Antibacterial activity of Barbatimão (Stryphnodendron adstringens) against Staphylococcus aureus: in vitro and in silico studies.

We evaluated the activity of the aqueous fraction and the ethyl acetate fraction of Stryphnodendron adstringens against Staphylococcus aureus and proposed their mechanism of action. The antibacterial activity of S. adstringens fractions was evaluated against S. aureus and the cell targets were rated by docking. The fractions showed moderate antibacterial activity against S. aureus without toxicity on two mammalian cell lines. They also showed synergistic antibacterial activity with tannic acid (TA). In silico assays indicated FabG, FabZ and FabI as probable targets. The metabolic pathway for fatty acid biosynthesis in S. aureus was affected by components of S. adstringens. The synergistic effect when combining TA with S. adstringens fractions suggests a natural alternative to S. aureus control. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study describing the possible targets of action of Stryphnodendron adstringens on Staphylococcus aureus. Molecular dynamics simulations showed that the components of S. adstringens affected the metabolic pathway for fatty acid biosynthesis (FAS II) in S. aureus, inhibiting the FabI, FabG and FabZ enzymes. As tannic acid (TA) is a known inhibitor of some targets identified, we showed synergistic antibacterial activity of S. adstringens in combination with TA. This combination did not show toxicity against HaCaT and Vero cells and based on all these results we suggest that S. adstringens can be a natural and sustainable alternative to S. aureus control.

Conserved baculoviral ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus.

ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus (BmMNPV) were amplified, cloned and sequenced. Nucleotide analysis of these genes and those of other baculoviruses showed that these genes are highly conserved. The p10 protein from BmMNPV ORF10 has 70 amino acid residues similar to that of the four other known BmNPV strains. The BmMNPV ORF14 alignment showed a higher identity with the nucleopolyhedrovirus ORF14 from the baculovirus BmNPV and from Autographa californica multiple nucleopolyhedrovirus. The BmMNPV ORF14 protein has a putative transmembrane domain in the C-terminal region, which is similar to that of other baculoviruses. A phylogenetic analysis showed that BmMNPV ORF14 protein has higher similarity with BmNPV ORF14 and ORF23 of A. californica multicapsid nucleopolyhedrovirus (Ac23). We conclude that proteins produced by ORFs 10 and 14 from BmNPV and BmMNPV are highly conserved in NPVs and MNPVs. The high degree of conservation among members of these genera indicates the importance of these proteins, which could mean an important function that is active throughout the infection cycle.

Novel allosteric conformation of human HB revealed by the hydration and anion effects on O(2) binding.

The effect of anions on the stability of different functional conformations of Hb is examined through the determination of the dependence of O(2) affinity on water activity (a(w)). The control of a(w) is effected by varying the sucrose osmolal concentration in the bathing solution according to the "osmotic stress" method. Thus, the hydration change following Hb oxygenation is determined as a function of Cl(-) and of DPG concentration. We find that only approximately 25 additional water molecules bind to human Hb during the deoxy-to-oxy conformation transition in the absence of anions, in contrast with approximately 72 that bind in the presence of more than 50 mM Cl(-) or more than 15 microM DPG. We demonstrate that the increase in the hydration change linked with oxygenation is coupled with anion binding to the deoxy-Hb. Hence, we propose that the deoxy-Hb coexists in two allosteric conformations which depend on whether anion is bound or not: the tense T-state, with low oxygen affinity and anion bound, or a new allosteric P-state, with intermediate oxygen affinity and free of bound anions. The intrinsic oxygen affinity of this unforeseen P-state and the differential binding of Cl(-), DPG, and H(2)O between states P and T and P and R are characteristics which are consistent with those expected for a putative intermediate allosteric state of Hb. These findings represent a new opportunity to explore the structure-function relationships of hemoglobin regulation.

Crystallization and x-ray diffraction data analysis of human deoxyhaemoglobin A(0) fully stripped of any anions.

In this work, initial crystallographic studies of human haemoglobin (Hb) crystallized in isoionic and oxygen-free PEG solution are presented. Under these conditions, functional measurements of the O(2)-linked binding of water molecules and release of protons have evidenced that Hb assumes an unforeseen new allosteric conformation. The determination of the high-resolution structure of the crystal of human deoxy-Hb fully stripped of anions may provide a structural explanation for the role of anions in the allosteric properties of Hb and, particularly, for the influence of chloride on the Bohr effect, the mechanism by which Hb oxygen affinity is regulated by pH. X-ray diffraction data were collected to 1.87 A resolution using a synchrotron-radiation source. Crystals belong to the space group P2(1)2(1)2 and preliminary analysis revealed the presence of one tetramer in the asymmetric unit. The structure is currently being refined using maximum-likelihood protocols.

Alcoholism, Alcoholics Anonymous attendance, and outcome in a prison system.

The purpose of this study was to assess the relationship between attendance at meetings of Alcoholics Anonymous (AA) and follow-up status in a sample of prison inmates. Subjects (N = 102) were administered three self-report measures of alcoholism: the MAST, CAGE, and Rosett Quantity-Frequency tests. AA attendance during incarceration was recorded. One-year follow-up status, ranging from transfer to a more secure facility to discharge from the prison system, was used as an outcome indicator. ResuLts revealed that 56% of the subjects met the criteria for alcoholism on at least one measure, and that scores on the alcoholism measures were significantly correlated with AA attendance. Thus, the most severe alcoholics were the best AA attenders. The hypothesis that greater AA attendance would predict follow-up outcome was not confirmed. However, the extent of drinking reported prior to admission (average alcohol quantity per week) was related to security status at 1-year follow-up. The greater the drinking quantity, the more likely the inmate was to be in a more secure facility. Possible explanations for the findings and the need for a longer follow-up period are discussed.

The Missouri Alcoholism Severity Scale as a predictor of transfer from outpatient to inpatient treatment.

102 patients (41 women) who were enrolled in Appleton 's Outpatient Treatment service between June 1, 1977 and June 1, 1978 required transfer to an inpatient setting. This comprised 17% of all admissions. The entry records of these individuals were scored for the Missouri Alcohol Severity Scale by entering retrospectively the data collected on admission. When, some time after their entry to the outpatient service, these individuals were transferred to an inpatient setting, they became part of the study sample. A like number of controls was also scored for alcoholism severity. The controls remained in the outpatient program successfully. Comparing the score of transferees and controls, the individuals had a statistically significant higher score on the Missouri Alcohol Severity Scale when they had first entered the outpatient clinic (p + 0.03). With addition of other questions, the Appleton Modification, the probability of this happening by chance was 0.001. The data support the concept that inpatient units may play a meaningful role in the course of alcoholism treatment. High dropout rates from outpatient treatment were among the limiting factors of the outpatient setting.

Drug/alcohol interactions: avert potential dangers.

Alcoholism is not uncommon among older people, but "binge" or facilitative drinking is more characteristic of this age group. Alcohol interacts with many drugs frequently prescribed for older patients--antidepressants, sedatives, hypnotics, tranquilizers, and others--and the combination can sometimes be fatal.

Alcohol and its drug interactions.

Alcohol interacts with a suprising number of commonly used drugs: antibiotics, anticoagulants, antihistamines, digitalis, monoamine oxidase inhibitors, nitroglycerine, diuretics, heavy metals, insulin, iron, puromycin C, and many others. It also interacts specifically with sedatives, opiates, phenothiazines, antidepressants, and other psychoactive drugs. This review calls attention to these interactions and what we know of their mechanisms. The physician is cautioned about the use of alcohol by his patients taking other medications and about the frequent difficulty of ascertaining the extent of the patient's alcohol ingestion.