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[Blood-activating and anti-inflammatory actions of Polygala fallax].

OBJECTIVE: To observe the blood-activating and anti-inflammatory actions of Polygala fallax Hesml. (PFH) in this paper. METHODS: A series of experiments were performed to show the blood-activating and anti-inflammatory actions of PFH, including acute blood-stagnation model in rats induced by dextran of high molecular mass, observation on microcirculation in mice, platelet aggregation in vitro in rabbits, acute inflammation in mice induced by xylene or histamine, and PC-DTH. RESULTS: PFH could remarkably decrease the whole blood relative viscosity. PFH could significantly dilate the micro-artery and micro-vein, increase the opening number of capillary in mice. However, PFH had no obvious effect on platelet aggregation induced by ADP in rabbits. PFH could significantly inhibit the increase of capillary permeability induced by histamine in mice, and decrease the mice ear-swelling induced by xylene. PFH could remarkably inhibit the induction-phase and attack-phase of PC-DTH in mice. CONCLUSION: The results suggested that PFH could improve the hemorrheologic character in blood-stagnation state, invigorate the micro-circulation, and inhibit inflammation process.

Animals↗

Pharmacological actions of tentacle extract of the jellyfish, Acromitus rabanchatu, occurring in the Bay of Bengal.

Tentacle extract of A.rabanchatu, produced a fall of blood pressure in cat, rat and guinea pig. Hypotension produced in cat remained unantagonized by blockers of acetylcholine, histamine and 5-HT. On isolated guinea pig heart, the extract significantly reduced the rate and amplitude of contraction leading to irreversible cardiac arrest. In cats and rats, the respiratory rate and amplitude was decreased significantly and resulted in temporary apnoea. The extract also produced vasoconstriction in perfused rat hindquarter preparation and increased cutaneous capillary permeability. The extract produced contraction in several isolated smooth muscle preparations. Contraction on guinea pig ileum was partly antagonized by atropine and cyproheptadine. On isolated rat phrenic nerve diaphragm and chick biventer cervicis, the extract produced irreversible blockade of the electrical stimulation-induced twitch responses. Haemolytic and myonecrotic activity was exhibited by the extract. LD50 was found to be 7.7 mg/kg (iv, mice).

Animals↗

[State of the microcirculation in myocardial ischemia and its alterations after depositing bioresorbing microspheres of Sephadex in the coronary bed].

It is shown that the diffusion capacity of the capillary channel diminishes in myocardial ischemia. In unchanged or increased capillary permeability this effect may only be explained by a functional shunt of the affected cardiac area. Intracoronary administration of a carrier of biologically active substances in the form of microspheres of modified Sephadex does not aggravate irregularity in the blood supply to the zone of ischemia, which is evidence of the adequacy of the organ reserves of the functional shunt in this situation.

Absorption↗

[Ovarian hyperstimulation syndrome (OHS): borderlines between physiology and pathology].

The use of gonadotropins in therapy has led to the appearance of a complication due to hyperstimulation, referred to as "syndrome due to ovarian hypertension" (SOH). There are three clinical stages of SOH: slight, moderate and severe, caused by a pathogenetic mechanism which is thought to involve the action of prostaglandins and the renin-angiotensin system leading to an alteration in capillary permeability with increased ovarian diameter. SOH can be prevented using a protocol to evaluate clinical conditions during therapy mainly based on hormone assays and echographic monitoring. SOH can be predicted but not prevented, thus making it important to commence immediate treatment for in-patients so as to restore the volume of blood and the blood protein load in the most severe cases.

Adult↗

Albumin metabolism in rabbits and rats with transplanted tumours.

Albumin distributions and turnover rates have been studied using (131)I labelled tracer material in rabbits with Vx2 carcinoma and rats bearing SP7 fibrosarcoma in comparison with control animals. Albumin concentrations were reduced in the tumour bearing animals but plasma volumes increased as the tumours developed. Relative increases were seen in the extravascular distribution of albumin, due partly to albumin pooling in and around the tumours and possibly also to general increases in capillary permeability. In the rats there was a considerable increase in the catabolic rate of albumin which was not related to urinary protein loss. The tumour bearing rabbits showed evidence both of increased catabolism and of decreased synthesis and the combination of the two effects resulted in a greater lowering of albumin concentration than was seen in the rats. Possible mechanisms for these findings and their significance in human malignant disease are discussed.

