Coxsackievirus B3 replication and persistence in intestinal cells from mice infected orally and in the human CaCo-2 cell line

Although the transmission of coxsackievirus B3 occurs mainly via the oral route, little is known about the primary replication and persistence of this agent in the intestine. To address this question, BALB/c mice were inoculated by gavage with coxsackievirus B3, Nancy strain. The mice were killed from 1 hr to 90 days after infection. The viral markers were detected in the small intestine using RT-PCR, cell culture and detection of VP1 protein. Coxsackievirus B3 was detected positive by the three methods from hr 2 to day 45 after infection. By using monoclonal antibodies directed towards VP1, CD40 and CD26, the virus was shown to be present in the lymphocytes of the mucosa as soon as 2 hr after infection; in contrast, no virus was detected in the epithelial cells lining the intestinal lumen. Further experiments were performed to evaluate the capacity of coxsackievirus B3 to establish a persistent infection in two intestinal cell lines. In contrast to HT29 cells, the CaCo-2 cells were shown to develop a persistent infection for up to 20 passages, as demonstrated by the detection of viral RNA and VP1 protein. This study provides further evidence that, after infection by the oral route, the viral particles are concentrated in the lymphocytes of the mucosal layer. In addition, the results suggest that coxsackievirus B3 is capable of establishing a persistent infection in the small intestine that may act as a reservoir of viral particles for the delayed spread of the virus to other target organs.     

Hereditary sideroblastic anemia: a rare diagnosis

Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.     

Suture patterns and corneal graft rotation in the cadaver eye

Torque and antitorque running sutures as described by Eisner are commonly used in penetrating keratoplasty. We tested the rotational effect of three different 16-bite running suture patterns on eight cadaver eyes, with the following results: (1) the torque pattern rotates the corneal graft counterclockwise by 0.7 +/- 0.1 mm at the wound or 11 degrees; (2) the antitorque pattern rotates the corneal graft clockwise by 0.7 +/- 0.1 mm at the wound or 11 degrees; (3) an intermediate "no torque" pattern, the bites of which form an isosceles triangle, produces no rotational effect. We recommend the use of a "no torque" pattern to minimize corneal graft rotation.     

Prognostic study of cell proliferative markers ki67, PCNA and p53 oncoprotein in bladder tumors

We report a study of cell proliferative factors Ki67, PCNA and p53 oncoprotein in 55 patients with bladder tumors. Fifty-three of the patients were male and two were female, with a mean age of 56.6 and 68.5 years, respectively. These tumors were of transitional cell type in 97.9% of the cases. Staging was, respectively, pTis (4.76%), pTa (30.9%), pT1 (19.04%), pT2 (23.8%) and Pt3 (21.4%). Our study of proliferative nuclear markers Ki67 showed that cell proliferation increased in bladder tumors according to grade in the same stage. This variation was highlighted by our results for PCNA but was not verified for Ki67. However, these results revealed an increase of cell proliferation for a same grade (grade I and II) in different stages (pTa, pT1, pT2) for PCNA; this was not ascertained for Ki67. The study of p53 oncoprotein showed that detection of mutated p53 protein increased according to grade only for grades II and III and to stage only when moving from pTis to superficial tumors (pTa, pT1) and to deep tumors (pT2, pT3), thus individualizing two groups without significant variation within these groups. A variation according to grade in the same stage was noted only for stages pT1 and pT2. A variation for a same grade (grades II and III) was reported between stages pTa, pT1 and pT2. The combined study of Ki67, PCNA and p53 oncoprotein showed a prognostic correlation between these three markers in general.     

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides.     

Primary mitochondrial arteriopathy

AimWhether arteries are affected in mitochondrial disorders (MIDs) was under debate for years but meanwhile there are strong indications that large and small arteries are primarily or secondarily affected in MIDs.Data synthesisWhen reviewing the literature for appropriate studies it turned out that vascular involvement in MIDs includes primary or secondary micro- or macroangiopathy of the cerebral, cervical, and retinal arteries, the aorta, the iliac arteries, the brachial arteries, or the muscular arteries. Arteriopathy in MIDs manifests as atherosclerosis, stenosis, occlusion, dissection, ectasia, aneurysm formation, or arteriovenous malformation. Direct evidence for primary cerebral microangiopathy comes from histological studies and indirect evidence from imaging and perfusion studies of the brain. Microangiopathy of the retina is highly prevalent in Leber's hereditary optic neuropathy. Macroangiopathy of the carotid arteries may be complicated by stroke. Arteriopathy of the aorta may result in ectasia, aneurysm formation, or even rupture. Further evidence for arteriopathy in MIDs comes from the frequent association of migraine with MIDs and the occurrence of premature atherosclerosis in MID patients without classical risk factors.ConclusionsMitochondrial arteriopathy most frequently concerns the cerebral arteries and may result from the underlying metabolic defect or secondary from associated vascular risk factors. Vascular involvement in MIDs has a strong impact on the prognosis and outcome of these patients.