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Introduction: biopeptides are amino acid sequences with biological functions about metabolism and carbohydrates absorption., Objective: the aim of this study was the evaluation of the inhibitory effect of peptide fractions derivatives of the hydrolysis of Salvia hispanica against α-amylase and α-glucosidase enzymes to know their activity on the carbohydrates metabolism., Material and Methods: the fraction rich in protein was hydrolyzed by two enzymatic systems: Alcalase®-Flavourzyme® and pepsin-pancreatine. The grade of hydrolysis was determined for the samples. The hydrolyzed samples were centrifuged and the soluble portion was ultra-filtered using different cut membranes. The content of protein was determined for each fraction. An in vitro analysis was made, measuring the percentage of inhibition of the Salvia hispanica fractions against α-amylase and α-glucosidase., Results: the enzymatic system showing the highest grade of hydrolysis (63.53%) was pepsin-pancreatine. From the ultrafiltration, five peptide fractions were obtained: 10 kDa, 5-10 kDa, 3-5 kDa, 1-3 kDa and 1 kDa. The highest protein content was for these fractions: 10 kDa and 5-10 kDa, (0.90 and 0.93 mg/ml, respectively) for pepsin-pancreatine. The inhibition percentages obtained were 85.61% and 79.19% for the 10 kDa and 5-10 kDa fractions, respectively, for the α-amylase enzyme. With respect to the α-glucosidase enzyme, the highest inhibition was for the 10 kDa fraction, with 96.91%., Conclusion: the peptide fractions obtained from the chia may increase the natural sources for the preparation of functional foods important for the diabetic patient's diet.

Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research., (Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.)

Background: several diseases such as sepsis can affect the ileum. Lipopolysaccharide (LPS), an endotoxin present in the cell wall of gram negative bacteria, is a causative agent of sepsis., Objectives: the aims of this study were: a) to investigate the role of mitogen activated protein kinases (MAPKs) in the effect of LPS on the acetylcholine-induced contractions of rabbit ileum; and b) to study the localization of MAPKs in the ileum., Material and Methods: ileal contractility was studied in an organ bath and MAPKs were localized by immunohistochemistry., Results: acetylcholine-induced contractions decreased with LPS. SB203580, SP600125 and U0126 blocked the effect of LPS on the acetylcholine-induced contractions. Phosphorylated p38 and ERK were detected in neurons of myenteric plexus and Phosphorylated p38 and JNK in smooth muscle cells of ileum., Conclusion: we can suggest that p38, JNK, and ERK MAPKs are involved in the mechanism of action of LPS in the ileum.

At the present time, we have effective and potent antiparkinsonian drugs available which allow patients to have an acceptable functional capacity during the early years of Parkinson's disease. Yet, as time goes by, motor and functional deterioration develop, partly due to the presence of motor and non-motor complications. The conventional medication is unable to provide an adequate response if the motor fluctuations are beyond 3-4 hours of duration. At this point, it is reasonable to consider other therapies; among them subcutaneous apomorphine injection must be taken into account due to its simplicity and efficacy and later on, subcutaneous apomorphine infusion. Apomorphine is a very effective and clearly underused drug in the treatment of advanced Parkinson's disease.

Background: The nitric oxide (NO) synthesis blockade is characterized by an increase in the cardiac sympathetic activity and the physical training promotes the decrease in the sympathetic activity., Objective: We investigated the effect of the NO synthesis blockade on the autonomic cardiovascular control in rats submitted to aerobic exercises during a 10-week period., Methods: Male Wistar rats were divided in four groups: control rats, treated with chow food and water ad libitum for 10 weeks (CR); control rats, treated with N G-nitro-L-arginine methyl ester (L-NAME) during the last week (CRL); rats trained during 10 weeks on an electrical treadmill (TR); rats trained for 10 weeks and treated with L-NAME during the last week (TRL). The autonomic cardiovascular control was investigated in all groups with the use of a double blockade with methylatropine and propranolol and analysis of variability., Results: The CRL and TRL groups presented hypertension. The CRL group presented tachycardia and predominance of the sympathetic tonus in heat rate (HR) measurement after the pharmacological autonomic blockade. The TR group presented bradycardia and lower intrinsic HR when compared to the others. The evaluation of the HR variability showed lower absolute and normalized values in the low frequency (LF) band in the CRL group. On the other hand, the TRL presented an increase in the LF band in absolute values. The analysis of variability of the systemic arterial pressure (SAP) showed that the CRL and TRL groups presented higher values in the LF band., Conclusion: The previous physical exercise prevented the deficit in the autonomic cardiac control induced by the treatment with L-NAME, but did not prevent the increase in the SAP variability.

