IgG accumulates in inhibitory hippocampal neurons of experimental antiphospholipid syndrome

Mice immunized with β₂-glycoprotein I (β₂GPI) are an experimental model of the antiphospholipid syndrome (eAPS) displaying elevated titers of antiphospholipid antibodies (aPL). We presently studied whether the behavioral hyperactivity in eAPS mice is associated with in vivo binding and accumulation of IgG in the brain. At 6 weeks post immunization eAPS mice had significantly higher levels of aPL (1.32 ± 0.28 and 0.02 ± 0.01 AU, p < 0.001 by t-test) compared to adjuvant immunized controls, as measured by ELISA. Significant hyperactivity in a staircase test in the eAPS mice compared to controls was found in stair-climbing (18.4 ± 0.9 and 12.0 ± 1.7, respectively) and rearing measures (23.5 ± 2.1 and 12.5 ± 1.9, p < 0.01 by t-test). Immunofluorescence staining in eAPS mice revealed significant in vivo accumulation of IgG in cortical and hippocampal neurons which was not seen in controls. Staining for IgG was markedly intense in inhibitory interneurons co-stained for GAD67 in the hippocampus of eAPS mice. The integrity of the blood brain barrier (BBB) evaluated by injection of Evans blue (EB) was impaired in eAPS and adjuvant immunized mice compared to naïve mice. Electrophysiological recordings in hippocampal brain slices showed altered response to paired pulse stimulation as well as dysregulation of carbachol-induced γ- oscillations in eAPS mice compared to control. Penetration into the brain and direct interaction of aPL with inhibitory interneurons in the hippocampus may explain the hyperactive behavior of the eAPS mice. A direct role of aPL in causing CNS dysfunction points to these antibodies as an important therapeutic target in APS.     

8-Isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as markers of inflammation and oxidative stress in antiphospholipid syndrome: a pilot study

Objective

To test the inflammation and oxidative stress hypothesis in antiphospholipid syndrome (APS) patients and to identify possible associations with clinical and laboratory features of the disease.

Methods

Serum amyloid A (SAA), C-reactive protein (CRP), 8-isoprostane and prostaglandin E2 (PGE) were assayed in the sera of 45 APS patients and then compared to control groups made up of 15 antiphospholipid antibody (aPL) negative patients with systemic lupus erythematosus, 15 aPL negative subjects with pregnancy-related morbidity, 15 aPL negative patients with thrombosis, 15 subjects with persistently positive aPL with no signs or symptoms of APS, and 15 healthy volunteers from among the hospital staff.

Results

APS patients showed significantly higher CRP (p?=?0.01), SAA (p?p?=?0.05) and PGE2 (p?=?0.001) plasma levels as compared to controls. Among APS subjects, significantly higher 8-isoprostane and PGE2 levels were observed in patients with triple positivity for aPL (lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies) compared to APS patients with single or double aPL positivity.

Conclusion

Both inflammation and oxidative stress, as measured by SAA, CRP, 8-isoprostane and PGE2, occur in APS and seem to be related to triple positivity for aPL.     

Persistence of antiphospholipid antibodies over time and its association with recurrence of clinical manifestations: A longitudinal study from a single centre

PurposeTo analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL persistence over time.Patients and methods200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-β2 glycoprotein-I (aβ2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used.Results112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity [OR 78 (95%CI 16.9–359.7, p < 0.001)] and double aPL positivity [OR = 7.6 (95%CI 3.7–15.7, p < 0.001)] correlated with persistent aPLs over time, while isolated LAC [OR = 0.26 (95% CI 0.08–0.49, p = 0.002)] or isolated IgG/IgM aCL [OR = 0.20 (95% CI 0.11–0.59, p = 0.004)] positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs [OR = 2.48 (95%CI 1.34–4.58, p = 0.003)].ConclusionsMore than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.     

