The identification of the UV degradants of melatonin and their ability to scavenge free radicals

Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2-. and particularly the.OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC-MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2-. generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC-MS results show that the degradants of melatonin are 6-hydroxymelatonin and N1-acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)-induced superoxide generation compared to non-irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.     

Prevalence and reliability of treatment-based classification for subgrouping patients with low back pain

Objectives: To observe the distribution of patients who presented with low back pain (LBP) and to determine the between therapists’ interrater reliability of assessments in a private outpatient setting using treatment-based classification (TBC) subgroups.

Methods: An observational and methodological study was conducted. Four hundred and twenty-nine patients (231 male; 198 female) presenting LBP symptoms and referred to conservative treatment were assessed by 13 physical therapists who conducted a 60-min examination process utilizing TBC subgroups. Interrater reliability analyses from six raters were assessed using Fleiss’ kappa and previously recorded data (n = 30).

Results: In this study, 65.74% of patients were classified in only one subgroup, the most prevalent being stabilization (21.91%), followed by extension (15.38%), traction (11.89%), flexion (10.96%), manipulation (5.13%), and lateral shift (0.47%). Approximately 20.98% of patients were classified in two subgroups, where the most frequent overlaps were flexion + stabilization (7.46%), extension + stabilization (6.06%), flexion + traction (4.20%), extension + manipulation (1.86%), and 13.29% of patients were not classified in any TBC subgroup. Analysis of interrater reliability showed a kappa value of 0.62 and an overall agreement of 66% between raters.

Discussion: LBP is a heterogeneous clinical condition and several classification methods are proposed in the attempt to observe better outcomes for patients. Eighty-five percent of patients assessed were able to be classified when using the TBC assessment and reliability analysis showed a substantial agreement between raters.

Level of Evidence: 2c.     

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images

Purpose

Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease.

Procedures

Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)].

Results

Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho?=?0.5650, rho?=?0.5741, rho?=?0.5068; p?<?0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p?<?0.05). SD and MAD correlated with diastolic function by echocardiography (rho?=?0.3837, p?=?0.0071; rho?=?0.3330, p?=?0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function.

Conclusions

Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.     

Unilateral Direct Carotid Cavernous Fistula Causing Bilateral Ocular Manifestation

Unilateral carotid cavernous fistula presents with ipsilateral ocular findings. Bilateral presentation is only seen in bilateral fistulas, usually associated with indirect (dural) carotid cavernous fistulas. Direct carotid cavernous fistulas are an abnormal communication between the internal carotid artery and the cavernous sinus. They typically begin with a traumatic disruption in the artery wall into the cavernous sinus, presenting with a classic triad of unilateral pulsatile exophthalmos, cranial bruit and episcleral venous engorgement. We report the case of a 38-year-old male with traumatic right carotid cavernous sinus fistula and bilateral ocular presentation successfully treated by interventional neuroradiology.Key Words: Exophthalmos, Papilledema, Carotid artery injury, Carotid cavernous sinus fistula, Endovascular procedure, Therapeutic embolization     

Pharmacokinetic Interaction of the Direct Renin Inhibitor Aliskiren with Furosemide and Extended‐Release Isosorbide‐5‐Mononitrate in Healthy Subjects

This study investigated the pharmacokinetics, safety, and tolerability of aliskiren administered alone or in combination with either the loop diuretic furosemide or an oral extended‐release formulation of isosorbide‐5‐mononitrate (ISMN). In separate studies, 22 healthy subjects (ages 18–45 years) received either ISMN 40 mg or furosemide 20 mg once‐daily for 3 days followed by a 3‐day washout. Subjects then received aliskiren 300 mg once‐daily for 7 days followed by combination therapy for 3 days. Pharmacokinetic assessments were taken at regular intervals over 24 h after dosing on the last day of each treatment period. At steady state, aliskiren AUC_τ was decreased by 7% (geometric mean ratio [90% CI], 0.93 [0.84, 1.04]), and C_max by 20% (0.80 [0.65, 0.97]) with furosemide coadministration compared with aliskiren administration alone. Aliskiren coadministration reduced furosemide AUC_τ by 28% (0.72 [0.64, 0.81]) and C_max by 49% (0.51 [0.39, 0.66]) compared with furosemide alone. Coadministration of aliskiren and ISMN was associated with only minor changes in the pharmacokinetic parameters of aliskiren (AUC_τ 1.03 [0.90, 1.18]; C_max 0.94 [0.69, 1.29]) and ISMN (AUC_τ 0.88 [0.71, 1.10]; C_max 0.94 [0.79, 1.13]). Headache and dizziness were the most common adverse events in both studies; dizziness and BP values below normal (SBP <90 and/or DBP <50 mmHg) were more frequent with aliskiren and ISMN coadministration than with either agent alone. Coadministration of aliskiren and ISMN had no clinically relevant effect on either aliskiren or ISMN pharmacokinetics. In conclusion, coadministration of aliskiren and furosemide reduced furosemide exposure and had a minor effect on aliskiren pharmacokinetics. The clinical significance of reduced systemic exposure to furosemide during coadministration of aliskiren is uncertain.     

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study

OBJECTIVES: The causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths. METHODS: Analyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients. Incidence rates of pre-AIDS deaths were compared to overall rates. Factors relating to pre-AIDS deaths were identified using Cox regression. RESULTS: Death rates declined from 15.6 to 2.7 per 100 person-years of follow-up (PYFU) between 1994 and 2001. Pre-AIDS incidence declined from 2.4 to 1.1 per 100 PYFU. The ratio of overall to pre-AIDS deaths peaked in 1996 at 8.4 and dropped to < 3 after 1998. The adjusted odds of dying following one AIDS defining event (ADE) increased yearly (odds ratio, 1.53; P < 0.001), conversely the odds of dying following three or more ADE decreased yearly (odds ratio, 0.79; P < 0.001). The proportion of deaths that followed an HIV-related disease decreased by 23% annually; in contrast there was a 32% yearly increase in the proportion of deaths due to known causes other than HIV-related or suicides. Injecting drug users (IDU) were significantly more likely to die before an ADE than homosexuals (relative hazard, 2.97; P < 0.0001) and patients from northern/eastern Europe (relative hazard, 2.01; P < 0.0001) were more likely to die pre-AIDS than southern patients. CONCLUSIONS: The proportion of pre-AIDS deaths increased from 1994 to 2001; however, the incidence of pre-AIDS deaths and deaths overall declined. IDU and subjects from northern/eastern Europe had an increased risk of pre-AIDS death. HIV-positive patients live longer therefore it is essential to continue to monitor all causes of mortality to identify changes.     

Complete recovery from Cryptosporidium parvum infection with gastroenteritis and sclerosing cholangitis after successful bone marrow transplantation in two brothers with X-linked hyper-IgM syndrome

We describe two brothers who suffered from hyper-IgM syndrome (HIGM1) with similar clinical features: recurrent infections, especially cryptosporidium gastroenteritis with cholangitis. Their activated T cells did not express CD40L. Nucleotide sequencing revealed a mutation in both boys with respect to intron 4 and exon 5 boundaries of the CD40L gene in Xq26. They underwent successful bone marrow transplantation (BMT) from HLA-geno-identical siblings. The Cryptosporidium infection and cholangitis resolved thereafter. At 6 months after BMT, expression of CD40L on activated T lymphocytes was normal. After 1 year, both boys are well, and immune reconstitution has improved. Based on these two successful experiences, BMT with a genoidentical sibling seems a reasonable therapeutic approach for HIGM1, if Cryptosporidium infection occurs.