The members of the casein kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (a, ß, ?, d, e) and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, sleeping disorders and proliferative diseases such as cancer. In this review, we summarize the functions of CK1 and outline the participation of CK1 in signal transduction pathways linked to cancer development.

Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.

c Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m 2 ). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27. W hile antimicrobial resistance is one of the greatest threats to human health, the number of new antibiotics against multidrug-resistant bacteria declined drastically over the last 3 decades (1-3). Meropenem continues to serve as an important component of our antibiotic armamentarium and covers a large range of clinically relevant pathogens for antibiotic therapy, including those causing intra-abdominal infections or infections of the subcutaneous tissue. Meropenem is a potent, broad-spectrum ␤-lactam antibiotic that yields relatively rapid bacterial killing and is among the first antibiotic options for treatment of severe infections; it covers most of the pathogens relevant for intra-abdominal infections (4). Meropenem is a hydrophilic molecule, and it is unknown whether meropenem penetrates well into the subcutaneous tissue and peritoneal fluid of obese patients.Obese patients are at a high risk of postoperative and hospitalrelated infections (5), and optimal management of these infections is crucial to improve the outcome of obese patients with severe infections. The selection of the antibiotic and dose are critical to manage those infections (5, 6). Recommended daily doses are based on pharmacokinetic/pharmacodynamic (PK/PD) studies usually conducted in nonobese healthy volunteers (5). However, PK variables may differ in obese and nonobese patients, potentially resulting in inadequate antibiotic plasma and tissue concentrations. Thus, PK studies in obese, noninfected individuals are essential to avoid the risk of over-or underdosing.Only a few studies have assessed the PK of meropenem in obese patients (4-8), and some of these studies found considerably different clearances and volumes of distribution in obese and nonobese patients. These studies did not perform population pharmacokinetic modeling and did not assess the peritoneal fluid and subcutaneous tissue penetration of meropenem in obese patients.As meropenem is a hydrophilic molecule, it is important to determine whether its PK is...

Besides history and clinical examination, WBC, CRP, and US examination remain important factors for diagnosing acute appendicitis. Complications are related to the pathology, presence of bacteria, and type of operation. Early diagnosis within 48 h may be important. A laparoscopic procedure in adults may also cause fewer wound infections.

, 19-45 min). Follow-up for all recipients was at least 18 months. There was no reintervention necessary, no wound infections, no primary nonfunction or a delayed graft function, no need for dialysis, no acute rejection episodes, no graft loss, no wound dehiscence, no incisional hernia, or lymphocele. Furthermore, no urologic complications or vascular complications were observed. Conclusions: Our reported technique was used on heart-beating donor kidneys as well as on livingdonor organs and is safe with less comorbidity. This minimal access kidney transplant technique might be an alternative procedure for avoiding some of the disadvantages of conventional approaches used for kidney transplant.