Cytochrome P450 enzymes are very important to metabolize anti-carcinogenic agents. Therefore, understanding the role of these enzymes and their allele variants in the bioactivation or detoxification of drugs could greatly benefit antineoplastic pharmacotherapy. The aim of this manuscript is to give information about metabolizing enzymes for antineoplastic agents and to relate the current situation in antitumoral pharmacotherapy with recent knowledge about cytochrome P450 enzymes. This is crucial for the future perspectives towards personalized pharmacotherapy. We summarize the role of cytochrome P450 enzymes in the resistance and bioactivation of several antitumor agents, their induction and repression mechanisms and the effect of genetic polymorphisms on variability of drug metabolization. The understanding of genetic variability will help to develop new research lines on innovative therapeutic possibilities.

Background: Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation., Aim: To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein., Material and Methods: Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed., Results: The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90% of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63% (p <0.05). In all vessels, the dose response curves were significantly shifted to the right by L-arginine and to the left by L-NAME., Conclusions: Pre-incubation of human rings with L-ARG or L-NAME, changed the response to FE induced contraction, which may be related to different degrees of endothelial nitric oxide production or NO sensitivity. The basal NO production in radial artery seems to be larger than the other vessels.

Quinolone resistance is caused mainly by chromosomal mutations in gram negative bacteria. In 1998, plasmid-mediated resistance to quinolones in clinical isolates was first reported in a Klebsiella pneumoniae strain. Locus qnr (quinolone resistance) was responsible of the quinolone resistance in this plasmid. qnr codes a protein whose function is protect both DNA-girase and topoisomerase IV from these antimicrobials. Moreover, qnr is located in an integron-like structure upstream of qacEDelta y sul1. A review of the information obtained in the last years about this mechanism of resistance was performed.

Quinolones act by inhibiting enzymes (topoisomerases), which are indispensable to DNA synthesis. Their bactericidal activity is concentration-dependent. Their spectrum has become broader, especially since the introduction of a fluorine atom at position 6 (fluoroquinolones). They are used as the treatment of choice or as alternative therapy in a wide variety of infections, both in the hospital and non-hospital setting. Depending on the compound, they are used in urinary tract infections, sexually transmitted diseases, chronic osteomyelitis, respiratory tract infections, and severe systemic infections, among others. The upsurge and extent of quinolone resistance has limited the use of these agents in some cases and in future may determine their use in others. There are strategies to minimize the spread of resistance. Quinolones are safe and well tolerated. The most frequent adverse effects are gastrointestinal and those affecting the central nervous system.

Fenton systems (H2O2/Fe(II) or H2O2/Cu(II)) inhibited Trypanosoma cruzi and Crithidia fasciculata topoisomerase I activity. About 61-71% inactivation was produced by 25 mM Fe(II) or Cu(II) with 3 mM H2O2. Thiol compounds and free radicals scavengers prevented the Fenton systems effects, depending on the topoisomerase assayed. With the T. cruzi enzyme, reduced glutathione, DL-dithiothreitol, cysteine and N-acetyl-L-cysteine entirely prevented the effect of the H2O2/Fe(II) system, mannitol protected 37%, whereas histidine and ethanol were ineffective. With C. fasciculata topoisomerase, reduced glutathione, DL-dithiothreitol and N-acetyl-L-cysteine protected 100%, cysteine, histidine and mannitol protected 28, 34 and 48% respectively, whereas ethanol was ineffective. With the H2O2/Cu(II) system and T. cruzi topoisomerase, DL-dithiothreitol and histidine protected 100% and 60%, respectively but the other assayed protectors were less effective. Similar results were obtained with the C. fasciculata enzyme. Topoisomerase inactivation by H2O2/Fe(II) or H2O2/Cu(II) systems was irreversible since they were not reverted by the more effective enzyme protectors. It is suggested that topoisomerases could act either as scavengers of "reactive oxygen species" (ROS) generated by Fenton systems or bind the corresponding metal ions, whose redox cycling would generate reactive oxygen species "in situ".

