Increased osteoblast adhesion on nanoparticulate calcium phosphates with higher Ca/P ratios

The biological properties of calcium phosphate-derived materials are strongly influenced by changes in Ca/P stoichiometry and grain size, which have not yet been fully elucidated to date. For this reason, the objective of this in vitro study was to understand osteoblast (bone forming cells) adhesion on nanoparticulate calcium phosphates of various Ca/P ratios. A group of calcium phosphates with Ca/P ratios between 0.5 and 2.5 were obtained by adjusting the Ca/P stoichiometry of the initial reactants necessary for calcium phosphate precipitation. For samples with 0.5 and 0.75 Ca/P ratios, tricalcium phosphate (TCP) and Ca(2)P(2)O(7) phases were observed. In contrast, for samples with 1.0 and 1.33 Ca/P ratios, the only stable phase was TCP. For samples with 1.5 Ca/P ratios, the TCP phase was dominant, however, small amounts of the hydroxyapatite (HA) phase started to appear. For samples with 1.6 Ca/P ratios, the HA phase was dominant. Last, for samples with 2.0 and 2.5 Ca/P ratios, the CaO phase started to appear in the HA phase, which was the dominant phase. Moreover, the average nanometer grain size, porosity (%), and the average pore size decreased in general with increasing Ca/P ratios. Most importantly, results demonstrated increased osteoblast adhesion on calcium phosphates with higher Ca/P ratios (up to 2.5). In this manner, this study provided evidence that Ca/P ratios should be maximized (up to 2.5) in nanoparticulate calcium phosphate formulations to increase osteoblast adhesion, a necessary step for subsequent osteoblast functions such as new bone deposition.     

Carotid stenting vs surgery: parsing the risk of stroke and MI

The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is the largest randomized prospective study to date to compare carotid artery stenting and carotid endarterectomy in a patient population similar to that seen in everyday practice. CREST showed stenting and surgery to be equivalent in terms of the composite end point of stroke, myocardial infarction (MI), or death within 30 days, as well as for the rate of stroke at up to 4 years (N Engl J Med 2010; 363:11-23). Importantly, the risk of major stroke was low with either intervention. However, the results need to be considered in the context of the impact of each procedure on stroke and MI.     

5 alpha steroid reductase deficiency in Turkey

5 alpha steroid reductase 2 (5 alpha SR2) deficiency is an autosomal recessive enzyme defect causing male pseudohermaphroditism (MPH) because of an abnormally low peripheral conversion of testosterone to dihydrotestosterone (DHT), which is required for the normal differentiation of external male genitalia. The present report describes the distribution of 5 alpha steroid reductase gene mutations in the Turkish population in the light of published reports from different centers. Eight Turkish patients from unrelated Turkish families and a large pedigree of one of these patients are also discussed. These patients were followed up at Ankara University Department of Pediatric Endocrinology. The presence of Leu 55 Gln mutation in six patients out of 8 indicates the increased prevalence of this mutation in the Turkish population with different presentations. One patient out of six (patient FG) had a large pedigree of Leu 55 Gln mutation in exon 1. The pedigree of this family with marital consanguinity was very remarkable and extraordinary. A further 85 members of this family were analyzed for exon 1 Leu 55 Gln 5 alpha SR2 gene mutations. Forty two out of the 85 subjects (49.41% ) had this alteration in gene mutation. Thirty-one of them were heterozygous (18 genetic male, 13 genetic female) and 11 of them were homozygous (8 genetic male, 3 asymptomatic female carriers) for this mutation. A trinucleotid deletion at straddling codons 156 and 157 is responsible for a methionize residue at position 157 (delta Met 157) of 5 alpha SR type 2 gene which was first described in our patient NA. Two additional Turkish patients were reported by different investigators with this rare mutation and this also suggests an increased prevalence of this mutation in the Turkish population. In conclusion Leu 55 Gln mutation in exon 1 seems to be a hot spot in Turkish patients. Hence 5 alpha SR2 gene mutation analysis especially Leu 55 Gln mutation in exon 1 and delta Met 157 in exon 3, must be evaluated in Turkish patients with male pseudohermaphroditism according to our results and other Turkish patients reported by different investigators. It is important that homozygous asymptomatic female carriers be taken into consideration in this clinical entity especially in closed populations because of the risk of carrying the disease to their offspring.     

Long‐term safety and efficacy of etanercept in children with polyarticular‐course juvenile rheumatoid arthritis

Objective

Previous studies showed that etanercept treatment in patients with polyarticular‐course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA.

