[A pseudotumoral lesion revealing Meckel's diverticulum]. / Lésion pseudo-tumorale révélatrice d'un diverticule de Meckel.

INTRODUCTION: Meckel's diverticulum is a common malformation in children, usually asymptomatic, with complications in only 20% of cases. Exceptionally, a tumor can develop in Meckel's diverticulum in children, particularly Burkitt's lymphoma; in adults it can develop into a gastrointestinal stromal tumor, a leiomyosarcoma, or a neuroendocrine tumor such as a carcinoid tumor. The diagnosis of inflammatory pseudotumor following an insidious perforation is rare. OBSERVATION: We report the case of a 14-month-old boy who presented with fever, asthenia, food refusal, and digestive complaints such as vomiting and tender abdomen suggesting appendicitis. Computed tomography showed an ileal mass of 3cm in diameter, which led to the suspicion of Burkitt's lymphoma. Laparoscopy showed Meckel's diverticulum with a mass of 3×2.8×2cm. Histological examination confirmed the diagnosis of Meckel's diverticulum with gastric heterotopia and showed a proliferation of spindle cells in a myxoid background, with an inflammatory infiltrate made of lymphocytes and plasmocytes. Immunostaining ruled out a malignant tumor. The diagnosis of an inflammatory pseudotumor developing on a Meckel diverticulum with gastric heterotopias was made. The outcome was favorable after surgical resection. CONCLUSION: While perforation of a Meckel diverticulum with gastric heterotopia is a common finding, the discovery of an inflammatory pseudotumor following a perforation is rare; the differential diagnosis should include Burkitt's lymphoma.

[Video-assisted surgery in children: current progress and future perspectives]. / Vidéochirurgie chez l'enfant : progrès actuels et perspectives.

This review presents the evidence of video-assisted surgery in the pediatric population and discusses future progress in this field. Videosurgery minimizes the cosmetic impact and the pain induced by open procedures and has been in constant development in adults and children. Earlier training of surgeons and residents combined with advances in anesthetics and technology have expanded the use of videosurgery for more complex interventions. Although most feasible surgical procedures have been performed by laparoscopy, the literature has not yet defined it as the gold standard for most interventions, especially because of the lack of evidence for many of them. However, laparoscopy for cholecystectomy is now the preferred approach with excellent postoperative outcomes and few complications. Although no evidence has been demonstrated in children, laparoscopy has been shown to be superior in adults for gastroesophageal reflux disease and splenectomy. Laparoscopic appendectomy remains controversial. Nevertheless, meta-analyses have concluded in moderate but significant advantages in terms of pain, cosmetic considerations, and recovery for the laparoscopic approach. Laparoscopy is now adopted for undescended testes and allows both localization and surgical treatment if necessary. For benign conditions, videosurgery can be an excellent tool for nephrectomy and adrenalectomy. However, laparoscopy remains controversial in pediatric surgical oncology.

[Abnormalities of the penis in boys]. / Anomalies du pénis chez l'enfant.

Abnormalities of the male genitalia have increased in the last 2 decades in numerous developed countries and remain a frequent reason of consultation in pediatric surgery. The diagnostic spectrum is wide, and surgeons should pay particular attention to these abnormalities because of their potential psychological effect. Anatomically, these abnormalities can affect one of three parts of the penis. First, the foreskin may not be fully retracted. This is normal at birth and can be caused by prepuce adherents that can continue until adolescence. Today, true phimosis is treated with topical corticoids from the age of 3 years. If medical treatment fails, a surgical procedure is required. Second, the urethra can be affected by hypospadia, which is the most frequent abnormality of the urethra. It is associated with ectopic urethral meatus, hypoplastic foreskin, and penis curvature. Its pathogenic background is not clearly understood. Surgery options differ according to the type of hypospadia and according to the surgeon's experience. It is sometimes hard to deal with, especially in a perineal form, where genetic and hormonal studies are recommended. These interventions can lead to complications ranging from stenosis to fistula. Therefore, parents have to be informed of the benefits and risks of the surgical procedures. Epispadias is rare but more serious because of the increasing risk of urinary incontinence. Finally, abnormalities of the corpora cavernosa - often associated with hypospadias - can include penis curvature and micropenis, for which an endocrinological analysis is essential.

P53-mediated upregulation of DcR1 impairs oxaliplatin/TRAIL-induced synergistic anti-tumour potential in colon cancer cells.

