Search

Alpinia speciosa Schum or A. nutans is a plant of the Zingiberaceae family, known popularly as "colony" (colônia) and used as a diuretic and to control hypertension. We have determined the concentration of Na+ and K+ found in the alcoholic extract and in the tea concoction. They contained 51.0 mEq Na+, and 132 mEq K+ in the extract, and 0.0 mEq of Na+ and 26 mEq K+ in the tea. Phytochemical analysis of the leaves demonstrated the presence of catecquic tanins, phenols and alkaloids, and also some essential oils. When injected intra-peritoneally the hydroalcoholic extract, in a dose range of 100 to 1400 mg/kg, (or 2500-18000 mg/kg orally) produced in mice: writhing, psychomotor excitation, hypokinesis and pruritus. The LD50 by ip was 0.760 +/- 0.126 g/kg and 10.0 +/- 2.5 g/kg by oral administration for the hydroalcoholic extract. Subacute toxicity made by injecting daily for 30 days the LD10 in rats caused an increase in transaminases and lactate dehydrogenase, whereas other parameters such as blood glucose, urea and creatinine were normal. A histopathological analysis of liver, spleen, gut, lung and heart showed no alterations. The drug also produced a prolongation of the sleeping time. The hydroalcoholic extract induced in the rat and in the dog a dose-dependent fall in blood pressure in doses of 10 to 30 mg/kg. In isolated atria the extract induced a reduction of the frequency and in the inotropic responses. Neither the extract nor the tea had an effect on the diuresis of the rat.

The authors have reviewed the pharmacological studies done with essential oils obtained in the state of Ceará, in Northeast of Brazil, from 15 species of aromatic plants, some of which are native to the phytogeographic semiarid region characteristic of the Northeast, the "caatingas". These studies have dealt with the effect of these oils on muscle contraction and with their antispasmodic, analgesic, antiinflammatory, anticonvulsant and antibacterial activity. The essential oils of the medicinal species have shown activity coherent with the use of these plants in folk medicine. The review is aimed primarily at summarizing the information relevant for a critical evaluation of the perspectives and potential of these oils as pharmacological and therapeutic agents.

We compared the effects of infusing a chemically defined chiro-inositol glycan putative insulin mediator with an equivalent dose of insulin in low-dose (45 mg/kg) streptozotocin diabetic rats. Insulin decreased plasma glucose levels from 17.32 +/- 0.17 to 3.96 +/- 0.064 mmol/l (p < 0.0002) in 120 min, a decrease of 77.13%, while the putative mediator promoted a decrease in plasma glucose from 14.85 +/- 0.084 to 7.22 +/- 0.13 mmol/l (p < 0.007) in 60 min. The putative mediator maintained euglycaemia over the ensuing 60 min with a plasma glucose level of 7.01 +/- 0.10 mmol/l at 120 min. Thus, insulin further reduced the plasma glucose from euglycaemia at 60 min to produce hypoglycaemia at 120 min. The lack of production of hypoglycaemia by the putative mediator can be explained by its inhibition of glucose-stimulated insulin secretion by the islet beta cells, thus providing a potential negative feedback regulatory mechanism; or by its selective action on muscle to increase glycogen synthesis. The significance of these results in terms of future directions in drug design is herein considered.

Guanylin is an endogenous peptide synthesized by several mammalian species that mimics the effects of a thermostable enterotoxin of Escherichia coli (STa: NTFYCCELCCNPACAGCY) in the gut. We have cloned a lysine-1 derivative of rat guanylin (Lys-1-NTCEICAYAACTGC) and tested its effects on ileal tissue membranes in Ussing chambers and in the isolated perfused rat kidney. Rabbit ileal mucosa membranes were mounted into a Ussing chamber and the effects of Lys-1 guanylin (Lys-1 G) and STa enterotoxin peptide on chloride secretion were determined by changes in short-circuit current (Isc). Lys-1 G (10 to 100 nM) showed a dose-dependent effect on chloride secretion with a maximal response estimated to be 52 microA/cm2. Lys-1 G mimics the effect of STa peptide, but the enterotoxin elicited a greater maximal effect of 120 microA/cm2 (P0.01). Lys-1 G (2.5 micrograms/ml) promoted an increase in both urine flow (from 0.13 +/- 0.07 to 0.40 +/- 0.01 ml g-1 min-1, N = 4; P0.05) and glomerular filtration rate (from 0.68 +/- 0.02 to 0.85 +/- 0.00 ml g-1 min-1, N = 4; P0.01) in the isolated perfused kidney and a reduction of the fractional reabsorption of sodium (from 76.0 +/- 0.03 to 59.5 +/- 0.85%, N = 4; P0.01). These maximal effects were accompanied by intense natriuretic effect observed 30 and 60 min after drug administration. The Lys-1 G analog similar to STa enterotoxin elicited intestinal chloride secretion and a natriuretic effect. These data demonstrate that the cloned peptide analog retains the biological activity of the native hormone and presents activity similar to STa. The properties of Lys-1 G resemble those of a factor formed during perfusion of the hypoxic rabbit kidney and named by us factor natriureticus similis (FNS).

