Sergio Avondo

Hypophosphatemic rickets: etiology, clinical features and treatment

Abstract Hypophosphatemic rickets (HR) is a genetic disorder, which prevents sufficient reabsorption of phosphate in the proximal renal tubule, with increased phosphate excretion, resulting in rickets. The more common form of HR is an X-linked inherited trait, with a prevalence of 1/20,000. The defective gene is located on the X chromosome, but females may present with a wide variety of clinical manifestations. The less common form of HR is caused by autosomal-dominant transmission. Activating mutations of the fibroblast growth factor 23 (FGF-23) gene and inactivating mutations in the phosphate regulating gene (PHEX gene with homologies to endopeptidases on the X chromosome), involved in the regulation of FGF-23, have been identified and have been implicated in the pathogenesis of these disturbances. A review of etiopathogenesis and clinical, differential diagnostic and therapeutic aspects of HR, with a particular emphasis on bone impairment, is reported.

Operating theatre ventilation systems and microbial air contamination in total joint replacement surgery: Results of the GISIO-ISChIA study

BACKGROUND Recent studies have shown a higher rate of surgical site infections in hip prosthesis implantation using unidirectional airflow ventilation compared with turbulent ventilation. However, these studies did not measure the air microbial quality of operating theatres (OTs), and assumed it to be compliant with the recommended standards for this ventilation technique. AIM To evaluate airborne microbial contamination in OTs during hip and knee replacement surgery, and compare the findings with values recommended for joint replacement surgery. METHODS Air samplings were performed in 28 OTs supplied with unidirectional, turbulent and mixed airflow ventilation. Samples were collected using passive sampling to determine the index of microbial air contamination (IMA). Active sampling was also performed in some of the OTs. The average number of people in the OT and the number of door openings during the sampling period were recorded. FINDINGS In total, 1228 elective prosthesis procedures (60.1% hip and 39.9% knee) were included in this study. Of passive samplings performed during surgical activity in unidirectional airflow ventilation OTs (U-OTs) and mixed airflow OTs (M-OTs), 58.9% and 87.6% had IMA values >2, respectively. Of samplings performed during surgical activity in turbulent airflow OTs (T-OTs) and in turbulent airflow OTs with the surgical team wearing Steri-Shield Turbo Helmets (TH-OTs), 8.6% and 60% had IMA values ≤ 2, respectively. Positive correlation was found between IMA values and the number of people in the OT and the number of door openings (P < 0.001). In addition, correlation was found between active and passive sampling (P < 0.001). CONCLUSION These findings challenge the belief that unidirectional systems always provide acceptable airborne bacterial counts.

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the diagnosis and assist in subtyping bone tumors. Here, we review these markers and discuss their role in the diagnosis and prognosis of the three most frequent malignant bone neoplasms, namely osteosarcoma, chondrosarcoma, and Ewing sarcoma.

2-Benzisothiazolylimino-5-benzylidene-4-thiazolidinones as protective agents against cartilage destruction

We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs) 3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protective agents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulated by IL-1β. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs, was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover, selected derivatives 1h and 1g was studied for nuclear factor kappaB (NF-κB) inhibition by Western Blot analysis and for MMP-3 protein release using ELISA test. The structure-activity relationship of tested compounds demonstrates a favorable effect of the para substitution on the 5-benzilydene ring. Compound 1g shows a potent and selective activity on MMP-3 versus MMP-13. Accordingly, 1g possesses high antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production of MMPs and NF-κB expression. Thus 1g can be considered as new potential chondroprotective agents.

Evaluation of the anti-inflammatory/chondroprotective activity of aldose reductase inhibitors in human chondrocyte cultures

(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic acids (6) and 5-arylidene-4-oxo-2-thioxothiazolidines (7), which we recently synthesised and assayed as aldose reductase inhibitors, were evaluated as anti-inflammatory/antidegenerative agents in cultures of human chondrocytes stimulated by IL-1β. In this screening, most of the tested compounds were able to control key components of the IL-1β-induced inflammatory signalling, by reducing the levels of NF-kB, ICAM-1, and NO as well as increasing the production of glycosaminoglycans by chondrocytes. Moreover, these 4-thiazolidinone derivatives exhibited antioxidant properties and were shown to inhibit MMP-3 and MMP-13 at micromolar concentrations, with a generally marked preference toward MMP-13 which plays a major role in cartilage degeneration. Thus, on the whole, compounds 6 and 7 were shown to be capable of both counteracting inflammatory events and contributing to restore normal levels of cartilage components. This anti-inflammatory/antidegenerative profile makes them interesting cell-permeable molecules that can be assumed as lead compounds in the search for novel anti-inflammatory agents.