Febrifugine derivative antimalarial activity: quantum mechanical predictors

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

In vitro PHYTOTHERAPY OF VECTOR SNAILS BY BINARY COMBINATIONS OF LARVICIDAL ACTIVE COMPONENTS IN EFFECTIVE CONTROL OF FASCIOLIASIS

SUMMARY A food-borne trematode infection fascioliasis is one among common public health problems worldwide. It caused a great economic loss for the human race. Control of snail population below a certain threshold level is one of the important methods in the campaign to reduce the incidence of fascioliasis. The life cycle of the parasite can be interrupted by killing the snail or Fasciola larva redia and cercaria inside of the snail Lymnaea acuminata. In vitro toxicity of different binary combinations (1:1 ratio) of plant-derived larvicidal active components such as citral, ferulic acid, umbelliferone, azadirachtin and allicin against Fasciola redia and cercaria were tested. The mortality of larvae was observed at 2h, 4h, 6h and 8h of treatment. In in vitro condition azadirachtin + allicin (1:1 ratio) was highly toxic against redia and cercaria (8h LC50 0.006 and 0.005 mg/L). Toxicity of citral + ferulic acid was lowest against redia and cercaria larvae.

Boosting the suppressive effects of Ascaris suum components in IFN-γ-deficient mice

High molecular weight components from Ascaris suum extract suppress ovalbumin-specific immunity in mice. In IFN-γ-deficient mice, ovalbumin-specific delayed-type hypersensitivity reactions are more strongly downregulated by these suppressive components. Here, the cellularity of the delayed-type hypersensitivity reaction in IFN-γ-deficient mice and the increased downregulation induced by Ascaris suum components were analyzed. IL-12p40-dependent neutrophilic influx was predominant. Suboptimal doses of the suppressive fraction from this nematode completely inhibited the hypersensitivity reaction, thus indicating intensification of the immunosuppression under conditions of intense recruitment of IFN-γ-independent neutrophils.

Analysis of the chemical components of hydatid fluid from Echinococcus granulosus

Introduction The aim of this study was to explore the environment of Echinococcus granulosus (E. granulosus) protoscolices and their relationship with their host. Methods Proteins from the hydatid-cyst fluid (HCF) from E. granulosus were identified by proteomics. An inductively coupled plasma atomic emission spectrometer (ICP-AES) was used to determine the elements, an automatic biochemical analyzer was used to detect the types and levels of biochemical indices, and an automatic amino acid analyzer was used to detect the types and levels of amino acids in the E. granulosus HCF. Results I) Approximately 30 protein spots and 21 peptide mass fingerprints (PMF) were acquired in the two-dimensional gel electrophoresis (2-DE) pattern of hydatid fluid; II) We detected 10 chemical elements in the cyst fluid, including sodium, potassium, calcium, magnesium, copper, and zinc; III) We measured 19 biochemical metabolites in the cyst fluid, and the amount of most of these metabolites was lower than that in normal human serum; IV) We detected 17 free amino acids and measured some of these, including alanine, glycine, and valine. Conclusions We identified and measured many chemical components of the cyst fluid, providing a theoretical basis for developing new drugs to prevent and treat hydatid disease by inhibiting or blocking nutrition, metabolism, and other functions of the pathogen.

Ants in a hospital environment and their potential as mechanical bacterial vectors

Introduction We studied the richness and abundance of ant species, their bacteria and the bacteria isolated from patient clinical samples. Methods Ants were collected with baited traps at 64 sites in a public hospital in São Luis, State of Maranhão, Brazil. Results In total, 1,659 ants from 14 species were captured. The most frequent species were Crematogaster victima, Solenopsis saevissima, Tapinoma melanocephalum, Camponotus vittatus and Paratrechina fulva. Forty-one species of bacteria were isolated from the ants and 18 from patients. Conclusions Ants are potential vehicles for pathogenic and opportunistic bacteria, and they can represent a risk factor in nosocomial infections.