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 +/- 7 mmHg; L-NAME, 151 +/- 4.6 mmHg; L-NAME + SnCl2, 133 +/- 3 mmHg, and L-NAME + dexamethasone 152 +/- 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 +/- 0.32, 2) 1.031 +/- 0.23, 3) 1.616 +/- 0.33, and 4) 1.244 +/- 0.33 mumol/mL, while the concentration in blood was: 1) 0.293 +/- 0.06, 2) 0.150 +/- 0.05, 3) 0.373 +/- 0.13, and 4) 0.373 +/- 0.07 mumol/mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content.

Introduction: After ten years of clinical use of Finasteride in patients with BPH, we carried out a systematic review of the literature including the assessment of their quality and grading the level of evidence for clinical recommendations., Methods: Using Medline, Embase, Healthstar and Cochrane Library from 1990 until 2002, we select all the studies referring patients between 50 to 85 with symptoms of BPH, metrics of flow, prostatic volume, postmictional residue, detrusor pressure, adverse effects, cost-effectiveness and quality of life., Results: We found out 135 references, of which 36 accomplish the inclusion criteria. Of those, 3 have got level I of evidence, 12 level II, 6 level III and 10 level IV. Three are economic studies and two evaluate the quality of life., Discussion: With a high level of evidence and after ten years of clinical use, Finasteride shows its effectiveness in reducing the symptoms of patients with prostate bigger than 40 ml and/or PSA of more than 1.4 ngr/ml, with scarce adverse effects with a clear improvement of quality of life. Therefore, it is recommended (grade A) for clinical use., Conclusions: Finasteride, through prostate volume reduction, modify natural evolution of BPH, decreasing the risk of acute urine retention and surgery.

In this study we tested the influence of three ion pump-inhibiting drugs (digoxin, omeprazole and verapamil) on the accumulation of ofloxacin and grepafloxacin in human polymorphonuclear leukocytes. Two assay conditions were established: cell preincubation with the drug for 30 or 60 minutes before addition of quinolone, or addition of both drugs simultaneously. The maximum I/E for ofloxacin is different depending on the assay conditions: 7.69+/-0.88; 5.64+/-1.91 and 3.56+/-1.04 for the assay without preincubation and with preincubation for 30 or 60 minutes at 37 masculine C, respectively. Similarly, grepafloxacin reached the following maximums: 61.27+/-3.04; 32.18+/-3.25 and 22.52+/-3.86. Digoxin did not significantly modify the accumulation of the quinolones, but it increased the I/E compared with the control. In general, omeprazole reduced the accumulation of both quinolones. When omeprazole and ofloxacin were added together, ofloxacin's I/E was significantly lower; however, for grepafloxacin, 60 minutes of preincubation were necessary. Verapamil induced a significant increase in the I/E for both quinolones when the cells were preincubated at 10 times the plasma concentration.

The telomerase is a ribonucleoprotein enzyme to which multiple functions have been attributed, the most important of these is the maintenance of the telomere which is related with cellular immortalization and cancer. 85% of human tumors have telomerase activity, that in normal cells goes undetected. These characteristics make the telomerase an attractive target for chemotherapy.

Many of the resistance mechanisms of enterobacteria to antimicrobial agents are well understood; nevertheless several aspects remain unsolved, particularly with regard to prediction of clinical response. The resistance pattern observed in the antibiogram of a specific organism should be the sum of the natural resistance pattern, characteristic of the species, plus the acquired resistance. In enterobacteria the principal mechanism of resistance to beta lactams and aminoglycosides is enzyme production, Each enzyme recognizes one or more specific beta lactam or aminoglycoside, as a substrate. This translates as a specific resistance phenotype that allows one to infer the enzyme(s) implicated. Enzyme resistance is not, however, the only mechanism of resistance to these agents; often the pattern observed is multifactorial. Resistance to quinolones is due to point and sequence mutations which may be selected by initially active fluoroquinolones and cause a stepwise increase of resistance.

