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.

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.

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.

The effect of time and of vasoactive drugs on capillary leakage induced during myocardial contrast echocardiography.

BACKGROUND: Premature ventricular contractions (PVC), capillary leakage, and petechial hemorrhage can occur during myocardial contrast echocardiography (MCE). The effects occur as a result of the interaction of contrast agent microbubbles and the ultrasound, but the detailed etiology of the effects is not yet clear. This study tested the hypothesis that the capillary leakage results from a physiological response to injury, which might be protracted and modulated by vasoactive drugs. METHODS: Hairless rats were anesthetized and transthoracically scanned with a diagnostic ultrasound system (GE Vingmed System V) at 1.7 MHz with 1:4 triggered frames at end systole. The scan head and rats were mounted in a 37 degrees C water bath to assure free-field conditions and placement of the heart at a similar focal distance as humans. A tail vein was cannulated for injections of Optison contrast agent, vasoactive medications, and Evans Blue dye (EB). EB was injected as a marker of capillary leakage before or after scanning. RESULTS: PVCs, petechia, and capillary leakage occurred during ultrasound exposure of microbubbles in myocardium, with no effects detected in shams. The influence of the vasoactive medications propranolol and isoproterenol on the effects did not support the hypothesis. Capillary leakage occurred during and postexposure, but diminished for EB injection 20 minutes after scanning with or without isoproterenol pretreatment. CONCLUSION: MCE induced PVCs, petechia, and capillary leakage, all of which ended immediately or within 20 minutes after the examination. Contrary to the hypothesis of a physiological mechanism, the capillary leakage appears to be primarily a mechanical effect rather than a physiological response.

Polycystin 1 is required for the structural integrity of blood vessels.

Autosomal dominant polycystic kidney disease (ADPKD), often caused by mutations in the PKD1 gene, is associated with life-threatening vascular abnormalities that are commonly attributed to the frequent occurrence of hypertension. A previously reported targeted mutation of the mouse homologue of PKD1 was not associated with vascular fragility, leading to the suggestion that the vascular lesion may be of a secondary nature. Here we demonstrate a primary role of PKD1 mutations in vascular fragility. Mouse embryos homozygous for the mutant allele (Pkd1(L)) exhibit s.c. edema, vascular leaks, and rupture of blood vessels, culminating in embryonic lethality at embryonic day 15.5. Kidney and pancreatic ductal cysts are present. The Pkd1-encoded protein, mouse polycystin 1, was detected in normal endothelium and the surrounding vascular smooth muscle cells. These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD.

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.

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.

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.

Exodontia e fragilidade capilar / Extraction of teeth e capillary fragility

O autor apresenta dois casos de extração de dentes em pacientes com problemas de vasos sanguíneos (fragilidade capilar). As fotos mostram equimoses faciais em ambos os pacientes. A prova de Rumper - Leede foi positiva em ambos os casos. Os sintomas desapareceram quando os pacientes foram submetidos a tratamento por drogas - vitaminas C, K e P. Em seguida os pacientes não mais exibiram sinais da doença sistêmica

Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study.

Preliminary data from a prospective randomized study of the use of a short course of adrenocorticosteroids in 73 children with ITP demonstrates a significant advantage of moderate dose (60 mg/m2/day p.o. X 21 days) prednisolone therapy in decreasing the duration of severe thrombocytopenia in most patients. The period of risk for serious bleeding, as reflected in the Rumpel-Leede test, was also significantly reduced. The number of children who developed chronic thrombocytopenia, although small in both groups, appeared to be uninfluenced by steroid therapy. No side effects or serious complications were noted in this trial.

Role of sulfhydryls and early vascular lesions in gastric mucosal injury.

This paper reviews the recently discovered role of sulfhydryls and early vascular injury in the pathogenesis of acute gastric mucosal injury. In the rat ethanol caused a dose-dependent decrease in nonprotein sulfhydryl concentration in the gastric mucosa within 1-5 min following an intragastric dose. These biochemical changes were accompanied by increased vascular permeability in the glandular stomach as revealed by the measurement of extravasated Evans blue injected i.v. prior to the administration of ethanol. Morphologic evidence of vascular injury was provided by labelling of damaged blood vessels in the stomach following the i.v. administration of colloidal particles in the form of india ink or monastral blue. The functional and structural damage to capillaries and venules in the glandular stomach was also maximal within 1-6 min after 1 ml of 75 or 100% ethanol given orally. Pretreatment with sulfhydryl (SH) containing drugs (e.g., L-cysteine, N-acetyl-L-cysteine, cysteamine, dimercaprol) or prostaglandin (PG) F2 beta prevented the ethanol-induced increase in vascular permeability, the labelling of blood vessels with vascular tracers, and the subsequent haemorrhagic erosions. The desquamation of superficial epithelial cells, however, was not markedly modified by either SH or PG compounds. This organoprotective effect of SH and PG drugs was virtually counteracted in adrenalectomized rats that exhibited "vascular fragility". Glucocorticoid treatment restored the response of adrenalectomized animals. Thus, a SH- and glucocorticoid-sensitive early vascular injury seems to be of major significance in the pathogenesis of haemorrhagic gastric erosions and SH-containing compounds represent a new group of cytoprotective or organoprotective agents.

[Capillary fragility in diabetics and its modification by calcium dobesilate]. / Untersuchungen zur Kapillarfragilität bei Diabetikern und ihrer Beeinflussung durch Kalziumdobesilat.

Investigations of the peripheral capillary resistance with the congestion test after Rumpel-Leede resulted in a maximally increased vascular fragility in 172 diabetics in 72% of the cases and in 54 test persons with healthy metabolism in 11% of the cases. Clear sex or age relations could not be proved. The high proportion of pathological test results already after a short duration of diabetes (beyond the 5th year 75%) and in ophthalmoscopically not yet provable retinopathy (70%) renders evident the increased capillary fragility as a symptom of the functional prephase of the specific microangiopathy and at the same time confirms its generalized character. In 115 diabetics with high-degree pathological congestion test (IVb) a 4-week treatment with 750 mg calcium dobesilate led in 94 cases to an improvement of the findings, in 17 patients to a complete normalization. On the basis of this result as well as of pathogenetic considerations calcium dobesilate offers itself as an adjuvant treatment measure which is early to be used. The influence of a simultaneously present hypertension on the development of microangiopathy became clear at the significantly more frequent pathological and medicamentously essentially worse influencible capillary resistance.