Identification of phenolic compounds from the leaf part of Teucrium pseudo-Scorodonia Desf. collected from Algeria.

In the present paper,we reported for the first time, the identification of the phenolic compounds in butanolic fraction obtained from the leaf part of Teucrium pseudo-Scorodonia Desf. collected from Algeria using RP-HPLC-PDA (Reversed Phase High Performance Liquid Chromatography/Photo Diode Array) technique. Several standards were used for this purpose. The analysis led to the identification of six phenolic acids (ferulic, sinapic, rosmarinic, syringique, caffeic, p-coumaric acids) and one flavonoid (rutin), the last one, has interesting pharmacological properties.

Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit.

Experimental thrombocytopenia results in endothelial alterations associated with bleeding. In this study prednisone was shown to prevent or reverse these changes, which supports the clinical inference that adrenocorticosteroids decrease capillary fragility in thrombocytopenia. Rabbits (3-4 kg), intraperitoneally injected with busulfan, developed 98-99% reductions in platelet count and hemorrhaged profusely. Orally administered prednisone (0.2 mg/kg or 1.0 mg/kg daily) reduced bleeding despite persistent thrombocytopenia. Tongue biopsies obtained after 3 days of prednisone treatment were examined by electron microscopy. Normal rabbits served as controls. 25 consecutive capillaries or venules from each of four animals in the control group and each of five experimental groups were examined for fenestrations, "thin spots" (<800 A thick), and mean wall thickness as determined by planimetry. Vessels from control animals had no thin spots or fenestrations, and the mean vessel wall thickness was 4,254+/-105 A SEM. The 100 vessels from the thrombocytopenic animals had a mean vessel wall thickness of 2,081+/-218 A (P < 0.001), and 42 had thin spots of fenestrations. After administration of the smaller dosage of prednisone, the mean vessel wall thickness increased to 3,556+/-40 A (P < 0.001), and only nine vessels had thin spots or fenestrations. With the larger dosage, only six vessels had thin spots or fenestrations and the mean vessel wall thickness of this group increased to 3,704+/-206 A (P < 0.005). All preparations demonstrated normal endothelial junctions. The data are consistent with the hypothesis that the bleeding of thrombocytopenia is caused by altered capillary and venule endothelium and that diminished bleeding observed with prednisone administration results from amelioration of these endothelial changes.

Microvascular and capillary perfusion following glycocalyx degradation.

Systemic parameters and microvascular and capillary hemodynamics were studied in the hamster window chamber model before and after hyaluronan degradation by intravenous injection of Streptomyces hyaluronidase (100 units, 40-50 U/ml plasma). Glycocalyx permeation was estimated using fluorescent markers of different molecular size (40, 70, and 2,000 kDa), and electrical charge. Systemic parameters (blood pressure, heart rate, blood gases) and microhemodynamics (vascular tone, velocity, and blood flow) remained statistically unchanged after injection of hyaluronidase, compared with inactivated hyaluronidase. Conversely, capillary hemodynamics were drastically affected. Functional capillary density, the capillaries perfused with red blood cells (RBCs), decreased by 35%, capillary Hct of the remaining functional capillaries increased from 16 to 27%, and penetration of 70-kDa fluorescent marker increased. Furthermore, plasma-only perfused capillaries statistically increased 30 min after hyaluronidase. The decrease in functional capillary density accounted for an increased RBC flux in the remainder of the capillaries, since the same number of RBCs had to traverse a reduced number of capillaries. Flux balances showed a reduction from baseline of 11% for the RBC flux and 20% for the plasma flux after treatment. These discrepancies are within the margin of error of the techniques used and could be explained by accounting for RBC over-velocity compared with plasma. These findings suggest that the decrease in the glycocalyx leads to capillary perfusion impairments.

[Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the renal parenchyma under aspirin use. Electron microscopic findings in the rat kidney]. / Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS). Elektronenmikroskopische Befunde an der Rattenniere.

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.

Interventions for leg edema and varicosities in pregnancy. What evidence?