Introduction: Vigabatrin is an effective antiepileptic drug for treatment of partial crises with or without generalization. It acts by increasing GABA levels by irreversible inhibition of the enzyme GABA-transaminase. In recent years there have been several reports published on the appearance of alterations of the visual fields of patients treated with this drug., Objective: To study the prevalence and characteristics of the visual field changes associated with vigabatrin treatment in an adult epilepsy clinic., Patients and Methods: Ophthalmological examination, consisting of questions about eye symptoms, study of the fundus oculi, Humphrey-type campimetry, protocol 30-2, visual evoked potentials and electroretinogram were done on a group of 10 patients on long-term vigabatrin treatment., Results: Six of the ten patients (60%) had campimetric alterations, which were serious in two cases (20%). Only the two patients with severe field defects complained of sight changes when questioned and their complaints were mainly of repeatedly bumping into things. In two patients (20%) there was pallor of the optic nerve. In both cases, the patients with severe field defects showed alterations on the electroretinogram. Visual evoked potentials were normal in all cases., Conclusions: There is a very high prevalence of visual field defects in patients on long-term treatment with vigabatrin. Clinical ophthalmological signs are not usually seen until advanced stages. Pallor of the optic nerve was seen in a group of patients. It is very important that serial campimetric studies are done for early detection of such alterations.

Aims: Transcellular chloride transport is the key event underlying epithelial hydration in the intestine. Little is known about the role of protein tyrosine phosphatases in the regulation of basal and stimulated secretion in human intestinal epithelia. The aim of our study was to investigate the effects of the protein tyrosine phosphatase inhibitor sodium orthovanadate on vectorial chloride transport in native human colon., Methods: An electrophysiological technique was used to measure changes in short-circuit current via a dual voltage/current clamp in native human colon mucosa and in T84 (ATCC) human intestinal cells mounted in modified Ussing chambers., Results: Orthovanadate (1 mM) added to the serosal side of native human colon caused a net rise in short circuit current, reflecting the stimulation of serosal-to-mucosal chloride movement. Epithelial cells responded similarly to the same concentration of the compound. The stimulatory effect of orthovanadate was enhanced by pretreatment with the tyrosine kinase inhibitor genistein, but only when orthovanadate was added to the basolateral chamber. In contrast, the synergistic interaction did not occur when epithelial cells were previously exposed to the cAMP agonist forskolin., Conclusions: We show that tyrosine phosphatases may be involved in the regulation of epithelial chloride transport, and that orthovanadate stimulates secretion in the human colon.

The molecular mechanisms of azole resistance in Candida albicans include alterations in the target enzyme (lanosterol 14-demethylase) and overexpression of efflux transporters that decrease the intracellular concentration of the drug. Although the rate of azole resistance in systemic isolates of C. albicans remains very low, resistance to fluconazole appears as an important issue in the management of oropharyngeal candidiasis (OPC) in patients with AIDS. In order to establish the prevalence of resistance to azole antifungal agents in this setting, we investigated the molecular mechanisms of resistance to azoles in highly resistant C. albicans isolates (fluconazole MIC 64 mg/l) from HIV-infected patients with OPC. Antifungal susceptibility testing of serial C. albicans isolates was performed by NCCLS methodology. Strain identity was investigated by DNA-typing techniques. Overexpression of genes encoding lanosterol 14-demethylase (erg11) and efflux transporters (mdr1 and cdr) implicated in the development of resistance was monitored in matched sets of susceptible and resistant isolates. In addition, erg11 genes were PCR-amplified and their nucleotide sequences determined in order to detect point mutations. A combination of different mechanisms of resistance contributed to the development of resistance to fluconazole. The multifactorial character of the azole resistance in C. albicans makes necessary the development of approaches to overcome the problem. Accordingly, new triazoles have been developed; new classes of antifungals are being investigated; and combinations with inhibitors of efflux transporters are being studied.

Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in rats receiving dexamethasone. In sham-operated rats, dexamethasone administration caused similar changes as observed in cirrhotic animals. Endotoxemia was observed in five of six cirrhotic rats while it was not detected in the control group. Our results show that dexamethasone administration does not modify systemic and splanchnic hemodynamic parameters in endotoxemic cirrhotic rats. This finding suggests that stimulation of the inducible nitric oxide synthase may not play a role in the increased nitric oxide production in portal hypertension.

