Phase I study of single‐dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12‐17 years receiving a stable calcineurin inhibitor–based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein‐Barr virus were enrolled; all completed the 6‐month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [C_max] and area under the serum concentration‐time curve from time zero extrapolated to infinity [AUC_0‐INF] were 20% and 25%, respectively). Mean half‐life (T_1/2) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady‐state (V_ss) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.     

Intradetrusor injection of botulinum toxin A in children: a 10-year single centre experience

International Urology and Nephrology - We evaluated the efficacy and safety outcomes of endoscopic intradetrusor botulinum toxin A (BTA) injections for the treatment of children with neuropathic...     

Establishment and characterization of a prostate cancer cell line from a prostatectomy specimen for the study of cellular interaction

Though human prostate cancer (PCa) heterogeneity can best be studied using multiple cell types isolated from clinical specimens, the difficulty of establishing cell lines from clinical tumors has hampered this approach. In this proof-of-concept study, we established a human PCa cell line from a prostatectomy surgical specimen without the need for retroviral transduction. In a previous report, we characterized the stromal cells derived from PCa specimens. Here, we characterized the epithelial cells isolated from the same tumors. Compared to the ease of establishing prostate stromal cell lines, prostatic epithelial cell lines are challenging. From three matched pairs of normal and tumor tissues, we established one new PCa cell line, HPE-15. We confirmed the origin of HPE-15 cells by short tandem repeat microsatellite polymorphism analysis. HPE-15 cells are androgen-insensitive and express marginal androgen receptor, prostate-specific antigen and prostate-specific membrane antigen proteins. HPE-15 expresses luminal epithelial markers of E-cadherin and cytokeratin 18, basal cell markers of cytokeratin 5 and p63 and neuroendocrine marker of chromogranin A. Interestingly, HPE-15 Cells exhibited no tumorigenicity in different strains of immune-deficient mice but can become tumorigenic through interaction with aggressive cancer cell types. HPE-15 cells can thus serve as an experimental model for the study of PCa progression, metastasis and tumor cell dormancy.     

A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

Introduction

We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.

Type 1 diabetes mellitus and eating disorders

The choice of type and quantity of food is vital to achieving glycaemic control in diabetes, more so in type 1 diabetes mellitus. The attention to detail could however reach a level of obsession of an eating disorder and thereby have a negative impact on glycaemic control. We conducted a study to see if there was a risk of developing eating disorders among adolescent, young and middle-aged adults with type 1 diabetes mellitus and whether it has an association with HbA₁C levels. A cross-sectional study was conducted on 113 type 1 diabetes mellitus patients and age-gender-matched healthy controls. The two groups were screened using the Eating Attitude Test-26 (EAT-26) questionnaire. EAT-26 identified type 1 diabetes as having a high risk for developing eating disorder when compared to those without diabetes (OR = 38.5 with 95% CI 8.7, 170.7; p < 0.001). The risk of developing eating disorder increased with the duration of diabetes. There was no significant difference in the risk between males and females. The risk of developing eating disorder did not correlate with glycaemic control. EAT-26 identified subjects with type 1 diabetes as high risk for developing eating disorder in comparison to those without diabetes. In our setting, this did not reflect on poor glycaemic control.     

Knowledge,attitude and anxiety pertaining to basic life support and medical emergencies among dental interns in Mangalore City,India

BACKGROUND: This cross-sectional study aimed to assess the knowledge, attitude and anxiety pertaining to basic life support (BLS) and medical emergencies among interns in dental colleges of Mangalore city, Karnataka, India.     

Protein metabolism in severe childhood malnutrition

The major clinical syndromes of severe childhood malnutrition (SCM) are marasmus (non-oedematous SCM), kwashiorkor and marasmic-kwashiorkor (oedematous SCM). Whereas treatment of marasmus is straightforward and the associated mortality is low, kwashiorkor and marasmic-kwashiorkor are difficult to treat and have high morbidity and mortality rates. Despite extensive research, the pathogenic factors which cause a child to develop the oedematous instead of the non-oedematous form of SCM in response to food deprivation are still not clear. Over the years, two attractive hypotheses have been put forward. The first proposed that a dysadaptation in protein metabolism was involved and the second proposed that free radical damage of cellular membranes might be involved. To address aspects of these hypotheses, in this article we have reviewed work done by our group and by others on protein metabolism and pro-oxidant/anti-oxidant homeostasis in children with the oedematous and non-oedematous syndromes of SCM. A significant finding is that when there is chronic food deprivation children with non-oedematous SCM can maintain body protein breakdown at the same rate as when they are well nourished, but children with oedematous SCM cannot. The slower protein breakdown rate of children with oedematous SCM reduces the supply of most amino acids, resulting in decreased availability for the synthesis of plasma proteins involved in nutrient transport and the acute phase response to infection. Another consistent finding is that children with oedematous SCM have oxidative stress as there is evidence of oxidant-induced cellular damage and impaired synthesis of the primary cellular anti-oxidant glutathione.