Animals↗

Coagulatory response after femoral instrumentation after severe trauma in sheep.

OBJECTIVE: Pulmonary complications after intramedullary femoral nailing have been attributed to bone marrow fat embolization and a variety of cascade effects. We investigated whether the coagulatory response after intramedullary femoral nailing in merino sheep is altered after severe trauma. METHODS: Adult merino sheep were submitted to hemorrhagic shock (2 hours, 50 mm Hg) and unilateral lung contusion. After recovery (day 3 of the study), reamed femoral intramedullary nailing (RFN), unreamed femoral intramedullary nailing (UFN), or plate osteosynthesis of the femur (P) was performed. Pulmonary artery pressure, central venous levels of factor V, protein C, antithrombin III, and fibrinogen, were determined. At 1 and 3 days before and after femur instrumentation, pulmonary capillary permeability was assessed on the basis of the comparative albumin content in bronchoalveolar lavage fluid. RESULTS: Group RFN, n=8; group UFN, n=7; group P, n=6. A significant (p < 0.05) postoperative increase in the relative albumin content in terms of the BAL/plasma albumin ratio was measured in group RFN (day 3 preoperatively: 0.38+/-0.05 day 3 postoperatively: 0.53+/-0.06, p < 0.05 (RFN vs. P), which contrasted with group UFN (day 3 preoperatively: 0.44+/-0.09, day 3 postoperatively: 0.46+/-0.09, no significant difference). This evidence of increased pulmonary permeability occurred in association with evidence of increased activation of coagulation factors (data presented as percentage of day 3 preoperative baseline values). The data for fibrinogen (15 min postoperatively) is as follows: group RFN, 74+/-9% (p < 0.05 vs. P); group UFN, 83+/-8% (not significant); group P, 98+/-6%. The data for antithrombin III (15 min. postoperatively) is as follows: group RFN, 72+/-6% (p < 0.05 vs. P); group UFN, 79+/-8% (not significant); group P, 92+/-8% (not significant). CONCLUSION: After severe trauma, an increase of pulmonary permeability after reamed femoral nailing was associated with increased consumption of coagulation factors. After unreamed nailing, a similar trend was apparent, but this was not found to be statistically significant. These data provide support for the theory that after severe trauma, unreamed femoral nailing reduces but does not abolish pulmonary sequelae when compared with reamed femoral nailing.

Adolescent↗

Intermittent fluid retention in women. Is it idiopathic edema?

When a capillary or renal disturbance is not apparent in a woman of reproductive age who presents with edema, a disorder referred to as idiopathic edema should be considered. This disorder, which is often intermittent, causes fluid to accumulate when the patient is upright. Because of this postural relationship, research into pathogenesis has focused on homeostatic adjustments to changes in posture. A number of mechanisms have been proposed, the most tenable of which seem to be increased capillary permeability, increased mineralocorticoid activity, and a faulty "escape mechanism." The diagnosis of idiopathic edema is established by documenting an excessive intradiem weight gain (greater than 1 kg) and performing a water-loading test. Because the pathogenesis remains obscure, no specific or uniformly successful therapy yet exists. Besides recumbency, restriction of calories, sodium, and fluids may be tried. If these measures do not bring adequate relief, diuretics or sympathomimetics may be prescribed.

Adolescent↗

[Cardiovascular effects of a calcium channel blocker in hypoxia caused by altitude].

OBJECTIVE: High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers. Moreover, calcium entering in the cells could explain the congestive phenomena of acute mountain sickness (AMS). These findings led us to study the action of a calcium channel blocker, isradipine, in the prevention of non-complicated AMS. METHODS: In a double blind randomized study, 20 healthy volunteers received 5 mg of isradipine (n = 6) or placebo (n = 6) for 8 days. After 5 days of treatment in normoxia, the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score, haemodynamic parameters and renal function. RESULTS: The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia. Heart rate was an average of 15 b/min lower in the isradipine group, probably because of a direct action of isradipine on the sinus node. Otherwise, the effects of hypoxia were similar in both groups and were in accordance with the literature. There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to standing position. Renal blood flow, measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia. Cerebral blood flow was elevated, due to the direct vasodilator effect of hypoxia. However this increase did not seem to be the main mechanism responsible for the congestive phenomena. On the other hand, the increase in capillary permeability (demonstrated by the increased transcapillary escape rate of albumin, and albuminuria) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema. Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema.

