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Biomedical subjects

M A Maciel

Publications and source records attributed to M A Maciel.

18 recordsLinked to original sources

[Comparative studies on endemic areas of bancroftian filariasis in Greater Recife, Brazil].

Two districts in Recife (Santo Amaro and Campo Grande) and two districts in Olinda (Sapucaia and Salgadinho), were selected for a comparative study of bancroftian filariasis in Greater Recife. Selection parameters included similar socio-economic, demographic, and endemic levels of lymphatic filariasis. In the districts studied, streets were chosen randomly. These clusters consisted of 110 people each. A population sample was stratified by sex and age: 0-4, 5-9, 10-14, 15-19, 20-29, 30-39, 40-49, 50-59 and 60 years old and over. The parasitological data were obtained by measuring thick blood smears (60 micro l), collected from 8:00 to 12:00 PM and processed and stained with hematoxylin. The data were described in tables, and logarithimic expression graphics were used to analyze parasitic densities. In general, Recife showed a prevalence of 13.5%, and Olinda 12.3%. Mean parasitic densities were 41 and 70 microfilariae/60 micro l (mf/60 micro l), respectively. Higher microfilaremic rates were observed in Recife for the 20-29-year age bracket and in Olinda in the 30-39-year bracket. The authors concluded that the disease has returned to former endemic levels, and the data described call for a reevaluation of control campaigns carried out by the Brazilian National Health Foundation, since the endemic has already reached serious proportions.

English Abstract↗

Blood glucose- and triglyceride-lowering effect of trans-dehydrocrotonin, a diterpene from Croton cajucara Benth., in rats.

AIM: The objective of this study was to assess in rats the antidiabetic effects (i.e. reduction of hyperglycaemia and hypertriglyceridaemia) of trans-dehydrocrotonin (t-DCTN), a bioactive diterpene isolated from the popular medicinal plant Croton cajucara. METHODS: Hyperglycaemia was induced by intraperitoneal injection of streptozotocin (STZ) and hypertriglyceridaemia by oral administration of ethanol in rats. The blood glucose levels were measured by the glucose oxidase method using commercially available enzyme kits. RESULTS: Treating rats with t-DCTN (50 mg/kg) significantly reduced STZ-induced increases in blood glucose levels as well as ethanol-induced increases in blood triglycerides. CONCLUSION: The results suggest that t-DCTN has an antidiabetic potential that warrants further research on its mechanism and clinical significance.

Animals↗

Effect of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara on experimental hypertriglyceridaemia and hypercholesterolaemia induced by Triton WR 1339 (tyloxapol) in mice.

The effect of trans-dehydrocrotonin (t-DCTN) from Croton cajucara Benth. was investigated in mice on Triton WR 1339 (tyloxapol)-induced hypercholesterolaemia and hypertriglyceridaemia. Mice treated with single application of tyloxapol (400 mg/kg, i.p.) demonstrated significantly increased blood levels of total cholesterol and triglycerides at 24 h and 48 h after its injection, compared to normal controls. These increases were found to be markedly suppressed in animals treated orally with 25 and 50 mg/kg t-DCTN or 100 mg/kg gemfibrozil, an established antihypercholesterolaemic drug. These results suggest that t-DCTN may be a suitable candidate for combating pathologies associated with hyperlipaemia.

Animals↗

Antigenotoxicity of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara.

The antigenotoxic action of three doses of trans-dehydrocrotonin (t-DCTN), the active ingredient obtained from the bark extract of Croton cajucara, a plant native to the Amazon, was determined in Swiss mice in vivo. Mice were submitted to acute intraperitoneal and gavage treatments, then their bone marrow cells were subsequently analyzed by micronucleus (MN) and chromosome aberration (CA) assays. Comparisons were performed between the three doses of t-DCTN and the negative-control group. Statistical analysis indicated that doses of 50 and 75 % of the LD(50), via intraperitoneal treatment or gavage injection, were antimutagenic with regard to cyclophosphamide. However, the dose of 25 % of the LD(50) was only antimutagenic when administered by gavage. Based on these observations, it can be suggested that gavage is the most effective method of administering t-DCTN. In addition, t-DCTN showed no cytotoxic effects in the bone marrow cells regardless of the route of exposure.

Animals↗

The lipid-lowering effect of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara Benth. in mice fed on high-fat diet.

The clerodane diterpene trans-dehydrocrotonin extracted and isolated from the stem bark of Croton cajucara Benth. was investigated for its lipid-lowering effect in mice fed on a high-fat diet. Mice fed on a high-fat diet for a two-week period demonstrated significantly increased blood levels of total cholesterol and triglycerides, compared with normal controls. Oral treatment with trans-dehydrocrotonin at a dose of 25 or 50 mg kg(-1) daily markedly suppressed the high-fat-diet associated rise in total cholesterol and triglyceride levels. The hypocholesterolaemic effect of trans-dehydrocrotonin was more prominent at the dose of 50 mg kg(-1) with significant decreases in high-density lipoprotein, very-low-density lipoprotein and low-density lipoprotein cholesterol levels. The lower atherogenic index of the trans-dehydrocrotonin-treated groups suggests the hypolipidaemic potential of this plant-based drug. These results indicate that orally administered trans-dehydrocrotonin is effective in suppressing high-fat-diet-induced hyperlipidaemia in mice and suggest its likely beneficial use as anti-atherogenic agent.

