Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD50 values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opuntia ficus indica seeds were extracted and analyzed for its chemical and physical properties such as acid value, free fatty acid percentage (% FFA), iodine index, and saponification value as well as refractive index and density. LD50 values obtained by single doses, orally and intraperitoneally administered in mice, were respectively 43 ± 0,8 ;[40.7– 45.4 ] ml/kg body wt. p.o. and 2.72 ± 0,1 ;[2.52–2.92] ml/kg body wt. i.p. for Opuntia ficus indica ; and 37 ± 1 ;[34.4 − 39.8 ] ml/kg body wt. p.o. and 2.52 ± 0,2 ;[2.22 − 2.81 ] ml/kg body wt. i.p. for Pistacia lentiscus respectively. The yields of seed oil were respectively calculated as 20.25% and 10.41%. The acid and free fatty acid values indicated that the oil has a low acidity
Opuntia ficus indica L.; Pistacia lentiscus L.; seed oil; acute toxicity
Objective: Iodine deficiency and excess are the most important factors that affect screening and recall rates of congenital hypothyroidism. The purpose of this study was to investigate the urinary iodine status in newborns and their mothers and its effects on neonatal thyroid-stimulating hormone (TSH) levels in a mildly iodine-deficient area.
Methods: A total of 116 newborns and their mothers were included in the study. Urinary iodine levels were measured from healthy mothers and their babies on the 5th day following birth. Neonatal TSH levels were screened, and TSH and free thyroxine (fT4) levels were measured on the15th day in the recall cases. T4 treatment was started in infants with high TSH and low fT4 levels. These measurements were repeated on the 30th day in these newborns.
Results: Ninety-nine percent of the mothers included in the study were using iodized salt. The median urinary iodine level in the newborns was 279 µg/L, while it was 84 µg/L in their mothers. The rate of iodine deficiency among the mothers was 56.8%, and the rate of iodine excess was 8.6%. This rate was 10.3% for iodine deficiency and 61.2% for iodine excess in the newborns. The recall rate at the screening was 9.5% (n=11). The urinary iodine levels were above 200 µg/L in three newborns who had transient hyperthyrotropinemia.
Conclusions: Iodine deficiency was more frequently observed in nursing mothers, and iodine excess was more frequently seen in their newborns. The iodine excess noted in the newborns was attributed to the use of antiseptics containing iodine. The iodine excess leads to increases in recall rates, screening costs, and frequency of transient hyperthyrotropinemia.
Conflict of interest:None declared.
Urinary iodine; maternal; neonatal; screening; hyperthyrotropinemia
[18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared.
Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors.
Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation.
This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666.
Dosimetry; Preclinical microPET; Organ harvesting; SV2
This study aimed to evaluate the influence of hormonal receptor and Ki-67 proliferation marker in predicting MRI accuracy of measuring residual tumor size in HER2 negative breast cancer receiving neoadjuvant chemotherapy (NAC).
Fifty-four women were studied. Patients received AC and/or taxane-based regimens. The accuracy of MR determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathology-diagnosed tumor size using Pearson’s correlation.
MRI correctly diagnosed 16 of the 17 pCR patients. There were 8 false negative diagnoses, 7 hormonal receptor (HR) positive and one HR negative. The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI-pathology tumor size correlation, HR negative cancers showed a higher correlation (R=0.79) than HR positive cancers (R= 0.58). A worse MRI-pathology size discrepancy was found in HR positive cancer than in HR negative cancer (1.6±2.8 cm vs. 0.56±0.9 cm, p=0.05). Tumors with a low Ki-67 proliferation (<40%) showed a larger size discrepancy than those with a high Ki-67 proliferation (≥40%) (1.2±2.0 cm vs. 0.4±0.8 cm p=0.05).
The results showed that the diagnostic performance of MRI for breast cancer undergoing NAC is associated with molecular biomarker profile. Among HER2 negative tumors, the accuracy of MRI was worse in HR positive than negative cancers, and also worse in low proliferative than high proliferative tumors. These findings may help in surgical planning.
