Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.     

Idiopathic infantile hypercalcemia and renal involvement

Idiopathic infantile hypercalcemia is recognized as a rare cause of infantile hypercalcemia. Its renal consequences include nephrocalcinosis with distal tubular dysfunction, nephrolithiasis, and finally renal failure. Herein we report the case of a two-month-old infant presenting with idiopathic infantile hypercalcemia complicated with distal renal tubular acidosis (RTA) and nephrocalcinosis. Despite correction of acidosis and dehydration, the persistant hypercalcemia could only be ameliorated with calcitonin treatment. Early diagnosis and appropriate treatment is life-saving in such cases.     

Comparison of plasma and saliva concentrations of lamotrigine in healthy volunteers

The relationship between lamotrigine (CAS 84057-84-1) concentrations in saliva and plasma in healthy volunteers were examined, as well as the possibility of using saliva to monitor levels for effective therapy. The study was performed with 14 healthy volunteers, mean age 23 +/- 2 (SD) years. After single oral doses of 200 mg, plasma and stimulated saliva samples were collected simultaneously at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and 96 h. The pH values of saliva samples were recorded. Lamotrigine concentrations were determined by a validated HPLC method. Fraction of drug bound to plasma proteins was calculated mathematically by the modified Henderson-Hasselbalch equation. Linear regression was used to evaluate the correlations. The remnant of orally administered drug contaminated the saliva samples and gave spuriously high values for up to 2 h, which were omitted. There was significant correlation (r2 = 0.677, p < 0.0001) between plasma and saliva concentrations from 2-96 h after administration. The mean ratio of saliva to plasma concentration was 0.426 +/- 0.153 (mean +/- SD). Protein binding, calculated from the concentrations in saliva was 57.5 +/-15.1% (mean +/- SD). Noncompartmental analysis was conducted with the program Kinetica. Plasma t1/2 and MRT were not significantly different from those found from saliva. The mean values of lamotrigine peak saliva concentrations (C(max)), areas under the curve of concentration versus time from zero to infinity (AUC(0-->infinity)), and areas under the curves of the product of time and concentration versus time from zero to infinity (AUMC(0-->infinity) were proportionally lower than in plasma. The results support the use of saliva concentration as a convenient, painless and noninvasive alternative to plasma for monitoring lamotrigine therapy.     

Multidisciplinary perspectives towards the education of young low-income immigrant children

This paper examines the issues surrounding low-income immigrants in the U.S. and the ways they shape the educational experiences of their young children. Using a multidisciplinary lens including sociology, family studies, education, and mental health, the authors analyse multiple perspectives towards the educational experiences of children in low-income immigrant families. After providing a sample case study focusing on the educational experiences of Burmese refugee parents with early elementary education (Grades K through 3) in the Midwestern United States, the authors frame desirable responses from policy and practice that would best support the educational experiences of young children in low-income immigrant families including (a) understanding cultural strengths, (b) creating a positive and inclusive classroom environment, (c) supporting bilingual and bicultural competencies, (d) providing immigrant families with leadership opportunities, (e) teacher professional development on mental health and poverty, and (f) building integrated supports for the family.     

Radium-223 in the Third-Line Setting in Metastatic Castration-Resistant Prostate Cancer: Impact of Concomitant Use of Enzalutamide on Overall Survival (OS) and Predictors of Improved OS

IntroductionRadium-223 (Ra-223) has been recommended for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). Second-generation hormone therapy in combination with Ra-223 in mCRPC has been utilized, yet its benefit has not been well elucidated. We investigated the potential survival benefit of concomitant enzalutamide with Ra-223 in the third-line setting and predictors of improved overall survival (OS).Patients and MethodsWe retrospectively identified 51 patients with bone-dominant mCRPC that were treated with Ra-223 in the postchemotherapy and post–hormone therapy setting, either alone (group A; n = 32) or with concomitant enzalutamide (group B; n = 19). The primary endpoint was to study the OS difference between groups A and B. The secondary endpoint was to identify predictors of improved OS with Ra-223 in the third-line setting.ResultsMean age was 70.9 years, median baseline prostatic-specific antigen (PSA) was 23.1 ng/mL, alkaline phosphatase was 91 IU/L, and hemoglobin was 12.5 g/dL. There was no difference in median OS between groups A and B, at 20.4 versus 17.5 months, respectively (P = .5186). In univariate and multivariate analyses, only pre–Ra-223 PSA < 30 ng/mL and Eastern Cooperative Oncology Group performance status < 2 were associated with improved OS.ConclusionIn our study cohort, concomitant use of enzalutamide with Ra-223 in the mCRPC setting was not associated with improved OS. Only pretreatment PSA < 30 ng/mL and pretreatment Eastern Cooperative Oncology Group performance status < 2 were associated with improved OS. Further prospective studies are warranted.     

Mind-Body Interventions for Individuals With Heart Failure: A Systematic Review of Randomized Trials

Background

The effects of mind-body interventions (MBIs) (eg, Tai Chi, yoga, meditation) for individuals with heart failure (HF) have not been systematically evaluated.

Preservative solution for skeletal muscle biopsy samples

Context:

Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80°C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved.

Aim:

Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory.

Materials and Methods:

A preservative solution called Kurt-Ozcan (KO) solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis.

Statistical method used:

Chi-square and Kruskal Wallis tests.

Results:

Samples kept in the KO and University of Wisconsin (UW) solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA) of β-actin gene was protected up to 6 hours in the KO and UW solutions.

Conclusion:

The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours.     

Evaluation of 28 cases of mucormycosis

Mucormycosis is a rare but invasive fungal disease with high mortality. The present study aimed to retrospectively investigate the demographic characteristics, as well as the clinical, radiological and laboratory features and the results of treatment, in the patients followed in our hospital because of mucormycosis. The present study retrospectively evaluated 28 cases, which were followed in our hospital because of mucormycosis between January 2002 and July 2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n = 6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases. Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the therapeutic outcomes; it was found that 14 (50%) cases died and six cases recovered with sequel. Today, when particularly the prevalence of immunosuppressive diseases and conditions are gradually increasing, the incidence of mucormycosis is also increased. Considering that the majority of our cases had atypical clinical involvement and complications, being familiar with the characteristics of this disease could be life‐saving together with early diagnosis and treatment.     

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.