Energetic and thermodynamical aspects of the cyclodextrins-cannabidiol complex in aqueous solution: a molecular-dynamics study.

Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, ß, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-ß-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and ß-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation.

Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17ß-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.

Chlamydophila pneumonia and increased TLR4 gene expression in leukocytes are associated with acute myocardial infarction.

We investigated the relationship of the positivity for Chlamydophila pneumoniae (Cpn) and Mycoplasma pneumonia (Mpn), inflammatory and metabolic markers, and mRNA expression and polymorphisms of the TLR2, TLR4, IL-6 and TNFA genes with acute myocardial infarction (AMI). Two hundred and eighteen individuals (98 AMI and 120 non-AMI) were selected at two Clinical Centers. Blood samples were drawn to extract DNA and RNA and to measure laboratory variables including anti-Cpn IgM and IgG. Cpn and Mpn genomic DNA as well as TLR2, TLR4, IL-6 and TNFA mRNA expression were evaluated by quantitative real-time PCR (qPCR). Gene polymorphisms were detected by PCR-HRM. AMI patients had higher positivity for Cpn-DNA (17.3%) than non-AMI group (6.7%, p=0.018). In addition, Cpn-DNA positivity was an independent predictor of risk for AMI (OR: 2.56, CI: 1.08 - 6.04, p=0.031). Positivity for anti-Cpn IgG and Mpn-DNA was similar between AMI and non-AMI (> 0.05). TLR4 mRNA expression was higher in AMI than non-AMI individuals (p=0.005). CD14 -260C> T, TNFA -308A> G, TLR2 c.2258G> A, TLR4 c.896A> G and TLR4 c.1196> T variants were not associated with increased risk for AMI (p> 0.05). In the AMI group, individuals carrying CD14 -260CC genotype had higher hsCRP levels than CT/TT carriers (p=0.041). These results are suggestive that Cpn-DNA positivity and increased TLR4 mRNA expression in blood leukocytes may be associated with AMI and could be useful markers to evaluate the severity and progression of the atherosclerotic disease in AMI patients.

Long-term follow-up of pregnant women after percutaneous mitral valvuloplasty.

The aim of this study was to evaluate long-term clinical follow-up and echocardiographic data on pregnant patients with mitral stenosis who underwent percutaneous mitral valvuloplasty (PMV) in our center and the development of their infants. PMV has proven to be an effective alternative to treat pregnant patients with mitral stenosis. However, long-term outcome of these patients, as well as the potential harmful effects caused by radiation on their infants, still awaits to be determined. From January 1988 to February 1999, 30 pregnant women (mean gestational duration, 24.95 +/- 5.59 weeks) underwent PMV. Twenty-three (77%) were subsequently followed by a medical interview during 5.33 +/- 3.12 years. Clinical variables such as NYHA functional class (FC), the need of a repeat PMV or surgical procedure, the presence of embolic events, and mortality rate were evaluated during follow-up. Mitral valve area, mean transmitral gradient, and the presence of mitral regurgitation were also assessed by Doppler echocardiography. Clinical data on the development of the infants were obtained from the assistant pediatricians. All patients were in NYHA FC III or IV before the procedure. During follow-up, 91% of them were in FC I and II. Two patients (9%) who had remained in FC III underwent a repeat successful PMV; no further surgery was required. There were no embolic events or death related to the procedure. Echocardiography showed an initial increase in mitral valve area from 1.14 +/- 0.22 cm(2) to 2.01 +/- 0.21 cm+/- (P < 0.0001). During long-term follow-up, it decreased to a mean of 1.75 +/- 0.24 cm(2) (P < 0. 0001). Initial transmitral valve gradient decreased from 17.73 +/- 4. 56 mm Hg to 5.91 +/- 1.80 mm Hg (P = 0.0001) and 8.95 +/- 3.58 (P = 0.002) during long-term follow-up. Twenty one children (96%), aged 4. 91 +/- 2.8 years, showed normal growth and development, and no clinical abnormalities were observed. These favorable long-term results suggests PVM to be the procedure of choice to treat pregnant women with mitral stenosis who remain in FC III or IV despite adequate medical therapy. No harmful effects due to the use of radiation were observed in the children.

[Phlebotomines collected in remaining forests and wild animal shelters from the zoological garden of the Maringa urban area, southern Brazil. Preliminary study]. / Flebotomíneos coletados em matas remanescentes e abrigos de animais silvestres de zoológico no perímetro urbano de Maringá, sul do Brasil. Estudo preliminar.

The present study was undertaken after the detection of one case of cutaneous leishmaniasis with presumed infection in one of the three remaining wooded areas in the urban area of the city of Maringá, Southern Brazil; also in view of the lack of knowledge about sand flies and their behavior. From June to September, 1995, sand flies were caught with Falcão traps during the night in the remaining wooded areas (Parque do Ingá, Bosque Dois and Horto Florestal). A total of 2,907 sand flies were caught in Parque do Ingá; 1,723 of them were aught in forest traps and 1,184 in wild animal shelter traps at the zoo. The results show that Lutzomyia whitmani is better adapted to the three areas under study and that it frequently occurs in wild animal shelters within the urban perimeter of Maringá.

[The students' page. Notes about patient records and the production and reproduction of knowledge. Written and oral presentations]. / Página do estudante. Registro de enfermagem em prontuários e produção/reprodução de conhecimentos: representações escritas e orais.

This paper relates a description about nursing notes in pactients promptuaries in relation to the distribution/reproduction/production process of knowledge in nursing. It was developed on an Intensive Care Unity from a Hospital in the teaching/assistance Sanitary District Barra/Rio Vermelho (Salvador-Bahia). The basic premise is that the nursing personal work superficial and sporadic notes just related to patients. Distribution/ reproduction/production process, that happen in the nursing work process isn't considered by it devaluation or just because, for nursing agents, only information about technical procedures related to patient care, expresses the nursing knowledge and so, must be registered. In order to reach the objective, 30% of the promptuaries of patients discharge from the ICU were studied and the nursing team was interviewed, during the months-november, december 1994. The analysis indicates that the way how the nursing notes are been made, results in hard communication among agents of health area and contributes to disqualify the nursing assistance that is given to patients, besides to limit the advance of the distribution/reproduction/production of knowledge in nursing.