Brucellosis is a zoonosis that affects several organs. The spine is the most common site of musculoskeletal involvement. However, multiple-level spinal involvement is rare in brucella spondylodiscitis. The authors report a case of a 56-year-old male shepherd who had developed a spondylodiscitis affecting simultaneously the cervical, thoracic and lumbar regions. The diagnosis was established by using MRI after the brucella-agglutination test was found to be positive. A high degree of suspicion in the diagnosis of brucellar spondylodiscitis is essential to reduce the delay for the treatment. Thus, it should be essentially included in the differential diagnosis of longstanding cervical, thoracic or back pain, particularly in regions where brucellosis is endemic. Screening serological tests for brucella should be used more widely in cases with low index of suspicion, especially in endemic areas.
The antifungal activity of selenium nanoparticles (Se NPs) prepared by Klebsiella pneumoniae has been reported previously for different fungi. In the present study, freshly prepared Se NPs produced by K. pneumoniae were purified and characterized by transmission electron microscopy and Energy-Dispersive X-ray spectroscopy (EDS) and its post antifungal effects for two fungi were evaluated.
Materials and Methods
The minimum inhibitory concentrations (MICs) of Se NPs, determined by serial dilution were 250 µg/ml for Aspergillus niger and 2,000 µg/ml for Candida albicans. The effect of exposure of A. niger and C. albicans to Se NPs on later growth was evaluated by incubating the fungi for 1 hour at 25 °C in media containing 0, 1, 2 and 4 x MIC of Se NPs and diluting the cultures 100 times with Se free medium. The kinetics of growth of the fungi in control cultures and in non-toxic Se NPs concentration of, 0.01 × MIC, 0.02 × MIC or 0.04 × MIC were measured.
The exposure of A. niger and C. albicans to 2 and 4 x MIC of Se NPs stimulated the growth of both fungi in the absence of toxic concentrations of Se. The strongest stimulation was observed for A. niger.
It is concluded that exposure to high concentration of the Se NPs did not have any post-inhibitory effect on A. niger and C. albicans and that trace amounts of this element promoted growth of both fungi in a dose- dependent-manner. The role of nanoparticles serving as needed trace elements and development of microorganism tolerance to nanoparticles should not be dismissed while considering therapeutic potential.
Selenium nanoparticle; Aspergillus niger; Candida albicans; Antifungal activity
In addition to being a risk factor for breast cancer, breast density has been
hypothesized to be a surrogate biomarker for predicting response to
endocrine-based chemotherapies. The purpose of this study was to evaluate whether
a noninvasive bedside scanner based on diffuse optical spectroscopic imaging
(DOSI) provides quantitative metrics to measure and track changes in breast tissue
composition and density. To access a broad range of densities in a limited patient
population, we performed optical measurements on the contralateral normal breast
of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI
parameters, including tissue hemoglobin, water, and lipid concentrations, were
obtained and correlated with magnetic resonance imaging (MRI)-measured
fibroglandular tissue density. We evaluated how DOSI could be used to assess
breast density while gaining new insight into the impact of chemotherapy on breast
This was a retrospective study of 28 volunteers undergoing NAC treatment for
breast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtained
from the contralateral normal breast before and during NAC. Longitudinal DOSI
measurements were used to calculate breast tissue concentrations of oxygenated and
deoxygenated hemoglobin, water, and lipid. These values were compared with
MRI-measured fibroglandular density before and during therapy.
Water (r = 0.843; P < 0.001), deoxyhemoglobin (r =
0.785; P = 0.003), and lipid (r = -0.707; P = 0.010)
concentration measured with DOSI correlated strongly with MRI-measured density
before therapy. Mean DOSI parameters differed significantly between pre- and
postmenopausal subjects at baseline (water, P < 0.001;
deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC
treatment measured at about 90 days, significant reductions were observed in
oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and
postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration
for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline.
Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and
water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6).
Percentage change in water at the end of therapy compared with baseline correlated
strongly with percentage change in MRI-measured density (r = 0.864; P
DOSI functional measurements correlate with MRI fibroglandular density, both
before therapy and during NAC. Although from a limited patient dataset, these
results suggest that DOSI may provide new functional indices of density based on
hemoglobin and water that could be used at the bedside to assess response to
therapy and evaluate disease risk.