Administration, Oral↗

Ethnopharmacology, phytochemistry and pharmacology: a successful combination in the study of Croton cajucara.

Phytochemical and pharmacological studies of Croton cajucara were oriented by traditional medicine. The stem bark of the mature plant is a rich source of clerodane-type diterpenes: trans-dehydrocrotonin (DCTN), trans-crotonin (CTN), cis-cajucarin B, cajucarin A, cajucarinolide and two novel clerodanes, trans-cajucarin B and sacacarin. In young (18-month-old) plants, the triterpene acetyl aleuritolic acid (AAA) was the major stem bark component and in these the diterpene DCTN was not present. The highest concentration of DCTN (1.4% of dry bark) was detected in 4-6 year-old plants, while 3-year-old plants contained only 0.26% of this diterpene. Three steroids (beta-sitosterol, stigmasterol and sitosterol-3-O-beta-glucoside), two flavonoids (kaempferol 3,4', 7-trimethyl ether and 3,7-dimethyl ether) and one diterpene (cajucarinolide) were isolated from the leaves of this Croton. The main pharmacological activity was correlated with DCTN. This clerodane produced anti-inflammatory and antinociceptive effects and a significant hypoglycemia in alloxan-induced diabetic rats. The compound also reduced the index of gastric lesions induced by restraint-in-cold. Dose-related DCTN and CTN inhibited in vivo the basal acid secretion in pylorus-ligature rats and oxyntic glands isolated from rabbit gastric mucosa, DCTN, CTN or AAA decreased in vitro uptake basal acid secretion induced by histamine and measured with the 14C-aminopyrine uptake method. Uniquely DCTN inhibited 14C-AP uptake induced by bethanechol. The terpenoids, DCTN and AAA, and the chloroform extract of 6-month-old plants reduced gastrointestinal transit in mice. The effects of DCTN and CTN on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumors, on the proliferation of cultured cells and TNFalpha were determined. DCTN was also evaluated for a possible antioestrogenic activity using the immature rat as a model system for bioassay of oestrogen and for an anti-implantation effect in regularly cycling rats. The biological experiments, using the plant extracts and the terpenoids DCTN, CTN and AAA, are herein discussed.

Animals↗

Antioestrogenic effect of trans-dehydrocrotonin, a nor-clerodane diterpene from Croton cajucara Benth. in rats.

This study examined trans-dehydrocrotonin (t-DCTN), a nor-clerodane diterpene isolated from the Brazilian medicinal plant Croton cajucara Benth., for a possible antioestrogenic activity using immature rats as a model system for bioassay of oestrogen, and for an antiimplantation effect in regularly cycling rats of proven fertility. In the antioestrogen test, t-DCTN (25 and 50 mg/kg) effectively prevented oestrogen-induced increases of uterine wet weights. In addition, the vaginal openings provoked by oestrogen were completely prevented by t-DCTN. However, blastocyst-implantation was only insignificantly affected in t-DCTN pretreated animals. These results suggest that t-DCTN may be an antioestrogen and warrants further studies with regard to its mechanism of action.

Animals↗

Investigation of genotoxic activity of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara.

The genotoxic action of three doses of trans-dehydrocrotonin (t-DCTN), an active ingredient obtained from the bark extracts of an Amazon native plant, Croton cajucara, were examined in Swiss mouse bone marrow cells in vivo, submitted to acute intraperitoneal treatment, by micronucleus (MN) and chromosomal aberration (CA) tests. The statistical tests (Anova and Tukey) made to compare the results obtained in each of the three doses of t-DCTN with the negative-control group showed that the frequencies of MN and mitotic index were equal to the negative-control and that the frequencies of CA were lower than that observed in the negative-control. Therefore, based on our results it can be said that t-DCTN is not genotoxic nor cytotoxic to mouse bone marrow cells, submitted to acute intraperitoneal treatment in vivo. Teratogenesis Carcinog. Mutagen. 19:377-384, 1999.

Animals↗

Anti-tumour activity of two 19-nor-clerodane diterpenes, trans-dehydrocrotonin and trans-crotonin, from Croton cajucara.

The effects of two nor-diterpenes, trans-dehydrocrotonin (DCTN) and trans-crotonin (CTN) from Croton cajucara (Euphorbiaceae), on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumours, on the proliferation of cultured Ehrlich cells and TNF alpha activity were determined. When the mice were treated with 80 and 120 mg/kg of DCTN or 38 mg/kg of 5-FU a significant anti-tumour activity was obtained (%T/C of 128-140). The cytotoxicity against Ehrlich carcinoma was 16 microM for DCTN and CTN whereas the flavonoid quercetin was cytotoxic at 44 microM in 48 h cell culture. No apoptosis was seen on in vitro electrophoresis of DNA extracted from the tumour cells treated with DCTN and CTN. A significant TNF alpha activity was detected in Ehrlich tumour-bearing mice treated with DCTN suggesting an enhanced immune function.

