Archives de l'Institut Pasteur de Tunis最新文献

Matrix metalloproteinases (MMPs) are a family of enzymes that have been recognized as promising therapeutic and diagnostic targets for the treatment and detection of human cancers. This rises from their unique ability to degrade all components of the extracellular matrix and their overexpression at different stages of tumor progression. The specific involvement of MMPs in the oncogenic processes has speeded up the efforts that have been made for the past 20 years to develop and evaluate MMP inhibitors (MMPIs) as potential anti-cancer agents. However, bringing an MMPI to the point of clinical approval is still a challenge. In this review, we provide an overview of the structure and function of MMPs along with their implication in cancer development. Furthermore, we focus on the literature concerning the development of broad spectrum natural and synthetic MMPIs, with emphasis on their limitations and the disappointing results of most clinical trials. The failure of broad spectrum MMPIs highlighted the need for the development of selective inhibitors that fully discriminate between different members of the MMP family. As a future perspective on the development of potent MMPIs, we also report in this review a novel structure-based strategy developed in our group to design new mini-protein ligands for MMP inhibition by functional motif grafting.

Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients, caused by Pneumocystis jirovecii (P. jirovecii). The co-infection with community-acquired P. jirovecii and Mycobacterium tuberculosis (M. tuberculosis) is exceptionally described in non immunocompromised patients. We herein report the case of a young woman, with no medical history, who developed an acute respiratory failure due to P. jirovecii pneumonia associated with miliary tuberculosis. An extensive immunological investigation ruled out any acquired or primary immunodeficiency, suggesting that she was most likely immunocompetent. This report shows that such infections are not restricted to immunocompromised hosts. Moreover, it is tempting to speculate that the development of M. tuberculosis infection in this patient could be a risk factor for transition from colonization status of respiratory tract by P. jirovecii to pneumocystosis.

Multiple myeloma (MM) is a still incurable adult's severe hematologic malignancy. It is characterized by deregulation of several cytokines and their receptors. Among these cytokines, Insulin growth factor 1 (IGF1) and its receptor (IGF1-R) are well documented as major factor of malignant plasma cells growth and survival in multiple myeloma. The objective of this study was to analyze the expression of IGF1-R in multiple myeloma at diagnosis in correlation with clinical and biological data. IGF1-R gene plasma cells expression was studied in 47 patients and 17 controls by Taqman technology RT-PCR. IGF1-R gene was down expressed in the malignant plasma cells of MM patients at diagnosis compared to normal plasma cells, isolated from healthy donors (p = 0.01). Expression decrease was accentuated in the disease advanced stage IIIB. A negative correlation was found between IGF1-R malignant plasma cells expression and the percentage of bone marrow invasion (p = 0.03). Bone marrow infiltration greater than 30% was significantly associated with a low level of IGF1-R gene expression (p = 0.04). Our results suggest that the decreased expression of IGF1-R by malignant plasma cells is a prognostic factor associated with severe disease. Understanding of mechanisms involved in IGF1-R expression negative regulation may contribute to the discovery of new targets therapy in myeloma. the discovery of new targets therapy in myeloma.

In Tunisia, the most important sector of aquaculture is shellfish farming industry. Unfortunately, in recent years this sub-sector knows many problems of shellfish contamination due to blooms of toxic algae. This phenomenon occurred for the first time in 1994 in the Gulf of Gabes after the proliferation of Karenia cf. selliformis which synthesizes gymnodimine, a potent neurotoxin. Following these effects, several collection sites especially Boughrara lagoon, were closed for extended periods. Recently, an atypical toxicity was detected, initial characterization studies carried out by LC-MS showed that the toxins detected probably belong to the family PSP toxins. The lagoon of Bizerte was also known since 2006, a repeatable events of contamination of mussels and oysters. As a result, many samples were DSP and PSP positive with concentrations up to 2100 microg eq.STX/100 g meat.

The aims of this study is to determine the hemogram reference values in a population of healthy adults of the region of Sfax, to compare our results with those from the literature, to estimate the age and sex variations in the blood count. The hemogram parameters were analyzed in 1000 blood donors. Hemogram was performed using Coulter ACT10's analyser. The differential leukocyte count was manually performed. The means of erythrocyte count, hemoglobin, haematocrit and red cell indices were significantly lower in women than in men. There was a significant variation in the red blood cell count, hemoglobin and haematocrit with age. There is also sex and age differences of the leukocyte count. The neutrophil and eiosinophil counts were higher in women than in men. The lymphocytes decreased with age in both sexes. The platelet count was significantly higher in women than in men. These results can be applied only to our local population of adults. The definition of reference values for the Tunisian population requires a study on a more diversified population, including more important number of individuals from various regions of the country.

