Immune tumoral microenvironment in gliomas: focus on CD3+ T cells,Vδ1+ T cells,and microglia/macrophages

Gliomas are histologically defined as low-grade gliomas (LGG) and high-grade gliomas (HGG). The most common type of HGG is the glioblastoma (GBM). We aimed to determine the immunological characteristics of CD3 T-cells, Vδ1 T-cells, and microglia/macrophages infiltrating brain gliomas. We collected 24 formalin-fixed paraffin-embedded samples issued from 19 cases of GBM and 5 cases of LGG. An immunohistochemical analysis was performed using anti-CD3, anti-Vδ1, and anti-iba-1 antibodies. Labelling indexes (LI) of CD3 and Vδ1 were evaluated quantitatively, and other CD3, Vδ1, and iba-1 staining characteristics were evaluated qualitatively. The median age of patients was 49 years in GBM and 52 years in LGG. The sex ratio was 1.4 and GBM predominated in males (p?=?0.05). In GBM, the medians of CD3-LI and Vδ1-LI were 30 and 3.5 respectively. CD3-LI inversely correlated with survival in GBM cases (r?=????0.543; p?=?0.016). CD3 staining intensity correlated with CD3-LI (p?<?0.0001) and with the survival in GBM cases (p?=?0.003). Compared to LGG, the CD3-LI, the intensity of intra-tumoral Vδ1 staining, and the amount of iba-1 were higher in GBM (p?=?0.042; p?=?0.014; and p?=?0.001 respectively). The iba-1 organization was more amoeboid in older patients and more branched in younger patients (p?=?0.028) and tended to be more amoeboid in cases with high iba-1 amount (p?=?0.09). Our results suggest that a high level of CD3-LI and a strong intra-tumoral infiltration of Vδ1 T-cells as well as a high involvement of TAM can be considered potential markers of poor prognosis of GBM. However, this requires further studies on more balanced GBM-LGG sample, including an expanded panel of biomarkers.

     

Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1

COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I. The skeletal clinical characteristics resulting from such mutations have not been characterized in detail. In this study we assessed 86 patients (36 male, 50 female; mean age 13.3 years; range, 0.6 to 54 years) with COL1A1 haploinsufficiency mutations, of whom 70 were aged 21 years or less (“pediatric” patients). Birth history was positive for fracture or long‐bone deformity in 12% of patients. The average rate of long‐bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0.62 fractures per year, one‐half of which affected the tibia/fibula. Long‐bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density. Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs. The median number of vertebral fractures was higher for females (median 4; range, 0 to 14) than for males (median 1; range, 0 to 8) (p = 0.03). Lumbar spine areal bone mineral density was negatively associated with the severity of vertebral compression fractures, as reflected in the spine deformity index. Scoliosis was present in about 30% of pediatric patients but the Cobb angle was <30 degrees in all cases. The average final height Z‐score was –1.1, representing a deficit of 8 to 10 cm compared to the general population. In summary, OI patients with COL1A1 haploinsufficiency mutations have high rates of significant skeletal involvement. Systematic follow‐up of growing patients with COL1A1 haploinsufficiency mutations including radiographic screening for vertebral compression fractures and scoliosis is warranted.     

Association of serum levels of aggrecan ARGS,NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients

ObjectivesProteolytic degradation of aggrecan is a hallmark of the pathology of osteoarthritis. The aim of this study was to develop enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of specific aggrecan fragments generated by aggrecanases-mediated cleavage. We investigated the relationships between these two aggrecan degradations fragments and urinary CTX-II levels.MethodsThe competitive ELISAs employ a polyclonal antibody raised against the aggrecan fragments containing two neoepitopes NITEGE³⁷³ and ³⁷⁴ARGSVI. We measured serum levels of ARGSV and NITEGE in 125 women with knee osteoarthritis (mean ± SD age of 53.6 ± 7.6 years, mean ± SD disease duration of 3.6 ± 3.8 years), and 57 women age-matched controls.ResultsAggrecan neoepitopes assays showed an intra- and inter-assay imprecision (CV) lower than 20% for both tests and good linearity. Median serum ARGSVI (by 18%; P = 0.002), and NITEGE (36.4%; P < 0.001) levels were significantly decreased in patients with knee osteoarthritis compared with controls. Minimal joint space width was negatively correlated with ARGSVI (r = –0.368, P = 0.04) and NITEGE (r = –0.274, P = 0.038) in knee osteoarthritis patients. Median urinary CTX-II levels were significantly increased by 39.5% (P = 0.001) in knee OA patients compared with controls.ConclusionMarkers of degradation aggrecan were analyzed for the first time in an African osteoarthritis population. These markers can be used to monitor aggrecanase activity in human joint disease. Their combination with CTX-II can improve clinical investigation of patients with osteoarthritis patients.     

