Systemic antibacterial activity of novel synthetic cyclic peptides

Cyclic peptides with an even number of alternating d,l-alpha-amino acid residues are known to self-assemble into organic nanotubes. Such peptides previously have been shown to be stable upon protease treatment, membrane active, and bactericidal and to exert antimicrobial activity against Staphylococcus aureus and other gram-positive bacteria. The present report describes the in vitro and in vivo pharmacology of selected members of this cyclic peptide family. The intravenous (i.v.) efficacy of six compounds with MICs of less than 12 microg/ml was tested in peritonitis and neutropenic-mouse thigh infection models. Four of the six peptides were efficacious in vivo, with 50% effective doses in the peritonitis model ranging between 4.0 and 6.7 mg/kg against methicillin-sensitive S. aureus (MSSA). In the thigh infection model, the four peptides reduced the bacterial load 2.1 to 3.0 log units following administration of an 8-mg/kg i.v. dose. Activity against methicillin-resistant S. aureus was similar to MSSA. The murine pharmacokinetic profile of each compound was determined following i.v. bolus injection. Interestingly, those compounds with poor efficacy in vivo displayed a significantly lower maximum concentration of the drug in serum and a higher volume of distribution at steady state than compounds with good therapeutic properties. S. aureus was unable to easily develop spontaneous resistance upon prolonged exposure to the peptides at sublethal concentrations, in agreement with the proposed interaction with multiple components of the bacterial membrane canopy. Although additional structure-activity relationship studies are required to improve the therapeutic window of this class of antimicrobial peptides, our results suggest that these amphipathic cyclic d,l-alpha-peptides have potential for systemic administration and treatment of otherwise antibiotic-resistant infections.     

Human Visceral Leishmaniasis in Kermanshah Province,Western Iran,During 2011-2012

Background

Visceral leishmaniasis (VL) or kala-azar is a parasitic disease caused by the species of Leishmania donovani complex. It is endemic in some parts of provinces of Iran. According to the reported cases of VL in Kermanshah Province in recent years, this study was conducted to determine the seroprevalence of VL in high risk villages of the province.

Methods

Totally, 1622 serum samples obtained from children under 15 years old and 178 from adults in 22 villages of studied areas. Serum samples were examined by direct agglutination test (DAT) for the detection of anti-Leishmania antibodies. Data were analyzed using SPSS software ver.11.5.

Results

Only 6 serum samples (0.33%) showed anti-Leishmania antibodies against L.infantum at titers ≥ 1/3200. Four of the seropositive cases had a history of kala-azar and Leishman bodies were seen in their bone marrows. The highest (0.5%) and lowest (0.29%) seroprevalence was seen in the age groups of 5-9 and 10-14 years old, respectively. None of the adults were seropositive. There were not any significant differences between the rate of seropositivity in males (0.36%) and females (0.31%). 66.7% of seropositive individuals showed clinical manifestations. The most important symptoms in Kala-azar patients were fever, hepato-spleenomegally and anemia.

Conclusion

Kala-azar is occurred sporadically in Kermanshah Province. But presence of significant number of positive sera confirms the necessity for attention of people and clinicians to kala-azar.     

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Purpose

Asthenozoospermia is a common cause of human male infertility characterized by reduced sperm motility. The molecular mechanism that impairs sperm motility is not fully understood. This study proposed to identify novel biomarkers by focusing on sperm tail proteomic analysis of asthenozoospermic patients.

Methods

Sperm were isolated from normozoospermic and asthenozoospermic semen samples. Tail fractions were obtained by sonication followed by Percoll gradient. The proteins were extracted by solubilization and subjected to two-dimensional gel electrophoresis (2-DE); then, the spots were analyzed using Image Master 2D Platinum software. The significantly increased/decreased amounts of proteins in the two groups were exploited by matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry.