Methods

Patients with active polyarticular‐course JRA who participated in an efficacy study continued etanercept treatment in an open‐label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of ≥30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by ≥30%.)

Results

Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for ≥4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient‐year, and the rate of serious infections was 0.04 per patient‐year, in a total etanercept exposure of 225 patient‐years. Eighty‐two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to ≤5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for ≥4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit.

Conclusion

Etanercept offers an acceptable safety profile in children with polyarticular‐course JRA and provides significant improvement in disease manifestations that are sustained for ≥4 years.

     

The presence of Helicobacter pylori in the larynx pathologies

Objective

The well-known relation of Helicobacter pylori to the MALT-lymphoma and gastric carcinoma suggested a possible presence in the laryngeal tissues of patients with squamous cell carcinoma of the larynx by using Polymerase Chain Reaction (PCR) investigations, and PCR results of benign laryngeal pathologies were compared.

Methods

Polymerase Chain Reaction investigations were carried out in biopsy samples of 21 patients with squamous cell carcinoma of the larynx and of 19 patients with benign laryngeal pathologies like vocal polyp and nodules.

Results

The PCR results of 17 out of the 21 samples (80.9%) of the patients with laryngeal squamous cell carcinoma were positive for H. pylori. Moreover, any genomic material of H. pylori was not found in the PCR results of the 19 patients with benign laryngeal pathology. It was also determined that the presence of the H. pylori in the patients with laryngeal squamous cell carcinoma was statistically significant (p = 0.0001).In the patients with laryngeal squamous cell carcinoma, the comparison of the H. pylori presence within the normal and tumoral tissues revealed that 16 normal tissue samples (76.19%) were positive, while 9 of the tumoral tissue samples (42.85%) were positive. The ratio of bacterial presence in both the normal and tumor tissue samples was 38.09% (8 patients). The rates of presence revealed a statistically significant difference between the normal and tumoral tissue samples (p = 0.039).

Conclusions

The presence of the genomic material of H. pylori within the laryngeal tissue of patients with squamous cell carcinoma of the larynx is a proof of the colonization of the bacterium in that tissue. While this may suggest a possible relation of the bacterium to the development of laryngeal squamous cell carcinoma, no conclusion is possible to be drawn about the mechanism of the process.     

Progressive vacuolar myelopathy and leukoencephalopathy in childhood acute lymphoblastic leukemia and transient improvement with vitamin B12

Vacuolar myelopathy (VM) in leukemia is rare. We report a boy with leukemia who developed isolated central nervous system (CNS) relapse during reinduction therapy. 5 months after cranial radiotherapy, he gradually developed quadriparesis. Magnetic resonance imaging revealed an intramedullary lesion which extended through the cervical spine. Serum vitamin B12, folic acid, cerebrospinal fluid methyl malonic acid were normal. Viral screening by ELISA was negative. He had lymphopenia, and reduced immunoglobulins, from a cardiac arrest. Biopsy revealed VM. He responded to weekly vitamin B12 treatment but on the 6th week of the therapy he died after developing periventricular, gliotic, hyperintense lesions in the brain.     

Early electroretinographic features of streptozotocin-induced diabetic retinopathy

Background: This study set out to document the early electrophysiological and immunohistochemical changes that occur in the retina of experimentally induced diabetic rats. Methods: Diabetes was induced in rats by intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Electroretinogram readings were taken monthly under either short‐duration or long‐duration stimuli for up to 3 months after STZ. Oscillatory potentials (OP) and the amplitudes and implicit times of a‐ and b‐waves were analysed, and b‐wave amplitudes were analysed using a Naka–Rushton fit. Scotopic a‐waves were analysed with photoreceptor models, and Rmp3 (the maximum a‐wave amplitude) and S (sensitivity) were calculated. Three months after STZ injection, immunohistochemistry for glial fibrillary acidic protein was performed on the retinas of the STZ‐treated rats and age‐matched controls. Results: The implicit OP times were significantly longer in the diabetic rats as compared with the controls, and this difference was noted as early as 1 month following STZ treatment. Other electrophysiological parameters, such as OP amplitudes, a‐ and b‐wave amplitude as well as the implicit times, did not differ from controls at this stage. The sacrificed STZ‐treated rats also demonstrated marked enhancement of glial fibrillary acidic protein immunoreactivity, suggesting that at least in experimentally induced diabetic retinopathy there is increased Müller cell reactivity. Conclusion: The results of this study indicated that functional alterations in the retina develop rapidly after the onset of diabetes. Analysis of each electroretinogram component may be useful in further investigating the development mechanisms of diabetic retinopathy.