A complex dietary supplement modulates nitrative stress in normal mice and in a new mouse model of nitrative stress and cognitive aging

We examined whether transgenic growth hormone mice (Tg) that exhibit accelerated cognitive aging and exceptional free radical damage also express elevated nitrative stress. We characterized age-related patterns of 3-nitrotyrosine (3-NT) in brain homogenate and mitochondria of Tg and normal (Nr) mice as modulated by a complex anti-aging dietary supplement. Levels of 3-NT rose rapidly with age in Tg brain homogenate whereas normal controls maintained constant lower levels. The age-related slope for 3-NT was 3.6-fold steeper in untreated Tg compared to treated Tg (p < 0.009), although treated Tg showed elevation in youth. Opposite to Tg, treated Nr mice had reduced 3-NT in youth (p < 0.02).The age-related pattern of mitochondrial 3-NT in Nr mice was parabolic (p < 0.005). Remarkably, levels in treated Nr were reduced by ∼50% (p < 0.0007). Untreated Tg showed strongly increasing mitochondrial 3-NT with higher mitochondrial activity (p < 0.01) whereas treated Tg showed lower nitrosylation at higher levels of mitochondrial activity. Tg mice also expressed a postural abnormality that is a biomarker of neurodegeneration and/or nitrative stress. Tg represent a promising new model of nitrative stress associated with brain deterioration and results provide proof of principle that complex dietary supplements may be ameliorating.     

Risperidone alters food intake, core body temperature, and locomotor activity in mice

Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p = 0.050) and gained more weight (p = 0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p = 0.046), but not body temperature (p = 0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p = 0.0001), and tended to be higher during the dark phase (p = 0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p = 0.006); there were no differences in activity during the light phase (p = 0.47). UCP1 (p < 0.01) and UCP3 (p < 0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p < 0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.     

Knee kinematics during walking at different speeds in people who have undergone total knee replacement

People who have undergone total knee replacement (TKR) experience difficulties in some daily activities including walking. Walking at faster speeds requires more knee flexion and may therefore present a greater challenge following TKR. The aim of this study was to compare the knee kinematics of patients following TKR and unimpaired controls during comfortable and fast walking speeds. Forty patients (22 women, 18 men) 12 months following TKR and 40 control participants (matched for age and sex) were assessed during walking at self-selected comfortable and fast speeds using three dimensional motion analysis. The group averages of spatiotemporal and peak kinematic characteristics in the sagittal, coronal and transverse movement planes were compared using univariate analysis of variance with walking speed as a co-variate. The TKR group walked with significantly reduced cadence (p < 0.001 at both speeds) and reduced stride length (p < 0.001 at both speeds), less knee flexion during stance and swing phases (p < 0.001 for both speeds) and less knee extension during stance phase (p < 0.024 for comfortable speed; p < 0.042 for fast speed). The TKR group also walked with less peak knee external rotation than controls at both speeds (p < 0.001 for both speeds). Both groups increased their velocity, cadence and stride length by a similar proportion when walking at fast speed. When walking at a faster speed, spatiotemporal gait parameters and knee motion are altered in a similar manner for both TKR patients and controls. However, at both walking speeds, TKR patients exhibit residual deficits 12 months following surgery.     

Abdominal pain in patient with antiphospholipid syndrome—the role of MDCT angiography on visceral blood vessels

