Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Background  

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.     

Anti-apoptotic gene transcription signature of salivary gland neoplasms

Background  

Development of accurate therapeutic approaches to salivary gland neoplasms depends on better understanding of their molecular pathogenesis. Tumour growth is regulated by the balance between proliferation and apoptosis. Few studies have investigated apoptosis in salivary tumours relying almost exclusively on immunohistochemistry or TUNEL assay. Furthermore, there is no information regarding the mRNA expression profile of apoptotic genes in salivary tumors. Our objective was to investigate the quantitative expression of BCL-2 (anti-apoptotic), BAX and Caspase3 (pro-apoptotic genes) mRNAs in salivary gland neoplasms and examine the association of these data with tumour size, proliferative activity and p53 staining (parameters associated with a poor prognosis of salivary tumours patients).     

Brain asymmetry,immunity, handedness

The principle of symmetry-asymmetry is widely presented in the structural and functional organization of the nonliving and living nature. One of the most complex manifestations of this principle is the left-right asymmetry of the human brain. The present review summarizes previous and contemporary literary data regarding the role of brain asymmetry in neuroimmunomodulation. Some handedness-related peculiarities are outlined additionally. Brain asymmetry is considered to be imprinted in the formation and regulation of the individual’s responses and relationships at an immunological level with the external and internal environment. The assumptions that the hemispheres modulate immune response in an asymmetric manner have been confirmed in experiments on animals. Some authors assume that the right hemisphere plays an indirect role in neuroimmunomodulation, controlling and suppressing the left hemispheric inductive signals.     

Quality assurance of sphincterotomy: A prospective single-centre survey

Quality assurance becomes an increasingly important part of clinical medicine and of the field of endoscopy. Endoscopic sphincterotomy is associated with a fairly high complication rate. We aimed to assess our quality of sphincterotomy for benchmarking by using a prospective electronic database registry, and to identify potential risk factors for post-interventional complications. Over 2 years, 471 sphincterotomies were performed in a single tertiary referral centre. Patient- and procedure-related variables were prospectively recorded with the support of a multi-centre international sphincterotomy registry. Multivariate analysis was performed. The overall post-interventional complication rate was 9.3%. Pancreatitis happened in 5.5%, bleeding in 2.1%, perforation in 1.3%, and cholangitis in 0.4%. In the multivariate analysis following variables remained highly significant and predictive for complications: ‘papilla only in lateral view’ (p=0.001), antiplatelet therapy (p=0.024), and opacification with contrast up to the pancreatic tail (p=0.001). The primary success rate of sphincterotomy was 95.1%. The rate of post-interventional pancreatitis did not differ significantly regardless of the presence of prophylactic pancreatic stent (p=0.56). The outcome of sphincterotomy in our centre matches with literature data. The extent of pancreatic duct opacification has an influence on the pancreatitis rate. Prevention of pancreatitis by inserting pancreatic stents is not confirmed.     

Association between weight status and recreational drug abuse in Korean adolescents

The purpose of this study was to investigate the relationship between weight status and recreational drug use in Korean adolescents. A total of 72,399 adolescent students (38,152 boys and 34,247 girls) from the middle first to high third grade participated in the 5^th Korea Youth Risk Behaviour Web-based Survey (KYRBWS-V) project in 2009. They were assessed for body mass index (BMI) and recreational drug abuse. The associations between BMI and recreational drug use were examined using multivariable logistic regression analysis after adjusting for the covariate variables of age, smoking frequency and cigarette consumption, frequency of alcohol consumption and severe alcohol intoxication, amount of alcohol consumed, parents’ education level, economic status, sedentary activities during the week, mental stress, sleep duration, frequency of vigorous and moderate physical activities, and muscular strength exercises during the week. For boys, the odds ratio (OR) (95% confidence interval [CI]) between overweight and drug use were 0.990 (0.723–1.356; p = 0.950) for almost none, 0.939 (0.521–1.693; p = 0.834) for past use, and 0.791 (0.385–1.624; p = 0.523) for present use. The OR (95% CI) between obesity and drug use was 0.731(0.508–1.052; p = 0.091) for almost none, 0.755 (0.389–1.465; p = 0.407) for past use, and 0.701 (0.314–1.565; p = 0.386) for present use. For girls, the OR (95% CI) between overweight and drug use was 1.112 (0.702–1.763; p = 0.650) for almost none, 1.103 (0.464–2.619; p = 0.825) for past use, and 0.927 (0.267–3.218; p = 0.905) for present use. The OR (95% CI) between obesity and drug abuse was 0.594 (0.261–1.352; p = 0.215) for almost none, 1.318 (0.462–3.764; p = 606) for past use, and <0.001(<0.001–<0.001; p = 0.998) for present use. We concluded that recreational drug use had no correlation with overweight and obesity in Korean adolescents.     

Posterior pusher syndrome — case report

Pusher syndrome is classically described as disorder of body orientation in the coronal plane. It is characterized by a tilt towards the contralesional paretic side and a resistance to external attempts to rectify. It occurs mainly in stroke patients, however, non-stroke causes have been described too. In 2010 the concept of the posterior pusher syndrome had been proposed, defined as disturbance of body orientation in the sagittal plane with imbalance, posterior tilt and an active resistance to forward pulling or pushing. The author describes, on the basis of the literature and own research, symptoms and methods of the treatment of the little-known posterior pusher syndrome.     

Hemangiomas of the external auditory canal:a literature review and two new case reports

Aim  

The aim of this paper is to present two case reports of patients with hemangiomas of the external auditory canal, and to overview all cases published in English language literature so far.     

Interactions between Tacrolimus and Metronidazole in a renal transplant patient

We present a case which reports the occurrence of a potential elevation of Tacrolimus (Tac) plasma levels to toxic values in a renal transplant recipient after adding Metronidazole (Met) to the medication regimen. A 30-year old female, status post living-related renal transplant, who was stabilized on Tac 4.5 mg, twice daily, for 4 months, presented to the clinic with diarrhea. We used Microparticle Enzyme Immunoassay (MEIA) to determine Tac trough concentration (trough concentrations 5–10 ng/ml). After 6 days of Met therapy on 1.5 g/d, Tac trough concentration and serum creatinine (sCr) increased to 20.2 ng/ml and 7.8 mg/dl respectively. Met therapy was discontinued, also one dose of Tac was withheld, while daily dose was decreased to 2 mg/d. Four days after Met discontinuation, Tac concentration dropped to 8.7 ng/ml, sCr to 2.1 mg/dl, warranting Tac dose increase to 3 mg/d. Co-administration of Tac with Met may result in elevated Tac concentrations, possibly leading to tacrolimus nephrotoxicity. Clinicians should be aware of this potential interaction and closely monitor Tac concentration and renal function.