Unlabelled: It has been demonstrated that coronary flow, through hemodynamic forces, stimulates ventricular contraction and atrio-ventricular transmission; however, the mechanisms involved in these effects remain unknown. A possibility to explain the transduction mechanism, from a mechanical stimulus into a physiological response, could be the stretch-activated ion channels. Additionally we explored the role of nitric oxide as mediator of these actions., Methods: We used the isolated perfused guinea pig heart according to the method of Langendorff, perfused with Krebs solution. We recorded the ventricular contraction by development of left ventricular pressure and the atrio-ventricular transmission. We studied the effects of the stretch activated ion channel blocker; gadolinium. Synthesis of nitric oxide was inhibited by L-NAME and induced with L-arginine., Results: Gadolinium inhibited the stimulating effect of flow on atrio-ventricular transmission and ventricular contraction. Verapamil, a specific blocker of calcium channels, had no effect in the stimulatory effect of flow indicating that this type of calcium channel, do not play significant role in the effects of flow. L-NAME and L-arginine did not have effects on the effects of flow., Conclusion: The stimulating effect of coronary flow in these parameters is regulated by stretch-activated ionic channels. This effect is independent of nitric oxide.

Motor fluctuations are a common problem in the long-term treatment of Parkinson's disease (PD). Entacapone (Comtan) is a potent, peripherally acting, reversible and selective inhibitor of catechol-O-methyltransferase (COMT). Used as an adjuvant to levodopa therapy, entacapone slows the elimination of levodopa by decreasing peripheral conversion to 3-O-methyldopa, increasing central extracellular levodopa and striatal dopamine concentrations. Coadministered with levodopa/carbidopa or levodopa/benserazide, at doses of 200 mg 2 to 10 times daily in patients with end-of-dose fluctuations, entacapone may increase the duration of clinical response, both after the first single dose and after repeated dosing. At this dosage, it has a time to peak plasma concentration of 1.2 h and an elimination half life of 3.4 h. In two multicentric, long-term (24 weeks), parallel, randomized and placebo-controlled studies, entacapone increased the duration of 'on' time (by approximately 1 hour daily) and decreased the duration of 'off' time with a concomitant reduction in the mean daily levodopa dose. In these and other phase III studies, entacapone was generally well tolerated, with most adverse effects being dyskinesias and gastrointestinal disorders. Increased dyskinesia were generally controlled by reducing levodopa doses. Entacapone appears to be a useful adjunct in extending the benefit of each levodopa dose in PD patients with end-of-dose fluctuations.

Objective: To analyze the behaviour of free PSA percentage in finasteride-treated patients and to evaluate whether this ratio allows an increased PSA specificity in the early diagnosis of prostate cancer., Material and Methods: Evaluation of PSA serum levels and free PSA ratio in 336 patients initially diagnosed with prostate benign hyperplasia (PBH). A group of 82 patients were treated with finasteride for 14 to 58 months. A second group of 254 patients received no treatment. All patients were within the same age range and had similar PSA serum levels. In total, 141 prostate biopsies were performed: 19.5 (16/82) and 49.1 (125/254) respectively., Results: Median PSA level in PBH patients was 1.6 ng/mL for the finasteride-treated group and 3.5 for the untreated group, p < 0.0001. Free PSA ratio was 18.6 and 18.8%, respectively, p > 0.05. Carcinoma detection rate was 25% (4/16) for the finasteride group and 27.2% (34/125) for the untreated group. If biopsy had been requested when PSA percentage was below 25%, 17.7 and 19.8% respectively would have been prevented and all carcinoma detected., Conclusion: Long-term treatment with finasteride reduces PSA serum concentration about 50% without changing the free PSA ratio. Carcinoma detection rate was similar in finasteride-treated and untreated patients. Free PSA ratio allows to increase PSA specificity and avoid unnecessary biopsied also in finasteride-treated patients.

The action of piperacillin-tazobactam on 4,137 of the 4,364 strains collected in a Spanish multicenter study involving 46 participating hospitals was studied. The samples were from the following: 41% urine, 18% exuded from wound abscesses, 13% respiratory, 9% blood, 3% peritoneal liquid, and the remainder from other various sources. The gram-negative bacteria included 2,778 strains from 13 genera: Escherichia (1,289), Pseudomonas (451), Proteus (230), Klebsiella (203), Haemophilus (172), Enterobacter (145), Acinetobacter (88), Salmonella (60), Bacteroides (57), Morganella (53), Serratia (46), Citrobacter (46), Stenotrophonomas (23) and Moraxella (21). The gram-positive bacteria were S. aureus (316), E. faecalis (239), S. epidermis (130), S. pneumoniae (115) and Clostridium spp. (12). The global susceptibility of the gram-negatives to piperacillin-tazobactam was 94%: E. coli 98%, P. aeruginosa 92%, and P. mirabilis, Morganella, K. pneumoniae, Serratia and Salmonella spp. all greater than 94%. The susceptibility of other bacteria was as follows: 91% Citrobacter, 77% E. cloacae, 42% A. baumannii, 61% S. maltophilia, 97% E. faecalis, 93% S. epidermidis, 100% M. catarrhalis, 99% H. influenzae and 100% anaerobic bacteria. The action on S. pneumoniae and S. aureus varied according to the susceptibility or lack there of to penicillin or methicillin. In comparison to other antibiotics (piperacillin, cefoxitin, cefotaxime, ceftazidime, cefepime, imipenem and ciprofloxacin), piperacillin-tazobactam was far better than piperacillin alone and better or similar to the others.

