Domain swapping in a COOH-terminal fragment of platelet factor 4 generates potent angiogenesis inhibitors

A few peptide residues in structurally important locations often determine biological functions of proteins implicated in the regulation of angiogenesis. We have shown recently that the short COOH-terminal segment PF-4(47-70) derived from platelet factor 4 (PF-4) is the smallest sequence that conserves potent antiangiogenic activity in vitro and in vivo. Here we show that modified COOH-terminal PF-4 peptides containing the sequence ELR (or related DLR), a critical domain present in proangiogenic chemokines, surprisingly elicit several times greater antiangiogenic potential than the original peptide. The modified peptides inhibit binding of iodinated vascular endothelial growth factor and fibroblast growth factor 2 to endothelial cell receptors, endothelial cell proliferation, migration, and microvessel assembly in the rat aortic ring model at lower doses than PF-4(47-70). On the differentiated chick chorioallantoic membrane, topical application of 40 micro g of modified peptides potently reduces capillary angiogenesis induced by vascular endothelial growth factor(165), a dose where peptide PF-4(47-70) was inactive. Established intracranial glioma in nude mice decreased significantly in size when treated locally with a total dose of 250 micro g of peptide PF-4(47-70)DLR (n = 10) compared with the same dose of the original PF-4(47-70) peptide (n = 10) or controls (n = 30). Tailored PF-4 peptides represent a new class of antiangiogenic agents with a defined mode of action and a strong in vivo activity.     

Experience with unoperated cleft lip and palate patients in a Nigerian teaching hospital

A review of 31 cases of unoperated cleft lip and palate patients aged 10 years and above managed over a 6 years period at a suburban Nigeria teaching hospital is presented. There was an overall preponderance of the female gender and isolated cleft lip (58%) was the most predominant. Although clefts were very wide on presentation, there was adequate well-developed soft tissue in adults to achieve a cosmetically and functionally acceptable repair. This study also confirms the views that late primary repair of facial cleft is less likely to produce impaired growth of the maxillaas is commonly observed in early repair. However, the advantages of early repair cannot be over-emphasized.     

The role of graftskin (Apligraf) in difficult-to-heal venous leg ulcers

A relatively recent option for treating leg ulcers that have lasted longer than a month is to use living bilayered skin equivalent alongside cornerstone compression therapy. This article discusses Graftskin and considers its practical use.     

Physiological cyclic variation of the myocardial integrated backscatter signal in athlete's heart

BACKGROUND: Left ventricular hypertrophy which realizes in athlete's heart could create some problems of acoustic reflection related to the increase of myocytic and not-myocytic elements of the heart. The aim of the present study was to analyze the ultrasonic backscatter myocardial indexes both as peak end-diastolic signal intensity and as its cardiac-cyclic variation in athlete's heart, compared to healthy sedentary controls. METHODS: Two groups of ten subjects each, all males of mean age (31.6+/-3.5), and of comparable weight and height were analyzed: group (A) comprised ten cyclists of good professional level and group (C) included ten healthy subjects acting as controls. A 2D-color Doppler echocardiography with a digital echograph Agilent Technologies (AT) Sonos 5500 was carried out on all subjects in the study for the conventional analysis of the left ventricular mass and function. The ultrasonic myocardial integrated backscatter signal (IBS) was analyzed with an "Acoustic Densitometry" module implemented on an AT echograph. The signal was also sampled with a R.O.I. placed at interventricular septum and at posterior left ventricular wall level. The systo-diastolic variation of the backscatter was also considered as Cyclic Variation Index (CVIibs). RESULTS: The left ventricular mass was significantly higher in athletes in comparison with controls (LVMbs: A: 154.5+/-18.7; C: 101.4+/-12.4; p<0.001). The end diastolic IBS signal did not show significant statistical differences between the two groups. The CVIibs both at septum (A: 30.5+/-5.3; C: 27.2+/-7.3; p<0.002) and posterior wall level (A: 43.7+/-9.1; C: 40.7+/-9.1; p<0.001) though was comparable in both groups. CONCLUSION: The conclusions reached in the present study confirmed the physiology of the left ventricular hypertrophy of the athlete's heart evaluated with an ultrasonic integrated backscatter tissue characterization, in particular through the cyclic variation of integrated backscatter myocardial signal. This finding is probably the expression of a preserved intramural myocardial function in the athlete's heart despite the increase of left ventricular mass induced by physical training.     

Results in displaced radial neck fractures in children. Metaizeau technique versus arthrotomy

The aim of the present article is to ascertain the differences between two surgical treatments commonly used in displaced radial neck fractures in children. We report the retrospective results of 20 displaced radial neck fractures with > 30 degrees of tilt (Judet grades 3-4) in children aged between 7 and 14 years treated with closed intramedullary pinning according to the Metaizeau technique (6 cases) or with arthrotomy and pinning (14 cases). Sex distribution was 14 girls and 6 boy. The average follow-up was 43 months. We found no relationship between delay in the surgical treatment and functional results. On the other hand, a relationship between residual final tilt and poorer functional results appears. The Metaizeau technique produced better results and fewer complications than arthrotomy and pinning, and, in our opinion, is the treatment of choice in this type of fracture.     

Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398

The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher in high-grade glioma than low-grade glioma and normal brain specimens. For a subset of these tumors (nine gliomas and three normal brain), Western blot analysis was also performed. COX-2 protein was detected in all specimens by Western blot analysis. The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and three-dimensional glioma spheroids was investigated using U-87MG and U-251MG human glioblastoma cell lines. The proliferation rate was assessed in monolayer cultures. In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor invasion assay were performed in a three-dimensional spheroid culture system. NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner. There was also a moderate increase in the number of apoptotic cells in the treated spheroids. NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system. Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may exist.     

Effect of 4-aminopyridine on cardiovascular functions in the dog

The drug 4-aminopyridine (4-AP) at a dose of 0.2 mg kg^-1 body weight intravenously is an effective antagonist of non-depolarizing neuromuscular blockade. We studied its cardiovascular effects in the canine heart using a right-heart bypass with extracorporeal circulation in seven dogs. This study demonstrates that 4-aminopyridine significantly augments arterial blood pressure, left ventricular dp/dt maximum, as well as left ventricular pressure at dp/dt mx. The highest values were obtained between two and 20 minutes after administration of 4-AP. Left ventricular end-diastolic pressure diminished slightly, but this was not statistically significant. Although the exact mechanism of action of 4-AP is not known, its positive inotropic effects may be of value in the reversal of non-depolarizing neuromuscular blockade in patients with impaired myocardial function of diverse aetiologies and it would be contraindicated in patients with arterial hypertension and/or coronary artery disease.