Serum leptin levels in children and adolescents with spinal muscular atrophy types 2 and 3✰.

AIM: It has been reported that in patients with spinal muscular atrophy (SMA), lower levels of motor function are associated with hyperleptinemia. Additionally, hyperleptinemia has been found to be more frequent in underweight SMA patients. Therefore, we aimed to analyze serum leptin levels in patients with SMA. METHOD: This was a cross-sectional study of pediatric patients (2-19 years old) with SMA types 2 and 3. The investigations included anthropometric measurements, assessment of pubertal status, motor function evaluation using the Hammersmith Functional Motor Scale - Expanded (HFMSE), and serum leptin levels. RESULTS: In total, 37 patients (22 with type 2 and 15 with type 3 SMA) were included in the study. The male-to-female ratio was 1:1.3 and 62.2% of patients were prepubertal. No statistically significant correlation was found between the HFMSE score and leptin levels, rs(35) = 0.24, p = 0.15. There was, however, a strong positive relationship between the body mass index (BMI) z-score and leptin levels, rs(35) = 0.87, p < 0.001. CONCLUSION: Serum leptin levels do not seem to be a useful marker of disease severity in children and adolescents with types 2 and 3 SMA. As in the general pediatric population, leptin levels are strongly correlated with BMI, which is a surrogate measure of body fat.

Metformin inhibits melanoma development through autophagy and apoptosis mechanisms.

Metformin is the most widely used antidiabetic drug because of its proven efficacy and limited secondary effects. Interestingly, recent studies have reported that metformin can block the growth of different tumor types. Here, we show that metformin exerts antiproliferative effects on melanoma cells, whereas normal human melanocytes are resistant to these metformin-induced effects. To better understand the basis of this antiproliferative effect of metformin in melanoma, we characterized the sequence of events underlying metformin action. We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy. The relevance of these observations were confirmed in vivo, as we showed that metformin treatment impaired the melanoma tumor growth in mice, and induced autophagy and apoptosis markers. Taken together, our data suggest that metformin has an important impact on melanoma growth, and may therefore be beneficial in patients with melanoma.

Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth.

We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPARγ activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone inhibits expression of the CXCL1 chemokine gene. CXCL1 is overexpressed in melanoma and contributes to tumorigenicity. We show that ciglitazone induces a diminution of CXCL1 level in different human melanoma cell lines. This effect is mediated by the downregulation of microphthalmia-associated transcription factor, MITF, the master gene in melanocyte differentiation and involved in melanoma development. Further, recombinant CXCL1 protein is sufficient to abrogate thiazolidinedione effects such as apoptosis induction, whereas extinction of the CXCL1 pathway mimics phenotypic changes observed in response to ciglitazone. Finally, inhibition of human melanoma tumor development in nude mice treated with ciglitazone is associated with a strong decrease in MITF and CXCL1 levels. Our results show that anti-melanoma effects of thiazolidinediones involve an inhibition of the MITF/CXCL1 axis and highlight the key role of this specific pathway in melanoma malignancy.

Air pollution in Sibenik before and after the shutdown of major local industries.

This study compares the values of the critical air pollution indicators (including-sulphur dioxide, smoke, total deposited matter, gaseous fluorides, fluorides, and manganese in suspended particulates and deposited matter) measured in Sibenik for years 1989/90 when the industry was working with full capacity, and for years 1994/95 and 1995/96 when most plants were shut down due to Serbian aggression. The purpose of this study was to assess the influence of industrial air pollution sources on the air quality in Sibenik. The pollution indicators show that the air in Sibenik was excessively polluted until the major industries were shut down as a result of Serbian aggression in Croatia, while it is only slightly polluted today. These findings prove the dominant influence of industrial emissions on the air quality in Sibenik.

[The importance of physical therapy in the treatment of Volkmann's contracture in children]. / Znacaj fizikalne terapije u lecenju Folkmanove kontrakture kod dece.

Over the period from 1981 to 1991 twenty-eight children were treated for neurovascular posttraumatic complications (Volkman's contracture), in the Centre for rehabilitation and physical medicine of the Children's surgical department in Belgrade. The success of the treatment depended on how a patient was examined for the first time, and how soon a proper diagnosis was established. On the basis of our experience we insist on an early physical treatment, i.e. while the injured segment is immobilized. An early kinesitherapy followed later by electrotherapy, parafino-therapy, vitamin B therapy and use of corrective plaster cast splints is the best way in treating lesions. The treatment lasted from 3 to 6 months depending on the seriousness of an injury. If there was no good result with physical therapy we carried out surgery followed by physical therapy upon the removal of immobilisation devices.

Acoustic correlates of individuality in the cries of human infants.

The acoustic features that differentiate the cries of individual human infants were examined in this study. A recognition task, performed by 400 nonparent adults, was used to classify twenty 30-day-old infants as easy or difficult to recognize on the sole basis of their tape-recorded cries. The cries of easy- vs difficult-to-recognize infants were then compared on measures of duration, fundamental frequency, peak frequency in the spectrum, signal-to-noise ratios, and energy in selected frequency bands. The results indicated that each of these measures differentiated the cries of easy- vs difficult-to-recognize infants. Such redundancy should make the cry robust to degradations of selected acoustic parameters, thus enhancing its ability to carry information about individual identity across distances.