Complexos triazenidos de platina (II): Avaliação in vitro da atividade antibacteriana e citotóxica frente a bactérias e células de medula óssea de pacientes leucêmicos de um hospital escola / Triazenidos complexes of platinum (II): In vitro evaluation of antibacterial and cytotoxic activity against bacteria and bone marrow cells from leukemic patients in a university hospital

Atualmente, apesar da ampla gama de substâncias ativas existentes, progressivamente tem se limitado o arsenal terapêutico disponível na prática clínica, isto se deve, especialmente, pelo surgimento da resistência aos agentes terapêuticos utilizados no tratamento de tumores e infecções bacterianas. Em virtude das diversas propriedades farmacológicas demonstradas pelos triazenos (TZCs), avaliaram-se compostos inéditos na busca de novos agentes biologicamente ativos, estes foram denominados C1 e C2. A atividade antibacteriana foi realizada pelo método convencional da microdiluição em caldo, através da técnica da Concentração Inibitória Mínima (CIM), frente a cepas bacterianas de referência American Type Culture Collection (ATCC) e isolados clínicos com resistência múltipla as drogas (RMD). A citotoxicidade foi analisada através do ensaio colorimétrico baseado na redução do brometo de 3-(4,5-dimetiltiazol-2-il)-2,5?difeniltetrazólio frente a células da medula óssea de dois pacientes (P1 e P2) atendidos no Hospital Universitário de Santa Maria. Os dois compostos testados apresentaram atividade antibacteriana em 26,08% (6/23) das cepas testadas, sendo ativos em 38,46% (5/13) das cepas ATCC e 10% (1/10) dos isolados clínicos RMD, apenas em espécies caracterizadas como Gram positivas. Os resultados foram satisfatórios para ambos os compostos frente à amostra P2, células mononucleares de Leucemia Mielóide Crônica, pois demonstraram indução da morte celular. Pode-se concluir que os resultados obtidos desses compostos demonstraram a existência de atividade antibacteriana, bem como, atividade antileucêmica promissora. Pesquisas complementares relacionadas a esses compostos estão em andamento.(AU)

Currently, despite the wide range of existing active substances has been progressively limited therapeutic arsenal available in clinical practice, this is, in particular, the emergence of resistance to therapeutic agents used in treating tumors and bacterial infections. Because of the diverse pharmacological properties demonstrated by triazenes (TZCs) - evaluated whether unpublished compounds in the search for new biologically active agents, they were called C1 and C2. The antibacterial activity was performed by the conventional method of broth microdilution, using the technique of Minimum Inhibitory Concentration (MIC) against the bacterial strains reference American Type Culture Collection (ATCC) and clinical isolates with multiple drug resistance (MDR). Cytotoxicity was analyzed by colorimetric assay based on the reduction of the bromide of 3 - (4,5- dimethylthiazol-2- yl) -2,5- diphenyltetrazolium against bone marrow cells from two patients (P1 and P2) seen at the Hospital university of Santa Maria. The two compounds tested showed antibacterial activity in 26.08% (6/23) of the strains, being active in 38.46 % (5/13) of the ATCC strains and 10 % (1/10) of clinical isolates MDR only characterized in species such as Gram positive. The results were satisfactory for both the sample compounds front P2, mononuclear cells from chronic myeloid leukemia, as demonstrated induction of cell death. It can be concluded that the results demonstrated the existence of these compounds to antibacterial activity, as well as promising antileukemic activity. Additional research related to these compounds are in progress.(AU)

Rio de La Plata study: a multicenter, cross-sectional study on cardiovascular risk factors and heart failure prevalence in peritoneal dialysis patients in Argentina and Uruguay.

A multicenter cross-sectional study was performed to evaluate the prevalence of heart failure (HF) and the associated cardiovascular (CV) risk factors in 298 peritoneal dialysis (PD) patients from Argentina and Uruguay, representing almost 30% of the total number of PD patients in the two countries. Bidimensional echocardiography, electrocardiography, and biochemical analysis were performed. Systolic HF was defined as an ejection fraction <50%. According to echocardiography, 84.6% showed left ventricular hypertrophy (LVH), 38.3% valvular heart disease, and 35.4% valvular calcification, whereas 20% showed intraventricular conduction disturbances on the electrocardiogram. The prevalence of CV risk factors was of 73% hypertension, 51% sedentarism, 18% diabetes, 16.8% obesity, 12% smokers, 42.3% phosphorus >5.5 mg per 100 ml, 42.3% parathyroid hormone>300 pg ml(-1), and 29.6% calcium phosphate product >55. The prevalence of systolic HF was 9.9%, being significantly associated with diabetes: odds ratio (OR)=4.11 (P<0.006) and hypoalbuminemia: OR=3.45 (P<0.011). Forty percent of patients with a diagnosis of left ventricular dysfunction at the time of the study were asymptomatic. Variables associated with LVH in the multivariate analysis were anemia (OR=4.06; P<0.001) and previous hemodialysis (OR=1.99; P<0.031). The identification of reversible risk factors associated to HF and the diagnosis of asymptomatic ventricular dysfunction in this PD population will lead our efforts to establish guidelines for prevention and early treatment of congestive HF in patients on PD.

Comparing peritonitis in continuous ambulatory peritoneal dialysis patients versus automated peritoneal dialysis patients.