Toxin A peptide from Clostridium difficile caused damage and secretion in the intestinal mucosa. These effects are mediated in part by pro-inflammatory substances. In order to evaluate and compare the biologic effect of toxin A on renal vascular, glomerular and tubular functions, we studied this toxin in isolated rat kidneys. Isolated kidneys from adult male Wistar rats (260-320 g) were perfused with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin. We studied the effect of toxin A peptide (3.2 x 10(-6) M, injected into perfusate) on glomerular filtration rate (GFR), urinary flow rate (UF) and total sodium reabsorption (TNa+, %). All experiments were preceded by a 30-min basal period, and in another group of kidneys the time course of the variables was followed without toxin infusion for unpaired control. Toxin A (TxA) reduced the perfusion pressure (PP), from PPcontrol/30min = 124.89 +/- 1.91 to PPTxA/120min = 88.13 +/- 5.1 mmHg (N = 6, P0.01) with a maximal effect at 120 min after toxin infusion. TxA also caused a significant decrease in GFR with maximal effect at 90 min after toxin infusion (GFRcontrol/30min = 0.53 +/- 0.05 to GFRTxA/90min = 0.30 + 0.05 ml min-1g-1; N = 6, P0.01). TxA did not alter renal tubular sodium transport when compared with a control without toxin infusion. In addition, toxin-treated kidneys caused a time-dependent increase in urinary flow from UFcontrol/30min = 0.16 +/- 0.08 to UFTxA/120min = 0.35 +/- 0.1 ml min-1g-1 (N = 6, P0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholera toxin peptide stimulates adenylyl cyclase activity in several tissues and causes severe intestinal water and electrolyte secretion. To evaluate the regulatory function of sodium transport in renal tubules, we studied the effect of cholera toxin peptide on rat kidneys. Isolated kidneys from adult male hooded rats weighting 240-335 g were perfused with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin (BSA). The effects of Vibrio cholerae peptide (CT; molecular weight, approximately 82,000 Dalton) on glomerular filtration rate (GFR), proximal sodium reabsorption (%pTNa+) and urinary flow rate (UF) were studied. All experiments were preceded by a 30-min control period and in another group of kidneys the time course of the variables was followed without toxin infusion, for a paired control. Control kidneys perfused with Krebs-Henseleit solution plus 60 mg/ml BSA presented stable GFR (paired internal control GFR30 min = 0.596 +/- 0.248 ml g-1 min-1 vs GFR120 min = 0.694 +/- 0.362, N = 32; P0.05) and %pTNa+ (%pTNa+ 30 min = 75 +/- 8.3 vs 84 +/- 1.6 for the internal control, N = 32; P0.05). CT caused a dose (0.03, 0.75 and 1.0 microgram/ml)-dependent decrease in GFR starting at 30 min and with a maximal peak of effect at 90 min after toxin infusion (GFRCT = 0.130 +/- 0.086 ml g-1 min-1, N = 12, vs paired internal control GFRControl/30 min = 0.660 +/- 0.132, N = 12; P0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

An ANF-like material was detected by radioimmunoassay in the isolated perfused rabbit kidney. The production of ANF-like material after 90 min of perfusion under hypoxia was 3000 pg/ml vs 500 pg/ml under normoxia or control conditions. This material is partially inactivated by heat treatment at 100 degrees C for 5 min and is absorbed on a SEP-PAK column (C18, Waters) but, unlike ANF, cannot be recovered from the column. On Sephadex G25 chromatography, elution in water yielded two active fractions, one corresponding to the solvent front and the second obtained after one column volume. Four fractions with biological activity were eluted with water from Sephacryl 200. Several fractions were tested on rabbit aorta preconstricted with 1 microM phenylephrine, without removal of endothelial cells. Treatment of T84 cells in culture by the crude material promoted a dose-related increase (1:2, 1:5, 1:10) of the generation of cyclic GMP. In contrast to our material, ANF (atriopeptin III, 1 microM-10 fM) failed to activate guanylate cyclase in T84 cells, while the heat-stable E. coli enterotoxin (STa) significantly increased cyclic GMP levels at the dose of 5 microM. We propose that a new ANF/urodilatin/ST-like material was generated by the hypoxic kidney under perfusion, which we name FNS (Factor Natriureticus Similis).

