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PubMed2004

Vitamin C treatment reduces transcapillary escape rate of albumin in type 1 diabetes.

BACKGROUND: Latent tissue scurvy in clinical and experimental ascorbic acid (AA) deficiency resembles diabetic microangiopathy as reflected in capillary hyperperfusion and increased transcapillary escape rate (TER), von Willebrand factor (vWf), and capillary fragility (CF). We aimed to investigate the possible clinical impact of the low plasma AA level observed in type 1 diabetes mellitus. METHODS: Twenty normoalbuminuric patients with retinopathy were included in a randomized, double-blinded, placebo-controlled 6-month study with AA (6 g/day; n=10, mean age+/-S.D. 35.3+/-8.5 years, diabetes duration 17.2+/-3.3 years) or placebo (n=10; mean age 37.8+/-6.6 years, diabetes duration 18.4+/-1.7 years). RESULTS: An inverse correlation between log plasma AA (HPLC method) and TER of (125)I-labelled albumin was found (r=-0.66, p=0.002). TER decreased in the AA-treated group from 6.8+/-1.0 to 5.4+/-1.5%/h compared to the unchanged placebo group (from 5.6+/-1.5 to 5.9+/-1.1%/h; p=0.031). The CF (capillary resistance test) decreased in the AA group compared to the placebo group (p=0.028), while vWf, fibrinogen and fibronectin levels, and glomerular filtration rate (clearance of (125)I-iothalamate) remained unchanged. CONCLUSIONS: The results suggest that a low plasma AA level might be associated (pathogenetic?) with development of microangiopathy in type 1 diabetes mellitus and points to a possible treatment modality.

Journal Article↗
PubMed1989

Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analyses.

Capillary sprouting was studied by a combination of intravital video recording and subsequent electron microscopy in the mesentery of young female rats without previous experimental manipulation. Selected segments of the mesenteric microvascular bed with capillary sprouts were carefully surveyed and mapped at a monitor magnification of 255 times and submitted to detailed in vivo analysis concerning flow pattern and cells at 2000 times magnification. The mesentery was preserved for light and electron microscopy by a superfusion of glutaraldehyde while observed and recorded on video, confirming earlier investigations that this type of fixation does preserve exceptionally well vascular topography and diameters of the mesenteric microvascular bed. Capillary sprouts originated as endothelial spurs from arteriolar-venular arcades and continued to grow in size through a bipolar rearrangement of endothelial cells, forming a solid sprout tip which progressively lengthened by alternately rapid and slow growth phases. The extended leading tip of the migrating endothelial cells displayed microspikes and pseudopodia denuded of basal lamina. The cytoplasm of the leading tip contained an array of microtubules, 75 A filaments and many small vesicles. In similarity with the situation in nerve growth cones, all these organelles probably participate in cytoplasmic streaming and cell migration. The sprout lumen arose between endothelial cells of the solid sprout. Mesenteric connective tissue fibroblasts approached and settled down on the sprouts, being converted to pericytes as the fibroblasts became enveloped by a basal lamina. The pericytes reinforced the wall of the delicate and fragile capillary sprouts, and trapped plasma, platelets and red blood cells which had leaked out temporarily, in the process assuming an umbrella shape. The arteriolar feeder of the arcades was surrounded by cells which were classified as intermediate between pericytes and true smooth muscle cells. Sprouts that presumably were on the verge of merging with other capillaries were analyzed for indications of how anastomoses are formed.

Animals↗
PubMed2005

Conservative management of symptomatic and/or complicated haemorrhoids in pregnancy and the puerperium.