Leg oedema from venous insufficiency is not dangerous but it can cause women symptoms such as pain, feelings of heaviness, night cramps and paraesthesiae. Leg oedema can be a sign of pre-eclampsia when associated with raised blood pressure or proteinuria. The objective of this review was to assess the effects of treatment to relieve the symptoms associated with varicosity in pregnancy and to reduce leg oedema. We searched the Cochrane Pregnancy and Childbirth Group trials register in October 2004 for randomised trials of any form of treatment for varicosity and or leg oedema in pregnancy. Trial quality was assessed and data were extracted. Four trials of three different treatments were included. In one trial, women given rutoside capsules in the last 3 months of pregnancy noted an improvement in symptoms compared with placebo (relative risk 0.54 95% CI 0.32, 0.89). They had a decrease in ankle circumference at 36 weeks' gestation after 8 weeks of treatment, while women given placebo had a small increase. In one trial, women with ankle oedema had a small non-significant reduction in lower leg volume when treated with external pneumatic intermittent compression for 30 min. In another trial compression stockings prophylactically reduced the emergence of leg symptoms but not venous varicosities (relative risk 0.74 95% CI 0.59, 0.93). Lymphatic reflexology was studied in too few women to draw conclusions. In conclusions, rutosides appear to relieve symptoms of venous insufficiency in late pregnancy. However, it is not known if the drug is safe in pregnancy. External pneumatic compression appears to reduce ankle swelling and compression stockings reduce leg symptoms but not varicose veins.

HR, 0-(beta-hydroxyethyl)-rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study.

The aim of this independent study was to investigate differences in efficacy between HR, (0-[beta-hydroxyethyl]-rutosides) and D+H (500 mg, diosmin+hesperidin) in patients with chronic venous insufficiency (CVI). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) were randomized into an HR or a D+H group. The HR group received oral HR (2 g/day, 8 weeks); the D+H group received a 500 mg tablet 3 times daily for 8 weeks. A second group of comparable patients was included in a registry following the same study format. Patients were openly included; the 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable to those described in the randomized study. Patients treated for at least 8 weeks were included in the registry. A number of physicians (specialists or general practitioners) included patients when they considered that clinical conditions were compatible with using 1 of the 2 treatments on the basis of their personal evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case. Patients were evaluated without interfering with the treatment. Main targets of evaluation were skin flux at rest (RF), strain-gauge-derived rate of ankle swelling (RAS), and analogue symptoms score (ASLS). Ninety subjects completed the study in the first group; 122 in the second, registry group (total of 212 patients). The first and second (registry) groups and the 2 treatment groups were comparable for age and sex distribution. The pooled mean age was 42 years (SD +/-5.5) in the HR group (46+62 patients) and 41.5 (SD +/-6) in the D+H group (44+60 patients). Considering pooled data there were no differences in microcirculatory parameters between the pooled treatment groups at inclusion. A significant decrease (p<0.05) in RF and RAS was observed in the HR group at 8 weeks. The decrease in resting skin flux and in capillary filtration was associated with a significant improvement in signs/symptoms (analogue scale line) from an average of 9.4 (range 3-10) to 3.3 (4-6) (p<0.05). Significantly smaller variations were observed in the D+H group. The decrease in RF was 47.6% in the HR group vs 15.7% in the D+H group. The decrease in RAS was 40.9% in the HR group vs 12.8% in the D+H group. The decrease in ASLS was 64.8% in the HR group vs 12.9% in the comparative group. In conclusion venous microangiopathy and edema were improved by the treatment with HR both in the randomized study and in the pooled analysis. The comparison with D+H indicates that HR is comparatively more effective both on microcirculatory parameters and on signs/symptoms of CVI.

Basal normoglycemia attained with chlorpropamide in mild diabetes.