Animals↗

T-lymphocytes from individuals with filarial inflammatory disease have increased transendothelial migration in vitro.

The in vitro transendothelial migration of circulating filarial antigen-specific T-cells was examined in Wuchereria banerofti infection. Circulating T-cells from individuals with filaria-induced lymphatic pathology (LP) had significantly greater migration through unstimulated HUVEC monolayers than did T-cells from asymptomatic infected (MF) individuals (P = 0.04). In contrast to the MF individuals where no effect was seen, transendothelial migration of 48-hr filarial antigen stimulated T-cells from LP individuals was significantly (P = 0.01) greater than migration of 48-hr media-stimulated T-cells. In six of seven patients examined, inhibition of the VLA-4/VCAM-1 pathway resulted in greater than 50% inhibition of transendothelial migration of T-cells.

Adult↗

Hypoglycemic effect of trans-dehydrocrotonin, a nor-clerodane diterpene from Croton cajucara.

trans-Dehydrocrotonin (t-DCTN), a 19-nor-clerodane diterpene isolated from the bark of Croton cajucara Benth. (Euphorbiaceae) demonstrated a significant hypoglycemic activity in alloxan-induced diabetic rats but not in normal rats, at oral doses of 25 and 50 mg/kg body weight. The drug also effectively lowered the blood sugar levels in glucose fed normal rats. The hypoglycemic effect of t-DCTN was almost comparable to that produced by glibenclamide (2 mg/kg), a clinically useful drug. The results indicate the antihyperglycemic potential of t-DCTN.

Animals↗

Investigation of anti-inflammatory and antinociceptive activities of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara. Part 1.

The anti-inflammatory and antinociceptive effects of trans-dehydrocrotonin, isolated from the bark of Croton cajucara (Euphorbiaceae), were investigated using several animal models. The trans-dehydrocrotonin produced a significant inhibition of carrageenin-induced paw edema and cotton pellet granuloma in rats. It also inhibited the writhings in mice induced by acetic acid, but did not show a significant effect in the hot-plate test in mice. The LD50 of t-DCTN was 555.0 mg/kg (p.o.) for mice.

Analgesics↗

The presence or absence of active infection, not clinical status, is most closely associated with cytokine responses in lymphatic filariasis.

Twenty-eight Brazilians from an area in which Wuchereria bancrofti is endemic were classified as asymptomatic microfilaremic or having clinical filariasis with active infection or without current active infection. Total accumulation of antigen-specific interleukin (IL)-4 and IL-5 in 48 h peripheral blood mononuclear cell supernatants was not significantly different between groups. However, when cytokine kinetics were examined, responses segregated according to infection status. Sustained production of IL-4 and IL-5 beyond the first 24 h of stimulation and production of interferon-gamma were seen only in the group with clinical filariasis without active infection. CD8 T cells were the major source of IL-5 production in this group, while CD8 production of IL-5 was undetectable in any subject with active infection (asymptomatic microfilaremic or with clinical filariasis and active infection). These findings indicate that active infection, rather than clinical status, is most closely associated with cytokine patterns in lymphatic filariasis.

Adult↗

Bancroftian filariasis in two urban areas of Recife, Brazil: pre-control observations on infection and disease.

Bancroftian filariasis is a major public health problem in the city of Recife in north-eastern Brazil. In some of its urban areas microfilaraemia prevalence reaches 14%. This study describes epidemiological characteristics, infection and disease, in 2 urban areas, Coque and Mustardinha, before control measures were applied. The parasitological survey was performed by a 'door-to-door' census covering 5563 subjects, aged between 5 and 65 years. Microfilaraemia was detected by the thick drop technique, using 45 microL of peripheral blood collected between 20:00 and 24:00. In both areas the prevalence of microfilaraemia was 10%, and males had higher prevalences of infection and disease than females. The prevalence of microfilaraemia was higher in the 15-24 and 25-34 years age groups in both sexes. Most microfilaria (mf) carriers (72.1% in Coque and 79.7% in Mustadrinha) had mf densities < 100/60 microL of blood. Females of reproductive age had significantly lower mf densities than males. The overall disease prevalence in both areas was 6.3%. Amongst the subjects who presented with chronic disease 15.7% were microfilaraemic. Chronic disease prevalence increased from 1.4% in the 5-14 years age group to 11.3% in the oldest age group. The most frequent clinical manifestation was hydrocele (5.4%), followed by lymphoedema (1.8%). The epidemiological pattern of filariasis in the populations studied was marked by high prevalence of microfilaraemia, low mf density, and relatively low prevalence of filarial disease considering the level of endemicity.

Acute Disease↗