In order to compare the function of sodium transport between the intestine and renal tubule, we studied the effect of thermostable E. coli enterotoxin on rat kidneys. Isolated kidneys from adult male hooded rats weighing 240-335 g were perfused with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin. The effects of E. coli enterotoxin (STa; molecular weight approximately 2000; 18 amino acids with three disulfide bonds) were studied on glomerular filtration rate (GFR), net urinary flow rate (UF) and fractional sodium reabsorption (% TNa+). All experiments were preceded by a 30-min control period, and in some kidneys the time course of the variables was followed without toxin infusion, for a paired control. STa (0.1 microgram/ml) infused into the perfusate 30 min after the beginning of the experimental period promoted a significant decline in % TNa+ from 78.4 +/- 1.6 (control period) to 51.6 +/- 6.8 (P0.001) 90 min after the administration of the toxin. This effect was followed by an increase in net urinary flow (UF) in toxin-treated kidneys (UFSTa = 0.120 +/- 0.009 vs UFcontrol = 0.056 +/- 0.011 ml g-1 min-1, P0.008). The GFR of control and STa-treated kidneys did not change during the total time of perfusion and after toxin infusion. Our data demonstrate that STa promotes a specific decrease in tubular sodium transport in the rat kidney.

The participation of platelet-activating factor (PAF, PAF-acether) in a mouse model of pulmonary edema was studied using specific antagonists. Mice were treated before induction of edema with the PAF antagonists BN52021 (10 mg/kg, ip), PCA4248 (10 mg/kg, po) or WEB2170 (10 mg/kg, ip), the lipoxygenase inhibitor EP10161 (10 mg/kg, ip), the cyclo-oxygenase inhibitor aspirin (250 mg/kg, po), or with the mixed cyclo-lipoxygenase inhibitor BW755C (50 mg/kg, ip). The test drugs were administered to animals either 30 min (when the ip route was used) or 60 min (when given po) prior to the induction of pulmonary edema. Pulmonary edema was induced by intravenous administration of adrenaline (2 mg/kg). When the lung-body index was used as the criterion for comparison between groups, BN52021, PCA4248 and WEB2170 were found to have no significant effect on pulmonary edema. In contrast, EP10161, aspirin and BW755C significantly inhibited pulmonary edema by 49%, 30% and 27%, respectively. The results suggest that arachidonate metabolites are likely to play a major role in adrenaline-induced pulmonary edema in mice, whereas PAF-acether does not seem to play an important role in this model.

Renal metabolism of Glycyl-glycine (Gly-gly), Glycyl-proline (Gly-pro) and Prolyl-glycine (Pro-gly) was studied in the non-filtering, isolated perfused rat kidney. Gly-gly is metabolized by more than 90% after 120 min of perfusion. Gly-pro is more resistant to degradation and about 75% of the original peptide can be found intact in the perfusate at the end of perfusion. For Pro-gly, only 25% remains intact at the end of the experiment. Glycine was also monitored as another marker for dipeptide degradation and its production increased throughout the perfusion time. In some experiments we also determined the production of proline. We conclude from these experiments that the basolateral membrane, or perhaps the kidney blood vessels, possess an efficient apparatus for the hydrolysis of Gly-gly and Pro-gly. This mechanism is less efficient in the case of Gly-pro. This confirms an earlier hypothesis that dipeptide metabolism does not occur solely in the brush-border membranes.

Extratos hidroalcoólicos de plantas do Nordeste brasileiro foram testados nas preparações reto abdominal de sapo, duodeno isolado de coelho, coração isolado de anfíbio e útero isolado de rata. As seguintes plantas foram consideradas inativas: Marmeleirinho (Croton sp-33), Azeitona (Eugenia jambolana), Pimenta de macaco (Piper sp-06), Imburana de espinho (Bursera leptophilococos), Espirro (Siperuna guianensis), Araticum (Annona careacea) e Hyptis sp. No tocante aos que se apresentam ativos destacam-se Jurema (Mimosa acutistipula), canafístula de boi (Pithecolobium multiflorum) Castanha de burro (Dipterix alata), Goiabeira (Psidium guajava), Flamboyan (Delonix regia) e Capim cidreira (Cymbopogon citratus). Hydroalcoholic extracts of plants from north east Brazil were teste in the following preparations: toad rectus abdomins, isolated duodenum of rabbits, isolated heart of amphibia and isolated uterus of rats. The following plants were considered inactíve: Marmeleirinho (Croton sp-33), Azeitona (Eugenia jambolana), Pimenta de macaco (Piper sp-06), Imburana de espinho (Bursera, leptophilococos), Espirro (Siparuna guianensis) Araticum (Annona careacea) e Hyptis sp. Several other plants showed activity such as Jurema (Mimosa acutistipula) Canafístula de boi (Pithecolobium multiflorum, Castanha de burro (Dipteryx alata), Goiabeira (Psidium guajava), Flamboyan (Delonix regia) and Capim cidreira (Cymbopogon citratus).