A “novel” protocol is presented for easy and reliable estimation of soluble hydroxycinnamate levels in Cichorium intybus L. leaf tissue in large-scale experiments. Samples were standardized by punching 6 discs per leaf, and hydroxycinnamates were extracted by submerging the discs in 80% ethanol with 5% acetic acid for at least 48 h in the darkness at 4°C. Residual dry mass of the discs was used for a posteriori correction of compound levels. Chlorophyll was eliminated by chloroform, and the aqueous phases were transferred to microplates, dried, and dissolved in 50% methanol for HPLC analysis and storage. An HPLC program of 8 min was developed for the analysis of the extracts. Comparisons with extractions of liquid nitrogen powders indicated that the novel extraction method was reliable. No degradation of the major hydroxycinnamates—caftaric, chlorogenic, and chicoric acids—was observed, during maceration at ambient temperatures, or after storage for 1 year.
Breast MRI acquires many images from the breast, and computer-aided algorithms and display tools are often used to assist radiologist’s interpretation. Women with lifetime risk greater than 20% in developing breast cancer are recommended to receive annual screening MRI, but the current breast MRI computer-aided-diagnosis systems do not provide the necessary function for comparison of images acquired at different times. The purpose of this work was to develop registration methods for evaluating the spatial change pattern of fibroglandular tissue between two breast MRI scans of the same woman taken at different times. The registration method is based on rigid alignment followed by non-rigid Demons algorithm. The method was tested in 3 different subjects who had different degree of changes in the fibroglandular tissue, including two patients who showed different spatial shrinkage patterns after receiving neoadjuvant chemotherapy before surgery, and one control case from a normal volunteer. Based on the transformation matrix, the collapse of multiple voxels on the baseline images to one voxel on the follow-up images is used to calculate the shrinkage factor. Conversely, based on the reverse transformation matrix the expansion factor can be calculated. The shrinkage/expansion factor, the deformation magnitude and direction, as well as the Jacobian determinate at each location can be displayed in a 3D rendering view to show the spatial changes between two MRI scans. These different parameters show consistent results, and can be used for quantitative evaluation of the spatial change patterns. The presented registration method can be further developed into a clinical tool for evaluating the therapy-induced changes and for early diagnosis of breast cancer in screening MRI.
Mycetoma or Maduramycosis is a localized chronic suppurative infection characterized by exuberant granulation tissue, discharging sinuses, and bone involvement later in the course of the disease. Early clinical diagnosis before the appearance of sinuses and grains (aggregates of organism surrounded by granulation tissue, which are discharged from the draining sinuses) is difficult. Delay in diagnosis may lead to amputation of the affected part. Definitive diagnosis is through biopsy and microbiological examination. However, at times diagnosis may still be difficult. The recently described “dot in circle” sign on magnetic resonance imaging (MRI) is easy to recognize and highly specific. We present a case of mycetoma foot with characteristic MRI features.
Dot in circle sign; maduramycosis; MRI; mycetoma
To investigate the effects of body mass index (BMI) on intraocular pressure (IOP) and ocular pulse amplitude (OPA).
Totally 140 healthy individuals without any systemic diseases were included in the study. BMI (kg/m2) was calculated for every individual. IOP and OPA were measured with Pascal Dynamic contour tonometer (DCT). Blood pressure was also measured along with the DCT. The patients were divided into three groups according to BMI as: Group1, BMI<25; Group2, 25≤BMI<30; Group3, BMI≥30. Mean values of IOP, OPA, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were used in statistical analysis.
In Group1, the means of IOP, OPA, were 16.8±2.3mmHg, 2.7±0.7mmHg respectively; and SBP, DBP were 120.0±6.1mmHg, and 77.4±5.6mmHg respectively. In group2, the mean IOP, OPA, SBP, and DBP were found to be 16.6±2.1mmHg, 2.4±0.7mmHg, 121.7±5.3mmHg, and 79.5±4.9mmHg respectively. In group3, the mean IOP, OPA, SBP, and DBP were found to be 17.3±1.7mmHg, 2.1±0.7mmHg, 122.4±5.7mmHg, and 79.7±5.2mmHg respectively. There were no statistically significant difference between groups in terms of IOP, SBP and DBP, while OPA values were significantly lower in group3 (P=0.001).
