Isolation of a new chlamydial agent from infected domestic poultry coincided with cases of atypical pneumonia among slaughterhouse workers in France

Three cases of atypical pneumonia in individuals working at a poultry slaughterhouse prompted an epidemiological survey in 10 poultry farms that had supplied birds. Using a Chlamydiaceae-specific real-time PCR assay, chlamydial agents were detected in 14 of 25 investigated flocks. Rather unexpectedly, Chlamydophila psittaci was identified only in one of the positive flocks, whereas ArrayTube DNA microarray testing indicated the presence of a new, so far unclassified member of the genus Chlamydophila.For further characterization of the agent involved, positive cloacal swabs were used to inoculate embryonated chicken eggs and isolates were obtained from 6 different flocks. Sequencing of 16S rRNA genes revealed nearly identical sequences of all samples. Alignment with representative sequences of Chlamydiaceae showed the separate position of the present strains outside the currently recognized species of Chlamydophila, but clearly within this genus. In contrast, partial ompA gene sequences displayed considerable diversity among the isolates, which had already been observed in restriction enzyme analysis of ompA PCR products. These data suggest that each farm had been infected with a different strain of this new chlamydial agent, the zoonotic potential and the exact taxonomic status of which have yet to be defined.     

(R)-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) blocks polymodal activation of transient receptor potential vanilloid 1 receptors in vitro and heat-evoked firing of spinal dorsal horn neurons in vivo

The transient receptor potential vanilloid (TRPV) 1 receptor, a nonselective cation channel expressed on peripheral sensory neurons and in the central nervous system, plays a key role in pain. TRPV1 receptor antagonism is a promising approach for pain management. In this report, we describe the pharmacological and functional characteristics of a structurally novel TRPV1 antagonist, (R)-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102), which has entered clinical trials. At the recombinant human TRPV1 receptor ABT-102 potently (IC(50) = 5-7 nM) inhibits agonist (capsaicin, N-arachidonyl dopamine, anandamide, and proton)-evoked increases in intracellular Ca(2+) levels. ABT-102 also potently (IC(50) = 1-16 nM) inhibits capsaicin-evoked currents in rat dorsal root ganglion (DRG) neurons and currents evoked through activation of recombinant rat TRPV1 currents by capsaicin, protons, or heat. ABT-102 is a competitive antagonist (pA(2) = 8.344) of capsaicin-evoked increased intracellular Ca(2+) and shows high selectivity for blocking TRPV1 receptors over other TRP receptors and a range of other receptors, ion channels, and transporters. In functional studies, ABT-102 blocks capsaicin-evoked calcitonin gene-related peptide release from rat DRG neurons. Intraplantar administration of ABT-102 blocks heat-evoked firing of wide dynamic range and nociceptive-specific neurons in the spinal cord dorsal horn of the rat. This effect is enhanced in a rat model of inflammatory pain induced by administration of complete Freund's adjuvant. Therefore, ABT-102 potently blocks multiple modes of TRPV1 receptor activation and effectively attenuates downstream consequences of receptor activity. ABT-102 is a novel and selective TRPV1 antagonist with pharmacological and functional properties that support its advancement into clinical studies.     

Neurological manifestations and ATP7B mutations in Wilson's disease

Wilson's disease (WD) is a rare inborn metabolic error characterized by deficient biliary copper excretion secondary to ATP7B gene mutations. Neurological presentations are variable in respect to both pattern and age of onset; commonly a movement disorder presents in the second or third decade. The aim of this study was to ascertain genotype correlations with distinct neurological manifestations in 41 WD patients in a Brazilian center for WD. A total of 23 distinct mutations were detected, and the frameshift 3402delC had the highest allelic frequency (31.7%). An association between 3402delC and dysphagia was detected (p=0.01) but the limited number of patients is insufficient to allow one to draw conclusions. Both clinical studies analyzing larger cohorts and basic research on ATP7B protein function could potentially shed more light on our understanding of WD.     

Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice

Oxidative stress is involved in many acute and chronic diseases including cancer, cardiovascular disorders and neurodegenerative diseases. We studied the relationship between the level of intracellular reactive oxygen species in peripheral granulocytes and the estimated anxiety level of mice using the behavioral light/dark choice test. Our results indicate a linear and significant relationship between the intracellular redox status of peripheral blood granulocytes and different parameters of anxiety-related behavior including latency time (R(2)=0.737, P<0.001), cumulative time spent in the lit box (R(2)=0.612, P<0.01) and number of entries into the lit box (R(2)=0.661, P<0.01). These results suggest a positive relationship between peripheral oxidative status and level of anxiety in mice.     

Pisiform-hamate synostosis with ulnar neuropathy. Case report

Entrapment of the ulnar nerve at the wrist is rare compared with the more commun site at the elbow. This condition was secondary to reccurent blunt trauma, ganglion cyst, vasculitic disorders, and fibrous bands. Compression of the ulnar nerve caused by pisiform-hamate coalition is rare entity. One case of this condition is reported.     

Characterization of the potency of epidermal growth factor (EGFR)-DNA targeting combi-molecules containing a hydrolabile carbamate at the 3-position of the triazene chain

Previous strategies for stabilizing combi-triazenes were based on masking the 1,2,3-triazene chain with a 3-acetoxymethylene group. The half-lives of the latter molecules were only ca 5 min longer than those of their parent 1,2,3-triazenes. The novel combi-molecules described herein contain a hydrolysable carbamate group that modulates their kinetics of degradation. Their half-lives were prolonged by ca 20–55 min when compared with their acetoxymethyltriazene counterparts. While they decomposed slowly in serum-containing medium, their intracellular decomposition was extremely rapid. They blocked EGFR tyrosine kinase in an isolated enzyme assay and in MDA-MB-468 breast cancer cells. Similarly, they all induced a dose-dependent DNA damage and G2/M cell cycle arrest in MDA-MB-468 cells, except the most stable compound ZRL2 (a 3-vinyl carbamate). ZRL4 (a chloromethyl carbamate) was the most potent and ZRL2 was the least active of the series against MDA-MB-468 cells. In selectivity assay with NIH-3T3 and NIH-3T3/HER-14, all compounds selectively blocked proliferation of NIH-3T3/HER-14. ZRS1 exerted the strongest growth inhibitory potency of the series. The results in toto suggest that ZRL2, despite being the most stable compound, could not hydrolyze at a rate that permitted the generation of DNA damaging species, thereby behaving primarily as an EGFR inhibitor. Thus the study permitted the definition of an optimized combi-molecule as one that decomposes at a rate that is slower than that of acetoxymethyltriazenes, but rapid enough to generate strong EGFR-DNA targeting potential and growth inhibition. Based on the latter criteria, ZRS1 and ZRL4 were tested in vivo and ZRS1 has proven the more effective.     

Male breast cancer]

This study has been realized to determine epidemiological profile and clinico-pathologic aspects of male breast cancer in the south of Tunisia. We has counted and analysed all male breast cancers diagnosed in the general surgery department of the Sfax university teaching hospital with proof pathologic or to defect cytologic of malignancy, between 1989 and 2000. In the court of these years 23 new cases of mammary cancer has been diagnosed at the man. The average patient age was 68 years (extremes 40 and 95 years). According to TNM classification of 1988, 4.3% were classified T1, 26.1% T2, 8.6% T3 and 61% T4; 22% of tumors were M1. Histology found: 3 in-situ carcinomas (13%), 18 ductular infiltrating carcinomas (79%), 1 papillary cystadenocarcinoma, and 1 neuro-endocrin tumor. The clinic profile of male breast cancer in our country rest again relatively little frequent and its clinic profile resist alarming. To get better prognosis it is important to increase information and to promote early detection.     

Transradial approach for coronary angiography and angioplasty]

The transradial approach of coronary angiography and angioplasty is now become a good alternative to the femoral approach in patients with normal Allen test results, because low rate of access site complication, improved patient comfort and early ambulation. This approach is particularly interesting in obese patients, aortoiliac disease or in patients under anticoagulation treatment or thrombolytics.