The purpose of our study was to compare the incidence of peritonitis between continuous ambulatory peritoneal dialysis (CAPD) treatment (Group I) and automated peritoneal dialysis (APD) treatment (Group II) taking into account the same population. We compared 20 patients with a follow-up of 215 patient-months on CAPD and 252 patient-months on APD. Demographic data, diagnosis, peritoneal equilibration test (PET) results, adequacy, and peritonitis rate were analyzed. Diagnoses included glomerulopathy 35%, autosomal dominant polycystic kidney disease (ADPKD) 20%, Type II diabetes 10%, systemic lupus erythematosus 5%, interstitial nephritis 5%, nephrolitiasis 5%, and unknown 20%. PET results showed that the group consisted of 30% high transporters, 45% high-average transporters, and 25% low-average transporters. Kt/V for Group I was 1.3 +/- 0.3, and for Group II, 1.83 +/- 0.48. Creatinine clearance for Group I was 43.64 +/- 7.31 L/week/1.73 m2, and for Group II, 52.42 +/- 13.47 L/week/1.73 m2. Group I presented a peritonitis rate of 8.3 episodes/patient-month, and Group II presented a rate of 18.9 episodes/patient-month. Gram-positive organisms were responsible for 49.8% of episodes of peritonitis in Group I (S. aureus 26.6%, S. epidermidis 16.6%, others 10%) and 83% of peritonitis episodes in Group II (S. epidermidis 46.6%, S. aureus 20%). Gram-negative organisms were responsible for 16.5% of episodes of peritonitis in Group I. No gram-negative peritonitis was seen in Group II. APD patients developed two cases of candida peritonitis. Our preliminary results show that Group II exhibited a decrease in peritonitis rate while achieving better adequacy. In CAPD and APD peritonitis, gram-positive organisms predominated. In APD, we observed an increase in S. epidermidis incidence. No gram-negative organisms were observed in APD. It seems that APD is a safer treatment owing to the lower peritonitis incidence.

Treatment of recurrent and resistant CAPD peritonitis by temporary withdrawal of peritoneal dialysis without removal of the catheter.

Recurrent and resistant continuous ambulatory peritoneal dialysis (CAPD) peritonitis is usually treated by removal of the catheter and temporary hemodialysis. We treated 3 patients: 1 with resistant Klebsiella peritonitis and 2 with recurrent peritonitis (one due to Staphylococcus and the other to Enterococcus), by stopping CAPD for a 2-4 week period, leaving the catheter in situ and continuing antibiotic therapy. All 3 patients had resolution of their infections and restarted CAPD. This therapeutic modality reduced catheter replacements, limited admissions to the hospital, reduced psychological impact, and diminished risks and costs of CAPD.

Atrial natriuretic factor modifies noradrenaline release in a sodium-free medium.

1. The effects of atrial natriuretic factor (ANF) on 3H-noradrenaline (3H-NA) release evoked by a sodium-free medium (SFM) were studied. The experiments were carried out in rat hypothalamic slices incubated in vitro. 2. ANF (1, 10 and 100 nM) decreased NA release evoked by the omission of sodium in a concentration-dependent way. When calcium was omitted from a SFM, NA output was partially diminished. However, if ANF was added to the SFM/calcium free medium NA secretion showed no modifications. 3. Present results suggest that, in rat hypothalamus, NA release evoked by Na+ omission is divided into two fractions: one independent of and the other dependent on extracellular calcium. In addition, ANF modifies NA release evoked by SFM dependent on extracellular calcium.

Effects of atrial natriuretic factor on norepinephrine release in the rat hypothalamus.

The effects of atrial natriuretic factor on the mechanisms involved in norepinephrine release were studied 'in vitro' in slices of Wistar rat hypothalamus. Atrial natriuretic factor (10, 50 and 100 nM) decreased spontaneous [3H]norepinephrine secretion in a concentration dependent way. In addition, the peptide (10 nM) also reduced acetylcholine induced output of norepinephrine. The atrial factor (10 nM) was unable to alter the amine secretion when the incubation medium was deprived of calcium or when a calcium channel blocker such as diltiazem (100 microM) was added. In conclusion, atrial natriuretic factor reduced both spontaneous and acetylcholine evoked [3H]norepinephrine release in the rat hypothalamus. These findings suggest that the atrial natriuretic factor may alter catecholamine secretion by modifying the calcium available for the exocytotic process of catecholamine output.

Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla.

Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla.

Effects of atrial natriuretic peptide and angiotensin III on the uptake and intracellular distribution of norepinephrine in medulla oblongata of the rat.

1. Ten micromoles angiotensin III decreased total 3H-norepinephrine uptake in medulla oblongata of the rat and 100 nM atrial natriuretic peptide increased it. These were the threshold concentrations for the peptides to modify the uptake of the amine. 2. A threshold concentrations (1 nM) of atrial natriuretic peptide reversed the effects produced by 10 microM angiotensin III on total 3H-norepinephrine uptake, but subthreshold angiotensin III concentrations failed to alter the effects produced by 100 nM atrial natriuretic peptide. 3. Angiotensin III, as well as atrial natriuretic peptide, modified only neuronal norepinephrine uptake and did not alter non-neuronal norepinephrine uptake. 4. Angiotensin III and atrial natriuretic peptide did not modify the intracellular distribution of norepinephrine in medulla oblongata.