The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg), imipramine (2.5, 7.5, 15 or 30 mg/kg), fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg), mirtazapine (1.25, 2.5, or 5 mg/kg) and a combination of a fixed dose of aspirin (100 mg/kg) with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT) of the lowest dose (by 23%) and the highest dose (by 20%). The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively).Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae

Pathways to emotional closeness in neonatal units – a cross-national qualitative study

Background: Research shows evidence for the importance of physical and emotional closeness for the infant, the parent and the infant-parent dyad. Less is known about how, when and why parents experience emotional closeness to their infants in a neonatal unit (NU), which was the aim of this study. Methods: A qualitative study using a salutogenic approach to focus on positive health and wellbeing was undertaken in three NUs: one in Sweden, England and Finland. An ‘emotional closeness’ form was devised, which asked parents to describe moments/situations when, how and why they had felt emotionally close to their infant. Data for 23 parents of preterm infants were analyzed using thematic networks analysis. Results: A global theme of ‘pathways for emotional closeness’ emerged from the data set. This concept related to how emotional, physical, cognitive and social influences led to feelings of emotional closeness between parents and their infants. The five underpinning organising themes relate to the: Embodied recognition through the power of physical closeness; Reassurance of, and contributing to, infant wellness; Understanding the present and the past; Feeling engaged in the day to day and Spending time and bonding as a family. Conclusion: These findings generate important insights into why, how and when parents feel emotionally close. This knowledge contributes to an increased awareness of how to support parents of premature infants to form positive and loving relationships with their infants. Health care staff should create a climate where parents’ emotions and their emotional journey are individually supported

Amyloid in the islets of Langerhans: Thoughts and some historical aspects

Deposition of amyloid, derived from the polypeptide hormone islet amyloid polypeptide (IAPP; ‘amylin’) is the single most typical islet alteration in type 2 diabetes. Islet amyloid was described as hyalinization already in 1901, but not until 1986 was it understood that it is a polymerization product of a novel β-cell regulatory product. The subject of this focused review deals with the pathogenesis and importance of the islet amyloid itself, not with the biological effect of the polypeptide. Similar to the situation in Alzheimer's disease, it has been argued that the amyloid may not be of importance since there is no strict correlation between the degree of islet amyloid infiltration and the disease. However, it is hardly discussable that the amyloid is important in subjects where islets have been destroyed by pronounced islet amyloid deposits. Even when there is less islet amyloid the deposits are widely spread, and β-cells show ultrastructural signs of cell membrane destruction. It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells. Interestingly, development of islet amyloid may be an important event in the loss of β-cell function after islet transplantation into type 1 diabetic subjects

Short term non-invasive ventilation post-surgery improves arterial blood-gases in obese subjects compared to supplemental oxygen delivery - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>In the immediate postoperative period, obese patients are more likely to exhibit hypoxaemia due to atelectasis and impaired respiratory mechanics, changes which can be attenuated by non-invasive ventilation (NIV). The aim of the study was to evaluate the duration of any effects of early initiation of short term pressure support NIV vs. traditional oxygen delivery via venturi mask in obese patients during their stay in the PACU.</p> <p>Methods</p> <p>After ethics committee approval and informed consent, we prospectively studied 60 obese patients (BMI 30-45) undergoing minor peripheral surgery. Half were randomly assigned to receive short term NIV during their PACU stay, while the others received routine treatment (supplemental oxygen via venturi mask). Premedication, general anaesthesia and respiratory settings were standardized. We measured arterial oxygen saturation by pulse oximetry and blood gas analysis on air breathing. Inspiratory and expiratory lung function was measured preoperatively (baseline) and at 10 min, 1 h, 2 h, 6 h and 24 h after extubation, with the patient supine, in a 30 degrees head-up position. The two groups were compared using repeated-measure analysis of variance (ANOVA) and t-test analysis. Statistical significance was considered to be P < 0.05.</p> <p>Results</p> <p>There were no differences at the first assessment. During the PACU stay, pulmonary function in the NIV group was significantly better than in the controls (p < 0.0001). Blood gases and the alveolar to arterial oxygen partial pressure difference were also better (p < 0.03), but with the addition that overall improvements are of questionable clinical relevance. These effects persisted for at least 24 hours after surgery (p < 0.05).</p> <p>Conclusion</p> <p>Early initiation of short term NIV during in the PACU promotes more rapid recovery of postoperative lung function and oxygenation in the obese. The effect lasted 24 hours after discontinuation of NIV. Patient selection is necessary in order to establish clinically relevant improvements.</p> <p>Trial Registration#</p> <p>DRKS00000751; <url>http://www.germanctr.de</url></p

Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours

The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERalpha, both encoding for transcription factors with a potential involvement in the ERalpha-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERalpha-negative/poor prognosis breast cancer group.The present study was supported by a research grant (SFRH/BD/15316/ 2005 to AA) financed by the Portuguese Science and Technology Foundation (FCT). The authors thank Prof. Raquel Seruca ( coordinator from the Cancer Genetics group at IPATIMUP) for scientific assistance, Dr Jose Luis Costa (postdoctorate at IPATIMUP) for critically reading the manuscript before submission, and Dr Nuno Marcos ( PhD student at IPATIMUP) for artwork assistance

A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far

Relationship between Expression of the Family of M Proteins and Lipoteichoic Acid to Hydrophobicity and Biofilm Formation in Streptococcus pyogenes

Background: Hydrophobicity is an important attribute of bacteria that contributes to adhesion and biofilm formation. Hydrophobicity of Streptococcus pyogenes is primarily due to lipoteichoic acid (LTA) on the streptococcal surface but the mechanism(s) whereby LTA is retained on the surface is poorly understood. In this study, we sought to determine whether members of the M protein family consisting of Emm (M protein), Mrp (M-related protein), Enn (an M-like protein), and the streptococcal protective antigen (Spa) are involved in anchoring LTA in a manner that contributes to hydrophobicity of the streptococci and its ability to form biofilms. Methodology/Principal Findings: Isogenic mutants defective in expression of emm, mrp, enn, and/or spa genes of eight different serotypes and their parental strains were tested for differences in LTA bound to surface proteins, LTA released into the culture media, and membrane-bound LTA. The effect of these mutations on the ability of streptococci to form a hydrophobic surface and to generate biofilms was also investigated. A recombinant strain overexpressing Emm1 was also engineered and similarly tested. The serotypes tested ranged from those that express only a single M protein gene to those that express two or three members of the M protein family. Overexpression of Emm1 led to enhanced hydrophobicity an

Host-Detrimental Role of Esx-1-Mediated Inflammasome Activation in Mycobacterial Infection

The Esx-1 (type VII) secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium marinum. However, the molecular events and host-pathogen interactions underlying Esx-1-mediated virulence in vivo remain unclear. Here we address this problem in a non-lethal mouse model of M. marinum infection that allows detailed quantitative analysis of disease progression. M. marinum established local infection in mouse tails, with Esx-1-dependent formation of caseating granulomas similar to those formed in human tuberculosis, and bone deterioration reminiscent of skeletal tuberculosis. Analysis of tails infected with wild type or Esx-1-deficient bacteria showed that Esx-1 enhanced generation of proinflammatory cytokines, including the secreted form of IL-1β, suggesting that Esx-1 promotes inflammasome activation in vivo. In vitro experiments indicated that Esx-1-dependent inflammasome activation required the host NLRP3 and ASC proteins. Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection. These findings define an immunoregulatory role for Esx-1 in a specific host-pathogen interaction in vivo, and indicate that the Esx-1 secretion system promotes disease and inflammation through its ability to activate the inflammasome