Effects of forest structure components on the occurence, group size and density of groups of bare-face tamarin (Saguinus bicolor - primates: Callitrichinae) in Central Amazonia

This study analyzed the influence of forest structural components on the occurence, size and density of groups of Bare-face Tamarin (Saguinus bicolor) - the most threatened species in the Amazon - and produced the first map of distribution of groups in large-scale spatial within the area of continuous forest. Population censuses were conducted between November 2002 and July 2003, covering 6400 hectares in the Ducke Reserve, Manaus-AM, Brazil. Groups of S. bicolor were recorded 41 times accordingly distributed in the environments: plateau (20); slopes (12); and lowlands (09). The mean group size was 4.8 indiv./group, and ranged from 2 to 11 individuals. In the sites where the groups were recorded, and in an equivalent number of sites where no tamarins were found located at least 500 m from those where they had been recorded, we placed 50 m x 50 m plots to record the following forest structural components: abundance of trees; abundance of lianas; abundance of fruiting trees and lianas; abundance of snags; abundance of logs; percentage of canopy opening; leaf litter depth; and altitude. Bare-face Tamarin more often uses areas with lower abundance of forest logs, smaller canopy opening and with higher abundance of snags, areas in the forest with smaller canopy opening present higher density of S. bicolor groups. Apparently this species does not use the forest in a random way, and may select areas for its daily activities depending on the micro-environmental heterogeneity produced by the forest structural components.

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

OBJECTIVE: To assess the effect of food restriction (FR) on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR). METHODS: Isolated papillary muscle preparations of the left ventricle (LV) of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY) rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet) for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1) reduction in the body weight and LV weight of SHR and WKY rats; 2) increase in the time to peak shortening and the time to peak developed tension (DT) in the hypertrophied myocardium of the SHR; 3) diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Clinical significance of in-hospital reocclusion after mechanical reperfusion and percutaneous transluminal coronary angioplasty for acute myocardial infarction

OBJECTIVE: To analyze the effects of in-hospital reocclusion of reperfused AMI culprit coronary arteries in mortality and to identify the predictors. METHODS: The present study comprises a sample of 155 patients with AMI who underwent successful mechanical reperfusion by direct coronary angioplasty and angiographic control during hospitalization or before discharge. Patients were classified into group A: reoccluded patients (n=30) and group B: non-reoccluded patients (n=125). RESULTS: We identified in-hospital reocclusion predictors and found a greater significance in mortality among reoccluded patients (23,3% x 1.6%; p=0.00004). Silent reocclusion or typical angina at reocclusion had a good prognosis. The independent predictors of in-hospital mortality were hypertension, multiarterial lesions, totally occluded AMI culprit lesions, failed redilatation, failed redilatation in comparison with no intention to redilate, no redilatation in comparison with no atempt to redilate, and reocclusion within the first 48 to 72 hours. The decision to redilate, independently of the result, led to a 50.0% reduction in hospital mortality (p=0.0366). CONCLUSION: In-hospital AMI culprit coronary artery reocclusion had an adverse effect similar to that reported in clinical studies with high mortality rates (23.3% x 1.6%; p=0.00004). The major contribution of this study is to recommend the reopening of reoccluded AMI culprit coronary arteries as a means for the management of coronary artery reocclusion.

Percutaneous mechanical mitral commissurotomy performed with a Cribier's metallic valvulotome. Initial results

OBJECTIVE: To evaluate the immediate results of percutaneous mechanical mitral commissurotomy. METHODS: Thirty patients underwent percutaneous mechanical mitral commissurotomy performed with a Cribier's metallic valvulotome from 8/11/99 to 2/4/00. Mean age was 30.7 years, and 73.3% were women. With regards to functional class, 63.3% were class III, and 36.7% were class IV. The echocardiographic score had a mean value of 7.5± 1.8. RESULTS: The mitral valve area increased from 0.97±0.15cm² to 2.16±0.50cm² (p>0.0001). The mean diastolic gradient decreased from 17.9±5.0mmHg to 3.2±1.4mmHg. The mean left atrial pressure decreased from 23.6±5.4mmHg to 8.6±3.1mmHg, (p>0.0001). Systolic pressure in the pulmonary artery decreased from 52.7±18.3mmHg to 32.2±7.4mmHg. Twenty-nine cases were successful. One patient developed severe mitral regurgitation. Interatrial septal defect was observed and one patient. One patient had cardiac tamponade due to left ventricular perforation. No deaths occurred. CONCLUSION: This method has proven to be safe and efficient in the treatment of rheumatic mitral stenosis. The potential advantage is that it can be used multiple times after sterilization, which decreases procedural costs significantly.

