Adenovirus inhibition by peptidomimetic integrin antagonists

Many viruses and bacterial pathogens are capable of exploiting host cell surface integrins during their replication cycles. The ligands for many integrins contain an arginine-glycine-aspartic acid (RGD) amino acid sequence that is essential for protein-protein interaction. Human adenovirus particles contain this sequence in the penton base protein, and previous studies support a role for this RGD in integrin-dependent internalization of the virus by the cell. As synthetic peptidomimetics of RGD have been shown in other experimental systems to be antagonists of the activities of specific integrins both in vitro and in vivo, we sought to determine whether these small molecules are antagonists of adenovirus infection. Such compounds inhibited viral infection of cultured cells with similar rank order potency to that determined in assays utilizing purified extracellular matrix proteins as integrin ligands. The maximal level of inhibition achieved with the peptidomimetics was comparable to that of RGD-containing peptides, whereas no significant effects were apparent with an RGE-containing peptide. An engineered adenovirus having a mutated RGD sequence in the penton base was not susceptible to the inhibition. The results obtained with these synthetic antagonists, which have varied structures and potencies, suggest that integrins interact with adenoviral RGD in a manner similar to that of other protein ligands such as vitronectin. Furthermore, the results confirm the role of RGD in the replication cycle, and suggest peptidomimetic compounds may be useful antimicrobial agents in the treatment of a variety of diseases.     

Tracheo-colonic fistula: an exceptional complication after total replacement of an esophagus injured by acid

A 49-year-old woman underwent emergency gastrectomy for suicidal caustic ingestion, followed later by transhiatal esophagectomy and left colonic interposition. A fistula developed postoperatively between the trachea and interposed segment of colon. This exceptional complication was successfully treated by resection of the fistula, closure of the colonic defect and tracheal myoplasty using the sterno-cleidomastoid muscle.     

Doxazosin and soluble guanylate cyclase in a rat model of hypertension]

BACKGROUND: Although different studies have evaluated the ability of endothelial cells to produce NO in the setting of the endothelial dysfunction associated with hypertension, less it is known about the soluble guanylate cyclase system. AIM: To analyze the level of expression of sGC in the vascular wall in Stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated. METHODS: The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12). RESULTS: Isolated aortic segments from SHRSP showed impaired response to SNP. Doxazosin treatment prevented impaired vasodilatory response to SNP. Expression of the beta1 sGC in the vascular wall of SHRSP determined by Western blot and immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin treatment increased of beta1 sGC expression in treated SHRSP particularly at the medium level with respect to that of untreated SHRSP. CONCLUSION: SHRSP showed reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator response to SNP which improved with doxazosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.     

Increased release of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone during immersion-induced central hypervolemia in cirrhotic humans.

The role of peptides from the N-terminus and C-terminus of the 126 amino acid (a.a.) atrial natriuretic factors (ANF) prohormone in modulating renal sodium and water handling in cirrhotic patients has not been defined. Eight cirrhotic individuals were evaluated; their mean basal circulating concentration of the C-terminus (a.a. 99-126; i.e., ANF) was 25 +/- 2 fmol/ml, not different from the 22 +/- 1 fmol/ml value found in 54 normal volunteers. On the other hand, the basal circulating concentrations of the whole N-terminus (a.a. 1-98) and the midportion of the N-terminus (namely a.a. 31-67; pro ANF 31-67) of the ANF prohormone in these cirrhotic subjects of 704 +/- 52 and 654 +/- 83 fmol/ml were significantly elevated (p less than 0.05; ANOVA) in comparison to control values (531 +/- 25, 317 +/- 22 fmol/ml, respectively). Following equilibration on a 10 mmol/day sodium diet, the responsiveness of the N-terminus and C-terminus of ANF prohormone to 3 h of water immersion, which induces marked acute central volume expansion, was evaluated in these 8 seated cirrhotic patients. There was a prompt increase in the circulating concentrations of immunoreactive (ir) pro ANF 1-98 (whole N-terminus), ir pro ANF 31-67, and ir ANF (C-terminus) within 15 min of immersion (p less than 0.05; ANOVA) compared to their preimmersion values. The response of circulating ir pro ANF 1-98, pro ANF 31-67, and ANF concentrations in these 8 cirrhotic subjects to immersion was significantly greater (p less than 0.05; ANOVA) than that of 7 healthy volunteers undergoing an identical 3-hour immersion study. With cessation of immersion, the C-terminus decreased within 30 min to a concentration not significantly different from preimmersion values, whereas the N-terminus and pro ANF 31-67 remained significantly elevated after 1 h.     

Centralised treatment of soft tissue sarcomas in adults

The clinical research developed in specialised centres and oncologic cooperative groups has permitted various scientific societies to collect recommendations used in the treatment of soft tissue sarcomas (STS) and incorporate them into clinical practice guidelines (CPG). Some studies have been conducted in diverse healthcare ambits to assess the influence of CPG. This revision of the medical literature analyses the impact that healthcare management -centralised or otherwise- and clinical practice in conformity with CPG have on the clinical outcome variables of STS. Eight CPG have been identified, as well as 12 conformity studies or audits. These conformity studies and audits demonstrate that the grade of adaptation of medical interventions with CPG, medical healthcare in reference centres and procedures of referrals to these centres, as well as the process of organising healthcare teams into Sarcoma Committees, have a significant influence on clinical outcome. We can conclude that excellent healthcare of STS implies the adaptation of healthcare practice to CPG, the existence of Reference Centres guided by Sarcoma Committees, and the observance of strict referral procedures within the Healthcare Area.     

Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines

Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study.     

The measurement of osteoporosis in clinical practice

Summary It has been reported that metacarpal morphometry does not correlate with iliac crest histomorphometry in patients with hip fractures. Such disagreement led us to study the correlation between both types of measurements on 35 patients who had suffered hip fracture. We observed a significant correlation between metacarpal morphometry and iliac crest cortical width (p<0.001), and to a lesser degree with the trabecular bone volume (p<0.01). The same was also true if we assessed separately the patients with cervical or trochanteric hip fractures.