Sixteen adult-onset diabetics, who were thought by current criteria to be well controlled on diet alone, had substantially elevated overnight, basal plasma glucose concentrations. Chlorpropamide had a sufficiently prolonged stimulatory effect on the beta cells such that normal basal plasma glucose levels were obtained in 13 patients. Both basal plasma C-peptide levels and the C-peptide response to meals became normal, with improved postprandial glycemia. Diurnal plasma triglyceride levels were reduced. Plasma growth hormone levels were normal both before and after therapy. When diet alone is insufficient to maintain basal normoglycemia in mild diabetes, chlorporpamide is as effective as basal insulin supplements in producing normal basal plasma glucose levels.

Experimental lead encephalopathy in the suckling rat: concentration of lead in cellular fractions enriched in brain capillaries.

Five-day old rats subjected to short-term (2-day) lead exposure by gastric gavage of aqueous lead acetate at the highest non-lethal dosage (1mgPb/g body weight/day) developed a hemorrhagic encephalopathy. Capillaries and microvessels isolated from brains of these rats showed abnormal morphology consisting of an increased number of irregularly dispersed endothelial nuclei and swollen, vacuolated endothelial cells. Lead was concentrated in isolated brain capillary-microvessel fractions, as demonstrated by both atomic absorption and 210Pb tracer methods. When lead exposure was continued for 20 days (at the maximal dosage regime compatible with a 60% survival rate), the rats recovered from the initial encephalopathy and capillaries and microvessels isolated from brains of these rats appeared morphologically normal. This recovery occurred despite continued high levels of lead in the blood and in the isolated capillary-microvessel fractions, suggesting that, as capillary endothelial cells mature, they are able to adapt to the presence of large amounts of lead.

Vasoactive agonists prevent erythrocyte extravasation in thrombocytopenic hamsters.

The mediating action of selected vasoactive amines and their respective antagonists on vascular fragility, visible as cutaneous petechiae, was assayed with thrombocytopenic (TCP) hamsters. Serotonin (5-HT), norepinephrine (NE), epinephrine, dopamine and isoproterenol administered IP reduced petechiae significantly within 10 min; phenylephrine had no effect. Of the natural amines, 5-HT and NE were most effective in reducing petechial sensitivity to values obtained with untreated, normal animals; hence these two amines only were tested pharmacologically. Pretreatment of TCP animals with Ketanserin or propranolol, administered IP or IV, abolished any petechial inhibitory action of 5-HT and NE respectively; pretreatment with phenoxybenzamine reduced significantly the NE inhibition of petechiae, but to a lesser degree than propranolol. In contrast, atenolol, prazosin and yohimbine had no significant effect. Ketanserin abolished the action of NE, but adrenoceptor blockers had no effect on 5-HT-treated TCP hamsters. The results suggest that 5-HT and NE inhibition of petechiae may be receptor-mediated and that there may be receptor interaction. This was supported by the observation that non-additive subthreshold doses of 5-HT and NE, which individually did not prevent petechial formation in TCP hamsters, when combined totally inhibited petechiae. The theorized importance of endogenous 5-HT and NE to maintain postcapillary venule junctional integrity (site of petechial hemorrhaging) was also demonstrated by treating normal hamsters with drugs known to block or antagonize either 5-HT or NE uptake. In every instance petechial sensitivity rapidly occurred, and the loss of microvascular integrity in Ketanserin-treated hamsters mimicked quantitatively the petechial sensitivity observed with TCP animals.

Correction of subclinical ascorbate deficiency in patients receiving dialysis: effects on plasma oxalate, serum cholesterol, and capillary fragility.

Whole blood ascorbate, plasma oxalate, serum cholesterol, and capillary fragility were measured at monthly intervals for 3 mth in 7 patients receiving continuous ambulatory peritoneal dialysis and 4 receiving haemodialysis, to whom ascorbate supplements had not been prescribed for at least 12 mth. Ascorbate supplements, 25 mg/day, were prescribed for the first month and 50 mg/day for the second month; in the final month patients received no supplements. Whole blood ascorbate was below normal in 6/11 patients at the start of the study but was normal in 10/11 patients when taking ascorbate 50 mg/day. No significant changes in plasma oxalate were observed with these doses of ascorbate, and correction of ascorbate deficiency had no effect on serum cholesterol, mean cell volume, or the results of capillary fragility tests. In a supplementary study, ascorbic acid 500 mg/day was administered for 3 wk to 11 patients. This resulted in a significant rise in mean plasma oxalate from 30.3 (SEM 3.5) to 48.4 (SEM 20.3) mumol/l.

