Intravenous treatment with liposome-encapsulated dichloromethylene bisphosphonate (C12MBP)suppresses nitric oxide production and reduces genetic resistance to Marek's disease

In this study the functional effectiveness of in vivo macrophage depletion using liposome-encapsulateddichloromethylene bisphosphonate (C12MBP) was examined in the chicken. The main target organs forsystemic liposome-encapsulated C12MBP treatment are the spleen and the liver. Intravenous treatment withC12MBP of B²¹/B²¹ chickens, genetically resistant to Marek's disease (MD), before challenge with the very virulent strain RB-lB, increased viral load in the blood and spleen after the first week and up to 6 weeks postinfection. In addition, C12MBP treatment dramatically increased tumour incidence and tumour load, especially in the spleens and livers of sick animals, but without affecting MD-specific mortality of B²¹/B²¹ cickens infected with RB-1B at 12 days of age. Nitric oxide (NO) is an important effector of the macrophage and has antiviral and antitumoural properties. NO has been shown to be one of the mechanisms triggered in resistance to Marek's disease. Intravenous treatment with Cl2MBP before infection with RB-1B induced a long-lasting decrease in numbers of macrophages and reduction in splenic inducible NO production associated with an absence of nitrate induction in the serum (up to 6 weeks pi). These results do not identify macrophage and NO production as major effector components in genetic resistance to Marek's disease, but underline their roles in limiting viraemia and tumour development in organs such as the spleen and the liver.     

In vivo macrophage activation in chickens with Acemannan, a complex carbohydrate extracted from Aloe vera

Acemannan (ACM 1), a beta-(1,4) -acetylated mannan isolated from Aloe vera, can be used as an effective adjuvant in vaccination against some avian viral diseases. Our results demonstrate a quick and lasting in vivo priming effect of ACM 1 on macrophage response after intramuscular inoculation in chickens (500 microg per 2-month-old bird). In response to IFN-gamma in vitro, monocytes from ACM 1-treated chickens exhibited a strong enhancement of NO production from 3 to 9 days p.i., but a weaker effect on MHC II cell surface antigen expression on day 3 p.i. A stimulating effect of ACM 1 treatment was also observed on spontaneous and inducible NO production for splenocytes only on day 3 p.i. By that time, splenocytes exhibited a strong higher capacity to proliferate in response to the T cell-mitogen PHA. At the same time, the in vivo capacity to produce NO, measured by the (NO(-)(2)+NO(-)(3)) serum level after intravenous LPS injection, increased greatly from 3 to 9 days p.i. In conclusion, ACM 1 was able efficiently and durably to increase the activation capacity of macrophages from the systemic immune compartment (in particular from the blood and spleen after an intramuscular injection) in chickens, especially for NO production. These findings provide a better understanding of the adjuvant activity of ACM 1 for viral and tumoral diseases.     

Ex vivo all-trans retinoic acid modulates NO production and regulates IL-6 effect during rheumatoid arthritis: a study in Algerian patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.     

Kudoa azevedoi n. sp. (Myxozoa, Multivalvulida) from the oocytes of the Atlantic horse mackerel Trachurus trachurus (Perciformes, Carangidae) in Tunisian coasts

A new species Kudoa azevedoi sp. n. (Myxozoa, Multivalvulida) is described in Trachurus trachurus Linnaeus, 1758 (Carangidae) from fishing harbors in Tunisian coasts using spore morphology and SSU rDNA sequence data. The parasite occurs only in ovaries within oocytes of mature and immature specimens. Spores are quadrate in shape in apical view with rounded edges, having four shell valves and four symmetrical polar capsules. They are of small sizes and measure 3.5?±?0.41 (3–4.2)?×?4.5?±?0.44 (4–5.2) length by width. The polar capsules are pyriform in shape measuring 1.5?±?0.22 (1.5–2)?×?0.75?±?0.14 (0.5–1)?μm. Infected oocytes are hypertrophied, whitish colored, and filled with mature spores. Plasmodia are tubular and ramified from the inner membrane toward the center of the oocyte. Phylogenetic analysis based on small subunit ribosomal DNA sequences shows the highest similarity (96 %) with the ovary parasite Kudoa ovivora. Some morphological details and spore dimensions support the creation of a new species in the genus Kudoa. Mean prevalence among examined females is of about 55.5 %. It varies between localities and length of fish. The present myxosporea is the second Kudoa species reported in fish ovaries.     

Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet’s disease: a study in Algerian patients

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet’s disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.     