Antiphospholipid syndrome (APS) is an autoimmune disease defined by accelerated atherosclerosis, arterial and venous thrombosis, fetal loss, and the presence of antiphospholipid antibodies (aPL) in the serum and which leads to the occurrence of various vascular events. Nonspecific abdominal pain can be one of the symptoms due to changes on visceral blood vessels. The goal of our work is to show the results we obtained in multidetector computed tomography (MDCT) angiography examination of visceral arteries, comparing patients with primary antiphospholipid syndrome (PAPS) and secondary antiphospholipid syndrome (SAPS) with control group. In this study, we analyzed 50 patients with primary PAPS and 50 patients, with secondary SAPS. The results were compared to 50 patients in the control group. The groups were compared in terms of age, gender, and the most common risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. The study was conducted on 64-MDCT, on which we analyzed quantitative and morphological characteristics of the blood vessel lesions. Patients from the control group had statistically significant elevation of cholesterol and triglyceride levels compared to the patients with SAPS and PAPS (p?<?0.001 and p?<?0.05). The results showed that the frequency of changes is statistically (p?<?0.05 and p?<?0.001) more common in patients with PAPS and SAPS than in the control group. Statistically significant difference between the groups was found in superior and inferior mesentery arteries. Analyzing the number of lesions, there was statistically high difference between the patients with one and two lesions than in patients with four or more lesions (p?<?0.001), lower difference compared to the patients with three lesions (p?<?0.01), while there was low, but yet statistically important difference between the patients with three lesions and those with five or more blood vessel lesions (p?<?0.05). Analyzing percentage of diameter stenosis, we established that the lesions in the groups of 0–30% diameter stenosis (DS) and 30–50% DS in patients with PAPS (n?=?42) and SAPS (n?=?44) are more common than in the control group (n?=?18, p?<?0.05). Analyzing the qualitative characteristics of plaques, we established significantly higher frequency of soft tissue and mixed lesions than calcified ones in patients with PAPS and SAPS (p?<?0.001; p?<?0.05). Our study showed that the subclinical manifestation of the changes on visceral arteries is more common in patients with APS. Patients with abdominal pain were those with two or more lesions, and according to our results, majority had PAPS. Because of its safety and accuracy, the method of choice is MDCT angiography in monitoring the progression of disease.     

Genetic variations of SOCS1 are associated with chronic hepatitis B virus infection

Suppressor of cytokine signaling (SOCS)-1 is involved in viral infection through regulation of both innate and adaptive immunity. The SOCS1 gene polymorphisms may affect the outcome of viral infection. The relationship between SOCS1 polymorphisms and hepatitis B virus (HBV) infection has not yet been explored. This study genotyped SOCS1 rs243327 and rs33932899 polymorphisms in 477 patients with chronic HBV infection, 93 HBV infection resolvers and 215 healthy controls. In statistical analysis, p-values less than 0.05 in multiple comparisons were corrected by Bonferroni method and presented as p_c. The results showed that the allele T-containing genotypes (CT + TT) of rs243327 were higher in HBV patients than resolvers and lower in resolvers than healthy controls although the difference was not significant. The allele T of rs243327 was significantly lower in resolvers than controls (p = 0.033). The genotype GC and allele C of rs33932899 were significantly less frequent in HBV patients than controls (p_c < 0.001 and p < 0.001, respectively). The haplotype T/G of rs243327/rs33932899 was significantly more frequent in HBV patients than resolvers (p_c < 0.001) or controls (p_c = 0.009). These data indicate that SOCS1 polymorphisms might affect the susceptibility and outcome of HBV infection.     

Clinical and medial temporal features in a family with mood disorders

It is debated whether non-affected relatives of patients with affective disorders share a specific brain structure endophenotype. Aim of this work is to explore the medial temporal morphology in affected and non-affected members of a family with mood disorders. Hippocampi and amygdalae were manually traced from the 3D magnetic resonance imaging of five affected family members, 10 non-affected relatives, and 15 unrelated matched controls. Affected and non-affected relatives were characterized by larger left amygdalae (18%, p = 0.030), smaller right hippocampus (up to 18%, p < 0.0005), and reduced hippocampal asymmetry (p < 0.001) than controls. Abnormal, albeit non significant, positive correlations of MTL volumes with age were observed, with the exception of smaller volume of the left hippocampus with advancing age (r = −0.76) in the affected relatives. These data add to the evidence that abnormal medial temporal structures may constitute an endophenotype for affective disorders.     

