Anti-inflammatory and anti-oxidant activity of a new class of phenyl-pyrazolone derivatives.

The anti-inflammatory activity of a new class of phenyl-pyrazolone derivatives, structurally related to phenidone, has been evaluated using the Croton oil ear test in mice as model of acute inflammation. Derivative 5h reduces the percentage of oedema similarly to indomethacin and more efficiently than phenylbutazone. The anti-inflammatory activity of these two reference drugs depends on their COX inhibition, but for the synthesized derivatives it has not been demonstrated a significant COX or LOX inhibition, as previously reported. While the anti-inflammatory activity of phenidone is correlated to its anti-oxidant properties, the redox potential of these compounds appears not decisive in the inflammatory process inhibition. In order to investigate the mechanism of action for these compounds, we quantified their anti-oxidant activity and the lipophilicity, and a relationship between the calculated logP and the percentage of oedema reduction was found. We hypothesize that the anti-inflammatory activity, recorded in vivo, could be related to lipophilic parameter of these compounds.

Topical anti-inflammatory activity of Solenostemma argel leaves.

The topical anti-inflammatory activity of Solenostemma argel Hayne leaves was evaluated using the Croton oil ear test in mice. A bioassay-guided fractionation procedure led to a highly active chloroform extract: at 300 microg/cm(2), it induced 73% oedema reduction, while the reference drug indomethacin (100 microg/cm(2)) induced 56% reduction. The extract contained a new pregnene glycoside (1, solenoside A) and the known 14 beta,15 alpha-dihydroxy-Delta(4)pregnene-3,20 dione (2), kaempferol-3-O-glucoside (3) and kaempferol-3-O-rutinoside (4). Their structures were determined by ID and 2D NMR experiments as well as HRMS. Compounds 2 and 4 showed anti-inflammatory activity comparable to that of indomethacin.

Extracts and constituents of Lavandula multifida with topical anti-inflammatory activity.

The topical anti-inflammatory activity of the ethanol and aqueous extracts from the aerial parts of Lavandula multifida L. (Lamiaceae), used in the Moroccan traditional medicine, was investigated by inhibition of the Croton oil-induced ear edema in mice. The biological assay revealed a dose-dependent anti-inflammatory activity for the ethanol extract, while the aqueous one was less active. Bioassay-guided fractionation of the ethanol extract led to identify four triterpenic acids of oleanane series, four pimarane and one iso-pimarane diterpenes, as well as the phenolic monoterpene carvacrol and its glucoside. Some of these compounds revealed an anti-inflammatory activity comparable to that of indomethacin.

Aloeresin I, an anti-inflammatory 5-methylchromone from cape aloe.

A new diglucoside having a 5-methylchromone moiety was isolated from a commercial sample of Cape aloe, the dried exudate from Aloe ferox Miller, and named aloeresin I. Its structure was established as 1 on the basis of spectral and chemical evidence. Aloeresin I (1) (1 micromol/cm2) reduces in vivo the oedematous response (39 %) induced by Croton oil in the mouse ear with the same potency as aloesin, one of the most abundant Cape aloe constituents, and to a higher extent than aloeresin H (2). Indomethacin (0.3 micromol/cm2), the reference anti-inflammatory compound, provokes 61 % oedema inhibition.

In vivo topical anti-inflammatory and in vitro antioxidant activities of two extracts of Thymus satureioides leaves.

Four extracts at increasing polarity were prepared from the leaves of Thymus satureioides Coss. (Labiatae) and assayed for the in vivo topical anti-inflammatory effect using the croton oil ear test in mice, and for in vitro both antioxidant (DPPH degrees test) and anti-bacterial (broth microdilution method) activities. The chloroform extract showed a topical anti-inflammatory activity (ID50=282 microg cm(-2)), only three times lower than that of the reference drug indomethacin (ID50=93 microg cm(-2)) and its active components were identified as ursolic and oleanolic acids. The methanol extract, showing a significant radical-scavenging effect (SC50=14.54 microg), was characterized by the isolation and identification of some flavonoids. On the contrary, the extracts did not show any anti-bacterial effect against four standard aerobial bacteria strains.