Adult↗

Pathophysiology of hydrops fetalis.

Hydrops fetalis occurs when the rate of interstitial fluid production by capillary ultrafiltration exceeds the rate of interstitial fluid return to the circulation via lymphatic vessels. Developmental differences in the microcirculation and lymphatic system of the fetus, as compared with mature subjects, renders the fetus susceptible to interstitial fluid accumulation. These differences include greater capillary permeability, more compliant interstitial compartment, and greater influence of venous pressures on lymphatic return. The balance between interstitial fluid production and removal is most commonly disrupted as a consequence of homeostatic mechanisms serving to preserve adequate systemic delivery of metabolic substrate when cardiocirculatory function is impaired. The pathophysiology of two conditions of impaired cardiocirculatory function, atrial tachycardia and severe anemia, serve as examples of the mechanisms by which these homeostatic mechanisms perturb the balance of interstitial fluid movement.

Capillary Permeability↗

Anti-inflammatory and analgesic effects of a mixture of fatty acids isolated and purified from sugar cane wax oil.

The anti-inflammatory and analgesic effects of FAM, a defined mixture of fatty acids isolated from sugar cane (Saccharum officinarum L.), was evaluated. Oral administration of this mixture showed anti-inflammatory activity in the cotton pellet granuloma assay and in the carrageenin-induced pleurisy test, both in rats, as well as in the peritoneal capillary permeability test in mice. In addition, FAM showed analgesic properties in the hot-plate model and in the acetic acid-induced writhings test, both in mice. In conclusion, these results provide evidence on the potential usefulness of the mixture of fatty acids from sugar cane wax oil in inflammatory disorders.

Acetic Acid↗

Skin lesions due to okra (Hibiscus esculentus L.): proteolytic activity and allergenicity of okra.

The present report describes experimental studies on the proteolytic activity of the secretion on the surface of okra pods and the allergenicity of okra components, to clarify the etiology of skin lesions due to okra. Proteolytic activity was detected on the surface of immature okra pods and seemed to be sufficient to cause the skin lesions. Further, in vivo, intradermal injection of the enzyme solution prepared from immature okra pods led to increased capillary permeability in guinea pigs, in contrast to heated preparations. The fraction purified by preparative paper chromatography from an ethyl acetate extract of okra pods showed moderate allergenicity in the guinea pig maximization test. The present experimental evidence supports our suggestions from previous surveys that the proteolytic enzyme of okra may be responsible for development of skin lesions, and that allergic contact dermatitis may also play a part in addition to irritant contact dermatitis.

Allergens↗

Ligustrazine attenuates acute lung injury after burn trauma.

Acute lung injury is a common complication in patients with extensive burns in which the burned area exceeds 30% of the total body surface area (TBSA). This study was undertaken to evaluate the effect of Ligustrazine on burn-induced lung injury as well as the release of interleukin-8 (IL-8) in rats to characterize the role of Ligustrazine and IL-8 in lung injury after burn trauma. Sprague-dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% TBSA and lactated Ringer solution for resuscitation; and (3) Ligustrazine group, rats given burn injury and lactated Ringer's solution with Ligustrazine inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis, and lung myeloperoxidase (MPO) activity as well as lung wet/dry weight ratio. The IL-8 levels were measured in serum by enzyme-linked immunosorbent assay. These studies showed that burn trauma results in increased pulmonary leakage permeability and lung wet/dry ratio, elevated serum IL-8 levels and MPO activity, and worsened histologic condition. Ligustrazine inhibited these changes, prevented burn-mediated lung injury, and the production of IL-8. This will likely provide further evidence for ligustrazine as a therapeutic strategy in burn-induced lung injury.

Acute Disease↗

Biologically active substances in oak gall extracts. Part 11. The antihistamine-like activity of a substance (KC-18) isolated from oak gall extracts.