Adrenergic presynaptic functions were evaluated in the cat isolated perfused heart preparation. The sympathetic nerve endings were labelled with [3H]noradrenaline ([3H]NA) and the effect of electric neural stimulation was determined in the presence of drugs which inhibit neuronal or extraneuronal uptake, or which antagonize α-adrenoceptors. [3H]NA overflow was measured in control and diabetic cats and was significantly increased by electric neural stimulation on both conditions. Perfusion with 0.1 μM phentolamine increased transmitter overflow in control hearts but failed to do so on organs obtained from alloxan-treated cats. The data provide evidence that in alloxan diabetic cats there is an abnormality of the adrenergic synapse.

The presynaptic effects of aspirin and prostaglandin E2 (PGE2) were evaluated in the isolated perfused cat heart preparation. Tissue catecholamine stores were studied by labelling the sympathetic nerve endings with [3H]-noradrenaline ([3H]-NA) and the effect of electric neural stimulation (5 Hz, 0.5 ms, 8 V, 60 s) was determined in the presence of drugs which inhibit neuronal or extraneuronal uptake, or antagonize alpha-adrenoceptors. [3H]-NA overflow was significantly increased by electric neural stimulation. Perfusion with 0.1 microM phentolamine increased transmitter overflow. Infusion of 0.1 microM PGE2 reduced the [3H]-NA overflow induced by electrical stimulation. Administration of 1 microM aspirin increased the [3H]-NA overflow and PGE2 prevented this effect of aspirin. The results support the view that PGEs participate in the negative feedback of transmitter release in the isolated perfused cat heart.

e urna graminea de medio porte extensamente cultivado para a producao do oleo de "l'emon-grass" de largo uso industrial. Desta planta existem dois tipos de cultivares, o "East Indian" e o "West Indian", distinguiveis pelos teores de MIRCENO e CITRAL, sendo MIRCENO mais abundante no tipo "West lndian"(Guenther,1972). As folhas desta planta tem largo uso popular no Brasil, na preparacao de infusos ("chas" "abafados" etc) ora como simples bebida aromatica de paladar agradavel , ora como cha m£ dicinal calmante e antispasmodico de acordo com a crenca popular. Em razao da frequencia deste uso esta foi uma das plantas selecionadas pela CEME para estudos precl Fnicos e cl micos planejados para verificacao da validade deste uso. Com o objetivo de investigar possiveis diferencas entre plantas crescidas sob d_i_ ferentes condicoes ecologicas, os oleos essenciais de amostras de plantas cultivadas em Pentecoste-Ce (Capim-santo) e em Sao Paulo (Capim-cidrao) foram analisados por CGL/EM/ COMP.. Seus respectivos hidrolatos (agua codestilada com o oleo essencial e extratos hidroal cool icos foram comparados quanto suas acoes farmacologicas sobre orgaos isolados. Botânica Embora nao tenha sido possivel a preparacao de exsicatas para identificacao botâ­nica da planta em estudo, assumiu-se tratar-se de Cymbopogon citratus Stapf. por comp£ racao da composicao do oleo essencial com a registrada na literatura (Guenther, 1972) ι

The immunoperoxidase avidin-biotin-peroxidase complex method was used to investigate the presence of histiocyte markers such as lysozyme, alpha-1-antitrypsin (A1AT) and alpha-1-anti-chymotrypsin (A1ACT) and of vimentin, a specific marker for mesenchymal differentiation, in a spontaneous and transplantable rat tumor of supposed fibroblastic-histiocytic origin. Positive staining was obtained for lysozyme and vimentin but A1AT and A1ACT were not demonstrable in any of the tumor sections. These results provide evidence for the fibro-histiocytic nature of the tumor studied and suggest its classification as a malignant fibrous histiocytoma (MFH).