Histomorphometric study of hyperplastic human prostate explants coating grown "in vitro" to evaluate the response to a 5-alpha-reductase inhibitor (finasteride). Explants were grown for four weeks in three groups, one in growth medium alone (RPM1-1640), one supplemented with testosterone and one supplemented with testosterone plus finasteride. Explants underwent histological studies, quantifying the surface and thickness of the coating epithelium. Study of the values obtained from the different samples show significant differences (p < 0.001) for the coated surface and its thickness between groups supplemented with testosterone and testosterone + finasteride, and so it can be inferred that this compound (finasteride) would blockade basal cells proliferation and their migration on the explant surface.

Objective: This work attempts to study the cerebral alterations in rat offspring of hyperphenylalaninemic mothers, as well as the possibility of preventing them by means of administration of dietetic supplements of valine, leucine and isoleucine during the pregnancy., Patients and Methods: An experimental study in two consecutive pregnancies of 18 Wistar rats was carried out. The first pregnancy serves as the control group. In the second pregnancy, an experimental hyperphenylalaninemia was provoked by means of injection of phenylalanine and chlorophenylalanine (phenylalanine-hydroxylase inhibitor). In half of the mothers during the second pregnancy the diet was supplemented with branched-chain amino acids. In the offspring rats, a histological cerebral study was performed (conventional electron microscopy and study of synaptosomes). A behavioral study (T-water maze) was also performed at birth and on the 35th and 65th days of life., Results: The offspring of the group submitted to hyperphenylalaninemia were microcephalic (p = 0.0003) and had fewer synaptosomes that had a larger surface area (p = 0.0081 in newborn rats, p = 0.0028 on the 35th day of life) and of a more immature aspect (less vesicular content). In addition, alteration in the myelinization were detected. In the behavior test (65th day of life), the offspring of the mothers with hyperphenylalaninemia make significantly more mistakes (p = 0.0167) and they needed more time for their resolution (p = 0.059). None of these alterations could be prevented by the administration of supplements of branched-chain amino acids to the mother. These supplements resulted in a higher fertility rate, but this action results in affected young rats, so their administration seems to be counter-productive.

Background: The aim of this study was to characterize resistance of Escherichia coli in our environment to four associations of beta-lactams and beta-lactamase inhibitors (beta Lac) studying the influence of the type and level of beta Lac production., Methods: The minimum inhibitory concentration (MIC) to ampicillin/sulbactam (A/S), amoxycillin/clavulanic acid (A/C), ticarcillin/clavulanic acid (T/C) and piperacillin/tazobactam (P/T) assessed was in 245 strains of E. coli resistant to ampicillin, consecutively isolated in our laboratory from September 1995 to March 1996. The beta Lac produced by these isolates were identified by isoelectrofocusing and spectrophotometrically quantified., Results: The sensitivity to A/S, A/C, T/C and P/T was of 9.4, 86.9, 64.5 and 89.4%, respectively. The strains with only one beta Lac which cofocused with TEM-1 were the most frequent (215/245), followed by those producing a cofocusing enzyme with SHV-1 (7/245). A significant correlation was observed between beta Lact activity of the 215 TEM-1 strains and their MIC at A/S (r = 0.53; p < 0.001), A/C (r = 0.46; p < 0.001), T/TC (r = 0.58; p < 0.001), and P/T (r = 0.42; p < 0.001). The comparison between enzyme activity of the isolates of the different categories of susceptibility showed significant differences (p < 0.05) for the four associations studied., Conclusion: TEM-1 production is the main cause of resistance to beta-lactams in E. coli in our environment. The inhibitory efficacy of sulbactam, clavulanic acid and tazobactam over TEM-1 is inversely proportional to the amounts of enzyme produced. The high rate of resistance to A/S and T/C E. coli presents in our environment is mainly due to a hyperproduction of TEM-1.

