Transdermal patches loaded with L-cysteine HCL as a strategy for protection from mobile phone emitting electromagnetic radiation hazards

Mobile phone usage has been increased in the last few years emitting electromagnetic radiation (EMR), which disturbs normal cellular processes via oxidative stress. L-cysteine, a glutathione precursor, prevents oxidative damage. Transdermal patches (TDPs) loaded with L-cysteine hydrochloride (L-CyS-HCL) were fabricated by dispersion of L-CyS-HCL 5% w/w and different concentrations of sorbitol as a plasticizer in room-temperature vulcanizable synthetic silicone matrices (RTV-Si). The effect of sorbitol on patch physicochemical parameters was assessed; in-vitro L-CyS-HCL release profiles and ex-vivo permeation were studied. Pharmacokinetic parameters of endogenous synthetized in-vivo glutathione, after receiving IV bolus dose of L-CyS-HCl and L-CyS-HCl-RTV-Si-TDPs were studied in rat model. The influence of L-CyS-HCL-RTV-Si-TDPs against damaging effects of mobile phone EMR on rats' blood and brain tissues was studied. The results revealed that patch plasticity, intensity reflections, surface porosity, L-CyS-HCL release rate and skin permeation increased with increasing sorbitol concentration. Pharmacokinetic profile for IV dose and L-CyS-HCl-RTV-Si-TDPs revealed that the L-CyS-HCl-RTV-Si-TDPs provided a sustained glutathione plasma concentration–time profile over entire patch application. High significant differences in biological parameters (blood and brain samples) were observed for radiated rats using the patch in study compared with positive control rats. Promising long-term strategy for protection against mobile phone hazards was obtained.     

Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events : A Meta-Analysis of Statin Trials

Background

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.

Objectives

The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.

Methods

This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

Results

Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.

Conclusions

The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.     

Primary ciliary dyskinesia gene contribution in Tunisia: Identification of a major Mediterranean allele

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease of motile cilia. Even though PCD is widely studied, North‐African patients have been rarely explored. In this study, we aim at confirming the clinical diagnosis and explore the genetic spectrum of PCD in a cohort of Tunisian patients. Forty clinically diagnosed patients with PCD belonging to 34 families were recruited from Tunisian pediatric departments. In each proband, targeted capture PCD panel sequencing of the 40 PCD genes was performed. PCD panel sequencing identified bi‐allelic mutations in 82% of the families in eight PCD genes. Remarkably, 23.5% of patients carried the same c.2190del CCDC39 mutation. Single nucleotide polymorphism profiling in six unrelated patients carrying this mutation has revealed a founder effect in North‐African patients. This mutation is estimated to date back at least 1,400–1,750 years ago. The identification of this major allele allowed us to suggest a cost‐effective genetic diagnostic strategy in North‐African patients with PCD.     

Performance of the BioPlex 2200 Flow Immunoassay in Critical Cases of Serodiagnosis of Toxoplasmosis

The BioPlex 2200 automated analyzer (Bio-Rad Laboratories, Hercules, CA) is a recently developed multiplex analyzer that enables the detection of anti-Toxoplasma, -rubella, and -cytomegalovirus antibodies in the same assay. The aim of this study was to compare this new technology (using the BioPlex 2200 ToRC IgG/IgM kit) in critical cases of serodiagnosis of toxoplasmosis (acute, chronic, or congenital infections and cases with discrepant results) to the technologies used in our routine practice, i.e., the Platelia IgG/IgM enzyme-linked immunosorbent assays (ELISAs) (Bio-Rad Laboratories) and the Toxo-Screen direct agglutination assay (bioMérieux, Lyon, France). Overall, most cases of false-positive/negative results obtained with the Platelia IgG or Toxo-Screen assay were corrected by the BioPlex 2200 ToRC IgG (87.5%). Furthermore, the analysis of 35 sequences of sera showed a trend toward a more rapid decrease of IgM titers by BioPlex 2200 than by Platelia. These results for IgM detection can be explained by a weaker detection of residual IgM. Indeed, among 23 serum samples from patients with probable past infection with long-lasting IgM (Platelia M positive and IgG avidity index, ≥0.5), the BioPlex 2200 Toxoplasma IgM assay was positive for only 11 serum samples. In our panel of critical cases comprising 156 serum and 6 cord blood samples from 103 patients with acute, chronic, or congenital infection, the BioPlex 2200 IgG assay was a sensitive (97.8%) and specific (91.3%) method for IgG detection. The high specificity (97.4%) of IgM detection combined with the shorter kinetics of IgM titers may considerably reduce the number of residual IgM detections, thus yielding more precise diagnoses of acute infections.     

Emergence of Difficult-to-Treat Tinea Corporis Caused by Trichophyton mentagrophytes Complex Isolates,Paris, France

We describe 7 cases of extensive tinea corporis since 2018 in a hospital in Paris, France, after failure to cure with terbinafine. Molecular analysis indicated Trichophyton mentagrophytes internal transcribed spacer type VIII (T. indotineae). This strain, which has mutations in the squalene epoxidase gene, is spreading on the Indian subcontinent.     