BACKGROUND: Haemorrhoids (piles) are swollen veins at or near the anus, normally asymptomatic. They do not constitute a disease, unless they become symptomatic. Pregnancy and the puerperium predispose to symptomatic haemorrhoids, being the most common ano-rectal disease at these stages. Symptoms are usually mild and transient and include intermittent bleeding from the anus and pain. Depending on the degree of pain, quality of life could be affected, varying from mild discomfort to real difficulty in dealing with the activities of everyday life. Treatment during pregnancy is mainly directed to the relief of symptoms, especially pain control. The so-called conservative management includes dietary modifications, stimulants or depressants of the bowel transit, local treatment, and phlebotonics (drugs that cause decreased capillary fragility, improving the microcirculation in venous insufficiency). For many women, symptoms will resolve spontaneously soon after birth, and so any corrective treatment is usually deferred to some time after birth. Thus, the objective of this review is to evaluate the efficacy of conservative management of piles during pregnancy and the puerperium. OBJECTIVES: To determine the possible benefits, risks and side-effects of the conservative management of symptomatic haemorrhoids during pregnancy and the puerperium. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 June 2004). SELECTION CRITERIA: Randomised-controlled trials comparing any of the conservative treatments for symptomatic haemorrhoids during pregnancy and the puerperium (such as dietary modifications, stimulant/depressant of the bowel transit, local treatments, drugs that improve the microcirculation in venous insufficiency) with a placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently performed a methodological assessment for deciding which studies to include/exclude from the review and extracted data. MAIN RESULTS: From 10 potentially eligible studies, two were included in this review (150 women). Both compared oral rutosides against placebo. Rutosides seem to be effective in reducing the signs identified by the healthcare provider, and symptoms and signs reported by women, of haemorrhoidal disease. For the outcome no response to treatment: relative risk 0.07, 95% confidence interval 0.03 to 0.20. Regarding perinatal outcomes, one fetal death and one congenital malformation (possible not related to exposure) were reported in the control and treatment group respectively. AUTHORS' CONCLUSIONS: Although the treatment with oral hydroxyethylrutosides looks promising for symptom relief in first and second degree haemorrhoids, its use cannot be recommended until new evidence reassures women and their clinicians about their safety. The most commonly used approaches, such as dietary modifications and local treatments, were not properly evaluated during pregnancy and the puerperium.

Female↗
PubMed1992

Flow-limited tracer oxygen distribution in the isolated perfused rat liver: effects of temperature and hematocrit.

We used the multiple-indicator dilution technique to examine the kinetics of tracer oxygen distribution and uptake in the rat liver perfused in a nonrecirculating fashion with blood. 51Cr-labeled 18O2-saturated erythrocytes, labeled albumin, sucrose and water (the tracers for oxygen and vascular, interstitial and cellular references) were injected simultaneously into the portal vein. Timed anaerobic samples were collected from the hepatic vein and analyzed by mass spectrometry for relative 18O2 enrichment and radioactivity. In a set of experiments performed at 32 degrees C, oxygen uptake was substantially diminished; tracer oxygen profiles approached those expected for a completely recovered, flow-limited substance. At 37 degrees C, much larger tracer oxygen sequestration occurred. Experiments were carried out at each temperature at higher and lower hematocrit, and oxygen consumption at each temperature was found to be independent of hematocrit. The tissue space of distribution for tracer oxygen relative to the total sinusoidal vascular content was influenced by the hematocrit: it was smaller at higher hematocrit and larger at lower hematocrit, as expected. The derived partition coefficient of oxygen for liver cells relative to plasma (expressed in terms of the liver and plasma water spaces) was, on average, 2.62 ml/ml; it was independent of the hematocrit. Analysis of the indicator dilution experiments indicates that the tracer oxygen is distributed into tissue in a flow-limited rather than a barrier-limited fashion, and that with this, an ongoing concomitant intracellular sequestration of tracer can be seen.

Animals↗
PubMedDate not supplied

Mass spectrometry in grape and wine chemistry. Part I: polyphenols.

Mass spectrometry, had and still has, a very important role for research and quality control in the viticulture and enology field, and its analytical power is relevant for structural studies on aroma and polyphenolic compounds. Polyphenols are responsible for the taste and color of wine, and confer astringency and structure to the beverage. The knowledge of the anthocyanic structure is very important to predict the aging attitude of wine, and to attempt to resolve problems about color stability. Moreover, polyphenols are the main compounds related to the benefits of wine consumption in the diet, because of their properties in the treatment of circulatory disorders such as capillary fragility, peripheral chronic venous insufficiency, and microangiopathy of the retina. Liquid Chromatography-Mass Spectrometry (LC-MS) techniques are nowadays the best analytical approach to study polyphenols in grape extracts and wine, and are the most effective tool in the study of the structure of anthocyanins. The MS/MS approach is a very powerful tool that permits anthocyanin aglycone and sugar moiety characterization. LC-MS allows the characterization of complex structures of grape polyphenols, such as procyanidins, proanthocyanidins, prodelphinidins, and tannins, and provides experimental evidence for structures that were previously only hypothesized. The matrix-assisted-laser-desorption-ionization-time-of-flight (MALDI-TOF) technique is suitable to determine the presence of molecules of higher molecular weight with high accuracy, and it has been applied with success to study procyanidin oligomers up to heptamers in the reflectron mode, and up to nonamers in the linear mode. The levels of resveratrol in wine, an important polyphenol well-known for its beneficial effects, have been determined by SPME and LC-MS, and the former approach led to the best results in terms of sensitivity.