We report the diuretic, natriuretic and kaliuretic effects of dexamethasone (DEXA) on intact and adrenalectomized (ADX) male Wistar rats. Indomethacin (INDO) and spironolactone were used to evaluate the involvement of prostaglandin and mineralocorticoid receptors in these actions. DEXA (400 micrograms/kg) and INDO (20 mg/kg) were injected iv and spironolactone (8 mg/100 g) was administered by the oral route. The parameters analyzed were urinary volume (UV), sodium excretion (UNaV) and potassium excretion (UKV). DEXA increased UV and UKV in both intact and ADX rats. INDO administered to intact rats reduced UV by 28% (P less than 0.05) and caused anuresis in ADX rats, but did not interfere with the increased UV induced by DEXA in either ADX or intact animals. Spironolactone did not interfere with diuretic parameters in control animals, but in DEXA-treated animals it decreased UKV by 30% and inhibited DEXA-induced diuresis. These data rule out the possibility of prostaglandin involvement in the acute effects of DEXA and suggest that DEXA induces diuresis through its action on mineralocorticoid receptors or on specific receptors for glucocorticoid (the type II receptor). The latter might also be inhibited by spironolactone.

The influence of the calcium-entry blockers, verapamil, nifedipine and diltiazem on hydrochlorothiazide-induced diuresis was determined in hydrated conscious rats. Nifedipine significantly inhibited hydrochlorothiazide-induced 5-h excreted urine volume and urinary sodium with little effect on potassium excretion. Both verapamil and diltiazem significantly enhanced urinary sodium excretion with no effect on either urine volume or potassium excretion. These results are of interest in view of the current use of nifedipine as an anti-hypertensive agent, alone or in combination with a thiazide diuretic.

CONSTITUINTES QUIMICOS E PROPRIEDADES FARMACOLOGICAS DE DIPTERYX ALATA VOG * F.J. Abreu Matos (**) A.A. Craveiro (**) Fea. Noel ia P. Mendes(***) E.M.C. Fonteles (****) Dipteryx alata Vog . (Leguminosa papi1ionoi dea), arvoreta vulgarmente conhecida pelos nomes ele Castanha-de-burro (Pl), Garampara (MA) e Baru (MG) , ocorre pri nci palmen Seno cerradao do planalto central desde Minas Gerais ate o Piaui. Seus frutos foram selecionados para estudo por causa do uso como aromatizante dos frutos de suas congene­res D. odorata 6 outras fornecedoras das favas de Cumaru ou Fava-tonka da Amazonia. Es_ tudos anteriores (Kaplan et al , 19b6; Kaplan, 19b?) registram como componentes das tascas do caule desta planta, lupeol, lupen-3-ona e betulina Posteriormente encontrou-se como principal componente do oleo essencial do fruto o trans-fs-farneseno (Craveiro et al , I983) -Neste estudo obteve-se como principal constituinte quimico do extrativo dos fru-ffios o β-farneseno. Outros constituintes estao sendo estudados 0 extrato hidroa1 cooI ico dos frutos submetido a ensaio farmacologico em orgaos •otados apresentou como principal propriedade a capacidade de produzir intenso blo-nueio das contracoes produzidas pela acetileolina em preparacoes musculo reto abdominal lie sapo e utero isolado de rata Mostrou ainda bloqueio contratil do coracao isolado • sapo e das contracoes expontâneas do duodeno isolado de coelho Os graficos e a metodologia referentes aos ensaios farmacologicos sao mostrados I em ou tro trabalho do LPN-UFC noutro local destes Anais (Fonteles et al., 198*0. 0 material vegetal selecionado para estudo foi coletado nos municipios de Barra Rjo Corda e Santa Qui teria no Maranhao e suas respectivas exsicatas estao depositadas no [Herbario da UFC sob os numeros 7796 e 9^17, 0 extrato para estudo quimico foi obtido por maceracao de ^500g dos frutos secos •privados das sementes. Os extrativos foram reextrafdos com eter etilico que forneceu Rir concentracao um residuo oleoso (50 Om 1) 0 residuo oleoso foi croma tog ra fado err (*) Trabalho realizado com apoio financeiro do CNPq e FINEP (**) Laboratorio de Produtos Naturais da UFC - Associado ao CNPq-CC-DQOl-Quimica OrgI nica I***) Alunado Curso de Mestrado em Quimica Orgânica (Produtos Naturais) da UFC (****) Laboratorio de Produtos Naturais da UFC - Associado ao CNPq-CCS-DFF-Farmacologia SUPL. ACTA AMAZONICA, l8 (1-2):3^9-350. 1988.