The authors had for aim to study the distribution of HIV-1 subtypes in a cohort of HIV positive patients in the hospital General Peltier of Djibouti. An epidemiological study was made on 40 HIV-1 positive patients followed up in the Infectious Diseases Department over three months. All patients sample were subtyped by genotyping. Thirty-five patients (15 men and 20 women) were found infected by an HIV-1 strain belonging to the M group. Genotyping revealed that - 66% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. In fact, Subtype C prevalence has been described in the Horn of Africa and a similar prevalence was previously reported in Djibouti. However our study describes the subtype B in Djibouti for the first time. It is the predominant subtype in the Western world. The detection of CRF02_AG strains indicates that they are still circulating in Djibouti, the only country in East Africa in which this recombinant virus was found. CRF02_AG recombinant isolates were primarily described in West and Central Africa. The presence of this viral heterogeneity, probably coming from the mixing of populations in Djibouti, which is an essential economic and geographical crossroads, incites us to vigilance in the surveillance of this infection.

With nearly eight million new cases each year and two million deaths, tuberculosis (TB) remains a major health problem worldwide. The limited protection afforded by the only available vaccine, Bacille Calmette-Guerin BCG, and the emergence of multi-resistant strains to antibiotics along with the advent of AIDS, are three main causes that contributed to the increase of TB incidence during the last decade. The World Health Organization (WHO) estimates between 2000 and 2020, nearly one billion people will be newly infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, and 200 millions of them will develop the disease, of which 35 million will die if there is no improvement in controlling infection. Such improvement requires an increase in our knowledge of the fundamental biology of this very complex disease and in particular a better understanding and characterization of the types of interactions between mycobacteria and the immune system. The alveolar macrophage (MØA), the first immunological barrier that opposes the mycobacteria, plays a key role in the evolution of infection. In addition to the recognition and immediate elimination of the bacteria by phagocytosis and secretion of microbicidal products, MØA is extremely important in orchestrating the immune response and the establishment of a specific response provided by T cells. This review summarizes the state of our knowledge about the mechanisms deployed by the macrophage to contain Mtb infection with a focus on apoptosis as an innate immune response against this pathogen. We also describe the mechanisms developed by Mtb, during its coexistence with humans, in order to escape the macrophage response.

Beyond the obvious problems related to the sustainable management of wild stocks, current fish farming practices in the Mediterranean area entail important environmental risks and potential outbreaks of fish diseases linked to massive translocations across regional boundaries. Viral haemorrhagic septicaemia (VHS) and infectious hematopoietic necrosis (IHN) are well-known fish diseases caused by the VHSV and IHNV viruses, and positive cases are subject to obligatory reporting to the World Organisation for Animal Health (OIE). In August 2004, the OIE published the first record of a VHS outbreak in a sea bass (Dicentrarchus labrax) aquaculture facility on the coast of the Mediterranean Sea. However, D. labrax is not considered as a susceptible host species for viral hemorrhagic septicaemia according to OIE's International Aquatic Animal Health Code (2009) and VHSV was not previously reported in the Mediterranean. In this sense and given the high risk of disease translocation associated with farmed fish in marine aquaculture, the present study was aimed at investigating the presence of VHSV and IHNV in stocks of sea bass and sea bream (Sparus aurata) reared inside a Tunisian coastal fish farm. Cell culture, IFAT and RT-PCR were applied to screen for both VHSV and IHNV in 69 pooled samples of sea bass and 24 pooled samples of sea bream. All three techniques showed the absence of both viruses within fish at the selected site.

Colonic ameboma is a rare benign inflammatory tumor due to the infection by Entamoeba histolytica and poses frequently the problem of colon cancer. We report a case of a 52 year-old patient who presented a cecal amoeboma revealed by a painful mass in the right iliac fossa. Radiologic and endoscopic examinations depicted a parietal thickening of the right colon and the cecum. A presumptive diagnosis of colon cancer was firstly discussed. Confirmation of ameboma was made on pathological examination, PCR and serology.

This study aimed at investigating whether the efficiency of the leishmanin skin test (LST) to evaluate the immune status of individuals exposed to Leishmania (L.) infantum is age-related. It was conducted in two districts of the governorate of Kairouan, an endemic region for L. infantum infection in Tunisia. Healthy individuals (n = 119) were selected according to two criteria: no current or past history of visceral or cutaneous leishmaniasis, and their age range: 1-6 years (group I), 7-14 years (group II), and 20-66 years old (group III). Assessments comprised LSTs, in vitro lymphoproliferative response, and interferon-gamma (IFN-gamma) productions induced by soluble leishmanial antigens (SLA). LST recorded an overall of 89.07% and 89.9% concordance with T cell proliferation and IFN-gamma production induced by SLA, respectively. Using in vitro tests as gold standards, LST was found more sensitive for screening individuals from group I (96% and 100%, considering T cell proliferation and IFN-gamma production results, respectively), than group II (91% and 97%) and group III (70% and 74%,). Conversely, LST was less specific in group I (84% and 77%) than group II (100% and 94%) and group III (100% for both in vitro tests). Our results suggested that the strength of LST resided in its higher sensitivity, to unravel asymptomatic injections and cell mediated immunity to L. infantum parasite in infants and its higher specificity for screening adult individuals. Negative LST in adults and positive LST in children < 5 years, the population at risk of developing visceral leishmaniasis, remain the weaknesses of LST and should be interpreted with caution.