TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring

Background

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children.

Methods

The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels.

Results

There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism.

Conclusions

Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.     

TNF-α Blockade Efficiently Reduced Severe Intestinal Damage in Necrotizing Enterocolitis

Objectives: To ascertain the beneficial effects of infliximab an inhibitor of tumor necrosis factor alpha (TNF-α) on the development of NEC in an experimental NEC rat model. Material and Methods: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as NEC, NEC+ infliximab, and control. NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia and cold stress. Pups in the NEC+ infliximab group were administered infliximab at a dose of 10 mg/kg daily by intraperitoneal route from the first day until the end of the study. All pups were sacrificed on the 5th day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (TUNEL and caspase-3), and biochemical evaluation, including, total antioxidant status (TAS), total oxidant status (TOS), malonaldehyde (MDA), and myeloperoxdase (MPO) and TNF-α activities. Results: We observed better clinical sickness scores, weight gain, and survival rate in the NEC+ infliximab group compared to the NEC group (p < .05). Histopathological and apoptosis examination (TUNEL and immunohistochemical evaluation for caspase-3) revealed lower damage in the NEC+ infliximab group compared to the damage in the NEC group (p < .01). Tissue MDA, MPO, TNF-α levels, and TOS were significantly decreased in the NEC+infliximab group, whereas TAS was significantly increased in the NEC + infliximab group (p < .01). Conclusion: TNF-α blockade with infliximab efficiently reduced the intestinal injury and preserve the intestinal tissues from severe intestinal damage by its complex mechanisms on NEC. Therefore, it may be an alternative option for the treatment of NEC.     

Leptomeningeal dissemination and vertebral bone involvement in a child with pilocytic astrocytoma

In low‐grade glioma, metastasis is rarely seen. Few cases of leptomeningeal dissemination have been reported in children. Vertebral bone metastasis has not been reported so far. Herein is described the case of a pediatric patient with the diagnosis of pilocytic astrocytoma, and leptomeningeal dissemination detected at the time of diagnosis, who then received radiotherapy and chemotherapy upon development of vertebral bone metastasis during treatment.     

Choroidal and macular thickness changes in type 1 diabetes mellitus patients without diabetic retinopathy

Objectives: To explore choroidal thickness (ChT) and retinal thickness (RT) changes in patients with type 1 diabetes mellitus (DM).

Methods: Sixty patients with Type 1 DM and 60 age- and sex-matched healthy controls were included in this prospective case–control clinical study. All patients underwent a complete ophthalmological examination. ChT of each participant was measured at the fovea and horizontal nasal and temporal quadrants at 500-µm intervals to 1500 µm from the foveola using spectral-domain optical coherence tomography (SD-OCT). Age, gender, disease duration, serum glycosylated hemoglobin (HbA1c), fasting glucose level, axial length (AL) and refractive error were noted and analyzed.

Results: Mean disease duration, mean HbA1c and mean fasting blood glucose in diabetic patients were 6.1±2.8 years, (8.9±0.9)% and 287.5±69.1 mg/dl, respectively. Age, gender, AL, spherical equivalent differences between the patients and subjects were insignificant (p>0.05). Subfoveal ChT, nasal quadrant ChT measurements, temporal 1500 µm and mean nasal ChT were significantly lower in diabetic patients (p<0.05 for all). Temporal 500 µm and 1000 µm ChT measurements, mean temporal ChT, average ChT, central macular thickness and average macular thickness did not differ significantly between the groups (p>0.05 for all).

Conclusion: This study showed that there is choroidal thinning in young Type 1 diabetic patients with early period of disease duration without diabetic retinopathy nor any other systemic diseases. Choroidal changes in type 1 DM seem to begin at nasal and distal temporal retina. These results need to be verified by larger and longitudinal studies.     

Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases

46,XX testicular disorder of sex development (46,XX TDSD) is a relatively rare condition characterised by the presence of testicular tissue with 46,XX karyotype. The present study aims to reveal the phenotype to genotype correlation in a series of sex-determining region Y (SRY)-positive 46,XX TDSD cases. We present the clinical findings, hormone profiles and genetic test results of six patients with SRY-positive 46,XX TDSD and give the details and follow-up findings of our three of previously published patients. All patients presented common characteristics such as azoospermia, hypergonadotropic hypogonadism and an SRY gene translocated on the terminal part of the short arm of one of the X chromosomes. Mean ± standard deviation (SD) height of the patients was 164.78 ± 8.0 cm. Five patients had decreased secondary sexual characteristics, and three patients had gynaecomastia with varying degrees. Five of the seven patients revealed a translocation between protein kinase X (PRKX) and inverted protein kinase Y (PRKY) genes, and the remaining two patients showed a translocation between the pseudoautosomal region 1 (PAR1) of X chromosome and the differential region of Y chromosome. X chromosome inactivation (XCI) analysis results demonstrated random and skewed XCI in 5 cases and 1 case, respectively. In brief, we delineate the phenotypic spectrum of patients with SRY-positive 46,XX TDSD and the underlying mechanisms of Xp;Yp translocations.