Prevalence of malocclusions and orthodontic treatment need in 8- to 12-year-old schoolchildren in Casablanca,Morocco

ObjectivesThe purpose of this work was to evaluate the prevalence of malocclusions and orthodontic treatment need among schoolchildren in Casablanca, Morocco.Materials and methodsA sample of 1000 children aged between 8 and 12 years, with no history of orthodontic treatment, was chosen at random in state schools in different administrative areas of the city of Casablanca. Data was registered using the method of Bjork et al. (1964). Orthodontic treatment need was assessed with the index used by the Swedish National Board of Health (SweNBH).ResultsWe found Angle Class I malocclusions in 61.4%, Class II in 24%, Class III in 10% and an indeterminate molar class with one or more missing molars in 4.6% of the children. Overjet was 1–4 mm in 63.8%, 4–6 mm in 17.2% and >6 mm in 10%. Bite was normal in 65.4%, 23.6% presented an overbite greater than 4 mm, 1.7% an anterior open bite ≤3 mm, 1.2% an anterior open bite >3 mm and 0.2% a bilateral open bite. Half of the sample presented anterior crowding, while only 2.5% presented posterior crowding. In all, 84.2% of the subjects needed some orthodontic treatment, and 15.8% needed no treatment. No statistically significant difference was found between sex or age and orthodontic treatment need (P>0.05).ConclusionsThis study found a strong need for orthodontic treatment, confirming the utility of implementing a programme of bucco-dental prevention and screening for malocclusion.     

The effects of extraction method on the measured tocopherol level and antioxidant activity of L. nobilis vegetative organs

Tocopherol contents of Tunisian Laurus nobilis vegetative organs were screened for antioxidant activity. Tocopherol isomers extracted by probe sonication and micro-scale saponification were analysed by reversed-phase high performance liquid chromatography (RP-HPLC) with UV detection to determine the optimum extraction method. Total phenolic, flavonoid and proanthocyanidin contents were determined spectrophotometrically. Significant variations in the amounts of α-, γ- and δ-tocopherols were observed with the two different extraction methods as well as with different plant parts. Leaf extract contained the highest amount of α-tocopherol (139 mg/100 g fresh weight), but root extract contained the highest content of flavonoids (11.12 mg catechin equivalents (CE)/g dry weight or DW), total phenolics (55.45 ± 2.9 mg GAE/g DW) and condensed tannins (9.76 ± 0.1 mg CE/g DW). Acetonic extract of laurel leaf exhibited the highest antioxidant activity response to lipid peroxidation in the β-carotene-linoleic acid system, which may have been due to the high content of α-tocopherol. These findings suggest that laurel leaf may be a source of natural α-tocopherol and that it may be increasingly important for human consumption, as well as for the agro-food, cosmetic and pharmaceutical industries.     

Tumour-like lesions of the infrapatellar fat pad

Three different tumour-like lesions within the infrapatellar fat pad, an osteochondroma, a localised pigmented villonodular synovitis and a synovial cyst are reported. The osteochondroma and the pigmented villonodular synovitis were treated by marginal excision, and the synovial cyst was resected using arthroscopy.     

Oxidative stress and glutathione S-transferase genetic polymorphisms in medical staff professionally exposed to ionizing radiation

Purpose: Ionizing radiation (IR) is considered as a diagnostic and therapeutic tool in medicine. However, chronic occupational exposure of medical staff to IR may affect the antioxidant status and, as a result, DNA damage and cancers as well. The objective of our study was to evaluate the oxidative stress profile caused by IR in 29 Tunisian medical staff from radiology and radiotherapy departments, and to find an association between the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val polymorphisms and oxidative stress biomarkers.

Materials and methods: The oxidant biomarkers malondialdehyde (MDA) and advanced oxidation protein product (AOPP) and the activities of the antioxidant superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) enzymes were spectrophotometrically determined in erythrocytes hemolysates. The analysis of GSTT1 null, GSTM1 null, and GSTP1 Ile105Val polymorphisms was determined for each participant using PCR methods.

Results: A significant increase of white blood cell (WBC) numbers (p?<?.05) and a significant decrease by 11% of hemoglobin (Hb) (p?<?.01) were noted in the exposed subjects in our study. Moreover, we report a significant increase of MDA level and the activities of SOD and CAT enzymes of the IR-exposed group compared to controls (p?<?.001). Interestingly, a close association was noted between the genotypes GSTP1 low active, GSTT1 null, GSTM1 null, and both GSTT1/GSTM1 null and oxidative stress biomarkers, especially with MDA level, SOD, and CAT activities.

Conclusions: Our findings indicate that the medical staff exposed to low IR levels were under risk of significant oxidative stress that was enhanced by their glutathione S-transferase (GST) polymorphisms.