Mechanical versus biological aortic valve implants in the elderly. A comparison of early and mid-term results

OBJECTIVE: Our aim was to compare, in a non randomized study, the surgical outcome in elderly patients with mechanical (Group 1; n=83) and bioprosthetic valve implants (Group 2; n=136). METHODS: During a three year period, 219 patients >75 years underwent Aortic Valve Replacement. The groups matched according to age, sex, comorbidity, valve pathology and concomitant Coronary Artery Bypass Surgery. Follow-up was a total of 469 patient-years (mean follow-up 2.1 years, maximum 4,4 years). RESULTS: Operative mortality was zero and the overall early mortality was 2.3 % (within 30 days). Actuarial survival was 87.5 ± 4.0% and 66.1 ± 7.7% (NS) at 4 years in Group 1 and Group 2, respectively. Freedom from valve-related death was 88.9 ± 3.8% in Group 1 and 69.9±7.9% (NS) in Group 2 at 4 years. CONCLUSION: Aortic Valve Replacement in the elderly (>75 years) is a safe procedure even in cases where concomitant coronary artery revascularization is performed. Only a few anticoagulant-related complications were reported and this may indicate that selected groups of elderly patients with significant life expectancy may benefit from mechanical implants .

Evaluation of the marker of hypercoagulability prothrombin fragment F 1+2 in patients with mechanical or biological heart valve prostheses

OBJECTIVE: To investigate whether patients with heart valve prostheses and similar International Normalized Ratios (INR) have the same level of protection against thromboembolic events, that is, whether the anticoagulation intensity is related to the intensity of hypercoagulability supression. METHODS: INR and plasma levels of prothrombin fragment 1+2 (F1+2) were assessed in blood samples of 27 patients (7 with mechanical heart valves and 20 with biological heart valves) and 27 blood samples from healthy donors that were not taking any medication. RESULTS: Increased levels of F1+2 were observed in blood samples of 5 patients with heart valve prostheses taking warfarin. These findings reinforce the idea that even though patients may have INRs, within the therapeutic spectrum, they are not free from new thromboembolic events. CONCLUSION: Determination of the hypercoagulability marker F1+2 might result in greater efficacy and safety for the use of oral anticoagulants, resulting in improved quality of life for patients.

Assessment of factors that influence weaning from long-term mechanical ventilation after cardiac surgery

OBJECTIVE: To analyze parameters of respiratory system mechanics and oxygenation and cardiovascular alterations involved in weaning tracheostomized patients from long-term mechanical ventilation after cardiac surgery. METHODS: We studied 45 patients in their postoperative period of cardiac surgery, who required long-term mechanical ventilation for more than 10 days and had to undergo tracheostomy due to unsuccessful weaning from mechanical ventilation. The parameters of respiratory system mechanics, oxigenation and the following factors were analyzed: type of surgical procedure, presence of cardiac dysfunction, time of extracorporeal circulation, and presence of neurologic lesions. RESULTS: Of the 45 patients studied, successful weaning from mechanical ventilation was achieved in 22 patients, while the procedure was unsuccessful in 23 patients. No statistically significant difference was observed between the groups in regard to static pulmonary compliance (p=0.23), airway resistance (p=0.21), and the dead space/tidal volume ratio (p=0.54). No difference was also observed in regard to the variables PaO2/FiO2 ratio (p=0.86), rapid and superficial respiration index (p=0.48), and carbon dioxide arterial pressure (p=0.86). Cardiac dysfunction and time of extracorporeal circulation showed a significant difference. CONCLUSION: Data on respiratory system mechanics and oxygenation were not parameters for assessing the success or failure. Cardiac dysfunction and time of cardiopulmonary bypass, however, significantly interfered with the success in weaning patients from mechanical ventilation.