Epidemiologic profile of Haemophilus influenzae infection in Tunisia

Haemophilus influenzae, a commensal bacteria, is frequently incriminated in broncho--pulmonary surinfections and severe diseases as meningitis, pneumonia and septic arthritis, particularly in young children. A multicenter study was conducted to establish the epidemiological profile of Haemophilus influenzae diseases, to determine the rate of antibiotics resistance for guide therapeutic and preventive strategies. The identification was based on the requirements for X and V factors, and the serotype b determined by agglutination. The betalactamase production was done by nitrocefin test. Antimicrobial susceptibility testing was determined on Muller Hinton chocolate agar with isovitalex. During the two year period, (January 1998 December 1999), 192 isolates of H. Influenzae were collected, 61% were recovered from invasive infections (44 meningitis, 8 bacteremia, 2 arthritis). The serotype b was identified in 55.7% of cases, 67.3% were invasive strains. 24.5% of isolates were producing betalactamase particularly invasive serotype b strains. All isolates of H. influenzae were susceptible to cefotaxim and to ofloxacin. Resistance rates to other antibiotics were: erythromycin 56.2%, tetracyclin 10.3%, rifampin 12%, chloramphénicol 1%, cotrimoxazole 16.5%, 11.5% amikacin and 20% gentamicin. The incidence of meningitis remained frequent in our country, involving the introduction of the vaccination in official calendar. Nevertheless, the surveillance of H. influenzae invasives infections and the serotyping of isolates were necessary to evaluate the impact of the immunization.     

Progressive encephalomyelitis with rigidity presenting as a stiff-person syndrome

Diagnosis criteria of stiff-person syndrome (SPS) include progressive, fluctuating muscular rigidity and spasms with normal neurological examination. The presence of unusual features such as prominent limb rigidity with segmental signs and contracture, evidence of brainstem dysfunction, profound autonomic disturbances, CSF pleiocytosis or MRI abnormalities in patients with SPS presentation allows to classify these patients as progressive encephalomyelitis with rigidity (PER). We report a 50 year-old woman suffering from severe painful spasms of abdominal wall and limb muscles. Neurological examination showed pyramidal signs. EMG disclosed continuous muscle activity with superimposed discharges. Treatment with high doses of diazepam and baclofen led to moderate improvement of generalised stiffness. However, the right arm became more rigid with oedema and vasomotor changes. Subsequently, bilateral nystagmus and internuclear opthalmplegia appeared. There was mild CSF pleiocytosis. Associated auto-immune thyroiditis was found with positive anti-microsome antibodies and decreased thyroid hormones. Search for profound neoplasm was negative. The patient had three subacute bouts then she improved with methylprednisolone. The initial clinical presentation mimicking a SPS with subsequent diffuse involvement of the central nervous system and a striking localisation of a severe rigidity to one arm allowed to suspect the diagnosis of PER. The relationship between SPS and PER remains unclear because of the rarity of these disorders. The observation reported in this paper gives evidence that both the disorders are probably two clinical presentations of the same pathogenic process.     

Serum lactate dehydrogenase and its isoenzymes in nasopharyngeal carcinoma in Tunisia

Our prospective study interested 41 patients, from 13 to 70 years old, and present a nasopharyngeal carcinoma confirmed histologically, during the period going from September 1999 to March 2000, and 45 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure serum LDH and its isoenzymes. Two groups of patients were selected after a period varying from 12 to 37 months with a mean of 29 months: 29 with favourable evolution, 12 with non favourable evolution. The mean serum total LDH and its isoenzymes values were significantly higher in patients than those in controls with values of variable p of 0.001 to 0.05. A significant correlation was found between ganglionnary extension and serum values of total LDH, LDH3 and LDH5. No significant difference were observed between the means serum total LDH before treatment and the clinical evolution of patients. Diagnostic contribution of total LDH is limited, by its ubiquitary character, but could constitute for LDH3 a good marker of the disease progression.     

Vitamin A effects on morphometric adaptation after extensive small bowel resection in the rat

This work was conceived to study, in the rat short bowel syndrome, the effect of precocious administration of retinoic acid on morphometric adaptation in the remnant intestine. Mitotic index, villous height, crypt depth and mucosal aspect were determined in 2 groups of rats (n=12) after 60% small bowel resection. 100 microg of retinoic acid were perfused immediately after resection in the first group. Control group rats received placebo. Two similar groups (n=12) underwent intestinal transection with or without retinoic acid perfusion. Our results show that retinoic acid induced precocious and significant enhancement of all morphometric parameters when compared to placebo.     

Seric soluble interleukin-2 receptor alpha in nasopharyngeal carcinoma in Tunisia. Prospective study about 45 cases

BACKGROUND: Soluble interleukin-2 receptor alpha (slL-2Ralpha) is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma. METHODS: Our prospective study interested 45 patients (35M/10F) with a mean age of 49 years (15 to 78), presenting a nasopharyngeal carcinoma histologically confirmed and 61 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure sIL-2Ralpha by immunoenzymatic assay. According to the disease status after a period of follow-up ranging from three to 22 months (median 12 months), patients were divided into two groups: The remission group (n=28) represented those with favourable evolution and a second group of 15 patients with unfavourable evolution (2 death, 4 cases of persistent primary disease and 9 patients with distance metastasis). 2 patients were lost to follow-up. RESULTS: serum sIL-2Ralpha levels were significantly higher in patients vs healthy controls (p < 0.0001). The serum levels correlated with the stage T of NPC (p = 0.01). Patients having a favourable evolution have lower sIL-2Ralpha levels before treatment vs those with unfavourable evolution without statistical difference. CONCLUSION: Measurement of serum sIL-2Ralpha provides a good estimation of the nasopharyngeal tumor burden. The usefulness of this marker as a parameter to predict prognosis in NPC should be examined further.