Short-term oral toxicity of homoyessotoxins, yessotoxin and okadaic acid in mice.

A short-term toxicity study after 7 days oral daily administration of yessotoxin (YTX; 2 mg/kg/day), homoYTX (1 mg/kg/day), 45-hydroxy-homoYTX (1 mg/kg/day) and of the main diarrhoetic shellfish toxin okadaic acid (OA; 1 mg/kg/day) was carried out in mice. Symptoms, lethality, food consumption, body and organ weights, gross pathology and histopathology of the main organs and tissues, leukocytes formula as well as plasmatic levels of transaminases, lactate dehydrogenase and creatinine phosphokinase were evaluated. Heart tissue was studied also hystochemically for the presence of apoptotic nuclei and by transmission electron microscopy. No mortality, signs of toxicity or cumulative effects were induced by the repeated oral exposure to YTXs. Only ultrastructural changes in the cardiac muscle cells near the capillaries, such as package of rounded mitochondria and alteration of the cells boundary were observed, without any increase of lactate dehydrogenase, an index of cardiac damage. OA induced diarrhoea, body weight loss, reduced food consumption, and the death of 2/5 mice after 5 days. Necroscopy and/or light microscopy analysis revealed toxic effects mainly at forestomach (ulceration and hyperplasia), liver and, indirectly to body weight loss of mice, atrophic signs in the lymphoid organs and exocrine pancreas. Electron microscopy of heart tissue showed alterations of mitochondria and fibers in myocardiocytes, although no apoptotic change was recorded.

Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice.

The acute toxicity of yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxy-homoyessotoxin (45-OH-homoYTX) has been studied in comparison to that of okadaic acid (OA), the main diarrhogenic toxin, both after intraperitoneal (i.p.) and oral administration. After i.p. administration, homoYTX and YTX showed similar lethality (LD(50)=444 microg/kg and 512 microg/kg), higher than that of OA (LD(50)=225 microg/kg), while 750 microg/kg of 45-OH-homoYTX did not cause death. OA induced the already known toxic signs: before death, mice were motionless and cyanotic; small intestine and liver damage were shown at post-mortem. Mice treated with YTX and homoYTX were restless and jumped before death; necroscopy did not show major changes. After oral treatment, 2 mg/kg of OA induced diarrhoea and body weight loss, causing 4/5 deaths; necroscopy and/or histology revealed degenerative lesions to small intestine, forestomach and liver (confirmed by increased plasma transaminase), but no myocardium alterations. On the contrary, the oral treatment with YTX (1 and 2 mg/kg) and its derivatives (1 mg/kg) did not cause any death or signs of toxicity, except some ultrastructural myocardiocyte alterations, adjacent to capillaries, such as cytoplasmic protrusions (YTX, 1 and 2 mg/kg), fibrillar alteration (YTX, 1 mg/kg) or mitochondria assemblage (45-OH-homoYTX). Altogether, our data show that YTX and its derivatives are less toxic than OA after acute oral and i.p. treatments, at doses which may represent up to 100 times of the possible human daily intake.

Topical anti-inflammatory activity of Bauhinia tarapotensis leaves.

The topical anti-inflammatory properties of Bauhinia tarapotensis Benth. (Leguminosae) leaves have been studied by the inhibition of the croton oil-induced ear edema in mice. A bioassay-guided fractionation showed an interesting anti-inflammatory activity of the chloroform extract, that justifies the activity of the whole herbal drug. The main anti-inflammatory principles of B. tarapotensis leaves are triterpenic acids of ursane and oleanane series. The antiphlogistic activity of mixtures constituted of two ursane and oleanane isomers with different hydroxylation pattern, in the ratio 2:1, is comparable to that of indomethacin (ID50 ranging from 95 to 147 microg/cm2 and 93 microg/cm2, respectively).

Screening of the topical anti-inflammatory activity of some Central American plants.