Estudos citológicos em Hemíoteros da família Coreidae

A more or less detailed study of the spermatogenesis in six species of Hemiptera belonging to the Coreid Family is made in the present paper. The species studied and their respective chromosome numbers were: 1) Diactor bilineatus (Fabr.) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationaliv in the first division and passing undivided to one pole in the second. 2) Lcptoglossus gonagra (Fabr.) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationally in the first division and passing undivided to one pole in the second. 3) Phthia picta (Drury) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationally in the first division and passing undivided to one pole in the second. 4) Anisocelis foliacea Fabr. : spermatogonia with 26 + X fthe highest mumber hitherto known in the Family), primary .spermatocytes with 13 + X, X dividing equationally in the first division an passing undivided to one pole in the second. 5) Pachylis pharaonis (Herbtst) : spermatogonia with 16 + X, primary spermatocytes with 8 + X. Behaviour of the heteroehromosome not referred. 6) Pachylis laticornis (Fabr.) : spermatogonia with 14 + X, primary spermatocytes with 7 + X, X passing undivided to one pole in the first division and therefore secondary spermatocytes with 7 + X and 7 chromosomes. General results and conclusions a) Pairing modus of the chromosomes (Telosynapsis or Farasynapsis ?) - In several species of the Coreld bugs the history of the chromosomes from the diffuse stage till diakinesis cannot be follewed in detail due specially to the fact that lhe bivalents, as soon as they begin to be individually distinct they appear as irregular and extremely lax chromatic areas, which through an obscure process give rise to the diakinesis and then to the metaphase chomosomes. Fortunately I was able to analyse the genesis of the cross-shaped chromosomes, becoming thus convinced that even in the less favorable cases like that of Phthia, in which the crosses develop from four small condensation areas of the diffuse chromosomes, nothing in the process permit to interpret the final results as being due to a previous telosynaptic pairing. In the case of long bivalents formed by two parallel strands intimately united at both endsegments and more or less widely open in the middle (Leptoglossus, Pachylis), I could see that the lateral arms of the crosses originate from condensation centers created by a torsion or bending in the unpaired parts of the chromosomes In the relatively short bivalents the lateral branches of the cross are formed in the middle but in the long ones, whose median opening is sometimes considerable, two asymetrical branches or even two independent crosses may develop in the same pair. These observations put away the idea of an end-to-end pairing of the chromosomes, since if it had occured the lateral arms of the crosses would always be symetrical and median and never more than two. The direct observation of a side- toside pairing of the chromosomal threads at synizesis, is in foil agreement with the complete lack of evidence in favour of telosynapsis. b) Anaphasic bridges and interzonal connections - The chromosomes as they separate from each other in anaphase they remain connected by means of two lateral strands corresponding to the unpaired segmenas observed in the bivalents at the stages preceding metaphase. In the early anaphase the chromosomes again reproduce the form they had in late diafcinesis. The connecting threads which may be thick and intensely coloured are generally curved and sometimes unequal in lenght, one being much longer than the other and forming a loop outwardly. This fact points to a continuous flow of chromosomal substance independently from both chromosomes of the pair rather than to a mechanical stretching of a sticky substance. At the end of anaphase almost all the material which formed the bridges is reduced to two small cones from whose vertices a very fine and pale fibril takes its origin. The interzonal fibres, therefore, may be considered as the remnant of the anaphasic bridges. Abnormal behaviour of the anaphase chromosomes showed to be useful in aiding the interpretation of normal aspects. It has been suggested by Schrader (1944) "that the interzonal is nothing more than a sticky coating of the chromosome which is stretched like mucilage between the daughter chromosomes as they move further and further apart". The paired chromosomes being enclosed in a commom sheath, as they separate they give origin to a tube which becomes more and more stretched. Later the walls of the tube collapse forming in this manner an interzonal element. My observations, however, do not confirm Schrader's tubular theory of interzonal connections. In the aspects seen at anaphase of the primary spermatocytes and described in this paper as chromosomal bridges nothing suggests a tubular structure. There is no doubt that the chromosomes are here connected by two independent strands in the first division of the spermatocytes and by a single one in the second. The manner in which the chromosomes separate supports the idea of transverse divion, leaving little place for another interpretation. c) Ptafanoeomc and chromatoid bodies - The colourabtlity of the plasmosome in Diactor and Anisocelis showed to be highly variable. In the latter species, one may find in the same cyst nuclei provided with two intensely coloured bodies, the larger of which being the plasmosome, sided by those in which only the heterochromosome took the colour. In the former one the plasmosome strongly coloured seen in the primary metaphase may easily be taken for a supernumerary chromosome. At anaphase this body stays motionless in the equator of the cell while the chromosomes are moving toward the poles. There, when intensely coloured ,it may be confused with the heterochromosome of the secondary spermatocytes, which frequently occupies identical position in the corresponding phase, thus causing missinterpretation. In its place the plasmosome may divide into two equal parts or pass undivided to one cell in