The effects of the newly isolated antihistamine (KC-18) from the Hungarian oak gall extracts on some actions of histamine have been investigated. Intraperitoneally administered KC-18 into guinea pigs and cats in doses of 2.5-16 mg/kg exerted a significant dose-related inhibition of histamine-induced bronchoconstriction, increase in capillary permeability and hypotension. In guinea pigs, actively sensitized with ovalbumin, 4 mg/kg KC-18 administered intraperitoneally prevented the development of anaphylactic shock following antigenic challenge. Histamine-induced gastric acid secretion in the rat was also dose-relatedly reduced by the intravenous administraton of 72 and 120 mg/kg KC-18. However, KC-18 in doses up to 100 mug/ml did not modify the histamine-induced contraction of the isolated guinea pig ileum.

Aerosols↗

Role of pneumolysin for the development of acute lung injury in pneumococcal pneumonia.

OBJECTIVE: Acute respiratory failure is a significant complication of severe pneumococcal pneumonia. In a mouse model, we observed early-onset lung microvascular leakage after pulmonary infection with Streptococcus pneumoniae, and we hypothesized that the important virulence factor pneumolysin may be the direct causative agent. DESIGN: Controlled, in vivo, ex vivo, and in vitro laboratory study. SETTING: Laboratory. SUBJECTS: Female mice, 8-12 wks old. INTERVENTIONS: Ventilated and blood-free perfused murine lungs were challenged with recombinant pneumolysin via the airways as well as via the vascular bed. In addition, we analyzed the impact of pneumolysin on electrical cell impedance and hydraulic conductivity of human umbilical vein endothelial cell (HUVEC) and alveolar epithelial cell (A549) monolayers. MEASUREMENTS AND MAIN RESULTS: Aerosolized pneumolysin dose-dependently increased capillary permeability with formation of severe lung edema but did not affect pulmonary vascular resistance. Intravascular pneumolysin caused an impressive dose-dependent increase in pulmonary vascular resistance and in lung microvascular permeability. By immunohistochemistry, pneumolysin was detected mainly in endothelial cells of pulmonary arterial vessels, which concomitantly displayed strong vasoconstriction. Moreover, pneumolysin increased permeability of HUVEC and A549 monolayers. Interestingly, immunofluorescence of endothelial cell monolayers exposed to pneumolysin showed gap formation and moderate stress fiber generation. CONCLUSIONS: Pneumolysin may play a central role for early-onset acute lung injury due to severe pneumococcal pneumonia by causing impairment of pulmonary microvascular barrier function and severe pulmonary hypertension.

Aerosols↗

Immunological conversion of Vibrio chorlerae in gnotobiotic mice.

Cholera vibrios grow readily in the intestines of gnotobiotic mice and change their antigenic structure in response to immunological pressures. These changes were progressive, with the rough form persisting as the apparent end point in the mice. Inoculation of the rough form into fresh gnotobiotic mice resulted in the recovery of smooth forms. An untypable rough strain of Vibrio cholerae isolated from a chronic carrier in Calcutta in 1967 was passed serially in gnotobiotic mice. Smooth strains of V. cholerae were recovered from the feces after selective treatment with complement and antiserum against a rough strain. They were confirmed as O group I cholera vibrios belonging to the eltor biotype. The ability of these strains to produce diarrheal fluid in infant rabbits and to increase capillary permeability in rabbit skin was markedly increased over that of the original human isolate. This demonstrates that rough avirulent forms of V. cholerae from human carriers can undergo antigenic changes and concurrently increase in virulence when placed in an appropriate environment. The many inapparent cholera infections in endemic areas may provide a mechanism by which V. cholerae changes its serotype away from the immunological pressures in the population.

Animals↗

Hepatic cryoablation-induced acute lung injury: pulmonary hemodynamic and permeability effects in a sheep model.

