Concomitant focal fibrocartilaginous dysplasia of the tibia and eosinophilic granuloma of the jaw in a child

This 2-year-old child presented with concomitant eosinophilic granuloma of the lower jaw and focal fibrocartilaginous dysplasia of the right tibia. Her eosinophilic granuloma was diagnosed on the basis of the clinical picture, imaging studies and the characteristic histologic appearance. Focal fibrocartilaginous dysplasia was revealed incidentally during the eosinophilic granuloma staging process. After chemotherapy, all signs of eosinophilic granuloma subsided, but focal fibrocartilaginous dysplasia remained without signs of clinical or radiographic progression. The importance of differentiating these two conditions is stressed in order to avoid ineffective and inappropriate treatment of focal fibrocartilaginous dysplasia.     

Medio-thoracic esophageal stenosis,produced by pseudotumoral ulcer

A non-specific esophagitis developed in a young male, apparently determined by heavy abuse of alcohol. Shortly after, a stenotic pseudo-tumoral mediothoracic esophageal lesion was diagnosed. Although there was a high index of suspicion regarding the caustic origin of the lesion, cancer could not be excluded using current diagnostic methods. Temporary feeding jejunostomy was followed by uneventful total esophagectomy and gastric pull-up. Pathologic examination of the resected specimen was a surprise, revealing an esophageal ulcer based on massive severe non-specific esophagitis. Retrospectively, the ulcer was judged as primitive or idiopathic. We discuss some etiopathogenic aspects of common secondary esophageal ulcers (related or not to reflux disease), in contrast with idiopathic esophageal ulcers.     

Molecular diversity of disintegrin-like domains within metalloproteinase precursors of Bothrops jararaca.

Disintegrins are small peptides isolated from the venom of several snake families which act as integrin-antagonists or agonists, interacting with a variety of biological processes mediated by integrins. In this work we describe five new disintegrin-like domains within metalloproteinase precursor sequences, obtained from a Bothrops jararaca venom gland cDNA library. Among the new disintegrin-like domains, four were contained in PIII metalloproteinase precursors, with three of them presenting ECD-motifs and one presenting a new KCD-motif. Moreover, we found three disintegrin-like domains within PII metalloproteinase precursors. Two of them are similar to the already described disintegrins jarastatin and jararacin. The third molecule is unusual, presenting some typical PIII metalloproteinase characteristics but lacking the cysteine-rich domain being, thus, classified as a PII metalloproteinase. Only few reports presented molecules with these characteristics. Sequence analysis suggests that these molecules are intermediate steps between the more ancient PIII and the more recent PII metalloproteinases. We also investigated disintegrin N-terminus diversity in B. jararaca crude venom by purifying jarastatin and jararacin and analyzing them by mass spectrometry.     

Homeostatic regulation of sleep in a genetic model of depression in the mouse: effects of muscarinic and 5-HT1A receptor activation.

In depressed patients, sleep undergoes marked alterations, especially sleep onset insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM) sleep. Abnormalities of rest-activity rhythms and of hypothalamic-pituitary-adrenocortical function have also been described in these patients. In the present study, we examined the presence of such abnormalities in a recently developed line of mice (Helpless mice-H) that exhibit depression-like behaviors in validated tests, compared to the nonhelpless (NH) line derived from the same colony. Experiments were essentially carried out in females for which previous studies showed marked differences between H and NH lines. Compared to NH mice, the H line exhibited (i) lower basal locomotor activity, (ii) sleep fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep reflected by increased amounts and decreased latency, (iii) larger response to the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline). In contrast, H and NH mice were equally responsive to the REM sleep inhibitory effect of 5-HT1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency in delta power enhancement after sleep deprivation was observed in the H group, and acute immobilization stress in this group failed to elicit a REM sleep rebound and was associated with a long-lasting raise in serum corticosterone levels. These results further validate H mice as a depression model and suggest they might be of particular interest for investigating the neurobiological mechanisms and possibly genetic substrates underlying sleep alterations associated with depression.     

Purification and biological effects of C-type lectin isolated from Bothrops insularis venom

Bothrops insularis is a snake from Queimada Grande Island, which is an island located about 20 miles away from the southeastern coast of Brazil. Compared to other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood. Its C-type lectin is involved in several biological processes including anticoagulant and platelet-modulating activities. We purified the C-type lectin (BiLec) from Bothrops insularis venom and investigated its effect in the isolated kidney. BiLec was purified after two chromatographic steps; firstly, the whole venom was submitted to an HPLC molecular exclusion chromatography followed by a second purification through affinity chromatography. B. insularis lectin (BiLec) was studied as to its effect on the renal function of isolated perfused rat kidneys with the use of six Wistar rats. The concentration of 10 μg/mL increased perfusion pressure (PP; control₆₀=108.27±4.9; BiLec₆₀=112.9±5.4 mmHg; *p<0.05) and renal vascular resistance (RVR; control₆₀=5.38±0.51; BiLec₆₀=6.01±0.57 mmHg; *p<0.05). The urinary flow reduced significantly at 90 and 120 min of perfusion (UF; control₁₂₀=0.160±0.020; BiLec₁₂₀=0.082±0.008 mL g⁻¹ min⁻¹; *p<0.05). Glomerular filtration rate (GFR; control₁₂₀=0.697±0.084; BiLec₁₂₀=0.394±0.063 mL g⁻¹ min⁻¹; *p<0.05) diminished only at 120 min. BiLec did not change the percentage of sodium (TNa⁺), potassium (TK⁺) and chloride tubular transport (TCl⁻). The histological alterations probably reflected direct injury on glomerular and tubular renal cells, as demonstrated by the rise in permeability of glomerular endothelial cells, revealed by the presence of a proteinaceous material in the Bowman space. We postulate that the C-type lectin B. insularis promoted its effects probably through interactions with endothelial cells or through the release of other mediators by tubular, mesangial and endothelial cells.     

Cytostatic therapy and blood antioxidants/prooxidants balance in acute myeloblastic leukemia patients

To analyze the effects of conventional polychemotherapy of acute myeloblastic leukemia (AML) patients on the prooxidants/antioxidants balance in plasma total antioxidant status (TAS) and a single plasma antioxidant — uric acid (UA) were measured. Lipid peroxidation was assessed by malonedialdehyde (MDA) content. Total serum iron was monitored as a potential source of nontransferrin-bound iron with a role in initiation of oxidative burst. A group of patients in the acute phase of AML (group A) and a group of patients in complete remission of AML (group B) were studied. A strong correlation between UA values and TAS (r = 0.8 for group A, r = 0.9 for group B) was revealed in the course of the treatment. Strong negative correlation (r = −0.9) between TAS and MDA was shown for both groups. Total iron significantly increased in the course of chemotherapy. We have established that polychemotherapy leads to the consumption of antioxidants and increased lipid peroxidation in AML patients. An appropriate supplementation with antioxidants at the end of the polychemotherapy treatment could be considered.     

Treatment of primary g lioblastoma multiforme with c e tuximab, r adiotherapy and t emozolomide (GERT) – phase I/II trial: study protocol

Background  

The implementation of combined radiochemotherapy (RCHT) with temozolomide (TMZ) has lead to a significant increase in overall survival times in patients with Glioblastoma multiforme (GBM), however, outcome still remains unsatisfactory.     

Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development.

Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.