Background: Acarbose, an alpha glucosidase inhibitor is a drug used in the treatment of non insulin dependent diabetes mellitus, that interferes with the intestinal absorption of monosaccharides., Aim: To study the effect of acarbose in non insulin dependent diabetic patients that had an inadequate metabolic control with diet and sulphonylureas., Patients and Methods: Diabetic patients received acarbose, 150 mg/day during four weeks and this dose was increased to 300 mg/day during 3 months. Afterwards, patients were followed for a period of 12 weeks without acarbose. Fasting and post-prandial blood glucose and glycosilated hemoglobin were measured sequentially during the study., Results: Eighty five patients were recruited for the study but 64 complied with the treatment protocol. The age of these patients was 56 +/- 8.8 years old, their diabetes duration was 7.8 +/- 8.8 years and their body mass index was 27.6 +/- 3.6 kg/m2. During acarbose treatment, glycosilated hemoglobin decreased from 8.36 +/- 1.33 to 7.71+ 1.7% (p < 0.001), fasting blood glucose decreased from 173 +/- 48 to 159 +/- 59 mg/dl (p < 0.03) and post-prandial blood glucose decreased from 254 +/- 80 to 241 +/- 80 mg/dl (NS). After discontinuing acarbose glycosilated hemoglobin and blood glucose levels returned to basal levels. Body weight and blood pressure did not change during the treatment period. Fifty nine patients had gastrointestinal symptoms (meteorism, flatulence and abdominal distention) that were mild in 59% and moderate in 39%. Episodes of hypoglycemia were not observed., Conclusions: Acarbose, associated to sulphonylureas is an effective drug to reduce blood glucose and glycosilated hemoglobin levels in patients with non insulin dependent diabetes.

Background: Acinetobacter sp. is an important cause of nosocomial infections and it is often resistant to many antibiotics. In our hospital it often causes infections in patients on the intensive care unit. The aim of this study was to know the susceptibility of Acinetobacter sp. strains isolated in our hospital., Methods: The in vitro activities of nine antimicrobial agents (ticarcillin, piperacillin, ceftazidime, imipenem, meropenem, gentamicin, tobramycin, amikacin and colistin) and three beta-lactamase inhibitors (sulbactam, clavulanate and tazobactam) against 107 clinical isolates of Acinetobacter baumannii were studied. MICs were determined by a dilution agar method, except for colistin, which we used the disk-diffusion agar method., Results: Of the antimicrobial agents tested imipenem and colistin were highly active against all isolates (100% susceptibility), meropenem presented good activity (96.3% susceptibility), ticarcillin presented moderated activity (84.1% susceptibility). Most of the strains were resistant to ceftazidime (4.7% susceptibility), piperacillin (3.7% susceptibility) and the aminoglycosides (amikacin 21.5% susceptibility, gentamicin 2.8% susceptibility and tobramycin 4.7% susceptibility). Sulbactam was the most active agent among the beta-lactamase inhibitors studied (CMI90 = 4 micrograms/ml)., Conclusions: Recent trends indicate increasing antimicrobial resistance of Acinetobacter baumannii, posing a serious threat to hospitalized patients. An strict attention to maintain a good housekeeping and control of the environment and of the antimicrobial usage, appears the measures most likely to control the spread of Acinetobacter baumannii in hospitals.

Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms.

For the present work, cultures of hyperplastic human prostate explants were performed to evaluate the "in vitro" response of a 5-alpha reductase inhibitor-finasteride. Explants were cultured over a nine-week period in RPMI-1640 media supplemented with Penicillin-Streptomycin 4% and Fetal Bovine Serum 10%. Cultures were divided into one control group, one with testosterone added (1.25 x 10(4) micrograms/ml) and one which received testosterone (1.25 x 10(-4) micrograms/ml) plus finasteride (0,0038 mg/ml). Control explants showed involutive changes throughout the experience, which occurred later in those treated with testosterone and earlier and more marked in the case of finasteride. The testosterone-treated group showed intense positivity for PSA, a marker which reveals specific tissular functions, which remained uniformed in the control group through the entire experiment, and decreased gradually in the finasteride group. In summary, according to our work, culture of organs would be a useful tool for an in vitro evaluation of the hyperplastic human prostate response to the action of the 5-alpha reductase inhibitor, finasteride.