Results

Three hundred ninety protein spots were detected in both groups. Twenty-one protein spots that had significantly altered amounts (p < 0.05) were excised and exploited using MALDI-TOF-TOF mass spectrometry. They led to the identification of the following 14 unique proteins: Tubulin beta 2B; glutathione S-transferase Mu 3; keratin, type II cytoskeletal 1; outer dense fiber protein 2; voltage-dependent anion-selective channel protein 2; A-kinase anchor protein 4; cytochrome c oxidase subunit 6B; sperm protein associated with the nucleus on the X chromosome B; phospholipid hydroperoxide glutathione peroxidase-mitochondrial; isoaspartyl peptidase/L-asparaginase; heat shock-related 70 kDa protein 2; stress-70 protein, mitochondrial; glyceraldehyde-3-phosphate dehydrogenase, testis-specific and clusterin.

Conclusion

Fourteen proteins present in different amounts in asthenozoospermic sperm tail samples were identified, four of which are reported here for the first time. These proteins might be used as markers for the better diagnosis of sperm dysfunctions, targets for male contraceptive development, and to predict embryo quality.     

A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world

BackgroundNeisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000–2020) in the world.MethodsPublished researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.ResultsThe overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.ConclusionsTo properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.     

Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study

Background

The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes.

Methods

From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A_1c.

Results

Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m². Hemoglobin A_1c decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A_1c. Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly.

Conclusion

The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.     

Short Bouts of Intensive Exercise During the Workday Have a Positive Effect on Neuro‐cognitive Performance

Beside its positive impact on physical health, exercise is indicated to positively affect cognitive performance based on a relocation of cortical activity. This study examined the influence of different types of breaks on cognitive performance and related cortical activity in office‐based employees. Breaks were filled with exercise, resting or a usual break and a control condition where employees continued working without any break. Cognitive performance was assessed using the d2‐R test and two commercially available cognitive tasks. Brain cortical activity was recorded using electroencephalography before and after breaks. Individual's mood was analysed using a profile of mood state. Results indicate a positive effect of a 3‐min boxing intervention on cognitive performance, mirrored by a decrease in prefrontal cortex activity. Although perceived psychological state was increased after the usual break, this is reflected in neither cortical activity nor cognitive performance. With respect to the fact that also bike activity resulted an increase in prefrontal alpha‐2 activity, a positive effect of exercise on neuro‐cognitive performance can be stated. Health and economic benefits may result from brief physical activity breaks and help to maintain workplace performance and job satisfaction. Copyright © 2015 John Wiley & Sons, Ltd.     

Derivation of attenuation map for attenuation correction of PET data in the presence of nanoparticulate contrast agents using spectral CT imaging

Objective

Uptake value in quantitative PET imaging is biased due to the presence of CT contrast agents when using CT-based attenuation correction. Our aim was to examine spectral CT imaging to suppress inaccuracy of 511 keV attenuation map in the presence of multiple nanoparticulate contrast agents.

Methods

Using a simulation study we examined an image-based K-edge ratio method, in which two images acquired from energy windows located above and below the K-edge energy are divided by one another, to identify the exact location of all contrast agents. Multiple computerized phantom studies were conducted using a variety of NP contrast agents with different concentrations. The performance of the proposed methodology was compared to conventional single-kVp and dual-kVp methods using wide range of contrast agents with varying concentrations.

Results

The results demonstrate that both single-kVp and dual-kVp energy mapping approaches produce inaccurate attenuation maps at 511 keV in the presence of multiple simultaneous contrast agents. In contrast, the proposed method is capable of handling multiple simultaneous contrast agents, thus allowing suppression of 511 keV attenuation map inaccuracy.

Conclusion

Attenuation map produced by spectral CT clearly outperforms conventional single-kVp and dual-kVp approaches in the generation of accurate attenuation maps in the presence of multiple contrast agents.     

Antiinflammatory and anti‐cancer activities of pomegranate and its constituent,ellagic acid: Evidence from cellular,animal, and clinical studies

Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T‐cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.