Induction of Experimental Antiphospholipid Antibody Syndrome in PL/J Mice Following Immunization With β2GPI

PROBLEM: Immunization with β₂-glycoprotein I (β₂GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/++ mice following immunization with β₂GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of β₂GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week-old female PL/J mice (12 per group) were studied. Group A was immunized with β₂GPI and group B with ovalbumin; group C was not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72±0.6 and 0.699±0.25 for group A, 0.091 ±0.040 and 0.230±0.47 for group B, and 0.0435±0.003 and 0.119±0.026 for group C (comparing group A with groups B and C combined, P<0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P<0.001). The platelet counts were not significantly different among the three groups. The litter size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, and only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for β₂GPI-induced aPL in the development of experimental models of APS in PL/J mice.     

Age-related changes in dorsal root ganglia,circulating and vascular calcitonin gene-related peptide (CGRP) concentrations in female rats: Effect of female sex steroid hormones

The aim of the present study is to investigate whether immunoreactive (I) calcitonin gene-related peptide (CGRP) content is decreased in plasma and mesenteric arteries (resistance arteries) in middle-aged rats and if so, whether sex steroid hormones enhance I-CGRP in middle-aged female rats. We also examined whether vascular CGRP receptor components, calcitonin receptor like receptor (CRLR) and receptor activity modifying protein 1 (RAMP₁) are elevated by sex steroid hormones treatment in middle-aged female rats. Young adult (3 months old) and middle-aged (10–12 months old) ovariectomized rats were treated subcutaneously with estradiol-17β (E₂; 2 mg), progesterone (P₄; 5 mg), E₂ + P₄ (2 mg + 20 mg) or placebo (control). Radioimmunoassay and Western blot analysis were performed to measure I-CGRP content and CGRP receptor components in dorsal root ganglia (DRG), in resistance arteries and in plasma. Immunofluorescent staining methods were employed to determine cellular localization of CRLR, RAMP₁ in resistance arteries. Our data demonstrated that I-CGRP content was significantly (p < 0.05) lower in the plasma and resistance arteries of middle-aged female rats compared to young controls. Both RAMP₁ and CRLR were concentrated in vascular endothelium and the underlying smooth muscle cells. RAMP₁ but not CRLR appeared to be decreased in middle-aged rat vasculature. Chronic perfusion of sex steroid hormones to ovariectomized rats: (1) significantly (p < 0.05) elevated I-CGRP in the DRG and in the plasma, and (2) significantly elevated RAMP₁ (p < 0.05) but did not alter CRLR in resistance arteries. These data suggest that female sex steroid treatment enhances I-CGRP and its receptors, and thus regulate the blood pressure in aged female rats.     

The emerging role of multiple antiphospholipid antibodies positivity in patients with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by clinical symptoms of vascular thrombosis and/or pregnancy morbidity in the presence of autoimmune antiphospholipid antibodies (aPL). Current laboratory APS criteria include the presence of at least one of the three relevant aPL: lupus anticoagulant, anticardiolipin antibodies and anti-β₂ glycoprotein I antibodies. Therefore, patients could have a single aPL pattern or combinations of aPL. Evidence arising from clinical experience indicates that patients having the highest aPL titer and simultaneous aPL detected by different tests have a worse prognosis and a higher probability of recurrence of the APS clinical features. In recent years, an emerging role of multiple aPL positivity in the identification of high-risk patients with aPL/APS is evident. This paper will review the current knowledge on the clinical relevance of having single or multiple aPL positivity.     

Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer

Objective

Whether moderate to severe obesity (body mass index (BMI) ≥ 30 to <40 kg/m²) contributes to breast cancer recurrence and mortality remains uncertain.

Subjects and methods

1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.

Results

Of the 1155 included women, mean age, 58.4 ± 11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR = 1.71, 95%CI, 1.12–2.62, p = 0.014), disease beyond Stage 1 (HR = 2.87, 95% CI 1.73–4.75, p < 0.001), OAET (HR = 0.26, 95%CI 0.14–0.46, p < 0.001), mastectomy (HR = 3.28, 95%CI 1.98–5.44, p < 0.001) and radiotherapy (HR = 2.12, 95%CI 1.24–3.63, p = 0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48–7.03, p = 0.003) and OAET use (HR 0.41, 95%CI 0.17–0.98, p = 0.046) were significantly associated with an event.