Agriculture↗
PubMed1989

Massive pulmonary haemorrhage due to leptospirosis.

A young man with leptospirosis developed massive pulmonary haemorrhage. This was remarkable both in its severity and in its occurrence early in the clinical course - before the onset or presence of jaundice, renal failure or of a serological diagnosis. It occurred in the absence of a coagulopathy or thrombocytopenia and presumably was a consequence of the capillary fragility characteristic of the disease - perhaps precipitated in this instance by mechanical ventilation.

Adult↗
PubMed1991

A review of the pathophysiology of exercise-induced pulmonary haemorrhage in the equine athlete.

In the United States, more than 75% of equine athletes are reported to suffer from exercise-related haemorrhage of the respiratory tract (Voynick and Sweeney, 1986; Sweeney et al., 1990). Fiberoptic endoscopy has traced the source of blood to beyond the bifurcation of the trachea. In 1981, the term exercise-induced pulmonary haemorrhage (EIPH) was introduced (Pascoe et al., 1981). Racehorses of all breeds, polo ponies and three-day event horses of mixed heritage, even foxhunters, may 'bleed' (Voynick and Sweeney, 1986; Pascoe et al., 1981; Sweeney and Soma, 1983; Hillidge, 1986). Any horse working at speeds greater than 240 m/min is at risk (Voynick and Sweeney, 1986). The impact of exercise-induced pulmonary haemorrhage is difficult to assess. Most attempts to demonstrate statistically a negative correlation between EIPH and performance have been unrewarding, largely due to the number of uncontrollable variables (Pascoe et al., 1981; Raphel and Soma, 1982). In racing thoroughbreds (Mason et al., 1983) and standard breeds (MacNamara et al., 1990) approximately half as many EIPH-positive as EIPH-negative horses were placed in their races. Based on extensive intrapulmonary haemorrhage, a 3-year prospective study of sudden deaths in exercising thoroughbreds concluded that 9 out of 11 deaths were attributable to EIPH (Gunson et al., 1988). By correlation of clinical signs, thoracic radiographs, ventilation/perfusion scintigraphy, gross and subgross pathology and histopathology in 26 affected thoroughbreds, EIPH has been associated with chronic small airway inflammation, proliferation of subpleural, peribronchial and septal bronchial arterioles, interstitial connective tissue fibrosis and alveolar septal disruption in the dorsocaudal lung lobes (O'Callaghan et al., 1987). From this work it was proposed that the initial insult of EIPH started as focal, dorsocaudal pulmonary peribronchial inflammation which resulted in bronchial arterial neovascularization. Haemorrhage then occurred when, during exercise, bronchial blood pressure increased in fragile capillary buds. The incidence of bronchitis/bronchiolitis, regardless of aetiology, has been estimated to be 30% in non-racing equine athletes and close to 100% in one group of racing thoroughbreds (Sweeney et al., 1989). Histological study of lungs from horses with mild, moderate and severe chronic small airway disease consistently revealed a greater density of lesions in the diaphragmatic lobes (Winder and von Fellenberg, 1988). To understand further the aetiology and/or pathophysiology of EIPH, we will first explore some aspects of general mammalian and specific equine pulmonary and bronchial vascular anatomy and physiology. Exercise-related changes in these systems in normal and EIPH-positive horses will be briefly reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

[Rational hemostatic screening].

