Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats

Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.     

Excellent photocatalytic properties in 2D ZnO/SiC van der Waals hetero-bilayers: water-splitting H2-fuel production

This research unravels the photocatalytic properties of a 2D ZnO/SiC van der Waals hetero-bilayer for potential water-splitting applications by first-principles calculations. Four unique stacking patterns are considered in studying the electronic and optical properties in the presence and absence of biaxial external strain. For pattern-I and II, large negative binding energy and positive phonon frequencies are observed, denoting chemical and mechanical stabilities. Under the HSE-06 pseudo potential, the calculated bandgap value for pattern-I and II reaches 2.86 eV and 2.74 eV, respectively. 2D ZnO/SiC shows a high absorption coefficient (∼10⁵ cm⁻¹). The absorption peak under biaxial strain could reach ∼3.5 times the peak observed under unstrained conditions. Under strain, a shift from compressive to tensile biaxial strain (−6% to 6%) results in a bandgap decrease from 3.18 eV to 2.52 eV and 3.09 eV to 2.43 eV, for pattern-I and II, respectively. The observed strain-driven kinetic overpotential for 2D ZnO/SiC pattern-I and II easily engenders photocatalytic redox reactions. The excellent mechanical durability and strain-driven large kinetic overpotential suggest 2D ZnO/SiC heterobilayers as a prospective material for water-splitting H₂-fuel production.

This research unravels the photocatalytic properties of a 2D ZnO/SiC van der Waals hetero-bilayer for potential water-splitting applications by first-principles calculations.     

Detection of ‘best’ positive end-expiratory pressure derived from electrical impedance tomography parameters during a decremental positive end-expiratory pressure trial

Introduction

This study compares different parameters derived from electrical impedance tomography (EIT) data to define ‘best’ positive end-expiratory pressure (PEEP) during a decremental PEEP trial in mechanically-ventilated patients. ‘Best’ PEEP is regarded as minimal lung collapse and overdistention in order to prevent ventilator-induced lung injury.

Methods

A decremental PEEP trial (from 15 to 0 cm H₂O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients on the ICU. At each PEEP step, EIT measurements were performed and from this data the following were calculated: tidal impedance variation (TIV), regional compliance, ventilation surface area (VSA), center of ventilation (COV), regional ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal gas distribution. From the latter parameter we developed the ITV index as a new homogeneity parameter. The EIT parameters were compared with dynamic compliance and the PaO₂/FiO₂ ratio.

Results

Dynamic compliance and the PaO₂/FiO₂ ratio had the highest value at 10 and 15 cm H₂O PEEP, respectively. TIV, regional compliance and VSA had a maximum value at 5 cm H₂O PEEP for the non-dependent lung region and a maximal value at 15 cm H₂O PEEP for the dependent lung region. GI index showed the lowest value at 10 cm H₂O PEEP, whereas for COV and the RVD index this was at 15 cm H₂O PEEP. The intratidal gas distribution showed an equal contribution of both lung regions at a specific PEEP level in each patient.

Conclusion

In post-cardiac surgery patients, the ITV index was comparable with dynamic compliance to indicate ‘best’ PEEP. The ITV index can visualize the PEEP level at which ventilation of the non-dependent region is diminished, indicating overdistention. Additional studies should test whether application of this specific PEEP level leads to better outcome and also confirm these results in patients with acute respiratory distress syndrome.     

Serum IL-18 levels in tuberculosis: comparison with pneumonia, lung cancer and healthy controls

OBJECTIVE: The aim of the present study was to document the serum IL-18 levels in patients with pulmonary tuberculosis (P-TB), extrapulmonary tuberculosis (EP-TB), pneumonia, lung cancer and in healthy controls, and to investigate whether it may assist in the differential diagnosis of P-TB. METHODOLOGY: A total of 116 patients were included in the study. The study population consisted of patients with P-TB, EP-TB, pneumonia and lung cancer and controls. P-TB patients were graded according to sputum positivity and extent of disease. Serum levels of IL-18 (ELISA) were compared between groups and with other clinical measures of disease. RESULTS: Compared with the controls, all groups of patients had increased serum levels of IL-18. The highest mean concentration of IL-18 was observed in P-TB. Serum levels of IL-18 in the patients with P-TB correlated well with the extent of disease. CONCLUSIONS: Although increased serum levels of IL-18 were not specific for TB, the increased levels may favour active TB in radiologically advanced disease where CXR findings are difficult to interpret, and sputum smears or cultures are not helpful.     

Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo

The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes m06 and m152, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.     

Sodium-dependent recovery of ionised magnesium concentration following magnesium load in rat heart myocytes

Our objectives were to investigate regulation of intracellular ionised Mg²⁺ concentration ([fMg²⁺]_i) in cardiac muscle and cardiac Na⁺/Mg²⁺ antiport stoichiometry. [fMg²⁺]_i was measured at 37°C in isolated rat ventricular myocytes with mag-fura-2. Superfusion of myocytes with Na⁺ and Ca²⁺ free solutions containing 30 mM Mg²⁺ for 15 min more than doubled [fMg²⁺]_i from its basal level (0.75 mM). Re-addition of Na⁺ caused [fMg²⁺]_i to fall exponentially with time to basal level, the rate increasing linearly with [Na⁺]. Log(recovery rate) increased linearly with log([Na⁺]), the slope of 1.06 (95% confidence limits, 0.94–1.17) suggesting one Na⁺ ion is exchanged for each Mg²⁺. [fMg²⁺]_i recovery was complete even if the membrane potential was depolarised to 0 mV or if superfusate [Mg²⁺] was increased to 3 mM. Recovery was rapid in normal Tyrode (0.3 min^–1) with a Q₁₀ of 2.2. It was completely inhibited by 200 M imipramine but was unaffected by 20 M KB-R7943 or 1 M SEA0400, suggesting the Na⁺ /Ca²⁺ antiporter is not involved. Membrane depolarisation by increasing superfusate [K⁺] to 70 mM, or voltage clamp to 0 mV, increased recovery rate in Na⁺ containing solutions more than threefold. We conclude [fMg²⁺]_i recovery is by Mg²⁺ efflux on a 1 Na⁺:1 Mg²⁺ antiport.     

The course and branching pattern of pudendal nerve in fetus

The pudendal nerve is a considerably large branch of the sacral plexus. There are many articles in the literature concerning the pudendal nerve in adults, but as far as we know, there is none on the branching pattern and variations in pudendal nerve anatomy in fetus. This study investigates the pudendal nerve trunking with respect to the piriformis muscle in 25 formalin-fixed fetuses (50 sides of pelves, 15 females, 10 males), ranging from 20 to 37 weeks of gestation. We investigate pudendal nerve trunking in four types: Type I-a is defined as single-trunk with the inferior rectal nerve branching proximal to the dorsal nerve of penis/clitoris (38%), Type I-b is also single-trunk with the dorsal nerve of penis/clitoris branching proximal to the inferior rectal nerve (24%), Type II is double-trunk with medial trunk as an inferior rectal nerve (34%), and Type III is triple-trunk (4%). We measured the average diameter of the main trunk of pudendal nerve in Type I-a and I-b groups to be 0.98 +/- 0.33 mm. We also measured the average length of the pudendal nerve trunks before the dorsal nerve of penis/clitoris branch to be 7.35 +/- 3.50 mm. There was no significant statistical difference in the average length, diameter, number of trunks, and pudendal nerve variations between male and female and also right and left sides of the pelves. This first and detailed fetal study of pudendal nerve trunking with respect to the piriformis muscle would be useful for educational anatomy dissections and anatomical landmark definitions for relevant clinical procedures.