whose cytoplasm it breaks down giving rise to a few corpuscles of unequal sizes. In Pachylis pharaonis, as soon as the nuclear membrane breate down, the plasmosome migrates to a place in the periphery of the cell (primary spermatocyte), forming there a large chromatoid body. This body is never found in the cytoplasm prior to the dissolution of the nuclear membrane. It is certain that chromatoid bodies of different origin do exist. Here, however, we are dealing, undoubtedly, with true plasmosomes. d) Movement of the heterochromosome - The heterochromosome in the metaphase of the secondary spermatocytes may occupy the most different places. At the time the autosomes prient themselves in the equatorial plane it may be found some distance apart in this plane or in any other plane and even in the subpolar and polar regions. It remains in its place during anaphase. Therefore, it may appear at the same level with the components of one of the anaphase plates (synchronism), between both plates (succession) or between one plate and tbe pole (precession), what depends upon the moment the cell was fixed. This does not mean that the heterochromosome sometimes moves as quickly as the autosomes, sometimes more rapidly and sometimes less. It implies, on the contrary, that, being anywhere in the cell, the heterochromosome m he attained and passed by the autosomes. In spite of being almost motionless the heterochromosome finishes by being enclosed in one of the resulting nuclei. Consequently, it does move rapidly toward the group formed by the autosomes a little before anaphase is ended. This may be understood assuming that the heterochromosome, which do not divide, having almost inactive kinetochore cannot orient itself, giving from wherever it stays, only a weak response to the polar influences. When in the equator it probably do not perform any movement in virtue of receiving equal solicitation from both poles. When in any other plane, despite the greater influence of the nearer pole, the influence of the opposite pole would permit only so a slow movement that the autosomes would soon reach it and then leave it behind. It is only when the cell begins to divide that the heterochromosome, passing to one of the daughter cells scapes the influence of the other and thence goes quickly to join the autosomes, being enclosed with them in the nucleus formed there. The exceptions observed by BORING (1907) together with ; the facts described here must represent the normal behavior of the heterocromosome of the Hemiptera, the greater frequency of succession being the consequence of the more frequent localization of the heterochromosome in the equatorial plane or in its near and of the anaphase rapidity. Due to its position in metaphase the heterochromosome in early anaphase may be found in precession. In late anaphase, oh the contrary ,it appears almost always in succession. This is attributed to the fact of the heterochromosome being ordinairily localized outside the spindle area it leaves the way free to the anaphasic plate moving toward the pole. Moreover, the heterochromosome being a round element approximately of the size of the autosomes, which are equally round or a little longer in the direction of the movement, it can be passed by the autosomes even when it stands in the area of the spindle, specially if it is not too far from the equatorial plane. e) The kinetochore - This question has been fully discussed in another paper (PIZA 1943a). The facts treated here point to the conclusion that the chromosomes of the Coreidae, like those of Tityus bahiensis, are provided with a kinetochore at each end, as was already admitted by the present writer with regard to the heterochromosome of Protenor. Indeed, taking ipr granted the facts presented in this paper, other cannot be the interpretation. However, the reasons by which the chromosomes of the species studied here do not orient themselves at metaphase of the first division in the same way as the heterochromosome of Protenor, that is, with the major axis parallelly to the equatorial plane, are claiming for explanation. But, admiting that the proximity of the kinetochores at the ends of chromosomes which do not separate until the second division making them respond to the poles as if they were a single kinetochore ,the explanation follows. (See PIZA 1943a). The median opening of the diplonemas when they are going to the diffuse stage as well as the reappearance of the bivalents always united at the end-segments and open in the middle is in full agreement with the existence of two terminal kinetochores. The same can be said with regard to the bivalents which join their extremities to form a ring.

Effect of day time on foliar spraying of several levels of nitrogen fertilizer, NPKS solutions and its components, on common bean leaves

An experiment was carried out in order to determine the effect of day time of foliar spraying of several levels of nitrogen fertilizers, N-P-K-S station, and its components on common bean leaves. Results, based on the visual observations, indicated the maximum levels of each fertilizer that did not cause injuries and showed that the foliar spraying early in the morning is the best day time.

Fitness components of a recently-established population of Zaprionus indianus (Diptera, Drosophilidae) in Brazil

This study aimed to evaluate fitness components of Zaprionus indianus Gupta, 1970, a species recently introduced in Brazil and currently in process of colonization. Longevity, productivity, developmental speed and viability of flies sampled from a population from Mirassol (state of São Paulo, Brazil) were evaluated. Longevity was higher than that of some Indian populations and productivity was similar or higher than in other Drosophilidae. Time of development, one of the main fitness components for competition, was very similar to the values scored in Drosophila sturtevanti Duda, 1927, a species that occurs in high frequencies in the same area as Z. indianus. These data might contribute further for understanding the colonization success of this newcomer species in South America.