The efficacy of HBOC-201 in ex situ gradual rewarming kidney perfusion in a rat model

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin-based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post-transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.     

Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

Objective

To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil.

Methods

In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-α mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR.

Results

Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC₅₀ 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-α mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses.

Conclusions

T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions.     

Association of Elevated Pre-operative Hemoglobin A1c and Post-operative Complications in Non-diabetic Patients: A Systematic Review

Importance

Pre-operative hyperglycemia is associated with post-operative adverse outcomes in diabetic and non-diabetic patients. Current pre-operative screening includes random plasma glucose, yet plasma glycated hemoglobin (HbA1c) is a better measure of long-term glycemic control. It is not clear whether pre-operative HbA1c can identify non-diabetic patients at risk of post-operative complications.

Objective

The systematic review summarizes the evidence pertaining to the association of suboptimal pre-operative HbA1c on post-operative outcomes in adult surgical patients with no history of diabetes mellitus.

Evidence review

A detailed search strategy was developed by a librarian to identify all the relevant studies to date from the major online databases.

Findings

Six observational studies met all the eligibility criteria and were included in the review. Four studies reported a significant association between pre-operative HbA1c levels and post-operative complications in non-diabetic patients. Two studies reported increased post-operative infection rates, and two reported no difference. Of four studies assessing the length of stay, three did not observe any association with HbA1c level and only one study observed a significant impact. Only one study found higher mortality rates in patients with suboptimal HbA1c.

Conclusions and relevance

Based on the limited available evidence, suboptimal pre-operative HbA1c levels in patients with no prior history of diabetes predict post-operative complications and represent a potentially modifiable risk factor.

     

Test-retest reliability of transcarpal sensory NCV method for diagnosis of carpal tunnel syndrome

Background:

Carpal Tunnel Syndrome (CTS) is the most frequent entrapment neuropathy affecting the upper extremity. There are a variety of electrodiagnostic methods available for documenting median neuropathy in CTS. In some studies, determining the sensory NCV across the palm-wrist segment has been introduced as the most sensitive diagnostic procedure for CTS. The aim of this study was to investigate the test-retest reliability of transcarpal median sensory NCV method for the diagnosis of CTS.

Materials and Methods:

Twenty-three patients with clinical symptoms of CTS were tested two times by two different practitioners in one session and again by the first practitioner after one week. Stimulation of the median nerve was performed in the wrist and palm, with a conduction distance maximum of 7 cm, reliabilities of median nerves sensory nerve action potential latencies with stimulation at wrist and palm (W-SNAP, P-SNAP) and its transcarpal NCV were assessed with intraclass correlation coefficient (ICC).

Results:

Comparison of the obtained values, which were done by two practitioners in one session showed ICC of W-SNAP latency, P-SNAP latency and transcarpal NCV of 0.93, 0.88 and 0.87, respectively and values that were done by one practitioner in two sessions with one-week interval showed ICC of 0.60, 0.50 and 0.47, respectively.

Conclusion:

Our findings suggest excellent interpractitioner test-retest reliability of transcarpal median sensory NCV method for diagnosing CTS.     

Synthesis and Evaluation of a New Series of 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their Cyclized Products ‘Pyrimidinylthio Pyrimidotriazolothiadiazines’ as 15- Lipo-Oxygenase Inhibitors

A series of new 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products ‘pyrimidinylthio pyrimidotriazolothiadiazines’ were designed, synthesized, and evaluated as potential inhibitors of 15-lipo-oxygenase (15-LO). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of NaNH₂. The compounds 4d and 4f showed the best IC₅₀ of 15-LO inhibition (IC₅₀ = 9 and 12 μm , respectively). Compounds 4a – g were docked into 15-LO. We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo-oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations.     

Visual performance of four types of diffractive multifocal intraocular lenses and a review of articles

AIM: To compare the clinical outcomes of a variety of multifocal intraocular lenses(MIOLs) in patients diagnosed with presbyopia or cataracts. METHODS: This clinical trial study included 141 patients(282 eyes) with different MIOLs implantation. The Symfony(60 eyes), the Re STOR(100 eyes), the AT LISAtri(60 eyes), and the Pan Optix(62 eyes) intraocular lenses were evaluated in this prospective interventional study. The near, intermediate, and distant visual acuities, contrast sensitivity, and defocus curve were measured as valid criteria. To statistically analyze the results, we used the Statistical Package for Social Science software, the non-parametric Wilcoxon signed-rank t, the one-way analysis of variance and the Tukey’s post-hoc test in our analysis. Moreover, we conducted a detailed literature search on the Pub Med database in English about MIOLs, in total 59 studies were included in this review article.RESULTS: The four approaches did not show any significant difference in the best-corrected distance visual acuity(P>0.05). The defocus curves at the contrast of 100% showed that trifocal IOLs had better intermediate performance than the bifocal IOL(P<0.05). There were no statistically significant differences between AT LISAtri and Pan Optix lenses for visual acuity at all distances. The eyes with Pan Optix, Symfony, and AT LISAtri IOL showed better contrast sensitivity than those Re STOR at spatial frequencies of 1, 3, and 6 cpd in photopic and mesopic conditions(P<0.001). CONCLUSION: All four groups of the multifocal lenses were satisfying in terms of distance and near vision. Also, the group of trifocal lenses led to satisfactory outcomes in intermediate vision, without degradation in quality of vision.     

Advances in iron chelation: an update

INTRODUCTION: Oxidative stress (caused by excess iron) can result in tissue damage, organ failure and finally death, unless treated by iron chelators. The causative factor in the etiology of a variety of disease states is the presence of iron-generated reactive oxygen species (ROS), which can result in cell damage or which can affect the signaling pathways involved in cell necrosis-apoptosis or organ fibrosis, cancer, neurodegeneration and cardiovascular, hepatic or renal dysfunctions. Iron chelators can reduce oxidative stress by the removal of iron from target tissues. Equally as important, removal of iron from the active site of enzymes that play key roles in various diseases can be of considerable benefit to the patients. AREAS COVERED: This review focuses on iron chelators used as therapeutic agents. The importance of iron in oxidative damage is discussed, along with the three clinically approved iron chelators. EXPERT OPINION: A number of iron chelators are used as approved therapeutic agents in the treatment of thalassemia major, asthma, fungal infections and cancer. However, as our knowledge about the biochemistry of iron and its role in etiologies of seemingly unrelated diseases increases, new applications of the approved iron chelators, as well as the development of new iron chelators, present challenging opportunities in the areas of drug discovery and development.     

Randomized Controlled Trial of a Prenatal Breastfeeding Self-Efficacy Intervention in Primiparous Women in Iran

Objective

To determine the effects of a prenatal breastfeeding self-efficacy intervention on breastfeeding self-efficacy and breastfeeding outcomes.