Hexane, chloroform and methanol extracts of seven herbal drugs used in the folk medicine of Central America against skin disorders (Aristolochia trilobata leaves and bark, Bursera simaruba bark, Hamelia patens leaves, Piper amalago leaves, and Syngonium podophyllum leaves and bark) were evaluated for their topical anti-inflammatory activity against the Croton oil-induced ear oedema in mice. Most of the extracts induced a dose-dependent oedema reduction. The chloroform extract of almost all the drugs exhibited interesting activities with ID(50) values ranging between 108 and 498 micro g/cm(2), comparable to that of indomethacin (93 micro g/cm(2)). Therefore, the tested plants are promising sources of principles with high anti-inflammatory activity.

Hepatitis C virus infection in homosexual men: a seroepidemiological study in gay clubs in north-east Italy.

Seroprevalence of Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV antibodies was studied in a group of 259 apparently healthy homosexual men of the Veneto Region (Italy). Subjects were recruited between 1987 and 1989 from homosexual men's clubs. Seropositivity was evaluated in relation to main risk factors associated with the lifestyle and sexual behaviours of this population. Serological evaluation revealed an overall prevalence of HCV infection of 18.9% in the study population as a whole, but on breaking the samples down into three subgroups according to optical density (O.D.) values and to the year of sera collection, different seroprevalences were observed. Prevalence of anti-HCV was higher in 1987 and steadily decreased in 1988 and 1989; 4.1% of subjects gave positive results at O.D. greater than 2.0, while 6.2% were positive at O.D. between 0.8 and 2.0 and 9.6% at O.D. between cut-off and 0.8. Anti-HCV positivity was not correlated with HIV nor HBV positivity. No correlation was found between HCV seropositivity and either the type of anogenital intercourse or sexual promiscuity, but the prevalence increased (p = n.s.), as observed for HIV (p less than 0.05) and HBV (p = n.s.), with the number of intercourses per month. Epidemiological and preventive aspects arising from the investigation are discussed herein.

[The evaluation of serum angiotensin-converting enzyme in silicosis and silicotuberculosis]. / Valutazione dell'angiotensin converting enzyme sierico nella silicosi e silicotubercolosi polmonare.

In order to verify the value of the determination of serum angiotensin converting enzyme (ACEs) in the assessment of silicosis and silicotuberculosis, we studied 105 subjects: 61 suffering from silicosis, 12 from silicotuberculosis, 19 from tuberculosis and 13 from chronic obstructive pulmonary disease (COPD). The patients with silicosis and silicotuberculosis were classified into two categories on the basis of the radiological pattern of pneumoconiosis according to the ILO 1980 CLASSIFICATION: mild silicosis (from 1/1 to 2/1) and severe silicosis (from 2/2 to 3+ and/or conglomerate masses). ACEs values were higher in the subjects suffering from silicotuberculosis and silicosis; in the latter, however, we did not find any significant relation between ACEs values and the radiological pattern. The lowest values of ACEs were found in the COPD group. Our data showed a statistically significant difference between silicotic or silicotuberculotic patients and the COPD group (p less than 0.05). It can be supposed that COPD, which was also found in all subjects suffering from silicosis or silicotuberculosis, might have caused an underestimation of the observed ACEs values which, however, were higher than normal. This increase might have been caused by a numerical or functional enhancement of the macrophages, which produce ACE and play an important role in the pathogenesis of such diseases.

Incidence, significance, and subtypes of hemophilia BM in a large population of hemophilia B patients.

Eleven patients with hemophilia BM were found out of a population of 66 patients with hemophilia B. Factor IX activity in the hemophilia BM varied between less than 1% and 1.6% of normal but factor IX antigen was normal or only slightly reduced in each instance. Thrombotest clotting time was variably prolonged and was not corrected by the addition of normal plasma. Thrombotest mixing experiments and dilution curve studies confirmed the presence of the inhibitor in every patient. There are at least two forms of hemophilia BM, a severe one and a mild one. In the first form, Thrombotest is severely prolonged (90-120 s). In the other, the prolongation is mild or moderate (60-80 s). A positive correlation exists between the antigen-activity difference (delta antigen-activity) and the prolongation of Thrombotest both in the propositi and in obligatory carriers. The criteria for the diagnosis of hemophilia BM are the following: prolonged PTT, prolonged Thrombotest, lack of correction of Thrombotest by the addition of normal plasma while PTT is fully corrected. The lack of correction of Thrombotest in the presence of a full correction of PTT, is the unique clotting feature.