protective role against oxidative stress. The possible roles of oxidative stress in the pathogenesis of SM, together with the antioxidant activity of PON1, are enough to warrant the analysis of PON1 polymorphisms and allelic variants in incapacitated veterans. PON1 55 L/M and 192 Q/R polymorphisms were assayed in 289 male veterans with severe pulmonary conditions, who were exposed to SM 20-25 years ago, and 66 gender-, age- and ethnic-matched healthy controls. As we showed previously the PON1 activity decreased significantly in veterans. However, PON1 55 L/M and 192 Q/R genotype distributions were not significantly different between the veterans and the controls. R and L allele carriers have also significantly higher basal and salt-stimulated PON1 activity than Q and M allele carriers. Paraoxonase and arylesterase activities in individuals with the QQ+(MM or LM) genotype were significantly lower than those with the (RR or QR)+LL genotype. Furthermore, basal and salt-stimulated paraoxonase activity in veterans with the (RR or QR)+LL genotype was significantly lower than that in the controls. A positive correlation has been determined between serum PON1 activity and pulmonary function test in QR/LL genotypes. Some of the veterans with RR+QR genotypes have also shown a novel missense change of Asn227Ser in exon 6 of the enzyme. This substitution is close to the binding domain of PON1 and so modifies enzyme activity.