Effect of a flavonoid preparation (S 5682) on experimental capillary permeability increase in rat paw and rabbit skin.

S 5682 is constituted by a flavonoid mixture of 90% diosmin and 10% hesperidin. Its action has been studied in vivo on microcirculation by measuring experimental alterations of capillary permeability and of venous pressure. Rats were pretreated by IV injection of 25 mg S 5682/kg, one hour before being submitted to a transitory compression of the posterior paw, resulting in reversible oedema that was estimated by plethysmography. The swelling of the paw in pretreated rats was lower than in controls (p less than 0.02), indicating a smaller increase of capillary permeability in rats treated with S 5682. A direct action on capillary permeability has been examined by measuring accumulation of IV injected Evans blue at the site of injection of zymosan, this accumulation was lower in pretreated rats than in controls (p less than 0.05). Similarly, in CFY rats, the pressure required to evoke capillary fragilisation was higher in S 5682 pretreated rats. Evans blue extravasation was also studied in the rabbit in which skin was irritated by topical application of chloroform of by gamma rays. Subcutaneous accumulation of Evans blue was lower in animals pretreated either IV or by oral route than in controls (p less than 0.05). S 5682 has a complex effect on microcirculation as indicated by a smaller increase in femoral venous pressure after ligation of homolateral iliac vein. The above experimental results indicate that S 5682 is acting at the venous side of the microcirculation.

Efficacy of topical treatment with aescin + essential phospholipids gel on capillary fragility.

The aim of this efficacy study was to evaluate local capillary fragility with the vacuum suction chamber (VSC) in patients with chronic venous hypertension due to chronic venous disease. All included patients had important ankle edema due to venous hypertension because of a post-thrombotic syndrome. Severe, deep, venous incompetence was present. The VSC was applied onto the internal perimalleolar region. Negative pressure was applied for a variable period of 2, 4, 6, 8, and 10 minutes. The negative pressure in the plastic chamber (2 cm in diameter)-as previously described-was 50 mm Hg. A group of ten patients (mean age 56 years; SD 4; M:F = 5:5) were studied. The tests were repeated in steps of two tests on different days. Between the two tests, with the VSC applied in different skin areas of the perimalleolar region, an interval of at least 30 minutes was observed.

[Anthocyanosides and the walls of the microvessels: further aspects of the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility]. / Antocianosidi e parete dei microvasi nuovi aspetti sul modo d'azione dell'effetto protettivo nelle sindromi da abnorme fragilità capillare.

On the basis of previous biochemical observations, which have demonstrated the formation of complexes between anthocyanosides and some phospholipids, the AA. investigate the modifications induced by local and general administration of anthocyanosides 1) on the foreign body granuloma and 2) on the composition of the protein fractions in the exudate from the capillaries of the granulation tissue, growing on post-thromboflebitic or varicose leg ulcerations. The biochemical and histochemical data may show that the anthocyanosides protect the altered capillary walls with a double mechanism: a) increasing the endothelium barrier-effect through a stabilisation of the membrane phospholipids and b) increasing the biosynthetic processes of the acid mucopolysaccharides of the connective ground substance, by restoring the altered mucopolysaccharidic pericapillary sheat. This last effect may explain the marked increase of new-formed capillaries and collagen fibrils induced by the anthocyanosides.

A comparison of template bleeding time with mucosal petechiometry as a measure of the platelet function defect induced by aspirin.

The object of this study was to assess the value of mucosal petechiometry as a useful method of measuring the haemostatic defect induced by aspirin. The template bleeding time was done for comparison. The results indicated that mucosal petechiometry did not measure the haemostatic defect induced by aspirin and that aspirin-induced alterations in platelet function were not important in the development of petechiae in healthy subjects.