Oxaliplatin has emerged as a major chemotherapeutic drug in the treatment of advanced colorectal cancer, yet like most conventional cancer therapeutics, its efficacy is often compromised due to p53 mutations. Unlike oxaliplatin, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a p53-independent manner, and chemotherapy is known to overcome tumour resistance to TRAIL-induced cell death in most cancer cells. Using a panel of colon cancer cell lines, we assessed the ability of oxaliplatin to sensitize to TRAIL-induced apoptosis. We demonstrate that while both drugs additively or synergistically induced apoptosis in almost all cell lines tested, p53 wild-type colon cancer cells such as HCT116, LS513 or LS174T remained resistant. Impaired TRAIL-induced cell death resulted from a strong p53 dependent, oxaliplatin-mediated, DcR1 receptor expression increase. According to our finding, downregulation of DcR1 using siRNA, in p53 wild-type colon cancer cells, restored oxaliplatin/TRAIL synergistic apoptotic activity. On the contrary, exogenous DcR1 overexpression in SW480, a p53-mutated cell line, abolished the synergy between the two drugs. Altogether we demonstrate for the first time that p53 negatively regulates oxaliplatin-mediated TRAIL-induced apoptotic activity through DcR1 upregulation. Our findings could have important implications for future therapeutic strategies, and suggest that the association oxaliplatin/TRAIL should be restricted to patients harbouring a non-functional p53 protein.

The Mycobacterium bovis homologous protein of the Mycobacterium tuberculosis serine/threonine protein kinase Mbk (PknD) is truncated.

We previously identified a 70-kDa serine/threonine protein kinase (MbK or PknD) from Mycobacterium tuberculosis Erdman containing a transmembrane domain and bearing a 270-amino acid N-terminal kinase domain. With the use of a polyclonal serum, Mbk has now been identified by Western blotting in protein extracts from M. tuberculosis and confirmed to be localised in the envelope. An identical mbk gene has been found by sequencing different M. tuberculosis and M. africanum strains. Surprisingly, in two virulent M. bovis strains and four different strains of M. bovis BCG, an additional adenine after position 829 of the open reading frame was found that produces a frame shift resulting in a predicted truncated, presumably free cytoplasmic protein, encoding only the N-terminal 30-kDa Mbk kinase domain. This sequence polymorphism has been confirmed by Western blot analysis of M. bovis BCG protein extracts.

Compared recognition of di- and trisulfide substrates by glutathione and trypanothione reductases.

Trypanothione trisulfide was synthesized according to two strategies. It was found to be recognized and reduced by trypanothione reductase as the natural disulfide substrate. At the difference with the mechanism observed for the reduction of glutathione trisulfide by glutathione reductase, the intermediate trypanothione persulfide was rapidly reduced. The enzymatic reduction of another trisulfide derived from an alternative substrate of trypanothione reductase was also studied. The structure of the trisulfide bridge of the substrate (intra- or intermolecular) appeared to be a determining factor in the enzymatic reduction pattern. Moreover, in the case of the alternative substrate of trypanothione reductase, differences of kinetics appeared for the first time between a di- and a trisulfide species. All kinetic parameters are given.

Reduction of a trisulfide derivative of glutathione by glutathione reductase.

Glutathione trisulfide was synthesized from glutathione disulfide and its reduction by glutathione reductase was studied. A two-step reaction was observed. In a first step, the rate of reduction was similar to that observed with glutathione disulfide. In addition to glutathione, a persulfide intermediate was detected by an electrochemical method and was carboxymethylated by iodoacetate to be identified by Plasma Desorption Mass Spectrometry. During the second step the reduction of this intermediate led to the formation of hydrogen sulfide and a second equivalent of glutathione.

Preparation of anti-HIV-low-density lipoprotein complexes for delivery of anti-HIV drugs via the low-density lipoprotein pathways.

Lipophilic prodrugs of 3'-azido-3'-deoxythymidine (AZT) and of 2',3'-didehydro-3'-deoxythymidine (D4T) have been synthesized. 3 beta-(2'-carboxymethoxy)-cholest-5-ene acid, palmitic acid, linolenic acid, linoleic acid, and cholanic acid have been covalently bound to AZT and D4T. In some experiments the fluorescent molecule NBD was simultaneously linked. These prodrugs were incorporated into LDL or acetylated LDL. The best incorporation was obtained with drugs presenting a steroid moiety (cholesterol derivative or cholanic acid) in their structure. The incorporation of prodrugs into LDL was estimated as approximately 200 molecules of prodrug per LDL particle. Cytofluorimetric studies clearly show that the NBD-steroid LDL or NBD-steroid acetylated LDL are bound and then internalized by the B-E receptor (U937) or the scavenger receptor (mouse peritoneal macrophage), respectively. The antiretroviral activity of palmitate-D4T, cholanic-AZT, and cholanic-AZT-LDL complex was similar to the activity of free D4T and free AZT, respectively. Development of lipid nucleoside-LDL complexes to attach specifically to cells involved in HIV infection might have a direct clinical relevance.