Decreased OPA values in individuals with higher BMI may indicate that subjects with higher BMI have lower choroidal perfusion and lower ocular blood flow.
body mass index; choroidal perfusion; intraocular pressure; ocular pulse amplitude; obesity
Regulatory CD8+ T cells are critical for self-tolerance and restricting excessive immune responses. The variety of immune functions they fulfill, the heterogeneity of their phenotype, and the mechanism of action are still poorly understood. Here we describe that regulatory CD8+ T cells exhibiting immunosuppressive actions in vitro and in vivo are recognized as CD38high T cells and present in naive mice. CD38 is a glycosylated membrane protein with ectonucleotidase properties. CD8+CD38high (CD44+CD122+CD62Lhigh) lymphocytes suppress CD4+ effector T-cell proliferation in an antigen-non specific manner via IFN-γ. While direct cell-to-cell contact is needed for this suppressor activity, it is independent of membrane-bound TGF-β and granzyme B release. IL-15 potentiates the suppressive activity of CD8+CD38high T cells and controls their survival and expansion. In humans CD8+CD38high T cells inhibit CD4+ effector T cell proliferation. In vivo, CD8+CD38high, but not CD8+CD38− T cells mitigate murine experimental autoimmune encephalomyelitis (EAE) by reducing the clinical score and delaying disease occurrence. EAE suppression is enhanced by pre-treatment of CD8+CD38high T cells with IL-15. These findings add evidence that the expression of ectoenzyme receptor family members positively correlates with suppressor functions and identifies CD8+CD38high T cells as potential inhibitors of excessive immune responses.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state 18F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.
FDG uptake; neurosurgery; Parkinson's disease; positron emission tomography; SUV
Medical training is often regarded as a stressful period. Studies have previously found that 21.6%–50% of medical students experience significant psychological distress. The present study compared the prevalence and levels of psychological distress between 2 cohorts of first-year medical students that underwent different admission selection processes.
A comparative cross-sectional study was conducted by comparing 2 cohorts of first-year medical students; 1 group (cohort 1) was selected based purely on academic merit (2008/2009 cohort) and the other group (cohort 2) was selected based on academic merit, psychometric assessment, and interview performance (2009/2010 cohort). Their distress levels were measured by the General Health Questionnaire, and scores higher than 3 were considered indicative of significant psychological distress.
The prevalence (P = 0.003) and levels (P = 0.001) of psychological distress were significantly different between the 2 cohorts. Cohort 1 had 1.2–3.3 times higher risk of developing psychological distress compared to cohort 2 (P = 0.007).
Cohort 2 had better psychological health than cohort 1 and was less likely to develop psychological distress. This study provided evidence of a potential benefit of multimodal student selection based on academic merit, psychometric assessment, and interview performance. This selection process might identify medical students who will maintain better psychological health.
medical; psychology; school admission criteria; student
Environmental heterogeneity influences coevolution and local adaptation in host–parasite systems. This also concerns applied issues, because the geographic range of parasites may depend on their capacity to adapt to abiotic conditions. We studied temperature-specific adaptation in the wheat yellow/stripe rust pathogen, Puccinia striiformis f.sp. tritici (PST). Using laboratory experiments, PST isolates from northern and southern France were studied for their ability to germinate and to infect bread and durum wheat cultivars over a temperature gradient. Pathogen origin × temperature interactions for infectivity and germination rate suggest local adaptation to high- versus low-temperature regimes in south and north. Competition experiments in southern and northern field sites showed a general competitive advantage of southern over northern isolates. This advantage was particularly pronounced in the southern ‘home’ site, consistent with a model integrating laboratory infectivity and field temperature variation. The stable PST population structure in France likely reflects adaptation to ecological and genetic factors: persistence of southern PST may be due to adaptation to the warmer Mediterranean climate; and persistence of northern PST can be explained by adaptation to commonly used cultivars, for which southern isolates are lacking the relevant virulence genes. Thus, understanding the role of temperature-specific adaptations may help to improve forecast models or breeding programmes.