Practical compendium for psoriasis management

Psoriasis management is complex and challenging. It should be tailored for each patient. Treatment strategy differs according to patient's age, sex, disease type, disease severity, burden on patient's quality of life, comorbidities, involvement of specific sites, and pregnancy. The choice of the appropriate therapeutic must take into consideration the availability, the price, and the patient's preferences. It is very important that the chosen treatment is not more unpleasant, intolerable, or dangerous than the disease itself. According to the disease type, severity, and effect on patient's quality of life, dermatologist chooses whether to start with topical therapy, phototherapy or systemic therapy, or a combination of two or more of them. Under each category, there are different types of therapies that can be the first line therapeutics, second line, or even contraindicated. In this compendium, we provide dermatologists with different treatment plans considering all the mentioned variables so that a dermatologist can choose the optimum plan for the patient.     

Chemical profiles with cardioprotective and anti-depressive effects of Morus macroura Miq. leaves and stem branches dichloromethane fractions on isoprenaline induced post-MI depression

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane (DCM) fractions of Morus macroura leaves (L) and stem branches (S) on post-myocardial infarction (MI) depression induced by isoprenaline (ISO) in rats in relation to their metabolites. The study was propped with a UPLC-ESI-MS/MS profiling and chromatographic isolation of the secondary metabolites. Column chromatography revealed the isolation of lupeol palmitate (6) that was isolated for the first time from nature with eight known compounds. In addition, more than forty metabolites belonging, mainly to flavonoids, and anthocyanins groups were identified. The rats were injected with ISO (85 mg kg⁻¹, s.c) in the first two days, followed by the administration of M. macroura DCM-L and DCM-S fractions (200 mg kg⁻¹ p.o) for 19 days. Compared with the ISO exposed rats, the treated rats displayed a reduction in cardiac biomarkers (LDH and CKMB), anxiety, and depressive-like behaviour associated with an increase in the brain defense system (SOD and GSH), neuronal cell energy, GABA, serotonin, and dopamine, confirmed by histopathological investigations. In conclusion, DCM-L and DCM-S fractions'' cardioprotective and anti-depressive activities are attributed to their metabolite profile. Therefore, they could serve as a potential agent in amending post-MI depression.

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane fractions of Morus macroura leaves and stem branches on post-myocardial infarction depression induced by isoprenaline in rats in relation to their metabolites.     

Elevated procalcitonin and C‐reactive protein as potential biomarkers of sepsis in a subpopulation of thrombotic microangiopathy patients

Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis syndromes associated with multiple pathogenic factors. Deficient activity of ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a strong rationale for plasma exchange treatment. However, the subset of TMA patients with normal ADAMTS13 activity remains a heterogeneous group of patients in which the appropriate treatment is not well understood. In addition to the common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, the differential diagnosis of TMA may include sepsis, autoimmune disorders, and disseminated intravascular coagulation. Optimal treatment of TMA depends on timely recognition of treatable pathogenic factors. We hypothesized that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA patients. To test this hypothesis, we retrospectively measured the rapid biomarkers of sepsis C‐reactive protein (CRP) and procalcitonin (PCT), in a repository of pretreatment plasma samples from 61 TMA patients treated with plasma exchange. Levels were analyzed in 31 severely ADAMTS13‐deficient and 30 ADAMTS13‐normal patients. None of the 31 patients with severe deficiency of ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non‐ADAMTS13‐deficient patient samples were strongly positive for PCT. These patient samples also had a >10‐fold higher median CRP level than patients with normal PCT. We conclude that rapid assays may help identify sepsis in a subset of TMA patients. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Mivacurium arteriovenous gradient during steady state infusion in anesthetized patients

BACKGROUND: Mivacurium and isomers undergo rapid hydrolysis by plasma cholinesterase. As this enzyme is largely distributed, it cannot be excluded that these isomers might undergo peripheral elimination. This hypothesis was investigated in patients by measuring the difference between arterial and venous concentrations under a constant-rate continuous infusion of mivacurium. METHODS: During propofol-remifentanil anesthesia, eight adult consenting patients received an intravenous bolus dose of 0.2 mg/kg mivacurium, followed by a constant infusion (3, 5, or 7 microg. kg. min ) into the brachial vein. One hour after starting the infusion, arterial (radial artery) and venous (contralateral brachial vein) blood samples were drawn simultaneously at 15-min intervals for 45 min. Mivacurium isomers and metabolite plasma concentrations were determined by stereospecific high-performance liquid chromatography. Using the corresponding arterial and venous concentrations, the tissue extraction coefficient as well as total body clearance were calculated. RESULTS: During steady state conditions, the venous concentrations of the and isomers were 34 +/- 13% and 42 +/- 11% (mean +/- SD) lower than the corresponding arterial concentrations (P < 0.05), respectively. For the isomer, the difference between venous and arterial concentrations was 3 +/- 4% (P = 0.063). Total body clearances of the and isomers were greater when based on venous sampling (P < 0.05). CONCLUSION: Pharmacokinetic parameters derived from a constant infusion of mivacurium depend heavily on the sampling site (arterial or venous) for the rapidly hydrolyzed isomers. These results strongly suggest a significant metabolism of mivacurium within muscle tissue that may account for the large interpatient variability in response to mivacurium.