Conclusion

Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment.     

Immunoglobulins from sera of antiphospholipid syndrome patients are internalized in the HTR-8/SVneo cell line and cytotrophoblast in culture

Women with antiphospholipid syndrome (APS) experience pregnancy complications mostly due to impaired trophoblast cell functions. Antiphospholipid antibodies (aPL) affect extravillous trophoblast in vivo and in culture, but the mechanisms are still poorly understood. Previously, syncytiotrophoblast was shown to bind and internalize aPL, which was not replicated for extravillous cytotrophoblast in short term culture. Here, aPL binding and time dependent internalization was demonstrated with exposure to aPL in the extravillous cell line HTR-8/SVneo and isolated first trimester of pregnancy cytotrophoblast (CT) using immunocytochemistry and flow cytometry. Intracellular aPL were detectable from 2?h of culture, reaching 30.7?±?3.1% (p?<?0.001) positive cells in CT and 24.8?±?7% (p?<?0.01) in HTR-8/SVneo cells at 24?h and 33?±?4.2% (p?<?0.01) at 48?h. The data presented show that extravillous trophoblast cells internalize aPL in a time-dependent manner significantly more than control immunoglobulins after 24?h of exposure.     

Low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression

Objectives

To investigate the low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression.

Methods

Cross-sectional study with 180 women aged between 19 and 60 years who admitted to our outpatient clinic. Sexual function was assessed by female sexual function index and clinically significant depression was measured by Beck depression inventory test.

Results

The rate of low sexual function was 85.9% in postmenopausal (OR 2.9, 95% CI 1.8–4.8) and 47.7% in premenopausal women (OR 0.4, 95% CI 0.3–0.5) (p < 0.0001). The postmenopausal group reported significantly lower desire, arousal, lubrication, orgasm, satisfaction and pain scores than controls (p < 0.0001, for all of them). Low sexual function was positively correlated with age (r = 0.37, p < 0.0001), menopausal status (r = 0.40, p < 0.0001), gravidity (r = 0.44, p < 0.0001), parity (r = 0.43, p < 0.0001), abortion rates (r = 0.27, p = 0.001) and marriage period (r = 0.40, p < 0.0001). There were also significant negative correlations between low sexual function and education (r = −0.39, p < 0.0001) and family income (r = −0.29, p < 0.0001). However, multivariate regression analysis demonstrated that education, family income and menopausal status were the only independent variables for low sexual function after adjusted for age, gravidity, parity, abortion, marriage period and menopausal status.

Conclusion

Low sexual function was relatively high in postmenopausal women without clinically significant depression. Education, family income and menopausal status were the independent risk factors for low sexual function. Investigation of female sexuality was essential for these patients.     

The Catastrophic Antiphospholipid Syndrome in Serbia: Diagnostic and Management Problems

Antiphospholipid antibodies (aPL) are a common cause of acquired thrombophilia, termed antiphospholipid syndrome (APS, Huges syndrome). Catastrophic antiphospholipid syndrome (CAPS, Asherson’s syndrome) is an unusual form of APS characterized with multi-organ failure and high mortality. Fortunately, CAPS accounts for less than 1% of APS cases. The recurrence rate is low with a stable clinical course if these patients are treated with adequate anticoagulation therapy. Due to the rarity of the condition, an international registry of CAPS patients was created in 2000 supported by the European Forum on Antiphospholipid Antibodies held in Taormina, Italy at the Tenth International Congress on aPL. The objective of our study is to describe characteristics of 12 Serbian patients with CAPS included in the international CAPS registry.     