BACKGROUND: In order to exclude hemorrhagic diathesis, e.g. before diagnostic measures carrying the risk of bleeding or in preoperative situations, a graded screening is advisable. PROCEDURE: During the first stage, besides the anamnesis, clinical examination and classification of relevant concomitant diseases (e.g. liver cirrhosis or renal insufficiency), basic laboratory examinations such as prothrombin time, activated partial thromboplastin time (aPTT) and platelet count must be carried out. Should all these measures produce no noteworthy results, no further examinations are necessary. However, in the case of test results within normal limits accompanied by an unsatisfactory anamnesis and/or conspicuous clinical findings, the second stage should include examination of bleeding time according to Mielke to exclude a relevant platelet dysfunction. Should this be inconspicuous a third stage should follow in which successive implementation is made of fibrinogen according to Clauss, the Rumpel-Leede test (to exclude heightened capillary fragility), factor XIII and alpha 2-antiplasmin. The methodical snares of the parameters mentioned will be explained in full.

Blood Coagulation Tests↗
PubMed2002

Development of an arterial tree in C6 gliomas but not in A375 melanomas.

The microcirculation of tumors is severely disturbed. Tumors are usually supplied by fragile capillaries and do not possess the natural hierarchy of blood vessels. The detection of specific markers for arterial and venous endothelial cells (ECs) now enables us to study the vascular tree in tumors. We have injected rat C6 glioma and human A375 melanoma cells into 3.5- to 4-day-old avian embryos. After 10-12 days of reincubation the tumor cells formed solid tumors vascularized by host ECs. In contrast to the melanomas, the gliomas induced an almost normal vascular tree with arterial and venous vessels. The arterial vessels express the arterial EC marker ephrin-B2, and possess a media of smooth muscle alpha-actin (alphaSMA)-positive cells. Venular vessels in the gliomas are ephrin-B2-negative/alphaSMA-positive. Although the gliomas may represent a rare case of vascular tree induction in tumors, the results underline the heterogeneity of tumor-induced angiogenesis. This has an impact on tumor blood flow and thereby also on the efficacy of chemotherapy and radiotherapy.

Actins↗
PubMed1992

Octreotide and diabetes: theoretical and experimental aspects.

Diabetes is characterized by paradoxical hypersomatotropinemia and hyperglucagonemia. The latter appears to enhance the tendency in imperfect metabolic control to reduce nitrogen balance, and the former appears to accelerate the deterioration of carbohydrate and lipid metabolism, and also to induce peripheral insulin resistance and hyperinsulinemia. In addition to direct metabolic effects, increasing evidence points to an association between hypersomatotropinemia and a number of metabolically dependent, characteristic functional abnormalities linked to the development of late diabetic manifestations. These include increased capillary fragility, lipid and hemostatic aberrations, tissue hyperperfusion, including increased cardiac output and renal plasma flow, and kidney hypertrophy. In theory, octreotide's actions could reduce these aberrations, and, in fact, this has been confirmed in recent experimental trials.

Animals↗
PubMed1988

Otolaryngological problems associated with thrombocytopenia purpura in children.

Otolaryngological manifestations of 90 patients (of which 50 were under 16 years) with immune thrombocytopenia purpura (I.T.P.) appearing at the Pingdingshan Hematological Institute over 10 years have been studied. Among the sick children, epistaxis was the most common complaint (of which 60% responded to nasal packing), followed by gum, buccal, conjunctive, tongue, lips, eyelids, facial and throat bleeding, in this order. Severity and recurrence were correlated with the sick children's condition: the presence or absence of local trauma and infection, blood platelet level and capillary fragility, especially in acute I.T.P. Some therapeutic principles for these associated abnormalities are recommended. Other conditions included: hearing loss, vertigo, or dizziness, tinnitus, facial paralysis and so on. Our conclusion is that the role of immune responses may be important in the etiopathogenesis of these non-hemorrhagic abnormalities, and should not be ignored in treating the problems as result of I.T.P. In this paper, these immunological and pathological mechanisms implicated in the two problems described above are also discussed.

Adolescent↗
PubMed2000

[Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature].

PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed. Since their release unexpected adverse effects such as bleeding disorders have been described. METHODS: Thirty patients with either hematoma or muco-cutaneous bleeding have been selected from case reports of the Saint-Etienne Pharmacovigilance center and from a literature review. RESULTS: The female/male sex-ratio was 3:4 and the mean age 42 years. Two newborns who had been exposed in utero to SSRIs were also included in the study. Eleven patients presented an underlying disease or were at risk. Various adverse effects such as bruising, hematoma, petechiae or purpura, epistaxis, and more rarely intestinal hemorrhage, ocular bleeding or cerebral hemorrhage were encountered. Symptoms were sometimes associated with prolonged bleeding time and platelet aggregation disorders and usually resolved within two days to four months after treatment discontinuation. CONCLUSION: Hematoma and muco-cutaneous bleeding would therefore be related to treatment, including selective serotonin reuptake inhibitors. However, these adverse effects are still poorly known and rarely reported. The main mechanism suggested would be a decrease in serotonin platelet leading to a defect in platelet aggregation. However, an increase in capillary fragility or susceptibility related to the patient's condition might be involved. Study of hemostasis history in patients requiring treatment with SSRIs might be of value.

Adolescent↗
PubMed1999

Simultaneous spectrophotometric determination of rutin, quercetin and ascorbic acid in drugs using a Kalman Filter approach.

A UV-spectrophotometric analysis of severely overlapped spectra yielded by anti-capillary fragility pharmaceutical materials, viz. rutin, quercetin and ascorbic acid, in authentic mixtures and in tablets or soft elastic capsules was proposed. The method was based on Kalman Filter calibration of either orthogonal experimental design, i.e. standard solutions containing only one component at a time, or non-orthogonal experimental design, i.e. standard solutions containing more than one component. This calibration was followed by quantitative determinations of two- and three-component mixtures in synthetic mixtures or in oral dosages within the concentration range 2-10 microg ml(-1). A statistical analysis of the results was reported.

Ascorbic Acid↗
PubMed1989

[Hematoma of the adrenal glands and heparin].

The diagnosis of adrenal haemorrhage complicating heparin therapy is often delayed, despite computed tomography (CT). Moreover, its pathogenesis is not clear. Adrenal haemorrhages are often seen in cases where there is no unduly excessive anticoagulation, and can be accompanied by a paradoxical thrombosis of the central adrenal vein. Symptoms usually occur within the first 8 to 12 days after starting heparin. The difficulty in establishing the diagnosis stems from the fact that symptoms are rather nonspecific: abdominal pain and backache, nausea, vomiting, lethargy, weakness, hypotension, hyperpyrexia. To confirm the diagnosis, both hormonal proof of adrenal failure and anatomic evidence of haemorrhage must be found. Early CT scans may show the haemorrhage. Several possible causes have been put forward to account for these adrenal haemorrhages. The degree of anticoagulation did not seem to be a prerequisite, 30 to 50% of patients showing no evidence of other bleeding or coagulation tests outside the therapeutic range. Capillary fragility of old age might be a factor. Stress would seem to be an important factor predisposing to adrenal haemorrhage. Many authors consider the paradoxical central vein thrombosis as a result of the haemorrhage rather than its cause, whereas other conclude the opposite. Unfortunately, to date coagulation studies are often incomplete; platelet counts were missing in most reports published before 1985. Since that date, a heparin induced thrombosis-thrombocytopaenia syndrome (HITTS), in which thrombosis may occur in any vascular bed, has been recognized with increasing frequency. Nine cases of adrenal haemorrhage associated with HITTS have been reported. It seems highly likely that a proportion of cases of heparin-related adrenal destruction are due to HITTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Diseases↗
PubMed2000

Development of local patches containing melilot extract and ex vivo-in vivo evaluation of skin permeation.

Melilot extract could be effective in treating localised varicose syndrome or capillary fragility. The monolayer patch was selected to obtain a prolonged release of coumarin contained in the phytocomplex. Two types of methacrylic patches (patch 1 based on a blend of Eudragit E100 and Eudragit NE; patch 2 based on Eudragit L100) were prepared. Both patches were equivalent in terms of coumarin release and ex vivo skin permeation profiles. The two patches differed significantly as regards respective adhesive properties. At low peel rate only patch 1 showed adhesive failure as confirmed by the in vivo performance. When comparing the behaviour of the patches containing melilot extract with analogous patches containing synthetic coumarin, no melilot phytocomplex enhancer effect was shown. The data of the ex vivo coumarin skin permeation and those obtained by the in vivo stripping technique showed a good correlation (r(2)=0.9727 for patch 1, r(2)=0.9835 for patch 2).

Adhesiveness↗