climate change; genotype × environment interaction; local adaptation; plant pathogen; Puccinia striiformis f.sp. tritici; temperature adaptation; wheat; yellow/stripe rust
Background and Purpose. Dry socket syndrome is one of the most irritating complications after tooth extraction. This study aims to investigate the efficacy of pastille GECB compared to ZOE. Materials and Methods. 30 patients with dry socket syndrome were selected and divided into two groups. GECB pastille was produced with 3% Guaiacol, 3% Eugenol 1.6% Chlorobutanol, sized 3 × 7 × 10 mm. GECB was applied in one group, and ZOE was used for the other group. Duration of pain after treatment and painkiller intake values were recorded within 20 days. The data were analyzed with independent samples t-test, Mann-Whitney, and Chi-Square tests.
Results. Pain persisted for 45.53 ± 33.34 minutes in patients treated with ZOE and 19.87 ± 21.80 minutes in those treated with GECB (P = 0.19). Patients in the ZOE group reported more painkiller intake within 20 days (P = 0.031). Conclusion. GECB showed more significant efficacy in reducing complications after tooth extraction.
Primary pancreatic hydatid cysts are rare and its percutaneous treatment and catheterization technique has, to the best of our knowledge, not been published in literature. A 33-year-old male patient who presented with abdominal pain was evaluated by ultrasonography (US) and computed tomography examinations. Both examinations revealed a cyst in the neck of the pancreas. After the administration of albendazole chemoprophylaxis, the patient underwent diagnostic puncture showing high pressure spring water which harbored the scoleces and was treated percutaneously by the catheterization technique. In this technique, first the cyst was punctured, the fluid content aspirated, the radiocontrast material injected to see possible fistulisation, and then re-aspirated. The 20% hypertonic saline solution was injected and re-aspiration was performed to the best of our abilities, followed by the insertion of a catheter for drainage of the remaining non-aspiratable fluid content. At follow-up examination, the cyst was not visible on US after 6 months. There was no evidence of cyst recurrence or dissemination after 18 months at serologic and imaging follow-up.
Cyst; Echinococcosis; Interventional procedures; Pancreas; Percutaneous drainage; Catheter placement
Background. Separate studies involving people who survived atomic bombs have shown that the risk for cancer remains high after 40 years, compared with the risk in the general population. An elevated risk may also remain in regions of Turkey near the Chernobyl disaster. Patients and Methods. A multidisciplinary study conducted in 2008, 22 years after the Chernobyl disaster, examined the thyroid cancer incidence in Rize, a province of Turkey located on the shore of the middle Black Sea. Approximately 100,000 people were screened, and a fine-needle aspiration biopsy was performed in 89 patients. Results. Based on postoperative histopathological examinations, thyroid cancer was diagnosed in six of the 100,000 people screened. Conclusion. Given a thyroid cancer frequency of approximately 8 in 100,000 in the Turkish population, according to the Turkish Cancer Research Association, the rate in Rize reflects no increase in the thyroid cancer incidence 22 years after the Chernobyl disaster.
This is a prospective study.
This study is conducted to determine the prevalence of unrecognized vertebral fracture (VF) in patients who present with back pain.
Overview of Literature
VF is often unrecognized, and significantly increases the risk of further fractures. Unfortunately, the patients at a high risk for VF usually do not receive adequate therapy to reduce the fracture risk.
This is a prospective study of 344 patients who presented with back pain from April 2008 to May 2009. The patients underwent dual-energy X-ray absorptiometry (DXA) evaluation and vertebral fracture assessment from T4 to L4 using a hologic densitometer.
Three hundred forty four of 386 patients who presented with back pain were included. Forty two patients were excluded because of a prior history of VF or the lack of written consent. Most of the patients were female (95.3%). The mean age of the patients was 58.21 ± 11.74 years. According to the World Health Organization definition (based on the T-score), 13.4% of the patients had normal lumbar spine bone mineral density (BMD). 27.9% of them were osteopenic and 58.7% were osteoporotic. The overall prevalence of VF, as established by lateral vertebral assessment, was 39% (n = 134). Moreover, 62.6% (n = 84) of the patients with VF had more than one fracture and 64.1% (n = 86) of them had Grade 2 or 3 fracture.