HYPOTHESIS: Hepatic cryoablation of 30% to 35% or more of liver parenchyma in a sheep model results in eicosanoid and nuclear factor-kappaB (NF-kappaB)-mediated changes in pulmonary hemodynamics and lung permeability. SETTING: Laboratory. INTERVENTIONS: At initial thoracotomy, catheters were placed in the main pulmonary artery, left atrium, right carotid artery, and efferent duct of the caudal mediastinal lymph node for subsequent monitoring in adult sheep. After a 1- to 2-week period of recovery, animals underwent laparotomy and left-lobe cryoablation (approximately 35% by volume) with subsequent awake monitoring and on postoperative days 1 to 3. MAIN OUTCOME MEASURES: Cryoablation-induced lung permeability and hemodynamic changes were compared with baseline values in sheep that underwent instrumentation. Similarly handled sheep underwent resection of a similar volume of hepatic parenchyma or had pulmonary artery pressure increases induced by mechanical left atrial obstruction. Activation of NF-kappaB was assessed with electrophoretic mobility shift assay, and serum thromboxane levels were measured with mass spectroscopy. RESULTS: Cryoablation resulted in acutely increased mean pulmonary (20 to 35 cm water) and systemic pressures, which returned to baseline at 24 hours with no change in cardiac output. Serum thromboxane levels increased 30 minutes after cryoablation (9-fold) and returned to baseline at 24 hours. Activation of NF-kappaB was present in liver and lung tissue by 30 minutes after cryoablation. Lung lymph-plasma protein clearance markedly exceeded the expected increase from pulmonary pressures alone, and increased lymph-plasma protein ratio persisted after pulmonary artery pressures normalized. Similar changes were not associated with 35% hepatic resection. CONCLUSIONS: This study demonstrates that 35% hepatic cryoablation results in an acute but transient increase in pulmonary artery pressure that may be mediated by increased thromboxane levels. Increases in pulmonary capillary permeability are not accounted for by pressure changes alone, and may be a result of NF-kappaB-mediated inflammatory mechanisms. These data show that cryosurgery causes pathophysiological changes similar to those observed with endotoxin and other systemic inflammatory stimuli.

Animals↗

Mediators of pulmonary injury induced by inhalation of bacterial endotoxin.

The purpose of this study has been to further define the pathophysiologic aspects of lung injury caused by the inhalation of endotoxin (LPS) using the morphometric approach to identify mediators that influence distal lung structure and function. Hamsters were divided into 3 groups 24 h prior to low dose LPS inhalation exposure (4 micrograms/m3 for 5 h): (1) pretreated with cobra venom factor to deplete complement in vivo, (2) pretreated with indomethacin to block prostaglandin production, and (3) untreated control group. Both pretreatments abolished LPS-induced decreases in lung volume as well as increases in capillary PMN and platelets seen in untreated control animals. Neither pretreatment had any effect on the LPS-induced decreases of other capillary leukocytes. Similarly, both methods of pretreatment failed to block increases in cellular interstitium of distal capillary septa induced with LPS alone. LPS provoked changes in capillary endothelium, especially seen as an increase in numerical density of endothelial pinocytotic vesicles. Decomplementation failed to alter this increase, but indomethacin pretreatment blocked the effect. Neither treatment had any effect on their size. Low dose LPS inhalation also altered pulmonary capillary permeability to a 125I-BSA probe, which was found in significantly greater amounts in LPS-exposed lungs than in those of saline aerosol control lungs, but was not present in the air space as evidenced by negligible counts in bronchoalveolar lavages. It is evident that endotoxin on the epithelial side of the air-blood barrier leads to changes on the other side of that barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of the beta-1 selective blocker, metoprolol, on the development of pulmonary edema in tocolytic therapy.

Research on one group of nine anesthetized dogs pretreated with alpha-naphthyl-thiourea showed that doses of the beta-sympathicomimetic fenoterol such as those normally administered in clinical tocolysis (2 micrograms/kg per minute) lead to significant fluid displacement to the extravascular space of the lung in the sense of a preclinical interstitial edema. In a second group (N = 9) with the same pretreatment the addition of the beta-1 selective blocker, metoprolol (1.5 micrograms/kg per minute) served to antagonize the hemodynamic changes and possibly the increase of pulmonary capillary permeability induced by the beta-mimetic. Fluid displacement into the interstitium of the lung was prevented by metoprolol. These observations corroborate the hypothesis that pulmonary edema occurring during tocolytic therapy is largely a result of the use of beta-mimetics. In addition to its cardioprotective effect, the administration of the beta-1 selective blocker, metoprolol, may reduce the risk of the development of pulmonary edema in beta-sympathicomimetic therapy for premature labor.

Animals↗