Circulating levels of GDNF in bipolar disorder

Neurotrophic factors regulate the survival and growth of neurons, and influence synaptic efficiency and plasticity. Several studies suggest the existence of a relationship between changes in neurotrophic levels and bipolar disorder (BD). The glial cell-line derived neurotrophic factor (GDNF) influences monoaminergic neurons and glial cells, but its role in BD patients is controversial. In order to elucidate it we evaluated plasma levels of GDNF in a sample of 70 BD patients (35 in mania and 35 in euthymia) and compared with 50 healthy controls matched for age, gender and educational levels. GDNF plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were assessed by a Mini-International Neuropsychiatric Interview (MINI-plus), Young Mania and Hamilton Depression Rating Scales. Plasma GDNF levels were significantly increased in BD patients in euthymia compared with BD patients in mania and healthy controls (p < 0.05). GDNF plasma levels were correlated with age (ρ = 0.30, p < 0.05) and negatively correlated with manic symptoms in BD patients (ρ = −0.54, p < 0.05). Our results provide evidence that peripheral levels of GDNF are related with different mood states in BD, reinforcing the involvement of neurotrophic factors in its physiopathology.     

Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index

Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa.The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514 ± 2.03) and I-GCa (6.836 ± 2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071 ± 2.07; p = 0.0005, p < 0.0001). In addition, the mean GCRI for the I-GCa group was significantly greater than that for the D-GCa group (p < 0.005). The GCRI-positive rate was significantly higher in subjects with GCa than in H. pylori-positive controls (D-GCa: p < 0.005, I-GCa: p < 0.0001).Many H. pylori-positive Japanese still carry a high risk for gastric cancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI.     

The role of MSCT angiography in early detection of lower limb arterial lesions in patients with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease which is characterized by arterial and venous thromboses, fetal loss, and the presence of antiphospholipid antibodies in the serum. It is characterized by accelerated atherosclerosis. Increased tendency towards thrombosis leads to the occurrence of various vascular events. The objective of our study was to determine if there are subclinical changes on lower limb arteries in APS patients and what the best diagnostic choice for their establishment is. In this study, we analyzed 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients, who have secondary antiphospholipid syndrome (SAPS). The results were compared to 50 controls. The groups were comparable with respect to age, gender, and traditional risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. Study was conducted on 64-multi-slice computed tomography (64-MSCT), where we analyzed quantitative and morphological characteristics of blood vessel-detected lesions. Patients from the control group had statistically very significant elevated cholesterol and triglyceride levels in regard to the patients with SAPS and PAPS (p < 0.001 and p < 0.05). Analyzing percentage of diameter stenosis, we have established that lesions from group with 0–30% diameter stenosis (DS) in patients with PAPS (n = 47) and SAPS (n = 39) are more common than that in control group (n = 3, p < 0.001). The incidence of lesions higher than 70% DS in control group (n = 74) was statistically significant than that in patients with SAPS (n = 74, p < 0.05), while very statistically significant than that in patients with PAPS (n = 48, p < 0.001). Analyzing the qualitative characteristics of plaques, we have established significant higher frequency of soft tissue (n = 32) and mixed lesions (n = 36) in patients with PAPS than the calcified one (n = 7, p < 0.001). Our study showed that the subclinical manifestation of changes on lower extremity arteries is more common in patients with APS. Because of its safety and accuracy, the method of choice is 64-MSCT angiography in monitoring disease progression.     

Association of viral load with HPV16 positive cervical cancer pathogenesis: Causal relevance in isolates harboring intact viral E2 gene

We tested the hypothesis that cervical cancers (CaCx) harbor high HPV16 viral load compared to controls and this is influenced by E2 status and age of subjects. Viral load (natural log transformed values) per 100 ng genomic DNA was estimated (152 cases and 87 controls) by Taqman assay. Median viral load was significantly higher (Mann-Whitney U test) among cases (17.21) compared to controls (9.86), irrespective of E2 status or upon considering E2 status as a covariate in logistic regression model (p < 0.001). Viral load of E2 intact cases (17.80) was significantly higher (p < 0.001) compared to those with disrupted E2 (9.78). At equivalent probability of being a case, viral load was higher among individuals (i) of lower age, irrespective of E2 status, and (ii) with intact E2 but of similar age as those with disrupted E2. Thus viral load in association with E2 status and/or age might be of causal relevance in CaCx pathogenesis.