Autoactivation of human blood coagulation factor XII on dextran derivatives of different molecular weight

We prepared a derivative of dextran T40 (average Mr 43,000) from which fractions of different Mr but with equal charge density were obtained and tested for their ability to promote autoactivation of human blood coagulation factor XII. The mechanism of autoactivation appeared dependent upon the Mr of the polymer used. Thus, with polymers of 38,000 Mr or higher only -factor XIIa was formed and the reaction could be completely described in terms of a simple second-order mechanism of autoactivation. With smaller polymer molecules β-factor XIIa became a major reaction product and as a result of this the autoactivation kinetics did not adhere to the second-order mechanisms thus far described.     

Streptococcus pneumoniae can utilize multiple sources of hyaluronic acid for growth

The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan.     

Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.     

Familial extensive idiopathic bilateral pleural fibrosis.

The authors report three sisters with bilateral isolated apical pleural fibrosis of unknown origin, which did not respond to empirical antituberculosis therapy and oral corticosteroids. The disease evolved in an unrelenting fashion producing pleural fibrosis at the lung bases and leading to the death of two sisters and to lung transplantation in the other one. There was no history of other familial disease or consanguinity. The particular features of these cases and the differences from other reports of apparently cryptogenic pleural fibrosis are outlined.     

111In-pentetreotide scintigraphy in patients with Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis is a granulomatous disease that may involve multiple organs and the prognosis of which is highly variable. Because the prognosis depends particularly on the number of tissues involved, the accurate identification of the organs involved by granulomatous lesions is of critical importance. We hypothesized that 111In-pentetreotide scintigraphy would be useful for evaluation of patients with Langerhans' cells histiocytosis. METHODS: Thirteen patients (38.3+/-10.4 y) with Langerhans' cell histiocytosis (8 patients with unifocal lung disease, 5 with multifocal disease) received intravenous 111In-pentetreotide (111-222 MBq), and planar images were obtained at 24 h after injection. Pulmonary uptake was quantified using a lung-to-background ratio (L/B) and compared with a population of 10 normal scintigrams. For the other sites, uptake of radioactivity in disease-related areas was visually assessed. RESULTS: Ten of 12 patients with lung involvement had increased lung uptake (UB, 2.23+/-0.49 versus 1.34+/-0.07; P < 0.001). In the patients with multifocal disease, increased 111In-pentetreotide uptake was found in disease-related areas such as the salivary glands, the skin, the soft tissues, and the bones. However, somatostatin receptor imaging was insensitive for detecting central nervous system and liver involvement and most skin lesions. CONCLUSION: 111In-pentetreotide imaging may be useful in Langerhans' cell histiocytosis. Further study will indicate whether 111In-pentetreotide is a relevant tracer in the management of histiocytosis.     

Evaluation of the developmental toxicity of the aqueous extract from Trigonella foenum-graecum (L.) in mice

Aim of the study

The use of medicinal plant products to treat various ailments is a common practice in many developing countries. However, a lack of information on the adverse effects of these plants raises questions on their safety and possible adverse side effects. This study was undertaken to evaluate the potential toxic effects of fenugreek seeds on pregnant mice and foetal development.

Materials and methods

Lyophilized aqueous extract from fenugreek seeds (LAE-FS) was administered to mated female mice during the entire period of pregnancy, at doses of 500 and 1000 mg/kg/day. Females were examined for standard parameters of reproductive performance. Foetuses were weighed and examined for externally visible malformations.

Results

In pregnant females, there were no obvious symptoms of toxicity, LAE-FS-related deaths or macroscopic abnormalities. Developmental toxicity in offspring included an increase in the foetal death rate, a decrease in the litter size, and a reduction in the foetal body weight. In addition there was an increase in the incidence of morphological abnormalities.

Conclusions

Based on these results, it was concluded that fenugreek seeds extract may have deleterious toxic effects on reproductive performance and potential teratogenic effects in foetuses.