We recommend performing not only DXA scanning for BMD evaluation, but also VFA by DXA in old patients with back pain.
Osteoporosis; Vertebral fracture; Absorptiometry; Photon
Human leukocyte antigen G (HLA-G) is involved in regulating T-cell responses through its interaction with inhibitory receptors belonging to the immunoglobulin-like transcript family (ILT). In this context, we investigated the pathways involved in the control of cell-cycle entry of T cells following HLA-G interaction with its inhibitory receptor. We show that HLA-G acts through its interaction with the LILRB1 receptor expressed on T lymphocytes. Both HLA-G and LILRB1 antibodies block the inhibitory effect of HLA-G and restore T-cell proliferation. The interaction of HLA-G with T lymphocytes is associated with phosphorylation of SHP-2 phosphatase, but not SHP-1. In addition, in activated T cells, their incubation with HLA-G is not associated with a decrease in the TCR or CD28 downstream pathways, but is associated with dephosphorylation of the mTOR molecule and p70S6K. In contrast, Akt, which acts upstream of mTOR, is not affected by HLA-G. The inhibition of SHP-2 by NSC-87877(5 µM), a chemical inhibitor of SHP-2, or the use of siRNA, abrogates dephosphorylation of mTOR and impairs the overexpression of p27kip in the presence of HLA-G. Together, these results indicate that HLA-G is associated with activation of phosphatase SHP-2, which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry of human-activated T cells.
Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts.
In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart.
Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32.
IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies.
beta microprobe; arterial input function; PET; rat
The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.
Tunisian population; El Hamma group; skin color; Alu insertion polymorphisms; people movement history
A new species of parvovirus tentatively named human bocavirus 4 (HBoV4) was genetically characterized. Among 641 feces samples from children and adults the most commonly detected bocaviruses species were HBoV2>HBoV3>HBoV4>HBoV1 with HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children. HBoV3 and HBoV4 species combined were found in 12/192 cases of non-polio acute flaccid paralysis (AFP) from Tunisia and Nigeria and 0/96 healthy Tunisian contacts (p=0.01). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within species was found. The multiple species and high degree of genetic diversity seen among the human bocaviruses found in feces relative to the highly homogeneous HBoV1 suggest that this world-wide distributed respiratory pathogen may have recently evolved from an enteric bocavirus, perhaps after acquiring an expanded tropism favoring the respiratory track. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases including AFP and diarrhea will require further epidemiological studies.
Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative. Interestingly, it has been demonstrated that a combination of specific genotypes may be a more significant and powerful approach for predicting disease risk.
This study is aimed at investigating the combined effect of single nucleotide polymorphism (SNP) in IL-18 (−607C/A, −137G/C), interferon (IFN)-γ (+874T/A) and IL-10 (−1082G/A) genes on cirrhosis risk in HCV-infected patients.
Seventy-seven chronic hepatitis C Tunisian subjects were included in this study. The patients were divided into two groups: the first included 31 non-cirrhotic patients, and the second included 46 liver cirrhosis patients. IL-18 genotyping was performed using the PCR amplification and the restriction fragment length polymorphism analysis (RFLP). IFN-γ and IL-10 polymorphisms were analyzed using the allele-specific PCR (AS-PCR).
The combined high-risk genotype (IL-18 −607C/*, IL-18 −137G/*, IFN-γ +874T/*, IL-10 −1082A/A) frequency was compared between patients with and those without cirrhosis. Individuals were classified according the number of high-risk genotypes as follows: (0–2), patients with at most two high-risk genotypes; (3–4), patients with at least three of the high-risk genotypes. The logistic regression analysis showed that patients harboring 3–4 putative high-risk genotypes have a fivefold higher risk for developing cirrhosis in comparison to those harboring at most two high-risk genotypes (OR = 5.19; 95% CI = 1.49–18.05; p = 0.009).
Our study showed that the co-inheritance of IL-18, IFN-γ and IL-10 specific high-risk genotypes is associated with a greater risk for liver cirrhosis.
Hepatitis C; Cirrhosis; Cytokine; Polymorphism; Combined analysis