The interface between depression and cerebrovascular disease--some hope but no hype

Medical complications after stroke are an important problem not only for patients, but also for their families and the clinicians who take care of them, thus representing a major public health problem. Among medical illnessess complicating stroke, in the last several years much efforts has been directed to determine the role of affective disorders. Although depression coexisting with stroke has been shown to increase levels of functional disability and reduce the effectiveness of rehabilitation, we still have much to learn about the clinical interface between such disorders. This review focuses on the data concerning the potential relationship between depression and cerebrovascular disease (CVD) and the emerging insights which may be relevant to provide directions for the development of novel research strategies on the pathogenesis and treatment of post-stroke depression.     

Familial colloid cyst of the third ventricle: neuroendocrinological follow-up and review of the literature

Colloid cysts of the third ventricle are rare, benign cysts of endodermal origin. Between 1989 and 1999, eight patients with this lesion (five females, three males), with a mean age of 40.5 years (range 20–54), were identified out of 1354 operated for tumours of the central nervous system. Among the eight, two were familial. They were half sisters 38 and 28 years-old, who were diagnosed to have colloid cysts of the third ventricle on CT scanning. Transcortical excision yielded 10 and 15 mm sized colloid cysts, respectively. Moreover, both sisters developed a multinodular goiter associated with these congenital tumours. The second sibling developed hyperprolactinemia associated with macroprolactinemia. Pregnancy was only possible after bromocriptine treatment. These cases provide further evidences that colloid cysts probably have an autosomic recessive pattern of inheritance with variable penetrance.     

Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis

Preneoplastic and neoplastic hepatocytes undergo c-Myc up-regulation and overgrowth in rats genetically susceptible to hepatocarcinogenesis, but not in resistant rats. Because c-Myc regulates the pRb-E2F pathway, we evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrain differences in gene expression occurred in normal liver. Overexpression of c-myc, Cyclins D1, E, and A, and E2F1 genes, at messenger RNA (mRNA) and protein levels, rise in Cyclin D1-CDK4, Cyclin E-CDK2, and E2F1-DP1 complexes, and pRb hyperphosphorylation occurred in nodules and HCCs of F344 rats. Expression of Cdk4, Cdk2, p16(INK4A), and p27(KIP1) did not change. In nodules and/or HCCs of Wistar and BN rats, low or no increases in c-myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16(INK4A) overexpression and pRb hypophosphorylation. In conclusion, these results suggest deregulation of G1 and S phases in liver lesions of susceptible rats and block of G1-S transition in lesions of resistant strains, which explains their low progression capacity.     

Helicobacter infection in patients with HCV-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific for a conserved region in the H. pylori vacA gene were also used. The patients' H. pylori status was determined by ELISA. Forty-one patients (mean age 54.9, range 19–78 years; 24 men) were studied. Thirty patients had chronic viral hepatitis (CH) without (N = 18) or with (N = 12) cirrhosis (CIR), and 11 patients had HCC. Anti-H. pylori IgG was detected in 54%. The expected 422- and 210-bp fragments of Helicobacter 16S rRNA were amplified from 27% of liver samples, including 17% of CH-CIR and 55% of HCC (P = 0.004). The vacA sequence was amplified in 10 of 41(24%) samples (27% of those with HCC).: These data confirm the presence of H. pylori DNA sequences in human liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are needed to ascertain whether Helicobacter spp. infection plays a role in the development of HCC.     

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.